Cancer Research in Switzerland - Krebsliga Schweiz

Cancer Research in Switzerland 

A publication of the Swiss Cancer League 

and the Foundation Cancer Research Switzerland 

on their funded research projects 2009/2010 

Edition 2011

Imprint 

© Swiss Cancer League and Foundation Cancer Research 

Switzerland. All rights reserved by the Scientific office of 

the Swiss Cancer League and the Cancer Research Switzerland, 

including the right to reproduce this publication or portions 

in any form. 

Publisher and information: 

Scientific Office 

Swiss Cancer League 

Effingerstrasse 40 

P. O. Box 8219 

CH-3001 Bern 

Phone +41 (0)31 389 91 16 

Fax +41 (0)31 389 91 62 

scientific-office@swisscancer.ch 

www.swisscancer.ch 

Publication date: November 2009 

Edition German: 4400 Ex. 

Edition French: 1600 Ex. 

Edition English: 500 Ex. 

Responsible: 

Rolf Marti, PhD 

Head of Scientific Office 

Swiss Cancer League, Bern 

Editor: 

Wolfgang Wettstein 

Public Relations Consultant BR-SPRV, Zurich 

w.wettstein@sunrise.ch 

Kurt Bodenmüller 

Swiss Cancer League, Bern 

French translation: Sophie Neuberg, Berlin 

English translation: Ellen Russon, East Sandwich, 

Massachusetts, USA 

Images: Reto Camenisch, Bern 

Design: Atelier Richner, Visuelle Gestaltung, Bern 

www.atelierrichner.ch 

Print: Ast & Fischer AG, Wabern 

This edition of the report “Cancer Research in Switzerland” 

and also the 2009, 2006 and 2004 editions can be downloaded 

as a PDF file at: www.swisscancer.ch/researchreport 

This publication is also available in German and French at: 

www.swisscancer.ch/researchreport 

Printed on non-chlorine-bleached paper. 

Reto Camenisch (*1958) is a photographer and head of 

photography studies at MAZ – the Swiss School of Journalism 

in Lucerne. Camenisch has shown mainly portrait and 

landscape photographs at national and international exhibitions 

since 1983. He works exclusively in analogue photography 

using large format cameras. His work has been published 

in diverse monographs: 1993 Bürgerbilder, 1997 Bluesland, 

2006 Zeit, 2011 Berge Pilger Orte. 

www.camenisch.ch

Cancer Research in Switzerland

Table of contents 

4 Editorial 

Thomas Cerny and Jakob R. Passweg 

6 Better treatment thanks to research funding 

Rolf Marti 

16 Partner organizations and committees 


20 The Scientific Committee 

24 Research awards: Honouring outstanding cancer researchers 

26 100 years of the fight against cancer in Switzerland 

27 Does Switzerland need a new National Cancer Programme? 

Thoughts on research and therapy 

Richard Herrmann 

31 Research funding by the cantonal cancer leagues 

Rolf Marti 

33 List of funded research projects, institutions, and programmes in 2009/2010 

42 Programme research: Supporting translational and clinical research 


44 Collaborative Cancer Research Projects (CCRP) 

List of funded research projects 

The funded research projects in brief 

49 International Clinical Cancer Research Groups (ICP) 

List of funded research groups 

The funded research groups in brief

Basic biomedical research 

55 Cancer stem cells: The origin of cancer? 

Lukas Sommer 

59 List of completed research projects from July 2008 to December 2010 

63 Presentation of completed research projects from July 2008 to December 2010 

93 List of approved research projects in 2009/2010 

97 Presentation of approved research projects in 2009/2010 

Clinical research 

115 Challenges for clinical cancer research in Switzerland 

Beat Thürlimann and Arnoud Templeton 





Psychosocial research 

171 Palliative care research in Switzerland 

Steffen Eychmüller 





Epidemiological research 

193 Epidemiological studies on mobile telephones and cancer 

Martin Röösli and Kerstin Hug 




202 Presentation of approved research projects in 2009/2010

4 

Editorial 

For more than 100 years the Swiss Cancer League 

has been supporting cancer research in academia. 

And for the past 20 years, it has been doing so 

together with the Foundation Cancer Research 

Switzerland. Their goal is to support the highest 

quality research projects so as to achieve continuous 

advancements in order to better prevent cancer, to 

detect the disease earlier, to treat it more successfully, 

or at least to better alleviate the effects of 

cancer. For both organizations, the main focus of 

their funding strategy is patient-centred research. 

We are very pleased to report that we were able to 

invest new record sums in cancer-specific research in 

the years 2009 and 2010. In this period the number 

of research proposals submitted and the amount of 

funding applied for also reached new record highs. 

This trend began already 10 years ago: Whereas 

the amount of funding applied for tripled in the last 

10 years, it was at least possible to double the 

amount of the funds granted. Here we would like to 

express a special note of thanks to the members of 

the Scientific Committee for their outstanding work. 

This fourth edition of the cancer research report 

presents the results of the completed research pro- 

jects and the topics studied by the projects funded. 

Two changes here are worth mentioning: For the first 

time, the report presents research funding by the 

Cancer League as a whole – that is, the projects and 

funds of the Swiss Cancer League along with those 

of the cantonal cancer leagues. Also new as of 2009 

is that the Foundation Cancer Research Switzerland 

is responsible for distributing the funds to the researchers. 

Oncosuisse now focuses on strategy and

policy work and was in charge of developing the 

second National Cancer Programme for the period 

2011–2015 that was presented to the public in April 

2011. 

We have kept the same appearance of the publica- 

tion. This time, photographs by the well-known 

Bernese photographer Reto Camenisch design and 

structure the report. The portraits and landscape 

photographs are from Camenisch’s monograph, 

“Berge Pilger Orte”, taken in 2009 on a hiking trip 

through northern India, Nepal, and Tibet. 

In closing, we would like to extend heartfelt thanks 

to all of the donors for placing their trust in us over 

the last years and supporting our work so generously; 

all of the researchers for their great efforts in 

the fight against cancer; and all of the people who 

worked on this edition of the cancer research report. 

Thomas Cerny Jakob R. Passweg 

Prof. Dr. Thomas Cerny, MD 

President of the Foundation Cancer 

Research Switzerland 

Prof. Dr. Jakob R. Passweg, MD 

President of the Swiss Cancer League 

5

6 

In the last two years, the Swiss Cancer League (SCL) 

and Foundation Cancer Research Switzerland (CRS) 

once again provided record sums for funding cancer 

research in Switzerland: CHF 12.4 million in 2009 

and 15.9 million in 2010. This was made possible 

by the contributions of the many charitable donors, 

to whom we extend our thanks. Their donations are 

helping to improve cancer prevention, detection, 

and treatment. 

Funding cancer research is one of the core tasks of 

the partner organizations Swiss Cancer League and 

Foundation Cancer Research Switzerland. The focus 

is on high-quality and patient-centred research conducted 

at universities, hospitals, and academic research 

institutes. The SCL is engaged in the entire 

range of the fight against cancer: It supports and advises 

persons with cancer and their relatives, works 

towards early detection and prevention of cancer, 

and funds cancer research. The SCL is a non-profit 

organization, and a good 11% percent of its financial 

means goes towards funding research. As its name 

implies, the CRS, which is also financed by charitable 

donations, focuses exclusively on funding research. 

Professional and efficient utilization of resources 

The two organizations work together closely. The 

Scientific Office is the competence centre and operational 

hub for research funding and is responsible 

for the call for and the review of proposals and quality 

control of the funded research projects. The Scientific 

Office is supported by renowned scientists 

who provide their extremely valuable services for 

very little pay. As members of the Scientific Commit- 


Head of the Scientific Office, Swiss Cancer League 

Better treatment thanks to research funding 

tee they review the research proposals submitted 

according to clearly defined scientific criteria. With 

this, the Scientific Committee assures the high quality 

of the research in the framework of the competition 

for funding (see the article on the Scientific 

Committee on page 20). 

The SCL and CRS have pooled their resources by 

having one Scientific Office and one Scientific 

Committee for the two organizations. This makes 

research funding that meets the highest international 

quality standards possible, as confirmed by 

world-renowned universities such as ETH Zurich. It 

also minimizes administrative costs and makes efficient 

utilization of the charitable donations feasible, 

so that the greatest possible portion of the funds 

available can be put into the qualitatively best research 

projects. 

Research for patient benefit 

One in three people in Switzerland will develop some 

form of cancer during their lifetime. And unfortunately, 

soon more people will die of cancer than of 

any other disease. Directly or indirectly, we are all 

affected by cancer. Many patients with cancer and 

their families place their hopes in cancer research 

and await improvements in treatment options and 

chances of a cure. Supporting cancer research is also 

one of the most important concerns of the charitable 

donors.

The main focus of the research funding policy of 

the boards of the SCL and CRS is patient-centred research, 

or research that puts a priority on the needs 

of patients. Specifically, this means research funds 

are mainly granted to projects that aim to deliver 

findings that will lead to direct benefits for people 

affected by cancer – improvements in prevention, diagnosis, 

and treatment or improvements in dealing 

with the disease. 

Clinical research stands in the foreground of the pa- 

tient-centred research funding. In addition, projects 

are funded in the areas of psychosocial research, epidemiology, 

nursing sciences, prevention, public 

health, and cancer care and outcome research (that 

is, research on the quality, effectiveness, and cost 

control of medical care). Basic research, which lies at 

the other end of the research spectrum, delivers 

findings on the biological and molecular mechanisms 

of the development and spread of cancer. Based on 

the ever improving understanding of the different 

types of cancer, new and innovative methods in diagnosis 

and treatment can be developed over the 

longer term. 

New record sums for research 

The partner organizations SCL and CRS provided new 

record levels of funding for research in 2009 and 

2010. In those two years the total in funding for cancer 

research projects and organizations, research 

programmes, and bursaries was CHF 27.6 million, 

with an annual average of CHF 13.8 million. A total 

of 112 innovative research projects covering a broad 

range of topics as well as three Swiss research organizations 

were supported (Figure 1). Not included in 

these figures are contributions made to other projects. 

Also not included in these figures are the 

approximately 50 research projects that are funded 

by the cantonal and regional cancer leagues to 

the amount of CHF 4.2 million annually; this funding 

is included in this report for the first time (see 

page 31). 

These above-average levels of funding were made 

possible by the generous contributions of the donors. 

The new record sums are also due to another utilization 

of reserves of the CRS and to several large bequests. 

Figure 1 

Cancer research funding by the partner organizations Swiss Cancer League (SCL) and Foundation Cancer Research 

Switzerland (CRS) (independent research projects, bursaries, programme research, Swiss organizations) since the founding 

of CRS in 1990 

Total sum in million CHF: 42.6 (SCL), 131.4 (CRS) 

Amount (in million CHF) 

16 

14 

12 

10 

8 

6 

4 

2 

0 

3,5 

3,4 

2,2 

2,7 2,4 

3,2 

1,6 1,7 1,6 

3,6 3,9 

2,3 

1990 91 92 93 94 95 96 97 98 99 2000 01 02 03 04 05 06 07 08 09 2010 

Swiss Cancer League (SCL) Cancer Research Switzerland (CRS) 

4,4 

1,7 1,9 

5,1 

2,7 

3,9 

4,9 

1,6 1,7 2,0 

5,8 6,1 

8,9 

11,8 

9,2 

1,4 1,1 1,2 1,3 

9,5 

2,1 

11,5 

3,1 

8,9 

9,1 

7 

13,1 

2,6 

2,9 

2,4

8 

The funding in numbers 

Total spending on cancer research was CHF 12.4 million 

in 2009 and CHF 15.9 million in 2010 (Table 1). 

As in the previous reporting period (2006–2008), 

about 80 % of the funds came from CRS and 20 % 

from the SCL. The number of submitted grant applications 

in independent project research was 140 in 

2009 and 156 in 2010, which also sets new records. 

As compared to the previous reporting period 

(2006–2008), this represented an increase in the 

number of applications per year of over 10 %. In 2009 

and 2010, 31% of the funding applied for was 

granted (total applied for: CHF 90.7 million; total 

granted: CHF 28.3 million). Of the 370 grant applications 

submitted in total, 158 applications, or about 

53 %, were approved for funding. These figures include 

all grant applications, including applications 

for support for other projects. 

Table 1 

Research funding overview 

Distribution of cancer research spending 

On average, 78 % of the funding went to independent 

research projects; 5 % went to persons receiving 

bursaries; 2 % went to other projects. 6 % of the 

funds went to research projects in the programme 

Collaborative Cancer Research Projects (CCRP). In 

new spending this time, 9 % of the funds went to 

research organizations as research contributions for 

basic services. Taking the funds for research programmes 

and organizations together, it can be seen 

that the allocation of the research funds once again 

remained relatively constant compared to the previous 

years. 

On average, the annual funding for independent 

project research increased by about 10 %, from CHF 

10 million in the period 2006–2008 to CHF 11 million 

in the period 2009–2010. The discontinued pro- 

Number of grant applications and amount applied for; number of grants and amounts granted in 2009/2010 

(all funding areas) 

Independent Bursaries Research Research Other* Total 

research 

programmes organizations 

projects 

(ICP/CCRP) 

2009 

Number of grant applications 140 6 1 3 20 170 

Number of grants 44 5 0 3 17 69 

Amount applied for (in thousand CHF) 37 896 743 884 1 260 425 41 208 

Amount granted (in thousand CHF) 10 198 557 0 1 260 348 12 363 

Proportion of total funding (in %) 82 % 5 % 0 % 10 % 3 % 100 % 

2010 



Amount applied for (in thousand CHF) 45 070 1 138 713 1 710 813 49 444 

Amount granted (in thousand CHF) 11 899 826 1 597 1 260 351 15 933 


Average per year (2009 and 2010) 



Amount applied for (in thousand CHF) 41 483 941 799 1 485 619 45 326 



* Funding for scientific conferences, workshops, international organizations

gramme research funding decreased by 64 %, from 

CHF 2.2 million in 2006–2008 to CHF 0.8 million in 

2009–2010. This benefitted the contributions to the 

research organizations, to which an annual average 

of CHF 1.3 million were allocated in 2009–2010. As 

compared to the previous recording period, 73 % 

more funding went to persons receiving bursaries, 

and funding for other projects increased slightly 

by about 10 %. “Other” indicates for the most part 

financial support of scientific and medical conferences 

and workshops in Switzerland and contributions 

to international organizations such as EORTC 

Charitable Trust, the foundation of the European 

Organisation for Research and Treatment of Cancer. 

Figure 2 shows the two partner organizations’ distri- 

bution of funds to the cantons and the cantonal in- 

stitutions in the years 2009 and 2010. 

Funding of independent research projects: 

Distribution of spend and grant approval success 

rate 

The average funding of independent project research 

was CHF 11 million per year (Table 2). At 80 % of 

total spend, this is by far the most important area of 

research funding. Allocating the lion’s share of the 

funding to independent project research is in accordance 

with the strategic guidelines set by the SCL and 

CRS boards. Per year an average of 148 submitted 

grant applications were approved for funding in the 

period 2009–2010, which is a grant approval success 

rate of 33 %. Of the average CHF 41.5 million in 

funding applied for each year, CHF 11 million were 

granted, which is a monetary grant approval success 

rate of 27 %. Compared to the period 2006–2008, 

this represents a not insignificant decrease of 8 % in 

the grant approval success rate for projects and a decrease 

of 5 % in funds. This was the case even though 

in the period 2009–2010 more funding was available 

(over CHF 1 million more) for independent project 

research. The lower grant approval success rate can be 

explained by the increase in the number of ap plications 

submitted and the amount of funding applied for. 

For purposes of comparison: According to the 2010 

annual report of the Swiss National Science Foundation 

(SNSF) the SNSF grant approval success rate in 

project funding in biology and medicine was 49 % 

for number of applications submitted and approved 

and 45 % for amount of funding applied for and 

amount of funding granted. 

Once again, the greater part of all requests for funds 

in independent project research (58 %) came from 

the basic biomedical research sector. Again, only 

24 % of the funding applied for was granted (2009: 

22 %; 2010: 26 %), even though after the review 

process an increased number of applications were 

recommended for funding. This is a consequence of 

the quota described below, which targets increased 

funding of patient-centred research. Clinical research 

includes research projects with patients and also laboratory 

research using human biological material. In 

the area of clinical research 30 % of the funds applied 

for were granted (2009: 32 %; 2010: 27 %). 

The lowest grant approval success rate was in the 

area of psychosocial research; here 15 % of the funds 

applied for were granted (2009: 26 %; 2010: 8 %). 

This was mainly due to the relatively large number of 

grant applications submitted that did not pass the 

evaluation process according to international standards. 

The highest success rate for grant approval was 

in the area of epidemiological research: Here, 55 % 

of the funds applied for were granted (2009: 64 %; 

2010: 52 %). Comparing the number of approved 

applications to the number of submitted applications, 

the grant approval success rates in the different 

sectors were: 30 % in basic research, 35 % in clinical 

research, 27 % in psychosocial research, and 

71% in epidemiological research. 

The funding spend for independent research projects 

and patient-centred research was higher in the last 

two years than in the previous reporting period: It 

increased from CHF 5.2 million (2006–2008) to CHF 

5.9 million (2009–2010) annually for basic research 

and from CHF 4.8 million (2006–2008) to CHF 5.2 

million (2009–2010) per year for clinical, psychosocial, 

and epidemiological research. 

New ways to support excellent projects 

There are two deciding factors for the number of 

research projects approved for funding and for the 

amount of the funding for the projects that the SCL 

and CRS support each year: the international quality 

criteria of proposal evaluation and the monies available 

for funding. It is a difficult situation when the 

Scientific Committee rates projects as high in quality 

and recommended for a grant, but the boards cannot 

approve funding because there is not enough money. 

9

10 

Figure 2 

Distribution of cancer research funding to the cantons by Swiss Cancer League and Foundation 

Cancer Research Switzerland in 2009/2010 

Canton Number of Amount in Percentage 

projects thousand 

CHF 

of total 

AG Cantonal Hospital/UAS/PSI 5 212 100 

Total 5 212 1 

BE SAKK/IBCSG/SPOG 7 2 567 46 

University/Inselspital 18 3 037 54 

Total 25 5 604 21 

BL-BS FMI 5 760 15 

University/University Hospital 18 4 249 83 

Bursaries and awards 2 119 2 

Total 25 5 128 19 

GE University/University Hospital 10 2 085 95 


Total 13 2 189 8 

NE CSEM 1 135 100 

Total 1 135 0 

SG Cantonal Hospital 3 122 43 


Total 5 287 1 

TI Hospitals 5 593 51 

IOSI/SENDO/IELSG 7 540 47 


Total 13 1 159 4 

VD ISREC/EPFL 8 2 142 35 

University/CHUV 15 3 636 60 


Total 26 6 071 22 

VS IRO 1 197 100 

Total 1 197 1 

ZH ETHZ 6 488 8 

University/University Hospital 26 5 698 91 


Total 34 6 251 23 

Total 27 233 100 

in thousand CHF 0 2 500 5 000 7 500 

Abbreviations 

AG UAS = University of Applied Sciences 

PSI = Paul Scherrer Institute 

BE SAKK = Swiss Group for Clinical Cancer Research 

IBCSG = International Breast Cancer Study Group 

SPOG = Swiss Paediatric Oncology Group 

BL-BS FMI = Friedrich Miescher Institute 

NE CSEM = Swiss Center for Electronics and Microtechnology 

TI IOSI = Oncology Institute of Southern Switzerland 

SENDO = South European New Drug Organisation 

IELSG = International Extranodal Lymphoma Study Group 

VD ISREC = Swiss Institute for Experimental Cancer Research 

EPFL = Swiss Federal Institute of Technology Lausanne 

CHUV = University Hospital Lausanne 

VS IRO = Institute for Research in Ophthalmology 

ZH ETHZ = Swiss Federal Institute of Technology Zurich

Table 2 

Distribution of funds for independent research projects 


2009 2010 Average 

per year 

Number of grant applications 74 88 81 

Amount applied for (in thousand CHF) 21 632 26 611 24 122 

(in %) 57 % 59 % 58 % 

Number of grants approved 19 29 24 

Amount granted (in thousand CHF) 4 796 6 998 5 897 







Amount granted (in thousand CHF) 3 964 3 139 3 552 







Amount granted (in thousand CHF) 695 364 530 







Amount granted (in thousand CHF) 743 1 398 1 071 

All projects 






(in %) 

11

12 

In the period 2009–2010 there were 43 grant applications 

that were “approved but not funded” (ABNF) 

(Table 3). Biomedical research was the area that was 

the most affected by this problem, with 34 grant applications 

that were ABNF. In clinical research there 

were eight ABNF applications and in psychosocial 

research only one. In the area of epidemiological 

research, all projects that the Scientific Committee 

deemed worthy of funding were supported. 

Table 3 

High-quality research projects approved but not funded (ABNF) 

2009 2010 Average 

per year 


Number of ABNF applications 14 20 17 

in % of all ABNF 82 % 77 % 80 % 

Amount not granted (in thousand CHF) 2 860 4 227 3 544 





Amount not granted (in thousand CHF) 457 656 557 

iin % of all ABNF 14 % 13 % 13 % 











All projects 


Amount not granted (in thousand CHF) 3 317 5 050 4 184 

These figures for ABNF grant applications show 

clearly that more money is needed for the funding 

of high-quality research projects. The two partner 

organizations aim to apply new methods in fundraising, 

such as via cooperation with partners in industry 

or with foundations. As a new option, project-specific 

donations are now possible, which means that 

a partner can support a research project that has 

already been evaluated by the Scientific Committee 

and judged worthy of funding and that matches the 

partner’s aims in terms of content or objectives. 

85 2 13 

(in %) 

Example: Due to a lack of funds 20 projects in basic research could not be funded in 2010, even though they were rated 

as excellent in quality by the Scientific Committee and recommended for funding (= approved but not funded, ABNF). 

For these 20 projects, the grant amount applied for was CHF 4.2 million (in total). Hence in the area of basic research, 

the percentage of ABNF grant applications was 77 % with regard to number of grant applications and 84 % with regard 

to the amount of grant money applied for.

Funding patient-centred research 

Patient-centred research is essential for continuous 

improvement of the medical and psychosocial care of 

patients with cancer. Central here is clinical research 

conducted independently of the pharmaceutical industry. 

For example, very important for patients are 

research studies on treatment optimization, which 

aim to find the optimal combination and sequencing 

in time of existing treatment options, such as chemotherapy, 

radiation, and surgery, depending on type 

of cancer, stage of cancer, and the patient. Patientcentred 

research also includes psychosocial research, 

which focuses on the psychological and social consequences 

of cancer and aims to find ways to improve 

patients’ quality of life. Epidemiological research 

studies the prevalence and incidence of cancers in 

the population and analyzes the factors that affect 

cancer risk, such as age, sex, smoking, diet, exercise, 

social network, and environmental factors. Nursing 

research focuses on improving the care and support 

of patients with cancer and their families. 

The boards of the SCL and CRS have been striving 

for almost 10 years to increase the funding of patient-centred 

research. In past years, various instruments 

were introduced, tested, and continuously 

critically evaluated. One instrument in particular – 

quotas – has proved its worth, but other measures 

that did not have the desired effect have been discontinued 

or replaced by new ones. 

Quotas 

Within the area of independent research projects, 

60 % of the funding is earmarked for patient-centred 

research. Two-thirds of that (or 40 % of the total 

funds for independent research projects) are reserved 

for clinical research and one-third (20 % of the total 

funds) for research in the psychosocial area, nursing 

sciences, epidemiology, prevention, public health, 

health care and outcomes research. The remaining 

40 % of funding for independent research projects is 

for basic research.

14 

Quotas were introduced in 2002 and have since 

proved to be an effective instrument for increased 

support of patient-centred research; they are planned 

to remain in place in the future. Whereas in 2001, 

2002, and 2003 35 % of the funds for independent 

project research went to patient-centred research 

and 65 % to basic research, the cumulative percentage 

of funds for clinical, psychosocial, and epidemiological 

research has since been at a much higher 

level and a stable one of 45 % and more since 2004 

(Table 4). At the same time, it is apparent that this 

instrument alone is not sufficient to achieve the 

quota of 60 % for patient-centred research. This is 

especially due to the fact that too few grant applications 

have been submitted from these areas that 

meet the high standards of quality. And the most 

heavily weighted criterion in the decision to fund research 

is still the criterion of highest quality research. 

Simplified submission procedure 

To lower the threshold for submission of proposals 

from underrepresented disciplines in patient-centred 

research a simplified, two-step submission procedure 

was introduced. This instrument proved to have only 

limited success. Of the total 105 originally submitted 

shorter letters of intent in the period 2004–2009, 

only 22 led to a research project that was approved 

Table 4 

Distribution of funds for independent research projects by research area and year 

for funding, which is a success rate of only 21%. For 

this reason, this instrument, which also entailed a 

lot of effort for the evaluation process, was discontinued 

in 2010. 

Programme research 

In 2003 two special research programmes were 

launched: Collaborative Cancer Research Projects 

(CCRP) and International Clinical Cancer Research 

Groups (ICP). The CCRP programme provided targeted 

funding to translational research: Through supporting 

close collaboration between basic and clinical 

researchers, the aim was for basic research to move 

faster from discoveries in the laboratory to actual 

clinical applications. The ICP programme supported 

already existing international research collaborations 

that are coordinated by Switzerland (see also the section 

on programme research on page 42). 

After the launch of the research programmes, in the 

period 2004–2010 a total CHF 14.7 million was invested 

in this instrument, including CHF 10.1 million 

in six CCRP that are not yet completed. A critical 

evaluation of the results of the CCRP showed that 

these projects, which have a longer duration of five 

years, lock up too large a portion of the total funds 

available. Moreover, the desired translational added 

2003 2004 2005 2006 2007 2008 2009 2010 


Total in million CHF 4,75 6,00 4,18 5,14 6,12 4,35 4,80 7,00 

in % 65 % 56 % 49 % 52 % 56 % 48 % 47 % 59 % 


Total in million CHF 2,19 3,31 3,36 3,31 3,85 2,90 3,96 3,14 



Total in million CHF 0,14 1 0,61 0,74 1,05 0,84 0,7 0,36 



Total in million CHF 0,22 0,37 0,31 0,74 0 0,93 0,74 1,40 


All projects 

Total in million CHF 7,30 10,68 8,46 9,93 11,02 9,02 10,20 11,90

value was not clearly discernible. It was also unclear 

whether the collaborations between laboratory and 

clinic supported by the CCRP will continue in the 

longer term. For this reason, there have been no more 

calls for proposals under the CCRP programme since 

2009. Naturally, translational research projects continue 

to be funded via independent project research. 

Calls for proposals were also discontinued in 2009 

for the ICP programme. Two ongoing ICP will be 

completed in 2011: the International Childhood Liver 

Tumour Consortium and the International Extranodal 

Lymphoma Study Group (IELSG). In total, 

seven ICP were funded with a total of CHF 4.6 million. 

This instrument for promoting programme research 

was replaced by financial contributions to 

clinical cancer research institutions in Switzerland. 

Supporting clinical cancer research organizations 

In 2009 the boards of the SCL and CRS decided to 

change the strategy regarding support for cancer 

research organizations: Now, by means of performance 

agreements, important basic services are 

funded that diverse organizations perform within 

clinical cancer research, such as designing study protocols, 

managing data, obtaining authorizations from 

ethics committees and Swissmedic, coordinating 

multi-centre studies and international studies, and 

others. Through the structural contributions for specific 

activities, the aim is to reward and ensure the 

work of the organizations in the longer term. 

The following organizations were supported by the 

SCL in the reporting period 2009–2010: 

– Swiss Group for Clinical Cancer Research (SAKK): 

This non-profit organization has launched and 

coordinated clinical cancer trials in Switzerland 

and abroad since 1965. SAKK comprises a wide 

network of about 20 Swiss research groups 

and the SAKK Coordinating Centre in Bern. SAKK 

receives a contribution of CHF 600,000 per year. 

– International Breast Cancer Study Group (IBCSG): 

This study group has conducted academic clinical 

trials in breast cancer since 1977. It is dedicated 

to improving the treatment of women with breast 

cancer. IBCSG receives an annual contribution 

of CHF 560,000. 

– Swiss Paediatric Oncology Group (SPOG): 

This association is an academic research organization 

focusing on clinical, patient-centred research 

in paediatric oncology, particularly in the frame 

work of national collaborative studies. The SPOG 

receives CHF 100,000 per year. 

On the part of CRS, a maximum CHF 2 million, or 

maximum 20 % of the total research funding budget, 

is reserved for this instrument. These monies are 

used by CRS for targeted financial support of five to 

six research organizations. 

Dr. Rolf Marti, PhD 

Rolf Marti has headed the Scientific 

Office since 2002 and is 

responsible for research funding. 

He is a member of the managing 

board of the Swiss Cancer League 

and director of Foundation 

Cancer Research Switzerland. 

One of the focuses of his work 

is research policy. 

Phone +41 (0)31 389 91 45 

rolf.marti@swisscancer.ch 

www.swisscancer.ch/research 

15

16 

Brief portrait of the Swiss Cancer League (SCL) 

The Swiss Cancer League is a charitable, private nonprofit 

organization. Its work is dedicated towards the 

following aims: fewer people being diagnosed with 

cancer, fewer people dying of cancer, more people 

with cancer treated successfully, and providing care 

and aid to persons with cancer and their families 

in all phases of the disease and in dying. It funds 

cancer research, sensitizes the public to prevention 

measures, advocates for early diagnosis and treatment, 

provides advice to persons with cancer and 

their loved ones, and offers social support. The 20 

cantonal cancer leagues are active at the local and 

regional levels. They provide psychosocial advice and 

financial support to persons with cancer and their 

families locally. Most of the funding for the SCL’s numerous 

tasks comes from donations. The SCL funds 

cancer research, with a special focus on supporting 

patient-centred research projects. 

Contact information 

Swiss Cancer League 


P.O. Box 8219 

CH-3001 Bern 

Phone +41 (0)31 389 91 00 

info@swisscancer.ch 

www.swisscancer.ch 

Partner organizations and committees 


Communications manager of the Scientific Office, Swiss Cancer League 

Brief portrait of the Foundation Cancer Research 

Switzerland (CRS) 

In existence since 1990, the Foundation Cancer 

Research Switzerland generates donations that help 

provide funding for all areas of cancer research: basic 

research, clinical, epidemiological, psychosocial 

research, and paediatric research (research on childhood 

cancer). The CRS foundation board is responsible 

for distributing the funds to the researchers. 

The funding decisions are based on the recommendations 

made by the Scientific Committee. The Scientific 

Committee is made up of experts in cancer research 

and reviews the research proposals submitted 

according to clearly defined guidelines. The CRS also 

supports the development and implementation of 

measures to fight cancer in Switzerland – namely, the 

National Cancer Programme 2011–2015 (NCP II). 


Foundation Cancer Research Switzerland 


P.O. Box 7021 

CH-3001 Bern 

Phone +41 (0)31 389 91 16 

info@cancerresearch.ch 

www.cancerresearch.ch

New organization of the Foundation Cancer Research Switzerland and Oncosuisse 

In the fall of 2009 the course was determined for a new strategic and operational direction 

of the Foundation Cancer Research Switzerland (CRS) and Oncosuisse. The goal of the new 

organization was to simplify the structures and processes of research funding and to focus 

on the core competencies of the two organizations. Previously, Oncosuisse had been responsible 

for awarding the monies generated by the CRS to the researchers. Under the new 

organization, the CRS foundation board is responsible for this task. To this purpose, a new 

board was formed and expanded: The board now has one representative each from the 

Swiss Cancer League (SCL), the Swiss Group for Clinical Cancer Research (SAKK), and 

the Swiss Paediatric Oncology Group (SPOG), one expert in each of the different research 

areas, a financial specialist, and further independent persons. 

Within the framework of the new organization, Oncosuisse, the Swiss Federation Against 

Cancer founded in 1999, became a simple association. As a platform it focuses on coordinating 

and representing the strategic policies of the Swiss network working against cancer. 

Its most important task is developing and implementing the National Cancer Programme 

2011–2015 (NCP II). This policy instrument aims to coordinate at the national level and improve 

cancer research, prevention, early detection, cancer treatment, and coping with the 

effects of the disease. Since 2011, the NCP II functions as the national guide in the fight 

against cancer. Oncosuisse is financed by the membership fees of its five partners: CRS, SCL, 

SAKK, SPOG, and the National Institute for Cancer Epidemiology and Registration (NICER). 


Oncosuisse 


CH-3008 Bern 

Phone +41 (0)31 389 93 00 

Fax +41 (0)31 389 92 00 

info@oncosuisse.ch 

www.oncosuisse.ch 

17

18 

The board of the Swiss Cancer League (SCL) 

In April 2010 Prof. Jakob R. Passweg, MD, was elected president 

of the Swiss Cancer League. Gilbert Bernard Zulian, MD, is vice-president. 

The nine members of the SCL board are: 

Prof. Jakob R. Passweg, MD 

Head physician of Hematology 

University Hospital Basel 

President 

Since 2007 

PD Gilbert Bernard Zulian, MD 

Head physician of Department of 

Palliative Medicine 

Hôpital de Bellerive 

University Hospital Geneva 

Vice-president 


Gallus Mayer 

Member of management board 

Wegelin & Co., Private Bankers 

St Gallen 

Treasurer 


Irène Bachmann-Mettler 

Project head of Institute of General 

Practice and Health Services Research 

University of Zurich 

President of Oncology Nursing Society 

of Switzerland 


Prof. Daniel Betticher, MD 

Head physician of Clinic for Medical 

Oncology 

Fribourg Cantonal Hospital 


Lucienne Bigler-Perrotin 

Manager 

Geneva Cancer League 


Hans Neuenschwander, MD 

Medical Director of Palliative Care 

Regional Hospital of Lugano 


Martin Nobs, lic. phil. 

Manager 

Bern Cancer League 


Brigitta Wössmer, PhD 

Head psychologist of Department 

of Psychosomatics 


President of Swiss Society 

of Psycho-Oncology 

Since 2011

The board of the Foundation Cancer Research Switzerland (CRS) 

Prof. Thomas Cerny, MD, has been president of the Foundation Cancer Research Switzerland since 2009, 

and Prof. Richard Herrmann, MD, is vice-president. 

The nine members of the CRS board are: 

Prof. Thomas Cerny, MD 

Head physician of Medical Oncology/ 

Hematology 

Department of Internal Medicine 

Cantonal Hospital St. Gallen 

President 

Past President of SCL 


Prof. Richard Herrmann, MD 

Former head physician of Clinic 

for Medical Oncology 


Vice-president 

Past President of SAKK and 

representative for clinical cancer research 


Pascal Couchepin, lic. iur. 

Former Federal Councillor 

Martigny, Switzerland 

Independent person 


Prof. Matthias Egger, MD 

Director of Institute of Social and 

Preventive Medicine 

University of Bern 

Representative for epidemiological 

cancer research 


Prof. Hans Hengartner, PhD 

Langnau am Albis 

Representative for basic cancer research 


Eduard Holdener, MD 

Therwil 



Isabel Lechtman-Mortara 

Geneva 



Gallus Mayer 

Member of managing board 

Wegelin & Co., Private bankers 

St Gallen 

Financial expert 


PD Nicolas von der Weid, MD 

Co-head of Paediatric 

Hematology-Oncology Unit 

University Hospital Lausanne (CHUV) 

Past President of SPOG and 

represen tative for paediatric cancer 

research 


19

20 

The Scientific Committee 

Members of the Scientific Committee in 2010 (from left): Felix Niggli, Gerhard Christofori, Primo Schär, 

Brian A. Hemmings, Maria Blettner, Holger Moch, Martin F. Fey (president), Rolf Marti (head of the Scientific Office), 

Ellen Benhamou, Freddy Radtke, Martin Pruschy, Adrian Ochsenbein, Cristiana Sessa, Hans-Uwe Simon 

(not pictured: Kurt Fritzsche and Friedrich Stiefel). 

The Scientific Committee is responsible for evalua- 

ting the research grant applications submitted to the 

Foundation Cancer Research Switzerland and the 

Swiss Cancer League by researchers seeking research 

funding. The committee’s peer review process uses 

strictly defined evaluation criteria (see box, “Criteria 

for high-quality cancer research”, page 23). The central 

criterion is always whether a research project is 

expected to advance our understanding of cancer 

prevention, causes, or treatment. 

The 15 members of the Scientific Committee are recognized 

experts with outstanding achievements and 

expertise in all areas relevant to cancer research. 

Having all of the research areas represented on one 

committee prevents the formation of specialized subcommittees 

and also assures funding of research 

trends in all areas. The members serve on the committee 

for three years and can be re-elected twice.

The president of the Scientific Committee is 

Prof. Martin F. Fey, MD. The committee members 

are representatives of the following research areas: 

– basic biomedical research: 4 members 

– patient-centred clinical cancer research: 

2 members 

– laboratory-based clinical cancer research: 

2 members 

– epidemiology and cancer prevention: 2 members 

– psychosocial and other cancer research 

(public health research): 2 members 

– translational cancer research: 2 members 

Each member of the committee handles on average 

20 grant applications per year. More than half of the 

proposals are in basic research. As the time it takes 

for members to review basic research proposals has 

reached an upper limit, it has been decided that an 

additional representative of the discipline can be 

voted into the Scientific Committee. 

The Scientific Committee meets twice a year to dis- 

cuss in detail the research grant applications that 

have been reviewed by committee members and by 

external reviewers (see box, “The research grant application 

review process”). Based on the discussions 

the committee produces a ranked list of the research 

proposals that the committee recommends to the 

boards of the Foundation Cancer Research Switzerland 

and the Swiss Cancer League for grant approval. 

As the financial means are limited, it is never possi- 

ble to approve grants for all proposals that the com- 

mittee judges to be of good quality and worthy of 

funding. In the reporting period 2009–2010 there 

were on average 22 research proposals each year 

that could not be approved for funding despite their 

excellent quality. In total the Scientific Committee 

reviews almost 150 grant applications per year. 

Operational support for the Scientific Committee’s 

important tasks and responsibility is provided by 

the Scientific Office of the Swiss Cancer League 

and the Foundation Cancer Research Switzerland. It 

organizes the call for and review of proposals and is 

responsible for quality control of the supported 

research projects. 

The research grant application review process 

The research proposal is submitted to and recorded 

by the Scientific Office of the Swiss Cancer League. 

< 

The grant application is sent for review to two 

members of the Scientific Committee who are 

experts in the relevant specialist field 

(such as basic research or psycho-oncology). 

< 

The two Scientific Committee members recommend 

additional experts as external reviewers. 

< 

The Scientific Office asks the external reviewers 

to review the proposal. 

< 

The reviewers evaluate the proposal. Four to six 

reviews are obtained for each research proposal, 

two of which are by Scientific Committee members. 

< 

The Scientific Office collects the reviews and puts 

them in a file. 

< 

The research proposal is discussed in detail at 

the bi-annual meeting of the Scientific Committee. 

< 

After the meeting, the Scientific Office writes up 

detailed minutes and creates a list of all proposals 

ranked according to the committee’s recommendations. 

< 

The ranking list is forwarded to the boards of 

the Foundation Cancer Research Switzerland and 

the Swiss Cancer League, which then decide which 

proposals will be funded. 

< 

The Scientific Office notifies the applicant of the 

decision. Upon request, the reviews are made 

available to the applicant in an anonymous form. 

21

22 

Members of the Scientific Committee, 2009/2010 

Prof. Martin F. Fey, MD 

Institute of Medical Oncology 

University Hospital Bern 


Bern, Switzerland 

President 


Ellen Benhamou, MD 

Gustave Roussy Cancer Institute 

Villejuif Cedex, France 


Prof. Maria Blettner, PhD 

Institute of Medical Biostatistics, 

Epidemiology and Informatics (IMBEI) 

University Medical Center 

Johannes Gutenberg University Mainz 

Mainz, Germany 


Paolo Boffetta, MD 

Unit of Environmental Cancer 

Epidemiology 

International Agency for Research 

on Cancer (IARC) 

Lyon, France 

2005–2009 

Prof. Gerhard Christofori, PhD 

Department of Biomedicine 

University of Basel 

Basel, Switzerland 


Prof. Kurt Fritzsche, MD 

Department of Psychosomatic 

Medicine and Psychotherapy 

University Hospital 

Freiburg, Germany 


Brian A. Hemmings, PhD 

Friedrich Miescher Institute for 

Biomedical Research (FMI) 



Prof. Eugen B. Hug, MD 

Center for Proton Radiation Therapy 

Paul Scherrer Institute (PSI) 

Villigen, Switzerland 

2008–2010 

Prof. Joachim Lingner, PhD 

Swiss Institute for Experimental 

Cancer Research (ISREC) 

Swiss Federal Institute of 

Technology Lausanne (EPFL) 

Epalinges, Switzerland 

2003–2010 

Prof. Holger Moch, MD 

Institute of Surgical Pathology 

University Hospital Zurich 

Zurich, Switzerland 


Prof. Felix Niggli, MD 

Paediatric Oncology 

University Children’s Hospital Zurich 



Prof. Adrian Ochsenbein, MD 

Institute of Medical Oncology 

University Hospital Bern 



Since 2006

Prof. Martin Pruschy, PhD 

Department of Radiation Oncology 

University Hospital Zurich 



Prof. Freddy Radtke, PhD 

Swiss Institute for Experimental 

Cancer Research (ISREC) 

Swiss Federal Institute of Technology 

Lausanne (EPFL) 

Epalinges, Switzerland 


Prof. Primo Schär, PhD 

Department of Biomedicine 

University of Basel 



Criteria for high-quality cancer research 

The quality of research grant application is evaluated according to the following 

criteria: 

– Cancer relevance: Is the proposed research project expected to contribute 

important new observations or knowledge on the causes, prevention, 

or treatment of cancer? 

– Originality or socio-economic significance: Is the proposed research project 

original, innovative (basic research projects), or of socio-economic importance 

(clinical or epidemiological projects)? 

– Choice of methodology: Have the most appropriate methods for the project 

realization been chosen? 

– Feasibility: Is the project feasible in terms of finances, human resources, 

and organization? 

– The applicant’s previous productivity: What are the applicant’s (or the project 

group’s) previous research achievements? How good were the publications? 

Prof. Cristiana Sessa, MD 

Oncology Institute of Southern 

Switzerland (IOSI) 

Hospital San Giovanni 

Bellinzona, Switzerland 


Prof. Hans-Uwe Simon, MD, PhD 

Institute of Pharmacology 




Prof. Friedrich Stiefel, MD 

Psychiatry Service 

University Hospital Lausanne (CHUV) 

Lausanne, Switzerland 


23

24 

Research awards: 

Besides supporting research through funding 

projects, bursaries, and organizations, the Swiss 

Cancer League regularly gives the Robert Wenner 

Award for outstanding research work. In addition, 

each year the Scientific Office of the Swiss Cancer 

League organizes the call for research grant 

applications and the evaluation of proposals submitted 

for the SWISS BRIDGE AWARD. 

With the awarding of research prizes, the recipients 

are recognized for their excellent work in cancer research. 

For the researchers, this recognition means 

both honour for their previous achievements and 

incentive for future research efforts. As the greatest 

part of the award money must be invested in cancer 

research, research awards allow the recipients to 

continue their work or to initiate new projects. For 

the Swiss Cancer League the awarding of research 

prizes is also a way to inform the public about outstanding 

industry-independent cancer research. 

Robert Wenner Award 

Robert Wenner, a gynaecologist in Basel who died 

in 1979, endowed the Robert Wenner Award to 

support cancer researchers under the age of 45. 

The prize was awarded for the first time in 1985. 

The award winners receive CHF 100,000, with 

CHF 80,000 earmarked for an ongoing project and 

CHF 20,000 as discretionary funds. In 2010 the 

Robert Wenner Award was given to Prof. Dr. Melody 

Swartz at the Swiss Federal Institute of Technology 

Lausanne (EPFL) for her excellent work in basic research 

on tumour metastasis. No prize was awarded 

in 2009. 

Honouring outstanding cancer researchers 

Interdisciplinary cancer researcher 

Melody Swartz is a bioengineer who integrates different 

modern scientific disciplines in her research. 

Together with her team she combines cell biology, 

biochemistry, physiology, bioinformatics, and engineering 

to study cancer. Her interest centres on the 

lymphatic system and, specifically, on how tumour 

cells behave in the lymphatic system. The lymphatic 

system, which works with the circulatory system, 

is made up of lymph nodes and lymphatic vessels in 

which lymph fluid circulates. The lymphatic system 

transports pathogens to the lymph nodes, where 

antibodies are produced and an immune response is 

mounted. The immune response thus depends on the 

lymphatic system. 

Cunning cancer cells 

It is known that cancer cells also utilize lymphatic 

vessels to spread through the body and form metastases 

at new sites. However, this process is still largely 

unknown. Among other things, Swartz is studying 

how cancer cells move into the lymph vessels. It appears 

that tumours are able to stimulate the growth 

of the lymph vessels so that cancer cells can invade 

them. Also, the lymph vessels appear to actively 

support the tumour cells in this process. The immune 

system is fooled, and the cancer cells evade the 

immune defence.

Swartz wants to find out how tumours accomplish 

this trick. Using the lymphatic transport mechanisms, 

she is trying to deliver vaccines and other drugs to 

the lymph nodes. The drugs are aimed at affecting 

the immune cells of the lymphatic system and stimulating 

them to perform their actual task in the organism, 

which is to destroy cancer cells instead of aiding 

their spread. 

SWISS BRIDGE Foundation: Supporting outstanding cancer research 

SWISS BRIDGE was established upon the initiative of Thomas Hoepli, who was formerly 

managing director of the foundation and today is a member of the foundation board. 

The purpose of the foundation, which was set up in 1997 with the support of the Swiss 

Cancer League, is to support high-quality research projects in Switzerland and abroad in 

the fight against cancer using funds that come from private donors and foundations, such 

as the Stammbach Foundation in Basel. SWISS BRIDGE has a foundation board, an international 

scientific committee, a board of patrons, and a loyal circle of supporters and friends. 

Starting in 2000, each year the foundation has given the SWISS BRIDGE AWARD, totalling 

CHF 500,000. The award honours researchers whose research work promises to achieve 

milestones in the study of and in the fight against cancer. The Scientific Office of the Swiss 

Cancer League organizes the call for research grant applications and the review of the projects 

submitted for the award. Up to now, the SWISS BRIDGE AWARD has awarded a total 

of CHF 6.35 million for projects conducted by researchers in Belgium, England, France, 

Israel, Italy, Norway, Sweden, Spain, and Switzerland. 

The recipients of the SWISS BRIDGE AWARD in recent years were: 

2010 

Andrea Alimonti, MD Laboratory of Experimental Oncology, Oncology Institute of 

Southern Switzerland (IOSI), Bellinzona, Switzerland 

Ronit Satchi-Fainaro, PhD Department of Physiology and Pharmacology, 

Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel 

Anna Sablina, PhD Department of Molecular and Developmental Genetics, 

Research Institute VIB, University of Leuven, Leuven, Belgium 

2009 

Prof. Matthias Egger, MD Institute of Social and Preventive Medicine, University of Bern 

Prof. Wilhelm Krek, PhD Institute of Cell Biology, ETH Zurich 

Prof. Stephen C. West. PhD Clare Hall Laboratories, London Research Institute, 

Cancer Research UK, South Mimms, England 

Further information: www.swissbridge.ch 

Prof. Melody Swartz, PhD 

Melody Swartz was born in the 

United States in 1969. She studied 

at Johns Hopkins University 

in Baltimore, at Massachusetts 

Institute of Technology in Cambridge, 

and at Harvard Medical 

School. She completed her PhD 

in chemical engineering in 1998. 

From 1999 to 2003 she was 

assistant professor in the Departments of Biomedical 

Engineering and Chemical Engineering at Northwestern 

University in Chicago. Since 2003 she has been working 

at the Institute of Bioengineering at the School of Life 

Sciences at the Swiss Federal Institute of Technology 

Lausanne. In 2010 she was appointed full professor of 

bioengineering. She heads a research team at the Laboratory 

of Lymphatic and Cancer Bioengineering. Swartz 

is married and has a son. 

25

26 

On the occasion of its centennial 

in 2010, the Swiss Cancer 

League published a look at 

medical history titled “Vom 

Tabu zum Thema?” (From taboo 

to topic?). This interesting 

read by Daniel Kauz examines 

central facets of one 

hundred years of fighting 

cancer in Switzerland. The structure of the book is 

novel and unique in that it is not a chronological account 

starting in 1910 but rather an examination of 

six different self-contained topics. 

It investigates the development of treatment options, 

the institutionalization of cancer research, and the 

educational and prevention work of the Swiss Cancer 

League over time. How did interactions with the patients, 

and thus their status, change? What images 

and fantasies (mostly frightening) did people associate 

with cancer? How was it possible to gradually 

break down the taboo surrounding cancer? And how 

did the Swiss Cancer League evolve from a small 

association of medical specialists to an established 

non-profit organization active in health and research 

policy? Kauz looks at these and other topics from a 

perspective of medical history. The volume does not 

celebrate the Swiss Cancer League as an institution 

but presents its work in the context of the different 

topics. 

This is a highly readable, solid historical account with 

a modern structure. Kauz, born in 1971, completed 

a Master’s degree in history, German literature and 

philosophy at the University of Zurich and is the author 

of several history publications. This richly illustrated 

volume is available in German and French at 

bookstores or online at the Swiss Cancer League shop 

at www.krebsliga.ch/shop. The German edition was 

published by Schwabe Verlag, and the French edition 

was published by Editions Attinger. 

100 years of the fight against cancer in Switzerland 

Bibliography 

Daniel Kauz 

Vom Tabu zum Thema? 

100 Jahre Krebsbekämpfung in der Schweiz 1910–2010 

2010. 

267 pages, 149 illustrations (85 in colour), 

6 tables. Bound. DVD included. 

CHF 58.–/Euro 40.60 

ISBN 978-3-7965-2671-8 

Schwabe Verlag 

ISBN 978-3-03754-046-6 

EMH Schweizerischer Ärzteverlag 

Daniel Kauz 

Du tabou au débat? 

Cent ans de lutte contre le cancer en Suisse 1910–2010 

2010. 

255 pages, 149 illustrations (85 in colour), 

6 tables. Bound. 

CHF 58.–/Euro 41.– 

ISBN 978-2-940418-16-9 

Editions Attinger SA 

Further information in German at www.krebsliga.ch/ 

fachbuch or in French at www.liguecancer.ch/ouvrage 


Kurt Bodenmüller is a microbiologist 

who has worked in the 

field of science communications 

since 1997. He worked for many 

years as a consultant at an international 

PR company. He has 

been communications manager 

at the Scientific Office of the 

Swiss Cancer League since 2008. 

Phone +41 (0)31 389 93 31 

kurt.bodenmueller@swisscancer.ch 

www.swisscancer.ch/research

The scientific and medical research conducted 

in Switzerland is high level. Our medical care is 

excellent, too – also in oncology. So why does 

Switzerland need a five-year national cancer programme 

in which research and therapy play an 

important role? Almost 10 years ago, under the 

overall control of Oncosuisse the first National 

Cancer Programme was worked out for the period 

2005–2010; it also contained a number of aims 

in the areas of research and therapy. However, regarding 

achievement of these aims the end result 

was sobering. All in all, only little progress could 

be achieved. This was in part due to the fact that 

many of the stated aims were set for the more 

distant future. In April 2011, Oncosuisse launched 

the second National Cancer Programme for the 

period 2011–2015. Within cancer research and 

treatment, we face a number of challenges. 

Cancer research in the laboratory pursues various 

aims. For instance, a research study may aim to find 

out why from a healthy cell that has a defined function 

and divides only under very controlled conditions 

a cancer cell develops. This cell evades the normal 

control mechanisms, divides again and again, 

invades surrounding tissue and destroys it, separates 

from its normal united cell structure and spreads 

via the blood to other organs, where it continues to 

divide and forms metastases. All of these abnormal 

characteristics are based on changes in the genetic 

information (DNA) of these cells; these mutations 

occur on a huge scale in cancer cells. 

Does Switzerland need a new National Cancer 

Programme? Thoughts on research and therapy 

The stony way from the laboratory to the clinic 

To be able to intervene therapeutically, we have to 

know the genetic changes, or mutations, of the cancer 

cells. Based on this knowledge it is possible to 

block their effects. If this type of research is conducted 

using animal experiments or human cell lines 

in the test tube, the findings may not yet be directly 

applicable to tumour disease in humans. Although 

we have model systems that are used to investigate 

certain mechanisms and processes, their transferability 

to humans is limited. If we study human 

tumours, the results are frequently not uniform, as 

there is mostly considerable variability within the 

same tumour disease, such as within breast cancer. 

Moreover, it is very difficult to obtain a sufficiently 

large number of human tumour tissue samples to 

allow reliable findings. 

Consequently, there is a long and difficult way from 

the results of experimental laboratory research to 

successful medical treatment of patients, and it is 

here that we must push ahead more and more. For 

example, there is a need for more research with 

human tumour material that is aimed at directly influencing 

the course of the disease. The aim could 

be, for instance, to find specific molecular changes. 

If such markers were known, we could develop new 

medicines or study the mechanisms of resistance to 

currently prescribed cancer drugs. Through the latter, 

more efficient use of these in part very expensive 

drugs could be made possible and many patients 

could be spared the side effects of an ineffective 


President of Oncosuisse and former head physician of the Clinic for Medical Oncology at the University 

Hospital Basel 

27

28 

treatment. This kind of research is called translational. 

It could also be called “bridging research”, 

for it builds bridges between research in the laboratory 

and the treatment of patients with cancer. 

Translational research has a bridging function 

The National Cancer Programme 2011–2015 defines 

translational research as one of its priorities. For this, 

closer cooperation is needed among researchers 

involved on both sides – laboratory and hospital. 

Cooperation at the national level is also needed. 

Already today, for several cancers that are actually all 

the same disease such as breast cancer, lung cancer, 

or colon cancer, it is possible to identify specific subgroups 

of the particular tumour type on a molecular 

basis, and they require very different treatments. 

In this way, suddenly several different new clinical 

pictures arise. Today there are at least ten different 

types of lung cancer, for example. As a result, out of 

one common disease there suddenly emerge several 

rare diseases. Great cooperative effort is required all 

the more for their study. With its long-year tradition 

of cooperative clinical research through the Swiss 

Group for Clinical Cancer Research (SAKK), Switzerland 

is predestined to tackle this topic seriously and 

with the promise of succeeding. Through the collaboration 

of many committed researchers and physicians 

a great deal of knowledge and experience will 

be gathered together that will be crucial in answering 

important questions for the good of patients 

with cancer. 

Both laboratory research and the advances in clinical 

research should ultimately benefit the patients. However, 

this pathway of many small steps is subject to 

constant change. Research findings from the laboratory 

and from clinical studies always influence each 

other. The connection between these two branches 

of research – translational research – can help us to 

find out, for example, why a patient’s initially successful 

therapy is suddenly no longer effective. It has 

been found for many cases of cancer that an effective 

drug initially docks successfully with the receptor 

of the tumour cell. However, if the docking site 

changes due to mutations, the drug becomes ineffective 

and the tumour cell can continue to grow unhindered. 

Exact knowledge of these processes allows 

us to develop new substances whose effectiveness 

will not be disabled by this resistance mechanism. 

Complexity demands interdisciplinarity 

The developments within cancer treatment in the 

last five to ten years have made the area a great deal 

more complex and complicated, for several reasons: 

1. As mentioned above, there are many more diffe- 

rent types of cancer today. Great effort is required 

for precise diagnosis, and the therapies are different 

for each type. The use of new medicines is not only 

costly but also requires detailed knowledge of how 

the drugs work, the exact guidelines for their use, 

possible side effects and possible ways to treat or 

prevent these side effects. 

2. If a therapy has failed, for many tumour diseases 

there is a second option, often called second-line 

therapy; occasionally there is also a third or fourth 

line. This also increases the complexity as well as the 

time required for a patient, because prior to starting 

any new therapy the health care provider must talk 

with a patient to provide detailed information.

3. The original order/sequence of the modes of treatment 

for cancer – surgery, radiation therapy, chemotherapy 

– is becoming more and more seldom. Now, 

the therapy goal determines the mode of treatment 

to be used in the individual case. This means that 

chemotherapy – a better name is systemic therapy – 

may be the first-line therapy. Surgery can be required 

at different points in time in the course of the 

disease, such as to remove metastases. For optimum 

treatment results, patients’ medical conditions must 

be reviewed and discussed at multidisciplinary conferences 

called tumour boards. The experts in the 

different medical specialities involved discuss and 

make a plan for the patients’ further treatment based 

on their review of the current clinical findings. In 

large centres there is a tumour conference of this 

kind for every cancer type, that is usually scheduled 

weekly. This promotes the transparency within a centre 

considerably and increases the quality of treatment. 

These tumour conferences are very personnelintensive, 

however. 

4. The enormous knowledge gain in clinical cancer 

research combined with our growing basic under- 

standing of tumour biology inevitably requires subspecialization 

within medical oncology. No oncologist 

today can have the needed in-depth grasp of 

the entire range of the subject. However, to provide 

patients with cancer in Switzerland with the best 

possible care and treatment according to the latest 

research, the structures of patient care must be 

adapted to this development. For one, we need more 

centralization, which should not be too difficult in a 

country with a manageable size like Switzerland and 

with the help of electronic communications means. 

For another, we need defined competence centres 

for rare diseases – depending on prevalence perhaps 

one or two. This would make it possible to build the 

needed competence in a multidisciplinary way. Research 

projects with sufficient numbers of patients 

could be undertaken, among other things through 

international networking of these competence centres. 

These measures would boost development in 

the area of these very rare types of cancer that are 

often neglected by the pharmaceutical industry.

30 

The changes that are needed due to the develop- 

ments in oncology described above cannot be ex- 

pected to happen by themselves. For this reason, the 

National Cancer Programme 2011–2015 demands 

the necessary structural changes. As physicians and 

researchers committed to persons with cancer, we 

see it as our task to inform the public, to push for 

the needed policy decisions, and to convince our colleagues 

of the necessity of these changes. 

National Cancer Programme for Switzerland 2011–2015 


Richard Herrmann was head physician 

of the Clinic for Medical 

Oncology at the University Hospital 

Basel from July 1991 to June 

2011. From 2004 to 2010 he was 

president of the Swiss Group for 

Clinical Cancer Research (SAKK). 

Since 2009 he has been vicepresident 

of the Foundation Cancer 

Research Switzerland and in addition president of 

Oncosuisse, which is responsible for development and 

implementation of the National Cancer Programme 

2011–2015. 

herrmannr@uhbs.ch 

www.oncosuisse.ch 

The fight against cancer is a complex, multidisciplinary task that requires the 

coordination of many actors. To this purpose, the cancer organizations in 

Switzerland, with the support of the federal government and the cantons, 

have worked out the National Cancer Programme 2011–2015 (NCP II). 

The NCP II defines 10 areas of priority with specific measures to be followed 

within each. The programme has chosen an approach that transcends the individual 

disciplines, for only a complete chain of measures – from prevention 

to early diagnosis to therapy to rehabilitation or palliative care – has the chance 

of achieving effective improvements in the fight against cancer. There are three 

main goals: Every person living in Switzerland should be equally entitled to the 

lowest possible cancer risk through prevention and early diagnosis, to appropriate diagnostics and 

treatment according to the latest findings and psychosocial and – where unavoidable – palliative care 

in the case of illness. The NCP II aims to improve quality and to close gaps in services and care. 

The NCP II presents specific recommendations for the fight against cancer. It is directed at policy 

decision-makers at federal and cantonal levels, organizations in the health care system, researchers and 

decision-makers in hospitals and universities, and also the public, which is affected by cancer in many 

ways. The report presents an overview of the actions and ensures transparency for all actors. 

www.oncosuisse.ch

As a federation, the Cancer League comprises 

20 cantonal and regional cancer leagues, with 

the Swiss Cancer League (SCL) as the umbrella organization 

with headquarters in Bern. In addition 

to the SCL, eleven of the cantonal cancer leagues 

provided funds for research in 2009 and 2010: 

On average per year the cantonal cancer leagues 

awarded a total of CHF 4.2 million to close to 

50 research projects, mostly to projects in their 

own canton. 

A federation development project was launched in 

2009 with the aim to intensify cooperation within 

the organization as a whole and to offer nationally 

standardized services to patients. In the context of 

this process, the area of research funding was also 

discussed at length. 

The cantonal cancer leagues and the SCL came to a 

mutual agreement on the following principles for optimization 

of the quality, allocation of responsibilities, 

and services in the area of research funding: 

– Mutual exchange of information on funds, 

projects, processes, and selection criteria will be 

improved. 

– Large cantonal cancer leagues that have their 

own research funding activities will follow mutually 

determined minimal requirements with regard 

to the evaluation process and the evaluation 

criteria used in the review of grant applications. 


Head of the Scientific Office, Swiss Cancer League 

Research funding by the cantonal cancer leagues 

– If needed, cantonal cancer leagues can call upon 

the support and competence of the SCL in the 

review of grant applications. 

– Small cantonal cancer leagues without their 

own research funding activities can help to fund 

research projects that have already been evaluated 

and are supported by the SCL. 

– At the policy level, SCL works for good framework 

conditions for research, especially clinical 

research. 

A further goal of the federation development project 

of the Cancer League is to improve the transparency 

of supported research projects and their results 

both within the organization as a whole and for the 

public, partners, and politics/government. To this 

purpose, the SCL conducted a written survey of the 

cantonal cancer leagues in the spring of 2011. 

In the following, detailed information on research 

funding by the cantonal and regional cancer leagues 

in the years 2009 and 2010 is presented. Information 

is provided not only on research projects funded but 

also for funding in the broader sense, which includes 

support given to cancer registries or cancer screening 

programmes. In principle the cantonal cancer 

leagues support research projects and institutions 

in their own cantons. In part the cantonal cancer 

leagues also supported research projects that the 

SCL and the Foundation Cancer Research Switzerland 

evaluated and approved for funding but did not 

fund in full. 

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32 

In total, eleven cantonal cancer leagues awarded an 

average of CHF 4.2 million per year for cancer research. 

Three-quarters of that amount was given to 

research by the four largest cantonal cancer leagues 

– Basel, Bern, Geneva, and Zurich. The average number 

of projects and institutions supported each year 

was 50 (Table 5). 

Table 5 

Research funding by the cantonal cancer leagues in 2009/2010 

Cantonal cancer leagues 

Number of projects 

and institutions 

supported 

in 2009/2010 

Amount granted 

in 2009/2010 

(in CHF) 

Number of projects 

and institutions 

supported, average 

per year 

Amount 

granted, 

average per year 

(in CHF) 

Aargau 3 335 386 2 167 693 

Basel 23 1 539 225 12 769 613 

Bern 16 920 000 8 460 000 

Geneva 15 1 984 270 8 992 135 

Grisons 3 65 000 2 32 500 

Neuchâtel 2 349 094 1 174 547 

Schaffhausen 2 50 000 1 25 000 

St. Gallen-Appenzell 3 588 300 2 294 150 

Ticino 10 541 560 5 270 780 

Thurgau 1 25 000 1 12 500 

Zurich 28 1 976 885 14 988 443 

Total 106 8 374 720 50 4 187 360

List of funded research projects, institutions, and programmes in 2009/2010 

The list shows the financial contributions granted in 2009 and/or 2010. 

Aargau Cancer League 

Krebsregister Aargau | 2009: CHF 228,442.– | 2010: CHF 32,444.– 

Beitrag an Konzeptarbeit zum Aufbau des Krebsregisters 

Künzler Alfred | 2010: CHF 44,500.– 

Externer Psychiatrischer Dienst, Kanton Aargau, Aarau/Baden 

Individualisierte psychoonkologische Psychotherapie: Inanspruchnahme, Inhalte und Evaluation 

des Therapieprozesses und der Ergebnisse 

Recker Franz | Kwiatkowski Maciej | 2009: CHF 30,000.– 

Klinik für Urologie, Kantonsspital Aarau, Aarau 

Erfassung der Prostata-Todesfälle im Kanton Aargau im Rahmen des Forschungsprogramms «Eine prospektive, 

randomisierte Studie zur aktiven Vorsorgeuntersuchung des Prostatakarzinoms für Männer zwischen 

55–70 Jahren im Kanton Aargau» 

Basel Cancer League 

Bentires-Alj Mohamed | 2010: CHF 140,000.– 

Friedrich Miescher Institut für biomedizinische Forschung (FMI), Basel 

Role of the tyrosine phosphatase SHP2 in breast cancer 

Bubendorf Lukas | Zlobec Inti | 2009: CHF 63,940.– 

Institut für Pathologie, Universitätsspital Basel, Basel 

Development of optimized criteria for EGFR status by fluorescence in situ hybridization in human carcinomas 

and application to cytology specimens 

Bubendorf Lukas | 2010: CHF 50,000.– 


– Swiss Lung Pathology Working Group 

– Lung Cancer Group SAKK (Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung) 

– Urogenital Tumors Project Group SAKK 

– New Technology Committee, International Academy of Cytology 

Evaluation von potenziellen Zielgenen innerhalb des 10q22-Amplikons beim Prostata- und Mammakarzinom 

Burger Bettina | 2009: CHF 40,000.– 

Departement Biomedizin, Universitätsspital Basel, Basel 

New approach for improvement of early diagnosis and prediction in familial adenomatous polyposis coli (FAP) 

by genetic analysis of skin involvement – APC mutations and their influence to lesions of skin 

Christofori Gerhard | 2010: CHF 170,000.– 

Institut für Biochemie und Genetik, Universität Basel, Basel 

The role of miRNAs in epithelial to mesenchymal transition (EMT) and cancer metastasis 

Fischer Claude | 2010: CHF 30,000.– 

Departement Otorhinolaryngologie, Universitätsspital Basel, Basel 

A new tumor issue based classification on head and neck squamous cell carcinoma according to HPV expression 

and cell cycle regulator proteins allows an individualized treatment modality choice for HPV positive and 

negative carcinomas 

Grüth Uwe | Rochlitz Christoph | 2009: CHF 30,000.– 

Brustzentrum/Frauenklinik, Universitätsspital Basel, Basel 

Monika Eichholzer 

Institut für Sozial- und Präventivmedizin, Universität Zürich, Zürich 

Entwicklung von Übergewicht und Adipositas beim Mammakarzinom und ihre Bedeutung für Diagnose und 

klinisches Management 

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Heinimann Karl | 2009: CHF 80,000.– 


Identification of (epi)genetic alterations in colorectal cancers from hereditary non-polyposis colorectal 

cancer (HNPCC) patients 

Hess Christian | Funk Georg A. | 2009: CHF 60,000.– 

Departement Forschung, Universitätsspital Basel, Basel 

In silico enhanced modelling to assess the risk for Epstein-Barr virus associated posttransplant lymphoproliferative 

disease (PTLD); a prospective cohort study 

Hynes Nancy | Wodnar-Filipowicz Aleksandra | 2010: CHF 50,000.– 


The involvement of bone marrow in breast carcinoma metastasis 

Loeffler Sébastien | 2009: CHF 104,880.– 


The role of Shoca-2 in tumor development 

Mamot Christoph | Wicki Andreas | Rochlitz Christoph | 2009: CHF 147,805.– 

Klinik für Onkologie, Universitätsspital Basel, Basel 

Expanding immunoliposomal strategies towards vascular endothelial cells (VEGFR-2) and vascular 

endothelial tip cells (VEGFR-3) 

Moroni Christoph | 2010: CHF 75,000.– 

Departement Biochemie, Universität Basel, Basel 

Identification of «essential» genes in human leukemia cells as biomarkers and targets for intervention 

Müller Philipp | 2010: CHF 39,800.– 


Generation of cellular reporter systems to monitor the maturation and T-cell stimulatory capacity of dendritic 

cells upon treatment with anti-tumor therapeutics 

Nagamine Yoshikuni | Bentires-Alj Mohamed | 2009: CHF 82,800.– 


Roles of the DEAH helicase RHAU in RAS-dependent cancers 

Rentsch Cyrill A. | 2010: CHF 30,000.– 

Departement Urologie, Universitätsspital Basel, Basel 

Ruiz Christian | Bubendorf Lukas 

Departement für Pathologie, Universität Basel, Basel 

Evaluation of nuclear receptor binding protein 1 (NRBP1) expression and function in prostate cancer 

Roth-Chiarello Michael | 2009: CHF 80,000.– 

Pulmonary Cell Research Laboratory, Departement Forschung, Universitätsspital Basel, Basel 

Reactivation of C/EBP-� expression in pleural malignant mesothelioma in order to stop proliferation 

Schwaller Jürg | 2009: CHF 25,000.– 


Developing targeted therapeutic strategies for childhood acute leukemia 

Schwaller Jürg | 2010: CHF 25,000.- 


HIV-cofactors as therapeutic targets for infant leukemia 

Tapia Coya | Bubendorf Lukas | Savic Spasenija | 2010: CHF 20,000.– 


ING4 silencing as a diagnostic marker in breast cancer 

Zanetti Dällenbach Rosanna | Fabbro Thomas | Obermann Ellen | Rochlitz Christoph | 

Tschudin Sibil | Wight Edward | 2010: CHF 25,000.– 

Universitätsspital Basel, Basel 

Schöneberger Cora-Ann 

Maurice E. Müller-Institut für Strukturbiologie, Departement Biozentrum, Universität Basel, Basel 

Improving breast cancer diagnostics by novel sonographic techniques

Zippelius Alfred | 2009: CHF 100,000.– 

Departement Innere Medizin, Universitätsspital Basel, Basel 

Anti-tumor immunity upon treatment with chemotherapy and radiotherapy – potential synergism with specific 

immunotherapy approaches 

Zlobec Inti | Lugli Alessandro | 2010: CHF 70,000.– 


Investigation on possible intratumoral heterogeneity of K-RAS and B-RAF gene mutations in matched primary 

and metastatic colorectal cancer 

Bern Cancer League 

Angst Eliane | 2010: CHF 50,000.– 

Universitätsklinik für viszerale Chirurgie und Medizin, Inselspital Bern, Bern 

How does N-myc downstream regulated gene-1 affect the development, aggressiveness and host-tumor 

interaction of pancreatic cancer? 

Christe Andreas | 2010: CHF 70,000.– 

Universitätsinstitut für diagnostische, interventionelle und pädiatrische Radiologie, Inselspital Bern, Bern 

Optimal low-dose levels in CHEST-computed-tomography (CT) for minimal patient radiation and unimpaired 

detection of lung nodules and nodule volume measurement 

Frese Steffen | 2010: CHF 50,000.– 

Departement für klinische Forschung, Universität Bern, Bern 

Transcriptional regulation of sensitization to TRIAL-induced apoptosis in lung cancer cells 

Hegyi Ivan | 2010: CHF 50,000.– 

Klinik für Dermatologie, Inselspital Bern, Bern 

Identification of novel diagnostic and predictive tumor biomarkers for oral squamous cell carcinoma (OSCC) 

Hunger Robert | 2009: CHF 60,000.– 

Klinik für Dermatologie, Inselspital Bern, Bern 

Immuntherapie von Patienten mit kutanem T-Zell-Lymphom mit Telomerase-spezifischen Peptiden 

Karoubi Golnaz | 2009: CHF 90,000.– 

Forschungsgruppe Thoraxchirurgie, Departement für klinische Forschung, Universität/Inselspital Bern, Bern 

Isolation and characterization of cancer stem cells from human lung adenocarcinoma 

Klaeser Bernd | 2010: CHF 50,000.– 

Universitätsklinik für Nuklearmedizin, Inselspital Bern, Bern 

A new concept for breast imaging: breast-PET with multi-parametic tumor characterization and visualization 

by integration of metabolical and morphological imaging modalities and voxel-wise kinetic modeling 

Kuehni Claudia | 2009: CHF 34,000.– 

Institut für Sozial- und Präventivmedizin, Universität Bern, Bern 

The impact of prediagnostic symptomatic interval on mortality in childhood acute lymphoblastic leukemia – 

a cohort study 

Parmentier Laurent | 2010: CHF 21,000.– 


Secondary prevention of skin cancers and field concretization in organ-transplant-patients: 

open-label, comparative study evaluation of the impact of sequential mal-pdt 

Saar Bettina | 2009: CHF 10,000.- 

Universitätsinstitut für diagnostische, interventionelle und pädiatrische Radiologie, Universität/Inselspital Bern, Bern 

Bern cohort study of patients with hepatocellular carcinoma 

Stickel Felix | 2009: CHF 100,000.- 

Institut für klinische Pharmakologie und viszerale Forschung, Universität Bern, Bern 

Epithelial-to-mesenchymal transition in cholangiocarcinogenesis: functional role of �V � 6 integrin 

Stroka Deborah | 2010: CHF 90,000.– 


Targeting SIRT1 for the treatment of liver cancer 

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36 

Tschan Mario | 2009: CHF 60,000.– 


Characterization of microRNAs with a role in the pathogenesis of acute myeloid leukemia 

Vassella Erik | 2009: CHF 60,000.– 

Institut für Pathologie, Universität Bern, Bern 

Role of tumor suppressor microRNAs located at regions which are frequently deleted in oligodendrogliomas 

for their role in conferring chemo resistance, proliferation and differentiation of glioma tumors 

Zehnder Pascal | 2010: CHF 40,000.– 

Klinik für Urologie, Inselspital Bern, Bern 

Electrophysiological assessment of the male canine pelvic autonomic neural anatomy and translation 

to the perioperative human setting in the context of nerve-sparing radical cystectomy 

Zimmer Yitzhak | 2009: CHF 85,000.– 


Role of KRAS mutations in the response of tumor cells with oncogenic MET expression to anti MET targeted 

therapy 

Geneva Cancer League 

Ansari Marc | 2010: CHF 140,000.– 

Unité d’onco-hématologie, Hôpital des enfants, Genève 

La pharmacogénomic chez les enfants atteints de cancer 

Bridevaux Pierre-Olivier | 2010: CHF 50,000.– 

Service de pneumologie, Département de médecine interne, Hôpitaux universitaires de Genève (HUG), Genève 

Short-term pre-operative rehabilitation for patients with lung cancer: a randomized trial 

Clément Virginie | Radovanovic Ivan | Schatlo Bawarjan | 2009: CHF 86,140.– 

Service de neurochirurgie, Département des neurosciences cliniques, Hôpitaux universitaires de Genève (HUG), 

Genève 

Identification and characterization of biomarkers in human brain tumors and brain cancer-initiating cells 

Dietrich Pierre-Yves | 2009: CHF 97,500.– | 2010: CHF 101,300.– 

Service d’oncologie, Département de médecine interne, Hôpitaux universitaires de Genève (HUG), Genève 

Identification of glioma specific antigens: a step towards the development of multi-peptide vaccine 

Dietrich Pierre-Yves | 2009: CHF 177,540.– 


Soutien financier pour «Achat d’un cytomètre analyseur FACSCantoTMII» 

Dietrich Pierre-Yves | 2009: CHF 25,000.– 


Passweg Jakob 

Service d’hématologie, Département de médecine interne, Hôpitaux universitaires de Genève (HUG), Genève 

Soutien extraordinaire en vue de la campagne de vaccination contre la grippe H1N1 

Gumy Pause Fabienne | 2009: CHF 20,000.– | 2010: CHF 60,000.– 

Unité d’onco-hématologie pédiatrique, Département de pédiatrie, Hôpitaux universitaires de Genève (HUG), 

Genève 

ATM gene analysis in neuroblastoma 

Kern Lise | 2009: CHF 60,000.– 

Service de médecine de laboratoire & Service de pédiatrie, Hôpitaux universitaires de Genève (HUG), Genève 

Contribution de l’analyse de la méthylation du promoteur du gène MLH1 dans la stratégie de dépistage 

du syndrome de Lynch ou du syndrome du cancer colorectal héréditaire non polyposique (HNPCC) 

Kindler Vincent | 2010: CHF 108,000.– 


Immunomodulation of tumor cell growth by mesenchymal stromal cells: relevance of graft-versus host disease 

and graft-versus leukemia effect in patients reconstituted with allogenic hematopoietic stem cells

Kridel Robert | 2010: CHF 100,000.– 


Bourse de chercheur débutant «Ligue genevoise contre le cancer et Fondation Dr. Henri Dubois-Ferrière 

Dinu Lipatti» 

Mach Nicolas | 2010: CHF 96,600.– 


Développement d’un nouveau concept de traitement anti-cancéreux combinant deux approches innovatives 

dans le domaine de l’immunomodulation: thérapie cellulaire et bloquage de CTLA-4 

Mathes Thomas | Imhof Beat | 2009: CHF 96,667.– | 2010: CHF 96,667.– 


Role of junctional adhesion molecule C (JAM-C) in normal B cell differentiation and in the malignant proliferation 

of B-cells from lymphoproliferative syndromes 

Reith Walter | 2009: CHF 43,900.– | 2010: CHF 43,900.– 

Département de pathologie et d’immunologie, Faculté de médecine, Centre médical universitaire (CMU), Genève 

Identification des fonctions cellulaires et gènes régulés par le microARN oncogénique, microARN-155 

Rodriguez Yvan | 2010: CHF 70,000.– 

Département de génétique et évolution, Université de Genève, Genève 

Diagnostic olfactif des mélanomes 

Sappino André-Pascal | 2009: CHF 120,000.– | 2010: CHF 100,000.– 

Unité d’oncogénétique et de prévention des cancers, Service d’oncologie, Hôpitaux universitaires 

de Genève (HUG), Genève 

The ATM gene in carcinogenesis

38 

Schick Ulrike | 2010: CHF 100,000.– 

Radio-oncologie, Département de médecine interne, Hôpitaux universitaires de Genève (HUG), Genève 

Bourse de chercheur débutant «Ligue genevoise contre le cancer et Fondation Dr Henri Dubois-Ferrière 

Dinu Lipatti» 

Walker Paul | 2009: CHF 95,528.– | 2010: CHF 95,528.– 


Reconnaissance d’un antigène tumoral exprimé par les gliomes: le potentiel des cellules T de faible avidité 

pour l’immunothérapie 

Grisons Cancer League 

Buchli Christian | 2009: CHF 15,000.– | 2010: CHF 15,000.– 

Klinik für Chirurgie, Kantonsspital Graubünden, Chur 

Stipendium I und II zur Studie kolorektale Chirurgie/Rektumkarzinom 

Cathomas Richard | Köberle Dieter | Ruhstaller Thomas | Mayer Gisela | Räss Andrea | Mey Ulrich | 

von Moos Roger | 2009: CHF 20,000.– 

Departement für medizinische Onkologie, Kantonsspital Graubünden, Chur 

Oxaliplatin infusion in combination with capecitabine for metastatic colorectal carcinoma: 

can it reduce neuropathy? 

Cathomas Richard | von Moos Roger | 2009: CHF 15,000.– 

Departement für medizinische Onkologie, Kantonsspital Graubünden, Chur 

Granatapfelstudie PSA-Bio-Studie: Randomisierte Phase-IIb-Doppelblindstudie zur Testung der Wirkung 

von natürlichem Fruchtgetränk auf den PSA-Wert von Prostatakarzinompatienten 

Neuchâtel Cancer League 

Registre neuchâtelois des tumeurs | 2009: CHF 148,662.– | 2010: CHF 200,432.– 

Beitrag an Krebsregister 

Schaffhausen Cancer League 

Egger Matthias | 2009: CHF 25,000.– | 2010: CHF 25,000.– 


Stuck Andreas 

Geriatrische Abklärungsstation, Inselspital Bern, Bern 

Cancer epidemiology in older adults: population-based research of trends and factors associated with cancer 

mortality in Switzerland, 1990 – 2007 

St Gallen-Appenzell Cancer League 

Burkhard Ludewig | 2009: CHF 150,000.– 

Institut für Immunbiologie, Kantonsspital St. Gallen, St. Gallen 

Multiepitop-Impfung von Grad III/IV Melanompatienten mit dendritischen Zellen: Bedeutung von 

Peptidaffinität und -dichte für die optimale Generierung von tumorspezifischen zytotoxischen T-Lymphozyten 

Krebsregister St. Gallen-Appenzell | 2009: CHF 210,000.– | 2010: CHF 228,300.– 

Beitrag an Krebsregister

Thurgau Cancer League 

Biotechnologie-Institut Thurgau (BITG) | 2010: CHF 25,000.– 

in Kreuzlingen und an der Universität Konstanz, Deutschland 

Beitrag an einen neuen Zellsorter für die anwendungsorientierte Grundlagenforschung zur Entstehung und 

Behandlung von Krebs 

Ticino Cancer League 

Carbone Giuseppina | 2009: CHF 70,000.– | 2010: CHF 65,000.– 

Laboratorio di oncologia sperimentale, Istituto oncologico della Svizzera italiana (IOSI), Bellinzona 

MicroRNA network regulated by ETS transcription factors in prostate cancer 

Frattini Milo | 2009: CHF 55,000.– | 2010: CHF 50,000.– 

Laboratorio di diagnostica molecolare, Istituto cantonale di patologia (ICP), Locarno 

Investigation of the role of NEU3 in colorectal carcinogenesis and in the prediction of efficacy of EGFR 

targeted therapies 

Grassi Fabio | 2009: CHF 50,000.– | 2010: CHF 40,000.– 

Istituto di ricerca in biomedicina (IRB), Bellinzona 

Purinergic signaling in the pathophysiology of central nervous system infiltration in T-cell leukemia 

Molinari Francesca | 2010: CHF 46,560.– 


Characterization of Ras and BRAF mutations in GIST patients 

Napoli Sara | 2009: CHF 70,000.– 


Noncoding promoter-associated RNA and small RNA based transcriptional regulatory networks in cancer cells: 

mechanisms and therapeutic applications 

Thelen Marcus | 2009: CHF 55,000.– | 2010: CHF 40,000.– 

Istituto di ricerca in biomedicina (IRB), Bellinzona 

Detailed study of the interactions and subcellular distribution of the tumorigenic chemokine receptor 

CXCR7/RDC1 in lymphocytes 

Zurich Cancer League 

Arcaro Alexandre | 2009: CHF 64,777.– 

Klinik für Onkologie, Kinderspital Zürich, Universitäts-Kinderkliniken, Zürich 

Targeting P13K isoforms in human glioblastoma 

Arni Stephan | Weder Walter | 2010: CHF 64,668.– 

Klinik für Thoraxchirurgie, UniversitätsSpital Zürich, Zürich 

Activity based protein profiling in human lung cancer biopsies 

Bergsträsser Eva | 2009: CHF 51,048.– 

Kompetenzzentrum für pädiatrische Palliative Care, Kinderspital Zürich, Zürich 

Kuehni Claudia E. 


The Swiss childhood cancer survivor study: socio-economic outcomes in adulthood 

Bernasconi Michele | Schäfer Beat | 2009: CHF 63,777.– | 2010: CHF 67,668.– 

Zentrum für klinische Forschung, Departement für pädiatrische Onkologie, Kinderspital Zürich, Zürich 

Development of targeting systems for improved drug delivery and imaging of pediatric soft tissue sarcomas 

based on tumor specific peptides 

Favrot Claude | 2009: CHF 115,938.– 

Klinik für Kleintiermedizin, Vetsuisse Fakultät, Universität Zürich, Zürich 

Characterization of newly discovered canine papillomavirus 3 (CBV3) and assessment of its carcinogenic 

potential 

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40 

Felley-Bosco Emanuela | 2009: CHF 59,874.– 

Institut für molekulare Onkologie, UniversitätsSpital Zürich, Zürich 

Alterations in NF2 signaling pathway in malignant pleural mesothelioma 

Felley-Bosco Emanuela | 2010: CHF 51,353.– 


Sonic hedgehog signaling in malignant pleural mesothelioma 

Fontana Adriano | Birchler Thomas | 2009: CHF 60,828.– 

Institut für experimentelle Immunologie, Universität Zürich, Zürich 

Is fatigue and tumor development in EBV infection due to clock gene dysfunction? 

Gorr Thomas A. | Vogel Johannes | 2009: CHF 62,342.– | 2010: CHF 66,932.– 

Institut für Veterinärphysiologie, Vetsuisse Fakultät, Universität Zürich, Zürich 

Chorio-allantoic membrane assay for preclinical cancer therapy screening: simultaneous targeting of tumor 

vasculature and the metabolic symbiosis between oxygenated and hypoxic tumor cells 

Grotzer Michael | 2009: CHF 108,850.– 

Klinik für Onkologie, Kinderspital Zürich, Universitäts-Kinderkliniken, Zürich 

Identification and validation of novel c-Myc target genes in childhood medulloblastoma 

Heinzelmann Viola | 2009: CHF 58,412.– 

Institut für Frauenheilkunde und Gynäkologie, UniversitätsSpital Zürich, Zürich 

Wnt signaling in ovarian cancer SFRP4 and FGF9 as key regulators of the Wnt-Signaling pathway in ovarian 

cancer acronym: WOC-Study 

Hornung Rainer | 2009: CHF 26,834.– 

Psychologisches Institut, Universität Zürich, Zürich 

Parents caring for a child with a life-limiting illness: an assessment of individual and dyadic coping and 

personal growth 

Krek Wilhelm | 2009: CHF 130,106.– 

Institut für Zellbiologie, ETH Zürich, Zürich 

URI, a potential novel oncogene product in hepatocellular carcinoma 

Kristiansen Glen | 2010: CHF 48,000.– 

Institut für klinische Pathologie, Universität Zürich, Zürich 

Müntener Michael 

Klinik für Urologie, UniversitätsSpital Zürich, Zürich 

Funktionelle Analyse von CANT1 als neues Therapieziel und seine Eignung als diagnostischer Marker 

des Prostatakarzinoms 

Marra Giancarlo | 2010: CHF 134,601.– 

Institut für molekulare Krebsforschung, Universität Zürich, Zürich 

Functional characterization of KIAA1199: toward a novel biomarker of colorectal neoplasia 

Marti Thomas | Felley-Bosco Emanuela | Stahel Rolf A. | 2009: CHF 73,212.– 


Modulation of translesion synthesis: impact on chemotherapy resistance in malignant pleural mesothelioma 

Moch Holger | Rechsteiner Markus | 2009: CHF 100,000.– 

Institut für klinische Pathologie, Universität Zürich, Zürich 

VHL mutation analyses for risk profiling of sporadic clear cell RCC 

Müller Anne | 2009: CHF 55,828.– | 2010: CHF 59,932.– 


Prevention of gastric cancer through the development of a Helicobacter vaccine 

Nadal David | 2009: CHF 63,777.– 

Klinik für Infektiologie, Kinderspital Zürich, Zürich 

TLR9 agonist cancer therapy is rather detrimental than beneficial in EBV-harboring tumors 

Riediger Thomas | 2009: CHF 65,342.– 

Institut für Veterinärphysiologie, Vetsuisse Fakultät, Universität Zürich, Zürich 

Blockade of the pro-inflammatory neuromodulator nitric oxide as a possible clinical approach 

to treat cancer anorexia

Weller Michael | 2010: CHF 65,828.– 

Klinik für Neurologie, UniversitätsSpital Zürich, Zürich 

Dehler Silvia 

Krebsregister des Kantons Zürich, Zürich 

Ohgaki Hiroko 

International agency for research on cancer (IARC), WHO, Lyon, France 

A population-based study on glioblastoma in the Canton of Zurich 

Wollscheid Bernd | 2010: CHF 82,668.– 

Institut für molekulare Systeme, ETH Zürich, Zürich 

Quantitative proteomic analysis of Hodgkin’s and non-Hodgkin’s lymphoma plasma membrane glycoproteins 

Wüest Thomas | Renner Christoph | 2009: CHF 57,342.– | 2010: CHF 64,248.– 

Klinik für Onkologie, UniversitätsSpital Zürich, Zürich 

Fuchs Bruno | Muff Roman 

Forschungslabor Orthopädie, Klinik Balgrist, Zürich 

Sensitation of sarcomas for chemotherapy by tumor cell targeted TNF-Fusion 

Zaugg Kathrin | 2010: CHF 52,700.– 

Klinik für Radio-Onkologie, UniversitätsSpital Zürich, Zürich 

Carnitine palmitoyltransferase 1C (CPT1C): a novel p53-dependent regulator of human cancer resistance 

against hypoxia 

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Since 2003 the Foundation Cancer Research Switzerland 

(formerly Oncosuisse) has supported translational 

and clinical research with two funding programmes: 

Collaborative Cancer Research Projects 

(CCRP) and International Clinical Cancer Research 

Groups (ICP). The aim of both the CCRP and ICP is 

to support collaboration among different research 

disciplines and institutes at the national level – and in 

the case of the ICP at the international level. 

Collaborative Cancer Research Projects (CCRP) 

Cancer research is a complex undertaking, especially 

due to the enormous advances in molecular genetics 

in recent decades. Today it is impossible for individual 

disciplines or research teams to have an overview 

of this complexity. Central questions can only 

be tackled with close cooperation among various 

specialist areas and institutes. And it often takes 

many years or decades until a discovery in the laboratory 

finally results in a clinical application for patients. 

The CCRP are multidisciplinary research collabora- 

tions with a longer-term duration of five or more 

years. The focus is on supporting translational research 

studies that shorten the way from the laboratory 

to the hospital bed and thus seek to boost medical 

progress. The research projects are often complex 

and made up of several subprojects that are conducted 

at different institutes. The aim is for diverse 

specialists in research and medicine to pursue a common 

objective, exchange their ideas, expertise, and 

findings, and in this way to improve and accelerate 

the knowledge gain. 

Programme research: Supporting translational and 

clinical research 


Communications manager at the Scientific Office, Swiss Cancer League 

International Clinical Cancer Research Groups 

(ICP) 

In contrast to basic research in Switzerland, which is 

among the world’s best, clinical cancer research in 

this country is faced with a number of political, structural, 

and monetary difficulties. Over the last three 

decades, this has caused Swiss clinical research to 

drop down into the midfield in an international 

comparison. Supporting clinical research is therefore 

a pressing concern not only for the Swiss Cancer 

League and the Foundation Swiss Cancer Research. 

The ICP are clinical research groups in which re- 

searchers and physicians in several countries work 

together. These international research projects have 

their centres in Switzerland, which means that they 

are coordinated and managed from within Switzerland. 

A research group in the ICP programme receives 

funding of maximum CHF 200,000 per year, 

or a total of CHF 800,000 over the four years of the 

project duration. 

Since the funding launch, total grants of CHF 14.7 

million have been provided for programme research 

(in the period 2004 to 2010), of which CHF 10.1 million 

went to six CCRP and CHF 4.6 million went to 

seven ICP. The CCRP, which earmarked large funds, 

were discontinued in 2009 in favour of the better

manageable funding of individual projects. ICP calls 

for proposals are also no longer being announced. 

Instead, since 2009 funding has been given to clinical 

research institutions via research contracts and 

agreements (see here the article on research funding 

on page 6).

44 

Collaborative Cancer Research Projects (CCRP) 

List of funded research projects 

Brisken Cathrin et al. | CCRP OCS 01448-12-2003 | CHF 1,750,000.– 

Institut suisse de recherche expérimentale sur le cancer (ISREC), Faculté sciences de la vie, EPF de Lausanne, 

Lausanne 

The role of Wnt signalling in breast cancer 

Hemmings Brian A. | CCRP OCS 01613-12-2004 | CHF 800,000.– 


Development of molecular strategies for therapeutic interference with glioblastomas 

Continuation of the project: 

Merlo Adrian et al. | CCRP OCS 01613-12-2004 | CHF 1,276,200.– 

Neurochirurgische Klinik, Universitätsspital Basel, Basel 

Development of molecular strategies for therapeutic interference with glioblastomas 

Krek Wilhelm et al. | CCRP OCS 01262-06-2002 | CHF 1,684,900.– 


Identification of molecular signatures of human prostate cancer and their validation in animal models and 

application in the clinics 

Rüegg Curzio et al. | CCRP OCS 01812-12-2005 | CHF 2,209,500.– 

Division de pathologie expérimentale, Université de Fribourg, Fribourg 

Tumor-mediated mobilization of bone marrow cells: Implications in tumor angiogenesis, lymphangiogenesis 

and metastasis, and disease monitoring 

Sommer Lukas et al. | CCRP OCS 01972-12-2006 | CHF 1,898,500.– 

Abteilung Zell- und Entwicklungsbiologie, Anatomisches Institut, Universität Zürich, Zürich 

Neural crest-derived cancer stem cells in melanoma and Merkel cell carcinoma: Their role in initiation, 

progression and therapeutic response 

The funded research projects in brief 

Brisken Cathrin et al. | The role of Wnt signalling 

in breast cancer 

CCRP OCS 01445-12-2003 

Duration: 01.07.2004 – 31.06.2009 

CHF 1,750,000.– 

Breast cancer affects one out of 8 women in Western 

countries. In Switzerland 1,300 women die each year of 

the disease. Over the past years, there has been an increase 

in targeted therapies. In contrast to traditional 

chemotherapies, these aim at interfering with specific 

molecular signals. Herceptin © is one example of a drug 

that blocks a specific growth factor receptor (ErbB). 

In the course of this project we examined the role of the 

wnt signalling cascade in breast cancer development. Our 

aim was to provide biological insights for novel molecularbased 

therapeutic approaches. The wnt family comprises 

a number of signalling molecules that influence the development 

of colon cancer and melanoma. They bind to re- 

ceptors on the cell surface, which in turn send signals to 

the cell nucleus via the protein �-catenin. This results in 

the activation of target genes and the synthesis of new 

proteins. We analyzed the role of this signalling cascade in 

the development of breast cancer and found that it has a 

role both early on as well as at later stages of the disease. 

Three groups with different expertise collaborated in this 

project: Using the mouse model, Cathrin Brisken’s group 

demonstrated that the wnt signalling cascade is activated 

in the course of the hormonal cycle by the pregnancy hormone 

progesterone. Activation of wnt signalling results in 

cell proliferation. Together with pathologist Maryse Fiche, 

we analyzed breast epithelial and stromal cells from normal 

breast tissue and breast tumour samples and showed 

that activation of wnt signalling in normal human breast 

cells also results in increased cell proliferation. Nancy 

Hynes’ team examined the connection between wnt signalling 

and activation of the epidermal growth factor receptor 

EGFR/Erb1. That team showed that wnt signalling

enhances breast cancer cell motility – a finding that has 

important implications at later stages of the disease when 

tumour cells infiltrate into surrounding tissue and metastasize. 

Project coordinator 

Prof. Dr Cathrin Brisken 

Swiss Institute for Experimental Cancer 

Research (ISREC) 

School of Life Sciences 

Swiss Federal Institute of Technology 

Lausanne (EPFL) 

NCCR Molecular Oncology 

SV2.832, Station 19 

CH-1015 Lausanne 

Phone +41 (0)21 693 07 81 

Fax +41 (0)21 693 07 40 

cathrin.brisken@epfl.ch 

In collaboration with: 

– Dr. Maryse Fiche, Institut universitaire de pathologie, 

CHUV, CH-1011 Lausanne 

– Prof. Dr. Nancy Hynes, Friedrich Miescher Institute 

for Biomedical Research, CH-4058 Basel 

Hemmings Brian A. | Development of molecular 

strategies for therapeutic interference with glioblastomas 

KFP OCS 01613-12-2004 

Duration 01.01.2006 – 01.09.2011 

CHF 2,076,200.– 

Continuation of the project of Merlo Adrian et al. Neurochirurgische 

Klinik, Universitätsspital Basel, Basel 

Glioblastoma multiforme (GBM) is the most aggressive 

and lethal form of brain cancer, with a mean patient 

survival time of one year, with less than 10 % of patients 

surviving over five years. The high malignancy and low 

survival rates of GBM have been attributed to treatment 

resistance and invasion to the adjacent normal brain. Past 

experimental studies have identified protein kinases as 

potential therapeutic targets; however, the response rates 

of inhibitors of PDGF, VEGF and EGF receptors (overexpressed 

in GBM) have been somewhat disappointing in 

clinical studies. Therefore, there is currently a desperate 

need to identify the molecular mechanisms of therapy 

resistance and driving kinases which might be the Achilles 

heel of GBM. 

In a search for novel molecular targets, our kinome-focused 

microarray analysis identified overexpressed protein 

kinase expression in fresh brain tumours including primary 

and secondary glioblastoma, astrocytoma and oligodendroglioma. 

The study identified targets that have been 

previously associated with gliomagenesis (e.g. EGFR or 

PDGFR), as well as novel kinases that have not been previously 

reported in GBM. Our recent work has focused on 

the most promising novel targets that were highly overexpressed 

and activated in human gliomas. 

MAP kinase-interacting kinase 1 (MNK1) was highly expressed 

in GBM compared to normal brain, and its elevated 

protein level was confirmed in primary GBMs and in 

glioma cell lines. Targeting MNK1 activity together with 

rapamycin induced cell cycle arrest and strongly inhibited 

global translation and GBM cell proliferation. Furthermore, 

MNK1-signalling converged with TGF-� pathways 

and regulated glioma cell motility, identifying MNK1 

pathway as an attractive point for therapeutic intervention. 

TAM family of receptor tyrosine kinases (TAM-TKs) 

was shown to be overexpressed in gliomas and promoted 

survival in vitro upon etoposide treatment independent 

of PI3K/PKB and MAPK signalling. TAM-TK may thus mediate 

GBM resistance to therapy, which is a major obstacle 

in GBM treatment. Two other tyrosine kinases and 

their upstream receptors that are found normally only in 

haematopoietic cells were highly overexpressed in brain 

tumour samples, GBM cell lines and cancer spheres. Strikingly, 

treatment with two specific small molecule inhibitors 

strongly blocked basal and EGFR (hyperactivated 

in the most of GBMs) mediated proliferation and migration 

of GBM cells. Due to the known driving roles of these 

kinases, we will further investigate their role in GBM animal 

models to establish optimal therapeutic interference. 

Our study has analyzed signalling networks and has been 

the platform to establish the potential of identified deregulated 

pathways for development of novel targeted 

thera pies, as well as diagnostics and prognostic markers 

for gliomas. If our in vitro results are reflected in in vivo 

animal models, then inhibition of these kinases could be 

in fact novel therapeutic treatments that will ultimately 

improve the life quality of brain cancer patients. 


Dr. Brian A. Hemmings 

Friedrich Miescher Institut für 

biomedizinische Forschung (FMI) 

Maulbeerstrasse 66 

CH-4058 Basel 

Phone +41 (0)61 697 48 72 

Fax +41 (0)61 697 39 76 

brian.hemmings@fmi.ch 

Krek Wilhelm et al. | Identification of molecular 

signatures of human prostate cancer and their validation 

in animal models and application in the clinics 

KFP OCS 01262-06-2002 

Duration: 01.04.2008 – 01.04.2010 

CHF 684,900.– 

Prostate cancer is a frequent cause of death among men 

in Western countries. The causes underlying the development 

of prostate cancer are still incompletely defined. 

There are several risk factors contributing to prostate cancer 

development, including the environment, lifestyle and 

genetic predisposition. At early stages, prostate cancer is 

asymptomatic. However, as it progresses, it can take on 

aggressive behaviour leading ultimately to metastasis. It 

would therefore be highly desirable to define highly sensitive 

and specific molecular biomarkers that allow precise 

early diagnosis of prostate cancer, an accurate prognosis 

of the disease and predictions as to the response to specific 

therapies. 

In this project, researchers from different disciplines ranging 

from cancer biology and pathology to proteomics, 

computer sciences and clinical oncology collaborated to 

develop innovative strategies for the discovery of novel 

biomarker signatures for prostate cancer. The starting point 

of this project was the PTEN tumour suppressor gene, 

which is functionally inactivated in about 60 % of human 

prostate cancer patients. The loss of PTEN function in 

45

prostate epithelial cells leads to uncontrolled cell proliferation. 

In the first step of the new strategy, the PTEN gene 

was inactivated in the mouse in a prostate-specific manner, 

resulting in the development of prostate cancer in the 

mouse. Through the application of high-throughput proteomic 

analysis, hundreds of prostate-specific cell surface 

proteins were then identified and catalogued. The comparison 

of the protein data sets derived from healthy prostate 

tissue and prostate cancer tissue of the mouse then 

allowed the identification of a protein signature typical 

for the mutant version of PTEN and hence also prostate 

cancer. The second step of the strategy encompassed the 

validation of this new biomarker signature in tissue and 

serum samples of prostate cancer patients. This involved 

a comparative analysis of the identified signature in prostate 

cancer patients and control groups. Importantly, this 

work allowed the identification of a serum biomarker signature 

for the accurate diagnosis of prostate cancer in 

man. These new biomarkers must now be further tested 

and validated in larger clinical studies for their utility as a 

new suitable diagnostic test. 

The strategy developed within this project represents an 

important next step for the development and application 

of serum biomarkers that make it possible to predict the 

presence of prostate cancer with high precision, stability 

and reproducibility. This progress was only possible 

through an interdisciplinary research effort involving cancer 

biologists, proteomic experts, pathologists, computational 

scientists and clinical oncologists. 


Prof. Dr. Wilhelm Krek 

Institut für Zellbiologie 

ETH Hönggerberg 

HPM F42 

CH-8093 Zürich 

Phone +41 (0)44 633 34 47 

Fax +41 (0)44 633 13 57 

wilhelm.krek@cell.biol.ethz.ch 


– Prof. Dr. Rudolf Aebersold, ETH Zürich, Institute of 

Molecular Systems Biology, CH-8093 Zürich 

– Prof. Dr. Thomas Cerny, Fachbereich Onkologie/ 

Hämatologie, Dept. Innere Medizin, Kantonsspital, 

CH-9007 St. Gallen 

– Dr. Silke Gillessen, Kantonsspital, CH-9007 St. Gallen 

– Prof. Dr. Holger Moch, Universitätsspital Zürich, 

Institut für klinische Pathologie, CH-8091 Zürich

Rüegg Curzio et al. | Tumor-mediated mobilization of 

bone marrow cells: Implications in tumor angiogenesis, 

lymphangiogenesis and metastasis, and disease monitoring 

KFP OCS 01812-12-2005 

Duration: 01.11.2006 – 01.11.2011 

CHF 2,209,500.– 

Whereas localized cancer can be cured with a good success 

rate nowadays, metastatic, advanced cancers remain 

difficult to cure. The ability to detect and interfere with invasion 

and metastasis may open up new diagnostic, prognostic 

and therapeutic opportunities. The formation of 

“tumour vasculature” (i.e. tumour angiogenesis) is an important 

event contributing to tumour growth and metastasis. 

Since 2004 a treatment inhibiting the formation of 

tumour blood vessels has been in use in the clinic and prolongs 

survival of patients with metastatic cancers. In spite 

of this success, many important questions remain open on 

the use of anti-angiogenic drugs in patients, in particular 

how to assess angiogenesis, how to improve the use of 

these drugs and how to detect early events leading to metastasis. 

For example, bone marrow-derived cells are attracted 

to tumour sites to promote tumour angiogenesis, 

invasion and metastasis by releasing many growth factors, 

but the mechanisms involved are not fully understood. 

Goal 

The first goal of this project is to identify mechanisms by 

which bone marrow-derived cells promote tumour progression 

and metastasis as a basis for the development of 

novel therapeutic approaches to suppress metastasis. The 

second goal is to use these cells as indicators of tumour 

angiogenesis and metastatic spreading for early diagnosis 

and monitoring of cancer progression and therapy. 

Methods 

To address these questions we will combine molecular, 

cellular, and animal experiments with clinical studies. In 

animal studies we will use mouse tumour models to follow 

up the effect of the growing tumour on the mobilization 

of bone marrow-derived cells and of therapeutic interventions. 

Animal experiments are still necessary to study angiogenesis 

and metastasis, but whenever possible we will 

use substitution experiments in culture. In culture experiments 

we will study changes in function of these cells, and 

with molecular biology experiments and genetic experiments 

we will modify cells or mice to validate mechanisms. 

Analysis in patients will be limited to blood samples. 

Results 

We have obtained novel insights into the possible use of 

circulating bone marrow-derived cells for the monitoring 

of angiogenesis and have uncovered new potential therapeutic 

targets. Specifically we have: identified novel circulating 

bone marrow-derived cells as candidate biomarkers 

of angiogenesis; described a novel mechanism by which 

tumours instruct bone marrow progenitor cells to acquire 

pro-angiogenic properties; completed a clinical study 

aimed at validating preclinical results; characterized the 

role of two endothelial cell molecules in angiogenesis and 

shown that their inhibition suppresses tumour growth. 

Benefits for patients 

The results obtained in this project have three potential 

implications: 

– Prognosis/prediction: Results may allow the identification 

of patients at risk of developing metastases, 

which would be treated accordingly. Obtained results 

will help to design new clinical studies. 

– Monitoring: Detected parameters may be used to 

monitor patients during therapy to evaluate treatment 

efficacy. New clinical studies are currently being 

planned. 

– Therapy: Tools generated by this project may translate 

into new therapeutic approaches to suppress tumour 

spreading to lymph nodes and to distant sites. Drug 

development is beyond the scope of this application. 

However, if some of the tools developed in preclinical 

experiments appear particularly promising, we will 

establish appropriate collaborations with biotech or 

pharmaceutical companies. 


Prof. Dr Curzio Rüegg 

Department of Medicine 

Faculty of Science 

University of Fribourg 

1, rue Albert-Gockel 

CH-1700 Fribourg 

Phone +41 (0)26 300 87 66 

Fax +41 (0)26 300 97 33 

curzio.ruegg@unifr.ch 


– Prof. Dr. Gerhard Christofori, Institut für Biochemie 

und Genetik, Departement Biomedizin, 

Universität Basel, Mattenstrasse 28, CH-4058 Basel 

– Prof. Dr. Beat A. Imhof, Département de pathologie et 

immunologie, Faculté de médecine, Centre médical 

universitaire (CMU), Université de Genève, 

rue Michel-Servet 1, CH-1211 Genève 

– Prof. Dr. Christoph Rochlitz, Departement Biomedizin, 

Universität Basel, CH-4031 Basel 

– Prof. Dr. Cristiana Sessa, Istituto oncologico della 

Svizzera italiana (IOSI), Ospedale San Giovanni, 

CH-6500 Bellinzona 

– Prof. Dr. Roger Stupp, Multidisciplinary Oncology 

Center, Centre hospitalier universitaire vaudois 

(CHUV), CH-1011 Lausanne 

Sommer Lukas et al. | Neural crest-derived cancer 

stem cells in melanoma and Merkel cell carcinoma: 

Their role in initiation, progression and therapeutic 

response 

CCRP OCS 01972-12-2006 

Duration: 01.01.2008 – 31.12.2012 

CHF 1,898,500.– 

Cancer stem cells represent an emerging field for cancer 

research because of the increasing evidence that these 

cells have the capacity to sustain tumour formation and 

regeneration. Similar to normal stem cells, cancer stem 

cells display self-renewing capacity and have the potential 

to differentiate to a certain extent. Normally, tissue-specific 

stem cells are implicated in the generation, homeostasis 

and regeneration of particular organs. In analogy, 

47

48 

the cancer stem cell concept predicts that particular cancers 

arise from specific cancer stem cell types. Unfortunately, 

cancer stem cells appear to be relatively resistant 

to radiotherapy and chemotherapy. Thus, it is imperative 

to better characterize cancer stem cells in order to establish 

novel therapies specifically targeting these cells. 

The skin is the organ with the highest incidence of malignancies, 

and skin cancers occur more frequently than all 

other cancers combined. Of the various skin cancers, melanoma 

is responsible for most deaths. Melanoma cells 

arise by malignant transformation of melanocytes, the 

pigment cells in our skin. These cells, in turn, originate 

during development in the neural crest. In accordance 

with the hypothesis that melanoma might develop from 

cancer stem cells, we have identified melanoma stem cells 

with features of neural crest stem cells. These cells are responsible 

for both tumour initiation and tumour maintenance. 

Intriguingly, we found that melanoma stem cells 

appear to have specific capacities to evade anti-cancer 

immune responses. Based on our findings, we will investigate 

the specific genetic properties and growth requirements 

of melanoma stem cells with the goal of establishing 

novel targets for the elimination of cancer stem cells. 

Indeed, we have already identified chemical substances 

that counteract melanoma stem cell growth and tumour 

formation in animal models. Our study highlights the importance 

of collaborative efforts – involving stem cell biologists, 

pathologists, and pharmacologists – for cancer 

stem cell research and the development of new treatment 

strategies. 


Prof. Dr. Lukas Sommer 

Anatomisches Institut 

Zell- und Entwicklungsbiologie 

Universität Zürich 

Winterthurerstrasse 190 


Phone +41 (0)44 635 53 50/54 43 

Fax +41 (0)44 635 68 95 

lukas.sommer@anatom.uzh.ch 


– Prof. Dr. Michael Detmar, ETH Zürich, Institute of 

Pharmaceutical Sciences, CH-8093 Zürich 

– Prof. Dr. Reinhard Dummer, Universitätsspital Zürich, 

Dermatologische Klinik, CH-8091 Zürich 

– Dr. Daniela Mihic-Probst, Universitätsspital Zürich, 

Dept. Pathologie, CH-8091 Zürich

International Clinical Cancer Research Groups (ICP) 

List of funded research groups 

Ammann Roland A. et al. | ICP OCS 02061-03-2007 | CHF 118,000.– 

Departement Hämatologie/Onkologie, Medizinische Universitäts-Kinderklinik, Inselspital, Bern 

International childhood liver tumour consortium – research strategy for treatment and evaluation of 

hepatoblastoma and hepatocellular carcinoma 

Franceschi Silvia et al. | ICP OCS 01355-03-2003 | CHF 500,000.– 

Groupe épidémiologie des infections et cancer, Centre international de recherche sur le cancer (CIRC), 

Lyon, France 

Risk of cancer in persons infected with HIV 

Maibach Rudolf | ICP OCS 01688-03-2005 | CHF 791,510.– 

International Breast Cancer Study Group (IBCSG), Coordinating Center, Bern 

Academic research activity of the International Breast Cancer Study Group (IBCSG) 

Sessa Cristiana et al. | ICP OCS 01687-03-2005 | CHF 800,500.– 

Istituto oncologico della Svizzera italiana (IOSI), Ospedale San Giovanni, Bellinzona 

Towards an independent and efficient anticancer drug development in Switzerland: Potentiation of 

the Swiss SENDO Unit 

Zucca Emanuele et al. | ICP OCS 01356-03-2003 | CHF 983,000.– 


International Extranodal Lymphoma Study Group (IELSG): A network for improving the understanding and 

the clinical management of non-Hodgkin’s lymphomas arising at extranodal sites 

49

50 

The funded research groups in brief 

Ammann Roland A. et al. | International childhood 

liver tumour consortium – research strategy for 

treatment and evaluation of hepatoblastoma and 

hepatocellular carcinoma 

ICP OCS 02061-03-2007 

Duration: 01.07.2007 – 30.06.2011 

CHF 118,000.– 

Malignant liver tumours in children are extremely rare. 

Treatment results have improved considerably in the last 

15 years. It has therefore become quite a challenge for 

treating physicians to choose the correct approach in this 

rapidly changing field. The Epithelial Liver Tumour Study 

Group of the International Society of Paediatric Oncology 

(SIOP) known as SIOPEL has contributed substantially 

to progress through their programme of clinical studies 

for treatment of childhood liver cancer. SIOPEL recently 

joined forces with the US Children’s Oncology Group in a 

project called CHIC (Childhood Hepatic Tumours International 

Collaboration). 

Since 1990 clinical trials to optimize the treatment of 

hepatoblastoma and hepatocellular carcinoma have been 

and are continuing to be launched. Both more rational 

chemotherapy and improvements in surgical techniques 

have led to the better results. In these very rare tumours 

this was only possible by multidisciplinary international 

cooperation. In the case of SIOPEL, over 100 centres from 

32 countries have participated in SIOPEL trials and studies. 

In the first two trials the concept of preoperative chemotherapy 

was introduced and adapted according to two 

groups with different prognosis. In the third trial it was 

proven that for the group with the better overall prognosis 

the chemotherapy can be reduced to a single agent, 

thus reducing the potential for possible serious toxicity to 

the kidneys and the heart function while achieving an excellent 

long-term result. The next trial generation is now 

focusing on optimizing an aggressive chemotherapy for 

patients at high risk of relapse, and on reducing the hearing 

impairment caused by single agent chemotherapy in 

standard risk patients. In the context of surgery, liver 

transplantation has taken on a greater role. 

An Internet-based worldwide registry for these interventions 

(Pediatric Liver Unresectable Tumour Observatory, 

PLUTO) has been set up. Besides treatment optimization, 

the group is further investigating molecular biological 

characteristics and other scientific parameters to be able 

to include these into better defined risk groups. 

The coordination of all these activities is carried out by 

Clinical Trials Unit at the Cancer Research UK in Birmingham, 

England, and by the trial committees. The statistical 

support is provided by the Coordinating Center of 

the International Breast Cancer Study Group (IBCSG) 

(R. Maibach). The Swiss Paediatric Oncology Group 

(SPOG) conducts the trials in Switzerland. The laboratory 

of the University Children’s Hospital Zurich (M. Grotzer) 

collects the tissue samples for scientific investigation. 


PD Dr. Roland A. Ammann 

Departement Hämatologie/Onkologie 

Medizinische Universitäts-Kinderklinik 

Inselspital 

CH-3010 Bern 

Phone + 41(0)31 632 93 72 

Fax + 41(0)31 632 95 07 

roland.ammann@insel.ch 


– PD Dr. Michael Grotzer, Kinderspital Zürich, 

Onkologie/Neuroonkologie, CH-8032 Zürich 

– Dr. Rudolf Maibach, International Breast Cancer Study 

Group (IBCSG), Coordinating Center, CH-3008 Bern 

– Dr. Jack Plaschkes, Inselspital, University Children’s 

Hospital, Dept. of Pediatric Surgery, CH-3010 Bern 

– Prof. Dr. Arthur Zimmermann, Universität Bern, 

Institut für Pathologie, CH-3010 Bern 

Franceschi Silvia et al. | Risk of cancer in persons 

infected with HIV 

ICP OCS 01355-03-2003 

Duration: 01.01.2004 – 1.1.2009 

CHF 500,000.– 

Persons infected with HIV (PHIV) are at particular risk for 

many infection-related cancers due to the negative effect 

of immunosuppression on the outcome of co-infection 

with carcinogenic viruses. 

Objectives 

This collaborative project of the International Agency for 

Research on Cancer (IARC), the Swiss HIV Cohort Study 

(SHCS) and Swiss cantonal cancer registries (CRs) was 

initiated with the broad aim to improve knowledge on 

the causes and strength of the risk of cancer in PHIV in 

Switzerland. 

Methods 

The SHCS is a collaboration of seven centres throughout 

Switzerland that has enrolled over 15,000 PHIV since 

1988. Over the same time period, CRs in six of these 

seven regions have been recording comprehensive quality-checked 

epidemiological data on cancer incidence. 

First in 2003, and again in 2007, patient records were 

linked between the SHCS and CRs, using specifically developed 

software to ensure confidentiality and resulting in 

an anonymous dataset of cancer diagnoses and mortality 

in the SHCS. Cancers identified through linkage were 

used to estimate incidence rates in the SHCS and to compare 

them with expected numbers of cancers from the 

general CR population. 

Study Results 

1. Quantification of excess cancer risk in the SHCS in comparison 

to the general Swiss population (Clifford, Journal 

of the National Cancer Institute 2005; Franceschi, British 

Journal of Cancer 2010): In addition to the AIDS-defining 

cancers Kaposi sarcoma (KS), non-Hodgkin lymphoma 

(NHL) and cervical cancer, significantly elevated risks

in PHIV were shown for Hodgkin’s lymphoma (HL), nonmelanoma 

skin cancer and cancers of the anus, liver, lip/ 

mouth/pharynx and trachea/lung. 

2. Time trends and risk factors for cancer incidence within 

the SHCS (Polesel, AIDS 2008; Franceschi, British Journal 

of Cancer 2008; Clifford, Blood 2009): The incidence of 

NHL (particularly primary brain lymphoma) and KS were 

confirmed to have greatly decreased in the combination 

antiretroviral therapy (cART) era. This beneficial effect remains 

strong up to 10 years after cART initiation. HL risk, 

on the other hand, does not appear to have changed over 

time or to have been significantly affected by cART. 

3. Nested case-control studies of cancer aetiology (Franceschi, 

British Journal of Cancer 2006; Clifford, AIDS 

2008): Frequent co-infection with HCV/HBV means that 

the direct effect of HIV-related immunodeficiency on 

hepatocellular carcinoma (HCC) has proven difficult to 

elucidate. Nevertheless, we showed a significant association 

between lower CD4 + cell counts and HCC risk, which 

was particularly evident for HBV-related HCC arising in 

non-intravenous drug users. 

4. Sero-epidemiological studies (Sullivan, AIDS 2010): 

cART increases KS herpesvirus-specific humoral immune 

response and clearance of viremia among PHIV, consistent 

with the dramatic protection offered against KS. 

Recommendations 

Improving survival means that PHIV live long enough for 

the most severe long-term sequelae of carcinogenic viruses 

to manifest as non-AIDS-defining cancers (NADCs). 

Thus, NADCs can be expected to become an increasingly 

important complication of long-term HIV infection, and 

better cancer prevention strategies (control of immunosuppression, 

cervical cancer screening, control of hepatitis 

viral infections, smoking cessation) are a priority. 


Dr Silvia Franceschi 

Infections and Cancer Epidemiology Group 

International Agency for Research on Cancer (IARC) 

150, cours Albert Thomas 

F-69372 Lyon Cedex 08 

France 

Phone +33 472 73 84 02 

Fax +33 472 73 8345 

franceschi@iarc.fr 


– Prof. Dr. Christine Bouchardy, Registre genevois 

des tumeurs, Bd. de la Cluse 55, CH-1205 Genève 

– Prof. Dr. Fabio Levi, Institut universitaire de médecine 

sociale et préventive, Université de Lausanne, 

rue du Bugnon 17, CH-1005 Lausanne 

– Dr. Martin Rickenbach, Swiss HIV Cohort Study, 

CHUV, Mont-Paisible 16, CH-1011 Lausanne 

– Dr. Luigi Del Maso, Servizio di Epidemiologia e 

Biostatistica, via Pedemontana Occ 12, 

I-33081 Aviano, Italia 

Maibach Rudolf | Academic research activity of 

the International Breast Cancer Study Group (IBCSG) 

ICP OCS 01688-03-2005 

Duration: 01.07.2005 – 01.07.2009 

CHF 791,510.– 

The International Breast Cancer Study Group (IBCSG) is a 

cooperative group that has conducted high quality and 

important clinical trials of adjuvant therapy for patients 

with operable breast cancer for the past 30 years. With its 

network of investigators spanning five continents, the 

IBCSG is dedicated to designing and conducting relevant 

trials, evaluating primary and secondary study results and 

presenting and publishing its findings in the best journals 

and at scientific congresses. 

IBCSG has been supported by Cancer Research Switzerland 

(and formerly by Oncosuisse) in the conduct of a 

series of studies, some of which have been completed 

and evaluated. The following results are only a selection 

of IBCSG’s research activities: 

In two studies for pre- and postmenopausal patients conducted 

in the 1990s, IBCSG evaluated breast cancer treatment 

with chemotherapy and hormonal therapy. The 

IBCSG Tissue Bank serves as repository for tumour material 

from many of these patients. The IBCSG Pathology 

Review Office has now evaluated in 2,754 patients the 

role of peritumoural vascular invasion (PVI) for long-term 

outcome. It could be shown that this invasion is associated 

with larger and more aggressive tumours but does not 

have a negative impact on the prognosis of the patient 

if she has received adequate hormonal therapy. Nevertheless, 

the determination of PVI should be done to inform 

choice of the best therapy for the patient. 

In two other studies with a median observation time of 

13 years, we analyzed the influence of the extent of oestrogen 

receptor expression on the efficacy of the chemotherapy 

given in combination with the hormonal treatment. 

High oestrogen receptor expression allows good 

efficacy of the hormonal therapy, thus reducing the impact 

of chemotherapy on the success of the treatment. 

Therefore, oestrogen receptor expression is an important 

factor in the choice of the optimal therapy. 

Chemotherapy also has a direct influence on the hormonal 

situation of the patient by reducing or completely 

stopping the ovaries from producing hormones. In a study 

of high-dose chemotherapy for patients with a high risk of 

relapse, the highest treatment effect was observed in the 

group of patients whose tumours carried oestrogen receptors. 

This leads to the hypothesis that even high-risk 

patients may benefit from hormonal therapy if the tumour 

shows a sufficient quantity of receptors. 

In the same study, the quality of life of the patients was 

assessed repeatedly by questionnaires. The quality of life 

indicators were combined with the relatively high toxicity 

experienced by the patients and the long-term outcome 

of the treatment to produce “quality-adjusted time without 

symptoms and toxicity” (Q-TWiST). Although the 

quality of life of the patients subjected to high-dose 

chemotherapy was lower during the treatment, they had 

a longer Q-TWiST. It may therefore be worthwhile to accept 

a short-term reduction of the quality of life by a burdensome 

chemotherapy if it is compensated by long-term 

treatment success. 

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52 


Dr. Rudolf Maibach 

International Breast Cancer Study Group (IBCSG) 

IBCSG Coordinating Center 

Effingerstr. 40 

CH-3008 Bern 

Phone +41 (0)31 389 91 96 

Fax +41 (0)31 389 92 39 

rudolf.maibach@ibcsg.org 

Sessa Cristiana et al. | Towards an independent and 

efficient anticancer drug development in Switzerland: 

Potentiation of the Swiss SENDO Unit 

ICP OCS 01687-03-2005 

Duration: 01.01.2006 – 31.12.2010 

CHF 800,500.– 

The clinical activities of the Swiss SENDO Unit (called 

SAKK/SENDO because of the close collaboration with 

SAKK) started in May 2006 with the activation of the first 

phase I study, preceded by the implementation of the collaborative 

network among participating centres. Overall, 

seven studies have been activated, and 189 patients were 

entered by December 2010. Patient accrual and the number 

of participating centres and ongoing studies increased 

up to 2009, with a decrease of patient accrual in 2010 due 

to the logistics of the studies. 

The aim of the Swiss SENDO Unit is to establish central 

coordination of phase I and II studies in Switzerland and 

to ensure closer interaction among centres, investigators 

and the SAKK collaborative group. The coordinating 

centre of the Swiss SENDO Unit is at the Istituto oncologico 

della Svizzera italiana (IOSI) in Bellinzona. There are 

now five active members: IOSI, Kantonsspital St. Gallen, 

CHUV Lausanne, Kantonsspital Basel and Kantonsspital 

Graubünden. Among seven studies activated (one phase 

II, six phase I of which three Ib and three first in human) 

four were completed by December 2010, and three are 

still ongoing. 

Completed studies: 

1. SAT1-05-06: was started in May 2006 and closed in December 

2007. Four centres participated, and 37 patients 

were recruited. The schedule of administration of satraplatin 

(a novel oral platinum compound) and capecitabine was 

assessed in adult patients with advanced solid tumours 

(open label phase Ib study). The results are reported in a 

full paper that has been accepted for publication. 

2. SO43VELCO2: An open label phase II study of biweekly 

VELCADE TM and intermittent CAELYX TM in patients with 

ovarian cancer failing platinum containing regimens: two 

centres in Switzerland and five in Italy, 58 patients enrolled, 

activated in May 2006 and closed in January 2009. 

3. SO65APOX01: First in human phase I dose finding and 

pharmacokinetic study of intravenous APO010, a recombinant 

form of human Fas ligand, in patients with solid tumours: 

two centres in Switzerland, 25 patients enrolled, 

activated in February 2007 and closed in January 2010. 

4. SKSD00701: A phase Ib dose-finding study of satraplatin 

in combination with oral vinorelbine in patients 

with advanced solid tumours: two centres in Switzerland, 

27 patients enrolled, activated in December 2007 and 

accrual closed in April 2010. 

The three ongoing studies are: 

1. ST1968-DM-06-001: A phase I dose finding and pharmacokinetic 

study of intravenous camptothecin ST1968 in 

patients with solid tumours: two centres in Switzerland, 

62 patients enrolled, activated in June 2007. 

2. SKSD00702: A phase Ib study of the histone deacetylase 

inhibitor panobinostat (LBH589) given orally in combination 

with carboplatin and paclitaxel in patients with 

advanced solid tumours: three centres in Switzerland, 

33 patients enrolled, activated in May 2008. 

3. ST1968-DM-09-001: Phase I dose finding and pharmacokinetic 

study of daily administrations of the intravenous 

camptothecin namitecan (ST1968) in patients with 

refractory or recurrent solid tumours: two centres in Switzerland 

and one in Italy, 15 patients enrolled, activated in 

January 2010. 

The advantages of this network are that the investigators 

can have direct experience with the new compounds, they 

are accustomed to collaborating, and they are interested 

in continuing to work with the same drugs in phase II 

studies. This has been already proven by the positive findings 

achieved so far. Public opinion has become more 

aware of the need for and the importance of the development 

of anti-cancer drugs and, more generally, the importance 

of clinical research in Switzerland. 

In 2010 the number of new studies and patients enrolled 

decreased due to financial constraints of drug companies, 

the limited drug market in Switzerland as compared to 

other European countries, and competition with big European 

referral centres for phase I. 

The availability of the Swiss Sendo Unit allows the network 

to propose and implement innovative studies with 

limited financial support by drug companies but with 

greater scientific independence. 


Prof. Dr. Cristiana Sessa 

Istituto oncologico della Svizzera italiana (IOSI) 

Ospedale San Giovanni 


Phone +41 (0) 91 811 81 81 

Fax +41 (0) 91 811 90 44 

cristiana.sessa@eoc.ch 


– Prof. Dr. Franco Cavalli, Medical Oncology, IOSI, 

Ospedale San Giovanni, CH-6500 Bellinzona 

– Prof. Dr. Thomas Cerny, Fachbereich Onkologie/ 

Hämatologie, Departement Innere Medizin, 

Kantonsspital, CH-9007 St. Gallen 

– Prof. Dr. Richard Herrmann, Klinik für medizinische 

Onkologie, Kantonsspital, CH-4031 Basel 

– Prof. Dr. Serge Leyvraz, Service d’oncologie, 

Centre hospitalier universitaire vaudois (CHUV), 


– Dr. Roger von Moos, Kantonsspital Graubünden, 

CH-7000 Chur

Zucca Emanuele et al. | International Extranodal 

Lymphoma Study Group (IELSG): A network for improving 

the understanding and the clinical management 

of non-Hodgkin’s lymphomas arising at extranodal sites 

ICP OCS 01356-03-2003 

Duration: 01.01.2004 – 31.12.2011 

CHF 983,000.– 

Extranodal lymphomas represent approximately 30–40 % 

of all non-Hodgkin’s lymphomas, and their incidence is increasing. 

These lymphomas can develop from all organs 

and sites of the body, and their clinical history varies 

significantly depending on the organ of origin. Given the 

relative low frequency of cases per particular body site, no 

single institution worldwide would be ever able to accumulate 

enough cases in order to study the respective clinical 

history and to establish specific treatment strategies. 

The Oncology Institute of Southern Switzerland (IOSI) 

has been actively involved in this field in the last two decades. 

Twelve years ago, we decided to create the International 

Extranodal Lymphoma Study Group (IELSG) with 

the operational office located at the IOSI in Bellinzona. 

The IELSG is an international cooperative group of institutions 

that collaborate to perform studies in patients with 

extranodal lymphomas. The establishment of this group 

allowed collection of clinical data and biological material 

of several thousands of extranodal lymphoma cases. 

Thanks to this unique worldwide work, the group has performed 

more than 30 studies, many of which have been 

published (see www.ielsg.org). Several other studies are 

currently ongoing or planned. Originally, the IELSG conducted 

retrospective studies, but now the group is mainly 

engaged in prospective trials. 

Of the most recent contributions of IELSG, the conclusion 

of two important clinical studies is noteworthy. The IELSG 

20 study was the first randomised trial of chemotherapy 

for primitive lymphoma of the brain to be completed. The 

study (published in The Lancet) allowed us to document 

that the combination of two drugs (cytarabine and methotrexate) 

when given at high doses represents the most 

efficient chemotherapeutic approach for this particular 

disease. Based on these results, we started the IELSG 32 

study, which is currently ongoing and exploring the impact 

of stem cell transplantation on the survival of patients affected 

by this severe form of lymphoma. 

Another important recent achievement is the conclusion 

of the IELSG 19 randomised study, which showed the superiority 

of the combination of chlorambucil (a chemotherapeutic 

drug) and rituximab (a monoclonal antibody 

targeting the B-cells) as compared to treatment with 

chemotherapy alone in extranodal marginal zone lymphomas. 

The results of this study were presented to the scientific 

community at the most recent congress of the American 

Hematology Association in December 2010. 

In 2010 we also completed the accrual of a study aimed 

at evaluating the role of 18-FDG-PET scanning in the 

management of the primary mediastinal lymphoma. The 

results of this study will be presented to the scientific 

community at the 11th International Conference on 

Malignant Lymphoma in Lugano in June 2011. 


PD Dr. Emanuele Zucca 

Oncology Institute of Southern Switzerland (IOSI) 



Phone + 41 (0)91 811 90 40 

Fax + 41 (0)91 811 91 82 

ielsg@ticino.com 


– Prof. Dr. Franco Cavalli, Istituto oncologico 

della Svizzera italiana, Ospedale San Giovanni, 


– Dr. Mary Gospodarowicz, Ontario Cancer Institute, 

Princess Margaret Hospital, Dept. of Radiation 

Oncology, Toronto Ontario, Canada 

– Prof. Dr. Emilio Montserrat, Clinic Hospital Universitari, 

Servicio de Hematologia, E-08036 Barcelona, España 

53


Cancer stem cells: The origin of cancer? 

Although there have been great medical advances in 

fighting cancer over the past few years, we are often 

rather powerless in the face of this disease. A better 

understanding of how different types of cancer develop 

and spread throughout the body could pave 

the way towards new forms of therapy. Up to now, 

it has been assumed that tumours are composed of 

a group of cells that multiply malignantly and thus 

contribute to tumour growth. According to a new 

hypothesis, however, cancer could also arise from 

individual cancer stem cells, which have a different 

growth and spreading potential than most of the 

tumour cells. Efficient treatment of tumours must 

therefore deal mainly with these cancer stem cells. 

Prof. Lukas Sommer, PhD 

Head of the Division of Cell and Developmental Biology at the Institute of Anatomy at 

the University of Zurich 

During embryonic development, normal stem cells 

are responsible for building organs, and in the adult 

body they contribute towards maintenance and regeneration 

of tissues and organs. They can perform 

these functions thanks to their ability to multiply almost 

indefinitely and to develop into different cell 

types in the body. There are many indications that 

cells having stem cell characteristics are present in 

almost all tumours and that they are considerably 

involved in tumour growth and spread through metastases. 

Like normal stem cells, cancer stem cells 

can make unlimited copies of themselves and to a 

certain extent can develop into other, less malignant 

cell types. For this reason, it is believed that the tissue 

heterogeneity observed in most cancer types is 

caused by cancer stem cells, similar to the way that 

normal stem cells can produce organs with complex 

structures. In technical terminology we refer to the 

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56 

“hierarchical structure” of a tumour, which had its 

origins in one cancer stem cell from which all other 

tumour cells derived. 

Cancer stem cells – a new perspective in research 

and therapy 

With the discovery and experimental investigation of 

cancer stem cells, the way of looking at how cancer 

could be treated must be reconsidered. Namely, traditional 

therapy strategies cannot or can only insufficiently 

reach cancer stem cells. For example, chemotherapies 

aim to stop the growth and survival of the 

cancer as a whole. But cancer stem cells appear to 

possess a specific protective mechanism that allows 

them to send toxic chemical substances out of the 

cell. And so, chemotherapies seem to destroy a large 

part of the tumour cells – but without being able to 

get to the root of the actual cause of the carcinogenesis. 

Cancer recurrence following chemotherapy 

could therefore be due to just a few cancer stem cells 

surviving in the patient’s body. 

For this reason, cancer stem cell research must find 

new ways to fight cancer. Here the focus is on targeted 

destruction of the cancer stem cells producing 

the tumour. But methods are also being tested that 

specifically block the cell division of cancer stem cells 

or that accelerate their differentiation into less malignant 

cells. To be able to implement these new types 

of strategies of cancer therapy, research is needed on 

the molecular and cellular characteristics and growth 

conditions of cancer stem cells in different tumour 

types. As for normal stem cells, it can also be assumed 

for cancer stem cells that their characteristics, 

their growth conditions, and their potential for 

spreading are dependent upon the tissue of origin 

and thus on the type of cancer. 

Cancer stem cells have already been demonstrated in 

various types of cancer in different organs, such as 

breast cancer, colon cancer, brain tumours, different 

forms of blood cancer (leukaemias) and some other 

cancers. Depending on the cancer type and on the 

patient, cancer stem cells in the tumour tissue appear 

to differ in number. In our research, we are mainly 

studying malignant skin cancer (melanoma). This 

type of cancer is extremely aggressive, and the incidence 

rate of melanoma is rising. Melanoma develops 

from a malignant change in melanocytes, which 

are pigment cells and, in developmental biology, develop 

from what is called the neural crest. The neural 

crest is a structure in the embryo with great development 

potential. Not only pigment cells but also 

nerve cells in the peripheral nervous system, for example, 

and facial cartilage and bones derive from the 

neural crest. To be able to build these structures, 

neural crest stem cells must divide substantially and 

move across long distances in the embryo. 

Since pigment cells in the skin also derive from neu 

ral crest stem cells, we raised the question as to 

whether these normal stem cells could have something 

to do with the cause of skin cancer. We supposed 

that possible cancer stem cells in the melanoma 

could show the characteristics of normal 

neural crest stem cells. That kind of connection could 

also explain why melanoma cells are so aggressive – 

why they can multiply so strongly and spread through 

tissue to form metastases. And in fact, in numerous 

melanoma biopsies we found cells that clearly 

showed the features of neural crest stem cells. In

cooperation with dermatologists and pathologists at 

University Hospital Zurich, we made the important 

discovery that the number of these cells in the patient’s 

tumour was connected with the course of the 

disease: The higher the number of cells with characteristics 

of neural crest stem cells that are found in a 

biopsy, the greater the probability of metastasis and 

of the patient dying of cancer. 

Inhibition of melanoma stem cells 

Thanks to our experience in the area of neural crest 

development, we were able to more precisely characterize 

these tumour cells and test their cancerproducing 

effect in animal models. In these experiments, 

the cells prove to be actual melanoma stem 

cells that can multiply arbitrarily and are responsible 

for tumour growth in animal models. This finding is 

not undisputed, as no cells having stem cell characteristics 

could be found in melanoma in research 

work conducted in the United States. This also shows 

that research in this area is still in its beginnings. In 

particular, researchers need to develop standard 

protocols for how cancer cells are removed from the 

tumour and then cultivated. For example, we were 

able to demonstrate melanoma stem cells only using 

refined methods by which the tumour tissue was 

treated as carefully as possible. In addition, we 

discovered that melanoma stem cells have a special 

ability to evade detection by the immune system. 

Finally, this research work can create a foundation 

for the development of new strategies in cancer therapy. 

For example, target structures for therapies 

could be identified by comparing normal stem cells 

and cancer stem cells. Based on this, genetic characteristics 

and cellular properties of cancer stem cells 

are determined. The knowledge of stem cellspecific 

biomarkers and growth factors could aid the discovery 

of pharmaceutically active substances that inhibit 

cancer stem cell development. By using this 

approach, in cooperation with the Institute of Pharmaceutical 

Sciences at ETH Zurich, we have already 

identified chemical substances that suppress the 

division of melanoma stem cells and, in animal models 

at least, counteract with tumour formation. However, 

the exact mechanisms of how these substances 

work must still be investigated, and it will take some 

time and more research work before their clinical 

application with patients can be tested. However, it 

is definitely conceivable that knowledge gained via 

melanoma stem cells could considerably improve the 

therapy approaches available today. 

To achieve these goals, there are still many questions 

that must be clarified. Do tumour stem cells derive 

from normal stem cells? Do they form tumour tissue 

“hierarchically”, as in the healthy organ? Or is the 

opposite developmental direction in the tumour also 

possible, so that tumour cells without stem cell 

characteristics can again become tumour stem cells 

under certain conditions? That kind of neoplasm 

of cancer stem cells could take place in the course of 

metastasis or under the influence of the immune system, 

for example. If that were so, the aim of therapy 

would perhaps not consist so much in eliminating a 

certain (stem) cell population in the tumour. Instead, 

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58 

the attempt should be made to stop the specific mo 

lecular processes of stem cell multiplication and in 

this way to block the fatal activity of the cancer stem 

cells. 

Extensive investigations of this kind can only be 

successful through cooperation among different re 

search groups that complement each others’ compe 

tencies. Here, synergies between stem cell biologists, 

pathologists, clinicians, and pharmaceutical scientists 

are imperative. This is the only way we can increase 

our understanding of cancer stem cells and their 

effect – and that is urgently needed if we want to be 

able to possibly establish new specific and efficient 

strategies in cancer therapy. 

Prof. Lukas Sommer, PhD 

Lukas Sommer has been full professor 

and head of the Division of 

Cell and Developmental Biology 

at the Institute of Anatomy at 

the University of Zurich since 

2007. He completed undergraduate 

studies in biology at the 

Biocenter in Basel, Switzerland, 

and received his PhD in 1992 at 

the Swiss Institute for Experimental Cancer Research 

(ISREC) in Lausanne. After conducting research as a 

postdoctoral fellow at California Institute of Technology 

(CALTECH) in the United States, he returned to Switzerland 

in 1997 to join the Institute of Cell Biology at 

ETH Zurich, where he worked as a group leader and 

then as assistant professor. 

Phone +41 (0)44 635 54 43 

lukas.sommer@anatom.uzh.ch 

www.anatom.uzh.ch/research/DivisionSommer_en.html


List of completed research projects from July 2008 to December 2010 

Ballmer-Hofer Kurt | OCS 02100082007 | CHF 205,700.– 

Biomolekulare Forschung, Paul Scherrer Institut (PSI), Villigen 

Structural and functional analysis of ligand-mediated activation of VEGF receptor 2; identification and 

characterization of structural motifs for the development of new receptor inhibitory drugs for anti-vascular 

tumor therapy 

Beermann Friedrich | OCS 01500022004 | CHF 247,344.– 

Institut suisse de recherche expérimentale sur le cancer (ISREC), Faculté sciences de la vie, 

EPF de Lausanne, Lausanne 

In vivo screening of candidate genes in melanoma 

Bentires-Alj Mohamed | OCS 01922082006 | CHF 275,400.– 


Role of GAB2/SHP2 and 11q13 amplification in breast cancer 

Brunner Thomas | OCS 02025022007 | CHF 176,900.– 

Institut für Pathologie, Universität Bern, Bern 

Characterization and role of extra-adrenal glucocorticoid synthesis in colorectal cancer 

Christofori Gerhard | OCS 01932082006 | CHF 305,400.– 

Institut für Biochemie und Genetik, Departement Biomedizin, Universität Basel, Basel 

Podoplanin-mediated signalling and its role in collective cell invasion and metastasis formation 

Citi Sandra | OCS 01916082006 | CHF 195,000.– 

Département de biologie moléculaire, Sciences III, Université de Genève, Genève 

The role of tight junction proteins in epithelial morphogenesis and differentiation 

Donda Alena | OCS 02248082008 | CHF 138,300.– 

Département de biochimie, Université de Lausanne, Epalinges 

CD1d-anti tumor bifunctional molecules to redirect the innate and adaptive immune responses 

to the tumor site 

Dufour Jean-François | OCS 02112082007 | CHF 209,900.– 

Signal Transduction Group, Institut für klinische Pharmakologie, Universität Bern, Bern 

Roles of mTORC2 and mTOC1 in hepatocellular carcinoma 

Continuation in the project: 

Dufour Jean-François | KFS 02541022010 | CHF 202,200.– 

Institut für klinische Pharmakologie, Universität Bern, Bern 

Hepatocarcinogenic roles of mTOR, raptor and rapamycins in absence of Pten 

Duration: 01.08.2010 – 01.08.2013 

Frei Christian | OCS 01575082004 | CHF 167,000.– 


The function of Drosophila hypoxia-inducible factor (HIF-1) and its transcriptional targets in cellular 

growth control 

Frey-von Matt Brigitte M. | KLS 02015022007 | CHF 246,400.– 

Departement für Nephrologie und Hypertonie, Inselspital, Bern 

Androgen-mediated gene delivery (AMGD) 

Gasser Susan | OCS 02126082007 | CHF 187,700.– 


The RPA70 interaction domain of Sgs1 contributes to both replication checkpoint activation and fork stability 

Gönczy Pierre | OCS 01676022005 | CHF 171,100.– 

UPGON, Institut suisse de recherche expérimentale sur le cancer (ISREC), Faculté sciences de la vie, 


Coupling cell polarity and cell division in C. elegans embryos: Novel insights into proliferation control 

mechanisms 

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60 

Gönczy Pierre | KLS 02024022007 | CHF 335,100.– 

UPGON, Institut suisse de recherche expérimentale sur le cancer (ISREC), Faculté des sciences de la vie, 


Mechanisms of centrosome duplication in C. elegans and human cells: From model organism towards 

therapeutic opportunities 

Grassi Fabio | OCS 01933082006 | CHF 174,300.– 

Istituto di ricerca biomedica (IRB), Bellinzona 

Sinergy between oncogenic Notch and pre-T cell receptor (pre-TCR) signalling microdomains in leukemogenesis 

Hall Michael N. | KLS 01991022007 | CHF 350,500.– 

Departement Biozentrum, Universität Basel, Basel 

Proteomic analysis of the cancer-promoting mTOR pathway 

Heim Markus Hermann | OCS 02192022008 | CHF 245,200.– 

Klinik für Gastroenterologie und Hepatologie, Universitätsspital Basel, Basel 

Hepatocarcinogenesis in chronic hepatitis C 

Hemmings Brian A. | OCS 01667022005 | CHF 271,350.– 


Role of protein kinase B (PKB/Akt) in cell transformation and cancer 

Hemmings Brian A. | OCS 01942082006 | CHF 275,400.– 


The role of human protein kinase NDR in cell morphogenesis, cell division, growth control and cancer 

Herr Winship | OCS 02047022007 | CHF 301,900.– 

Centre intégratif de génomique (CIG), Faculté de biologie et de médecine, Université de Lausanne, Lausanne 

HCF-1 regulation of genomic stability during cell division 

Hübscher Ulrich | OCS 01996022007 | CHF 251,800.– 

Institut für Veterinärbiochemie und Molekularbiologie, Universität Zürich, Zürich 

Repair of oxidation damages in DNA: DNA synthesis over lesions by posttranslationally modified human 

DNA polymerase � 

Huelsken Joerg | OCS 01838022006 | CHF 336,600.– 

UPHUE, Institut suisse de recherche expérimentale sur le cancer (ISREC), Faculté des sciences de la vie, 


Role of inflammation in Wnt-mediated tumorigenesis 

Hynes Nancy | KLS 02187022008 | CHF 47,600.– 


Characterisation of the role of PN-1 in breast cancer and its potential as a therapeutic target 

Janscak Pavel | OCS 01730082005 | CHF 221,500.– 


Study of the role of the human mismatch repair system in telomere metabolism 

Krek Wilhelm | OCS 01787082005 | CHF 335,500.– 


Roles of F-box protein Skp2-based E3 ubiquitin protein ligases in cell cycle control and neoplastic signalling 


Krek Wilhelm | KFS 02690082010 | CHF 226,000.– 


Roles of the URI oncoprotein in B-RAF-signaling and melanoma cancer cell proliferation 

Duration: 01.02.2011 – 01.02.2013 

Lange Norbert | OCS 01948082006 | CHF 163,200.– 

Laboratoire de pharmaceutique et de biopharmacie, Section des sciences pharmaceutiques, 

Université de Genève, Genève 

Synthesis and evaluation of new water soluble polymeric photosensitizer prodrugs for photodynamic therapy 

MacDonald Hugh Robson | OCS 01863022006 | CHF 346,300.– 

Centre Ludwig de recherche sur le cancer, Epalinges 

The role of proto-oncogenes in hematopoietic and cancer stem cells

Moradpour Darius | OCS 01762082005 | CHF 250,700.– 

Division de gastroentérologie et d’hépatologie, Centre hospitalier universitaire vaudois (CHUV), Lausanne 

Development of a model system to study coinfection by hepatitis B and C viruses – the major causes of 

hepatocellular carcinoma 

Müller Anne | OCS 02099082007 | CHF 191,500.– 


The molecular pathogenesis of Helicobacter pylori-induced mucosa-associated lymphoid tissue (MALT) 

lymphoma in an animal model: Analysis of the role of tumor infiltrating accessory cells in vivo and ex vivo and 

of the specificity of tumor immunoglobulin 


Müller Anne | KFS 02640082010 | CHF 293,700.– 



lymphoma: Analysis of the role of small regulatory RNAs in lymphomagenesis and high grade transformation 

Duration: 01.11.2010 – 01.11.2013 

Nägeli Hanspeter | KLS 01827022006 | CHF 117,700.– 

Institut für Veterinärpharmakologie und toxikologie, Universität Zürich, Zürich 

Regulation of nucleotide excision repair activity by protein modifiers 

Ochsenbein Adrian F. | OCS 01627022005 | CHF 274,300.– 

Universitätsklinik für medizinische Onkologie, Inselspital, Bern 

Immunosurveillance of chronic myeloid leukemia in mice 

Orend Gertraud | OCS 01875022006 | CHF 304,100.– 

Unité Inserm 682, Institut national de la santé et de la recherche médicale (INSERM), Strasbourg, France 

Analysis of a potential oncogenic function of tenascin-C and tenascin-W in colon cancer 

Pabst Thomas | OCS 01833022006 | CHF 249,000.– 


The myeloid key transcription factor CEBPA and the pathophysiology of acute myeloid leukemia 

Pelkmans Lucas | OCS 02111082007 | CHF 198,000.– 

Institut für molekulare Systembiologie, ETH Zürich, Zürich 

How focal adhesion kinase (FAK) controls membrane partitioning and endocytosis of cell adhesion components 

in normal and in cancer cells 

Peter Matthias | OCS 02189022008 | CHF 229,400.– 

Institut für Biochemie, ETH Zürich, Zürich 

Regulation of genome stability by Rtt101p/cullin4-based E3-ubiquitin ligases in yeast and mammalian cells 

Plückthun Andreas | OCS 02128082007 | CHF 215,400.– 

Biochemisches Institut, Universität Zürich, Zürich 

Tumor targeting of ErbB2 with designed ankyrin repeat proteins 

Pruschy Martin | OCS 02129082007 | CHF 223,100.– 

Labor für molekulare Radiobiologie, Klinik für RadioOnkologie, UniversitätsSpital Zürich, Zürich 

Microtubule interference as target for combined cancer therapy with ionizing radiation 

Radtke Freddy | OCS 01560082004 | CHF 140,600.– 

UPRAD, Institut suisse de recherche expérimentale sur le cancer (ISREC), Faculté des sciences de la vie, 


The role of Notch2 in murine epidermis 

Radtke Freddy | KLS 01840022006 | CHF 346,300.– 

UPRAD, Institut suisse de recherche expérimentale sur le cancer (ISREC), Faculté des sciences de la vie, 


The role of Notch1 signalling in acute lymphoblastic T-cell leukaemia (T-ALL) 

Renner Christoph | OCS 02119082007 | CHF 192,200.– 

Klinik und Poliklinik für Onkologie, Medizinbereich Innere Medizin – Onkologie, UniversitätsSpital Zürich, Zürich 

Selective inhibition of intratumoral regulatoy T-cells by antibody-GITR ligand fusion proteins 

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62 

Romero Pedro | OCS 02011022007 | CHF 173,600.– 

Division d’oncologie clinique, Centre Ludwig de recherche sur le cancer, Lausanne 

Impact of lentiviral cancer vaccines on the anti-tumor T-cell response in vivo 

Rüegg Curzio | OCS 02020022007 | CHF 275,600.– 

Division de pathologie expérimentale, Université de Fribourg, Fribourg 

Role of integrins and Cyr61/CCN1 in tumor metastasis: Unraveling mechnisms and development of novel 

integrin inhibitors 

Rufer Nathalie | OCS 01995022007 | CHF 204,500.– 

Centre Ludwig de recherche sur le cancer, Université de Lausanne, Lausanne 

Defining molecular, structural and functional T-cell receptor properties of melanoma-specific human 

CD8 + T lymphocytes 

Ruiz i Altaba Ariel | OCS 01857022006 | CHF 321,900.– 

Département de génétique médicale et de développement, Faculté de médecine, Université de Genève, Genève 

Determination of the extent of participation of the sonic hedgehog-GLI signalling pathway in human gliomas 

and in their cancer stem cells 

Schär Primo | OCS 02193022008 | CHF 283,400.– 


The role of thymine DNA glycosylase in the maintenance of genetic and epigenetic stability and the suppression 

of tumorigenesis 


Schär Primo | OCS 01868022006 | CHF 210,800.– 


Clarification of newly emerging roles of DNA repair in mediating the cytotoxicity of 5-fluorouracil and in 

the maintenance of epigenetic stability 

Schübeler Dirk | KLS 01865022006 | CHF 179,500.– 


Role and plasticity of DNA methylation in stem cell pluripotency and cancer 

Schwaller Jürg | OCS 01830022006 | CHF 228,100.– 

Forschungsgruppe Kinderleukämie, Departement Biomedizin, Universitätsspital Basel, Basel 

PIM serine/threonine kinases as potential therapeutic targets in human hematological malignancies 

Skoda Radek C. | OCS 01742082005 | CHF 339,000.– 

Forschungsgruppe experimentelle Hämatologie, Departement Biomedizin, Universitätsspital Basel, Basel 

Pathogenesis of myeloproliferative disorders 

Stamenkovic Ivan | OCS 01656022005 | CHF 173,900.– 

Institut universitaire de pathologie de Lausanne (IUP), Centre hospitalier universitaire vaudois (CHUV), Lausanne 

Analysis of the molecular mechanisms underlying the pathogenesis of EWING’S family tumors 

Suter Beat | OCS 01834022006 | CHF 243,000.– 

Institut für Zellbiologie, Universität Bern, Bern 

Control of the cell cycle function of Xpd and Cdk7 

Tschan Mario P. | OCS 01823022006 | CHF 203,800.– 

Medizinische Onkologie/Hämatologie, Departement für klinische Forschung, Universität Bern, Bern 

Regulation of the DMP1-ARF-p53 tumor suppressor pathway in normal and leukemic hematopoiesis 

Walker Paul R. | OCS 01754082005 | CHF 269,200.– 

Centre d’oncologie, Hôpitaux universitaires de Genève (HUG), Genève 

Exploration of intracerebral immune responses in a spontaneous astrocytoma model and their exploitation 

in novel cancer therapies 

Wymann Matthias | OCS 01924082006 | CHF 293,500.– 

Forschungsgruppe Krebs und Immunbiologie, Departement Biomedizin, Universität Basel, Basel 

Phosphoinositide 3-kinases in melanoma

Zaugg Kathrin | OCS 02009022007 | CHF 195,500.– 

Labor für angewandte RadioOnkologie, UniversitätsSpital Zürich, Zürich 

Elucidating the role of the hypoxia-protective gene CPT1C in carcinogenesis 


Zaugg Kathrin | KLS 02569022010 | CHF 78,000.– 


Elucidating the role of the hypoxia-protective gene CPT1C (Carnitine Palmitoyl-transferase 1C) 

in carcinogenesis 

Duration: 01.05.2010 – 01.05.2011 


Presentation of completed research projects from July 2008 to December 2010 

BallmerHofer Kurt | Structural and functional analysis 

of ligand-mediated activation of VEGF receptor 2; 

identification and characterization of structural motifs 

for the development of new receptor inhibitory drugs 

for anti-vascular tumor therapy (OCS 02100082007) 

Vascular Endothelial Growth Factors (VEGFs) constitute a 

family of proteins that regulate blood and lymphatic vessel 

development. Vessel formation and the maintenance 

of proper vessel organization are absolutely required for 

sustaining organ function in higher organisms. Aberrant 

vessel formation is associated with various diseases, such 

as arteriosclerosis, retinopathies, lymphoproliferative or 

rheumatoid disease, and in tumour growth where newly 

formed vessels allow cancer cells to grow more rapidly 

and to disseminate into the entire body. Tumour vascularization 

is a hallmark of many types of highly aggressive 

malignancies, such as breast, colon and stomach cancer. 

VEGFs bind to receptors expressed on the surface of cells 

and thereby activate their target cells to migrate, proliferate 

and ultimately to form new vessels. VEGF binding to 

cell surface exposed receptors induces changes in receptor 

structure that lead to receptor activation thereby giving 

rise to the generation of signals transmitted across the 

cell membrane to the intracellular milieu of the cell. 

We investigated the molecular mechanism of VEGF receptor 

activation with the aim to develop new receptor inhibitors 

applicable for the treatment of disease associated 

with aberrant vessel formation. Studying the structure of 

VEGF receptors and VEGFreceptor complexes, we found 

that VEGF binding drastically alters the threedimensional 

structure of the receptor. These structural changes are re 

sponsible for receptor activation and give rise to signals 

that promote the formation of new vessels. We investigated 

VEGF receptors using electron microscopy, Xray 

crystallography and small angle solution scattering techniques. 

The structural and functional information gained 

in this project was used to develop a comprehensive molecular 

model of receptor function that was essential for 

further progress in the development of new receptor antagonists 

for future medical applications. 

Based on the newly gained insights into the activation 

mechanism of VEGF receptors, we developed new antibodylike 

molecules to block receptor activation. In a follow 

up study we are now investigating the potential of 

these new molecular tools to block tumour growth in an 

animal model. 


Prof. Dr. Kurt BallmerHofer 

Laboratory of Biomolecular Research 

Molecular Cell Biology 

Paul Scherrer Institut 

Bldg. OFLC 102 

CH5232 VilligenPSI 

Phone +41 (0)56 310 41 65 

Fax +41 (0)56 310 52 88 

kurt.ballmer@psi.ch 

63

64 

Beermann Friedrich | In vivo screening of candidate 

genes in melanoma (OCS 01500022004) 

Melanoma is a malignant tumour arising from melanocytes, 

which are pigment cells derived from the neural 

crest. In the mouse, melanoma does not occur spontaneously, 

and, thus transgenic mouse models are used to address 

genetic changes leading to melanomagenesis or to 

study melanocyte development. In this project we wanted 

to address the role of candidate genes, first in melanocyte 

biology and homeostasis and later in melanoma development. 

We used transgenic mouse models to analyze the 

Notch signalling pathway in normal melanocyte biology, 

and to address the lack of the oncogene cMyc during 

melanocyte development. Moreover, we addressed the 

relevance of bcatenin directly in a mouse model of melanoma. 

Notch signalling: Notch has been shown to be expressed 

in mouse melanocytes and human melanoma. Using 

transgenic mouse models, we showed that deletion of 

Notch signalling in the melanocyte lineage induces precocious 

hair greying, the intensity of which depends on the 

number of deleted alleles of Notch1 and Notch2. Further 

histological analysis showed that this is due to a loss of 

melanocyte precursors as well as melanocyte stem cells 

after birth. This confirms that Notch signalling affects hair 

pigmentation and melanoblast population in a gene dosagedependent 

manner. When we overexpressed Notch 

in melanocytes, we could not prevent normal hair greying 

or induce melanoma tumours, indicating that Notch signalling 

by itself is not sufficient for melanoma formation. 

The c-Myc oncogene: cMyc is expressed in many tumours, 

including melanoma. To understand its role in melanocytes, 

we removed it specifically in a transgenic mouse 

model. Removal of cMyc leads to a hair greying phenotype 

that is not due to an effect in stem cells. In contrast 

to Notch, the phenotype is caused by a problem in proliferation 

during midgestation. These results indicated that 

cMyc is an important player in melanocyte biology, and 

we plan to address its role in a mouse model of melanoma. 

b-catenin: This protein is part of the Wnt signalling pathway 

and has been reported to be mislocalized in human 

melanoma. In collaboration with Lionel Larue’s group 

(Orsay, France), we used mice that express a stable form 

of bcatenin that leads to repression of the tumour suppressor 

p16 by binding to its promoter. Double transgenic 

animals expressing both an activated NRas oncogene 

and an activated bcatenin had a high incidence of melanoma 

with a short latency period. Histopathological analysis 

suggested that most melanomas arose from melanocytes 

located in the hair follicles. The results thus reveal 

that synergy between the Wnt and mitogenactivated 

protein (MAP) kinase pathways (due to activated NRas) 

may represent an important mechanism underpinning the 

genesis of melanoma. 


Dr Friedrich Beermann 

Institut suisse de recherche expérimentale 

sur le cancer (ISREC) 

Faculté Sciences de la vie 

EPF de Lausanne (EPFL) 

Station 19, Bâtiment SV 

CH1015 Lausanne 

Phone +41 (0)21 693 07 27 

friedrich.beermann@epfl.ch 

BentiresAlj Mohamed | Role of GAB2/SHP2 

and 11q13 amplification in breast cancer 

(OCS 01922082006) 

Each year 1.1 million new cases of breast cancer will occur 

among women worldwide, and 400,000 women will die 

of this disease. Although progress has been made in understanding 

breast tumour biology, most of the relevant 

molecules and pathways remain undefined. Their delineation 

is critical to a rational approach to breast cancer therapy. 

This project focuses on the roles of the signalling proteins 

GAB2/SHP2 (part 1) and on amplification of the chromosomal 

region 11q13 (part 2) in breast cancer. To address 

these questions, we used a combination of 3D cultures 

and xenograft models. In the first part, we found that inhibition 

of SHP2 dramatically reduces proliferation and reverses 

the invasiveness of transformed breast cells grown 

in 3D cultures. Moreover, SHP2 knockdown after tumour 

formation blocks tumour progression. In the second part, 

we found two highly defined genomic regions of 11q13 

amplification in breast tumours and identified 8 genes 

that are coamplified and cooverexpressed in these tumours. 

Taken together, our studies revealed potential 

therapeutic targets for the treatment of breast cancer. 


Dr. Mohamed BentiresAlj 




CH4058 Basel 

Phone +41 (0)61 697 40 48 

Fax +41 (0)61 697 39 76 

bentires@fmi.ch 

Brunner Thomas | Characterization and role of 

extra-adrenal glucocorticoid synthesis in colorectal 

cancer (OCS 02025022007) 

Glucocorticoids are important immunoregulatory steroids, 

produced mainly in the adrenal glands. However, our 

past research demonstrated that the epithelial cells of the 

intestinal crypts are capable of producing glucocorticoids 

in response to immune cell activation and that intestinal 

glucocorticoids contribute to the control of local immune 

responses. The aim of this study was to investigate 

whether colon carcinoma can produce glucocorticoids, 

how tumour glucocorticoid synthesis is regulated and 

whether tumourderived glucocorticoids actively suppress 

immune cells. 

The expression and induction of transcription factors and 

enzymes involved in the synthesis of cortisol from cholesterol 

in colon carcinoma cell lines as well as primary tumours 

was investigated using quantitative PCR and luciferase 

reporter assays. The role of the transcription factor 

LRH1 (liver receptor homolog1) in the regulation of tumour 

glucocorticoid synthesis was assessed using overexpression 

and RNA interference. Cortisol production was 

measured using radioimmunoassay, thin layer chromatog

aphy and bioassay. The suppressive and apoptosisinducing 

activity of tumour glucocorticoids was assessed on activated 

T cells and thymocytes. 

Our study could show that colon carcinoma cell lines as 

well as primary tumours express all enzymes required for 

synthesis of glucocorticoids and secrete bioactive cortisol. 

Similar to primary intestinal epithelial cells, LRH1 was 

found to play a critical role in the regulation of tumour 

glucocorticoid synthesis and to be overexpressed in many 

primary colon carcinomas. Cortisol produced by colon 

carcinomas potently suppressed T cell activation and induced 

apoptosis in glucocorticoidsensitive thymocytes. 

This is the first demonstration of glucocorticoid synthesis 

in tumours not derived from steroidogenic organs, and it 

suggests that tumourderived glucocorticoids could play 

an important role in the regulation of antitumour immune 

responses. Whereas the glucocorticoid synthesis in 

primary epithelial cells contributes to intestinal immune 

homeostasis and prevents intestinal inflammation, glucocorticoid 

synthesis in colon carcinoma cells may represent 

a tumourpromoting factor. 


Prof. Dr. Thomas Brunner 

Lehrstuhl für biochemische Pharmakologie 

Fachbereich Biologie 

Universität Konstanz 

D78457 Konstanz 

Deutschland 

Phone +49 (0)7531 88 53 70 

thomas.brunner@unikonstanz.de

66 

Christofori Gerhard | Podoplanin-mediated signalling 

and its role in collective cell invasion and metastasis 

formation (OCS 01932082006) 

Tumour invasion is the first step in the formation of metastases, 

which is the actual cause of death in most cancer 

fatalities. Originally, tumour cell invasion was thought 

to be dependent on the loss of cellcell adhesion and on 

single cell migration. However, we showed previously that 

cancer cells can also invade the surrounding tissue in a cell 

collective. We identified the small mucinlike transmembrane 

protein podoplanin as a key regulator of collective 

cell migration and invasion, and we investigated the functional 

role of podoplanin during tumour progression. 

For example, expression of podoplanin in tumour cells of 

a transgenic mouse model of pancreatic cancer caused 

tumour cell invasion in the absence of any loss of cellcell 

adhesion. Moreover, forced expression of podoplanin in 

breast cancer cell lines also leads to increased cell migration 

and invasion without loss of cellcell adhesion. Finally, 

podoplanin expression correlates with tumour invasion 

in squamous cell carcinomas (SCC) of various organs. 

Together, the results indicate that podoplanin employs a 

novel molecular pathway of inducing collective tumour 

cell invasion. However, the regulation of podoplanin expression 

in the invading cancer front as well as the molecular 

mechanisms by which podoplanin confers its promigratory 

and proinvasive function have remained elusive. 

In the past years, we investigated how the curious expression 

of podoplanin in the invasive cancer front is regulated 

and how podoplanin mediates collective cancer cell migration. 

We isolated the podoplaninexpressing invading 

cells of squamous cell carcinoma by laser capture microscopy 

of tissue sections and employed gene expression 

profiling to determine the differences between podoplaninexpressing 

and podoplaninnegative cancer cells. The 

podoplaninexpressing cells exhibited a significant upregulation 

of inflammatory signalling pathways, including the 

interferong, tumour necrosisfactora (TNFa) and transforming 

growth factorb (TGFb) pathways. Subsequent 

studies showed that indeed podoplanin expression is induced 

by the treatment of cancer cells with these inflammatory 

cytokines. We are currently ablating these signalling 

pathways in squamous cell carcinoma cells in culture 

and in mouse models to study the effect of the lack of 

these inflammatory signalling pathways on podoplanin 

expression and collective cell invasion. 

The promigratory function of podoplanin is at least in 

part mediated by the remodelling of the actin cytoskeleton 

of cancer cells. We have set out to identify binding 

partners of podoplanin, which potentially play critical 

roles in transmitting the promigratory signals of podoplanin. 

However, various biochemical analyses did not identify 

proteins that interact with podoplanin in a specific and 

robust manner. From these experiments we conclude that 

podoplanin exerts its promigratory and invasive function 

via pathways that do not include a direct interaction with 

other signalling proteins. Based on this and other evidence, 

we are currently testing the possibility that podoplanin 

exerts its signalling functions by clustering on 

the cell surface and employing its highly glycosylated ex 

tracellular domain to act as a low affinity receptor for 

chemokines and growth factors. The elucidation of podoplanin’s 

mode of action in inducing collective cell invasion 

provides important new insights into the molecular mechanisms 

of cancer cell invasion and metastasis formation. 


Prof. Dr. Gerhard Christofori 

Institut für Biochemie und Genetik 

Departement Biomedizin 

Universität Basel 

Mattenstrasse 28 

CH4058 Basel 

Phone +41 (0)61 267 35 62 

Fax +41 (0)61 267 35 66 

gerhard.christofori@unibas.ch 

Citi Sandra | The role of tight junction proteins 

in epithelial morphogenesis and differentiation 

(OCS 01916082006) 

The majority of cancers originate from epithelial cells and 

tissues, which cover all surfaces and cavities of the body 

(skin, gastrointestinal, respiratory and urinary tracts, etc.) 

and constitute glands (breast, kidney, liver, pancreas). 

Normal epithelial cells proliferate in a controlled fashion, 

are closely bound together and have a characteristic “polarized” 

shape, with apical, basal and lateral sides. When 

epithelial cells become cancerous, they “dedifferentiate” 

and lose some or most of these properties. For example, 

they may lose their ability to adhere to one another, lose 

polarity, become more motile, migrate elsewhere in the 

body and start to divide in an uncontrolled way, thus 

forming metastases. Our research focuses on the role of 

proteins, which constitute specialized “cellcell junctions”. 

Junctions are structures that control adhesion between 

cells and are also implicated in signalling mechanisms that 

regulate epithelial cell growth and proliferation. There are 

different types of junctions, and we are focusing our attention 

on “tight” and adherens junctions, which are localized 

at the apicolateral border of epithelial cells. Tight 

junctions are involved in the maintenance of the polarized 

shape and also serve to form a barrier that controls the 

passage of molecules and pathogens across sheets of epithelial 

cells. Adherens junctions play a major role in cellcell 

adhesion and signalling mechanisms that regulate 

morphogenesis and cell sorting. 

The goal of our project was to understand the role of specific 

proteins of tight junctions (cingulin and paracingulin) 

in the establishment and maintenance of the differentiated 

state and signalling properties of epithelial cells, using 

as the main experimental approaches studies on cells 

in culture and on human epithelial lung cancer tissues. We 

made important discoveries about the role of cingulin and 

paracingulin in controlling the activities of RhoA and 

Rac1, molecular switches that regulate the assembly of 

the cytoskeleton and also in controlling proliferation and 

gene expression in epithelial cells. The activities of RhoA

and Rac1 are frequently altered in cancer tissues, which 

could account for their altered migratory properties. 

Therefore, our studies are directly relevant to understanding 

the molecular mechanisms of regulation of signalling 

pathways that are altered in cancer. We further studied 

the dynamics of cingulin and paracingulin in living cells 

and clarified differences in their behaviour and localization, 

which will help to clarify their redundant and nonredundant 

functions. Using antibodies that we developed in 

our laboratory, we studied the expression of cingulin in 

different types of human lung tumours in collaboration 

with the Department of Clinical Pathology at Geneva 

University Medical School. These results, and results obtained 

using several other antibodies against tight junction 

proteins and reversetranscription polymerase chain 

reaction to assess gene expression, allowed us to propose 

a new molecular classification of lung carcinomas based 

on expression of specific tight junction proteins. Recently, 

we identified a novel adherens junction protein, PLEKHA7, 

against which we developed specific monoclonal antibodies, 

and which we would like to use to examine its expression 

in human cancer, which has not been done so far. 

In summary, the results that we obtained have provided 

new information on the function of certain tight junction 

proteins, their role in the process of differentiation and 

cancer formation and their possible use in cancer diagnosis. 

In addition, our studies led to the discovery and preliminary 

characterization of a new adherens junction protein. 


Dr Sandra Citi 

Département de biologie moléculaire 

Sciences III 

Université de Genève 

4, boulevard d’Ivoy 

CH1205 Genève 

Phone +41 (0)22 379 61 82 

Fax +41 (0)22 379 68 68 

sandra.citi@unige.ch 

Donda Alena | CD1d-antitumor bifunctional molecules 

to redirect the innate and adaptive immune responses 

to the tumor site (OCS 02248082008) 

When activated by the CD1d protein expressed by antigenpresenting 

cells (APC), invariant natural killer T 

(iNKT) cells are able to transactivate the innate and adaptive 

immune system, and their antitumour activity is well 

demonstrated. In the initial phase of this project, we 

showed that repeated injections of a soluble recombinant 

CD1d protein loaded with the glycolipid ligand agalactosyl 

ceramide (aGalCer) was able to induce sustained iNKT 

cell activation, in contrast to the shortlived stimulation 

obtained with the ligand alone. Importantly, when CD1d 

was fused to an antitumour antibody fragment (CD1dantiHER2), 

delayed tumour growth was obtained, associated 

with tumour infiltration by iNKT, NK and T lymphocytes, 

all able to kill cancer cells. 

In order to get closer to a clinical application, the second 

phase of this project included the following aspects: 1) 

We extended the targeting of CD1d to different types 

of cancer. In addition to the targeting of HER2 overex 

pressed in breast cancer, we developed a CD1dantiCEA 

fusion protein specific of a tumour antigen overexpressed 

in colon cancer, as well as a CD1dantiVEGFR3 fusion 

protein targeting a marker of tumour neovascularization. 

Sustained iNKT activation and inhibition of tumour 

growth by these three CD1d bifunctional proteins were 

evidenced in several tumour models. 2) At the cellular 

level, in vivo and in vitro experiments demonstrated that 

iNKT cell activation by soluble CD1d proteins prevented 

the negative retrocontrol of PD1/PDL1 interaction that 

normally occurs during cellcell interaction between iNKT 

and APCs, leading to their subsequent unresponsiveness. 

The attenuated PD1 upregulation largely explains the 

sustained iNKT cells obtained with recombinant CD1d 

proteins, which is optimal for a systemic treatment. 3) 

Several in vivo experiments have shown that the adjuvant 

effect of CD1dmediated therapy on the adaptive immune 

response remains limited by immunosuppressive 

mechanisms developed in the periphery and at the tumour 

site. In particular, the expansion of myeloidderived 

suppressor cells (MDSCs) induced by the tumour environment 

is known to inhibit the antitumour immune response 

and remains a challenge for cancer immunotherapy. MD 

SCs act by various mechanisms, among which are several 

enzymatic activities such as arginase 1, which depletes arginine 

essential for the activity of T lymphocytes. We 

could demonstrate the inhibitory effect of arginase 1 on 

CD1dmediated therapy in a mouse model in which arginase 

1 has been eliminated in the myeloid compartment. 

In these mice, the antitumour effect of CD1dantitumour 

treatment was indeed far more potent than in mice with 

active arginase 1. 

In view of these results, we are testing chemotherapeutic 

agents able to deplete preferentially MDSCs, such as 

5fluorouracil. The next step is to combine CD1dmediated 

immunotherapy with chemotherapy, and these 

protocols will be tested in two transgenic mouse models 

developing spontaneous tumours, representative of melanoma 

tumours and prostate cancer in humans. Combination 

of multiple anticancer therapies is more and more 

considered, as it can result in a synergistic tumour inhibition 

and limit tumour escape. 


Dr Alena Donda 

Département de biochimie 

Université de Lausanne 

Chemin des Boveresses 155 

CH1066 Epalinges 

Phone +41 (0)21 692 58 57 

alena.donda@unil.ch 

67

68 

Frei Christian | The function of Drosophila hypoxia- 

inducible factor (HIF-1) and its transcriptional targets 

in cellular growth control (OCS 01575082004) 

Several studies in recent years have shown that tumours 

differ significantly from normal tissues: Primary tumour 

and cancer cells are often exposed to a low oxygen environment, 

called hypoxia, and have to adapt their metabolism 

accordingly. Essential for the adaptation is the transcription 

factor HIF (hypoxiainducible factor), which 

induces genes that are required for survival and growth 

of cancer cells under such conditions. Whereas HIF is 

stabilized under hypoxia, this factor is hydroxylated and 

degraded under a normal/high oxygen environment. The 

enzymes that hydroxylate HIF are PHD1, PHD2 and PHD3 

(prolyl hydroxylase domain) and belong to the family 

of oxygen and 2oxoglutaratedependent dioxygenases. 

Whether and how PHDs control growth and metabolism 

in an HIFindependent manner was not known and was 

the question of this study. 

The molecular functions of PHDs and HIF are conserved 

between the fruit fly Drosophila melanogaster and humans, 

suggesting that the cellular adaptation to hypoxia 

developed early during evolution. In our study, we used 

biochemical methods to find new PHDinteracting proteins, 

and we focused on proteins that would bind to 

PHDs in fly as well as human cells. One such protein was 

pyruvate kinase (PK), a glycolytic enzyme required for the 

synthesis of pyruvate. The human cancer cell line HeLa 

was used for subsequent characterization. We found that 

cells containing a reduced amount of PHD3 (using the 

RNAi methodology) show an increase in PK enzymatic 

activity, leading to more pyruvate. This effect was seen 

particularly under hypoxic conditions, suggesting that the 

binding of PHD3 and PK might be important for the cellular 

adaptation to low oxygen. Of note, PK is not a novel 

PHD3 hydroxylation target but is controlled by direct 

binding by PHD3 that blocks formation of the active tetramer 

form of PK. 

Most tumours show a characteristic increase in glucose, 

resulting in higher glycolytic rates. Since PK activity is reduced 

in response to PHD3 binding, we studied whether 

the cellular metabolism would adapt to low PHD3 levels. 

Indeed, we observed higher activity of the mitochondrial 

TCA cycle, an increase in reactive oxygen species and a reduction 

in cell proliferation. We concluded that the interaction 

between PHD3 and PK constitutes a novel mechanism 

to control glycolysis. Since PHD3 itself is a HIF target 

and accumulates under hypoxic conditions, this mechanism 

applies particularly to cells under a low oxygen environment. 

In the future, we would like to test whether the 

PHD3/PK interaction can be pharmacologically blocked, 

and whether this affects the growth of tumours. 

Project coodinator 

Prof. Dr. Christian Frei 


ETH Hönggerberg 

HPM F38.2 

Schafmattstrasse 18 

CH8093 Zürich 

Phone +41 (0)44 633 33 94 

Fax +41 (0)44 633 13 57 

christian.frei@cell.biol.ethz.ch 

Freyvon Matt Brigitte M. | Androgen-mediated gene 

delivery (AMGD) (KLS 02015022007) 

We recently developed a new procedure of transferring 

genes by targeting nuclear steroid receptors to achieve 

receptordependent enhanced transgene DNA expression 

(Rebuffat et al., Nature Biotechnology, 2001;12:1155 

1161). This strategy, termed “Steroid Mediated Gene Delivery” 

(SMGD), facilitates the nuclear uptake of transfected 

DNA using glucocorticoid receptors (GR), which 

are natural cytoplasmnucleus shuttles. We synthesized 

constructs consisting of the synthetic steroid dexamethasone 

coupled to a DNAbinding moiety. These ligand 

DNA constructs translocated and expressed transgene 

DNA only in cells possessing the GR, an effect even more 

pronounced in growtharrested cells. These results were 

the first proofofprinciple that a chemically modified 

steroid ligand can be used for cellspecific DNA delivery in 

vitro. A patent covers this strategy. 

As a potentially clinically relevant extension we proposed 

to apply this strategy for targeting androgen receptors 

(AR) in prostate cancer cells. These cells frequently become 

androgenindependent and therapyresistant partially 

attributed to alterations in the AR ligand binding domain. 

To target prostate cancer cells with mutated ARs, 

we synthesized >90 steroid derivatives and a novel gene/ 

drug delivery vehicle. The vehicle comprises branches, 

each of which can be selectively and efficiently functionalized 

with, first, an agent that allows to cross the cell 

membrane and, second, an agent that facilitates the 

crossing of the nuclear membrane. Another branch will be 

used to attach a cytotoxic gene or an anticancer drug. 

To some extent, as a coproduct this derivative library of 

more than 90 compounds offers an additional potential 

a) for androgenmediated imaging (AMI) using positron 

emission tomography (PET); b) to provide clinically relevant 

agonists or antagonists for AR; and c) for androgen 

mediated gene delivery (AMGD). All three aspects are in 

progress. 

Potential 1): Out of the >90 derivatives 3 compounds 

have excellent binding capacities to the AR – a prerequisite 

to be used for AMGD, AMI or as AR regulators. Since 

these 3 derivatives are iodinated and fluorinated, and since 

there is a high demand for specific PETimaging agents, 

these compounds will be evaluated for PET imaging in collaboration 

with the Department of Nuclear Medicine at 

Bern University Hospital (Prof. Krause). In addition, these 

derivatives will be used for the AMGD strategy. 

Potential 2): Very recently a promising antagonist, RB346, 

was identified within the derivatives. Importantly, the 

binding affinity of this ligand to wild type and mutant 

ARs is the same or even better than that of bicalutamide, 

a drug used for prostate cancer treatment in patients. Notably 

RB346 maintains its antagonistic effect towards the 

mutant W741L without the agonist action of bicalutamide. 

We will now study the mechanism of action in vitro 

and in vivo in more detail and analyze the binding affinity 

of all the other ligands to selected nuclear receptors.

Potential 3): During the past two years we have designed, 

developed and partially synthesized an innovative novel 

transport vector concept. To test the functionality of this 

vector we used fluorescent mimics for each of the single 

binding elements. We present evidence of a specific docking 

to the prostate cancer cell, internalization and binding 

to ARpositive but not ARnegative cells. At present we are 

attempting to attach a toxin/drug/plasmid and perform in 

vitro studies. If successful, we will investigate this tool in 

control and tumourbearing mice and analyze as recently 

published the efficacy by determining the apoptosis rate. 


Prof. Dr. Brigitte M. Freyvon Matt 

Departement Nephrologie und Hypertonie 

Inselspital 

Freiburgstrasse 15 

CH3010 Bern 

Phone +41 (0)31 632 94 39 

Fax +41 (0)31 632 44 36 

brigitte.frey@dkf.unibe.ch 

Gasser Susan | The RPA70 interaction domain of Sgs1 

contributes to both replication checkpoint activation 

and fork stability (OCS 02126082007) 

During DNA replication, eukaryotic cells are particularly 

sensitive to intrinsic sources, such as fork collapse, and to 

extrinsic DNA damaging agents. Oncogenically transformed 

cells show signs of replication stress even in the 

absence of exogenous damaging agents. To ensure genome 

integrity, stalled replication forks are stabilized by 

the checkpoint kinases (ATR) and a RecQ helicase, which 

in yeast is called Sgs1 and in humans BLM (Cobb et al. 

2005). BLM carries the mutations responsible for Bloom’s 

syndrome, a cancerprone genetic predisposition. In yeast, 

the ATR homologue, Mec1 and Sgs1 contribute to DNA 

polymerase stability independently, yet both interact with 

the singlestrand binding heterotrimeric replication protein 

A (RPA). RPA was shown to recruit Mec1Ddc2 to a 

stalled or damaged replication fork but also to be a target 

of Mec1 phosphorylation after checkpoint activation. 

Previous work from our laboratory also showed that RPA 

interacts tightly with Sgs1. 

To analyze if the Mec1 and Sgs1 polymerase stabilizing 

pathways converge on RPA, we examined the role of the 

Sgs1RPA interaction in stabilizing stalled replication forks 

by disrupting their interaction. We mapped the Sgs1RPA 

interaction site to the acidic region Nterminal of the Sgs1 

helicase domain. This region contains 3 T/SQ sites which 

are Mec1 target sites. We created two sgs1 mutants: 

sgs1-r1, which lacks the RPA interaction site, and sgs1 

4A, in which the phosphorylation sites are modified. 

These were examined for their effects on both checkpoint 

response and polymerase stability at stalled forks. The 

deletion construct reduces the affinity of Sgs1 and RPA 

in vivo and in vitro. We found that both this interaction 

site and the helicase activity of Sgs1 are important for stabilizing 

DNA pol a/primase at stalled forks. Unlike the 

synergism observed between sgs1D and the Sphase specific 

Mec1 mutation, mec1-100, sgs1r1 and mec1-100 

mutations are epistatic. This places sgs1-r1 downstream 

of mec1-100. Indeed, once the Sgs1 r1 domain is phosphorylated 

by Mec1, this site then binds the downstream 

checkpoint kinase Rad53, helping stimulate the checkpoint 

response to replicative stress. Our study thus links 

the ATR homologue and the BLM helicase in orchestration 

of the checkpoint response at stressed replication forks. In 

this way both proteins contribute to cancer prevention. 

They may also be useful targets for enhancing cancer cell 

death through combined chemotherapy. 


Prof. Dr. Susan M. Gasser 




CH4058 Basel 

Phone +41 (0)61 697 72 55 

Fax +41 (0)61 697 39 76 

susan.gasser@fmi.ch 

Gönczy Pierre | Coupling cell polarity and cell division 

in C. elegans embryos: Novel insights into proliferation 

control mechanisms (OCS 01676022005) 

Background 

Defective epithelial cell polarity is thought to contribute 

to tumour development. The PAR proteins were originally 

identified in the nematode C. elegans; they play a crucial 

role in establishing cell polarity across metazoan evolution, 

including in mammals. In fact, the human homologue 

of PAR4 is LKB1, a tumoursuppressor protein affected 

in the autosomal inherited PeutzJeghers syndrome, 

exemplifying the link between cell polarity and tumour 

development. Despite these and other findings, the mechanisms 

by which cell polarity impinges on cell cycle progression 

are poorly understood. 

Specific aim 

We set out to analyze the mechanisms coupling PARdependent 

polarity and cell division timing using the early 

C. elegans embryo as a model system. 

Principal results 

We had shown previously that activation of the DNA replication 

checkpoint contributes to coupling polarity cues 

and cell cycle progression in twocell stage C. elegans embryos, 

by retarding preferentially entry into mitosis in the 

cell located on the posterior side of the embryo. In the 

present study, we discovered that such coupling relies in 

addition on a mechanism that promotes mitosis preferentially 

in the anterior cell. We found that the Pololike kinase 

PLK1, an inducer of mitotic entry across eukaryotic 

evolution, is distributed in an asymmetric manner in twocell 

stage C. elegans embryos, with more protein present 

in the anterior. Moreover, we demonstrated that PLK1 

asymmetry is regulated by PARdependent polarity. We 

then conducted experiments that support the view that 

PLK1 asymmetry is important for asynchronous division 

of twocell stage C. elegans embryos. Together with the 

preferential retardation of mitotic entry in the posterior 

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cell, this novel mechanism serves to couple polarity cues 

with cell cycle progression during early development of 

C. elegans embryos. As the PAR proteins and PLK kinases 

are conserved across metazoan evolution, we anticipate 

the novel coupling uncovered here to be similarly conserved. 

Moreover, given that the Pololike kinase PLK1 

has been causally implicated in tumourigenesis, we expect 

our findings to ultimately result in advances for the understanding 

and treatment of cancer. 


Prof. Dr Pierre Gönczy 



Faculté des sciences de la vie 


SV 1526 

Station 19 


Phone +41 (0)21 693 07 11 

pierre.gonczy@epfl.ch 

Gönczy Pierre | Mechanisms of centrosome 

duplication in C. elegans and human cells: From model 

organism towards therapeutic opportunities 

(KLS 02024022007) 

Background 

The centrosome is the major microtubuleorganizing centre 

of animal cells. There is a single centrosome early in 

the cell cycle, which duplicates during S phase to direct 

bipolar spindle assembly during mitosis, thus ensuring 

faithful segregation of the genetic material. Formation of 

a new centriole next to each existing one is critical for centrosome 

duplication. Failure of centrosome duplication 

can result in monopolar spindle assembly, excess centrosome 

duplication in multipolar spindle assembly and thus 

genome instability. Furthermore, cancer cells often exhibit 

aberrations in centrosome number, the severity of 

which correlates with tumour progression. Therefore, centrosome 

duplication offers unique therapeutic and diagnostic 

opportunities in the fight against cancer. 

Specific aim 

We set out to combine the strengths of two experimental 

systems, embryos of the nematode C. elegans and human 

cells in culture, to gain novel insights into the mechanisms 

of centrosome duplication. 

Principal results 

We obtained the most significant results with the C. elegans 

protein SAS6 and the human protein CPAP. In C. elegans, 

the proteins SPD2, ZYG1, SAS6, SAS5 and 

SAS4 are essential for centriole formation, but the mechanisms 

underlying their requirement remained unclear. 

During this project, we uncovered that the kinase ZYG1 

phosphorylates the protein SAS6 at the serine residue 

123 in vitro. Importantly, we showed that this phosphorylation 

event is crucial for centriole formation in C. elegans 

embryos. Our results lead us to conclude that phosphorylation 

of the evolutionarily conserved protein SAS6 

is critical for centriole formation and thus for faithful cell 

division. Our most significant finding in human cells pertained 

to the role of CPAP in centriole elongation. Nor 

mally, the new centriole elongates to reach the same size 

as that of the old one. The mechanisms that govern elongation 

of centrioles and their potential relevance for cell 

division were not known prior to our work. In the course 

of this project, we demonstrated that overexpression of 

the SAS4related protein CPAP results in the formation 

of abnormally long centrioles in human cells, which eventually 

leads to the assembly of a multipolar spindle and 

defective cell division. Overall, these findings revealed 

that centriole length must be carefully regulated to ensure 

accurate cell division. 







SV 1526 

Station 19 


Phone +41 (0)21 693 07 11 


Grassi Fabio | Synergy between oncogenic Notch and 

pre-T-cell receptor (pre-TCR) signaling microdomains 

in leukemogenesis (OCS 01933082006) 

Tcell acute lymphoblastic leukaemia (TALL) is a malignant 

disease of thymocytes (the cell in the thymus that 

normally differentiates into a circulating T lymphocyte) 

that preferentially affects children with variable prognosis. 

The variable prognosis is determined by the heterogeneity 

of the “molecular alterations” involved in the initiation 

and progression of the disease. This disease also 

received attention because children cured with gene therapy 

for hereditary immunodeficiency three years later developed 

TALL, which was determined by the virus used 

to correct the genetic defect. The long latency of the disease 

demonstrates the requirement of successive multiple 

molecular alterations (after the original one determined 

by virus integration into a particular region of the patient 

genome) for TALL development. The strength of the 

therapy used in TALL is based on the risk of relapsing disease, 

which is determined by the nature of the molecular 

alterations responsible for the disease. Thus it is important 

to thoroughly characterize these molecular alterations 

and find new targets for TALL therapy. In refractory subjects, 

intensification of existing treatments is unlikely to 

raise cure rates substantially and will instead increase 

treatmentrelated mortality and the risk of second cancers. 

Leukaemic cells are characterized by uncontrolled 

proliferation, which at least in part depends on concentration 

of particular proteins that induce (e.g. signal) cell proliferation 

into specific plasma membrane microdomains. 

We studied and characterized signalling by CD3 chains 

upon their deliberate diversion out of glycosphingolipidenriched 

microdomains. To this end we used a modified 

version of calnexin (a chaperone protein normally residing 

in the endoplasmic reticulum, ER, and associated with

CD3 chains in thymocytes) in which the ER retention signal 

was removed to allow delivery of calnexin and associated 

proteins to the plasma membrane. Mutant calnexin 

isoforms, either palmitoylated or not or with different 

cytoplasmic tails, were used to deliver CD3 to glycosphingolipidenriched 

microdomains or plasma membrane or 

endosomes. Our study demonstrated that diversion of 

signalling complexes active in the generation of leukaemia 

in distinct signallingincompetent domains of the plasma 

membrane significantly attenuated cell proliferation. 

Therefore, therapeutic strategies aimed at destabilizing 

glycosphingolipidenriched signallingcompetent plasma 

membrane microdomains might help in controlling proliferation 

of TALL cells. 

Dr. Fabio Grassi 

Istituto di ricerca biomedica (IRB) 

Via Vincenzo Vela 6 

CH6500 Bellinzona 

Phone +41 (0)91 820 03 23 

Fax+41 (0)91 820 03 05 

fabio.grassi@irb.unisi.ch 

Hall Michael N. | Proteomic analysis of the cancer- 

promoting mTOR pathway (KLS 01991022007) 

The target of rapamycin is an atypical Ser/Thr kinase that 

positively regulates cell size, proliferation and cell motility 

in all eukaryotic organisms. TOR forms two functionally 

distinct multiprotein complexes, TORC1 and TORC2, 

which are conserved from yeast to human. Nutrients 

activate mammalian TOR (mTOR) complex 1 (mTORC1), 

whereas growth factors activate mTORC1 and mTOR 

complex 2 (mTORC2). Raptor and rictor are essential 

components of mTORC1 and mTORC2, respectively. Importantly, 

mTOR also promotes tumourigenesis by as yet 

incompletely understood mechanisms. The finding that 

some tumours respond to the rapamycin or its analogues 

(rapalogues) underscores a role of mTOR in tumourigenesis. 

Despite indepth knowledge of the mechanisms by 

which TOR exerts its control of transcription, translation, 

ribosome biogenesis, and autophagy, very few direct 

mTOR targets have been identified. 

Recently, we set out to find novel TOR targets by functional 

proteomics. Conceptually, we grew cells in a medium 

containing isotopically labelled amino acids (“heavy” 

culture) and mixed cell extracts in a 1:1 ratio with those 

from normally grown cells (“light” culture). The extracts 

were digested and phosphopeptides were enriched by 

way of immobilised metal affinity chromatography 

(IMAC/TiO2) and the phosphopeptides were measured in 

a highresolution mass spectrometer. Because TOR possesses 

kinase activity, potential TOR targets can be detected 

by a decreased extent of phosphorylation following 

inhibition of TOR or disruption of the TOR complexes. 

We first established the proteomics workflow in the “simple” 

eukaryote S. cerevisiae. In this study we were able to 

quantitate approximately 2,400 phosphorylation events. 

Interestingly, the study revealed that yeast TORC1 

controls phosphorylation of the regulatory subunit of 

cAMPdependent protein kinase A (PKA), suggesting that 

TORC1 controls PKA toward some substrates. The main 

goal of our studies, however, was to identify novel targets 

of mammalian TOR. To distinguish between mTORC1 

and mTORC2specific phosphorylation, we specifically 

deleted Raptor or Rictor using an inducible gene knockout 

system in mouse embryonic fibroblasts (MEFs). 

We detected 4,584 phosphorylation sites on 1,398 proteins 

and identified 26 novel mTOR effectors. Kinase 

motif analysis revealed that mTORdependent phosphorylation 

target sites comprise the pSer/ThrPro and Arg 

XXpSer motifs. These results suggest that mTOR phosphorylates 

its novel effectors directly or via AGC kinase 

activation. We then compared the biological properties of 

all novel mTOR effectors and identified several functional 

clusters. Many of the novel mTOR effectors are overexpressed 

in cancer or linked to metabolic disorders. Thus, 

mTOR regulates a large and diverse set of effectors to ultimately 

control cell growth and aging. 


Prof. Dr. Michael N. Hall 

Departement Biozentrum 


Klingelbergstrasse 50/70 

CH4056 Basel 

Phone +41 (0)61 267 21 50 

Fax +41 (0)61 267 21 59 

m.hall@unibas.ch 

Heim Markus Hermann | Hepatocarcinogenesis in 

chronic hepatitis C (OCS 02192022008) 

Background 

Chronic hepatitis C (CHC) is a major cause of liver disease 

worldwide and a risk factor for cirrhosis and hepatocellular 

carcinoma (HCC). Regardless of its aetiology, cirrhosis 

is a major clinical risk factor for HCC, and indeed, hepatitis 

C virus (HCV) associated HCC generally develops in 

patients with cirrhosis. There is also evidence for HCV 

specific tumourigenic pathways, mainly involving HCV 

core and NS5A proteins. However, the molecular pathways 

responsible for HCV induced hepatocarcinogenesis 

have not yet been characterized. A potential tumourigenic 

pathway could involve protein phosphatase 2A (PP2A) 

and protein arginine methyltransferase 1 (PRMT1), since 

both enzymes are dysregulated in chronic hepatitis C and 

both enzymes have been involved in chromatin remodelling 

and DNA damage repair. 

Aim 

The aim of the studies was to elucidate the role of PP2A 

overexpression and of PRMT1 inhibition for carcinogenesis. 

Methods 

We used cell lines that allow the inducible expression of 

hepatitis C virus proteins (UHCV57.3) and of the catalytic 

subunit of PP2A (UPP2AC8) as well as Huh7.5 cells 

infected with recombinant cell culturederived HCV 

(HCVcc) to study epigenetic histone modifications and 

DNA damage repair. We also investigated if the methyl 

group donor SadenosylLmethionine (SAMe) could reverse 

the HCV induced changes. 

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Results 

The induction of viral proteins, the overexpression of 

PP2Ac or the infection of Huh7.5 cells with HCVcc resulted 

in an inhibition of histone H4 methylation/acetylation 

and histone H2AX phosphorylation in a significantly 

changed expression of genes important for hepatocarcinogenesis 

and inhibited DNA damage repair. These 

changes were partially reversed by the treatment of cells 

with the methylgroup donor SadenosylLmethionine 

(SAMe). 

Conclusion 

The correction of defective histone modifications by SadenosylLmethionine 

makes this drug a candidate for 

chemopreventive therapies in patients with chronic hepatitis 

C who are at risk for developing hepatocellular carcinoma. 


Prof. Dr. Markus Hermann Heim 

Klinik für Gastroenterologie und Hepatologie 

Universitätsspital Basel 

Petersgraben 4 

CH4031 Basel 

Phone +41 (0)61 265 51 74 

markus.heim@unibas.ch 

Hemmings Brian A. | Role of protein kinase B (PKB/Akt) 

in cell transformation and cancer 

(OCS 01667022005) 

Conserved from primitive metazoans to humans, the serine/threonine 

protein kinase B (PKB, also known as Akt) 

belongs to the AGC group of protein kinases and has 

emerged as a critical signalling molecule as a mediator of 

the phosphoinositide 3kinase (PI3K) pathway. Activated 

upon PI3K signalling, PKB phosphorylates a wide range of 

substrates influencing diverse cellular and physiological 

processes, including cell cycle progression, cell growth 

and differentiation, cell survival/suppression of apoptosis, 

metabolism, angiogenesis and motility. As one of central 

node of signalling pathways, hyperactivation of PKB in 

most types of human cancers has been extensively studied 

towards an effective cancer therapy. 

Our research work led to the discovery of DNAdependent 

protein kinase (DNAPK) as a novel upstream kinase 

of PKB. We showed that PKB interacts and is phosphorylated 

by DNAPK adjacent to DNAdoublestrand breaks 

induced by girradiation, thus protecting the cell from 

DNAdamageinduced apoptosis. In addition, we also investigated 

the mechanisms of how activated PKB signalling 

inhibits p53 activity during DNA damage. We identified 

a novel PKB substrate, Twist1, a basic helixloophelix 

transcription factor that is phosphorylated by PKB on serine 

42 (S42) when the cells are exposed to girradiation 

or genotoxic drug Adriamycin. S42 phosphorylation of 

Twist1 inhibits p53 activity. Mutation of S42 to alanine 

to prevent PKBmediated phosphorylation sensitizes cells 

to DNA damage. Moreover, phosphorylation of Twist1 

was demonstrated in various human cancer tissues, suggesting 

that this posttranslational modification ensures 

functional activation of Twist1 following promotion of 

survival during carcinogenesis. In parallel and in collaboration 

with other laboratories, we showed that the promyelocytic 

leukaemia (PML) tumour suppressor protein 

was activated by homeodomaininteracting protein kinase 

(HIPK2) in early stage responses to DNA damage. 

Overexpression of Twist1 has been reported in 21 cancer 

types including breast cancer, melanoma and prostate 

cancer, and correlates with poor prognosis in clinic. 

We showed that Twist1 phosphorylation on S42 promotes 

full epithelialmesenchymal transition and this modification 

is essential for breast cancer metastasis to the lung 

in a mouse model. Furthermore, 1,532 invasive breast tumour 

samples were examined and revealed Twist1 phosphorylation 

in over 90 % of these tumour samples, including 

both invasive ductal and invasive lobular carcinomas, 

indicating an important regulatory role of Twist1 phosphorylation 

in cancer invasion and metastasis. As Twist1 

does not seem to be active postnatally in human physiology 

but is deregulated during tumour progression, we are 

continuing to investigate if phosphorylated Twist1 may be 

a novel biomarker for tumour metastasis and a potential 

therapeutic target for metastatic cancers. 






CH4058 Basel 

Phone +41 (0)61 697 48 72 

Fax +41 (0)61 697 39 76 


Hemmings Brian A. | The role of human protein 

kinase NDR in cell morphogenesis, cell division, 

growth control and cancer (OCS01942082006) 

The NDR proteins family is a group of serine/threonine kinases 

that is conserved from yeast to man. They are members 

of the AGC kinase family and include molecules such 

as LATS, Cbk1, Orb6, Cot1 and Dbf2. In budding yeast 

Dbf2 is an integral part of the mitotic MEN network, and 

Cbk1 is required for the regulation of morphological 

changes. Recent genetic studies have resulted in the isolation 

of various important factors controlling these processes. 

Significantly, these studies have also shown that 

the yeast counterparts of NDR interact with Mob1 and 

Mob2. These interactions are very important, since they 

are essential for the activity and biological function of 

these yeast kinases. 

Based on these findings our laboratory could show that 

the interaction between human MOB1 (hMOB1) and 

MOB2 (hMOB2) with the human NDR and LATS kinases 

plays a decisive role. By testing mutants of hMOB1, 

hMOB2, NDR and LATS, we observed that a direct interaction 

between hMOB1 and NDR or LATS is needed to 

ensure activation of these kinases, while the interaction of

hMOB2 with NDR results in inhibition of kinase activity. 

Furthermore, we could define the nature of the kinase responsible 

for the activating phosphorylation of NDR kinase. 

Interestingly, we found that the MST1 kinase is the 

main player. After we showed that human NDR plays a 

crucial role in centrosome biology, we described that this 

function is controlled by MST1. Moreover, our research 

revealed that MST1/NDR signalling also plays a role in the 

regulation of normal cell death. Therefore, our studies 

demonstrated that two important cell biological processes 

are regulated by NDR kinases. On the one hand, NDR 

plays a role in the accurate duplication of centrosomes, 

which can play a critical role in the correct distribution of 

DNA information. On the other hand, we could show that 

NDR is required for accurate execution of programmed 

cell death. Since both processes can play a role in the development 

of cancer, our data suggest that NDR kinases 

are very likely to play an important role in cancer. 

In this context it is noteworthy that we recently defined a 

function for NDR kinases in normal cell multiplication. By 

downregulating NDR expression using RNAi technology 

we found that human cells require NDR to progress into Sphase 

of the cell cycle. Furthermore, we have inactivated 

the NDR1 and NDR2 genes in the mouse in order to allow 

studies of the physiological functions of NDR kinases. Significantly, 

NDR1 knockout animals developed Tcell lymphomas, 

indicating that NDR kinases can play a role as 

tumour suppressor proteins. The analysis of NDR2 knockout 

mice is currently ongoing to obtain the full spectrum 

of the physiological functions that play a role in cancer development. 






CH4058 Basel 

Phone +41 (0)61 697 48 72 

Fax +41 (0)61 697 39 76 


Herr Winship | HCF-1 regulation of genomic stability 

during cell division (OCS 02047022007) 

We studied the function of a protein called HCF1 that 

controls human cell proliferation and is important for the 

correct distribution of the genome during cell division. 

The studies showed that HCF1 associates with a large 

number of cellular proteins, many of which are involved in 

the modification of chromatin – the integrated structure 

of DNA and proteins responsible for the regulation of 

gene expression and the proper chromosome replication 

and segregation during cell division. These studies also 

showed that a process of proteolytic maturation specific 

to HCF1 is achieved by the enzyme Olinked Nacetylglucosamine 

transferase (OGT), for which the only known 

activity until now was protein glycosylation. Given that 

OGT and glycosylation are linked to metabolism, these 

studies demonstrated a nexus between metabolism and 

cellcycle regulation. 

Objectives 

This project had three objectives: 1) to understand the 

roles of HCF1 in the cell cycle; 2) to uncover the mechanisms 

of HCF1 proteolytic maturation; and 3) to elucidate 

how the two HCF1 subunits can influence one another. 

Method and process 

To realize the first objective, proteins associated with 

HCF1 were identified via biochemical purification and 

mass spectroscopy, followed by bioinformatic analysis as 

well as studies of known HCF1 protein associations by 

molecular analysis. The second objective was realized by 

(i) biochemical purification; (ii) directed analysis of HCF1 

modifications linked to proteolysis of the protein; and (iii) 

determination of OGT activity. For the last objective we 

analyzed the cellcycle defects – in particular mitosis – resulting 

in the presence of HCF1 mutant proteins. 

Results 

The analyses of HCF1associated proteins showed that 

HCF1 associates with a large number of protein complexes 

that regulate chromatin function. The analysis 

of HCF1 activity in promoting DNA replication during the 

S phase of the cell cycle showed that the association of 

HCF1 with E2F1, a transcription factor crucial for entry 

into S phase, and the family of mixed-lineage leukaemia 

(MLL) histone methytransferases is important not only to 

activate S phase but also to activate apoptosis following 

DNA damage or inappropriate activation of E2F1. 

Our studies on the proteolytic maturation of HCF1 and 

the functional interaction between the resulting subunits 

demonstrated that the enzyme OGT responsible for protein 

glycosylation is unexpectedly also directly involved 

in the proteolysis of HCF1. The consequence of HCF1 

cleavage by OGT is that the Nterminal HCF1 subunit is 

glycosylated such that it does not repress the activities of 

the Cterminal subunit in M phase. These results reveal a 

nexus between the covalent modification and proteolysis 

of a protein and suggest an interaction pathway between 

metabolism and the regulation of cell proliferation. 


Prof. Dr Winship Herr 

Centre intégratif de génomique (CIG) 

Faculté de biologie et de médecine 


Génopode Building 

CH1015 Lausanne 15 

Phone +41 (0)21 692 39 22 

Fax +41 (0)21 692 39 25 

winship.herr@unil.ch 

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Hübscher Ulrich | Repair of oxidation damages in 

DNA: DNA synthesis over lesions by posttranslationally 

modified human DNA polymerase lambda 

(OCS01996022007) 

The maintenance of genetic stability is of crucial importance 

for any form of life. Prior to cell division in each 

mammalian cell, the process of DNA replication must 

faithfully duplicate the three billion bases with an absolute 

minimum of mistakes. On the other hand, DNA itself 

is highly reactive and is constantly attacked by endogenous 

factors and is also easily altered by intracellular 

processes such as oxidation. 7,8dihydro8oxoguanine 

(8oxoG) is recognized as one of the most important oxidative 

DNA lesions because of its prevalence in DNA and 

its mutagenic potential in cells. It has been estimated that 

the steadystate level of 8oxoG lesions is about 10 3 per 

cell in normal tissues and up to 10 5 lesions per cell in cancer 

tissues. All human DNA polymerases (DNA pols) studied 

so far show significant errorprone bypass of 8oxoG, 

since they preferentially incorporate an adenine opposite 

an 8oxoG instead of the correct cytosine. This would 

lead to subsequent GC to TA transversion mutations 

with the consequence of cell transformation and eventually 

leading to cancer. 

Findings and relevance 

We reconstituted with human proteins a completely errorfree 

bypass pathway for an 8oxoG lesion located in codon 

13 of the human HRAS gene. Specialized DNA pols 

are required for lesion bypass in human cells. Auxiliary 

factors play an important but so far poorly understood 

role. A major and specific effect was found for 8oxoG 

bypass with DNA pol l. PCNA and RPA allowed correct 

incorporation of dCTP opposite a template 8oxoG 

1200fold more efficiently than the incorrect dATP by 

DNA pol l. Our findings suggest a novel accurate mechanism 

to reduce the deleterious consequences of oxidative 

damage. In addition, they point to an important role for 

PCNA and RPA in determining a functional hierarchy 

among different DNA pols in lesion bypass. 

New data 

We identified several phosphorylation sites of DNA pol �. 

Experiments with phosphorylationdefective mutants 

suggest that phosphorylation of T553 is critical for maintaining 

DNA pol � stability, since it is targeted to the proteasomal 

degradation pathway via ubiquitination unless 

this residue can be phosphorylated. In particular, DNA pol 

� is stabilized during cell cycle progression in late S and G2 

phase. This likely enables DNA pol � to properly conduct 

repair of damaged DNA during and after S phase. 


Prof. Dr. Ulrich Hübscher 

Institut für Veterinärbiochemie und 

Molekularbiologie 




Phone +41 (0)44 635 54 72 

Fax +41 (0)44 635 68 40/59 04 

hubscher@vetbio.uzh.ch 

Huelsken Joerg | Role of inflammation in Wnt 

mediated tumorigenesis (OCS 01838022006) 

A large amount of data demonstrates the impact of the 

Wnt pathway on the intrinsic ability of the tumour cells to 

proliferate and survive, thereby promoting tumourigenesis. 

We have now obtained data suggesting a novel mechanism 

in which Wnt signalling promotes tumour formation 

by modulating the extrinsic milieu and in particular influencing 

immune cell recruitment and activation in the tumour 

microenvironment. 

Aim of the study 

We had recently studied a skin tumourigenesis model that 

relies on chronic inflammation for tumour promotion and 

outgrowth. In these skin tumours, we found that inhibition 

of Wnt pathway signalling by bcatenin depletion 

completely abolishes tumour formation (Malanchi et al., 

Nature 2008;452:650). The aim of the present study was 

to understand the crucial function of Wnt signalling at the 

onset of skin tumour formation. 

Methods 

The study was mainly conducted using in vivo models and 

chemical tumourigenesis which rely on chronic inflammation 

for tumour initiation. Orthotopic transplantation 

techniques were used to clarify the ability of tumour cells 

to grow when placed within different microenvironments. 

Results 

We found that bcatenin mutant skin shows a significant 

difference in the inflammatory reaction induced within 

the dermis. Using immunohistochemistry and fluorescentactivated 

cell sorting we were able to identify the immune 

cell subpopulation that was affected by this block of Wnt 

signalling. To link this observation with tumour initiation, 

transplantation and reconstitution experiments were performed 

using a combination of normal skin cells, keratinocytes 

and tumour cells. When tumour cells were placed in 

an immunocompromised environment characterized by 

dampened inflammatory activity, these tumour cells were 

not able to initiate tumourigenesis. On the other hand, 

forced stimulation of the inflammatory cascade was found 

to overcome the lack of Wnt signalling and could promote 

tumour formation. Detailed analysis revealed that keratinocytes 

are major contributors to this early inflammatory 

response, since they release a variety of stimulatory 

molecules that recruit immune cells. To this end, transcriptional 

profiles of activated keratinocytes were determined 

to discover potential mediators of this Wnt mediated 

response. This was followed by functional validation of 

some of these signals, which helped to identify the relevant 

ones. Notably, this suggests that the crucial crosstalk 

between resident cells and recruited immune cells is 

in part mediated by Wnt signalling. Moreover, we found 

that the same pathway is also involved intrinsically in immune 

cells to allow for chemoattraction and activation 

in response to proinflammatory stimuli. In combination, 

these data indicate a potent function of Wnt signalling in 

modulating the inflammatory response, which is fundamental 

in the initiation of cancer. Since the connection be

tween chronic inflammation and epithelial tumourigenesis 

is well established, this suggests that preventive treatment 

of risk patients should consider Wnt signalling as a new 

target. 


Prof. Dr Joerg Huelsken 

UPHUE 





SV 2823 (Bâtiment SV) 

Station 19 


Phone +41 (0)21 692 58 43 

Fax +41 (0)21 652 69 33 

joerg.huelsken@epfl.ch 

Hynes Nancy | Characterisation of the role of PN-1 in 

breast cancer and its potential as a therapeutic target 

(KLS 02187022008) 

Proteases mediate cancer cell invasion and metastasis via 

their ability to degrade the extracellular matrix surrounding 

the tumour. Extracellular serine protease inhibitors 

block the activity of many cancerexpressed proteases 

and have been considered to have cancer protective effects. 

However, it has been found that high levels of protease 

inhibitors, including protease nexin1 (PN1), as we 

show in the project supported by the Swiss Cancer League, 

correlate with poor patient prognosis, suggesting that 

these inhibitors have positive roles in cancer progression. 

Thus, our experiments were designed to test the role of 

PN1 in a metastatic breast cancer model. 

Goal 

Based on our in silico analysis of PN1 expression levels in 

>350 breast tumours, revealing that higher expression 

correlates with markers of poor clinical prognosis, the goal 

of our work was to uncover the mechanism whereby high 

levels of the serine protease inhibitor PN1 contribute to 

breast cancer.

76 

Methods and experimental approaches 

1) In silico approaches were used to examine RNA expression 

levels of PN1 in multiple primary breast tumours, to 

correlate PN1 expression levels with clinical parameters, 

and to investigate the possibility that high PN1 levels 

might have prognostic value in breast cancer. 2) Biochemical 

approaches were carried out with different ex vivo 

cultured cell lines to study the signalling pathways stimulated 

by treatment of cells with purified PN1 protein. 3) 

In vivo tumour studies were performed to examine the effects 

of PN1 ablation on the ability of a metastatic breast 

cancer model to form primary mammary tumours and to 

form lung metastases. 

Results 

In our work we used computational analyses to show that 

levels of the serine protease inhibitor PN1 are significantly 

higher in high grade compared to low grade breast 

cancer. Using breast cancer models with low and high 

PN1 levels we showed that PN1 treatment of mammary 

tumour cells not expressing PN1 stimulated ERK activity 

and matrix metalloproteinase9 (MMP9) production via 

lowdensity lipoprotein receptorrelated 1 (LRP1) binding. 

Moreover, shRNA mediated ablation of PN1 expression 

in PN1 overexpressing mammary cancer cells had a 

strong negative impact on the ability of the cells to form 

lung metastases. Thus, our work uncovered a novel pathway, 

whereby the serine protease inhibitor PN1, via 

LRP1 binding LRP1, activates signalling pathways that 

stimulate MMP9 upregulation and metastatic spread. 

Importantly, an analysis of 126 patients with breast cancer 

revealed that those whose breast tumours had elevated 

PN1 levels had a significantly higher probability to 

develop lung metastases but not metastases to other 

sites, on relapse. These results suggest that PN1 might 

become a prognostic marker in breast cancer. 


Prof. Dr. Nancy Hynes 




CH4058 Basel 

Phone +41 (0)61 697 81 07 

Fax +41 (0)61 697 39 76 

nancy.hynes@fmi.ch 

Janscak Pavel | Study of the role of the human 

mismatch repair system in telomere metabolism 

(OCS 01730082005) 

Telomeres are regions of repetitive DNA sequence at the 

ends of eukaryotic chromosomes that protect chromosome 

ends from being recognized as deleterious DNA 

doublestrand breaks. In normal cells, telomeres get progressively 

shortened due to the inability of DNA polymerases 

to fully replicate DNA ends. Critically short telomeres 

generate chromosome end fusions that cause loss of replicative 

capacity, leading to senescence or apoptosis. 

Therefore, it is believed that telomere shortening is a determinant 

of cellular life span and acts as a tumour suppressor 

mechanism. Cancer cells escape from this type 

of control of cellular proliferation by activating a telomere 

length maintenance mechanism. A substantial number 

of cancers employ a recombinationbased mechanism referred 

to as alternative lengthening of telomeres (ALT). In 

yeast cells lacking telomerase, a reverse transcriptase that 

can synthesize telomeric DNA, inactivation of the proteins 

involved in the initiation of mismatch repair (MMR), such 

as Msh2 and Mlh1, promotes cellular proliferation in a 

manner dependent on homologous recombination. 

The aim of this project was to explore the role of the MMR 

system in telomere metabolism in human cells. 

The project utilized different molecular and cell biology 

methods in combination with biochemical techniques. Using 

various human cell lines, we examined whether the 

MMR proteins are localized at telomeres and whether depletion 

of these proteins has an effect on telomere integrity. 

We found that the MMR proteins MSH2 and MLH1 were 

associated with telomeres in ALTpositive cancer cells but 

not in ALTnegative cells. We also found that MSH2 and 

MLH1 formed a complex with the Werner syndrome helicase/exonuclease 

(WRN), which plays a critical role in the 

maintenance of telomere integrity. Moreover, our biochemical 

experiments with purified proteins indicated 

that the MSH2/MSH3 and the MSH2/MSH6 heterodimers 

could enhance WRNmediated unwinding of synthetic 

DNA structures that resemble recombination 

intermediates. Finally, analysis of recombination events 

at telomeres in a human embryonic kidney cell line with 

inducible expression of MLH1 revealed an elevated frequency 

of telomeric sister chromatid exchanges upon inhibition 

of MLH1 expression. 

Defects in a subset of MMR genes including MSH2, 

MSH3, MSH6, MLH1 and PMS2 are associated with hereditary 

nonpolyposis colorectal cancer. Our findings 

have implications for understanding of the molecular 

events underlying the tumourigenic process initiated by 

the loss of mismatch repair capacity. 


Dr. Pavel Janscak 

Institut für molekulare Krebsforschung 




Phone +41 (0)44 635 34 70 

pjanscak@imcr.uzh.ch

Lange Norbert | Synthesis and evaluation of new 

water soluble polymeric photosensitizer prodrugs for 

photodynamic therapy (OCS 01948082006) 

Despite our increasing understanding of the mechanisms 

and pathways that lead to the development of cancer, in 

most cases our first line treatment options against this 

devastating disease have remained essentially unchanged 

for decades. At least every second of us has heard about 

or seen the dramatic traces that these “conventional cancer” 

therapies, including surgery, radiation therapy and 

chemotherapy, leave on patients that have to undergo 

such treatments with respect to side effects and quality of 

life. Therefore, one of the greatest challenges for scientists 

working in applied cancer research is to find new 

alternatives that can replace or complement these therapeutic 

approaches. One alternative that has attracted 

considerable attention in the past is photodynamic therapy 

(PDT). It is based on the administration of a photosensitizer 

(PS) that selectively accumulates in tumour 

tissue. Upon irradiation with light the photosensitizer triggers 

numerous photochemical processes that ultimately 

lead to the destruction of the tumour tissue. Interestingly, 

the action of PDT is confined to areas in which the PS, 

light and oxygen are concomitantly present. Despite early 

clinical promise and repeatedly reported successful results, 

the further development of PDT was hampered by 

some intrinsic drawbacks of the PS itself. 

The aim of our study financed by Oncosuisse was the development 

and evaluation of PS that can be easily formulated, 

selectively accumulate in tumour tissue, are inactive 

until they encounter certain cancerspecific signals and 

are readily eliminated from the body in their native form. 

Our research was inspired by the observation that high local 

densities of PS lead to its inactivation. 

We therefore coupled multiple copies of PS to a polymeric 

carrier through a peptide linker that can be specifically 

cleaved by proteases. Some of these enzymes that digest 

proteins are upregulated in tumours and play key roles in 

the invasion and metastasis of cancer. In initial studies we 

showed that these PS prodrugs depend on the number of 

PSs per polymer up to 700 times less active than in their 

free form. In absence of light and/or the target protease 

the compounds were void of any photoactivity. We then 

designed PS prodrugs that we specifically activated by 

urokinaselike plasminogen activator, upregulated in many 

kinds of cancer including breast, colon, and prostate cancer. 

In vitro, we showed that cells expressing this protease 

are effectively eliminated through PDT in the presence 

of the specific prodrug but not by a control substance. 

Further, we demonstrated the specific activation of our 

compounds in an experimental animal model for prostate 

cancer. 

In subsequent studies, we were able to optimize the pharmacokinetics 

of these newly developed PS prodrugs. 

Thanks to the financial support of Oncosuisse, we are able 

to prepare PS prodrugs specifically designed for any protease 

and to cure mice inoculated with highly invasive 

prostate cancer through PDT. These findings might now 

well lead to a new approach for the treatment of confined 

prostate cancer, without known side effects of resection 

or brachytherapy. 


Prof. Dr Norbert Lange 

Laboratoire de pharmaceutique et 

de biopharmacie 

Section des sciences pharmaceutiques 


30, quai ErnestAnsermet 

CH1211 Genève 4 

Phone +41 (0)22 379 33 35 

norbert.lange@unige.ch 

MacDonald Hugh Robson | The role of proto- 

oncogenes in hematopoietic and cancer stem cells 

(OCS 01863022006) 

The cMyc gene was the first member of the Myc family 

to be discovered thirty years ago. In mammals, the Myc 

family of transcription factors is comprised of three structurally 

similar proteins: cMyc, NMyc and LMyc. These 

proteins share the same biological properties and exert 

the same functions but they are usually mutually exclusively 

expressed, with only one member of the family 

highly expressed in each particular cell type. Due to its 

predominant role in tumour development, a comprehensive 

understanding of the mechanisms that regulate Myc 

proteins in normal tissues is necessary to develop novel 

anticancer therapies. 

Our laboratory recently demonstrated that cMyc elimination 

leads to the accumulation of haematopoietic stem 

cells (HSCs). HSCs are responsible for the lifelong production 

of all functional blood cells. They are defined by their 

capacity to produce other stem cells (selfrenewal) as well 

as cells called progenitors, which in turn generate all types 

of differentiated blood cells (B and T lymphocytes, red 

blood cells, monocytes and others, all specialized in specific 

functions). HSC deregulation participates in numerous 

haematological pathologies such as anaemias, leukaemias 

and lymphomas. 

To better understand the role of the Myc family members 

in HSCs, we chose to first systematically characterize 

where cMyc, NMyc and LMyc are expressed at each 

step of haematopoietic development, from HSCs to fully 

mature blood cells. By doing so we uncovered the first example 

of an adult cell that produces equivalent amounts 

of cMyc and NMyc transcripts: the most immature 

HSCs. As such, HSCs represent an excellent model to 

study the extent of functional redundancy between c 

Myc and NMyc. We thus generated a series of geneticallymodified 

mouse strains that express different levels 

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of cMyc and/or NMyc and demonstrated for the first 

time in vivo that these two proteins exert the same functions 

but with different efficiencies. Furthermore, when 

analyzing mice in which the cMyc and NMyc genes 

were simultaneously eliminated (double knockout), we 

uncovered that in order to survive, HSCs must repress 

granzyme B, an enzyme usually used by the innate immune 

system to eliminate cancer or virusinfected cells. In 

the absence of both cMyc and NMyc, HSC fail to silence 

granzyme B, which is then activated, resulting in rapid cell 

death. Finally, the investigation of our cMyc/NMyc double 

knockout model indicated that general Myc activity, 

contributed by the combined action of cMyc and NMyc, 

controls several other aspects crucial to HSC function, in 

particular their selfrenewal and differentiation into 

haematopoietic precursors. 

In summary, our genetic dissection of the individual and 

common contributions of cMyc and NMyc considerably 

improved our understanding of the physiological roles of 

the Myc family of proteins and opens new avenues for the 

treatment of several haematopoietic pathologies. 


Dr Hugh Robson MacDonald 

Centre Ludwig de recherche sur le cancer 


Phone +41 (0)21 692 59 89 

Fax +41 (0)21 692 59 95 

hughrobson.macdonald@licr.unil.ch 

Moradpour Darius | Development of a model system 

to study coinfection by hepatitis B and C viruses – 

the major causes of hepatocellular carcinoma 

(OCS 01762082005) 

Background and aim 

Hepatocellular carcinoma (HCC) is one of the most common 

malignant tumours worldwide. A rise in the incidence 

of and mortality from HCC has been documented in most 

industrialized countries, and the increase is expected to 

continue for at least the next two decades. Chronic infections 

with hepatitis B virus (HBV) and hepatitis C virus 

(HCV) account for well over 80 % of HCC cases worldwide. 

Coinfection with HBV and HCV is common due to 

shared modes of transmission. However, the virological 

and molecular aspects of HBVHCV coinfection are poorly 

understood. While the development of cirrhosis and HCC 

is more frequent and accelerated in HBVHCV coinfection, 

an inverse relationship in the replicative levels of the 

two viruses has been noted, suggesting direct or indirect 

viral interference. Understanding the mechanisms of viral 

interference in HBVHCV coinfection is likely to yield important 

clues to the pathogenesis of viral persistence and 

liver disease and, thereby, the development of HCC. How 

ever, interactions between HBV and HCV have been difficult 

to study because of the lack of appropriate model systems. 

On this background, the aim of this project was to 

establish a model system in which both viruses and their 

interactions can be studied in a wellcharacterized and 

meaningful cellular context. 

Experimental design and methods 

A tetracyclineregulated gene expression system, allowing 

the inducible expression of a replicationcompetent HBV 

construct, as well as selectable HCV replicons and cell culturederived 

HCV (HCVcc) were used to establish Huh7 

human HCC cell lines replicating both viruses simultaneously. 

Independent inducible cell lines as well as control 

cell lines inducibly expressing the green fluorescent protein 

were established, because significant clonal variation 

in HCV RNA replication and susceptibility to HCVcc infection 

had been noted in the past. 

Results 

Three successive transfection and selection steps allowed 

the establishment of Huh7 cell lines replicating HBV and 

HCV RNA. In these cell lines, it is possible to control the 

expression of HBV proteins, HBV replication and infectious 

viral particle formation by the concentration of tetracycline 

in the culture medium while HCV proteins are 

expressed and HCV RNA replicated constitutively. In this 

system, both viruses were found to replicate in the same 

cell without overt interference. Specific inhibition of one 

virus did not affect the replication and gene expression of 

the other. Further, cells harbouring replicating HBV could 

be infected with HCVcc, arguing against superinfection 

exclusion. Finally, cells harbouring replicating HBV supported 

efficient production of infectious HCV. Taken together, 

these results demonstrate that HBV and HCV can 

replicate in the same cell without evidence for direct interference 

in vitro. 

Conclusions and perspectives 

We established a novel model system allowing the study 

of HBVHCV coinfection under highly reproducible conditions 

in vitro. Our results demonstrate a remarkable lack 

of direct interference between HBV and HCV, implying 

that the two viruses rely on distinct and noncompeting 

sets of host factors for their replication. These observations 

suggest that the viral interference observed in coinfected 

patients is probably due to indirect mechanisms 

mediated by innate and/or adaptive host immune responses. 

Further study of such interactions may provide 

new clues to the pathogenesis and clinical management of 

HBVHCV coinfection and HCC. 


Prof. Dr Darius Moradpour 

Service de gastroentérologie et d’hépatologie 

Centre hospitalier universitaire vaudois (CHUV) 


Rue du Bugnon 44 


Phone +41 (0)21 314 47 14 

Fax +41 (0)21 314 47 18 

darius.moradpour@chuv.ch

Nägeli Hanspeter | Regulation of nucleotide excision 

repair by protein modifiers (KLS 01827022006) 

The frequency of skin cancer due to sunlight exposure is 

increasing dramatically. The ultraviolet (UV) radiation of 

sunlight induces damage in the genome by causing the 

crosslinking of adjacent DNA bases. According to the type 

of chemical link, these UV lesions are known as cyclobutane 

dimers or 6,4 photoproducts. They lead to genetic 

abnormalities and result in cancer unless they are readily 

removed by DNA repair. This removal of UV crosslinks 

from the genome is carried out by a multicomponent 

DNA repair system generally known as nucleotide excision 

repair. However, this DNA damage excision machinery 

faces the important problem that the cellular DNA 

substrate is tightly packaged in chromatin, raising the 

question of how UV lesions may be detected in such a 

poorly accessible environment. Another problem is that 

cyclobutane dimers cause minimal changes of the DNA 

structure, and therefore, this particular type of crosslink is 

poorly recognized by XPC protein, which is the initial 

damage sensor component of the DNA repair machinery. 

In the frame of our research project, we used cell biology 

methods to analyze the dynamic assembly and disassembly 

of active repair complexes in the chromatin context. 

This approach led us to discover two novel regulatory 

mechanisms that coordinate the DNA repair of UV lesions 

in human skin cells. As a master regulator in both control 

systems we have identified DDB2, a previously enigmatic 

factor known on the basis of its binding preference for 

UVdamaged DNA but whose function in the DNA damage 

response remained unclear. We discovered that DDB2 

is able to inspect the cellular chromatin to search for 

highly accessible sites and demarcate these hotspots for 

DNA repair activity. For that purpose, DDB2 recruits an 

enzyme complex that mediates the modification of the 

XPC sensor protein with ubiquitin residues. These attached 

ubiquitin modifiers mediate the retention of XPC 

protein at DNA repair hotspots, thus preventing its futile 

migration to more densely packed chromatin that is refractory 

to DNA repair. By this mechanism, DDB2 ensures 

the fast repair of DNA sites that are actively engaged in 

critical cellular processes, thus providing more time for the 

longterm and slow repair of less accessible chromatin 

sites. Independently of ubiquitin modifiers, we found that 

DDB2 is also able to exert a lever action on the DNA double 

helix to allow for the docking of the XPC sensor to the 

otherwise unrecognizable cyclobutane dimers and thus 

initiate their repair. 

In summary, our results show that DDB2 is a master organizer 

that optimizes the spatiotemporal distribution of 

DNA repair activity in the chromatin of human skin cells. 

In future experiments, we will test how vitamins, UV filters, 

antioxidants and other ingredients of cosmetics or 

sunscreens influence the quantity and function of DDB2 

in human cells. Knowledge of these regulatory systems 

provides a rational basis for preventive interventions to increase 

the efficiency and precision of DNA repair and 

hence to reduce the risk of skin cancer. 


Prof. Dr. Hanspeter Nägeli 

Institut für Veterinärpharmakologie und toxikologie 




Phone +41 (0)44 635 8763 

naegelih@vetpharm.uzh.ch 

Ochsenbein Adrian F. | Immunosurveillance of chronic 

myeloid leukemia in mice (OCS 01627022005) 

Chronic myelogenous leukaemia (CML) is a malignant 

clonal myeloproliferative disease arising from a haematopoietic 

stem cell expressing the BCR/ABL fusion protein. 

CML is characterized by a chronic phase lasting for several 

years. During this time period, immune responses coexist 

with the CML and probably control the disease. Eventually 

CML progresses from the chronic phase to terminal 

blast crisis. This might be due to failure in immunosurveillance. 

We identified peripheral and central tolerance 

mechanisms that impair the immunosurveillance of CML 

and contribute to disease progression in a murine CML 

model. To this end, we transduced bone marrow cells 

from donor mice with a retroviral construct that expresses 

the oncogene BCR/ABL and transferred these cells to recipient 

mice. 

We found that CMLspecific CTLs were functionally impaired. 

CTL did not produce effector cytokines, did not 

proliferate after antigenic stimulation and displayed very 

limited cytolytic function. This functional impairment of 

CTL is termed exhaustion. CTL exhaustion has been attributed 

to the signal transduction of different inhibitory 

receptors such as PD1. Indeed, CTL exhaustion in CML 

was mediated by the PD 1/PD L1 interaction. Blocking 

PD1 signal transduction by using PD1deficient recipient 

mice or by administration of aPDL1 antibody reversed 

CMLspecific T cell tolerance, and the time to disease progression 

was increased. In addition, PD1 was upregulated 

on CD8 + T cells from CML patients, suggesting that 

this inhibitory pathway may also be of importance in the 

regulation of CMLspecific CTLs in humans. 

The BCR/ABL fusion protein provides novel and potentially 

immunogenic tumourspecific antigens. The leukaemia 

BCR/ABL expressing stem cell differentiates to different 

cell populations including professional antigenpresenting 

dendritic cells (DC). BCR/ABLexpressing DCs were found 

in various organs. However, BCR/ABLexpressing DCs 

failed to efficiently induce leukaemiaspecific T cell responses 

due to low DC maturation and impaired migration 

to secondary lymphoid organs. Moreover, we demonstrated 

that BCR/ABLexpressing DCs preferentially 

migrated to the thymus where they induced a deletion of 

leukaemiaspecific CD8 + T. 

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In summary, this work improves our understanding of the 

contribution of the immune system in controlling CML. 

Functional impairment of CMLspecific CTLs by PD1 signalling 

and centraldeletion of leukaemiaspecific CTL by 

BCR/ABLexpressing DCs in the thymus contribute to the 

escape of CML from immunosurveillance. These findings 

open up new possibilities for immunotherapies against 

CML. 


Prof. Dr. Adrian Ochsenbein 

Universitätsklinik für medizinische Onkologie 

Inselspital 


CH3010 Bern 

Phone +41 (0)31 632 84 42 

Fax +41 (0)31 632 41 19 

adrian.ochsenbein@insel.ch 

Orend Gertraud | Analysis of a potential oncogenic 

function of tenascin-C and tenascin-W in colon cancer 

(OCS 01875022006) 

The extracellular matrix (ECM) molecule tenascinC, 

which is highly expressed in most solid cancers, plays an 

important role in angiogenesis, tumour proliferation and 

progression and correlates with signs of bad prognosis in 

several cancers. TenascinC is one of a few genes with 

predictive value in breast cancer metastasis to the lung. 

Its high expression also correlates with tamoxifen resistance 

in patients with breast cancer. Recently, an antibody 

targeting tenascinC was used to stimulate the immune 

system, thus destroying the experimental breast cancer. 

Thus, tenascinC plays a crucial role in cancer that is incompletely 

understood at the mechanistic level. 

Our recent published and unpublished research contributed 

to the understanding of the mechanisms of tenascin 

Cinduced tumour progression. We identified two independent 

mechanisms by which tenascinC inhibits cell 

adhesion to fibronectin, another ECM molecule with a 

high expression in cancer tissue. TenascinC competes 

binding of syndecan4, an essential coreceptor of integrin 

alpha5 beta1, to fibronectin, thus promoting tumour cell 

proliferation. TenascinC induces expression and signalling 

of endothelin receptor type A, which may be instrumental 

in cancer progression by stimulating angiogenesis 

and epithelialtomesenchymal transition. We also described 

that reduced cell adhesion by tenascinC serves as 

a prerequisite for growth factors to trigger tumour cell 

migration. In particular, lysophosphatidic acid together 

with platelet derived growth factor stimulated migration 

on a tenascinC substratum, which may be relevant in glioma 

progression and in the neuronal stem cell niche, 

which are places that exhibit a high expression of tenascinC 

and of both molecules and their receptors. 

This information could be important for refining tenascin 

C expression as diagnostic factor in cancer. We discovered 

that tenascinC activates oncogenic Wnt and endothelin 

receptor type A signalling. We were also involved in a 

study where activation of Tolllike receptor 4 signalling by 

tenascinC was found to be crucial in rheumatoid arthritis. 

In a xenograft model where minced human colon cancer 

tissue had been injected into immunecompromised mice 

we had analysed expression and organization of tenascin 

C and tenascinW in the arising tumours. We observed 

that both tenascins were highly expressed with eventual 

overlapping patterns. The organization of both tenascins 

into matrix tracks together with other matrix molecules 

was very similar in the xenograft tumour compared to the 

human tumour, suggesting that at least some characteristics 

of the original cancer can be preserved in the xenograft 

model. 


Dr Gertraud Orend 

Institut national de la santé et de la recherche 

médicale (INSERM) 

Unit 682 

3, avenue Molière 

F67200 Strasbourg 

France 

Phone +33 (0)3 88 27 53 55 

Fax +33 (0)3 88 26 35 38 

gertraud.orend@inserm.ustrasbg.fr 

Pabst Thomas | The myeloid key transcription 

factor CEBPA and the pathophysiology of acute 

myeloid leukemia (OCS 01833022006) 

In the focus of our current understanding of the pathogenesis 

of acute myeloid leukaemia is the leukaemic stem 

cell transformed from normal pluripotent blood precursor 

cells. Moreover, these leukaemic stem cells also represent 

the goal of therapeutic efforts. Deregulation of a small 

group of transcription factors seems to be involved in the 

transformation from normal precursor cells to leukaemic 

stem cells. In patients with acute myeloid leukaemia 

(AML), such transcription factors are often mutated or 

their expression is altered. A prominent example is the 

transcription factor CEBPA, which is necessary for the 

normal maturation of blood precursor cells towards mature 

white blood cells (granulocytes). In a substantial percentage 

of patients with AML, the CEBPA gene is mutated. 

In the present research project, we are analyzing a 

certain type of CEBPA mutations in patients with AML. 

We hope that the results will reveal the mechanism of how 

this type of CEBPA mutations contributes to the development 

of the disease in these patients. 


Prof. Dr. Thomas Pabst 


Inselspital 

CH3010 Bern 

Phone +41 (0)31 632 41 15 

Fax +41 (0)31 632 41 19 

thomas.pabst@insel.ch

Peter Matthias | Regulation of genome stability by 

Rtt101p/cullin4-based E3-ubiquitin ligases in yeast 

and mammalian cells (OCS 02189022008) 

Cullin 4 (Cul4)based ubiquitin ligases have emerged as 

critical regulators of DNA replication and repair. Over 50 

Cul4specific adaptors (DCAFs) have been identified and 

are thought to assemble functionally distinct Cul4 complexes. 

Using a livecell imagingbased RNAi screen, we 

analyzed the function of DCAFs and Cul4linked proteins 

and identified specific subsets required for progression 

through G1 and Sphase. We discovered C6orf167/ 

Mms22L as a putative human orthologue of budding 

yeast Mms22, which together with the cullin Rtt101 regulates 

genome stability by promoting DNA replication 

through natural pause sites and damaged templates. Loss 

of Mms22L function in human cells results in Sphasedependent 

genomic instability characterized by spontaneous 

double strand breaks and DNA damage checkpoint 

activation. Unlike yeast Mms22, human Mms22L does 

not stably bind to Cul4 but is degraded in a Cul4dependent 

manner and upon replication stress. Mms22L physically 

and functionally interacts with the scaffoldlike protein 

Nfkbil2 that copurifies with histones, several 

chromatin remodelling and DNA replication/repair factors. 

Together, our results strongly suggest that the 

Mms22LNfkbil2 complex contributes to genome stability 

by regulating the chromatin state at stalled replication 

forks. 


Prof. Dr. Matthias Peter 

Institut für Biochemie 

ETH Zürich 

HPM G8 



Phone +41 (0)44 633 65 86 

Fax +41 (0)44 632 12 98 

matthias.peter@bc.biol.ethz.ch 

Plückthun Andreas | Tumor targeting of ErbB2 with 

designed ankyrin repeat proteins 

(OCS 02128082007) 

In the last ten years, targeted tumour therapy has made a 

major leap forward, mainly due to improvements in the 

design and production of antibodies. However, despite the 

technological advances, targeting molecules such as antibodies, 

in particular as fusion proteins with toxic moieties, 

often suffer from unfavourable biophysical properties, expensive 

production and limited efficacy if used as monotherapy. 

Therefore, complementary molecular scaffolds 

are in high demand and the subject of intense research. 

We have developed a new class of binding molecules, 

termed “designed ankyrin repeat proteins” (DARPins) that 

display high affinities for their targets, outstanding biophysical 

properties and a wide range of targets, and they 

can be manufactured in bacteria in large amounts at low 

cost. 

We chose the ErbB2 receptor as a target tumour antigen. 

Overexpression of ErbB2 occurs in a broad range of human 

cancers, including up to 30 % of breast carcinoma, 

and high ErbB2 levels have been correlated with an aggressive 

metastatic tumour phenotype. Consequently, 

high expression of ErbB2 may be employed for tumour 

targeting, where the receptor is used as a cellular gate to 

convey therapeutic payloads into the tumour cells. Notably, 

the inhibition of tumour growth may be induced 

solely by the binding to the receptor in as much as ErbB2 

is required for the proliferation of tumour cells. In order to 

achieve high treatment efficiency, we aimed to construct 

ErbB2targeting molecules combining several favourable 

attributes. 

In the course of this project, we established an array of 

powerful methods for selection and maturation of the 

DARPin binders. By this means, a number of ErbB2directed 

binders were selected and profiled for their efficiency 

to inhibit tumour growth in cell culture models. 

Several binders were further engineered by methods of 

molecular biology and computational molecular design, 

and the resulting molecules reached tumouristatic activity 

that surpassed the efficacy of the antiErbB2 antibodies 

currently used in the clinic. The high antitumour activity 

of these novel binders has been related to a potent induction 

of cell death (apoptosis) and growth arrest selectively 

on the tumour cells expressing ErbB2. Importantly, due to 

the absence of any cytotoxic additives or moieties, these 

DARPin variants are expected to be devoid of adverse side 

effects. This property may translate into high therapeutic 

benefit in the clinical treatment. 

Finally, we conducted initial studies in animal models 

aimed at determining the cytotoxicity, biodistribution and 

pharmacokinetics of DARPins. The DARPins appeared to 

be well tolerated and localized to the tumour sites with 

very high specificities. We are therefore confident that 

DARPins can be used as effective vehicles for the ErbB2mediated 

tumour targeting. Based on their high tumouricidal 

activity, specificity of targeting and lowcost production, 

they can be potentially envisaged as candidates 

to complement or even substitute antibodies in a number 

of therapeutic applications. 


Prof. Dr. Andreas Plückthun 

Biochemisches Institut 



8057 Zürich 

Phone +41 (0)44 635 55 70 

Fax +41 (0)44 635 57 12 

plueckthun@bioc.uzh.ch 

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Pruschy Martin | Microtubule interference as target 

for combined cancer therapy with ionizing radiation 

(OCS 02129082007) 

Interference with microtubule function is a promising approach 

for anticancer therapy that has been extensively 

validated by the use of taxanes for the treatment of a wide 

variety of human malignancies. However, treatment with 

taxanes is limited by taxanerelated toxicities and the development 

of multidrug resistance. This has prompted an 

ongoing worldwide search for novel microtubuletargeting 

agents (MSA), e. g. epothilones. We recently demonstrated 

that epothilones also offer a significant therapeutic 

potential in combination with ionizing radiation (IR). 

Thus this potent, combined treatment modality represents 

a promising strategy for efficacyenhancement of 

tumourdirected radiotherapy and systemic but tumouroriented 

and rationally designed anticancer agents. Treatment 

with MSAs alone or in combination with IR directly 

targets tumour cells, but it also affects other critical structures 

of the tumour, e. g. the tumour vasculature, which 

codetermines the tumour treatment response. However, 

these processes and the signalling consequences relevant 

for their cytotoxic effect are far from clear. 

In this research project we investigated in a multilayered 

approach the mechanisms underlying the antitumour effects 

of microtubule interference with epothilones alone 

and in combination with IR. In multiple tumour cell lines 

(lung and colon adenocarcinoma cell lines, fibrosarcoma, 

glioblastoma and medulloblastoma) and in murine tumour 

models derived from these cells, the efficacy of 

epothilones and IR alone and in combination was determined. 

Having access to a geneticallydefined tumour cell 

system (wildtype lung adenocarcinoma cell line A549 

and the mutant A549EpoB40 cell line, which are resistant 

to epothilones due to a btubulin mutation) we could perform 

complementary in vitro and in vivo experiments 

specifically investigating the role of the tumour microenvironment 

to this combined treatment modality. We could 

demonstrate that the major cytotoxic effect of the combined 

treatment modality of IR and patupilone is directed 

against the tumour cell compartment and that the induced 

antiangiogenic effect, which contributes to the 

supraadditive treatment response of this combined 

treatment modality, derives indirectly from the tumour 

cell. At the same time, we demonstrated that the potency 

of patupilone alone is independent of tumour hypoxia. 

Besides classic additive cytotoxicity determined on the 

single cell level, we identified that microtubule interference 

counteracts radiationinduced stress responses and 

thereby downregulates treatment thresholds. In particular, 

we determined interference on the level of VEGF 

secretion and matrix metalloproteinase activity and demonstrated 

that regulation of these paracrine effects contributes 

to the supraadditive treatment response of this 

combined treatment modality on the in vivo level. 

Besides these mechanistic insights, these new data in 

combination with our previous studies have already contributed 

to the design and launch of clinical trials with this 

combined treatment modality at the international level. 

Furthermore, and based on our data, we are currently 

outlining several options to combine IR not only with 

epothilones but also with other microtubule de/stabilizing 

agents for clinical trials. 


Prof. Dr. Martin Pruschy 

Labor für molekulare Radiobiologie 

Klinik für RadioOnkologie 

UniversitätsSpital Zürich 

Rämistrasse 100 


Phone +41 (0)44 255 85 49 

martin.pruschy@usz.ch 

Radtke Freddy | The role of Notch2 in murine 

epidermis (OCS 01560082004) 

The skin epidermis and its appendages represent a constantly 

renewing physical barrier that protects against 

mechanical injuries, infective organisms and excessive loss 

of water. Cellular processes such as proliferation, migration 

and cell death must be highly regulated in order to 

ensure lifelong homeostasis. The Notch pathway plays a 

key role in differentiation of the epidermis and its appendages. 

Notch proteins comprise a family of four type I transmembrane 

receptors that influence cell fate decision and 

differentiation processes in multiple organisms and tissues. 

In the haematopoietic system, signalling via Notch1 or 

Notch2 is important for the generation of T cells and a certain 

subpopulation of B cells, both of which have an important 

function in the immune system. Moreover, aberrant 

Notch1 signalling in the haematopoietic system is 

oncogenic and causative of T cell leukaemia. Results from 

the blood system but also other tissues suggested that aberrant 

Notch signalling is mostly associated with oncogenic 

properties. 

However, evidence from our own laboratory and from 

others has shown that Notch1 can also function as a tumour 

suppressor in particular in the skin. Conditional inactivation 

of Notch1 in the mouse epidermis leads to the 

development of spontaneous basal cell carcinomalike tumours 

within 1 year after loss of Notch1 function. The relatively 

long latency for skin tumour development suggests 

that during this period additional mutations have to be acquired 

to cause malignant growth of Notch1 deficient 

skin. The murine skin expresses mostly two Notch receptors, 

Notch1 and Notch2. The function of the second 

Notch receptor in the skin was completely unknown. We 

therefore generated mice in which Notch2 alone or both 

Notch1 and Notch2 could be inactivated simultaneously 

in the skin. 

Our study showed that inactivation of Notch2 in the skin 

did not lead to any apparent phenotype, because loss of 

Notch2 function was fully compensated by the presence

of Notch1. However, simultaneous inactivation of both 

Notch1 and Notch2 in the skin differed from skin specific 

Notch1 mutant mice. Simultaneous loss of both receptors 

in the skin induced the development of a severe form of 

atopic dermatitis (also known as eczema), which is associated 

with massive inflammation within 4 weeks. Likewise, 

analysis of patients with atopic dermatitis but no other 

skin diseases (such as psoriasis) showed also a marked reduction 

of Notch receptor expression in the skin. Loss of 

Notch in keratinocytes induces the production of thymic 

stromal lymphopoietin (TSLP), a cytokine deeply implicated 

in the pathogenesis of AD. The ADlike associated 

inflammation is accompanied by a lethal myeloproliferative 

disorder (MPD) characterized by an increase in immature 

myeloid populations in the bone marrow and spleen. 

Transplantation studies revealed that the MPD is cell nonautonomous 

and caused by dramatic microenvironmental 

alterations. Genetic studies demonstrated that the increased 

GCSF concentration in the serum of the Notch 

mutant mice is responsible for the MPD. Our study demonstrates 

a critical role for both Notch receptors in repressing 

TSLP production in keratinocytes, thereby maintaining 

integrity of the skin and the haematopoietic system. 


Prof. Dr Freddy Radtke 





Station 19 


Phone +41 (0)21 693 07 71 

freddy.radtke@epfl.ch 

Radtke Freddy | The role of Notch1 signaling in acute 

lymphoblastic T cell leukaemia (T-ALL) 

(KLS 01840022006) 

T cells are haematopoietic cells that are part of our immune 

system to protect us against foreign invaders. T cell 

development occurs in the thymus, where unspecified 

bone marrow progenitors differentiate and mature within 

a period of approximately three weeks into functional 

T cells. This differentiation process is regulated and driven 

by several ligandreceptor interactions that induce a complex 

transcriptional network that assures proper growth 

and differentiation of functional T cells. Deregulation of 

these processes, combined with the acquisition of genetic 

alterations, is causative of leukaemogenesis. T cell acute 

lymphoblastic leukaemia (TALL) is an aggressive malignancy 

that originates in the thymus. The disease represents 

15 % of paediatric and 25 % of adult acute lymphoblastic 

leukaemia (ALL) cases. The general treatment 

consists of multiagent chemotherapy, which results in an 

overall survival rate of 70 % for children and 30–40 % for 

adults. Although the cure rates appear to be relatively 

high, 30 % of children and 60 % of adult patients relapse 

and have a poor prognosis. It is therefore important to 

better understand the molecular mechanisms contributing 

to malignant T cell growth. The Notch1 receptor is 

part of a family of transmembrane bound receptors that 

mediate signals from the outside to the inside of a cell and 

thereby influence development and growth. Physiological 

Notch1 signalling in the blood system and in particular in 

the thymus is essential for generating T cells. However, 

too much signalling causes malignant growth. More than 

50 % of all TALL patients have small changes within the 

receptor (called point mutations); this causes the receptor 

to signal too strong, too long and at inappropriate stages 

of development and thus causes leukaemia. 

We generated a Notch driven leukaemic mouse model 

that recapitulates the human disease and showed that 

Notch signalling is not only required for the development 

of the disease but continuous signalling is also essential 

for the maintenance of the disease. Thus Notch1 is a master 

regulator for malignant T cell growth. 

Further, we investigated the role of the transcription factor 

Hes1 for normal and malignant T cell growth and development. 

Hes1 is one of numerous transcription factors 

that become activated when Notch1 signals. Our studies 

showed that under physiological conditions Hes1 is important 

for normal T cell development. In its absence only 

very few T cells are able to develop. More importantly, we 

showed that Hes1 is essential for the development and 

maintenance of Notch1 driven leukaemia in our mouse 

model. Most importantly, reducing Hes1 protein levels 

in established patientderived human TALL samples 

resulted in growth retardation and cell death, strongly 

suggesting that the important role for Hes1 might not be 

restricted to TALL mouse models but could also apply 

to the human disease. Thus, our studies identified Hes1 as 

a main mediator of Notch1 signalling in the physiological 

and leukaemic situation and highlight it as a potential 

therapeutic target to fight against malignant growth of 

TALL. 







Station 19 


Phone +41 (0)21 693 07 71 


83

84 

Renner Christoph | Selective inhibition of intratumoral 

regulatory T cells by antibody-GITR ligand fusion 

proteins (OCS 02119082007) 

Cancer patients possess tumourreactive T cells, but these 

are suppressed by naturally occurring regulatory T cells 

(Treg cells). Activation or support of these tumourreactive 

T cells is therefore a major objective in cancer immunotherapy. 

Stimulation of glucocorticoidinduced tumour 

necrosis factorrelated receptor (GITR) represents a promising 

approach, since this receptor is expressed on both 

CD4 + and CD8 + effector T cells as well as on CD4 + 25 + 

Treg cells. 

Triggering of murine GITR with its natural ligand (GITRL) or 

antiGITR agonistic antibodies enhances T cell responses, 

inhibits Treg mediated suppression and thereby induces 

tumour immunity in a variety of murine tumour models. 

However, systemic administration of costimulatory agents 

can lead to global T cell activation and autoimmunity. 

Therefore, we proposed to specifically manipulate the 

T cell compartment in the tumour microenvironment by 

using a bispecific fusion protein combining mGITRL and a 

single chain antibody that targets fibroblast activation 

protein (FAP). Accumulation of antiFAPmGITRL in the 

tumour microenvironment can be mediated through binding 

to FAP, which is specifically expressed on sarcomas 

and on cancerassociated fibroblasts (CAFs) found in the 

stroma of epithelial cancers. 

The antiFAPmGITRL fusion protein generated in this 

study formed dimers and bound to murine GITR with 

an affinity of 1.2 μM and to murine FAP with an affinity 

of 4.5 nM. In vitro cell assays with murine splenocytes 

showed that our antiFAPmGITRL fusion protein can stimulate 

CD8 + and CD4 + effector T cells, as shown by their 

increased proliferation and production of IFNg and IL2. 

This costimulatory effect was enhanced when the fusion 

protein was presented by a FAPpositive cell line mimicking 

FAP + CAFs or FAP + tumours. Presumably, the membranebound 

antiFAPmGITRL allows for crosslinking of 

multiple GITR molecules on T cells, thus leading to increased 

signalling and enhanced costimulation. In vitro, 

Treg cells inhibit the expansion and function of CD8 + 

T cells. Addition of our antiFAPmGITRL to the Treg: CD8 + 

T cell coculture could restore proliferation and IFNg production 

of CD8 + T cells. Furthermore, cell membranebound 

antiFAPmGITRL was 100fold more effective in 

overcoming Tregmediated suppression compared to unbound 

fusion protein. 

To translate the in vitro results in a preclinical model, we 

established syngeneic murine cancer models to either target 

the tumour stroma or the tumour cells directly. Immunotherapeutic 

antiFAPmGITRL treatment of a colon carcinoma 

provoked no delay in tumour growth due to weak 

stroma formation. However, therapy of a FAP + osteosarcoma 

led to enhanced survival of mice treated with anti 

FAPmGITRL. The antibodydirected delivery of GITRL 

opens a new path to positively act on the local T cell environment 

in the tumour. Targeted delivery and thereby 

enhanced immunomodulatory effects of antiFAPmGITRL 

represent a promising approach in antibodybased tumour 

immunotherapy. 


Prof. Dr. Christoph Renner 

Klinik und Poliklinik für Onkologie 

Medizinbereich Innere Medizin–Onkologie 



CH8091 Zurich 

Phone +41 (0)44 255 21 54 

christoph.renner@usz.ch 

Romero Pedro | Impact of lentiviral cancer vaccines on 

the anti-tumour response in vivo (OCS 2011022007) 

The incidence of malignant melanoma continues to increase 

in our country in people of all ages. Except for early 

detection and surgical excision, the currently available 

treatments fail to cure this disease. Thus, new effective 

therapies for metastatic melanoma are urgently needed. 

The development of cancer vaccines is a promising approach, 

and recent results in this field are encouraging. To 

optimize them, it is necessary not only to enhance their 

ability to induce specific immunity but also to prove their 

ability to control or even reject established tumours. 

We have recently reported the development of recombinant 

lentivectors carrying tumour specific antigens as vaccines. 

Results with lentiviral immunization in mice demonstrate 

their ability to induce strong and longlived specific 

T cell responses, even with a single injection. Typically, the 

peak of specific T cell responses is attained during the 

third week post immunization, and stable levels of immune 

memory can be detected as long as six months later. 

Importantly, this response is sufficient to protect from 

melanoma tumour challenge, even when this is performed 

six months after a single immunization. However, the key 

quality expected from vaccination against cancer is its 

ability to control established large tumours rather than to 

confer a prophylactic protection. In this regard, we observed 

that the therapeutic vaccination failed to exert any 

detectable control of tumour growth. A detailed analysis 

of this vaccine failure revealed that while effector CD8 

T cells are able to home to the tumour sites, they are compromised 

in their ability to function normally. Indeed, vaccine 

induced T cells are inactivated by many immunosuppressive 

factors active in the tumour microenvironment. 

We identified the selective overexpression on specific 

T cells of the inhibitory receptor PD1 as one of the pathways 

leading to T cell dysfunction. We therefore tested 

combination therapies, whereby vaccination was either 

preceded by chemotherapy (single injection of cyclophosphamide) 

or followed by administration of antibodies 

blocking both PD1 and its main ligand PDL1. In both 

cases we clearly observed a stronger effect on retardation 

of tumour growth and increase of mouse survival. These 

results indicate that the combination therapies can synergize 

in affording protection.

Together, the results of this project demonstrate the 

promise of this lentiviral based vaccine. They also clearly 

illustrate the need for combining effective vaccines with 

immunomodulatory compounds that can leverage tumour 

protection by relieving the immunosuppressive tumour 

environment. Similar conclusions have been reached by 

independent laboratories using a relatively large variety of 

anticancer vaccines. Thus, translation of these results to 

the clinic calls for efforts to identify the best combination 

therapies in terms of clinical efficacy. We plan to continue 

our preclinical studies with the aim of accelerating the 

process of identification of effective combinatorial immunotherapies. 


Prof. Dr Pedro Romero 

Division d’oncoimmunologie clinique 


Avenue PierreDecker 4 


Phone +41 (0)21 314 01 98 

Fax +41 (0)21 314 74 77 

pedro.romero@inst.hospvd.ch 

Rüegg Curzio | Role of integrins and CYR61/CCN1 

in tumor metastasis: Unraveling mechanisms and 

development of novel integrin inhibitors 

(OCS 02020022007) 

Introduction 

Tumour progression to local invasion and metastasis formation 

are of utmost clinical relevance, since they often 

determine patient prognosis. Furthermore, cancers relapsing 

after initial therapy tend to become more aggressive, 

are more difficult to treat and form metastases more 

often. Despite the clinical relevance, however, the cellular 

and molecular mechanisms governing the formation of 

metastases are still not well understood. Thus, there is a 

profound need to develop new therapeutic tools capable 

of interfering with metastasis formation. We recently 

identified the extracellular matrix (CYR61/CCN1) and one 

of its receptors (integrin aVb5) as two proteins collaborating 

to promote metastasis of cancers relapsing after 

radiotherapy. Importantly, a pharmacological inhibitor of 

the receptor prevented metastasis formation. But the exact 

mechanisms beyond this effect are not well known.

86 

Goal 

Here we build on these observations to characterize the 

cellular and molecular mechanism by which these two 

proteins cooperate to promote invasion and metastasis. 

The goal is then to interfere with their function as a novel 

therapeutic strategy to prevent metastasis. Specifically, 

we are studying the effects of CYR61/CCN1 on cancer 

cell adhesion, invasion and metastasis by analyzing events 

in the cancer cell and by studying how these proteins favour 

cancer cell interactions with tumour vessels, the first 

step toward metastasis. In addition, we will develop novel 

small molecular inhibitors of the receptor based on computerassisted 

molecular modelling. 

Methods 

We use combined molecular biology, genomic, cell biology 

and biochemical experiments to address the research 

questions. These experiments will be largely performed in 

vitro without the need of mice. Computerassisted molecular 

modelling will benefit from recent technical advances 

at the Swiss Institute of Bioinformatics. 

Results 

We generated different normal and breast cancer cell lines 

expressing high level of CYR61 and observed that these 

cells become more invasive through a process called epithelialtomesenchymal 

transition. We also identified cellular 

signalling pathways associated with this effect. Their 

pharmacological targeting prevented epithelialtomesenchymal 

transition. These results demonstrated for the 

first time that CYR61 induces epithelialtomesenchymal 

transition. In the second part of the project we developed 

a model of the receptor integrin a5b1 obtained by modelling 

the experimental structures of homologous receptors 

as templates. The model can reproduce the correct 

ligand binding mode for a natural ligand. We then used 

this model to design structurally diverse ligands, which 

will be applied to generate novel inhibitors to test in competition 

assays. 

Benefits for patients 

Results obtained from these experiments are of broad relevance 

to both tumour biology and clinical oncology. 

For one, they aid understanding of some aspects of the 

mechanisms leading to metastasis, and for another, they 

may open up new therapeutic perspectives to prevent or 

treat metastases. Inhibitors of integrins are currently 

in advanced clinical trials in brain cancer, with promising 

results. We are now considering designing a clinical trial 

to test the safety and activity of integrin inhibitors in preventing 

metastasis in patients experiencing relapses after 

radiotherapy. 


Prof. Dr Curzio Rüegg 

Division de pathologie expérimentale 

Université de Fribourg 

1, rue AlbertGockel 

CH1700 Fribourg 

Phone +41 (0)26 300 87 66 

Fax +41 (0)26 300 97 33 

curzio.ruegg@unifr.ch 

Rufer Nathalie | Defining molecular, structural and 

functional T-cell receptor properties of melanoma- 

specific human CD8 + T lymphocytes 

(OCS1995022007) 

Although tumourreactive T lymphocytes can be detected 

in cancer patients, these immune responses often fail to 

control or eliminate the disease. It has been proposed that 

T cells directed against tumour antigens express Tcell receptors 

(TCR) of lower affinity/avidity for their antigenic 

ligands than pathogenspecific T lymphocytes. Today, recent 

progress unveiling the cellular and molecular basis of 

the immune response allows the design of novel strategies 

for tumour immunotherapy. Adoptive transfer of T cells 

engineered with TCRs has been recently developed with 

the aim to induce immune reactivity towards defined tumourassociated 

antigens to which the endogenous Tcell 

repertoire is nonresponsive. An attractive approach to 

improve this strategy is to optimize the TCR sequence to 

increase its affinity for cognate tumour antigen. Olivier 

Michielin’s group (at the Swiss Institute of Bioinformatics 

in Lausanne) recently developed and applied a novel in 

silico structurebased approach for rational design of sequence 

mutations that preserve precise antigenic specificity 

while increasing the affinity to the peptideMHC complex. 

The objectives of our study were: 1) to assess rigorously 

the impact of each optimized TCR variant on T cell function; 

and 2) to evaluate the potential usage of these TCRs 

for therapeutic interventions by adoptive T cell therapy. 

We generated a panel of T lymphocytes expressing tumourspecific 

TCR variants of incremental affinities. Essentially, 

TCR variants of increased affinity revealed enhanced 

T cell responses, in terms of cytokine secretion and target 

cell killing, correlating with upregulation of genes typically 

involved in T cell activation. Importantly, our results also 

allowed us, for the first time, to describe that optimal 

T cell function is limited to a given window of TCRpMHC 

binding affinity, with a drastic reduction in cell responsiveness 

of T cells expressing either lower or higher TCR 

affinities. 

In conclusion, we recently established novel experimental 

strategies, allowing us to generate tumourspecific T lymphocytes 

expressing sequenceoptimized TCRs. Thanks 

to this unique model we showed that T cell immune responses 

against cancer cells can be specifically and drastically 

improved. However, our study also revealed the 

presence of an affinity window for optimal T cell function. 

We are currently characterizing some of the parameters 

involved in regulation of TCR function. We propose that 

the rational optimization of TCRpMHC binding above a 

given affinity window not only has the potential to cause 

crossreactivity but also can result in drastic reduction 

of optimal effector function towards cancer cells. These 

results are of particular relevance for the treatment of 

patients with cancer by adoptive transfer of T cells genetically 

engineered to display affinityoptimized TCRs, as

they highlight the importance of assessing TCR avidity 

and efficacy for improved therapy. Identifying rationally 

optimized TCRs and expressing such tumourspecific receptors 

in T lymphocytes represents one of the most 

promising approaches to improving adoptive T cell therapy 

against cancer. 


Dr Nathalie Rufer 



c/o CHUV, HO 05/1532 

Avenue PierreDecker 4 


Phone +41 (0)21 314 01 99 

nathalie.rufer@unil.ch 

Ruiz i Altaba Ariel | Determination of the extent of 

participation of the sonic hedgehog-GLI signaling 

pathway in human gliomas and in their cancer stem 

cells (OCS 01857022006) 

Human gliomas are devastating brain tumours (~2 % of 

total cancers in Switzerland) that are extremely difficult to 

treat. Most of these tumours are resistant to the usual 

chemotherapeutical agents and to radiotherapy. Moreover, 

because they often spread to adjacent tissues, glioma 

tumours are almost impossible to remove by surgery and 

are therefore associated with a high mortality rate (within 

12 months). Even if it is known that gliomas develop from 

cancerous glial cells, the molecular mechanisms involved 

in this process are poorly understood. Recently, we and 

others found that the sonic hedgehog (SHH)GLI signalling 

pathway, a pathway known to participate in embryonic 

development, is required for the growth and the survival 

of many different type of tumours, including gliomas. 

Moreover, we and others showed previously that SHH 

GLI also regulates the behaviour of normal stem cells during 

brain development in the mouse. All together, these 

results prompt us to understand how the SHHGLI signalling 

pathway regulates the behaviour of glioma tumours 

and their cancer stem cells. To this purpose, we will analyse 

the growth and the survival of primary tumourigenic 

cells coming from patient biopsies and xenografted in 

mice. In parallel, we propose to study the properties of regeneration, 

differentiation and generation of tumours of 

the cancer stem cells present in gliomas. The advances in 

the understanding of the molecular mechanisms sustaining 

the biology of gliomas and their cancer stem cells produced 

by this study should be an aid to devising and developing 

new efficient therapies against this destructive 

cancer. 


Prof. Dr Ariel Ruiz i Altaba 

Département de génétique médicale et 

de développement 

Faculté de médecine 


1, rue MichelServet 


Phone +41 (0)22 379 54 46 

Fax +41 (0)22 379 59 62 

ariel.ruizaltaba@unige.ch 

Schär Primo | Clarification of newly emerging roles 

of DNA repair in mediating the cytotoxicity of 

5-fluorouracil and in the maintenance of epigenetic 

stability (OCS 01868022006) 

Background of the study 

Every day, damage occurs to DNA bases in our cells thousands 

of times, mostly in the form of small chemical modifications 

that are either cytotoxic or mutagenic. To avoid 

genetic mutation, cells need to repair the DNA damage. In 

this process, DNA glycosylases first recognize and excise 

the base lesions. TDG (thymine DNA glycosylase) is one 

of these enzymes, and its ability to remove uracil (U) and 

thymine (T) from DNA when mispaired with guanine (G) 

implicates a function in avoidance of genetic mutations 

from deaminated cytosine and 5methylcytosine bases in 

DNA. The failure of repair would generate C T muta 

tions that often contribute critically to carcinogenesis. 

However, TDG also detects and processes 5fluorouracil 

(5FU) in DNA. 5FU is a uracil analogue commonly used 

as a chemotherapeutic drug against cancer. Exposure of 

cells to 5FU favours misincorporation of uracil and 5FU 

into genomic DNA. The processing of these bases by DNA 

repair activities was proposed to account for the DNAdirected 

cytotoxicity of the drug, but underlying mechanisms 

have not been resolved. 

Aim 

The aim of this study was to clarify the contribution of 

TDGdependent base excision to the response of cells and 

cancers to 5FU, and to the suppression of carcinogenesis 

through the maintenance of genetic and epigenetic stability. 

Methods and approach 

We generated mouse cell lines with targeted disruptions 

of the Tdg gene. Matched TDG deficient and proficient 

cell lines were then used to assay the impact of 5FU 

treatment on cell survival, cell cycle progression and the 

generation of druginduced DNA damage. To address the 

role of TDG in tumour suppression and as a basis for followup 

studies, we started to profile TDG expression in 

human cancers. 

Findings of the study 

The following summarizes the results finalizing the first 

part of the study. These were published in PLoS Biology 

and establish a role for TDG in the cellular response to 

5FU. Genetic inactivation of TDG significantly increased 

cellular resistance towards 5FU. We found that excision 

of DNAincorporated 5FU by TDG generates persistent 

DNA strand breaks, delays DNA duplication and activates 

cellular DNA damage signalling. In the absence of TDG, 

however, repair of 5FU induced DNA strand breaks is 

more efficient. We thus concluded that excision of 5FU 

87

88 

by TDG prevents efficient downstream processing of 

repair intermediates, thereby mediating DNAdirected 

cytotoxicity. The status of TDG expression in a cancer is 

therefore likely to determine its response to 5FUbased 

chemotherapy. 


Prof. Dr. Primo Schär 





CH4058 Basel 

Phone +41 (0)61 267 07 67 

Fax +41 (0)61 267 35 66 

primo.schaer@unibas.ch 

Schär Primo | The role of thymine DNA glycosylase 

in the maintenance of genetic and epigenetic stability 

and the suppression of tumorigenesis 

(OCS 2193022008) 

Background of the study 

To maintain the integrity of genetic information, every cell 

of your body uses repair systems to remove damage occurring 

to DNA. The most prevalent DNA lesions are small 

chemical modifications of the DNA bases, and these are 

recognized and removed from DNA by specialized enzymes. 

TDG belongs to this class of enzymes. It removes 

uracil (U) and thymine (T) when mispaired with guanine 

(G). Such mispairs in DNA arise frequently by spontaneous 

deamination of cytosine or 5methylcytosine, respectively. 

In addition to the repair of these lesions, TDG has 

been implicated in the regulation of gene transcription 

and in the control of cytosine methylation. Cytosine 

methylation in DNA serves as a molecular tag to activate 

or inactivate genes. In cancerous cells these tags are often 

inaccurately set, thereby avoiding the expression of genes 

that act against tumour development. Although its biological 

function remains to be clarified, the available 

evidence strongly suggests that TDG act against genetic 

mutation and stabilizes gene expression, both of which 

are important tumour suppressor functions. Thus, TDG is 

likely to play a critical role in tumour suppression. This 

study was designed to address the putative tumour suppressor 

function for the first time directly in human cancers. 

Aims 

The aims of this study were to analyze the expression status 

of TDG in different human cancers and the respective 

normal tissue, to identify molecular causes of the potential 

loss of TDG expression in cancer cells and to characterize 

epigenetic and genetic instabilities in such cancers. 

Methods and approach 

We developed immunohistochemical methods for specific 

staining of TDG in tissue sections. These methods were 

used to compare presence and levels of TDG protein in 

various human cancers with those in the respective nor 

mal tissues. In addition, we established methods allowing 

the analysis of cytosine methylation in gene regulatory regions 

and used these to assess the effect of TDG expression 

on the status of cytosine methylation. 

Findings of the study 

The systematic analysis of TDG expression in normal and 

cancerous tissues generated interesting results. In most 

normal tissues, TDG was inhomogenously expressed and 

present only in a subset of cells. The mean number of TDG 

expressing cells varied in a tissuedependent manner, 

ranging from less than 10 % (breast) to over 80 % (brain). 

In tumours, however, such patterns of TDG expression 

were dramatically changed, most prominently in the colorectal 

cancers. In comparison to normal colorectal epithelium, 

which showed about 30 % TDG positive cells, the 

amount of TDG expressing cells in the cancer tissue was 

reduced to an average of 4 %. Strikingly, most colorectal 

tumours presented with a complete absence of TDG protein. 

Initial molecular analysis of these tumours revealed 

an increase of cytosine methylation in the regulatory regions 

of the Tdg gene and of other genes. Altogether, our 

data suggest that the absence of TDG brings about instability 

in gene expression, conferring a selective advantage 

to cancer forming cells. 







CH4058 Basel 

Phone +41 (0)61 267 07 67 

Fax +41 (0)61 267 35 66 


Schübeler Dirk | Role and plasticity of DNA methylation 

in stem cell pluripotency and cancer 

(KLS 01865022006) 

In recent years, stem cells have been discovered in many 

adult tissues throughout the body, where they differentiate 

into specific cell types and help to regenerate the tissue. 

In addition, scientific studies suggest that these adult 

stem cells can transform into cancer stem cells. Next to 

genetic mutations, epigenetics changes might play a role 

in this aberration. In this study we determined the dynamics 

of DNA methylation, an epigenetic modification, during 

normal differentiation and explored its potential to 

differentiate between normal and cancer stem cells. 

Aim 

The goal of the study was to identify epigenetic markers 

of cancer stem cells, i.e. genomic regions that are specifically 

DNA methylated or unmethylated in cancer stem 

cells. 

Method and Approach 

We employed embryonic stem (ES) cells as an in vitro 

model. We differentiated them into neuronal progenitors 

and terminal neurons and furthermore compared them to 

embryonic carcinoma (EC) cells. Using the MeDIP technique 

to measure DNA methylation and chromatin immunoprecipitation 

technique to measure histone modifica

tions in conjunction with microarrays, we determined the 

epigenetic state of 26,500 genes in each cell type and 

compared this with the respective expression patterns. A 

bioinformatics analysis system was developed to compare 

the different measurements in the different cell types. 

Results of study 

The DNA methylation profiles of the EC and ES cells 

showed only subtle differences, indicating that changes in 

DNA methylation might not be an early feature of promoters 

in the transition from ES to EC cells. Histone modification 

profiles were subsequently created and showed 

greater plasticity. The chromatin state of the promoters 

studied was also compared with the expression states of 

the respective genes. A study of the differentiation of ES 

cells into neurons revealed contextdependant crosstalk 

between Polycombmediated histone methylation and 

DNA methylation, leading us to the idea that Polycomb 

targets might become methylated at a later stage in cancer 

stem cell development. Promoters becoming methylated 

in the differentiation to neurons are enriched for 

pluripotency genes, which are unmethylated in both the 

ES and the EC cell lines studied. 


Dr. Dirk Schübeler 




CH4058 Basel 

Phone +41 (0)61 697 82 69 

Fax +41 (0)61 697 39 76 

dirk@fmi.ch 

Schwaller Jürg | PIM serine/threonine kinases as 

potential therapeutic targets in human haematological 

malignancies (OCS 01830022006) 

Malignant disorders of the haematopoietic system are often 

associated with uncontrolled activity of proteins with 

enzymatic activity of protein kinases. These kinases transfer 

phosphate molecules on their substrates (on serine, 

threonine or tyrosine residues) and hereby deliver a wide 

variety of cellular signals. We showed previously that 

most cases of acute and chronic leukaemias are associated 

with overexpression of the constitutively active PIM serine/threonine 

kinases (PIM1, PIM2) that are essential for 

uncontrolled growth and survival of leukaemic cell lines 

and primary blasts. The goals of this project were: 1) to 

characterize novel small molecule PIM inhibitors; and 

2) to better understand the molecular mechanisms underlying 

the leukaemogenic activity of PIM kinases. Working 

in close collaboration with structural chemists, we were 

able to identify several small molecules that selectively interacted 

and blocked PIM kinases. These PIM kinase inhibitors 

also significantly reduced growth and survival of 

leukaemic cell lines and primary blasts from patients. 

We studied the role of PIM kinases in induction and maintenance 

of the disease in a mouse leukaemia model. Our 

experiments revealed that PIM1 (but not PIM2) has a so 

far unknown function in regulation of cellular migration to 

the bone marrow. PIM1 seems to functionally regulate the 

CXCL12/CXCR4 chemokine ligand/receptor signal trans 

duction pathway. After binding the ligand, the CXCL12/ 

CXCR4 ligand/receptor complex gets internalized and activates 

multiple signals that control cellular adhesion and 

migration. A part of the molecules becomes degraded and 

newly formed, but the majority of the receptor is “recycled” 

to the cell surface. 

We were able to show that PIM1 phosphorylates a distinct 

amino acid residue (serine 339) located in the intracellular 

tail of the CXCR4 receptor. Cells lacking PIM1 show reduced 

“recycling” to the cell surface, resulting in lower 

numbers of CXCR4 receptor molecules at the surface, 

which is associated with reduced homing and migration of 

haematopoietic stem cells to the bone marrow. Leukaemic 

cells (cell lines or primary blasts) with elevated PIM1 levels 

exhibit more CXCR4 molecules on the surface and 

enhanced cellular adhesion and migration. Interestingly, 

treatment of the cells with our novel PIM inhibitors significantly 

reduced the number of surface CXCR4 molecules 

and migration of leukaemic cells. 

Our work not only revealed a previously unknown molecular 

mechanism underlying the leukaemogenic activity of 

PIM kinases but also opened up the possibility to modulate 

adhesion and migration of normal and leukaemic 

haematopoietic stem cells with small molecule PIM kinase 

inhibitors. These observations have provided additional 

rationale for PIM kinase inhibitors to enter first clinical trials. 


Prof. Dr. Jürg Schwaller 

Forschungsgruppe Kinderleukämie 



Hebelstrasse 20 

CH4031 Basel 

Phone +41 (0)61 265 35 04 

Fax +41 (0)61 265 23 50 

j.schwaller@unibas.ch 

Skoda Radek C. | Pathogenesis of myeloproliferative 

disorders (OCS 01742082005) 

Myeloproliferative disorders (MPD) are chronic blood diseases 

characterized by overproduction of blood cell precursors 

in the bone marrow. Patients with MPD bear an 

increased risk (5–20 %) to develop an acute leukaemia after 

a variable latency. Therefore, MPD is often considered 

a „preleukaemia“. We found that in about 70–80 % of 

MPD patients, the blood stem cells carry a mutation in the 

gene “Janus kinase 2” (JAK2). JAK2 is an enzyme that 

transmits signals coming from the outside into the cell and 

the mutation (JAK2V617) amplifies the growthpromoting 

effect of these signals, so that more blood cells are 

formed. The aim of our studies is to better understand 

how the JAK2V617F mutation causes MPD, with which 

partner genes it collaborates in this process and what the 

predisposing events are that can favour the acquisition of 

MPD. 

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To address these questions, we are combining detailed 

analysis of cells and tissues from patients with MPD with 

mouse models of MPD. Our studies in patients revealed 

that JAK2V617F may be preceded by as yet unknown 

mutations. To follow up on this observation, we studied 

patients with MPD that in addition to JAK2V617F have 

deletions of chromosome 20q (del20q) or carry mutations 

in a gene called TET2, and we determined the temporal 

order in which these mutations were acquired. Our studies 

showed that there is no fixed order of events, and 

some patients acquire JAK2V617F first, followed by 

del20q or TET2 mutations, whereas in other patients with 

MPD the inverse order can be observed. Thus, deletions 

of chromosome 20 and mutations in TET2 are unlikely to 

represent predisposing events for JAK2V617F, and we 

are examining other candidate genes for such a function 

in familial forms of MPD. 

A second question that we are addressing is why the 

JAK2V617F mutation can cause 3 different subtypes of 

MPD, namely, essential thrombocythemia (ET) with elevated 

platelet levels, polycythemia vera (PV) with increased 

numbers of red cells and in some cases primary 

myelofibrosis (PMF) with fibrosis of the bone marrow and 

blood formation in the spleen and liver. We generated a 

mouse model of MPD that expresses the mutant JAK2 

V617F and displays all 3 types of MPD. We found that ET 

develops when the mutant human JAK2V617F is expressed 

at lower levels, while at higher levels PV phenotype 

can be observed. Myelofibrosis occurred later in 

these mice and appears to correlate with the platelet 

counts. Interestingly, when we made a mutation in a different 

position in JAK2 that is associated with a pure red 

cell phenotype in patients (JAK2 exon 12 mutation), we 

observed a pure red cell elevation in the mice, i.e. the 

same phenotype as in patients. Thus, in addition to expression 

levels, the different JAK2 mutations may also 

cause different quality of signals that favour the expansion 

of specific blood cell types. Finally, inhibitors have 

been developed that can reduce the enzymatic activity of 

JAK2 and are undergoing clinical trials in patients with 

MPD. Our mouse models have proven to be valuable in 

testing such compounds. 

Our projects on JAK2 have contributed to changing the 

diagnostic and therapeutic approach to patients with 

MPD. We are now examining how other known gene mutations 

collaborate with JAK2 mutations and are searching 

for as yet unknown new gene mutations in MPD. 


Prof. Dr. Radek C. Skoda 

Forschungsgruppe experimentelle Hämatologie 




4031 Basel 

Phone +41 (0)61 265 22 72 

Fax +41 (0)61 265 32 72 

radek.skoda@unibas.ch 

Suter Beat | Control of the cell cycle function of Xpd 

and Cdk7 (OCS 01834022006) 

The Xpd gene aids our body in different ways to prevent 

cells from turning into tumour cells. Many patients with a 

genetic defect in the Xpd gene have a one to two thousandfold 

increase in cancer risk. Whereas skin cancer is 

the most prevalent form, other tissues can be affected as 

well. It was known for some time that one of the functions 

of this XPD is to repair the genetic material once it gets 

damaged in certain ways. However, it was also known 

that the reduced repair capacity alone does not necessarily 

lead to this very high cancer incidence in patients. We 

tried to elucidate novel functions of Xpd, and we wanted 

to find out whether these functions could play important 

roles in preventing tumour formation. 

To be able to identify additional novel functions of XPD 

and to analyze them, we developed a model system in 

which the previously known activities of XPD are not required. 

We were able to develop such a model in an intact 

organism by using the embryo of the fruit fly Drosophila. 

Using this model we found that the XPD protein is a truly 

multifunctional protein that helps to organize the division 

of cells and that coordinates this process with other cellular 

processes. If it fails to function properly, the genetic 

material is not distributed equally to the ensuing daughter 

cells. As a consequence, daughter cells arise that lack 

pieces of chromosomes or even entire chromosomes. This 

instability of the genome is a decisive step in tumour formation. 

Identifying the need for XPD to prevent this instability 

in our model system was a big step forward in finding 

out the causes of this devastating disease. 

The diverse functions of XPD make it a truly fascinating 

multifunctional protein. It performs diverse cellular functions 

and acts through several different cellular processes. 

The cells need to tightly coordinate these diverse processes 

for the body to function properly. In the course 

of our experimental work we realized that XPD is able to 

coordinate these processes by acting as a dispatcher for 

another protein complex named CAK. XPD sends CAK at 

the correct time to the appropriate place in the cell, where 

it can act on the local target substrates. At the same time, 

the localization to a new region terminates CAK activity 

towards a previous target that should no longer be activated 

at this point. Therefore, by sending CAK to the right 

place at the right time, the dispatcher controls and coordinates 

these different cellular processes. 

As described at the beginning, malfunctioning of this XPD 

in human patients can lead to highly elevated cancer risk 

in Xpd patients. Combining our own studies with earlier 

studies we came to the conclusion that the very strongly 

elevated cancer risk arises most likely in Xpd patients in 

which the failure to repair the genetic material combines 

with defective Xpd activity in organizing and controlling 

the cell division. It seems likely that as long as one of the 

two functions is still active, the cancer risk is only moder

ately elevated. In summary, Xpd protects our genetic material 

in different ways, and it therefore acts as a veritable 

bodyguard to our genetic material. 


Prof. Dr. Beat Suter 


Universität Bern 

Baltzerstrasse 4 

CH3012 Bern 

Phone: +41 (0)31 631 47 15 

beat.suter@izb.unibe.ch 

Tschan Mario P. | Regulation of the DMP1-ARF-p53 

tumor suppressor pathway in normal and leukemic 

hematopoiesis (OCS 01823022006) 

Cyclin D binding myblike protein 1 (DMP1) is a haploinsufficient 

tumour suppressor involved in positively modulating 

the alternative reading frame (ARF)p53 signalling 

pathway. This pathway is inactivated in most cancers, including 

leukaemias, and further understanding of its regulation 

might provide novel options for cancer treatment. 

DMP1 is a direct transcriptional activator of ARF and of 

CD13, a gene involved in myeloid differentiation. Using 

lentiviral vectors to express shRNA for gene knockdowns 

or transgenes as well as promoter reporter and proliferation 

assays, we identified novel transcriptional, posttranscriptional 

and posttranslational regulators of the DMP1 

tumour suppressor. 

Moreover, we showed that a dominant negative splice 

variant of DMP1, DMP1 beta has oncogenic properties by 

inhibiting the fulllength DMP1 and promoting cellular 

proliferation. In addition, we found aberrant expression of 

this splice variant in acute myeloid leukaemia patients’ 

samples as compared to healthy controls. In summary, we 

discovered a variety of novel mechanisms to inactivate the 

DMP1 tumour suppressor in myeloid leukaemias, or other 

tumours, and propose the following DMP1 repression 

models: 1) enhanced expression of the dominant negative 

DMP1 beta splice variant leading to reduced ARF levels 

and thus aberrant proliferation; 2) altered expression of 

microRNAs, which target DMP1; and 3) inactivation of 

positive DMP1 regulators, such as the transcription factor 

OCT1 and or the kinase DAPK2. 


Dr. Mario P. Tschan 

Medizinische Onkologie/Hämatologie 

Departement für klinische Forschung 


MEM E829 

Murtenstrasse 35 

CH3010 Bern 

Phone +41 (0)31 632 87 80 

mtschan@dkf.unibe.ch 

Walker Paul R. | Exploration of intracerebral immune 

responses in a spontaneous astrocytoma model and 

their exploitation in novel cancer therapies 

(OCS 1754082005) 

In this study we used a transgenic mouse model in which 

brain tumours spontaneously arise to understand the interactions 

of the immune system with the developing cancer. 

This is difficult to study in patients, because the limited 

tumour samples that are available for analysis are 

generally from advanced cancers, or after treatment. We 

studied mice before they developed any cancer related 

symptoms, and also when they became ill. We isolated 

immune cells from lymph nodes and spleen, as well as 

from the brain, to assess the leukocyte subsets present 

and their functions. We then tested a vaccination approach 

to improve the potential antitumour immune response. 

Objectives 

Immunotherapy for patients with malignant gliomas may 

be a useful future treatment option. However, it is not 

clear whether this should aim to reinforce or reprogram a 

preexisting immune response. By analyzing the spontaneous 

gliomas that arise in the brains of GFAPV 12 HAras 

transgenic mice, we aimed to determine whether brain tumours 

were detected by the immune system at an early 

stage, and whether antitumour immunity was functional 

at any stage, or could be induced or restored by vaccination. 

Methods 

In the GFAPV 12 HAras model, mice spontaneously form 

astrocytomas that develop progressively and gradually 

increase in malignancy. We sacrificed individual mice at 

fixed time points while they were still healthy (4, 8, and 

12 weeks of age) and also once they became terminally ill. 

Immune cells were isolated from dissociated brain and 

lymphoid tissues and were stained with antibodies to 

identify all principle leucocyte subsets. We stained for 

cytokines and cytotoxic molecules important for anti 

tumour activity. Analysis was principally by flow cytometry. 

To augment the number of immune cells infiltrating 

the brain we used a vaccine comprised of a recombinant 

virus to induce immunity to brain tumour cells. 

Results 

There was an immune response induced by the tumour at 

early, nonmalignant stages of glioma development, before 

the mice developed symptoms. However, the immune 

cells that first infiltrated the brain included many regulatory 

T cells that are capable of suppressing cytotoxic 

T cells that could otherwise attack the glioma. Consistent 

with this, the CD8 T cells that coinfiltrated the brain had 

low or absent expression of the cytotoxic molecule granzyme 

B and cytokines useful in antitumour immunity 

(interferong, TNF and IL2). Peripheral vaccination with 

recombinant virus could augment interferong expression 

by CD8 T cells, but only direct intracranial stimulation 

could restore granzyme B expression. 

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Translational relevance 

The results suggest that immunotherapy for glioma may 

be partially successful with peripheral approaches such as 

vaccination, but locally applied treatments or reducing 

immunosuppressive factors may be necessary for full efficacy. 


PD Dr Paul R. Walker 

Laboratoire d’immunologie des tumeurs 

Centre d’oncologie 

Hôpitaux universitaires de Genève (HUG) 

4, rue GabriellePerretGentil 


Phone +41 (0)22 372 98 80 

paul.walker@hcuge.ch 

Wymann Matthias P. | Phosphoinositide 3-kinases 

in melanoma (OCS 01924082006) 

Advanced metastatic melanoma is refractory to conventional 

chemotherapy. Phosphoinositide 3kinases (PI3Ks) 

are lipid kinases – enzymes phosphorylating lipids at the 

plasma membrane – and act as a key relay of growth, proliferation 

and cell migration. Initial studies using potent, 

broadband PI3K inhibitors have demonstrated the sensitivity 

of melanoma to PI3K inhibition. Work with genetically 

targeted mice shows that broadband PI3K inhibitors 

affect metabolic control, the immune system and cardiovascular 

parameters. To minimize side effects, the role of 

specific PI3K isoforms on tumour autonomous control in 

melanoma will be investigated. In this context, a murine 

B16 cell tumour transfer model will be used. Altogether, 

the proposed work will define the prospect and the profile 

of future therapies targeting PI3Ks in melanoma. 


Prof. Dr. Matthias P. Wymann 





CH4058 Basel 

Phone +41 (0)61 695 30 46 

matthias.wymann@unibas.ch 

Further completed research projects from July 2008 to December 2010 

Pelkmans Lucas | OCS 02111082007 | CHF 198,000.– 

Institut für molekulare Systembiologie, ETH Zürich, Zürich 

How focal adhesion kinase (FAK) controls membrane partitioning and endocytosis of cell adhesion components 

in normal and in cancer cells 

Stamenkovic Ivan | OCS 01656022005 | CHF 173,900.– 


Analysis of the molecular mechanisms underlying the pathogenesis of EWING’S family tumors


List of approved research projects in 2009/2010 

Total funds allocated: CHF 11,792,000.– 

Aguet Michel | KFS 02674082010 | CHF 234,400.– 

Institut suisse de recherche expérimentale sur le cancer (ISREC), Faculté des sciences de la vie, EPF de Lausanne, 

Lausanne 

Role of BCL9/BCL9L in regulating Wnt-mediated epithelial-mesenchymal transition, stem cell traits and drug 

sensitivity in Wnt-activated human cancers 

Basler Konrad | KFS 02443082009 | CHF 169,400.– 

Institut für molekulare Biologie, Universität Zürich, Zürich 

Characterization of the role of histone binding by the WnT-signalling components Pygo2 in murine models 

of breast cancer and colon cancer 

Becher Burkhard | KFS 02441082009 | CHF 203,000.– 

Institut für experimentelle Immunologie, Departement Pathologie, UniversitätsSpital Zürich, Zürich 

Cellular and molecular characterization of IL-12-mediated tumor suppression 

Boyman Onur | KFS 02672082010 | CHF 343,400.– 

Dermatologische Klinik, UniversitätsSpital Zürich, Zürich 

Preclinical testing of interleukin-2-antibody complexes for tumor immunotherapy 

Brisken Cathrin | KFS 02462082009 | CHF 331,200.– 

NCCR Molecular Oncology, Institut suisse de recherche expérimentale sur le cancer (ISREC), Faculté des sciences 

de la vie, EPF de Lausanne, Lausanne 

Mechanisms of action of progesterone in the human breast 

Brown Steven A. | KFS 02642082010 | CHF 240,100.– 

Institut für Pharmakologie und Toxikologie, Medizinische Fakultät, Universität Zürich, Zürich 

The mechanism of cancer and circadian clock interactions and its usefulness in the design of therapeutic 

strategies 

Christofori Gerhard | KLS 02535022010 | CHF 283,200.– 


The functional role of the transcription factors DIx2 and Lhx2 in epithelial-mesenchymal transition (EMT) 

and in malignant tumor progression 

Constam Daniel | KFS 02487082009 | CHF 307,600.– 

UPCDA, Institut suisse de recherche expérimentale sur le cancer (ISREC), Faculté des sciences de la vie, 


Role of activin signalling in metastatic melanoma 

Dotto Gian-Paolo | OCS 02361022009 | CHF 314,350.– 

Département de biochimie, Faculté de biologie et de médecine, Université de Lausanne, Epalinges 

Tumor suppressing function of calcineurin/NFAT in keratinocytes 

Dufour Jean-François | KFS 02541022010 | CHF 202,200.– 

Institut für klinische Pharmakologie, Universität Bern, Bern 

Hepatocarcinogenic roles of mTOR, raptor and rapamycins in absence of Pten 

Gönczy Pierre | KLS 02584022010 | CHF 197,000.– 

UPGON, Institut suisse de recherche expérimentale sur le cancer (ISREC), Faculté des sciences de la vie, 


Mechanisms of centrosome duplication: From model organism towards therapeutic opportunities 

Grassi Fabio | KFS 02445082009 | CHF 144,000.– 

Istituto di ricerca biomedicina (IRB), Bellinzona 

Purinergic signalling in the pathophysiology of central nervous system infiltration in T-cell leukemia 

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Grünberg Jürgen | KFS 02546022010 | CHF 192,400.– 

Zentrum für radiopharmazeutische Wissenschaften, ETHPSIUSZ, Paul Scherrer Institut, Villigen 

Combinational therapy of ovarian cancer metastases expressing the L1 cell adhesion molecule 

(L1-CAM) based on radioimmunotherapy and growth inhibition 

Hall Jonathan | KFS 02648082010 | CHF 226,000.– 

Institut für pharmazeutische Wissenschaften, ETH Zürich, Zürich 

Targeting pre-let-7 biogenesis in cancer 

Hemmings Brian A. | KFS 02714082010 | CHF 278,700.– 


Dissecting translation reveals therapeutic prospects for malignant gliomas 

Hottiger Michael O. | KLS 02396022009 | CHF 261,700.– 


Multiplex analysis of the ionizing radiation-induced signalling network at the single cell level 

Huard Bertrand | KFS 02464082009 | CHF 283,400.– 

Département de pathologie et immunologie, Faculté de médecine, Université de Genève, Genève 

APRIL blockade for the treatment of multiple myeloma 

Hübscher Ulrich | KLS 02339022009 | CHF 203,100.– 


Regulation of base excision repair by human DNA polymerase 1 through posttranslational modification: 

degradation versus stabilization 

Huelsken Joerg | KFS 02667082010 | CHF 344,700.– 

UPHUE, Institut suisse de recherche expérimentale sur le cancer (ISREC), Faculté des sciences de la vie, 


Stemness control in cancer stem cells 

Hynes Nancy | KFS 02528022010 | CHF 183,100.– 


Reciprocal cross-talk between low-density lipoprotein receptor-related protein 1 and receptor 

tyrosine kinases: Implications for modulating in vitro and in vivo properties of breast tumor cells 

Janscak Pavel | KLS 02344022009 | CHF 74,800.– 


Study of the role of mismatch-repair proteins in the cellular response to DNA double-strand breaks 

Krek Wilhelm | KFS 02690082010 | CHF 226,000.– 


Roles of the URI oncoprotein in B-RAF-signaling and melanoma cancer cell proliferation 

Martinou Jean-Claude | KLS 02370022009 | CHF 209,100.– 

Département de biologie cellulaire, Faculté des sciences, Université de Genève, Genève 

Studies on the role of TRAIL as a tumor metastasis promoter 

Meraldi Patrick | KFS 02707082010 | CHF 226,000.– 

Institut für Biochemie, ETH Zürich, Zürich 

How does overexpression of the Aurora-A oncogene override the spindle checkpoint? 

Merdes Gunter | KFS 02695082010 | CHF 116,700.– 

Departement Biosysteme, ETH Zürich, Basel 

Systems biology of tumor suppression and malignancy in the model system Drosophila 

Michielin Olivier | KFS 02555022010 | CHF 304,500.– 

Molecular Modelling Group (MMG), Institut suisse de bioinformatique (ISB), Lausanne 

Rational design of anti-MART-1 TCR sequences for adoptive transfer immunotherapies 

Müller Anne | KFS 02640082010 | CHF 293,700.– 



lymphoma: Analysis of the role of small regulatory RNAs in lymphomagenesis and high grade transformation

Münz Christian | KFS 02652082010 | CHF 347,200.– 

Institut für experimentelle Immunologie, Universität Zürich, Zürich 

Tumorigenesis and immune control of the Epstein Barr virus in vivo 

Ochsenbein Adrian F. | KLS 02342022009 | CHF 320,450.– 


Immunogenicity of chronic myeloid leukaemia stem cells 

Pertz Olivier | KFS 02485082009 | CHF 333,000.– 


A slit/robo signalling pathway regulating contact mediated repulsion during cell migration: 

Implications of its deregulation for the acquisition of an invasive phenotype during breast cancer 

Petrova Tatiana | KLS 02570022010 | CHF 198,300.– 

Centre pluridisciplinaire d’oncologie (CePO), Centre hospitalier universitaire vaudois (CHUV) 

et Université de Lausanne, Epalinges 

Lymphatic endothelial calcineurin/NFAT signalling in tumor lymphangiogenesis and metastasis 

Plückthun Andreas | KFS 02448082009 | CHF 238,600.– 

Biochemisches Institut, Universität Zürich, Zürich 

Tumor targeting of ErbB2 with designed ankyrin repeat proteins 

Pruschy Martin | KFS 02551022010 | CHF 303,700.– 

Labor für molekulare Radiobiologie, Klinik für RadioOnkologie, UniversitätsSpital Zürich, Zürich 

Differential response to proton versus photon radiotherapy: Biological implications for new indications 

and combined treatment concepts 

Radtke Freddy | KLS 02387022009 | CHF 316,700.– 

UPRAD, Institut suisse de recherche expérimentale sur le cancer (ISREC), Faculté sciences de la vie, 


The role of Notch and TSLPR signalling during skin cancer 

Renner Christoph | KFS 02500082009 | CHF 194,500.– 

Klinik und Poliklinik für Onkologie, Medizinbereich Innere MedizinOnkologie, UniversitätsSpital Zürich, Zürich 

Inhibition of tumour growth by targeting cancer associated fibroblasts 

Ruiz i Altaba Ariel | OCS 02359022009 | CHF 339,500.– 

Département de génétique médicale et de développement, Faculté de médecine, Université de Genève, Genève 

Role and prevalence of hedgehog signalling in human colorectal cancer 

Santamaria Anna | KFS 02657082010 | CHF 194,400.– 


Control of chromosome segregation fidelity by the Ska complex, a key regulator of stable kinetochore- 

microtubule attachments during mitosis 

Schär Primo | KFS 02585022010 | CHF 237,500.– 


DNA repair, epigenetic stability, and CpG island hypermethylation in colorectal tumorigenesis 

Schorderet Daniel | KFS 02565022010 | CHF 197,000.– 

Institut de recherche en ophtalmologie (IRO), Sion 

Retinoblastoma: Understanding its development for better treatment 

Swartz Melody | KFS 02696082010 | CHF 405,300.– 

Institute of Bioengineering and Institute for Experimental Cancer Research, EPF de Lausanne, Lausanne 

Roles of tumor VEGF-C and CCL21 in immunological tolerance 

Thoma Nicolas | OCS 02365022009 | CHF 186,300.– 


The molecular basis of the defense against skin cancer: Structural studies of the DDB1-DDB2-XPC/Rad23 

UV-damage handover complex 

Thome-Miazza Margot | KFS 02561022010 | CHF 198,300.– 

Département de biochimie, Université de Lausanne, Epalinges 

Analysis of the role of the protease MALT1 in human lymphomas 

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Tschan Mario P. | KFS 02486082009 | CHF 262,500.– 

Medizinische Onkologie/Hämatologie, Departement für klinische Forschung, Universität Bern, Bern 

The importance of autophagy in normal and leukemic myelopoiesis 

Weller Michael | KFS 02694082010 | CHF 195,700.– 

Klinik für Neurologie, UniversitätsSpital Zürich, Zürich 

Angiogenesis and invasion in glioblastoma: The therapeutic options and risks of co-targeting VEGF and 

TGF-beta 

Widmann Christian | KFS 02543022010 | CHF 205,300.– 

Département de physiologie, Faculté de biologie et de médecine, Université de Lausanne, Lausanne 

The 317-326 sequence of RasGAP as potential anti-metastatic agent 

Wymann Matthias Paul | KFS 02680082010 | CHF 343,000.– 


Identification and modulation of targets to reprogram glioblastoma cancer stem cells 

Zaugg Kathrin | KLS 02569022010 | CHF 78,000.– 


Elucidating the role of the hypoxia-protective gene CPT1C (Carnitine Palmitoyl-transferase 1C) in 

carcinogenesis 

Zavolan Mihaela | KFS 02477082009 | CHF 303,000.– 


Identification of cancer-related targets of individual members of the miR-17~92 cluster of miRNAs 

Approved bursaries in 2009/2010 

Total funds allocated: CHF 722,132.– 

Cornaz Sandrine | MDPhD 02607062010 | CHF 180,533.– 

Mechanisms that regulate primary cell genetic reprogramming and differentiation by sarcoma-associated 

fusion genes (SAMW MD-PhD bursary) 

Zielort: Institut de pathologie, Centre hospitalier universitaire vaudois (CHUV), Lausanne 

Ecsedi Matyas | MDPhD 02431062009 | CHF 180,533.– 

Regulation of the let-7 tumor suppressor microRNA in development and cancer (SAMW MD-PhD bursary) 

Zielort: Labor Grosshans, Friedrich Miescher Institut für biomedizinische Forschung (FMI), Basel 

Essig Martin | MDPhD 02606062010 | CHF 180,533.– 

Transition from paediatric to adult care for childhood cancer survivors (SAMW MD-PhD bursary) 

Zielort: Forschungsgruppe Kinder und Jugendlichengesundheit, Institut für Sozial und Präventivmedizin (ISPM), 

Universität Bern, Bern 

Özdemir Berna | MDPhD 02430062009 | CHF 180,533.– 

Tumour-stroma interactions in prostate cancer bone metastasis (SAMW MD-PhD bursary) 

Zielort: Forschungsgruppe Urologie, Departement für klinische Forschung, Universität Bern, Bern


Presentation of approved research projects in 2009/2010 

Aguet Michel | Role of BCL9/BCL9L in regulating 

Wnt-mediated epithelial-mesenchymal transition, 

stem cell traits and drug sensitivity in Wnt-activated 

human cancers (KFS 02674082010) 

Duration: 01.09.2010 – 01.09.2012 

A major problem of anticancer therapies is tumour relapse, 

typically associated with resistance to therapy. Recent 

observations suggest that tumour cells with stem 

celllike properties, including notably reduced susceptibility 

to common chemotherapeutic agents, are often at the 

origin of relapses. Our group recently reported that in a 

mouse model of colon cancer, inactivation of BCL9 proteins 

suppresses malignancy traits, including stem cell 

markers. Our current studies focus on validating the relevance 

of these observations for human colon cancer. Specifically, 

we will address to what extent inhibition of BCL9 

results in attenuated stem cell properties and, most importantly, 

whether susceptibility to therapy might thereby 

get enhanced. The project should therefore contribute to 

establishing BCL9 proteins as targets for a novel therapy 

aimed at restoring responsiveness to therapy, and to justifying 

the search for small compound BCL9 inhibitors. 


Prof. Dr Michel Aguet 




Faculté sciences de la vie 


c/o Département de pathologie 



Phone +41 (0)21 314 72 17 

michel.aguet@epfl.ch 

Basler Konrad | Characterization of the role of histone 

binding by the WnT signaling components Pygo2 in 

murine models of breast cancer and colon cancer 

(KFS 02443082009) 

Duration: 01.01.2010 – 01.01.2013 

Colon and breast cancer are two of the most common 

types of tumours. Dysregulation of the Wnt signalling 

cascade is known to underlie their formation. The goal of 

this project is to better understand the role played by Pygopus, 

a key component of the Wnt signalling pathway. It 

is now well accepted that “decoding” the marks found on 

histones is an essential part of the process that determines 

if expression of a gene is turned on or off. Histones are the 

proteins that together with DNA form chromatin – the basis 

of our genome. We want to find out if Pygopus can act 

as a histone code reader and in this way contributes to the 

activation of the genetic program triggered by the Wnt 

signal. The insights gained from this study will provide important 

insights into how the Wnt signalling cascade contributes 

to colon and breast cancer progression and will 

open new avenues for the treatment of these cancers. 


Prof. Dr. Konrad Basler 

Institut für molekulare Biologie 




Phone +41 (0)44 635 31 10 

basler@molbio.uzh.ch 

Becher Burkhard | Cellular and molecular characterization 

of IL-12-mediated tumor suppression 

(KFS 02441082009) 

Duration: 01.05.2010 – 01.05.2012 

Immune cells (white blood cells) and their secreted signalling 

molecules play a critical role in tumour control and 

elimination. In a variety of tumour models, the signalling 

molecule interleukin12 (IL12) has been shown to repress 

tumour growth. Yet, IL12 injection into the blood of human 

patients led to severe adverse effects, and therefore 

the development of IL12 therapies has been halted. To 

this day, the molecular and cellular events of IL12 have 

been illunderstood. By defining the mechanistic underpinnings 

of how IL12 works, we shed light on how tumour 

cells and immune cells interact in general, and in 

particular we will enhance the therapeutic targeting of 

malignancies in humans. The tumouricidal activity of IL12 

was widely held to be mediated by two specific subsets of 

white blood cells, the natural killer cells and the T lymphocytes. 

However, we found that tumour suppression is mediated 

independently of these two subsets. Instead, we 

were able to demonstrate that IL12 initiates powerful 

local antitumour immunity by stimulating a subset of 

lymphoid tissue inducer (LTi) cells. These cells seem to alter 

the blood vessels within the tumour mass in a way that 

allows immune cells to enter the tumour and actively fight 

it. Lastly, our findings also demonstrate that IL12 should 

be injected directly into the tumour, thereby limiting the 

adverse effects observed after injection into the blood 

stream. 


Prof. Dr. Burkhard Becher 

Institut für experimentelle Immunologie 


Y44J92 (Office), J38/42 (Lab) 



Phone +41 (0)44 635 37 03 

Fax +41 (0)44 635 68 83 

burkhard.becher@neuroimm.uzh.ch 

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Boyman Onur | Preclinical testing of interleukin-2- 

antibody complexes for tumor immunotherapy 

(KFS 02672082010) 

Duration: 01.02.2011 – 01.02.2014 

Despite the use of improved treatment options, most 

patients with metastatic tumours die within a few years. 

This is also the case for metastatic malignant melanoma, 

a deadly skin tumour. 

Apart from chemotherapeutic regimens, the use of interleukin 

2 (IL2) immunotherapy in the treatment of metastatic 

melanoma has shown promising results. IL2 belongs 

to the family of cytokines that are produced by the 

body’s defence system (immune system) and is able to activate 

cytotoxic T lymphocytes (also called CD8 + T cells). 

Activated CD8 + T cells are able to attack and kill tumour 

cells. For these properties, IL2 was used at high doses in 

metastatic melanoma, and it led to a longterm survival of 

about 13 % of patients for over twenty years, which is 

considerable, given the survival rate of below 5 % within 

five years in untreated patients. However, IL2 immunotherapy 

can lead to serious side effects, such as lung 

oedema or liver damage, which is the reason why this 

treatment is not used more frequently. 

Recently, we showed in an animal model that IL2/anti 

IL2 antibody complexes are more efficient against malignant 

melanoma and show fewer (or no) side effects. 

Based on these promising results in a mouse model of melanoma, 

we will examine the effects of human IL2/anti 

IL2 antibody complexes on the activation of human CD8 + 

T cells against melanoma cells. To this end, we will use humanized 

mice, which carry human immune cells, including 

CD8 + T cells. Testing of IL2/antiIL2 antibody complexes 

on human T cells using humanized mice is a crucial step towards 

being able to proceed to clinical studies. 


Prof. Dr. Onur Boyman 

Dermatologische Klinik 


Gloriastrasse 31 


Phone +41 (0)44 255 25 60 

onur.boyman@usz.ch 

Brisken Cathrin | Mechanisms of action of progesterone 

in the human breast (KFS 02462082009) 

Duration: 01.02.2010 – 01.02.2013 

The mechanisms by which the pregnancy hormone progesterone 

acts on the human breast and contributes to 

breast carcinogenesis are poorly understood, because we 

lack adequate models to study them. 

Our work in the mouse model revealed that progesterone 

acts on a subset of cells in the milk ducts and induces 

them to secrete a protein called RANKL that in turn acts 

on neighbouring cells and makes them proliferate. We are 

developing a novel approach using fresh tissue from reduction 

mammoplasties to preserve the microenvironment 

and essential interactions between the cells to identify 

the mediators of progesterone in the human breast. 

New drugs that interfere with progesterone or RANKL signalling 

are already in clinical trials for different purposes, 

and many inhibitors of specific signalling pathways have 

been developed. The insights gained will be instrumental 

to determine whether progesterone indeed has cancerpromoting 

effects in the human breast. As a consequence, 

drugs blocking progesterone receptor (PgR) signalling and/ 

or its mediators may be useful as novel therapeutic and 

preventive strategies in the management of breast cancer. 


Prof. Dr Cathrin Brisken 






SV2.832 Station 19 


Phone +41 (0)21 693 07 81 

Fax +41 (0)21 693 07 40 

cathrin.brisken@epfl.ch 

Brown Steven A. | The mechanism of cancer and 

circadian clock interactions and its usefulness in 

the design of therapeutic strategies 

(KFS 2642082010) 

Duration: 01.01.2011 – 01.01.2014 

The circadian clock and the cell cycle are cell autonomous 

processes. The interaction between them is complex; the 

clock gates the cell cycle but ticks on even if the cell cycle 

is halted. Perturbations of the clock and the cell cycle can 

lead to cancer. In our project, we want to elucidate how 

the clock interacts with the cell cycle and then use this 

knowledge to improve the timing and thereby the efficiency 

of radiotherapeutic treatment regimes in models 

of brain tumours. 

Tumour clocks and/or clocks in the tissue surrounding the 

tumour could play a major role in tumour growth and 

prognosis for the patient. Thus, our goal is to understand 

the interaction of the various clocks with the cell cycle 

that determines tumour growth, and with this knowledge 

determine an optimal timing of treatment. 

We propose first to analyze circadian clock function in 

multiple different tumour cell lines to understand how the 

circadian clock is affected by oncogenic transformation. 

We will then test synthetically engineered clockcontaining 

and clockless tumours for growth in mice with or 

without circadian clocks to understand the contributions 

of clocks in the tumour and in the organism to tumour 

growth. Finally, we will treat these clockcontaining and 

clockless tumours radiotherapeutically to assess the 

contribution of clock function in both tumour and host to 

treatment outcome. 

Our results – especially the results of the therapeutic 

models – could lead to an improved efficacy of existing 

patient treatments by modifying already existing treatment 

regimes. 


Prof. Dr. Steven A. Brown 

Institut für Pharmakologie und Toxikologie 

Medizinische Fakultät 




Phone +41 (0)44 635 59 99 

Fax +41 (0)44 635 57 07 

steven.brown@pharma.unizh.ch

Christofori Gerhard | The functional role of the 

transcription factors Dlx2 and Lhx2 in epithelial- 

mesenchymal transition (EMT) and in malignant tumor 

progression (KLS 02535022010) 

Duration: 01.09.2010 – 01.09.2013 

The actual cause of death of most patients with cancer 

is due to metastasis. Malignant cancer cells leave their 

primary tumours, invade blood vessels and disseminate 

throughout the body to seed metastasis in distant organs. 

In this project, we investigated the functional contribution 

of the transcription factors Lhx2 and Dlx2 to metastasis. 

We found that both factors regulate genes that are critically 

required for cancer cell migration and metastasis formation. 

Lhx2 appears to directly regulate genes stimulating 

cell migration and invasion, whereas Dlx2 modulates 

the expression of genes required for cell survival during 

the metastatic process. Currently, we are identifying the 

genes that are regulated by Lhx2 and Dlx2 and investigating 

their functional contribution to cancer metastasis. The 

elucidation of the regulatory circuits underlying the metastatic 

process is a prerequisite for the development of 

innovative therapy to prevent cancer metastasis and thus 

patients’ death. 


Prof. Dr. Gerhard Christofori 





CH4058 Basel 

Phone +41 (0)61 267 35 62 

Fax +41 (0)61 267 35 66 

gerhard.christofori@unibas.ch

100 

Constam Daniel | Role of activin signalling in 

melanoma metastasis (KFS 02487082009) 

Duration: 01.02.2010 – 01.02.2013 

Malignant melanomas arise from the transformation of 

pigment cells. These aggressive tumours are characterized 

by a poor prognosis, since the available treatments at best 

afford transient improvement. Cell proliferation and the 

synthesis of UVabsorbing melanin in pigment cells are 

governed by specific nuclear proteins that are themselves 

regulated by extracellular factors. Thus, other skin cells 

can supply themselves with pigment according to their 

needs. However, in the course of tumour progression, 

melanomas frequently “learn” how to produce these or 

similar signals by themselves. One of these signalling molecules 

is activin. To elucidate the role of activin during 

melanoma growth and metastasis, we are comparing the 

behaviour and tumourigenic potential of cell lines from a 

human melanoma that spontaneously progressed from an 

activinnegative to an activinproducing state, and we are 

manipulating activin signalling to determine which of its 

target genes may influence tumour progression. 


Prof. Dr Daniel Constam 





SVISRECUPCDA SV 2837 

Bâtiment SV, Station 19 



Phone +41 (0)21 693 07 41 

daniel.constam@epfl.ch 

Dotto GianPaolo | Tumor suppressing function of 

calcineurin/NFAT in keratinocytes 

(OCS 0236102.2009) 

Duration: 1.10.2009 – 30.09.2012 

Squamous cell carcinomas have a very high incidence in 

the human population, encompassing skin, oral and esophageal 

cancer, squamous (bronchial) lung carcinoma 

and carcinoma of the cervix and other parts of the urogenital 

system. A distinguishing feature of these tumours 

is their high level of heterogeneity, with selfrenewing cell 

populations admixed with cells at different stages of differentiation. 

Important mechanisms involved in restraining cells with 

oncogenic potential are the induction of cellular senescence 

and/or differentiation. Counteracting these failsafe 

mechanisms are conditions of perturbed tissue homeostasis, 

such as those resulting from wound healing or inflammation. 

The immune system is also thought to play a major 

role in preventing or limiting tumour spread. Calcineurin 

is the only known serine/threonine phosphatase under 

calcium/calmodulin control and key regulator of the immune 

system. In the clinics, treatment of patients with 

calcineurininhibitory drugs like cyclosporin A and FK506 

to prevent graft rejection dramatically increases the risk of 

cutaneous squamous cell carcinoma (SCC), which are a 

major cause of death after organ transplants. The main 

goal of this project is to test whether, in parallel with its 

function in the immune system, calcineurin/NFAT signalling 

plays an intrinsic role in keratinocyte/SCC tumour 

suppression. Clinically, we will validate the findings by 

analysis of a large cohort of cutaneous SCCs at various 

stages of malignancy in the general patient population 

versus patients under treatment with calcineurin inhibitors. 


Prof. Dr GianPaolo Dotto 


Faculté de biologie et de médecine 


Chemin de Boveresses 155 


Phone +41 (0)21 692 57 20 

Fax +41 (0)21 692 57 05 

paolo.dotto@unil.ch 

Dufour JeanFrançois | Hepatocarcinogenic roles 

of mTOR, raptor and rapamycins in absence of 

Pten (KFS 0254102201) 

Duration: 01.08.2010 – 01.08.2013 

Hepatocellular carcinoma is a tumour of worldwide significance: 

a) it is the fifth most common tumour; b) it is the 

third leading cause of cancerrelated death; and c) its incidence 

has doubled in the last 2 decades. The PI(3)K/ 

AKT/mTOR pathway is activated in about half of the cases 

of hepatocellular carcinoma. mTOR forms two enzymatic 

complexes with other proteins: The mTOR complex 1 is 

downstream of AKT and regulates protein synthesis; the 

mTOR complex 2 is upstream of AKT and activates AKT. 

Clinical trials testing drugs inhibiting the mTOR complex 1 

as antitumoural agents are underway. Concerns exist: 

1) that inhibition of mTOR in a liver with downregulated 

PTEN may lead to hepatocyte attrition and recruitment of 

progenitor cells; and 2) that rapamycins have effects additional 

to the well characterized inhibition of mTORC1. 

We will compare mice with genetic ablation of the mTOR 

complex 1 (lacking raptor) with mice without mTOR as 

well as with mice treated with an mTOR inhibitor. A better 

appreciation for the elusive role of these 2 complexes 

in the development of hepatocellular carcinoma will be 

partly elucidated by this research. 


Prof. Dr. JeanFrançois Dufour 

Institut für klinische Pharmakologie 



CH3010 Bern 

Phone +41 (0)31 632 09 00 

Fax +41 (0)31 632 49 97 

jf.dufour@ikp.unibe.ch

Gönczy Pierre | Mechanisms of centrosome duplication: 

From model organism towards therapeutic opportunities 

(KLS 02584022010) 

Duration: 01.09.2010 – 01.09.2013 

The centrosome comprises two centrioles and is the principal 

microtubule organizing centre of animal cells. Centrosome 

duplication occurs solely in proliferating cells and 

is required for proper cell division and genome integrity. 

Cancer cells often exhibit aberrations in centrosome number 

or structure. Therefore, centrosome duplication offers 

significant therapeutic opportunities in the fight against 

cancer. Here, we propose to combine the strengths of two 

experimental systems, C. elegans and human cells, to gain 

further insights into the mechanisms of centrosome duplication. 

We will focus on SAS6/HsSAS6 and SAS4/ 

CPAP, two evolutionarily conserved proteins critical for 

this process. We will notably investigate centriole inheritance 

and the impact of aberrant centriole number and 

structure in a stem cell lineage of C. elegans. Moreover, 

we will undertake further analysis of HsSAS6 and CPAP 

in human cells and identify interacting partner proteins. In 

the end, we will seek to identify chemical compounds that 

preferentially target proliferating cells with aberrant centrosomes, 

as is the case of many cancer cells. 







SV 1526, Station 19 


Phone +41 (0)21 693 07 11 


Grassi Fabio | Purinergic signalling in the pathophysiology 

of central nervous system infiltration in 

T-cell leukemia (KFS 02445082009) 

Duration: 01.01.2010–01.01.2013 

Tcell acute lymphoblastic leukaemia (TALL) is characterized 

by increased risk of central nervous system (CNS) infiltration 

by leukaemic cells. TALL patients at increased 

risk of CNS relapse receive, in addition to intensified intrathecal 

chemotherapy, prophylactic cranial irradiation, 

which can cause severe complications. Therefore, therapies 

with improved efficacy and reduced sideeffects remain 

a longterm objective in the treatment of CNS relapse 

in TALL. Adenosine 5’triphosphate (ATP) constitutes the 

source of chemical energy for the majority of cellular 

functions. However, ATP is also released in the extracellular 

space and activates purinergic receptors in the plasma 

membrane, known as P2. The aim of this project is to understand 

the molecular bases of the extended survival 

and reduced brain infiltration we observed in immunodeficient 

mice adoptively transferred with TALL cells upon 

treatment with a pharmacological antagonist of purinergic 

P2X receptors, periodateoxidized ATP. 


Dr. Fabio Grassi 

Istituto di ricerca in biomedicina (IRB) 


CH6500 Bellinzona 

Phone +41 (0)91 820 03 23 

fabio.grassi@irb.unisi.ch 

Grünberg Jürgen | Combinational therapy of ovarian 

cancer metastases expressing the L1 cell adhesion 

molecule (L1-CAM) based on radioimmunotherapy and 

growth inhibition (KFS 02546022010) 

Duration: 01.08.2010 – 01.08.2013 

The aim of this project is to expand and improve the treatment 

options for metastatic ovarian cancer. This will 

be achieved through the use of the chimerized antiL1 cell 

adhesion molecule (L1CAM) antibody chCE7 in conjunction 

with other treatment modalities. Histological examination 

of tumour tissues showed that 79 % of all ovarian 

carcinomas overexpress the L1CAM. Here we will use 

therapeutic radionuclides (lutetium177, copper67), which 

are particularly suitable for the irradiation of small metastases. 

Different combinations of radioimmunotherapy 

(RIT) with kinase inhibitors and chemotherapy (carboplatin, 

paclitaxel) and antiL1 antibodymediated tumour 

growth inhibition will be investigated in ovarian cancer 

xenograft models to find an optimal postoperative treatment 

regimen. 


Dr. Jürgen Grünberg 

Bereich Biologie und Chemie 

Paul Scherrer Institut 

Zentrum für radiopharmazeutische Wissenschaften 

ETHPSIUSZ 

OIPA 10A 

CH5232 Villigen 

Phone +41(0)56 310 28 48 

Fax +41(0)56 310 28 49 

juergen.gruenberg@psi.ch 

Hall Jonathan | Targeting pre-let-7 biogenesis 

in cancer (KFS 02648082010) 

Duration: 01.02.2011 – 01.02.2013 

The dysregulation of microRNA expression by loss or gainoffunction 

is linked to several human cancers. MicroRNAs 

therefore represent a new class of therapeutic targets. The 

function of mature microRNAs may be inhibited in vivo by 

chemicallymodified singlestranded RNAs in the cell. For 

example, recent publications showed the importance of 

the interaction between Lin28 and the let7 microRNA 

precursor in the development of various cancers. Here we 

propose to find molecular inhibitors of this interaction 

by targeting the RNA precursor, the Lin28 protein or 

the RNAprotein complex. We will use a multidisciplinary 

approach with smallmolecule assay combined with a 

structural study to optimize the interactions and biological 

assays to assess their effects in vitro and in vivo. From 

101

102 

this study we will examine the therapeutic potential of 

let7 microRNA precursors and other microRNAs in the 

development of cancer. 


Prof. Dr. Jonathan Hall 

Institut für pharmazeutische Wissenschaften 

ETH Zürich 

HCI H 437 

WolfgangPauliStrasse 10 


Phone +41 (0)44 633 74 35 

Fax +41 (0)44 633 13 69 

jonathan.hall@pharma.ethz.ch 

Hemmings Brian A. | Dissecting translation reveals 

therapeutic prospects for malignant gliomas 

(KFS 02714082010) 

Duration: 01.03.2011 – 01.03.2014 

Glioblastoma multiforme (GBM) is the most common and 

aggressive brain tumour entity, with a median survival of 

approximately one year. The proposed study aims to uncover 

novel molecular mechanisms regulating gene expression 

at the translation level triggered by deregulated 

signalling pathways. Further, therapeutic perspectives of 

the results obtained will be validated in the GBM animal 

models. Understanding of the novel molecular mechanisms 

that regulate selective translation will not only explain 

principles underlying rapid signalling responses controlling 

translation and its phenotypical consequences but 

will also allow proposal and development of molecular 

strategies for therapeutic interference for malignant brain 

tumours. 






CH4058 Basel 

Phone +41 (0)61 697 48 72 


Hottiger Michael O. | Multiplex analysis of the 

ionizing radiation induced signaling network at 

the single cell level (KLS 02396022009) 

Duration: 01.05.2009 – 01.05.2012 

Every cell is exposed to genotoxic stresses such as radiation 

or chemicals that can cause harmful and deleterious 

mutations in the genome. Cells have evolved an intricate 

regulatory protein network to detect and repair DNA 

damage with the aim to maintain genomic stability and 

thus prevent tumourigenesis. Until now, technical and 

practical limitations prohibited comprehensive deciphering 

of this regulatory network. 

The goal of this study is to measure, with reverse protein 

micro arrays, simultaneously changes and modifications 

of hundreds of proteins in human cells (fibroblasts) upon 

exposure to genotoxic stress. Thereby, we will define key 

players of the genotoxic signalling network and predict 

functional interaction between different signalling components, 

which will be experimentally probed further for 

their function and connections. 

The results of this project will provide a comprehensive 

picture of a cell’s response to genotoxic stress and the opportunity 

to improve our possibilities to detect and treat 

tumours. 


Prof. Dr. Michael O. Hottiger 


Molekularbiologie 




Phone +41 (0)44 635 54 74 

hottiger@vetbio.uzh.ch 

Huard Betrand | APRIL blockade for the treatment 

of multiple myeloma (KFS02464082009) 

Duration: 01.05.2010 – 01.05.2013 

Multiple myeloma (MM) is a tumour arising after transformation 

of antibodyproducing plasma cells residing in 

the bone marrow (BM). There are about 450 new MM 

cases yearly in Switzerland. MM develops in BM and induces 

severe bone lesions. Nowadays a high response rate 

(95 %) in MM patients is achieved by the introduction 

of new chemotherapeutic drugs and their combination. 

Unfortunately, MM remains an incurable disease, due to 

uncontrolled relapse events, even when heavy treatment 

such as BM transplantation is performed. Current treatments 

are not highly specific to MM cells. However, the 

exclusive MM growth in BM revealed that BM must contain 

MM specific growth factor(s). Identifying them will 

lead to new targets for MM treatment. In the laboratory, 

we have recently observed that the BM is constitutively 

rich in a molecule called a proliferationinducing ligand 

(APRIL). The physiological function of APRIL is to support 

longterm survival of plasma cells in BM, by this means 

maintaining our immune antibody memory. All these observation 

render APRIL a good candidate for a key MM 

growth factor. 


To test whether antibodymediated APRIL blockade induces 

MM regression. 

Methods 

One major problem in MM research is the lack of an appropriate 

animal model. In collaboration with a Norwegian 

group, we created a mouse model highly relevant to 

the human pathology. The cell that we isolated, called 

MOPC315BM, develops actively in BM after intravenous 

injection and leads to paralysis and death. In addition, we 

generated the first blocking antibody against mouse 

APRIL. In this research project, we plan to test whether 

APRIL blockade impairs MOPC315BM development.

Patients’ perspectives 

In the case that we observe an inhibition of MOPC315BM 

development by APRIL blockade, we will be able to quickly 

generate a similar antibody reacting with human APRIL. 

This antibody could be tested in MM patients. This will 

lead to a highly specific treatment targeting a growth factor 

used by MM cells. 


Dr Bertrand Huard 

Département de pathologie et immunologie 





Phone +41 (0)22 379 58 11 

Fax +41 (0)22 379 57 46 

bertrand.huard@unige.ch 

Hübscher Ulrich | Regulation of base excision repair 

by human DNA polymerase l through posttranslational 

modifications: Degradation versus stabilization 

(KLS 02339022009) 

Duration: 01.04.2009 – 01.04.2011 

The maintenance of genetic stability is of crucial importance 

for any form of life. The genetic material, the DNA 

itself, is highly reactive and is constantly attacked by endogenous 

factors and is also easily altered by intracellular 

processes such as oxidation. The base guanine as 8oxo 

G is recognized as one of the most important oxidative 

DNA lesions because of its prevalence in DNA and its mutagenic 

potential in aging, tumourigenesis and neurodegenerative 

diseases. We identified that DNA polymerase l 

can correctly incorporate C opposite 8oxoG and identified 

the initial steps of how this protein is regulated in the 

cell. In particular it is stabilized during cell cycle progression, 

enabling proper repair of damaged DNA. With this 

project we would like to understand the molecular mechanisms 

of DNA polymerase l regulation during the cell cycle 

and thus investigate the role of the two posttranslation 

modifications phosphorylation and ubiquitination. 


Prof. Dr. Ulrich Hübscher 


Molekular biologie 




Phone +41 (0)44 635 54 72 

Fax +41 (0)44 635 68 40/5904 

hubscher@vetbio.uzh.ch 

Huelsken Joerg | Stemness control in cancer stem cells 

(KFS 02667082010) 

Duration: 01.01.2011 – 01.01.2014 

As the cellular target for initiation of cancerogenesis, we 

and other laboratories recently identified normal, tissuespecific 

stem cells. These stem cells usually drive the continuous 

replenishment of tissues. Similarly, also tumours 

contain a small population of cancer stem cells that are responsible 

for formation and maintenance of the cancer. 

We were able to show that the Wnt signalling pathway 

controls essential stem cell properties, such as their apparent 

unlimited proliferation potential in normal and cancer 

tissues (Malanchi et al., Nature 2008). We now want to 

understand in more detail how Wnt signalling controls this 

process and will study the components of the epigenetic 

control of stem cell identity and mechanisms of their regulation. 

Our results will aid understanding of the fundamental 

processes that control tumour maintenance and 

will allow development of better targeted approaches for 

the elimination of such cancer stem cells. 


Prof. Dr Joerg Huelsken 

UPHUE 





SV 2823 (Bâtiment SV) 

Station 19 


Phone +41 (0)21 693 07 52 

Fax +41 (0)21 693 07 70 

joerg.huelsken@epfl.ch 

Hynes Nancy | Reciprocal cross-talk between low- 

density lipoprotein receptor-related protein 1 and 

receptor tyrosine kinases: Implications for modulating 

in vitro and in vivo properties of breast tumor cells 

(KFS 02528022010) 

Duration: 01.08.2010 – 01.08.2012 

Lowdensity lipoprotein receptorrelated protein 1 (LRP1) 

is a 600 kDa transmembrane protein that binds more than 

40 distinct ligands, many of which are involved in regulation 

of extracellular protease activity. LRP1 is also crossregulated 

by various receptor tyrosine kinases (RTK). Ligand 

binding to LRP1 stimulates intracellular signalling 

pathways by unknown mechanisms. We have shown that 

binding of the serpin protease nexin1 (PN1) to LRP1 in 

mammary cancer cell lines stimulates the ERK pathway, 

regulates MMP9 expression and, in vivo, is responsible 

for the metastatic spread of a breast cancer model to the 

lungs. Based on this, the goals are: 1) in vitro experiments 

analyzing crosstalk between LRP1 and RTKs; 2) in vivo 

studies on metastatic breast tumour models, targeting 

PN1 alone or in combination with RTK inhibitors. 


Prof. Dr. Nancy Hynes 




CH4058 Basel 

Phone +41 (0)61 697 81 07 

Fax +41 (0)61 697 39 76 

nancy.hynes@fmi.ch 

103

104 

Janscak Pavel | Study of the role of mismatch repair 

proteins in the cellular response to DNA double-strand 

breaks (KLS 02344022009) 

Duration: 01.07.2009 – 01.07.2011 

DNA damage is a frequent event in the life of a cell. Failure 

to repair DNA damage can lead to cell death, and inaccurate 

DNA repair can give rise to genomic instability, 

which promotes the onset of cancer in mammals. The 

most deleterious form of DNA damage is DNA doublestrand 

break (DSB). In eukaryotic cells, two mechanistically 

distinct pathways are known to efficiently repair 

DSBs: nonhomologous end joining and homologous recombination. 

However, molecular mechanisms underlying 

these DNA repair pathways are not completely understood. 

Our recent experiments with human cells revealed 

that proteins involved in the initiation of postreplicative 

mismatch repair (MMR), such as MSH2, MSH3, MSH6 

and MLH1, accumulate at sites of chromosomal DSBs generated 

by UVA laser. Ongoing research in our laboratory 

aims to gain insight into the function of MMR proteins at 

the sites of DNA damage in human cells. 

The project utilizes various cell biology methods in combination 

with laser microdissection technology and immunofluorescence 

microscopy. Using RNA interference, we 

intend to identify the DNA repair factors that are required 

for the recruitment of MMR proteins to the sites of DSBs. 

DNA repair capacity of cells depleted for the individual 

MMR proteins will be assessed using chromosomallybased 

reporters for specific DSB repair pathways and by 

testing sensitivity of depleted cells to DNA damaging 

agents. 

Our preliminary data indicate that the MMR proteins accumulate 

at DSBs in a manner dependent on MRE11 and 

CtIP, which are involved in the initiation homologous recombination. 

Germline mutations in the MLH1, MSH2 and MSH6 genes 

are the major cause of hereditary nonpolyposis colon 

cancer. It is anticipated that our study will advance understanding 

of the molecular events leading to this most 

common form of inherited colon cancer. 


Dr. Pavel Janscak 





Phone +41 (0)44 635 34 70 

pjanscak@imcr.uzh.ch 

Krek Wilhelm | Roles of the URI oncoprotein in 

B-RAF-signaling and melanoma cancer cell proliferation 

(KFS 02690082010) 

Duration: 01.02.2011 – 01.02.2013 

Malignant melanoma (“black skin cancer”) is one of the 

most aggressive cancers. Prognosis for advanced stages is 

dismal due to a lack of efficient systemic therapies, with 

classical cytotoxic chemotherapy being particularly inefficient. 

Elucidating the molecular and cell biological bases of melanomagenesis 

is therefore of prime importance and has 

already led to findings that have been translated successfully 

to the clinics. A central player in melanomagenesis is 

BRAF V600E , which is a constitutively active mutant form of 

the BRAF kinase, a component of the RAS/RAF/MEK/ 

ERKsignaling cascade. BRAF V600E is found in about 70 % 

of all melanomas, and mouse models demonstrated its 

oncogenic potential. Selective BRAF V600E inhibitors have 

been developed and their therapeutic efficiency in first 

clinical trials is promising. However, after some months 

clinical resistance develops, and therefore new therapeutic 

strategies are still very much needed. BRAF V600E provokes 

overactive RAS/RAF/MEK/ERKsignalling leading 

to un con trolled cellular proliferation. Several mechanisms 

regulate the activity of this pathway at multiple levels. 

Particularly important in the negative regulation of pathway 

activity are negative feedback systems mediated by 

phosphatases that dampen overactive signalling. That 

might also be one of the reasons why the BRAF V600E alone 

does not suffice for malignant transformation, but secondary 

changes (“second hits”) are a prerequisite. 

We recently discovered a novel phosphatase (PP)1dependent 

negative feedback system that acts to restrain 

S6K1 survival signalling in response to nutrient and growth 

factor stimulation. Moreover, PP1 is a target of oncogenic 

alterations that disable PP1mediated feedback inhibition 

on survival signalling in different human cancers. In this 

project we are testing whether this PP1dependent feedback 

system also acts on the RAS/RAF/MEK/ERK pathway 

and is oncogenically targeted in human melanoma. 

In this work we are combining human tissue microarrays 

(TMA), quantitative phosphoproteome analyses, RNA 

interference and mouse models of melanomagenesis. 

From these studies, we expect to discover novel regulatory 

mechanisms of oncogenic BRAF V600E signalling and of 

RAS/RAF/MEK/ERKsignalling in general. 


Prof. Dr. Wilhelm Krek 


ETH Zürich 

HPM F42 



Phone +41 (0)44 633 34 47 

Fax +41 (0)44 633 13 57 

wilhelm.krek@cell.biol.ethz.ch

Martinou JeanClaude | Studies on the role of TRAIL 

as a tumor metastasis promoter (KLS 02370022009) 

Duration: 01.11.2009–01.11.2011 

TRAIL is a protein that is able to trigger apoptosis of cancer 

cells but is inefficient in killing non tumour cells, hence 

its interest in cancer treatment. We noticed that TRAIL 

can induce apoptosis of various cancer cells but is unable 

to kill cells that display a dysfunctional mitochondrial 

pathway of apoptosis. In this case, TRAIL stimulates cell 

detachment from their substrate, which raises the possibility 

that administration of TRAIL for cancer treatment 

could lead to metastatic dissemination of the tumour. This 

is the hypothesis that we are currently testing using mice 

in which tumours are implanted and treated with TRAIL. 

Our results may have consequences for cancer treatment 

with TRAIL and may limit its administration to tumours 

with a functional apoptosis mitochondrial pathway. 


Prof. Dr JeanClaude Martinou 

Département de biologie cellulaire 

Faculté des sciences 


30, quai ErnestAnsermet 


Phone +41 (0)22 379 64 43 

Fax +41 (0)22 379 64 42 

jeanclaude.martinou@unige.ch 

Meraldi Patrick | How does overexpression of the 

Aurora A oncogene override the spindle checkpoint? 

(KFS 02707082010) 

Duration: 01.06.2011–01.06.2013 

Taxol is one of the most potent cancer drugs available. It 

is a spindle poison that perturbs orderly cell division. Cells 

possess a checkpoint that blocks cell division in the presence 

of such defects, which is why Taxol treatments block 

the uncontrolled growth of cancer cells. Unfortunately, 

many cancer patients are resistant to Taxol, as they overexpress 

the Aurora A protein, a condition that disrupts the 

cell division checkpoint. 

Although we have learned a lot about the functions of Aurora 

A in normal cells, we still do not understand how the 

cell division checkpoint is impaired by the pathological 

overexpression of Aurora A. Our goal is to understand this 

mechanism by identifying the proteins that interact specifically 

with overexpressed Aurora A. This knowledge will 

form the basis for new drugs that could prevent such 

pathological interactions with Aurora A and abolish Taxol 

resistance in cancer patients. 


Prof. Dr. Patrick Meraldi 

Institut für Biochemie 

ETH Zürich 



Phone +41 (0)44 632 63 47 

Fax +41 (0)44 632 15 91 

patrick.meraldi@bc.biol.ethz.ch 

Merdes Gunter | Systems biology of tumor 

suppression and malignancy in the model system 

Drosophila (KFS 02695082010) 

Duration: 01.03.2011– 01.03.2014 

To study the development of cancer, researchers use cells 

from patients and animals like the mouse or the fruit fly. 

At first sight, fruit flies seem inappropriate based on obvious 

differences between fruit flies and us. However, it was 

discovered not only that are we very similar even in the 

number of genes but also that important findings about 

the development of cancer are directly transferable from 

fruit flies to humans. Accordingly, we plan to identify all 

the genes involved in tumour suppression in the fruit fly 

by systematically switching on and off single genes and by 

studying the interconnectivity of the identified cancer 

genes. It is our longterm goal to recognize new therapeutic 

strategies in humans based on these results. 


Dr. Gunter Merdes 

Departement Biosysteme 

ETH Zürich 


CH4058 Basel 

Phone +41 (0)61 387 31 24 

Fax +41 (0)61 387 39 94 

gunter.merdes@bsse.ethz.ch 

Michielin Olivier | Rational design of anti-MART-1 TCR 

sequences for adoptive transfer immunotherapies 

(KFS 02555022010) 

Duration: 01.03.2010 – 01.03.2013 

Tcell receptors (TCRs) control the specificity and efficacy 

of the cellular specific immune system by recognizing foreign 

and abnormal antigens presented by the MHC molecules. 

However, their low affinity constitutes a critically 

limiting factor of tumour immunity. 

We therefore designed a new structurebased computational 

approach using free energy calculations to rationally 

design TCRs. By controlling the mutations’ structural 

and functional effect, the approach is likely to suggest 

TCRs with optimal activity and lower risk of crossreactivity. 

We engineered TCRs specific for NYESO1, a cancer 

testis antigen peptide expressed not only in melanoma but 

also in several other types of cancers. We obtained specific 

antigens with controlled affinities up to 160fold 

higher than that of the wild type TCR. Corresponding engineered 

Tcells exhibited improved killing of melanoma 

cell lines and better proliferative capacity, thus paving the 

road to clinical trials. We are now using this technique to 

design TCRs specifically recognizing the MART1 antigen, 

which is expressed by melanoma cells. 


Prof. Dr Olivier Michielin 

Molecular Modelling Group (MMG) 

Institut suisse de bioinformatique (ISB) 

Quartier Sorge – Bâtiment Génopode 



Phone +41 (0)21 692 40 53 

Olivier.michielin@unil.ch 

105

106 

Müller Anne | The molecular pathogenesis of Helicobacter 

pylori-induced mucosa-associated lymphoid 

tissue (MALT) lymphoma: Analysis of the role of small 

regulatory RNAs in lymphomagenesis and high grade 

transformation (KFS 02640082010) 

Duration: 01.11.2010 – 01.11.2013 

We are studying the pathogenesis of mucosaassociated 

lymphoid tissue lymphomas, which arise in chronically inflamed 

tissues. The most common site of MALT lymphomagenesis 

is the inflamed gastric mucosa of Helicobacter 

pylori-infected individuals. Whereas gastric MALT lymphoma 

is a relatively indolent disease, its high gradetransformed 

disease counterpart, gastric diffuse large Bcell 

lymphoma (DLBCL) , represents a clinically relevant disease 

entity with poor prognosis. Through the use of patient 

material we have identified a small regulatory RNA 

(called a microRNA) that may play a role in high grade 

transformation. miR34a was found to be transcriptionally 

repressed in all examined cases of high grade but not of 

low grade gastric lymphoma. The forced expression of 

miR34a very efficiently blocks proliferation of two high 

grade diffuse large Bcell lymphoma cell lines, suggesting 

a tumour suppressive role of miR34a in this disease entity. 

We have further identified a miR34a target with a likely 

functional significance in gastric lymphomagenesis, the 

haematopoietic oncoprotein FoxP1. We now plan to investigate 

in a larger set of DLBCL cells lines as well as in a wellestablished 

DLBCL xenograft model whether miR34a 

indeed has tumour suppressive properties – and its target 

FoxP1 has oncogenic properties – in MALT lymphoma. 

Specifically, we postulate that the silencing of miR34a and 

the resulting overexpression of FoxP1 promote high grade 

transformation of gastric MALT lymphoma. 


Prof. Dr. Anne Müller 





Phone +41 (0)44 635 34 74 

Fax +41 (0)44 635 34 84 

mueller@imcr.uzh.ch 

Münz Christian | Tumorigenesis and immune control 

of the Epstein Barr virus in vivo (KFS02652082010) 

Duration: 01.02.2011–01.02.2014 

A substantial proportion of human tumours are caused by 

viruses. Among these, Epstein Barr virus (EBV) induces 

lymphomas and carcinomas. Mutations in EBV have been 

observed in patients with aggressive lymphomas. This 

project is designed to understand tumourigenesis and immune 

control of these mutant EBV viruses. For this purpose 

mice with reconstituted human immune system 

components will be used, since EBV infects only human 

cells. A better understanding of the mechanisms by which 

mutant EBV causes aggressive tumours will reveal interesting 

aspects of EBV immunobiology, aid diagnostic assessment 

of risks associated with mutant EBV infection in 

patients and provide therapeutic avenues for aggressive 

EBVassociated malignancies. 


Prof. Dr. Christian Münz 

Institut für experimentelle Immunologie 




Phone +41 (0)44 635 37 16 

Fax +41 (0)44 635 68 83 

christian.muenz@uzh.ch 

Ochsenbein Adrian F. | Immunogenicity of chronic 

myeloid leukaemia stem cells (KLS 02342022009) 

Duration: 01.01.2010 – 01.01.2013 

Chronic myeloid leukaemia (CML) is a clonal myeloproliferative 

disorder resulting from the neoplastic transformation 

of a haematopoietic stem cell. Consequently, characterizing 

the leukaemia stem cell (LSC) is a key to understanding 

leukaemia pathogenesis and to developing more effective 

therapeutic regimens. However, LSC are selectively resistant 

to various forms of therapy, including imatinib, irradiation 

or cytotoxic drugs. 

We established a murine model of a CMLlike disease by 

retroviral transduction of bone marrow stem cells expressing 

the onocogenes BCR/ABL. In this model we are studying 

the role of CD27 on LSC in leukaemia development. 

CD27 is a costimulatory receptor, leading to Tcell expansion, 

generation of effector function and increased cell 

survival. We found that CD27 signalling on LSC increases 

LSC proliferation and differentiation to malignant granulocytes. 

Since the ligand of CD27 (CD70) is solely expressed 

on activated lymphocytes and on mature dendritic cells, 

the adaptive immune response favours leukaemia progression. 

Therefore, blocking the CD27CD70 interaction may 

be a strategy to interfere with leukaemia progression on 

the level of the LSC. 


Prof. Dr. Adrian F. Ochsenbein 


Inselspital 


CH3010 Bern 

Phone +41 (0)31 632 84 42 

Fax +41 (0)31 632 41 19 

adrian.ochsenbein@insel.ch 

Pertz Olivier | A slit/robo signaling pathway regulating 

contact mediated repulsion during cell migration: 

Implications of its deregulation for the acquisition 

of an invasive phenotype during breast cancer 

(KFS 02485082009) 

Duration: 01.05.2010 – 01.05.2013 

In healthy tissue, individual cells are kept in the right order 

through constant interaction with neighbouring cells. 

This process involves sampling of adjacent cells and sensing 

of repulsive cues that suppress cell motility. During the 

metastatic switch, cancer cells acquire the ability to move 

out and to squeeze between surrounding cell layers, finally 

spreading through the body and colonizing distinct 

organs. Thus, cell sensing may serve as an important early 

mechanism to impede the invasive phenotype. The aim of 

this project is to apply a gene inactivation approach to

identify signalling pathways that generate and/or sense 

repulsive signals. Understanding the molecular mechanisms 

underlying metastasis will be crucial for a successful 

cancer therapy. 


Prof. Dr. Olivier Pertz 





CH4058 Basel 

Phone +41 (0)61 267 35 41 

olivier.pertz@unibas.ch 

Petrova Tatiana | Lymphatic endothelial calcineurin/ 

NFAT signaling in tumor lymphangiogenesis and metastasis 

(KLS 02570022010) 

Duration: 01.09.2010 – 01.09.2013 

Tumour metastasis is a major cause of cancer related mortality. 

Malignant cells frequently escape from the primary 

tumour using nearby lymphatic vessels, which normally 

serve to regulate body fluid balance, fat transport and immune 

surveillance. Understanding the process of lymphatic 

metastasis is thus important for developing new 

treatment approaches to interfere with tumour spread to 

distant sites. Previously we discovered that the calcineurin/NFAT 

signalling pathway is needed for normal lymphatic 

vascular development. 

The goal of the present study is to establish the role of calcineurin/NFAT 

in tumour lymphatic vessels and tumour 

cell dissemination. We plan to use genetic models in which 

we will inactivate calcineurin/NFAT in tumourassociated 

lymphatic vessels and then monitor their ability to transport 

tumour cells to lymph nodes. In addition, we aim to 

identify important targets regulated by calcineurin/NFAT 

in lymphatic endothelial cells. Identification of specific 

targets of calcineurin signalling is important for the development 

of treatment approaches targeting vascular system 

in diseases, such as cancer and inflammation. 


Prof. Dr Tatiana Petrova 

Centre pluridisciplinaire d’oncologie (CePO) 


et Université de Lausanne 



Phone +41 (0)21 692 58 28 

Fax +41 (0)21 692 58 72 

tatiana.petrova@unil.ch 

Plückthun Andreas | Tumor targeting of ErbB2 with 

designed ankyrin repeat proteins 

(KFS 02448082009) 

Duration: 01.01.2010 – 01.01.2012 

Over the last few years, we have developed a new class of 

alternative binding molecules, termed “designed ankyrin 

repeat proteins” (DARPins). These binders are expected 

to significantly improve the efficiency of tumour targeting 

in many types of human cancer. In contrast to conventional 

therapeutic antibodies, they possess outstanding 

biophysical properties and can be readily produced in different 

molecular formats, e.g. as fusion proteins with various 

cytotoxic moieties. Due to the many favourable attributes 

of DARPins, it has become possible to construct 

vehicles capable of inducing programmed cell death of 

tumour cells (apoptosis) in the absence of therapeutic 

payloads or other tumouricidal additives. Thus, the adverse 

side effects associated with unspecific toxic substances 

should be eliminated in the DARPin tumour therapy. Such 

pharmacological aspects and the overall efficacy of DARPin 

treatment are being presently addressed in comparative 

studies in animal tumour models. 


Prof. Dr. Andreas Plückthun 

Biochemisches Institut 




Phone +41 (0) 44 635 55 70 

Fax +41 (0) 44 635 57 12 

plueckthun@bioc.uzh.ch 

Pruschy Martin | Differential response to proton 

versus photon radiotherapy: Biological implications 

for new indications and combined treatment concepts 

(KFS 02551022010) 

Duration: 01.04.2010 – 01.04.2013 

The most commonly used mode of radiotherapy uses an 

externally generated photon beam directed towards the 

exact delineated tumour site. But proton radiotherapy is 

also gaining much attention due to its improved localized 

delivery of radiation to the tumour site. However, there is 

presently a gap between the rapid introduction of proton 

therapy in clinical practice and the introduction of new 

proton treatment concepts – with a lack of solid radiobiological 

evidence to support the expansion of new clinical 

indications. In collaboration with the Paul Scherrer Institute 

we will investigate in genetically defined tumour cells 

and murine tumour models the impact of specific physicochemical 

and molecular parameters on the relative biological 

effectiveness of proton radiation. We will thereby 

increase our general knowledge of particle interaction 

with tissue and the cellular stress response to proton 

radio therapy. The results obtained will directly influence 

our clinical practice of proton therapy. 


Prof. Dr. Martin Pruschy 

Labor für molekulare Radiobiologie 

Klinik für RadioOnkologie 


Rämistr. 100 


Phone +41 (0)44 255 85 49 

martin.pruschy@usz.ch 

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108 

Radtke Freddy | The role of Notch and TSLPR signaling 

during skin cancer (KLS 02387022009) 

Duration: 01.08.2009 – 01.08.2012 

Our studies previously showed that loss of Notch signalling 

in the skin results in a severe form of inflammation 

characterized as atopic dermatitislike disease (AD, also 

known as eczema) due to excessive production of thymic 

stromal lymphopoietin (TSLP) by Notch deficient keratinocytes. 

TSLP is a secreted cytokine that is deeply implicated 

in the pathogenesis of AD and asthma in mouse 

and human. We genetically removed the TSLPR to prove 

that TSLP signalling is indeed causative of the development 

of AD in mice having lost Notch1 and Notch2 in the 

skin. These mice were rescued from developing AD; however, 

unexpectedly they developed rapidly growing invasive 

skin tumours, suggesting that TSLP induces a type of 

inflammation that protects premalignant lesions from 

progressing into tumours. We are currently trying to identify 

the cellular and molecular mechanisms of the TSLPmediated 

protective inflammation. This should lead to 

novel insights into how the immune system tries to fight 




UPRAD 





Station 19 


Phone +41 (0)21 693 07 71 


Renner Christoph | Inhibition of tumor growth by 

targeting cancer-associated fibroblasts 

(KFS 02500082009) 

Duration: 01.01.2010 – 01.01.2013 

Tumours are composed of tumour cells and a variable degree 

of stroma, which includes extracellular matrix and fibroblasts. 

These tumour fibroblasts support tumour growth 

and are characterized by the expression of fibroblast activation 

protein (FAP). FAP is a dipeptidyl peptidase known 

to cleave extracellular matrix (such as collagen), which in 

turn leads to enhanced metastasis formation. 

We postulate that FAPblocking molecules can inhibit this 

process and stop tumour metastasis. Therefore, we developed 

mousehuman crossreactive FAPspecific antibodies 

that downregulate FAP expression, and we will analyze 

them in mouse models for their potential to impact on 

metastasis formation using new imaging approaches. It is 

our final goal to transfer this approach into a clinical setting 

for the benefit of patients with advanced malignant 

diseases. 


Prof. Dr. Christoph Renner 

Klinik und Poliklinik für Onkologie 

Medizinbereich Innere Medizin – Onkologie 




Phone +41 (0)44 255 21 54 

christoph.renner@usz.ch 

Ruiz i Altaba Ariel | Role and prevalence of hedgehog 

signalling in human colorectal cancer 

(KFS 02359022009) 

Duration: 01.07.2010 – 01.07.2013 

Despite huge efforts to improve treatments, metastatic 

cancers are still linked to a high rate of mortality. This is 

the case for colon cancer, which accounts for about 10 % 

of all cancer deaths worldwide, with 25 % of the cases being 

out of any surgical therapy because of metastasis. The 

transition step from primary tumour to metastatic state 

therefore appears to be critical in the development of the 

disease and should be considered as a priority target for 

future therapies. 

In this imperative perspective, we propose to study, in a 

collaborative effort involving surgeons of the University 

hospital Geneva (HUG), the molecular mechanisms underlying 

this metastatic transition step. Our data suggest 

that the development of colorectal cancer requires the 

activity of the sonic hedgehog (SHH)Gli pathway, a cell 

signalling pathway that we have previously identified as 

being deregulated in other cancers, namely, brain, skin 

and prostate cancers. 

From these data, (SHH)Gli pathway should play an essential 

role in the tight regulation of colon cancer stem 

cells from which the tumour arises, as well as in later 

phases of the disease, like the metastatic transition. To 

validate these working hypotheses, we propose to compare 

the tumourigenic properties of colon carcinoma cells 

obtained from patient biopsies at different stages of the 

disease by using mice xenograft models. These experiments 

are expected to bring new insights into the molecular 

mechanisms underlying the biology of intestinal tumourigenesis 

and should allow for the identification and 

development of specific (SHH)Gli pathway antagonists 

to treat colorectal tumours and their cancer stem cells 

more efficiently. 


Prof. Dr Ariel Ruiz i Altaba 

Département de génétique médicale et 

de développement 





Phone +41 (0)22 379 54 46 

Fax +41 (0)22 379 59 62 

ariel.ruizaltaba@unige.ch

Santamaria Anna | Control of chromosome segregation 

fidelity by the Ska complex, a key regulator of 

stable kinetochore-microtubule attachments during 

mitosis (KFS 02657082010) 

Duration: 01.02.2011– 01.02.2014 

During development of every organism, each dividing cell 

must partition its replicated genome equally into each 

new daughter cell. Errors in this process lead to aneuploid 

daughter cells with abnormal numbers of chromosomes. 

Aneuploidy is a remarkably common characteristic of aggressive 

tumours. Compelling evidence suggests that excessively 

stable kinetochoremicrotubule (KTMT) attachments 

are the root cause of chromosomal instability (CIN) 

in many cancer cells. Central to the machinery required 

for establishing stable KTMT attachments is the Ska (for 

spindle and kinetochoreassociated) complex. Our goal is 

to elucidate the role of the Ska complex in generating stable 

KTMT attachments during mitosis in human cells by: 

1) identifying its interaction partners and studying the 

regulation of the Ska complex by phosphorylation using 

biochemical and cell biological techniques; 2) resolve the 

structure of the Ska complex by Xray crystallography; 

3) analyze the abundance, stochiometry and dynamics of 

endogenous Ska proteins in both normal and tumour cells 

using mass spectrometrybased techniques. These studies 

should allow us to determine whether protein imbalances 

in key regulators of KTMT attachments are a likely root 

cause of CIN in cancer cells. This will provide an opportunity 

to explore KTrelated pathways and strategies that 

elevate chromosome missegregation beyond tolerable 

levels for therapeutic applications. 


Dr. Anna Santamaria 



Klingelbergstrasse 50/70 

CH4056 Basel 

Phone +41 (0)61 267 18 93 

Fax +41 (0)61 267 20 09 

anna.santamaria@unibas.ch

110 

Schär Primo | DNA repair, epigenetic stability, 

and CpG island hypermethylation in colorectal tumorigenesis 

(KFS 2585022010) 

Duration: 01.07.2010 – 01.07.2012 

Cancer arises as a consequence of genetic mutations and 

epigenetic alterations in normal cells of our body. Unlike 

genetic mutations, epigenetic changes do not concern the 

DNA sequence itself but affect the patterns of heritable 

chemical modifications on the DNA. These are methylations 

of cytosine bases that act as flags to direct accurate 

cell typespecific gene expression. In cancer cells, these 

flags are often misplaced for reasons that are currently 

unknown. Our research has led to the discovery that a 

bona fide DNA repair enzyme, the thymine DNA glycosylase 

(TDG), does not primarily engage in the repair of 

DNA damage but associates specifically with gene regulatory 

sequences to correct errors of cytosine methylation. 

This newly described epigenetic function is likely to play a 

critical role in tumour suppression. This research project is 

designed to clarify if and how the loss of TDG contributes 

to both the development and nature of epigenetically unstable 

colorectal cancers. 







CH4058 Basel 

Phone +41 (0)61 267 07 67 

Fax +41 (0)61 267 35 66 


Schorderet Daniel | Retinoblastoma: Understanding its 

development for better treatment 

(KFS 02565022010) 

Duration: 01.08.2010 – 01.08.2013 

Retinoblastoma is a malignant tumour of childhood affecting 

the developing retina due to the inactivation of 

both. We propose to induce apoptosis in tumoural cells by 

modifying molecular pathways with small peptides. Cellular 

and animal models will be used to study the molecular 

pathways involved, and new therapeutic molecules will be 

identified and evaluated. Availability of new therapeutic 

molecules will aid development of new treatments for advanced 

retinoblastoma stages. 


Prof. Dr Daniel Schorderet 

Institut de recherche en ophtalmologie (IRO) 

EPF de Lausanne et Université de Lausanne 

Avenue du GrandChampsec 64 

CH1950 Sion 

Phone +41 (0)27 205 79 00 

Fax +41 (0)27 205 79 01 

daniel.schorderet@irovision.ch 

Swartz Melody | Roles of tumor VEGF-C and CCL21 in 

immunological tolerance (KFS 2696082010) 

Duration: 01.03.2011 – 01.03.2014 

Lymph node metastasis of many cancers, including breast 

and skin, is the leading cause of cancer mortality. Lymph 

nodes that contain metastases are typically surgically removed, 

and tumourassociated lymphatic vessels have 

mainly been considered as routes for tumour dissemination. 

We have hypothesized that tumours can use lymphatic 

vessels and drainage to lymph nodes to reprogram 

the immune system, promoting immunological tolerance, 

where tumour cells are considered “normal” by the immune 

system. 

This research project will explore this new hypothesis and 

test its validity in skin cancer models in mice. Specifically, 

we will determine how tumourassociated lymphatics and 

their drainage to the lymph node affects host immunity 

to the tumour and explore strategies to reverse this immunological 

tolerance. We believe that this research will introduce 

a new paradigm in our understanding of how tumours 

modulate the host immune system, leading to new 

immunotherapeutic strategies targeting lymphatic vessels 

and tumourdraining lymph nodes for breaking this tolerance 

and driving efficient antitumour immune responses. 


Prof. Dr. Melody Swartz 

Institute of Bioengineering and 

Institute for Experimental Cancer Research 


Station 15 


Phone +41 (0)21 693 96 86 

melody.swartz@epfl.ch 

Thoma Nicolas | The molecular basis of the defense 

against skin cancer: Structural studies of the DDB1- 

DDB2-XPC/Rad23 UV-damage handover complex 

(OCS 02365022009) 

Duration: 01.09.2009 – 01.09.2011 

Genetic instability is a hallmark of all cancer cells. The loss 

of genetic information functions as initiator in the formation 

of the tumour cells, as well as in driving the malignant 

transformation process. Persistent UV irradiation of exposed 

skin cells leads to an accumulation of a number 

DNA lesions. If left unrepaired, this DNA damage facilitates 

formation of skin tumours ranging from malignant 

melanomas, squamous cell carcinomas to basal cell carcinomas. 

The proposal focuses on the DDB1DDB2 protein 

complex and its interactions with the XPCRad23 complex. 

Together these complexes recognize DNA damage 

and initiate the repair response. We aim to use a combination 

of Xray crystallography and biochemical techniques 

to understand how these crucial protein complexes detect 

and repair DNA damage and thus serve as a safeguard 

against skin cancer. 


Dr. Nicolas Thoma 




CH4058 Basel 

Phone +41 (0)61 697 86 30 

nicolas.thoma@fmi.ch

ThomeMiazza Margot | Analysis of the role of 

the protease MALT1 in human lymphomas 

(KFS 02561022010) 

Duration: 01.08.2010 – 01.08.2013 

The activation and subsequent proliferation of lymphocytes 

is normally initiated by the detection of the presence 

of an infection. This process is perturbed in lymphomas or 

leukaemia, a form of cancer characterized by uncontrolled 

lymphocyte proliferation. 

Our goal is to clarify the relevance of the protease MALT1 

in this process, since MALT1 plays an important role in the 

proliferation of lymphocytes. By comparing resting and 

activated lymphocytes, we could show that MALT1 is only 

active in activated lymphocytes. Through systematic comparison 

of cell lines derived from diffuse large Bcell lymphomas 

(DLBCL), we then showed that MALT1 is hyperactive 

in a subset of this type of lymphoma, called the 

ABC subtype of DLBCL. Moreover, treatment of cells derived 

from this lymphoma type with a MALT1 inhibitor led 

to inhibition of the growth of the cells in vitro. 

The goal of our ongoing studies is to find out whether the 

activity of MALT1 is also relevant for other types of lymphomas, 

such as cutaneous Tcell lymphomas or lymphomas 

induced by the oncogenic human herpesvirus8 

(HHV8). We hope that these studies of the relevance of 

MALT1 for different lymphoma types will contribute to 

the development of novel strategies for the diagnosis and 

therapy of this form of cancer. 


Prof. Dr Margot ThomeMiazza 



155, chemin des Boveresses 


Phone +41 (0)21 692 57 37 

Fax +41 (0)21 692 57 05 

margot.thomemiazza@ib.unil.ch 

Tschan Mario P. | The importance of autophagy 

in normal and leukemic myelopoiesis 

(KFS 02486082009) 

Duration: 01.02.2010 – 01.02.2012 

Autophagy, literally selfeating, is a mechanism involved 

in the degradation of organelles or protein aggregates. Its 

role in cancer is controversial: First, autophagy contributes 

to genome stability of healthy cells; second, it promotes 

tumour cell survival upon anticancer therapy. This 

study aims at elucidating the function of autophagy in the 

pathogenesis of acute promyelocytic leukaemia (APL). 

Using an RNA interferencebased reverse genetics screen, 

we found that inhibiting autophagy impairs neutrophil 

differentiation of APL cells. Characterizing the autophagic 

molecular pathways involved in neutrophil development 

may lead to novel strategies to treat APL. One might imagine 

combining current APL differentiation therapy with 

autophagyinducing drugs. 


PD Dr. Mario P. Tschan 

Medizinische Onkologie/Hämatologie 



MEM E829 


CH3010 Bern 

Phone +41 (0)31 632 87 80 

mtschan@dkf.unibe.ch 

Weller Michael | Angiogenesis and invasion in 

glioblastoma: The therapeutic options and risks of 

co-targeting VEGF and TGF-beta (KFS 02694082010) 

Duration: 01.02.2011– 01.02.2014 

Glioblastoma, the most common intrinsic brain tumour, 

has a very poor prognosis. At present, clinical research in 

glioma therapy is focusing strongly on novel agents targeting 

angiogenesis, mostly antagonists of vascular endothelial 

growth factor (VEGF) signalling. However, there 

is increasing evidence that the inhibition of angiogenesis 

alone is insufficient to control glioma growth for more 

than a few months and that gliomas may develop dangerous 

escape strategies including a more invasive phenotype 

in response to antiangiogenic therapy. This research 

project will address the hypothesis that the switch to invasiveness 

triggered by antiangiogenic agents depends critically 

on the biological effects of the cytokine transforming 

growth factor beta (TGFbeta). Here, we will try to 

dissect the complex interactions between the VEGF and 

TGFbeta signalling pathways in glioblastoma. 

Our aim is to optimize antiangiogenic therapies against 

glioblastomas. To achieve this, we perform a preclinical 

study using standard approaches for in vitro and in vivo 

analysis. In the long term we aim to develop new strategies 

for clinical trials for the benefit of patients. 


Prof. Dr. Michael Weller 

Klinik für Neurologie 


Frauenklinikstrasse 26 


Phone +41 (0)44 255 55 00 

Fax +41 (0)44 255 45 07 

michael.weller@usz.ch 

Widmann Christian | The 317-326 sequence of RasGAP 

as potential anti-metastatic agent 

(KFS 02543022010) 

Dissemination of cancer cells in the organism from primary 

tumours is the event most dreaded by oncologists. 

Indeed, metastasis formation is the primary cause of 

death resulting from cancer. In our laboratory, we have 

discovered that a peptide derived from the RasGAP protein 

increases in vitro the adherence of cancer cells and inhibits 

their migratory capacity. This peptide therefore has 

an antimetastatic potential. 

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In this project we will investigate whether the RasGAP 

peptide can indeed block the formation of metastases in 

mice. We will also study the mode of action of the peptide 

on tumour cells by investigating the effect of the peptide 

on cell adhesion molecules and on the cytoskeleton. These 

experiments might lead to clinical application in humans. 


Prof. Dr Christian Widmann 

Département de physiologie 




Phone +41 (0)21 692 51 23 

Fax +41 (0)21 692 55 95 

christian.widmann@unil.ch 

Wymann Matthias Paul | Identification and modulation 

of targets to reprogram glioblastoma cancer stem 

cells (KFS 02680082010) 

Duration: 01.01.2011– 01.01.2014 

Glioblastoma multiforme (GBM) is a very aggressive brain 

tumour. A signalling pathway connecting a lipid kinase 

(phosphoinositide 3kinase (PI3K)) to a nutrient sensor 

complex (target of rapamycin (mTOR)) constitutes a central 

piece of GBM aetiology. To date, little is known regarding 

relevant signalling downstream of the lipid product PtdIns(3,4,5)P3 

of PI3Ks. Exploring structural determinants 

of putative phosphoinositideinteracting proteins, we will 

assemble pathway modules to be targeted in GBM. We 

have developed enrichment protocols for GBMderived 

cancer stem cells (GBM CSCs). These will be monitored for 

phenotypic outputs of pharmacologically and genetically 

modulated PIiPsdependent pathways. Pilot studies indicate 

that reprogramming GBM CSCs could drive them 

towards differentiation and cell death. The identification 

of novel signalling elements in GBM CSCs is of critical importance 

for developing novel strategies for the treatment 

of this devastating disease. 


Prof. Dr. Matthias Paul Wymann 





CH4058 Basel 

Phone +41 (0)61 695 30 46 

matthias.wymann@unibas.ch 

Zaugg Kathrin | Elucidating the role of the hypoxiaprotective 

gene CPT1C (Carnitine Palmitoyl-transferase 

1C) in carcinogenesis (KLS 02569022010) 

Duration: 01.05.2010 – 01.05.2011 

Hypoxia is a key regulator in tumour growth and can lead 

through an epigenetic phenomenon to more resistant 

cancer cells. In our laboratory we are investigating the 

mechanism of a gene that modulates cancer cell death under 

hypoxic conditions. In addition, it promotes migration 

and invasion when overexpressed. 


Dr. Kathrin Zaugg 

Labor für angewandte RadioOnkologie 


NUK E 17 



Phone +41 (0)44 255 29 30 

Fax +41 (0)44 255 44 35 

kathrin.zaugg@usz.ch 

Zavolan Mihaela | Identification of cancer-related 

targets of individual members of the miR-17~92 cluster 

of miRNA (KFS 02477082009) 

Duration: 01.01.2010 – 01.01.2013 

MicroRNAs (miRNAs) are short RNA molecules that regulate 

expression of proteincoding genes that play important 

roles in the growth, division, differentiation and apoptosis 

of cells. Some act as cancer suppressors, downregulating 

cancerpromoting cellular factors, while others are oncogenic, 

promoting malignancies. We are studying the miR 

17~92 miRNA family, which consists of six related miRNAs 

that collectively have been implicated in various lymphomas, 

as well as lung, bladder and colon cancers. Our project 

aims to uncover the targets and pathways that individual 

members of the miR17~92 cluster affect in bringing 

about carcinogenesis. We combine highthroughput experiments 

with computational predictions and direct molecular 

biology techniques for target validation. By observing 

the behaviour of tumourderived cells in which we 

deplete these targets with small interfering RNAs, we will 

further identify the role of these targets in tumour formation. 

The targets that we hope to identify would constitute 

potential factors for novel drugs that prevent or slow 

down cancer formation. 


Prof. Dr. Mihaela Zavolan 



Klingelbergstrasse 50–70 

CH4056 Basel 

Phone +41 (0)61 267 15 77 

mihaela.zavolan@unibas.ch

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Challenges for clinical cancer research in Switzerland 

The aim of patient-centred clinical cancer research is 

to develop new cancer therapies and to optimize 

existing tumour therapies so as to improve the prognosis 

and tolerability of treatment in patients with 

cancer. Typical research questions are, for example: 

Will a combination of different chemotherapy drugs 

produce better results? Will this cause more side effects? 

What is the optimal combination of the three 

types of treatment – chemotherapy, radiation therapy, 

and surgery – for certain types of cancer and 

patient groups? As chemotherapy is often very expensive, 

an increasing number of investigations are 

also examining the cost and benefits of treatments. 

For patients with cancer, clinical cancer research has 

two benefits: For one, participation in clinical trials 

gives the patient early access to new treatments. For 

another, treatment quality is the highest at institutions 

that conduct clinical studies, as a recent study 

on breast cancer treatment in Switzerland showed 

[1]. 

Since also medium-sized and large hospitals are fre- 

quently not able to conduct a research project by 

themselves, clinical cancer research in Switzerland 

depends upon good networking of the research 

groups and centres. For many years now, this task 

has been taken on by the Swiss Group for Clinical 

Cancer Research (SAKK) for adults and by the Swiss 

Paediatric Oncology Group (SPOG) for children. The 

activities of the two non-profit organizations are 

funded for the most part by research grants from the 

Swiss government (State Secretariat for Education 

Prof. Beat Thürlimann, MD 

Head of the Breast Centre at the Cantonal Hospital of St Gallen and president of the Swiss Group 

for Clinical Cancer Research (SAKK) 

Arnoud Templeton, MD 

Senior physician at the Cantonal Hospital of St Gallen and medical advisor of the Swiss Group 

for Clinical Cancer Research (SAKK) 

115

116 

and Research). Other financial sponsors are companies, 

the Foundation Cancer Research Switzerland, 

the Swiss Cancer League, santésuisse (the association 

of Swiss health insurers), and private foundations 

like the Swiss Foundation for Clinical Cancer 

Research. 

Even though clinical cancer research in Switzerland 

receives international attention and the findings 

have an influence on everyday clinical practice, benefitting 

patients directly, there is always the question 

as to how clinical research can be improved, how existing 

resources can be utilized even better and benefit 

more patients. 

Approval process for a clinical study 

A clinical research project or study usually begins 

with an idea or a specific question formulated by a 

research group or a trial investigator, the study 

leader. First, the study design is worked out, defining 

the hypothesis and how the hypothesis will be tested 

and establishing the number of patient participants 

that will be required. This number provides a first 

clue as to whether a study can be conducted at all or 

whether international cooperation is appropriate. 

The actual study plan, the protocol, is usually written 

in cooperation with the organization that will conduct 

the study. For many cancer-related studies in 

Switzerland, this organization is the SAKK. The SAKK 

funds the study, secures the insurance coverage, and 

has the main responsibility for the quality of the 

study data. The protocol is a document outlining the 

background and reason, the objectives, and the exact 

procedure for performing the study, and it describes 

the conditions under which the study will be 

conducted and monitored. 

In addition to study protocol and patient informa- 

tion, the complete proposal for a clinical trial also 

contains information documenting the necessary 

qualifications of the physicians involved. The proposal 

is sent first to the responsible cantonal ethics 

committees, which may request a revised version 

prior to approval or rejection. The ethics committees 

carefully examine the study’s compliance with national 

and international ethical guidelines and conformance 

with the guideline for Good Clinical Practice 

(GCP) [2]. If the ethics committees approve a 

study, the documents are then submitted to Swissmedic, 

the Swiss Agency for Therapeutic Products, 

which either approves the proposal within 30 days or 

sends it back for revision. Once Swissmedic has given 

approval, the clinical trial can be conducted and 

evaluated in accordance with the study protocol. 

Difficulties in clinical research 

In many Swiss hospitals, knowledge of the eminent 

importance of clinical research has grown in past 

years. However, it is a great challenge for a hospital 

to provide – in addition to its routine operation – the 

human and financial resources required for a clinical 

trial. Many researchers, doctors, and patients have 

complained about the increasing bureaucratization 

of research in recent years. The administrative and 

financial expense is absolutely prohibitive for small 

studies with only a small number of patients (for example 

in paediatrics or rare diseases), with the result 

that these kinds of studies are increasingly no longer 

being conducted. It is also problematic when reviewing 

proposals for research projects that use alreadyregistered 

drugs, the authorities apply the same 

strict criteria as they do for new or less well-known 

drugs. This occasionally leads to requirements that 

are hardly comprehensible, and it ultimately slows 

progress in cancer treatment. Less detailed regula

tory requirements would also be desirable for therapies 

that in addition to chemotherapy also include 

surgery and/or radiation therapy, or for projects such 

as quality of life research and studies on health economics 

(for example, requirements in the areas of 

bookkeeping, safety reporting, reporting of insignificant 

protocol changes) [3]. 

To make the best possible use of the existing leeway 

in the regulations, all parties involved (study leader, 

organization conducting the trial, ethics committee, 

Swissmedic) need more training, experience, mutual 

trust, and a good eye for realistic risk assessment. 

Through this, for instance, unnecessary duplication 

such as the review of one and the same study by 

multiple ethics committees could be avoided. In addition, 

clear designation of responsibilities is important: 

For instance, Swissmedic could recognize the 

decisions by ethics committees or by the Federal 

Data Protection and Information Commissioner 

(FDPIC), without having to evaluate these aspects of 

the study proposals all over again. These are certainly 

ways to increase the efficiency of research and 

improve utilization of the available resources without 

any loss of quality [3]. Some studies even showed 

that duplicative reviews and in part contradictory 

decisions worsen the quality of research rather than 

improve it [4]. 

Issues concerning the new Swiss law on research 

involving humans 

Elaboration of the law on research involving humans 

(Humanforschungsgesetz, HFG) is very important 

for the future of clinical research. Fortunately, some 

of the suggestions mentioned above were already 

discussed in the first parliamentary deliberations on 

the HFG. Many research institutions agree that the 

law should not strictly adhere to the GCP guideline 

word-for-word in all areas of clinical research but 

should rather lay down the fundamental principles of 

the GCP. It would also seem appropriate to exempt 

clinical trials using already approved medicines from 

the requirement to obtain approval by Swissmedic as 

well as to provide a simplified approval process for 

international studies that have already been approved 

by responsible foreign authorities. In countries having 

comparable regulatory and legal standards (such as 

EU countries, the United States, and Canada), the research 

topic and the ethical context are reviewed in 

an analogous manner as they are in Switzerland before 

a clinical trial is approved. For that reason, yet 

another scientific review by the Swiss authorities is 

unnecessary. What should be reviewed in Switzerland 

would then be only the national and local conditions, 

such as the qualifications of the study leader and the 

competency of the centre. 

Unquestionably, all clinical trials should be recorded 

in study registries that are accessible to the public. 

This improves the coordination of research efforts 

and also makes it difficult for those conducting the 

study to conceal unwanted findings. This should include 

recording the studies in international study 

registry databases that are already being run successfully, 

as the SAKK and its cooperation partners in 

national and international patient-centred cancer research 

have done for years. 

Cost coverage for standard medical procedures 

in studies 

One problem in clinical research that should be better 

regulated by law is cost coverage by the health insurer 

for the study patients’ routine diagnostics and 

routine treatments. The medical treatment and care 

costs in patient-centred clinical studies should be – 

as in other industrialized countries – covered by 

the health insurance companies [5, 6]. Without this 

prerequisite, clinical research in Switzerland would 

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118 

be totally unaffordable for academic organizations 

and institutions, and, in the end, unfeasible. In addition 

to elaborating the HFG, solving this cost coverage 

problem through a revision of the Swiss health 

insurance law (Krankenversicherungsgesetz, KVG, 

Art. 49) is an urgent concern. 

Institutions like SAKK or the six competence centres 

for clinical research (Clinical Trial Units, CTUs) in 

Swiss hospitals can also conduct successful research 

within the current regulatory conditions. But this is 

only possible with clearly higher costs and human 

resources. If the right course is set through the legislation, 

Swiss research can become more attractive in 

international comparison, the quality of patient care 

and access to new medications can be improved, and 

support of the young generation of physicians and 

researchers can be optimized. Implementation of the 

suggestions offered above would contribute towards 

ensuring that Swiss research remains innovative and 

of the highest quality – to the benefit of all persons 

affected by cancer. 

Prof. Beat Thürlimann, MD 

Beat Thürlimann is head physician 

and head of the Breast Centre 

at the Cantonal Hospital of 

St Gallen. After completing his 

medical studies at the University 

of Zurich and working as an 

assistant physician at University 

Hospital Zurich, he worked at 

Pretoria Academic Hospital 

in South Africa and then at the Cantonal Hospital 

St Gallen. He has been an active member of the SAKK 

board for many years and was appointed president in 

July 2010. He served as president of the breast cancer 

project group from 1993 to 2005. His main professional 

interests are breast cancer, adjuvant therapy, new 

medications, international research and gynaecological 

tumours. 

Phone +41 (0)71 494 18 88 

beat.thuerlimann@sakk.ch 

www.brustzentrum-sg.ch 

Arnoud Templeton, MD 

Arnoud Templeton works as 

medical advisor at the SAKK 

Coordinating Centre in Bern. 

He has been a senior clinical and 

research fellow in oncology and 

haematology at the Cantonal 

Hospital of St Gallen since April 

2011. His main clinical and 

research interests are urogenital 

tumours and integrative oncology. 

Phone +41 (0)71 494 10 62 

arnoud.templeton@sakk.ch 

www.onkologie-sg.ch

References 

1. Ess S, Joerger M, Frick H, Probst-Hensch N, Vlastos G, 

Rageth C, Lütolf U, Savidan A, Thürlimann B. Predictors 

of state-of-the-art management of early breast 

cancer in Switzerland. Ann Oncol 2011;22(3):618-624. 

2. International Conference on Harmonisation of Technical 

Requirements for Registration of Pharmaceuticals 

for Human Use. Guideline for Good Clinical Practice E6 

(R1). http://www.ich.org/fileadmin/Public_Web_Site/ 

ICH_Products/Guidelines/Efficacy/E6_R1/Step4/E6_ 

R1__Guideline.pdf 

3. Stewart DJ, Whitney SN, Kurzrock R. Equipoise lost: 

ethics, costs, and the regulation of cancer clinical 

research. J Clin Oncol 2010;28:2925-2935. 

4. Menikoff J. The paradoxical problem with multiple-IRB 

review. N Engl J Med 2010;363(17):1591-1593. 

5. U.S. Department of Health & Human Services (DHHS). 

Medicare Clinical Trial Policy. http://www.cms.gov/ 

transmittals/downloads/R74NCD.pdf 

6. Department of Health, United Kingdom (UK). Attributing 

revenue costs of externally-funded non-commercial 

research in the NHS. (ARCO)http://www.dh.gov.uk/ 

prod_consum_dh/groups/dh_digitalassets/@dh/@en/ 

documents/digitalasset/dh_4125282.pdf 

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120 



Aebersold Daniel M. | OCS 01681-02-2005 | CHF 172,800.– 

Klinik und Poliklinik für Radio-Onkologie, Inselspital, Bern 

The role of activating point mutations in the met receptor tyrosine kinase in tumor radioresistance 

Baege Astrid | KLS 02220-02-2008 | CHF 220,100.– 

Klinik für Gynäkologie, UniversitätsSpital Zürich, Zürich 

The role of adult stem cells in HPV-associated carcinogenesis: Identification of the HPV target cell capable 

of driving viral persistence 

Ballmer Peter E. | OCS 02000-02-2007 | CHF 155,800.– 

Klinik für Innere Medizin, Departement für Medizin, Kantonsspital Winterthur, Winterthur 

Influence of a nutritional intervention on clinical course and quality of life in cancer patients 

Benhattar Jean | OCS 01638-02-2005 | CHF 203,000.– 


Identification of biomarkers for early cancer detection in Barrett’s esophagus patients using methylation 

profiles and the Wnt pathway 

Bertoni Francesco | KLS 01835-02-2006 | CHF 177,900.– 

Gruppo genomica funzionale e linfomi, Laboratorio di oncologia sperimentale, Istituto oncologico della Svizzera 

italiana (IOSI), Bellinzona 

Evaluation of the tyrosine kinase SYK as a possible therapeutic target in lymphomas 

Bertoni Francesco | OCS 01939-08-2006 | CHF 226,800.– 



Genome-wide DNA profiling as outcome predictor in diffuse large B-cell lymphoma 

Bertoni Francesco | OCS 02034-02-2007 | CHF 157,800.– 



Extranodal, nodal and splenic marginal zone B-cell lymphomas: How much are they related to each other? 

Bohlius Julia | OCS 02146-10-2007 | CHF 128,100.– 

Forschungsgruppe Krebs, Institut für Sozial- und Präventivmedizin (ISPM), Universität Bern, Bern 

Individual patient data meta-analysis on the effects of erythropoiesis-stimulating agents in cancer patients 

Bourquin Jean-Pierre | KLS 02124-08-2007 | CHF 226,600.– 

Abteilung Onkologie, Kinderspital Zürich, Universitäts-Kinderkliniken, Zürich 

A leukemia xenotransplantation model to evaluate combinatorial approaches for the treatment of de novo drug 

resistant childhood acute lymphoblastic leukemia 


Bourquin Jean-Pierre | KFS 02453-08-2009 | CHF 125,500.– 


Pre-clinical evaluation of a new pharmacological approach using obatoclax for chemosensitization of drug 


Duration: 01.03.2010 – 01.03.2011 

Carbone Giuseppina | OCS 01913-08-2006 | CHF 183,800.– 


Functional and clinical implications of deregulated expression of ETS transcription factors in prostate cancer 

Cozzi Luca | OCS 01821-02-2006 | CHF 80,800.– 

Servizio di fisica medica, Istituto oncologico della Svizzera italiana (IOSI), Ospedale regionale di Bellinzona 

e valli, Bellinzona 

Heterogeneity management in advanced algorithms for photon dose calculation and the clinical impact on 

breast and lung cancer radiotherapy. Validation of existing models against experimental studies, Monte Carlo 

simulations and determination of potential

De Libero Gennaro | KLS 02211-02-2008 | CHF 159,500.– 

Experimentelle Immunologie, Departement Biomedizin, Universität Basel, Basel 

Lipid-specific T-cells against leukaemic blasts 

Dirnhofer Stephan | OCS 01792-10-2005 | CHF 297,800.– 


Inducing cell death in apoptosis-resistant hematological tumors: Impact on diagnosis and therapeutic 

intervention 

Doucey Marie-Agnès | OCS 02069-04-2007 | CHF 214,800.– 

Centre pluridisciplinaire d’oncologie (CePO), Centre hospitalier universitaire vaudois (CHUV), Lausanne 

Functional and biochemical characterization of human monocyte-like circulating cells in breast cancer patients: 

Relevance to tumor growth and angiogenesis 

Dubey Raghvendra K. | OCS 01551-08-2004 | CHF 258,300.– 

Klinik für Reproduktions-Endokrinologie, UniversitätsSpital Zürich, Zürich 

Pathophysiological role of estrogen metabolism in breast cancer 

Frattini Milo | OCS 01921-08-2006 | CHF 102,300.– 


Characterization of EGFR deregulation and EGFR downstream cascade in colorectal cancer patients, and 

relationship to new targeted therapies 

Garayoa Elisa Garcia | KLS 02040-02-2007 | CHF 150,700.– 

Zentrum für radiopharmazeutische Wissenschaften, Paul Scherrer Institut (PSI), Villigen 

Development of new bombesin-based radiopharmaceuticals with improved pharmacokinetics as potential 

imaging and therapeutic agents for bombesin receptor-positive tumours 

Gautschi Oliver | KLS 02164-02-2008 | CHF 218,200.– 

Departement für klinische Forschung, Universität Bern, Inselspital, Bern 

Regulation of lD1 expression by Src in cancer: Clinical implications 

Heim Markus Hermann | OCS 02192-02-2008 | CHF 245,200.– 




Heim Markus Hermann | KLS 01832-02-2006 | CHF 231,700.– 



Heinzelmann-Schwarz Viola | OCS 02115-08-2007 | CHF 232,100.– 

Translational Research Group, Klinik für Gynäkologie, Medizinbereich Frau-Kind, UniversitätsSpital Zürich 

Detection of anti-glycan autoantibodies as biomarkers of high stage serous ovarian cancer; acronym: 

GOS-study 

Herrmann Richard | KLS 02067-04-2007 | CHF 490,000.– 

Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK), Koordinationszentrum, Bern 

The SAKK initiative for regional hospitals 

Hess Christoph | OCS 02266-08-2008 | CHF 103,700.– 

Ambulante Innere Medizin, Medizinische Poliklinik, Universitätsspital Basel, Basel 

Innate immunity, cytokine polymorphisms, and development of post-transplant lymphoproliferative disease 

in kidney transplant recipients 

Hess Viviane | KLS 01881-04-2006 | CHF 87,800.– 

Medizinische Onkologie, Universitätsspital Basel, Basel 

Improving treatment for patients with advanced pancreatic cancer (APC): A Swiss-wide effort 

Hoek Keith | OCS 01927-08-2006 | CHF 145,500.– 

Dermatologische Klinik, Medizinbereich Trauma-Derma-Rheuma-Plastische Chirurgie, UniversitätsSpital Zürich, 

Zürich 

Clinical implications of Wnt signal-driven regulation of melanoma metastatic potential 

121

122 

Hunger Robert E. | OCS 02262-08-2008 | CHF 91,500.– 

Universitätsklinik für Dermatologie, Inselspital, Bern 

Malignant melanoma: Correlation of dendritic cell (DC) and T-cell markers with prognosis 

Imhof Beat A. | OCS 01653-02-2005 | CHF 177,600.– 

Département de pathologie et immunologie, Faculté de médecine, Centre médical universitaire (CMU), 


The mechanism of anti-JAM-C antibodies blocking tumor angiogenesis 

Irminger-Finger Irmgard | KLS 01962-10-2006 | CHF 204,000.– 

Laboratoire de gynécologie-obstétrique moléculaire, Département de gynécologie et d’obstétrique, 

Maternité, Hôpitaux universitaires de Genève (HUG), Genève 

BRCA1-associated protein, BARD1, a molecular target for breast cancer screening and cancer therapy 

Kalberer Christian P. | OCS 01870-02-2006 | CHF 155,000.– 

Labormedizin, Diagnostische Hämatologie, Universitätspital Basel, Basel 

Role of NKG2D receptor-ligand interactions in the recognition of human B-cell neoplasms by natural killer cells 

Kalia Yogeshvar N. | OCS 01753-08-2005 | CHF 168,600.– 

Section des sciences pharmaceutiques (Ecole de pharmacie Genève Lausanne), 


Non-invasive transdermal iontophoretic delivery of antiemetic drugs for the treatment of chemotherapy- 

induced nausea and vomiting 

Maiwald-Urosevic Mirjana | OCS 01934-08-2006 | CHF 237,200.– 


Zürich 

Role of versican in the biology of Sézary cells 

Matthes Thomas | OCS 01781-08-2005 | CHF 201,900.– 


Analysis of transcription factors PU.1 and GATA-1 functions in myelodysplastic syndromes, in acute myeloid 

leukemia and in leukemia stem cells 

Müller Beatrice U. | OCS 01731-08-2005 | CHF 249,000.– 

Departement für allgemeine Innere Medizin und klinische Forschung, Inselspital, Bern 

The master transcription factor PU.1 is essential for normal hematopoiesis: Analysis of PU.1 alterations in 

patients with acute myeloid leukemia (AML) 

Perrier Patrick | OCS 01911-08-2006 | CHF 150,000.– 

Service de dermatologie, Département de médecine, Centre hospitalier universitaire vaudois (CHUV), Lausanne 

Impact of UV light on melanoma development 

Renevey Philippe | OCS 01777-08-2005 | CHF 188,600.– 

Centre suisse d’électronique et de microtechnique (CSEM), Neuchâtel 

Development of a voice restoration system for laryngectomees in order to improve their social interaction 

Schäfer Beat W. | OCS 02264-08-2008 | CHF 200,600.– 


Oncogenic fusion proteins as therapeutic targets in pediatric sarcomas 


Schäfer Beat W. | OCS 01944-08-2006 | CHF 173,200.– 


Prognostic classification of rhabdomyosarcoma: A combined retro- and prospective study 

Speiser Daniel E. | OCS 01917-08-2006 | CHF 211,500.– 

Ludwig Institut für Krebsforschung, Universitätsspital Lausanne, Lausanne 

Analysis of key mechanisms of human melanoma specific CD8 + T-cell responses: Long term persisting 

clonotypes and strong effector functions 

Stahel Rolf A. | OCS 01915-08-2006 | CHF 148,800.– 

Klinik und Poliklinik für Onkologie, Medizinbereich Innere Medizin-Onkologie, UniversitätsSpital Zürich, Zürich 

SAKK trial 17/04 on neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural 

mesothelioma (MPM) with or without hemithoracic radiotherapy, including translational research

Taverna Christian | OCS 02125-08-2007 | CHF 223,700.– 

Onkologie, Kantonsspital Münsterlingen, Münsterlingen 

Comparing two schedules of rituximab maintenance in rituximab-responding patients with untreated, 

chemotherapy resistant or relapsed follicular lymphoma: A randomized phase III trial of the SAKK 

(Swiss Group for Clinical Cancer Research) 

Terracciano Luigi M. | OCS 02005-02-2007 | CHF 208,600.– 

Abteilung für Molekularpathologie, Institut für Pathologie, Universität Basel, Basel 

HOX A13 hyper-expression in liver cancer: A potential node toward angiogenesis 

Thalmann George N. | OCS 01752-08-2005 | CHF 190,300.– 

Klinik und Poliklinik für Urologie, Inselspital, Bern 

Impact of therapeutic and preventive strategies in prostate cancer on prostate-specific antigen (PSA), 

gene expression and tumor cell survival 

Theurillat Jean-Philippe | KLS 02014-02-2007 | CHF 173,300.– 

Institut für klinische Pathologie, UniversitätsSpital Zürich, Zürich 

Synthetic lethality in the context of autophagy-deficiency 

Timmermann Beate | OCS 01694-04-2005 | CHF 113,300.– 

Westdeutsches Protonentherapiezentrum Essen (WPE), Universitätsklinikum Essen, Essen, Deutschland 

Prospective evaluation of late effects and quality of life in childhood cancer after spot-scanning proton therapy 

at the Paul Scherrer Institute 

von der Weid Nicolas | KLS 01605-10-2004 | CHF 265,900.– 

Service de pédiatrie, Centre hospitalier universitaire vaudois (CHUV), Lausanne 

Long-term outcome of childhood cancer: Incidence and spectrum of late effects 

Wodnar-Filipowicz Aleksandra | OCS 02175-02-2008 | CHF 162,000.– 

Basel Stem Cell Center of Competence, Medizinische Fakultät, Universität Basel, Basel 

Immunotherapy of human leukemia with natural killer cells: From bench to bedside 


Wodnar-Filipowicz Aleksandra | OCS 01664-02-2005 | CHF 301,500.– 

Basel Stem Cell Center of Competence, Medizinische Fakultät, Universität Basel, Basel 

Role of the natural killer cell receptors NCR and KIR in immune defence against human leukemia 

Zaman Khalil | OCS 02029-02-2007 | CHF 54,200.– 

Centre pluridisciplinaire d’oncologie (CePO), Centre hospitalier universitaire vaudois (CHUV), Lausanne 

Monitoring of angiogenesis-related molecules during first line chemotherapy with bevacizumab (Avastin) and 

pegylated liposomal doxorubicin (Caelyx) for advanced stage breast cancer: A substudy of the SAKK 24/06 trial 

Zhong Xiao Yan | OCS 01993-02-2007 | CHF 173,600.– 

Forschungsgruppe pränatale Medizin und gynäkologische Onkologie, Departement Biomedizin, 

Universität Basel, Basel 

Investigating tumour-derived methylation DNA in circulation as markers for non-invasive screening, 

early diagnosis, monitoring and determination of the prognosis of breast cancer 

Zucca Emanuele | OCS 01709-04-2005 | CHF 111,600.– 


A prospective clinico-pathologic study of primary mediastinal B-cell lymphoma (PMBCL) 

123

124 



Aebersold Daniel M. | The role of activating point 

mutations in the met receptor tyrosine kinase in tumor 

radioresistance (OCS 1681-02-2005) 

The growth factor receptor Met activates various pathways 

and corresponding biological functions that are implicated 

in the development of malignant tumours, including 

critical roles in tumour progression and metastasis. 

Moreover, it was demonstrated that the activation of this 

receptor can adversely affect the response of malignant 

tumour cells to chemotherapy and radiotherapy. Consequently, 

Met is considered to be a promising molecular 

target for the development of new cancer drugs. Various 

mechanisms that can lead to excessive activation of the 

Met receptor in tumours have been described. In this regard, 

Met receptor overexpression and the occurrence of 

activating point mutations are the most prevalent. The 

aim of this research project was to investigate in more detail 

the importance of activating Met mutations, from 

both the biological and clinical point of view. For this purpose, 

the following sub-projects were pursued: 

1) The clinical study focused on the potential role of the 

MET variant Y1253D, for which we previously suggested 

a role in tumour response to radiation therapy, in metastatic 

head and neck squamous cells carcinoma. This work 

– performed on biopsy samples from a prospective randomised 

trial combining radiotherapy and chemotherapy 

– confirmed a role for an activating MET mutation in metastasis 

of these tumours. 

2) The scope of this sub-study was to perform a characterization 

of the response of four MET mutated variants, 

all of clinical significance, to the small molecule inhibitor 

SU11274 before a combination treatment with IR could be 

performed. The data obtained suggest that although all 

four mutants are responsive to SU11274, considerable differences 

in IC50 were observed on various MET-dependent 

biochemical and biological endpoints. Those response 

differences would have to be taken into consideration 

once SU11274 is combined with IR. 

3) This study focused on mechanistic aspects that underlie 

the molecular cross-talk between MET and the DNA 

damage response in cells harbouring both overexpression 

of MET and MET mutations. The work shows that MET 

inhibition results in reduced clonogenic survival of cells 

to IR, which is accompanied by increased apoptosis. The 

work also shows that MET inhibition cooperates with 

DNA damaging agents to induce double strand DNA 

breaks (DSBs) in a synergistic manner, and one of the reasons 

for this synergism is the fact the MET inhibition alone 

results in high levels of DSBs. The study also shows that 

Met inhibition results in blocking of a major checkpoint 

signalling pathway, the ATR-CHK1-CDC25, which results 

in disruption of a post-damage S-phase associated cell cycle 

arrest, which could eventually lead to mitotic entry of 

cells that harbour high levels of unrepaired DSBs. 

4) In this study we further explored previous findings, 

published in 2008, coupling MET to effectors of DSBs repair 

via homologous recombination. In that respect, by 

using the DR-GFP homologous recombination (HR) assay, 

we show that MET inhibition results in attenuation of HR 

in a dose-dependent manner in cells harbouring MET 

overexpression and MET mutants. Moreover, mechanistically 

the study shows that this MET-dependent inhibition 

of HR is coupled to a reduction of nuclear RAD51 and a 

disruption of the physical association between RAD51 

and BRCA2, which is crucial for successful HR. 

The overall objective of the research project was to pave 

the way for the implementation of genetic and mechanistic 

evidence related to the growth factor receptor Met in 

clinical research protocols to test the combination of Met 

inhibition with conventional radiotherapy or chemotherapy. 


Prof. Dr. Daniel M. Aebersold 

Universitätsklinik für Radio-Onkologie 

Inselspital/Universität Bern 

Freiburgstrasse 

CH-3010 Bern 

Phone +41 (0)31 632 24 31 

Fax +41 (0)31 382 23 42 

daniel.aebersold@insel.ch 

Baege Astrid | The role of adult stem cells in HPV- 

associated carcinogenesis: Identification of the HPV 

target cell capable of driving viral persistence 

(KLS 02220-02-2008) 

Objective 

Cervical cancer is still the second most common malignancy-related 

cause of death worldwide. Persistent infection 

with high risk human papillomavirus (HPV) is necessary 

for the emergence of cervical cancer, but the crucial 

factors determining persistence are largely unknown. The 

overall goal is to identify stem cells within the human cervical 

epithelium to further investigate their role during 

HPV-transmission, establishment of persistent infection 

and HPV-induced transformation. 

Methods 

Epithelial cells are isolated from fresh human cervical tissue 

and fractionated by FACS sorting. Subpopulations of 

putative stem cells, transit amplifying cells and differentiating 

cells are sequentially subjected to microarray analysis 

to compare gene expression pattern. Recruited stem 

cell markers will be used to localize stem cells within the 

cervical epithelium. Advanced organotypic cervical explant 

models will be infected with fluorescent high risk 

HPV pseudoviruses, and the course of infection will be 

monitored to identify the HPV target cell capable of maintaining 

the viral DNA over a course of time.

Results 

Transcriptional profiling of putative stem cells suggested 

an undifferentiated and slowly cycling phenotype. Genes, 

encoding transcripts involved in self-renewal of stem cells, 

negative regulation of proliferation via TGF-b signalling, 

organogenesis and inhibition of the WNT signalling pathway 

were overrepresented, whereas genes responsible for 

cell division and DNA replication and DNA repair were underrepresented. 

Markers for cervical stem cells were validated 

at the protein level, permitting localization of stem 

cells in a scattered pattern within the basal layer of the 

cervical epithelium. Isolation and characterization of 

these cells confirmed an undifferentiated, slowly cycling 

phenotype with high proliferative potential. We successfully 

optimized a cervical organ culture model developed 

in our laboratory, now maintaining original organ architecture, 

tissue heterogeneity and expression of cellular 

markers for up to 4 weeks. These cervical explants provided 

the basis for monitoring virus binding and the 

course of infection within the regenerating epithelium after 

exposure to HPV pseudoviruses. Long-term infection 

was detected in only a small number of cells within the basal 

cell layer. These cells possess characteristics and functional 

properties of stem cells, thus suggesting that stem 

cells are the targeted cell type to achieve viral persistence. 

Conclusion 

Our results permit the first time phenotypic and functional 

distinction of viable cervical stem cells, describe 

their localization within the human cervical epithelium 

and define their role in HPV-associated carcinogenesis. 

We describe the development of the first cervical organ 

culture system maintaining all cell types of squamous epithelium 

over a period of 4 weeks and permitting monitoring 

of high risk HPV infection. Data recruited from this 

model suggest that infection of stem cells within the cervical 

epithelium is indeed necessary to establish long-term 

infection. These findings represent an important step forward 

to thoroughly define the role of stem cells in HPVassociated 

carcinogenesis, not only within the cervix but 

also in other HPV-related malignancies, such as anal, vulvar 

and oropharyngeal cancers. Insights may be gained 

into the pathogenesis of cancers attributable to other oncogenic 

viruses, such as hepatocellular cancer and Burkitt 

lymphoma. Identification and characterization of tumour 

stem cells driving overall proliferation and malignant 

potential will be the key to developing effective treatments 

in the future. This project will continue until fall 

2011. A follow-on project to translate results into an in 

vivo animal model is planned. 


Dr. Astrid Baege 

Klinik für Gynäkologie 




Phone +41 (0)44 255 11 11 

astrid.baege@usz.ch 

Ballmer Peter E. | Influence of a nutritional intervention 

on clinical course and quality of life in cancer 

patients (OCS 02000-02-2007) 

Involuntary loss of body weight is common in patients 

presenting with malignant tumours. The disease itself and 

various oncological treatments may further deteriorate 

the nutritional status. A deficient nutritional status potentially 

increases the side effects of the therapy and may increase 

the complication rate and length of hospital stay 

and decrease the effect of antitumoural therapies. In a 

pilot-study with undernourished hospitalized patients we 

showed that intensive nutritional counselling increased 

energy intake and protein intake as well as quality of life. 

The present study investigated the impact of nutritional 

intervention on energy and protein intake and quality of 

life in malnourished cancer patients in the ambulatory setting. 

The primary endpoints were improvement of the energy 

and protein intake and of quality of life. 

Methods 

Undernourished outpatients with cancer were randomised 

in two groups. One group was individually counselled by a 

professional dietician, and the other group received the 

usual oncological care without specific nutritional intervention. 

Study duration was 6 months. Patients in the 

counselled group were individually counselled and supported 

during the first 3 months. Study measurements 

were carried out at baseline and after 6 weeks, 3 and 6 

months. Energy and protein intake was assessed at each 

study visit with dietary records, and quality of life was 

measured by standardized protocols (EORTC-QLQ-C30 

and a visual analogue scale concerning dietary items). 

Results and Recommendations 

The study showed that the nutritional intervention significantly 

increased energy and protein intake. In contrast to 

our pilot study with hospitalized patients, there was no 

effect on quality of life. 

We hypothesize that the nutritional intervention may 

have been too late to result in a beneficial effect of the increased 

dietary intake on quality of life in these patients 

with already advanced cancer disease and deteriorated 

nutritional status. We therefore suggest that individual 

nutritional support be initiated at an early stage of the disease 

to avoid or delay nutritional deterioration; however, 

this hypothesis needs to be proven in a new clinical trial. 


Prof. Dr. Peter E. Ballmer 

Klinik für Innere Medizin 

Departement Medizin 

Kantonsspital Winterthur 

Brauerstrasse 15 

CH-8401 Winterthur 

Phone +41 (0)52 266 23 01 

Fax +41 (0)52 266 47 06 

peter.ballmer@ksw.ch 

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126 

Benhattar Jean | Identification of biomarkers for 

early cancer detection in Barrett’s esophagus patients 

using methylation profiles and the Wnt pathway 

(OCS 01638-02-2005) 

Barrett’s oesophagus (BE) is a lesion resulting from chronic 

gastro-oesophageal reflux disease, in which the stratified 

squamous epithelium of the oesophagus is replaced by 

metaplastic columnar epithelium that predisposes to the 

development of oesophageal adenocarcinoma. Barrett’s 

oesophageal adenocarcinoma is characterized by one of 

the most rapidly increasing incidence rates of any cancer 

in the Western world. Despite advances in staging and 

treatment, this malignancy is highly lethal, with a 5-year 

survival rate of less than 10 %. Early detection represents 

one of the most promising approaches to reducing the 

growing cancer number, as already demonstrated in other 

malignancies such as cervical and breast cancer. Early detection 

research has recently been revitalized by the advent 

of novel molecular technologies that can identify 

cellular changes at the genome level. These molecular 

technologies offer many new opportunities for developing 

biomarker-based tests that could be used in addition 

to or in substitution for some of the existing screening 

tests. 

A variety of molecular genetic and epigenetic events appear 

to coincide in the progression of BE to adenocarcinoma. 

Our research activities are focused on the detection 

and the development of epigenetic biomarkers that 

can predict the likelihood of the neoplastic progression in 

Barrett’s patients. To increase knowledge on methylation 

changes, a Methylation Ligation-dependent Macroarray 

(MLM) has been generated. This array-based DNA methylation 

profiling allows the screening of 45 promoter 

genes on 20 samples at the same time. This technology 

can be used: 1) in clinical trials to identify methylation 

profiles for appropriate drug delivery; 2) to distinguish 

pathologies with or without potential progressive evolution; 

3) for metastases prognosis; and 4) for diagnosis. 

In oesophageal adenocarcinoma, aberrant methylation of 

promoter regions occurs with a high frequency not only 

in advanced cancer but also in BE. Hypermethylation of 

a subset of tumour suppressor gene promoters strongly 

predicts progression to high-grade dysplasia or cancer 

in patients with BE. On the other hand, rare occurrence of 

tumour suppressor gene hypermethylation is associated 

with a benign course in BE. 

Our research also focuses on the aberrant activation of 

the Wnt signalling pathway, which is a key feature 

of many cancers. While mutations in APC or b-catenin are 

exceptional in Barrett’s adenocarcinomas, alterations of 

upstream components, such as overexpression of Wnt2 

ligand or downregulation by promoter methylation of 

several Wnt antagonists, may play dominant roles in the 

activation of the Wnt pathway. 

Our data suggest that inhibiting the Wnt pathway could 

become a new targeted therapy for the treatment of cancers 

and could therefore be promising for the prevention 

and cure of oesophageal adenocarcinoma. Furthermore, 

methylation biomarker-based panel to predict neoplastic 

progression in BE has potential clinical value in improving 

both the efficiency of surveillance endoscopy and the 

early detection of neoplasia. 


Dr Jean Benhattar 

Institut universitaire de pathologie 

de Lausanne (IUP) 




Phone +41 (0)21 314 71 53 

Fax +41 (0)21 314 71 15 

jean.benhattar@chuv.ch 

Bertoni Francesco | Evaluation of the tyrosine 

kinase SYK as a possible therapeutic target 

in lymphomas (KLS 01835-02-2006) 

SYK is a non-receptor tyrosine kinase involved in the 

B-cell receptor (BCR) signalling pathway. When activated, 

it leads to intracellular calcium mobilization, activation of 

AKT, mitogen-activated protein kinases (MAPKs) and 

NFkB. Inhibition of SYK had been proposed as a new 

promising therapeutic approach for lymphoid neoplasms. 

In this project we evaluated the efficacy of a series of SYK 

inhibitors in lymphoma cell lines and primary cells and 

studied the pattern of SYK expression in mature B-cell 

lymphomas. 

Material and methods 

We exposed cell lines of diffuse large B-cell lymphoma 

(DLBCL), mantle cell lymphoma (MCL) and primary cells 

of a variety of lymphomas to increasing doses of different 

SYK inhibitors. SYK expression was evaluated on a series 

of 303 lymphoma biopsies by immunohistochemistry. 

Results 

We first evaluated the potentiality of SYK inhibition (Rinaldi 

et al., Hematological Oncology 2011). Based on our 

previous data on MCL cell lines (Rinaldi et al., British Journal 

of Haematology 2006), we first treated six DLBCL cell 

lines with increasing doses of the SYK inhibitor piceatannol. 

The cell line that was the most sensitive and that 

showed a clear dose response had the highest level of 

SYK, and it presented an extra copy of the locus containing 

SYK. Three of the 6 DLBCL cell lines and 4 MCL cell 

lines were then exposed to increasing doses of a potent 

SYK/ZAP70 inhibitor, NVP, for 72 h. Only the two cell 

lines expressing high levels of SYK showed an IC50 at a 

dose suggestive of a SYK-mediated cytotoxic effect. Due 

to the suggested capacity of the BCR-ABL inhibitor 

imatinib to bind SYK, MCL and DLBCL cell lines were exposed 

to the BCR-ABL inhibitors imatinib and nilotinib, 

which are already in clinical use. No cell line responded to 

doses of imatinib lower than the concentration clinically 

achievable and used for chronic myeloid leukemia and 

other sensitive neoplasms. Still, the two cell lines with

constitutively high SYK levels showed progressive inhibition 

of cell proliferation, indicating a possible dose-dependent 

cytotoxic effect. 

To obtain further data on the relevance of SYK inhibition 

in lymphoma, we treated 5 lymphoma primary cells derived 

from DLBCL and 3 from leukemic MALT lymphomas 

with increasing doses of NVP and piceatannol and with 

nilotinib at the clinically reachable dose. The data obtained 

on lymphoma primary cells confirmed the cytotoxic 

activity of tyrosine kinase inhibitors in lymphoma 

primary cells, but the heterogeneous pattern of response 

suggested that the effect could be due to inhibition of 

molecules other than SYK and contributing to the constitutive 

BCR signaling. 

Regarding protein expression in clinical specimens, four 

patterns of SYK localization were shown to have a peculiar 

distribution among different types of lymphoma and 

lymphoid tissues analyzed (Ponzoni et al., Leukemia Re- 

search 2011). SYK was statistically significantly more frequently 

detected mainly or exclusively in the cytoplasm in 

DLBCLs, splenic marginal zone lymphomas and reactive 

spleens. The kinase was statistically significantly found 

mainly or exclusively in the nucleus in MCL. 

Conclusions 

Our functional characterization of SYK in lymphoma cell 

lines and lymphoma primary cells support the design of 

prospective trials testing different molecules targeting 

SYK. Our extensive immunohistochemical characterization 

pointed towards divergent SYK localization in different 

lymphoma subtypes, suggesting different functions in 

the different subtypes. 


Dr. Francesco Bertoni 

Laboratorio di oncologia sperimentale 




Phone +41 (0)91 8200 367 

Fax +41 91 8200 397 

frbertoni@mac.com

128 

Bertoni Francesco | Genome-wide DNA profiling 

as outcome predictor in diffuse large B-cell 

lymphoma (OCS-1939-8-2006) 

Diffuse large B-cell lymphoma (DLBCL) represents the 

most common non-Hodgkin’s lymphoma in Western 

countries, and it is a very heterogeneous group of disorders. 

With current therapies, at least 40 % of the patients 

are not cured. The aims of the study were to identify 

genomic lesions predicting response to the current standard 

therapy, R-CHOP, to characterize DLBCL subgroups 

and to identify new DLBCL genes. 


The study was performed on 166 DLBCL clinical samples, 

thanks to an international network of collaborating investigators. 

Genomic profiles were obtained using the Affymetrix 

Human Mapping 250k Arrays, and gene expression 

profiling was done using Affymetrix U133 plus 2.0. 

Results 

Genomic losses affecting the short arm of chromosome 8 

appeared associated with a poor outcome in patients with 

DLBCL treated with R-CHOP (Scandurra, Mian, et al., 

British Journal of Haematology 2010). The role of del(8p) 

is under evaluation by fluorescence in situ hybridization 

(FISH) analysis in a large series of patients treated with R- 

CHOP. 

By comparing the genomic profiles of DLBCL in immunocompetent 

individuals versus genomic profiles of HIV-related 

DLBCL (HIV-DLBCL) and post-transplant DLBCL 

(PT-DLBCL), we identified a series of previously unknown 

features of immunodeficiency-related DLBCL (Rinaldi et 

al., British Journal of Haematology 2010; Capello et al., 

British Journal of Haematology 2010). 

We then looked at cases of DLBCL with concordant or discordant 

bone marrow involvement, an important prognostic 

factor for DLBCL patients (Chigrinova et al, Hematological 

Oncology 2010). The main finding was that 

cases with gains at chromosome 7/7q, a common DLBCL 

lesion, never had bone marrow involvement. We therefore 

studied DLBCL cases with these lesions by combining 

genomic profiling, gene expression profiling and miRNA 

profiling (Chigrinova et al., British Journal of Haematology 

2011). Gains affecting chromosome 7, mostly of the 

whole chromosome, do not directly alter gene expression, 

but they appear to deregulate a series of miRNA mapped 

on chromosome 7. 

Finally, to identify new genes involved in the pathogenesis 

of DLBCL, by combining our array CGH with a mutational 

screening of NFkB genes performed by Laura Pasqualucci’s 

group in New York, the tumour suppressor gene 

TNFAIP3/A20 was identified as frequently inactivated in 

non-germinal centre DLBCL (Compagno et al., Nature 

2009). 

Conclusions 

We identified lesions predicting the outcome in patients 

treated with the current standard therapy, and once this is 

validated in an external series, it might help to provide a 

patient-tailored therapeutic plan. Also, we characterized 

different DLBCL subgroups and genomic lesions. Additional 

work is still ongoing on both the characterization of 

new DLBCL genes and DLBCL subgroups and the identification 

of outcome/response predictors. 







Phone +41 (0)91 820 03 67 

Fax +41 (0)91 820 03 97 

frbertoni@mac.com 

Bertoni Francesco | Extranodal, nodal and splenic 

marginal zone B-cell lymphomas: How much are they 

related to each other? (OCS 02034-02-2007) 

Marginal zone B-cell lymphomas (MZL) have been divided 

into 3 distinct subtypes (extranodal MZL of MALT 

type, nodal MZL, splenic MZL), but the relationship between 

the subtypes has remained unclear. We performed 

a comprehensive analysis of genomic DNA copy number 

changes in a very large series of MZL cases with the main 

aims of addressing this issue of the subtypes and of identifying 

new genes involved in MZL pathogenesis. 


The study was performed on 218 MZL clinical samples (25 

nodal, 57 MALT, 134 splenic and two not better specified 

MZL) thanks to an international network of collaborating 

investigators. Genomic profiles were obtained using Affymetrix 

Human Mapping 250k Arrays for all cases; gene 

expression profiling was available for a subset of the samples. 

Results 

Regarding the differences among the subtypes (Rinaldi et 

al., Blood 2011), MALT lymphoma presented gains at 3p, 

6p, 18p and del(6q23) significantly more frequently, 

whereas splenic MZL had del(7q31) and del(8p). Nodal 

MZL did not show statistically significant differences 

when compared with MALT lymphoma but lacked the 

splenic MZL-related 7q losses. Gains of 3q and 18q were 

common to all three subtypes. Del(8p) was often present 

together with del(17p). Whereas del(17p) did not determine 

a worse outcome and del(8p) was only of borderline 

significance, the presence of both deletions had a highly 

significant negative impact on the outcome of splenic 

MZL.

Regarding new genes, in collaboration with Riccardo 

Dalla Favera’s group in New York we identified the tumour 

suppressor gene TNFAIP3/A20, an inhibitor of the NFkB 

pathway, as being frequently deleted and mutated, especially 

in MALT lymphomas (Novak et al., Blood 2009). 

We also studied the relationship between immunogenetics 

and genomic lesions in splenic MZL (Rinaldi et al., British 

Journal of Haematology 2010). Splenic MZL express 

mutated (M-) or unmutated (U-) immunoglobulin heavy 

chain (IGHV) genes. We combined SNP arrays and IGHV 

sequencing in 83 cases. Clinical features and outcome 

were similar between U- and M-IGHV cases. Recurrent lesions 

frequency was higher in U-IGHV cases, including 

poor prognosticators. Frequencies differed among cases 

bearing individual VH genes or lambda light chains. We 

also studied the role of antigen stimulation in splenic 

MZL (Zibellini et al., Haematologica 2010). The occurrence 

of stereotyped B-cell receptors was investigated in 

133 SMZL (26 HCV + ) and compared with 4,414 HCDR3 

sequences from public databases. Sixteen SMZL (12 %) 

showed stereotyped BCR; 8 % of SMZL sequences 

retrieved from public databases also belonged to stereotyped 

HCDR3 subsets. Three categories of subsets were 

identified: 1) “SMZL-specific subsets”; 2) “Non-Hodgkin’s 

lymphoma-like subsets”; and 3) “CLL-like subsets”. 

Immunoglobulin 3D modelling of 3 subsets revealed similarities 

in antigen binding regions not limited to HCDR3. 

Conclusions 

We identified the different patterns of genomic aberrations 

in MZLs, thus aiding differential diagnosis. We identified 

a lesion predicting a poor outcome in splenic MZLs, 

which could be useful to better manage patients. Also, we 

identified a new gene strengthening the NFkB pathway as 

an important therapeutic target for these patients. Splenic 

MZLs present distinctive features in terms of immunogenetics. 

Additional studies are ongoing, and data will be reported 

in the future. 







Phone +41 (0)91 820 03 67 

Fax +41 (0)91 820 03 97 


Bohlius Julia | Individual patient data meta-analysis 

on the effects of erythropoiesis-stimulating agents in 

cancer patients (OCS 02146-10-2007) 

Patients with cancer have an increased risk for anaemia, 

which may negatively impact their quality of life (QoL). 

Erythropoiesis-stimulating agents (ESAs) reduce anaemia 

in cancer patients and may improve QoL, but there are 

concerns that ESAs might increase mortality. 

Study aim 

We collected patient data from randomised controlled trials 

to evaluate the effect of ESA on mortality and survival 

in patients with cancer and to identify subgroups of patients 

that may benefit from ESAs. 

Methods 

We identified randomised controlled trials comparing 

epoetin alfa, epoetin beta or darbepoetin alfa plus red 

blood cell transfusions versus transfusion alone, for 

prophylaxis or therapy of anaemia in patients with cancer 

receiving chemotherapy, radiotherapy or no anticancer 

therapy. Study investigators from eligible trials were invited 

to collaborate and submit raw data of their studies. 

Main analyses were defined in a peer-reviewed protocol 

and a statistical analysis plan. A steering committee consisting 

of clinicians and methodologists reviewed results 

and agreed on their interpretation. The raw patient-level 

data were meta-analyzed by independent statisticians at 

two academic departments, using fixed-effects and random-effects 

meta-analysis. Primary endpoints were onstudy 

mortality, defined as duration of ESA study plus 1 

month follow-up, and overall survival, defined as the 

longest follow-up available. Analyses were conducted 

separately for all patients with cancer regardless of anticancer 

therapy and for patients receiving chemotherapy. 

Tests for interactions were used to identify differences in 

effects of ESAs on mortality and survival for pre-specified 

subgroups. 

Findings 

A total of 13,933 patients with cancer from 53 trials were 

analyzed: 10,411 patients were scheduled to receive 

chemotherapy, 799 radiotherapy, and 737 radiotherapy 

combined with chemotherapy. 1,690 patients received no 

anticancer treatment during the ESA study, and 266 received 

other treatment modalities. 1,530 patients died on 

study and 4,993 overall. Including all patients with cancer 

regardless of anticancer therapy, ESAs increased on-study 

mortality (hazard ratio [HR] 1.17; 95 % confidence interval 

[CI] 1.06–1.30) and worsened overall survival (HR 

1.06; 95 % CI 1.00–1.12), with little heterogeneity between 

trials (I 2 0 %, p=0.87 and I 2 7.1 %, p=0.33, respectively). 

Restricting the analysis to patients receiving chemotherapy, 

the HR for on-study mortality was 1.10 (95 % 

CI 0.98–1.24) and 1.04 (95 % CI 0.97–1.11) for overall 

survival. There was little evidence of a difference between 

trials of patients receiving different cancer treatments (p 

for interaction=0.42). 

129

130 

Interpretation 

ESA treatment in patients with cancer increased on-study 

mortality and worsened overall survival. For patients 

undergoing chemotherapy, the increase was less pronounced, 

but an adverse effect could not be excluded. 


Dr. Julia Bohlius 

Forschungsgruppe Krebs 

Institut für Sozial- und Präventivmedizin (ISPM) 


Finkenhubelweg 11 

CH-3012 Bern 

Phone +41 (0)31 631 35 10 

jbohlius@ispm.unibe.ch 

Carbone Giuseppina | Functional and clinical implications 

of deregulated expression of ETS transcription 

factors in prostate cancer (OCS 01913-08-2006) 

Cancer of the prostate is a leading cause of cancer death 

in Western countries. There is great need to understand 

the factors governing disease progression and identify 

new therapeutic strategies. Transcription factors of the 

ETS family have emerged as important elements in the 

pathogenesis of prostate cancer. About half of prostate 

cancers harbour chromosomal translocations involving 

ETS genes. ETS factors act as nodal points of various signalling 

pathways controlling cell proliferation, differentiation 

and survival. In many tissues, ETS factors constitute 

a complex network of transcriptional regulators with biological 

responses depending on the balance between factors 

exhibiting similar or opposite functions. Our hypothesis 

is that an endogenous network of ETS factors controls 

to a significant extent the differentiation status of prostate 

epithelial cells. An altered balance between these ETS 

factors, which may result from environmental, genetic or 

epigenetic events, could promote cell transformation and 

drive tumour progression. 

Objectives 

The overall goal of this project was to understand the 

functional and clinical implication of ETS transcription 

factors in prostate cancer initiation and progression. 

Methods 

To reach our goals we applied an integrative approach 

that combines translational and bioinformatic studies in 

prostate cancer tumours with experiments in vitro in 

transgenic cell lines and in vivo in mouse models. We performed 

gain-of-function and loss-of-function studies using 

transgenic cell lines. Cell phenotypes were evaluated 

with a variety of cellular assays that measure growth, cell 

cycle, apoptosis, cell migration, invasion and stem cell-like 

properties. Biochemical assays such as chromatin immunoprecipitation 

were used to evaluate direct promoter occupancy 

by ETS factors and histone modifications in cells 

and also in prostate cancer specimens. To define the ETS 

transcriptional network, we applied genomic tools such as 

microarray data from prostate cancer patients to perform 

differential gene expression and correlation analysis. 

Results 

The results of our studies substantially advanced our understanding 

of the functional and clinical role of ETS factors 

in prostate cancer. We showed that additional ETS 

factors, besides the known translocated ETS genes, are 

frequently deregulated in prostate tumours and may 

contribute significantly to prostate tumourigenesis. We 

showed for the first time that the epithelial-specific ETS 

factor ESE3 is frequently underexpressed in prostate tumours 

and, in experimental models, acts as tumour suppressor 

gene. Further, our studies demonstrated for the 

first time the activation of ESE1 in prostate tumours. 

Based on the ETS alterations identified by array and qRT- 

PCR data, we divided tumours in subgroups with predominant 

deregulation of either ERG, ESE1 or ESE3. A fourth 

group included tumours that had normal-like levels of ETS 

genes (NoETS). 

Additional bioinformatic analyses were done to determine 

whether distinct transcriptional profiles were associated 

with the prostate cancer subgroups identified on the basis 

of ETS expression patterns using differential gene expression 

analysis. ERG and ESE3 tumours had robust signatures 

with the largest number of differentially expressed 

genes. 

This analysis allowed us to uncover the transcriptional 

network of selected ETS factors in prostate tumours. Further, 

by integrating genomic data and functional assays 

in cells, we established a direct link between aberrantly 

expressed ETS factors and epigenetic reprogramming of 

the prostate cancer transcriptome. An important finding 

of our study was the demonstration that the Polycomb 

group protein EZH2 is a direct target of oncogenic and tumour 

suppressor ETS factors, like ERG and ESE3. Further, 

we showed that EZH2 is a key player in transcriptional silencing 

of the Nkx3.1 tumour suppressor gene. This may 

represent a general mechanism linking aberrantly expressed 

ETS with deregulation of epigenetic pathways and 

reprogramming of prostate epithelial cell transcriptome 

during tumourigenesis. 

Clinical relevance for patients 

The presence of prostate cancer subgroups with distinct 

ETS expression patterns and biological features may have 

important implications and suggests that assessment of 

ETS expression levels might be useful to distinguish tumours 

with different clinical outcome. Further, the link 

between altered ETS factors activity and EZH2 mediated 

epigenetic gene silencing may suggest selective therapeutic 

strategies for prostate cancer. 

Project Coordinator 

Dr. Giuseppina Carbone 





Phone +41 (0)91 820 03 66 

Fax +41 (0)91 820 03 97 

pina.carbone@irb.unisi.ch

De Libero Gennaro | Lipid-specific T cells against 

leukaemic blasts (KLS 02211-02-2008) 

We identified highly polar lipid fractions derived from 

THP1 AML and C1R LCL cell lines able to stimulate two 

different CD1c-restricted T cell clones. These fractions 

were obtained using two different procedures from total 

cellular lipids, extracted according to the Folch method. 

LC-MS-MS analysis of the fractions confirmed the presence 

of several ion masses in the biologically active ones, 

and some of these masses were shared between the stimulatory 

fractions, independently of the procedure used. 

However, the low yield and purity of active lipids achieved 

using both methods did not allow us to identify the structures 

of these molecules. Therefore, we developed a new 

extraction procedure and established a new HPLC purification 

strategy. Using this novel method, we divided total 

lipids into 10 different fractions according to their polarity 

and charges. Only one fraction strongly stimulated the selected 

T cell clones with high efficacy and potency. The 

antigenic capacity of this fraction was further confirmed 

by CD1c plate-bound assays, in which soluble recombinant 

CD1c molecules were attached to plastic wells, 

loaded with the fraction and then used to stimulate T cell 

clones. The high and specific T cell clone activation induced 

by fraction-loaded CD1c complexes clearly suggested 

that contained lipids behave as minimal antigens 

and do not require processing by APC to become immunogenic. 

The LC-MS-MS profile of the stimulatory fraction revealed 

the presence of few molecular species. In order to 

separate these molecules and to isolate the active ones, 

we further sub-fractionated the T cell activating fraction 

by HPLC and LC-MS-MS. Three out of 60 sub-fractions 

showed potent stimulatory activity, and in each of them 

only one predominant molecular species was present, as 

indicated by the MS-MS analysis performed in real time 

during the collection. 

A further LC-MS-MS analysis, performed with two different 

mass spectrometers (ESI ion trap and triple quadrupole) 

in both positive and negative ionisation modes, indicated 

that two of these molecules are characterized by 

a fragmentation pattern in part similar to that of lysophosphatidic 

acid. To confirm this finding and to assign exact 

molecular mass to these compounds, we analyzed the active 

sub-fractions with an Orbitrap mass spectrometer 

equipped with a nanospray system. This allowed us to 

confirm the structure of the previously identified molecules 

and to determine length and features of the single 

acyl chain present in the two active molecules. In a new 

series of studies we performed nuclear magnetic resonance 

(NMR) analysis of the antigenic lipid compounds 

after extensive purification. NMR confirmed the proposed 

structure and provided complementary information on 

the nature of lipids. 

All together, these findings show that a unique lipid with 

a structure never described before accumulates in leukaemic 

cells. This novel lipid family seems to be very abundant 

in rapidly proliferating cells. It will be important to 

investigate the metabolic pathways responsible for the 

synthesis of these lipids and how they are regulated in leukaemic 

cells. 


Prof. Dr. Gennaro De Libero 

Experimentelle Immunologie 




CH-4031 Basel 

Phone +41 (0)61 265 23 65 

gennaro.delibero@unibas.ch 

Dirnhofer Stephan | Inducing cell death in apoptosisresistant 

hematological tumors: Impact on diagnosis 

and therapeutic intervention (OCS 01792-10-2005) 

Study outline 

Patients with DLBCL (diffuse large cell B cell lymphoma) 

and AML (acute myeloid leukaemia) have been evaluated 

for potential therapeutic markers regarding CD44 and its 

interaction partners. DLBCL and AML belong to the most 

abundant lymphomas and leukaemias with a wide-ranging 

prognosis. A long-term goal is to develop tailor-made 

therapies for defined groups of patients to allow for more 

potent and specific treatment. 

Study design 

Our main objective was to find out how the resistance 

against apoptosis of malignant hemopoietic cells (from 

DLBCL and AML patients) can be favourably affected, i.e. 

abolished. 

Study results 

We showed that co-expression of CD44 variant isoforms 

(all isoforms analyzed) and CD168 (RHAMM, receptor 

for hyaluronan mediated motility) identifies a subgroup of 

patients with DLBCL who have a very adverse prognosis. 

This prognosis was independent of the international prognostic 

index (IPI). Expression of CD168 RHAMM in AML 

patients turned out to be a central prognostic indicator. 

When CD168 is expressed in association with CD44, active 

caspase-3 (as indicator for spontaneous apoptosis) 

and the oncogenic transcriptions factors STAT-3 and -5 a 

very adverse prognosis is implied for these patients. 

Benefit for the patient 

A therapeutic application of antibodies against surface 

molecules such as CD44 and CD168 could exert a blocking 

effect on the resistance against apoptosis. The group 

of patients in which CD44 and CD168 are co-expressed 

could have better survival odds with accordingly adjusted 

therapies. When patients with AML receive stem cell therapies 

the beneficial graft vs. leukaemia (GvL) reaction indicates 

the importance of leukaemia associated antigens 

(LAA). In search for potent LAA in patients with AML, 

CD168 is an auspicious candidate for specific vaccination. 

131

132 

Our results could pave the way for further prospective 

analyses in larger cohorts of patients and allow for the development 

of innovative and target-oriented therapies. 


Prof. Dr. Stephan Dirnhofer 

Institut für Pathologie 


Schönbeinstrasse 40 

CH-4003 Basel 

Phone +41 (061 265 27 89 

Fax +41 (0)61 265 31 94 

sdirnhofer@uhbs.ch 

Doucey Marie-Agnès | Functional and biochemical 

characterization of human monocyte-like circulating 

cells in breast cancer patients: Relevance to tumor 

growth and angiogenesis (OCS 02069-04-2007) 

Tumour angiogenesis is a prominent mechanism driving 

tumour development and progression, and drugs targeting 

VEGF (vascular endothelial growth factor) and its receptors 

have been approved for the treatment of human 

cancer. However, primary and acquired resistance to 

VEGF pathway blockade represents a critical obstacle to 

further improvement of anti-angiogenic therapy and calls 

for additional therapeutic targets. Myeloid cells are such 

candidates. Indeed, tumour-mediated recruitment of myeloid 

cells with angiogenesis and tumour-promoting activity 

is one of the most remarkable observations made in 

experimental oncology in recent years. The presence of 

tumour-associated macrophages was shown to be associated 

with unfavourable prognosis in cancer patients and 

correlated with increased microvessel density in a variety 

of human solid tumours. More recently, Tie-2-expressing 

monocytes (TEM) were identified in humans and mice as 

a functionally distinct myeloid-derived cell population 

with potent proangiogenic activity. In experimental mouse 

models, TEM ablation fully suppressed angiogenesis, thus 

making them attractive targets for anti-angiogenic therapies. 

However, to date, the molecular basis of TEM proangiogenic 

and protumoural activities is largely unknown. 

Thus, the goal of this study was to unravel tumour specific 

signals and associated TEM pathways supporting TEM 

functions in early breast cancer. This approach represents 

the first step to TEM targeting in anti-cancer therapies. 

Methods and findings 

We examined TEM in peripheral blood and tumours of patients 

with early breast cancer. We reported that tumour 

TEM specifically triggered the initial phase of breast tumour 

vascularization, whereas other myeloid cell populations 

are associated with sustained breast tumour angiogenesis. 

Using mouse corneal vascularization assay, we 

reported that tumour TEM consistently displayed a higher 

proangiogenic activity relative to their blood counterparts, 

suggesting that the tumour microenvironment 

shapes TEM phenotype and functions. Indeed, we showed 

that the expression levels of Tie-2, VEGFR1 and TGFR1 at 

the surface of patient TEM represent a proangiogenic 

phenotypical signature specifically induced by the tumour 

microenvironment. We used TEM differentiated in vitro 

from CD34 + haematopoietic precursors to identify the 

tumour signals controlling TEM phenotypical signature 

and proangiogenic activity. Examination of 12 combinations 

of angiogenic and inflammatory ligands revealed 

that TNF-a, PlGF and Ang-2 synergistically promote TEM 

proangiogenic function. The synergistic effect of these 

signals relies on cross-talks between TNFR1, VEGFR1 and 

Tie-2 pathways. Tie-2 and VEGFR1 pathways cooperate 

and compensate each other to control TEM proangiogenic 

function, whereas TGFb impaired it. Further, we validated 

these effects in patient TEM and reported that blood- 

circulating patient TEM treated with synergistic ligands 

increased their proangiogenic activity and shifted their 

paracrine profile toward angiogenesis. Importantly, 

guided by the understanding of this pathway interplay, we 

demonstrated that the combination of TGFb with a Tie-2 

inhibitor abrogates the proangiogenic activity of TEM- 

derived from patient tumours. 

Conclusions and patient benefit 

This study highlighted the contribution of TNF-a, PlGF 

and Ang-2 as specific tumour microenvironmental signals 

in TEM proangiogenic and protumoural functions and 

identified TGFb/Tie-2 axis as a potential therapeutic target 

to abrogate the proangiogenic function of TEM at 

breast tumour sites. These results open up new opportunities 

for anti-angiogenic cancer therapies by targeting 

TEM and suggest that these cells may contribute to resistance 

to VEGF pathway blockade. 


Dr Marie-Agnès Doucey 



Le Génopode 

CH-1015 Lausanne 15 

Phone +41 (0)21 692 39 47 

marie-agnes.doucey@unil.ch 

Dubey Raghvendra K. | Pathophysiological role 

of estrogen metabolism in breast cancer 

(OCS 01551-08-2004) 

Breast cancer is one of the leading causes of premature 

death in women worldwide. Although exposure to increased 

oestrogen is an established risk factor in both 

young women and postmenopausal taking hormone therapy 

(HT), the mechanisms involved (cancer progression / 

metastasis) are unclear. Oestrogens not only have a physiological 

and biological role but also are implicated in the 

development of breast cancer by simultaneously stimulating 

abnormal cell proliferation and gene expression potentially 

via the oestrogen receptor (ER). The fact that ERs 

are expressed in breasts of most women but not all of 

them get oestrogen-induced cancer suggests that an 

alternative pathway that counteracts the carcinogenic 

effects of oestrogens may be active, and lack of this pathway 

may make women more susceptible to oestrogen induced 

breast cancer. In this context, endogenous estradiol 

is metabolized to methoxyestradiol (2-ME), a potent anticarcinogenic 

and antimitogenic agent. Since breast cells 

express enzymes that convert estradiol to 2-ME, this may 

serve as a pathway to counteract ER-mediated proliferative 

actions of estradiol. Hence, using molecular and 

pharmacological approaches, the objective of this project

was to explore whether sequential conversion of 17b- 

estradiol to 2-ME is an intrinsic growth inhibitory pathway 

that counteracts/suppresses the ER-dependent proliferative 

actions of 17b-estradiol. 

Results 

Growth studies using ER-positive breast cancer cells revealed 

that estradiol has a biphasic effect on their growth, 

with proliferative and inhibitory effects at low (physiologic) 

and high concentrations respectively. Importantly, 

studies with ER-negative cells and ER antagonists show 

that the proliferative phase is ER-dependent, whereas the 

inhibitory effects of estradiol are mediated via conversion 

of estradiol to 2ME. Molecular and gene-silencing studies 

provide evidence that the inhibitory effects of estradiol 

are mediated by 2-ME via upregulation of p21, a negative 

regulator of cell cycle. 

Potential Implications 

Because 2-ME, an endogenous non-estrogenic oestrogen 

metabolite, counteracts/suppresses the proliferative/carcinogenic 

actions of estradiol, this non-estrogenic and 

non-carcinogenic oestrogen metabolite could be employed 

for the prevention of breast cancer. Metabolic disorders 

and inter-individual differences in estradiol metabolism 

might affect the balance between the proliferative 

and anti-proliferative pathways and define the potential 

risk for an individual to develop breast cancer. Moreover, 

assay of 2-methoxyestradiol or the key enzymes responsible 

for 2-ME formation, i. e. catechol-O-methyltransferase, 

in biopsy tissues may serve as a diagnostic marker 

in women with potential risk of oestrogen associated 

breast cancer. Finally, in postmenopausal women using 

hormone replacement therapy, 2-ME could be employed 

for prevention of cardiovascular disease without increasing 

the risk of cancer. Finally, the presence of the negative 

regulatory metabolic pathway may also help explain the 

protective effects of oestrogens and the deleterious effects 

of oestrogens plus medroxyprogesterone on breast 

cancer in the recently concluded Women’s Health Initiative 

(WHI) study, as medroxyprogesterone inhibits the 

formation of 2-hydroxyestradiol, the precursor of 2-methoxyestradiol. 


Prof. Dr. Raghvendra K. Dubey 

Klinik für Reproduktions-Endokrinologie 




Phone +41 (0)44 255 86 08 

raghvendra.dubey@usz.ch 

Frattini Milo | Characterization of EGFR deregulation 

and EGFR downstream cascade in colorectal cancer 

patients, and relationship to new targeted therapies 

(OCS 01921-08-2006) 

Colorectal cancer (CRC) is the second leading cause of 

cancer-related death in Western countries. Newer therapeutic 

options for treating metastatic CRC (mCRC) include 

targeted biological therapies, with those against epidermal 

growth factor receptor (EGFR) showing promising 

data. Cetuximab and panitumumab are two monoclonal 

antibodies that block EGFR and, therefore, block its activation 

and the transduction cascade of mitogen signals. 

EGFR-targeted therapies have significantly increased the 

follow-up of affected patients but are effective only in 10- 

20 % of cases. In addition, they are quite toxic and expensive. 

Objective 

As no molecular markers able to predict the efficacy of 

EGFR-targeted therapies were available at the time, the 

overall goal of this research project was to better understand 

the significance of deregulation of EGFR (the target) 

and/or proteins of its downstream signalling cascade 

(PTEN, KRAS, BRAF, PIK3CA), on EGFR-targeted therapies 

response in CRC patients. 

Methods and procedure 

A series of patients with mCRC were identified in Ticino 

and then treated with cetuximab or panitumumab. Patients’ 

tissue specimens were evaluated for EGFR gene 

status by fluorescence in situ hybridization, for PTEN protein 

expression by immunohistochemistry and for KRAS, 

BRAF and PIK3CA mutational status by direct sequencing. 

A series of 44 patients with primary CRC and paired distant 

metastatic lesion were investigated with the same 

markers. 

Results 

In our cohort, we found that a normal gene status of 

EGFR, the presence of KRAS mutations, BRAF mutations, 

PIK3CA mutations and the PTEN loss of expression all represent 

independent predictive markers of resistance to 

EGFR-targeted therapies, because they occurred only in 

patients who experienced no response to these drugs. By 

comparing the molecular profile of primary tumour with 

that of the metastatic lesion, we observed some differences, 

especially at EGFR gene status level, thus indicating 

that it should be better to perform analyses of metastatic 

specimens than analyses of primary tumours. 

Recommendations and patient benefit 

Our results were subsequently confirmed by other studies 

and therefore concurred with the definition of KRAS as a 

molecular marker that has to be tested before considering 

the use of cetuximab or panitumumab as a treatment. The 

international agencies FDA and EMA approved KRAS 

testing as a prerequisite before drug administration. The 

other markers, due to either low frequency of alteration or 

to lack of standardized methodologies, are currently on 

stand-by. Therefore, at least 30 % of patients (characterized 

by KRAS mutation) are not treated with drugs and 

can be addressed with new combinatorial treatments or 

133

134 

new drugs that specifically target KRAS and that are now 

entering clinical trials. As a corollary, KRAS testing decreases 

the cost of the management of these patients. 


Dr. Milo Frattini 

Laboratorio di diagnostica molecolare 

Istituto cantonale di patologia (ICP) 

Via in selva 24 

CH-6600 Locarno 

Phone +41 (0)91 816 08 05 

Fax +41 (0)91 816 07 19 

milo.frattini@ti.ch 

Gautschi Oliver | Regulation of lD1 expression by Src 

in cancer: Clinical implications (KLS 02164-02-2008) 

Invasion and metastasis are important hallmarks of cancer, 

but only few drugs are currently available that target 

these mechanisms in patients. Most anticancer drugs target 

cell proliferation and survival. Members of the Src 

family of non-receptor tyrosine kinases are part of the 

focal adhesion complex, which mediates migration and 

invasion in normal and cancer cells. Src is frequently activated 

in human cancer by growth factor and cytokine receptors. 

Therefore, Src is a promising cancer drug target, 

and several Src kinase inhibitors are currently in clinical 

trials. Although preliminary results indicate that these 

agents have clinical activity against solid tumours including 

lung cancer, the activity appears to be limited to a 

group of patients. As for many other molecular targeted 

agents, predictive factors for Src inhibitors remain to be 

identified. 

The aim of our project is to better understand the Src signalling 

pathway in human lung cancer, which may lead to 

a rational development of Src inhibitors in oncology. Using 

pharmacological small-molecule Src kinase inhibitors, 

viral vectors carrying Src mutant constructs and gene expression 

microarrays, we previously identified inhibitor of 

differentiation 1 (ID1) as a new and functionally relevant 

target gene of Src kinase in human lung cancer cells. The 

ID1 gene mediates stem cell function and is a potent regulator 

of cancer cell invasion. More recently, using an established 

lung cancer biobank, we demonstrated that Src 

and ID1 are frequently and strongly co-expressed in primary 

human lung cancer, compared with matched lung 

tissue. ID1 expression correlated with poor tumour differentiation 

and with expression of matrix metalloproteinase 

9 (MMP9). Interestingly, ID1 was also overexpressed in 

pre-invasive lung lesions. In lung cancer cell lines, forced 

expression of ID1 enhanced Matrigel invasion and caused 

resistance to Src kinase inhibitors, which was supported 

by preliminary animal experiments. Using Src inhibitors 

and microarrays, we identified two microRNAs that target 

ID1 expression. Manipulation of these microRNAs in lung 

cancer cell lines again changed the effect of Src kinase inhibitors 

on migration and invasion. Tumour microRNA expression 

in patient samples inversely correlated with ID1 

expression and with patient survival. These results suggest 

that ID1 and microRNAs are dysregulated in lung 

cancer and can modulate and predict the activity of Src kinase 

inhibitors. 

As a consequence, ongoing work includes further experiments 

to confirm the predictive value of ID1 and microR- 

NAs for Src inhibitors in preclinical models of metastatic 

lung cancer. Further efforts are focused on the pharmacological 

targeting of microRNAs to develop rational drug 

combinations with Src inhibitors and other targeted agents. 


Dr. Oliver Gautschi 



Inselspital 


CH-3010 Bern 

Phone +41 (0)31 632 25 18 

Fax +41 (0)31 632 09 46 

oliver.gautschi@onkologie.ch 

Heim Markus Hermann | Hepatocarcinogenesis 

in chronic hepatitis C (OCS 02192-02-2008) 

Background 

Chronic hepatitis C (CHC) is a major cause of liver disease 

worldwide and a risk factor for cirrhosis and hepatocellular 

carcinoma (HCC). Regardless of its aetiology, cirrhosis 

is a major clinical risk factor for HCC, and indeed, hepatitis 

C virus (HCV) associated HCC generally develops in 

patients with cirrhosis. There is also evidence for HCV 

specific tumourigenic pathways, mainly involving HCV 

core and NS5A proteins. However, the molecular pathways 

responsible for HCV induced hepatocarcinogenesis 

have not yet been characterized. A potential tumourigenic 

pathway could involve protein phosphatase 2A (PP2A) 

and protein arginine methyltransferase 1 (PRMT1), since 

both enzymes are dysregulated in chronic hepatitis C and 

both enzymes have been involved in chromatin remodelling 

and DNA damage repair. 

Aim 

The aim of the studies was to elucidate the role of PP2A 

overexpression and of PRMT1 inhibition for carcinogenesis. 

Methods 

We used cell lines that allow the inducible expression of 

hepatitis C virus proteins (UHCV57.3) and of the catalytic 

subunit of PP2A (UPP2A-C8) as well as Huh7.5 cells 

infected with recombinant cell culture-derived HCV 

(HCVcc) to study epigenetic histone modifications and 

DNA damage repair. We also investigated if the methyl 

group donor S-adenosyl-L-methionine (SAMe) could reverse 

the HCV induced changes. 

Results 

The induction of viral proteins, the overexpression of 

PP2Ac or the infection of Huh7.5 cells with HCVcc resulted 

in an inhibition of histone H4 methylation/acetylation 

and histone H2AX phosphorylation in a significantly 

changed expression of genes important for hepatocarcinogenesis 

and inhibited DNA damage repair. These 

changes were partially reversed by the treatment of cells 

with the methyl-group donor S-adenosyl-L-methionine 

(SAMe).

Conclusion 

The correction of defective histone modifications by Sadenosyl-L-methionine 

makes this drug a candidate for 

chemo-preventive therapies in patients with chronic hepatitis 

C who are at risk for developing hepatocellular carcinoma. 






CH-4031 Basel 

Phone +41 (0)61 265 51 74 

markus.heim@unibas.ch 

Heinzelmann-Schwarz Viola | Detection of anti-glycan 

autoantibodies as biomarkers of high stage serous 

ovarian cancer; acronym: GOS-study 

(OCS 02115-08-2007) 

Serous ovarian cancer (SOC) is the most common subtype 

of ovarian cancers in the Western world, contributing to 

its high overall mortality rate. It is known that altered glycosylation 

of cell-surface proteins and lipids as well as 

extracellular proteins are associated with transformation 

into a cancer, producing specific tumour-associated antigens. 

Utilizing a printed glycan array (PGA), we aimed to 

identify abnormal patterns in serum samples of healthy 

controls and patients with SOC in order to develop a new 

generation of tumour markers for the early detection of 

ovarian cancer. 

Serum samples were collected from healthy control patients 

with known negative intra-operative findings 

(n=26) and patients with advanced SOC (n=16) at University 

Hospital Zurich and Limmattal Hospital following 

ethical approval. The printed glycan array incorporates 

211 carbohydrate structures, which are printed on glass

136 

slides in two different concentrations. After incubation of 

samples, bound antibodies were detected via a fluorescence 

signal. Data were preprocessed and statistically analyzed. 

Using this array technology, we were able to identify a 

panel of blood antibodies with different levels in healthy 

controls compared to SOC. Two antibodies had an identical 

core structure, which had significantly lower antibody 

levels in patients with SOC. The combination of five antibodies 

reached significance for the detection of SOC with 

an excellent discrimination capability. 

Our data indicate that using printed glycan array technology 

we are able to recognize the transformation of a cancer 

via its abnormal carbohydrate binding, hereby measuring 

an individual person’s immune response. With this 

technology we are able to define an individual profile 

for patients with SOC. Further experiments are ongoing 

to validate these results in a double-blind manner for a 

bigger independent patient cohort. 


Dr. Viola Heinzelmann-Schwarz 

Translational Research Group 

Klinik für Gynäkologie 

Medizinbereich Frau-Kind 




Phone +41 (0)44 255 5374 

Fax +41 (0)44 255 4553 

viola.heinzelmann@usz.ch 

Herrmann Richard | The SAKK Initiative for regional 

hospitals (KLS 02067-04-2007) 

The SAKK initiative for regional hospitals aimed to provide 

strategic, operational and financial support to middlesized 

regional hospitals to give patients with cancer living 

in peripheral areas the opportunity to be treated within a 

clinical trial. 

The Swiss Group for Clinical Cancer Research (SAKK) has 

conducted clinical trials in oncology since 1965. Today, 

thanks to medical progress in general and clinical research 

in particular, many cancer types are detected at early 

stages and will be successfully cured. Hence, the number 

of patients with cancer requiring therapeutic intervention 

has increased rapidly. As a consequence, most hospitals 

have expanded their infrastructure and personnel qualifications 

to ensure adequate treatment of patients with 

cancer. But not all hospitals offer clinical trials, since clinical 

research is very expensive and increasing administrative 

and regulatory requirements impede the conduct of 

clinical trials. In Switzerland research-related structures in 

the clinical setting exist mainly at the university hospitals 

and the larger cantonal hospitals, whereas regional hospitals 

are mostly oriented towards service provision and not 

research. In general, patients with early stage cancer are 

treated at regional hospitals, whereas patients with an ad- 

vanced stage or rare disease that requires intensive treatment 

are commonly treated at a university hospital or large 

cantonal hospital, where the patients also have access to 

clinical trials. The risk of this practice is that clinical trial results 

may not present a real-world view of how these treatments 

and drugs actually work in patients’ populations. 

Regional hospitals can offer a much more realistic picture 

of the efficacy and safety of a treatment or drug. This potential 

bias might be reduced by offering patients the possibility 

to access clinical trials at their regional hospitals. 

To enforce clinical cancer research at regional hospitals, 

SAKK initiated the “middle-sized hospitals” project. Eight 

hospitals met the requirements of the initiative (Spitalzentrum 

Biel, Hôpital fribourgeois, Kantonsspital Graubünden, 

Klinik Hirslanden Zürich, Kantonsspital Luzern, Stadtspital 

Triemli, Centre hospitalier du centre du Valais, Kantonsspital 

Winterthur) and received strategic, operational and financial 

support to set-up the required structures to perform 

clinical cancer research. The hospitals invested grant 

money to hire a data manager who supports the medical 

staff in all administrative and coordinative aspects of a 

clinical trial. 

The funded hospitals all started to participate in SAKK 

trials shortly after project start, and their activities have 

increased markedly over the last three years. In 2010 the 

eight hospitals recruited 242 patients into clinical trials 

coordinated by SAKK out of a total of 787 patients. 

Clinical cancer research performed by SAKK cares about 

the interest of the patients and addresses research questions 

related to practical work. In addition, cancer treatment 

within a clinical trial complies with medical treatment 

guidelines and is a quality measurement. As a direct 

result of the SAKK initiative, more cancer patients have 

access to clinical trials and thereby to treatment of a high 

quality standard. Importantly, patients have the possibility 

to stay at their regional hospitals, where they are 

treated by their local oncologists and remain within their 

social environments. 


Prof. Dr. Richard Herrmann, Basel 

Correspondence: 

Annik Steiner 

Head Partner Relations 

SAKK-Koordinationszentrum 


CH-3008 Bern 

Phone +41 (0)31 389 93 96 

Fax +41 (0)31 389 92 00 

annik.steiner@sakk.ch

Hess Christoph | Innate immunity, cytokine polymorphisms, 

and development of post-transplant 

lymphoproliferative disease in kidney transplant 

recipients (OCS 2266-08-2008) 

After transplantation of solid organs, patients must undergo 

lifelong pharmacological immunosuppression to prevent 

rejection of the transplant. Post-transplant lymphoproliferative 

disorders (PTLDs), i. e. lymphomas arising 

in patients under immunosuppressive therapy, are a rare 

yet severe complication after transplantation. Prior to 

PTLD development, most patients experience Epstein- 

Barr virus (EBV) re-activation or de novo infection. Due to 

lack of immunological control of EBV, this usually benign 

infection can mediate lymphomagenesis in immunosuppressed 

patients. 

Several potential risk factors for PTLD development have 

previously been studied. It is known that the incidence of 

PTLD rises with increasing intensity of the immunosuppressive 

regimen applied. Transplantation of an EBV-positive 

organ into a patient that has previously not been infected 

with EBV also represents an important risk factor. 

In small series of patients the potential impact of various 

components of the immune system on PTLD development 

was analyzed. Results of these analyses have remained 

controversial, as several associations could not be confirmed 

in other cohorts of patients. 

In conjunction with the Collaborative Transplant Study 

(University of Heidelberg, Germany), we therefore analyzed 

a very large cohort of patients developing PTLD 

after transplantation. The aim of this investigation was to 

determine possible risk factors in the development of 

PTLD, as well as factors that influence the course of this 

disease once it is established. We analyzed 236 patients 

using genotyping. We were particularly interested in factors 

influencing the immune system and polymorphisms 

in genes that are important in the development of inflammatory 

responses. 

We showed that none of the genetic polymorphisms that 

code for proteins important in the inflammatory response 

(specifically interferon alpha, transforming growth factor 

beta and interleukin 10) have any influence on the development 

of PTLD or on the course of this disease. This contradicts 

previous studies, which, however, had included 

only a few dozen patients at most. The factors influencing 

the innate immune system that were analyzed in parallel 

also did not predict which patients were at risk for PTLD 

development. However, two polymorphisms in genes that 

code for proteins expressed on the surface of natural killer 

cells (KIR2DL2/3 and FcgRIIIa) were found to have a 

strong influence on the survival of patients that had developed 

PTLD. Natural killer cells are a subgroup of lymphocytes 

that are important in the defence against tumours 

and viral infection. 

The results of our investigation indicate that none of the 

investigated factors can help to identify which patients 

are at particularly high risk for PTLD development. This 

stands in clear contrast to previous smaller studies. Future 

studies will have to determine whether the polymorphisms 

identified to determine the course of established 

PTLD will have an impact on the treatment of this disease. 


Prof. Dr. Christoph Hess 

Ambulante Innere Medizin 

Medizinische Poliklinik 



CH-4031 Basel 

Phone +41(0)61 265 44 75 

Fax +41(0)61 265 43 00 

chess@uhbs.ch 

Hess Viviane | Improving treatment for patients 

with advanced pancreatic cancer (APC): A Swiss-wide 

effort (KLS 01881-04-2006) 

Pancreatic cancer is the fifth leading cause of cancer 

deaths in the Western world, and incidence is increasing. 

Furthermore, the vast majority of patients are diagnosed 

with advanced, incurable disease with a median survival 

time of four to eight months. Our clinical research projects 

all aim at improving treatment options for these patients. 

Methods 

We conducted three multicentre clinical studies focusing 

on 1) translational, 2) therapeutic, and 3) Swiss-specific 

epidemiological aspects. 

Results 

1) The serum tumour marker CA 19-9 is elevated in most 

patients with pancreatic cancer, and measuring its changes 

during therapy would represent an ideal way of judging 

treatment efficacy (surrogate marker). Surprisingly, however, 

in our large prospective cohort of patients, we found 

that a decrease of the CA 19-9 serum concentration during 

chemotherapy was not associated with lengthened 

survival – regardless of whether a 25 %, 50 % or 75 % decrease 

was examined. 

2) Combining the three most efficient drugs in pancreatic 

cancer – gemcitabine, oxaliplatin and capecitabine 

(GEMOXEL) – was well tolerated at the recommended 

dose (determined through inter-patient dose escalation) 

and showed a decrease in tumour volume in 41 % of 

patients in our multicenter prospective setting. The percentage 

of patients with substantial tumour shrinkage by 

far met the pre-defined criteria for further investigating 

this triple combination and makes it particularly interesting 

in the pre-operative setting. 

3) Between 2001 and 2004, six large Swiss centres actively 

recruited patients with advanced pancreatic cancer 

for a therapeutic trial. Yet, during this period, only 23 % 

(out of a total of 275 patients) were treated on protocol. 

The majority (88 %) of patients treated outside of a study 

setting were in a medical condition allowing for chemotherapy 

treatment. Therefore, study participation was 

hindered by factors other than medical condition. Survival 

times for patients treated on or off study protocols did not 

differ statistically. 

137

138 

Conclusions 

A strong network of committed centres throughout Switzerland 

has been built allowing work towards the progress 

so desperately needed in this disease setting. Given that 

only one out of five patients is treated on a trial protocol, 

there is a huge potential for further increasing clinical research 

activities. The triple combination therapy GEMOXEL 

is well tolerated, and given the large percentage of patients 

experiencing tumour shrinkages, further investigation 

in the preoperative setting is warranted. Decrease of 

the serum tumour marker CA 19-9 during chemotherapy 

is not a surrogate marker for survival. This finding has major 

implications for future study design. This project was 

awarded the 2009 Pfizer Research Award. 


PD Dr. Viviane Hess 

Medizinische Onkologie 



CH-4031 Basel 

Phone +41 (0)61 265 50 59 

vhess@uhbs.ch 

Hunger Robert E. | Malignant melanoma: Correlation 

of dendritic cell (DC) and T-cell markers with prognosis 

(OCS 02262-08-2008) 

In patients with malignant melanoma the most important 

parameters for prognosis are tumour thickness according 

to Breslow, ulceration of the primary tumour and sentinel 

lymph node status. However, sentinel lymph node dissection 

to determine nodal status of the patient is costly and 

requires surgery. 

The aim of this study was to find markers to assess the risk 

to form metastasis that do not require surgery. To this end 

we immunohistochemically stained semiserial tissue sections 

of 200 primary melanoma with monoclonal antibodies 

for the dendritic cell related markers CD1a, DC-LAMP, 

langerin, BDCA-2 and the T-cell markers granzyme B, TIA 

and FOXP3. Marker expression was assessed for all samples 

by counting positive cells under a microscope and by 

a digitalized image analysis system. 

The results of both counting systems revealed similar results 

with a highly significant correlation coefficient. In 

primary melanoma with positive sentinel lymph node we 

found a higher expression of the markers BDCA-2 and 

DC-LAMP compared to tumours with negative sentinel 

lymph nodes. Further analysis, especially the assessment 

of the T-cell related markers and the analysis of both sets 

of markers, will hopefully provide more prognostic information 

for patients with melanoma by just analyzing the 

primary tumour. 


Prof. Dr. Robert Hunger 

Universitätsklinik für Dermatologie 

Inselspital 

CH-3010 Bern 

Phone +41 (0)31 632 2613 

robert.hunger@insel.ch 

Imhof Beat A. | The mechanism of anti-JAM-C 

antibodies blocking tumor angiogenesis 

(OCS 01653-02-2005) 

For several years, our laboratory, which specializes in 

studies of regulatory proteins in vascular physiology, has 

been searching for novel actors implicated in tumour angiogenesis. 

Angiogenesis is characterized by the formation 

of new blood vessels that sprout from the existing 

vasculature. This mechanism is essential for tumour 

growth and development, as the newly formed vessels 

provide oxygen and nutrients to tumour cells. For this reason, 

it is important to understand and thereby inhibit the 

molecular mechanisms involved in the formation of new 

blood vessels, so as to starve the tumours and halt their 

development. Our laboratory previously discovered JAM- 

C, a novel molecule that is involved in tight junctions 

between endothelial cells and controls permeability of 

vessels. By blocking JAM-C during angiogenesis with 

monoclonal antibodies, we were able to block the formation 

of new blood vessels in the developing retina of mice 

and in aortic cultures in vitro. 

During discussions with Prof. Pierre-Yves Dietrich, head of 

oncology at University Hospital of Geneva, we decided to 

test whether our anti-JAM-C antibodies could inhibit the 

growth of glioblastoma and their fatal invasion into the 

brain. These tumours are particularly aggressive, and current 

treatments are not very effective in preventing tumour 

progression. We first used a mouse glioblastoma cell 

line and implanted these cells into the brain of mice. Tumour 

progression and invasion were imaged in vivo by 

magnetic resonance image technology. Treatment of 

these mice with anti-JAM-C antibodies reduced the size 

and spreading of glioblastoma tumour in the brain. Closer 

analysis revealed that the antibody reduced the vascular 

density but also affected the tumour itself, as glioblastoma 

cells also expressed JAM-C. This was surprising, for 

normal glial cells do not express JAM-C. We then investigated 

whether JAM-C would regulate the expression of 

genes in tumour cells and found several candidate genes 

whose expression was upregulated with potential roles in 

cell migration and invasion. 

In conclusion, JAM-C is a molecule involved in the angiogenic 

development of blood vessels and the regulation of 

invasive migration of tumour cells, in particular glioblastoma. 

In the long term, we plan to use humanized anti- 

JAM-C antibodies as a novel targeted weapon for anticancer 

treatment. 


Prof. Dr Beat A. Imhof 

Département de pathologie et immunologie 


Centre médical universitaire (CMU) 


Rue Michel-Servet 1 

CH-1211 Genève 

Phone +41 (0)22 379 57 47 

Fax +41 (0)22 379 57 46 

beat.imhof@unige.ch

Irminger-Finger Irmgard | BRCA1-associated protein, 

BARD1, a molecular target for breast cancer screening 

and cancer therapy (KLS 01962-10-2006) 

Breast cancer is the most frequently diagnosed cancer in 

the Western world, and the numbers are increasing in the 

emerging economies, such as China, India and Brazil. It is 

assumed that this latter increase is due to a change in nutritional 

lifestyle and might be explained by the increased 

consumption of oestrogens through the food chain. Oestrogens 

act through the oestrogen receptor alpha (ER-alpha), 

which induces the transcription and upregulation of 

a variety of target genes, among which are the breast 

cancer genes BRCA1 and BRCA1-associated RING domain 

protein 1 (BARD1). BARD1 is often described as a protein 

binding to BRCA1. It acts as stabilizer of BRCA1 and enhancer 

of the E3 ubiquitin ligase activity of BRCA1, which 

is important for controlled turnover of many target proteins, 

and one of these is ER-alpha. However, BARD1 isoforms 

that lack the BRCA1-interaction domain are upregulated 

in breast and ovarian cancer, and their expression 

is correlated with poor prognostic factors, such as tumour 

size, stage and grade. Thus BARD1 isoforms are biomarkers 

of cancer progression. 

The overall goal of our project was: 1) to characterize the 

oncogenic functions of breast cancer-specific BARD1 isoforms 

and generate tools for their inhibition; and 2) to 

develop methods for their detection in the blood. To reach 

these goals we cloned individual isoforms in expression 

vectors, expressed them in breast cancer cell lines and 

generated antibodies against epitopes specifically expressed 

on BARD1 isoforms. With this approach we could 

demonstrate that BARD1 isoform delta acts antagonistically 

to the function of the BRCA1-BARD1 E3 ubiquitin ligase 

in the controlled degradation of the ER-alpha. We 

also demonstrated that overexpression of BARD1-delta 

leads to ER-alpha accumulation, as it is observed by repression 

of full length BARD1 or BRCA1. Importantly, ERalpha 

induces expression of BARD1 but also BARD1 isoforms 

when activated by oestrogen, which leads to a 

feedback loop of increased expression of isoforms. Since 

oestrogen is the biggest risk factor for breast cancer, inhibition 

of ER-alpha upregulation, based on the inhibition of 

BARD1 delta, could be an important novel tool for targeted 

cancer therapy. 

We also showed that expression of isoform beta antagonizes 

the degradation of the mitotic kinase Aurora B, while 

the turnover of Aurora B is normally regulated by BRCA1- 

BARD1 E3 ubiquitin ligase. Inhibition of Aurora B expression 

or activity is important for controlling the proliferation 

of tumour cells. Repression of BARD1-beta by small 

interfering RNA (siRNA) leads to growth arrest in several 

cancer cell lines tested in vitro. Thus, inhibiting BARD1beta 

isoform expression can be exploited for the development 

of a novel targeted cancer therapy. 

To demonstrate that BARD1 isoforms could be detected in 

the blood, we used sera from breast cancer patients and 

performed enzyme-linked immunosorbent assay (ELISA) 

using antibodies specifically recognizing BARD1 isoforms 

to detect them in sera from patients with breast cancer. 

Further work will be necessary to clearly prove whether 

BARD1 isoform detection in the patient’s blood can be 

used as diagnostic tool. 


Dr Irmgard Irminger-Finger 

Laboratoire de gynécologie-obstétrique moléculaire 

Département de gynécologie et d’obstétrique 

Maternité 


Boulevard de la Cluse 30 


Phone +41 (0)22 382 43 27 

irmgard.irminger@unige.ch 

Kalberer Christian P. | Role of NKG2D receptor-ligand 

interactions in the recognition of human B-cell neoplasms 

by natural killer cells (OCS-01870-02-2006) 

Human natural killer (NK) cells are important effectors of 

the innate immune system and contribute to the first line 

of defence against virus-infected cells and tumour cells. 

Cognate interactions of activating NK cell receptors and 

their ligands result in target cell killing. The activating receptor 

NKG2D recognizes ligands that, in humans, belong 

to the ULBP and MIC gene families and are crucial determinants 

in anti-tumour immunity. Our recent studies in 

patients with acute myeloid leukaemia showed that malignant 

cells express low levels of ULBP and MIC ligands, resulting 

in evasion of leukaemic blasts from immune surveillance 

by NK cells. This study addresses the molecular 

mechanisms regulating ULBP1 leading to low surface expression 

levels in acute leukaemias. 

The goal was to investigate the role of the 3’ untranslated 

region (3’UTR) in post-transcriptional regulation of ULBP1 

expression. Considerable differences in length and sequence 

of the 3’UTRs of the ULBP genes suggest that this 

region plays a role in differential expression of ULBPs. Indeed, 

sequence analysis of 2.4 kb-long ULBP1-3’UTR revealed 

potential binding sites for more than 200 micro- 

RNAs and the presence of four AU-rich elements (ARE), 

the regulatory components of RNA degradation and 

translational suppression. Stable or transient delivery of 

luciferase reporter constructs containing the full-length 

ULBP1-3’UTR sequence with lentiviral vectors or expression 

plasmids resulted in a strong reduction of luciferase 

activity to 7 – 22 % in Jurkat, HeLa cells and human primary 

fibroblasts, indicating a contribution of 3’UTR to the 

regulation of ULBP1 gene expression. To determine the 

position of regulatory sequences in the ULBP1-3’UTR, we 

generated nine vectors carrying different fragments of 

ULBP1-3’UTR that all led to significant reductions of luciferase 

activity to 19 – 62 %. The suppressive effects were 

seen with every fragment along the 3’UTR, suggesting 

that the regulatory sequences are distributed over the entire 

3’UTR rather than restricted to specific areas. Muta- 

139

140 

tions introduced to ARE motifs significantly diminished luciferase 

activity, suggesting an mRNA stabilizing effect of 

ARE. Among ULBP1-specific candidate microRNAs, we 

found miR-140-5p/-409-3p/-433-3p/-650 expressed in 

HeLa and Jurkat cells, and the microRNA involvement was 

supported by luciferase reporter assays with constructs 

carrying seed sequence mutations. However, microRNA 

overexpression or partial silencing of the microRNA processing 

enzyme Drosha did not equivocally clarify the role 

of microRNAs in regulation of ULBP1. 

Altogether, these results provide evidence for a novel 

3’UTR-mediated mechanism of regulation of ULBP1 at the 

post-transcriptional level. Given that NKG2D ligand expression 

is crucial for tumour recognition, targeting 3’UTR 

of ULBP1 may represent a tool to upregulate tumour-associated 

ligands for the activating immunoreceptor 

NKG2D. Revealing the different gene expression mechanisms 

will open up important new therapeutic outlooks by 

modulating ligand levels, which will potentiate the effect 

of NK cell immunotherapy against leukaemias. 


PD Dr. Christian Kalberer 

Diagnostische Hämatologie 

Labormedizin 



CH-4031 Basel 

Phone +41 (0)61 265 25 25 

Fax +41 (0)61 265 44 50 

ckalberer@uhbs.ch 

Kalia Yogeshvar N. | Non-invasive transdermal iontophoretic 

delivery of antiemetic drugs for the treatment 

of chemotherapy-induced nausea and vomiting 

(OCS 01753-08-2005) 

Chemotherapy-induced nausea and vomiting (CINV) affects 

70–80 % of cancer patients. Two distinct phenomena 

have been reported, acute and delayed emesis. Intravenous 

(IV) administration of antiemetics is effective in 

treating acute emesis; however, it is less practical for the 

treatment of delayed emesis. Oral administration is more 

convenient but poses problems for patients suffering from 

emesis and prone to vomiting. Diarrhoea, malabsorption, 

gastrointestinal ulceration and the occurrence of oral mucositis 

can also severely reduce oral bioavailability. There 

is a need to develop non-invasive methods for the controlled 

delivery of antiemetics that can improve their efficacy 

against delayed emesis. Dosing can be problematic, 

particularly in children; the ideal delivery system should 

function as a “needle-free” pump, providing tight control 

over drug input without the invasiveness of an IV infusion. 

Transdermal delivery is convenient and the ease-of-use of 

modern patches means they are well-accepted by the 

public. However, the skin’s excellent barrier function restricts 

drug delivery into the body and limits the number 

of drugs that can be delivered by this route. Iontophoresis 

uses a small electric current to enable the controlled delivery 

of molecules that cannot otherwise overcome the skin 

barrier. The amount of drug delivered (or the dose) depends 

directly on the intensity and duration of current ap- 

plication. The long-term goal of our research is to develop 

an efficacious alternative to the oral and IV administration 

of antiemetics and to improve the quality of life of patients 

with cancer. 

Purpose 

The aim of the project was to evaluate the feasibility of 

using transdermal iontophoresis for the controlled non-invasive 

delivery of antiemetics used in the treatment of 

CINV; in particular with a view to developing more patient-friendly 

treatment options for delayed emesis. 

Method 

The first part of the study investigated the iontophoretic 

delivery of the different therapeutic agents – granisetron 

(GST), metoclopramide (MCP) and dexamethasone sodium 

phosphate (DEX) – singly. Then, since the complex 

aetiology of CINV has resulted in the co-administration of 

drugs that target the different receptors responsible for 

stimulating the emetic centre within the brain, we investigated 

the co-iontophoresis (that is, simultaneous delivery) 

of these agents. 

Results 

Initial experiments demonstrated the feasibility of delivering 

therapeutic amounts of each of the antiemetic agents, 

GST, MCP and DEX across the skin. This was also the case 

for the co-iontophoresis studies – i. e. the experiments involving 

simultaneous administration of multiple agents 

(GST, MCP and DEX). Preclinical animal studies were also 

successful. The project provided the first demonstration 

of the feasibility of administering a “polytherapy” by using 

transdermal iontophoresis. 

Potential benefits for patients 

The results confirmed the potential of iontophoretic systems 

to deliver the antiemetics used to treat CINV. During 

the course of this project, the first “conventional” transdermal 

patch for granisetron was launched – highlighting the 

utility of this route for treating CINV. However, iontophoretic 

patch systems would be smaller and provide faster 

symptom relief. In the future, we intend to investigate the 

transdermal delivery of newer, more potent antiemetics 

and to develop an effective alternative to their administration 

by the oral and IV routes. 


Dr Yogeshvar N. Kalia 

Section des sciences pharmaceutiques 

(Ecole de pharmacie Genève Lausanne) 


Quai Ernest-Ansermet 30 

CH-1211 Genève 4 

Phone +41 (0)22 379 33 55 

Fax +41 (0)22 379 33 60 

yogi.kalia@unige.ch

Maiwald-Urosevic Mirjana | Role of versican in 

the biology of Sézary cells (OCS 01934-08-2006) 

Sézary syndrome (SS) belongs to cutaneous lymphomas, 

a heterogeneous group of lymphatic malignancies characterized 

by red and scaly skin, lymph node enlargement 

and the presence of atypical tumour lymphocytes, called 

Sézary cells (SCs) in peripheral blood. In contrast to other 

skin lymphomas with a T-cell phenotype, SS has an unfavourable 

prognosis. The exact mechanisms underlying accumulation 

of malignant SCs in the skin and/or enabling 

their circulation in peripheral blood are still poorly defined. 

Accordingly, the various treatments for SS are generally 

disappointing, reflecting the need for new targets. 

SCs appear to lack regulatory activity governing their response 

to chemokines, which might potentate their homing 

to the skin. 

By using high-throughput gene expression profiling of SCs 

obtained from peripheral blood of patients, we could 

identify a highly overexpressed gene, termed versican. 

Versican is one of the major components of the extracellular 

matrix and is able to bind various chemokines, thus 

influencing the cellular response to chemokines and 

changing the migratory behaviour of lymphoid cells. 

Moreover, overexpression of versican (or its different isoforms) 

appears to be responsible for the changes in the 

susceptibility of tumour cells to apoptosis. 

The results obtained in this project provide new information 

that can be used in the development of treatment 

strategies targeting migratory behaviour of lymphoid tumour 

cells. This could be of importance not only in skin 

lymphomas but also in other T-cell malignancies with possible 

blood involvement. 


PD Dr. Mirjana Maiwald-Urosevic 

Dermatologische Klinik 


Gloriastrasse 31 


Phone +41 (0)44 255 11 11 

mirjana.maiwald@usz.ch 

Matthes Thomas | Analysis of transcription factors 

PU.1 and GATA-1 functions in myelodysplastic 

syndromes, in acute myeloid leukemia and in leukemia 

stem cells (OCS 01781-08-2005) 

Transcription factors are intracytoplasmic proteins that 

regulate the normal cell differentiation from undifferentiated 

omnipotent stem cells to fully mature end-differentiated 

cells with specialized functions in different organs. In 

the haematopoietic system, they orchestrate the differentiation 

into the various different red and white blood cells 

that circulate in the peripheral blood and populate the 

various lymphoid organs of the body. They also play a role 

in acute myeloid leukaemia (AML), in which this normal 

differentiation program is blocked, as well as in myelodysplastic 

syndromes (MDS), preleukaemic states in which 

transcription factor expression is dysregulated. 

Aim 

To study the function of two particular transcription factors, 

PU.1, the key regulator of myelopoiesis, and GATA-1, 

the key regulator of erythropoiesis, in normal haematopoietic 

differentiation, in AML and in MDS. 

Methods 

We used lentivectors, which code for PU.1 or GATA-1, to 

transduce normal stem cells, primary blast cells from patients 

with AML, and AML cell lines, and from patients 

with MDS. In in vitro cultures we analyzed the effect of 

overexpressed PU.1 or GATA-1 on the differentiation and 

proliferation potential of the transduced cells, on their 

phenotype and on their resistance to apoptotic stimuli. 

Results 

Transduction of cells with the two lentivectors led to overexpression 

of mRNA and protein of the corresponding 

transcription factors. After several days of culture, blasts 

transduced with PU.1 showed myelomonocytic differentiation 

and phenotypic changes compatible with restored 

blast differentiation. These effects were similar to the effects 

observed by adding all-trans retinoic acid (ATRA) to 

the cell cultures, a treatment currently used in the clinics 

in a subtype of AML. At later time points cells showed 

morphologic changes typical of macrophages, and increased 

apoptosis, characteristic of end-differentiated 

cells. The observed effects were dose-dependent and occurred 

only when PU.1 levels were above a certain threshold. 

Blast cells transduced with GATA-1 did not show any 

of the effects observed in PU.1 transduced cells, although 

GATA-1 protein levels were increased. 

Conclusion 

Our results show that artificially induced changes in transcription 

factor levels can influence the destiny of leukaemic 

blast cells by overcoming the differentiation block 

typical of these cells and restoring their normal differentiation 

program. Targeting PU.1 or one of the other known 

molecules in the PU.1 signal transduction pathway in AML 

could therefore constitute an interesting alternative approach 

for the treatment of this still incurable disease. 


Dr Thomas Matthes 

Service d’hématologie 

Département de médicine interne 


6, rue Gabrielle-Perret-Gentil 


Phone +41 (0)21 372 39 30 

Fax +41 (0)21 372 72 88 

thomas.matthes@hcuge.ch 

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Müller Beatrice U. | The master transcription factor 

PU.1 is essential for normal hematopoiesis: Analysis of 

PU.1 alterations in patients with acute myeloid leukemia 

(AML) (OCS 1731-08-2005) 

The majority of patients with acute myeloid leukaemia 

(AML) still die of the disease, and novel therapeutic concepts 

are needed. In leukaemic cells, the normal development 

of white blood cells is typically blocked at a particular 

stage, and blocked differentiation is, in fact, the 

hallmark of acute leukaemia. 

Timely regulation of the key transcription factor PU.1 is 

crucial for normal haematopoiesis. We previously showed 

that PU.1 expression is specifically suppressed in patients 

with AML-M3. In addition, targeted disruption of an upstream 

regulatory element (URE) located 15 kb upstream 

in the PU.1 promoter was reported to decrease PU.1 expression 

by 80 % and lead to AML in mice. Here, we 

screened patients with AML for mutations in the entire 

URE sequences of PU.1. We detected two polymorphisms 

in 4 out of 120 patients with AML (3.3 %) and in 1 out of 

141 healthy volunteers (0.7 %). Both polymorphisms were 

localized in the distal homology region (DHR) of the URE 

within 10 bp affecting a putative NF-kB site. We found 

that NF-kB p50/p65 heterodimers and p50/p50 homodimers 

were indeed binding to this site and that NF-kB p50/ 

p65 activated PU.1 expression through this site in the 

URE. Remarkably, NF-kB mediated activation was abolished 

by the polymorphisms detected in patients with 

AML. Further, NF-kB synergistically activated PU.1 together 

with CEBPB, whereas this synergy was lost in the 

presence of these polymorphisms. Finally, patients with 

AML with the polymorphic NF-kB sequence showed suppressed 

PU.1 mRNA expression. 

Our results demonstrate that NF-kB mediated activation 

of PU.1 is deregulated by polymorphisms in the URE of 

PU.1, which are more frequent in patients with AML than 

in healthy individuals. Moreover, our study suggests that 

an insertion of even only a single base pair in a distal element 

critically affects the regulation of a tumour suppressor 

gene and thus contributes to the development of cancer. 


Dr. Beatrice U. Müller 

Departement für allgemeine Innere Medizin 

und klinische Forschung 

Inselspital 

CH-3010 Bern 

Phone +41 (0)31 632 03 78 

Fax +41 (0)31 632 0514 

beatrice.mueller@insel.ch 

Perrier Patrick | Impact of UV light on melanoma 

development (OCS 01911-08-2006) 

Incidence of cutaneous melanoma is constantly increasing 

in our latitudes in fair-skinned individuals. The principal 

aim of our project was to try to dissect some of the effects 

of UV light leading to development of melanoma. To do 

so, we started from a postulate formulated in 1995 by 

Tronnier and colleagues. This group showed that UV irradiation 

of benign nevi was able to reversibly simulate in 

situ malignant melanoma by promoting pagetoid migration 

of melanocytes towards superficial epidermal layers. 

They showed that melanocytes were activated and expressed 

higher levels of HMB-45. After 3 weeks, however, 

the initial morphological aspect of the nevus could be 

seen again, without any sign of melanocytic atypia. 

Tronnier et al.’s observations could be reproduced in our 

laboratory 7 days after irradiation of human normal nevi 

by both UVA and UVB. The interplay between melanocytes 

and keratinocytes in response to UV is probably 

based, at least in part, on the production of immune mediators. 

We are currently exploring the expression of several 

inflammatory and angiogenic factors. On the other 

hand, chemokines and chemokine receptors are under 

study for their expression in keratinocytes and melanocytes, 

respectively. Besides their role in orchestrating leukocyte 

trafficking, chemokines have been described for 

their capacity to participate in driving organ-specific 

metastasis from primary tumours. A. Muller et al. were 

among the first active in this field and were subsequently 

followed by many others who demonstrated the capacity 

of these molecules to induce primary tumoural cells to migrate. 

Several groups then studied the expression of these 

chemokines in primary melanomas, in lymph node and organ 

metastasis and in melanocytic lesions; expression 

differs for each histological setting. So far, to our knowledge, 

little work has been done on chemokine/chemokine 

receptor expression by keratinocytes and melanocytes in 

response to UV light, and this is our next point of interest. 

Our project is still underway. The description of the complex 

interplay between melanocytes and keratinocytes is 

necessary to better understand the first steps of melanoma 

development. 


Dr Patrick Perrier 

Service de dermatologie 

Département de médecine 



Phone +41 (0)79 556 58 36 

Patrick.Perrier@chuv.ch

Renevey Philippe | Development of a voice restoration 

system for laryngectomees in order to improve their 

social interaction (OCS 01777-08-2005) 

Laryngectomy denotes a treatment of laryngeal cancer requiring 

partial or total removal of the larynx. The loss of 

the vocal function is one of the very distressing consequences 

of this pathology. Medical rehabilitation techniques 

allow laryngectomees to partially recover vocal 

function, but it results in poor voice quality and insufficient 

speech intensity. 

The main goal of this project was to develop speech signal 

processing methods for the restoration of the voice 

quality in laryngectomees’ speech. In particular, the proposed 

scheme estimates parameters from the pathological 

speech and uses a voice model to restore missing or 

degraded voice characteristics. The naturalness and emotional 

paralinguistic features found in healthy voices are 

restored from different cues estimated from the pathological 

voice. Healthy speech is then reconstructed by recombining 

the previously estimated speech parameters 

and the new voice source. 

The procedure adopted for this project was initially based 

on the enhancement and adaptation of existing speech 

signal processing algorithms to the particular characteristics 

of pathological speech. The first results indicated that 

the investigated methodologies needed further development 

and innovation in order to obtain satisfactory results. 

The following aspects have been investigated: The parameter 

estimation has focused mainly on a reliable estimation 

of rudimentary variations of the fundamental 

frequency and of the articulation parameters. After evaluation 

of state-of-the-art methods, a novel method called 

adaptive wavetable oscillator was developed; it provides a 

good theoretical match to the revealed problems with 

pathological voice excitation. This new method exhibits 

reduced computational costs and provides similar performance 

to state-of-the-art methods. For the estimation of 

the articulation parameters, a method based on sub-space 

projection was developed, but it led to unsatisfactory results. 

Alternatively, a sub-band approach was developed, 

which led to increased estimation results but requires a 

dedicated method for the reconstruction of the speech 

signal.

144 

A novel method was developed for the reconstruction of 

a voice with more natural fundamental frequency and increased 

voice quality. It became obvious that the variability 

in the fundamental frequency may not be sufficient to 

restore prosody. This finding led to the development of 

a multi-resolution approach, where voluntary variations 

in the voice are restored based on different vocal cues 

on different time scales. 

The algorithmic solutions developed in the framework of 

the project represent a significant step in the understanding 

and processing of pathological voices. However, the 

results obtained also highlighted the difficulty and complexity 

of the restoration process. The actual restoration 

results are not yet sufficient to be integrated in a device 

aiming at improving the quality of life of laryngectomees 

(vocal aid, improvement of telephone calls, public audience 

amplification, etc.), but the research work is still underway. 


Dr Philippe Renevey 

Centre suisse d’électronique et 

de microtechnique (CSEM) 

Rue Jaquet-Droz 1 

CH-2007 Neuchâtel 

Phone +41 (0)32 720 55 27 

prv@csem.ch 

Schäfer Beat W. | Oncogenic fusion proteins as 

therapeutic targets in pediatric sarcomas 

(OCS 02264-08-2008) 

Childhood sarcomas are aggressive tumour entities. This 

is especially true of the type of sarcomas that are characterized 

by the presence of a chromosomal translocation 

and include rhabdomyosarcoma and Ewing’s sarcoma. 

Several previous studies from different laboratories demonstrated 

that the fusion proteins produced by chromosomal 

translocations are important for both tumour development 

and tumour cell survival. Therefore, these 

oncogenic transcription factors represent important target 

molecules for the development of novel treatment 

strategies. Unfortunately, this development is challenging 

due to the nature of the proteins involved, and for this 

reason it is not actively pursued by industry. 

The aim of the current project was therefore to develop a 

method by which the activity of these fusion proteins can 

be measured and subsequently inhibited by small-molecule 

chemical compounds. The method developed for this 

relies on measuring transcriptional activity based on a few 

carefully selected target genes. We successfully implemented 

and validated such a method. Next, we screened a 

library composed of small-molecule chemical compounds 

and a library composed of the latest drugs under development 

in oncology. Interestingly, we first identified a novel 

drug called fenretinide, a retinoic acid analogue that is 

now under development for Ewing’s sarcoma and neuroblastoma, 

as also being effective for rhabdomyosarcoma. 

Equally interesting were results from the second library, 

which is mainly composed of very specific kinase inhibitors 

that allow targeting of specific signalling pathways. 

Using Ewing’s sarcoma cells, we identified drugs targeting 

the PI3K/mTOR pathway as being the most effective. 

Strikingly, rhabdomyosarcoma cell did not react that well 

on this group of inhibitors but was most sensitive to drugs 

targeting components of the cell cycle. We found that an 

important cell cycle kinase is directly involved in stabilizing 

the fusion protein. Both drugs are now being further 

evaluated for anti-tumourigenic activity in an in vivo 

mouse model. 

The results of this project represent the first step towards 

improvement of current therapies for sarcomas by inhibiting 

the activity of the fusion proteins lying at the centre 

of tumourigenicity. These drugs now need to be further 

developed in pre-clinical models. 


Prof. Dr. Beat W. Schäfer 

Abteilung Onkologie 

Kinderspital Zürich 

Universitäts-Kinderkliniken 

Steinwiesstrasse 75 


Phone +41 (0)44 266 75 53 

Phone +41 (0)44 634 88 52 

beat.schaefer@kispi.uzh.ch 

Schäfer Beat W. | Prognostic classification of 

rhabdomyosarcoma: A combined retro- and prospective 

study (OCS 1944-08-2006) 

Childhood sarcomas are aggressive tumour entities. When 

metastatic, these tumours often have a fatal course despite 

aggressive treatment with chemo- and radiotherapy. 

Therefore, there is an urgent need to improve therapy 

in this tumour group. The most frequently occurring sarcoma 

in childhood and adolescence is rhabdomyosarcoma. 

The aim of our study was to simplify pathological classification 

into different rhabdomyosarcoma subgroups that 

are based on biological criteria. Historically, subgroup 

classification is based on histological analysis and divides 

rhabdomyosarcoma into tumours with embryonal and 

alveolar histology. Biological analysis in the past also revealed 

two subgroups: One subgroup is characterized by 

the presence of a specific genetic aberration, a chromosomal 

translocation that is lacking in the other subgroup. 

These two genetic groups only partially overlap with the 

ones based on histology. However, identification of this 

genetic aberration is crucial, since treatment and prognosis 

depend by and large on its presence. Whereas genetic 

methods are clearly able to identify the aberration, applying 

those methods can be sophisticated. 

To improve recognition of the genetic aberration, we 

therefore searched for biomarkers that would be indicative 

on simple histological sections. In our previous work, 

we could indeed identify four biomarkers based on gene 

expression profiles that fulfilled all criteria necessary. In 

the present project, we have now validated these markers 

on a large cohort of patients with rhabdomyosarcoma in 

collaboration with the German Cooperative Soft Tissue

Sar coma study (CWS study) (chaired by Prof. E. Koscielniak, 

Stuttgart, and Prof. T. Klingebiel, Frankfurt). We indeed 

confirmed differential expression of these markers in 

the genetic subgroups. Expression of the markers therefore 

also correlated with overall survival of the patients. 

The biomarkers identified in this study have now been incorporated 

into the clinical risk stratification. Hence, our 

study made a substantial contribution to improved diagnostics 

of patients with rhabdomyosarcoma. 


Prof. Dr. Beat W. Schäfer 






Phone +41 (0)44 266 75 53 

Phone +41 (0)44 634 88 52 

beat.schaefer@kispi.uzh.ch 

Speiser Daniel E. | Analysis of key mechanisms of 

human melanoma specific CD8 + T cell responses: 

Long term persisting clonotypes and strong effector 

functions (OCS-01917-08-2006) 

Immunotherapy can enhance the capacity of the immune 

system to protect the body against cancer. Our aims are 

to optimize this type of therapy for patients with cancer 

towards increased clinical efficacy. During this development, 

we identify key properties of human immune cells 

(T cells) that are associated with protective immunity. 

After vaccination of patients with melanoma with tumour 

antigenic peptides, CpG and Incomplete Freund’s Adjuvant 

(IFA), peptide-specific T cells expanded rapidly and 

reached high frequencies and reached on average > 1 % of 

CD8 T cells in peripheral blood. Our analysis revealed 

considerable tumour-specific cytolytic function and cytokine 

production by these T cells. This represents the first 

“direct ex vivo” demonstration of human cancer-specific 

multifunctional T cells that readily produced multiple cytokines 

(IFNg, TNFa and IL-2) and upregulated LAMP-1 

(CD107a) correlating with strong lytic activity. Interestingly, 

these responses were independent of patient age 

and gender, suggesting that elderly patients can also benefit 

from immunotherapy. Multiple subsequent monthly 

booster vaccinations promoted progressive differentiation 

to (CD28 negative) effector T cells with enhanced function. 

T cell receptor (TCR) and T cell clonotype analysis revealed 

that these T cells persisted over several years. The 

clinical responses were mixed, with about half of the 

patients that remained tumour free or progression free. 

In some patients, however, we observed progression of 

tumours, in part due to “immune escape”, i. e. by progression 

of antigen- or HLA-loss variant tumours. Fortunately, 

this immune escape was slow (on average only after several 

years). Together, our study shows for the first time 

that a cancer vaccine can induce multifunctional and thus 

immune competent tumour-specific T cells. Therefore, the 

data fully support further development of this approach, 

particularly by vaccinating with multiple tumour-antigens, 

which presumably minimizes the risk for immune escape. 

A few years ago, monitoring of T cell responses was limited 

to techniques based on the detection of antigen-specific 

T cells using tetramers and analysis of their function 

essentially by the assessment of cytokine production such 

as Interferon-g. However, these techniques have limitations, 

because they fail to determine major correlates of 

T cell mediated protection. Therefore, we developed additional 

strategies. Although labour intensive, our new techniques 

allow the assessment of T cell precursor frequency, 

T cell affinity / avidity, molecular and functional TCR 

properties and extended gene profiling of tumour-specific 

T cells. 

Our novel techniques combining tetramers with functional 

analysis allowed elucidation of key signalling mechanisms 

in tumour-specific T cells. Further, we investigated 

the roles of inhibitory receptors (e. g. PD-1, CTLA-4, BTLA) 

in functional T cell deficiency. We found that the latter 

is particularly important in metastases. Our strategy of 

functional analysis “directly ex vivo” of blood-derived T 

cells, and also of T cells from tumour tissue of patients 

with cancer, is well suited to evaluate the biological efficacy 

of available cancer therapies. Comprehensive characterization 

of biological and medical effects of novel 

therapies provides the basis for overall improvement of 

cancer therapy but also for better care of individual patients. 


Prof. Dr. Daniel E. Speiser 

Ludwig Institut für Krebsforschung 

Universitätsspital Lausanne 

HO 05/1552 

Avenue Pierre-Decker 4 


Phone +41 (0)21 314 01 82 

daniel.speiser@hospvd.ch 

Taverna Christian | Comparing two schedules of rituximab 

maintenance in rituximab-responding patients 

with untreated, chemotherapy resistant or relapsed 

follicular lymphoma: A randomized phase III trial of 

the SAKK (Swiss Group for Clinical Cancer Research) 

(OCS 02125-08-2007) 

Malignant lymphomas are malignancies that arise in the 

lymph nodes or in the lymphatic system. Follicular 

lymphoma is the second most common non-Hodgkin’s 

lymphoma. It is an indolent, i. e. non aggressive, malignant 

lymphoma. At the time of diagnosis the median age 

is about 60 years, and patients are often in an advanced 

stage of disease. Patients with follicular lymphoma usually 

have a slowly progressive course, and there are cases with 

stable disease for years without any treatment. Despite 

good response to systemic treatment, there is a high incidence 

of relapse. A cure can be attained in rare cases. The 

median overall survival is 10 years. The monoclonal antibody 

rituximab, which binds to the cell surface antigen 

CD 20, has remarkably improved treatment results. Rituximab 

is effective as a single agent as well as in combination 

with conventional chemotherapy. The side effect 

profile of the monoclonal antibody differs from the side 

effects of conventional chemotherapeutic agents. Different 

strategies have been evaluated to minimize the high 

relapse rate in follicular lymphoma. In a previous trial 

145

146 

(SAKK 35-98) the Swiss Group for Clinical Cancer Research 

(SAKK) showed that maintenance treatment with 

rituximab four times every two months significantly improved 

event-free survival. Rituximab is usually well tolerated 

and is well suitable for maintenance treatment. The 

optimal duration of maintenance therapy is unknown. The 

current study is investigating whether prolongation of the 

maintenance therapy leads to improved results. 

Patients with newly diagnosed, chemotherapy resistant or 

recurrent follicular lymphoma were included in this trial. 

After an induction therapy of four weekly infusions of 

rituximab, patients with partial or complete remission 

were randomised to a short maintenance or a prolonged 

maintenance for a maximum of five years or until progression 

or unacceptable toxicity. Primary endpoint is eventfree 

survival. Secondary endpoints are progression-free 

survival, overall survival, response rate, toxicity, molecular 

remission, duration of molecular remission and evolution 

of immunologic competence. Molecular analyses 

were performed by Dr. Francesco Bertoni (Experimental 

Oncology, Oncology Institute of Southern Switzerland, 

Bellinzona). 

From October 2004 to November 2007, 270 patients 

from 24 centres in seven countries were included and received 

induction treatment with rituximab. Many patients 

are still under trial treatment, and therefore an efficacy 

analysis has not yet been performed. Two safety analyses 

showed that rituximab maintenance therapy beyond two 

years is safe. 


Dr. Christian Taverna 

Onkologie 

Medizinische Klinik 

Kantonsspital Münsterlingen 

CH-8596 Münsterlingen 

Phone +41 (0)71 686 22 02 

Fax +41 (0)71 686 26 51 

christian.taverna@stgag.ch 

Terracciano Luigi M. | HOXA13 hyper-expression 

in liver cancer: A potential node toward angiogenesis 

(OCS 02005-02-2007) 

HOX genes control normal development and primary cellular 

processes and are characterized by a unique genomic 

network organization. The comparison of the HOX gene 

network expression between nontumourous livers and 

hepatocellular carcinomas highlights significant differences 

in the expression of locus A HOX genes with a consistent 

over-expression of HOXA13, thus validating this gene as a 

marker of HCCs. HOXA13, a determinant of gut primordia 

and posterior body structures, generates a fusion protein 

with NUP98 nucleoporin involved in leukaemogenesis. 

Transcriptome analysis on HCC/nontumourous liver 

mRNAs, selected on the basis of HOXA13 overexpression, 

recognizes a set of deregulated genes. The matching of 

these genes with reported HCC transcriptome analysis 

identifies cell-cycle and nuclear pore related HCC phenotype 

displaying poor prognosis. HOXA13 and HOXA7 homeoproteins 

share a consensus sequence that physically 

links eIF4E nuclear bodies acting on the export of specific 

mRNAs (c-myc, FGF-2, VEGF, ODC, cyclin D1). 

A series of 47 frozen liver biopsies were collected from 35 

patients identified by searching the files of the pathology 

institutes at the University of Basel, Switzerland, and at 

Federico II Medical School, Naples, Italy. Twelve patients 

underwent two liver biopsies, one of HCC and the second 

one of adjacent nontumourous liver tissue; 23 patients 

underwent a single HCC biopsy. Thirteen single liver biopsies 

were obtained during visceral surgery for gallbladder 

lithiasis and morbid obesity and were used as normal controls. 

A second series of 123 liver samples was used: 

1) partially (57 HCC samples), to detect the transcriptome 

expression of the 33 out of 39 HOX genes included in the 

Affymetrix Chip 133A 2.0 and of the deregulated genes 

identified through the Affymetrix analysis of HOXA13 hyper-expressing 

HCC/nontumourous liver pairs; 2) in toto, 

to detect HOXA13 mRNA real-time expression through 

G1-G6 HCC groups in the Zucman-Rossi laboratory. 

No substantial differences in the HOX gene expression 

were detectable by comparing normal and nontumourous 

livers, whereas major differences were found by comparing 

the frequency of active locus A HOX genes such as 

HOXA5, HOXA7, HOXA10 and HOXA13 in HCCs vs nontumourous 

and normal livers. Further, by analyzing the 

sequences of HOXA13 and HOXA7 homeoproteins, encoded 

by the two most deregulated locus A HOX genes of 

our HCC survey, we identified a consensus sequence 

(YQPWALP and YYVNALF=YXXXXLF) respectively responsible 

for their potential interaction with the rate-limiting 

step of eukaryotic cap-dependent translation initiation 

factor eIF4E. 

In this study the comparison of HOX gene network expression 

in hepatocellular carcinomas and nontumourous 

liver tissue identified the HOX A locus as the part of the 

network more significantly involved in hepatocarcinogenesis. 

Among locus A HOX genes, HOXA13 appears to be 

a marker of hepatocellular carcinomas as well as an important 

transcriptional and post-transcriptional node in 

the cancerous liver’s reversion to an embryonal stage 

towards gut primordia. The deregulation of genes identified 

through transcriptome analysis of highly HOXA13expressing 

pairs of HCC/nontumourous liver matched to 

the G1-G6 classification of hepatocarcinomas identifies 

the poor prognosis HCC G3 group, suggesting the inclusion 

of HOX genes transcriptome as a potential prognostic 

tool in liver cancer. 


Prof. Dr. Luigi M. Terracciano 

Abteilung für Molekularpathologie 



Schönbeinstrasse 40 

CH-4003 Basel 

Phone +41 (0)61 265 28 49 

Fax +41 (0)61 265 31 94 

lterracciano@uhbs.ch

Thalmann George N. | Impact of therapeutic and 

preventive strategies in prostate cancer on prostatespecific 

antigen (PSA), gene expression and tumor 

cell survival (OCS 01752-08-2005) 

Because of the progress made in the treatment of the primary 

tumour, mortality in patients with cancer is increasingly 

linked to progressive and metastatic disease, which 

is often occult at the time of diagnosis/therapy of the primary 

tumour. Despite treatment, tumours may progress 

by outgrowth of tumour cells resistant to treatment. It is 

unclear whether this selection is adaptive or clonal. Therefore, 

understanding the effect of preventive or therapeutic 

strategies on PSA and the tumour is essential. 


The working hypothesis of the project is that preventive 

and therapeutic agents may have an impact on the regulation 

and production of PSA and on gene expression 

in general. In addition, the cell subpopulation surviving 

treatment needs to be isolated and characterized. 

Methods and study design 

In order to study these interactions we used prostate cancer 

cell lines to test whether compounds used or under 

evaluation for prevention and treatment of prostate cancer 

have an impact on PSA production on the messenger 

RNA and protein level and on cancer cell growth. In addition, 

primary cell cultures from radical prostatectomy 

specimens were cultured under therapeutic conditions, 

and the therapy (hormone) refractory population was isolated 

and characterized, and tissue was used for the evaluation 

of potential novel prognostic markers. 

Study results 

We demonstrated that several compounds used for the 

prevention and therapy of prostate cancer, such as genistein 

or bicalutamide, inhibit PSA production, whereas 

genistein only inhibited hormone-sensitive cell growth. In 

primary cultures the treatment refractory hormone independent 

cell population evidenced a cancer stem-/progenitor-like 

phenotype that produces little of PSA but 

overexpresses genes of self-renewal and proliferation. 

Further, genes involved in angiogenesis (development of 

blood vessels) could be evaluated for their predictive 

value in patients undergoing radical prostatectomy. 

Recommendations and patient benefit 

Compounds foreseen for use in the prevention or treatment 

of prostate cancer should be evaluated for their influence 

on PSA expression prior to clinical use. The identification 

and characterization of the cell subpopulation 

surviving hormonal treatment of prostate cancer may allow 

development of novel treatment strategies for this 

disease. Finally, markers of neo angiogenesis could be 

tested for their predictive value in patients undergoing 

radical prostatectomy. A gene expression signature defining 

primary tumours with high malignant potential from 

such with low malignant potential could be determined. 


Prof. Dr. George Thalmann 

Klinik und Poliklinik für Urologie 

Inselspital 

Anna-Seiler-Haus 

CH-3010 Bern 

Phone +41 (0)31 632 36 64 

urology.berne@insel.ch 

Theurillat Jean-Philippe | Synthetic lethality in the 

context of autophagy-deficiency (KLS 02014-02-2007) 

Autophagy is a normal cellular process that mediates the 

breakdown of long-lived proteins. However, if autophagic 

activity is pathologically elevated, cells die as a consequence 

of self-digestion. Using an RNA-interference approach, 

we found that the loss of a specific signal-molecule 

termed S6K1 causes an excessive increase in autophagy 

flux followed by induction of programmed cell death (apoptosis). 

Constitutively, we found that S6K1 activity and 

hence survival of cancer cells is positively influenced by 

a novel oncogene called URI. Increased URI activity mediates 

resistance against many physiological and therapyinduced 

stressors. 

Study results 

We identified and described the function of the URI gene 

as an oncogene in ovarian cancer. URI translates into a 

protein that acts as a compound of a negative feedback 

loop dedicated to regulate S6K1 activity and ultimately 

influences the threshold for the induction of cell death 

(apoptosis). Normal cells die under physiological stress 

conditions, such as low availability of energy through induction 

of programmed cell death. However, when URI is 

upregulated, apoptosis induction is largely abolished. 

We found that about 35 % of patients with ovarian cancer 

display an upregulation of URI. One out of ten women 

exhibited, furthermore, an amplification of the URI gene. 

In the case of gene amplification, the gene is dramatically 

multiplied and integrated into the genome, which results 

in an increase in activity. Additionally, URI amplification 

could be detected in various other cancer types, suggesting 

that the importance of the present scientific results is 

not restricted to ovarian cancer. 

Interestingly, we were able to detect that women harbouring 

an amplified URI locus in their cancer genome 

were characterized by very aggressive tumour behaviour 

and failed to respond to chemotherapeutic treatment. In 

contrast to normal cells, URI is in those tumours essential 

for the survival of the tumour cells. On a molecular level, 

URI inhibits selectively in these tumour cells the inactivating 

function of a protein called PP1gamma on S6K1. As a 

direct consequence of our molecular understanding, we 

expect to find novel, more specific therapeutic approaches 

to treat patients with ovarian cancer characterized by URI 

amplification who do not respond to the standard chemotherapy 

regime. 

Patient benefit 

These findings will predict in the future the response of 

patients with ovarian cancer to a considered chemotherapy 

and help to judge whether a patient will benefit or 

not. Moreover, the results open up new perspectives for a 

more specific and personalized cancer treatment of women 

with ovarian cancer. This study, which is a result of collaboration 

with ETH Zurich, made a significant step towards 

the understanding of a novel oncogene, and will be published 

in 2011 in Cancer Cell. 


Dr. Jean-Philippe Theurillat 

Institut für klinische Pathologie 


Schmelzbergstrasse 12 


Phone +41 (0)44 633 76 58 

jean-philippe.theurillat@usz.ch 

147

148 

Timmermann Beate | Prospective evaluation of late 

effects and quality of life in childhood cancer after 

spot-scanning proton therapy at the Paul Scherrer 

Institute (OCS 01694-04-2005) 

Proton therapy offers promising characteristics to reduce 

the burden of radiation therapy. Especially children are 

highly vulnerable to radiation injury. Details on the clinical 

impact of physical characteristics of protons on the 

outcome are still unknown. Therefore, all children treated 

with proton beam therapy at the Paul Scherrer Institute 

(PSI) in Switzerland were to undergo prospective evaluation 

of quality of life (QoL) and treatment complications. 

Reliable, well-established tools for evaluation of treatment 

complications and quality of life were selected. The 

registry for late effects of irradiated children collects all 

data on radiation therapy in children. The forms were created 

by the working group for paediatric radiation oncology. 

It was agreed to collect all data on the children 

treated at PSI at the head office in Münster (Germany). 

Documentation consisted of data before therapy, 2 months 

after completion of therapy and yearly up-dates thereafter. 

For QoL, the Pediatric Quality Of Life (PEDQOL) instrument 

was chosen as the questionnaires for parents 

and children. The forms assessed different domains of 

QoL, including autonomy, body image, emotional behaviour, 

relation to friends and family and physical and cognitive 

performance. 

120 children were registered into the RiSK registry study. 

Median age was 3.6 years (range, 1–18.3). The majority 

of children had bone or soft tissue sarcomas (n=56) or tumours 

of the CNS (n=40). Radiation doses ranged from 

36 Gy to 75.8 Gy (med. 55.8). Predominantly mild acute 

reactions were observed, except for skin or bone marrow 

depression when simultaneous chemotherapy was applied 

(n=6). Higher scaled late complications were reported in 

lens (n=2) and brainstem (n=2). Brainstem complications 

were only observed after predisposing events. No correlation 

with treatment doses was found. 

As to the PEDQOL, in 142 children in total 626 forms were 

obtained, consisting of 142 basic information forms, 260 

parental questionnaires, 135 children’s questionnaires, 

and 89 parental forms for toddlers. In two-thirds of the 

children, significant morbidity was reported already before 

start of treatment. QoL seemed to be rated more 

positively by the children as compared to their parents 

and after 1 year even better as compared to their healthy 

references. Children older than 3 years of age showed 

improvement of QoL within 1 year after proton therapy. 

In children with tumours of the CNS, QoL seemed to be 

slightly more compromised as compared to children with 

sarcomas. 

First results after proton therapy are promising and suggest 

high tolerance and limited treatment burden despite 

relatively large doses of radiation therapy in a very young 

patient cohort. The compliance of the participants and 

their parents was high. To evaluate further details, larger 

cohorts and longer observation time is needed. Therefore, 

we suggest accompanying any innovative treatment 

method with studies on late effects and QoL. 


PD Dr. Beate Timmermann 

Westdeutsches Protonentherapiezentrum Essen 

Universitätsklinikum Essen 

Am Mühlenbach 1 

D-45147 Essen 

Deutschland 

Phone +49 (0)201 723 18 01 

Fax +49 (0)201 723 51 69 

beate.timmermann@uk-essen.de 

von der Weid Nicolas | Long-term outcome of 

childhood cancer: Incidence and spectrum of late 

effects (KLS 01605-10-2004) 

The Swiss Childhood Cancer Survivor Study (SCCSS) is a 

joint project of the Swiss Childhood Cancer Registry and 

the Swiss Paediatric Oncology Group and is run at the 

Institute for Social and Preventive Medicine of the University 

of Bern. All known survivors of paediatric cancer diagnosed 

in Switzerland received a postal questionnaire looking 

at current quality of life, health status, education, 

family situation and health behaviours. These data were 

compared to data of the general population and published 

in different scientific papers. 

The aim of the SCCSS was to know, in general and in 

many specific aspects, how survivors were doing, what 

kind of late effects they suffered from, to detect them as 

early as possible and to treat or alleviate them. Knowledge 

about long-term toxicities would aid the design of newer 

treatment strategies with the same efficacy and less morbidity. 

Included in the SCCSS were all children and adolescents 

diagnosed with a malignant disease in Switzerland between 

1976 and 2003. We looked for current addresses in 

the former medical files of the patients and through an Internet-based 

search system. Survivors with established 

addresses received at their home a comprehensive health 

questionnaire in the years 2007–2010 with questions in 

following domains: current quality of life, somatic and 

psychological health, current medication, fertility/offspring, 

current use of the medical system (physician and 

hospital visits), health behaviours (drinking, smoking, use 

of illegal drugs), socio-economic status and education 

level. 

This prospective cohort study is very important for both 

patients and paediatric oncologists. It shows the spectrum 

of potential late effects and their dynamics and will be 

able to identify what risk factors are associated with what 

late toxicities. In the same way, we think that it will be 

possible also to demonstrate the beneficial effects of 

more recent therapies, which are much more adapted to 

the biological behaviour of the disease, sparing unnecessary 

toxicity in good risk patients (“tailored therapy”, individualized 

oncology). In the last 50 years, paediatric 

cancer has moved from an almost always fatal to a usually 

curable disease. It is therefore compulsory to early detect, 

prevent, treat or at least reduce late toxicities in the majority 

of survivors. Another crucial topic is the transition 

from paediatric to adult medical care. This topic will be the

centre of a new study, based on the same data and also 

supported by the Foundation Cancer Research Switzerland 

(CRS) and the Swiss Cancer League (SCL). 


PD Dr Nicolas von der Weid 

Service de pédiatrie 




Phone +41 (0)21 314 13 34 

Fax +41 (0)21 314 33 32 

nicolas.von-der-weid@chuv.ch 

Wodnar-Filipowicz Aleksandra | Immunotherapy of 

human leukemia with natural killer cells: From bench 

to bedside (OCS 02175-02-2008) 

Acute leukaemias are rapidly progressing blood cell malignancies 

with poor prognosis. Front-line therapies with 

high doses of cytostatic agents and transplantation of 

allogeneic stem cells from the healthy bone marrow of 

donors offer the best chance of cure, but relapses are 

frequent and often fatal. This study aims at increasing the 

cure rate of patients with acute leukaemia by developing 

clinically-suitable approaches to immunotherapy with 

natural killer (NK) cells, a subpopulation of white blood 

cells capable of recognizing and eliminating malignant 

cells. 

The following goals have been achieved: 

1) The protocol of large-scale clinical-grade in vitro expansion 

of highly purified human NK cell products, which 

was developed at the Laboratory of Experimental Haematology, 

was adapted to rigorous good manufacturing 

practice (GMP)-compliant conditions suitable for clinical 

implementation. NK cells were purified from the peripheral 

blood of 6 healthy blood donors, and cultured in 

closed air-permeable culture bags with certified culture 

medium and components approved for human use. NK 

cell numbers increased 117.0±20.0 fold in 19 days. 

2) GMP-certified cell sorting was introduced to obtain 

cells with a high anti-leukaemic potential, called “single 

KIR NK cells”. The subsequent GMP-compliant expansion 

of cells was 268.3±66.8 fold, with a contaminating T cell 

content of only 0.006 %±0.002 %. The cell sorting step 

preceding the expansion step offered important advantages 

of increased tumour specificity with reduced culture 

volume, as well as lowered the costs of NK cell expansion. 

3) To implement our project in clinical practice, the GMP 

Laboratory was designed and built in 2010 at the Division 

of Diagnostic Hematology of University Hospital Basel. 

The construction and infrastructure conform to current 

regulations in Switzerland. The personnel, including academics 

and technicians, were trained, and the standard 

operating procedures were established. After the final 

certification of the GMP laboratory by Swissmedic, the 

feasibility, safety and efficacy of administration of expanded 

NK cells will be evaluated in phase I/II trials in the 

following clinical settings: a) in patients with leukaemia, 

after haploidentical stem cell transplantation; b) in patients 

with multiple myeloma, after autologous transplantation; 

and c) in elderly leukaemia patients not eligible for 

intensive chemotherapy and stem cell transplant. 

4) Our experimental studies designed to characterize the 

efficacy of alloreactive NK cells against leukaemia demonstrated 

that NK cells generated ex vivo with a GMP-compatible 

expansion protocol specifically recognize and destroy 

primary leukaemic blasts. 

We provided the first evidence that expanded “single-KIR 

NK” cells had a significant tumour-reducing effect in vivo 

in mice inoculated with human leukaemic cells. We also 

showed that NK cells are active against leukaemic stem 

cells, a small cell population responsible for both the initiation 

and recurrence of the malignancy, and therefore 

representing an important target for immunotherapy. 

The preclinical studies described in this project delivered 

important information as to the anti-leukaemic potential 

of high dose of activated NK cells, and the obtained results 

are contributing to the development of novel immunotherapeutic 

approaches increasing the chances of leukaemia 

cure. Our translational project combines the 

expertise of the Laboratory of Experimental Hematology 

in the Department of Biomedicine and the Stem Cell 

Transplant Team at the Hematology Clinic in the University 

Hospital Basel. 


Prof. Dr. Aleksandra Wodnar-Filipowicz 

Basel Stem Cell Center of Competence 



Klingelbergstrasse 61 

CH-4056 Basel 

Phone +41 (0)61 265 33 87 

aleksandra.wodnar-filipowicz@unibas.ch 

Wodnar-Filipowicz Aleksandra | Role of the natural 

killer cell receptors NCR and KIR in immune defence 

against human leukemia (OCS 01664-02-2005) 

Acute leukaemias are rapidly progressing blood cell malignancies 

with poor prognosis. Therapies with high dose of 

cytostatic agents and transplantation of stem cells offer 

the best chance of cure, but relapses are frequent and often 

fatal. Immunotherapy with natural killer (NK) cells 

represents a novel strategy to eliminate the residual malignant 

clones and prevent recurrence of the disease. 

This research project addressed the mechanisms of antileukaemic 

function of human NK cells. In a collaborative 

effort with the clinics of haematology in Basel and Aarau 

and in Warsaw, Poland, we were able to acquire a large 

number of leukaemia patient-derived blood and bone 

marrow samples. We demonstrated that expression of cell 

surface molecules serving as ligands for activating and inhibitory 

NK cell receptors defines the recognition and 

elimination of tumour cells by the cytotoxic function of 

NK cells. Therefore, our next goal was to design experimental 

approaches to enhance the leukaemia recognition 

process by means of selecting the anti-leukaemic, alloreactive 

NK cell populations. To strengthen the activating 

interactions between NK cells and leukaemic targets, we 

developed pharmacological treatments that enhanced the 

expression of cell surface ligand molecules specific for NK 

cells. To optimize the NK cell-mediated immunity against 

149

150 

recurrence of the disease, we addressed the recognition of 

leukaemic stem cells by NK cells. This is a small subpopulation 

of malignant cells that is implicated in the development 

and persistence of leukaemia. 

Results of these studies demonstrated that NK cell therapy, 

together with the use of pharmacological anti- 

neoplastic drugs, should be considered as an innovative 

combinatorial approach for treatment of leukaemia. The 

important outcome of our project is the translational 

“bench to bedside” clinical trial initiated in 2008 at University 

Hospital Basel. Altogether, the results of our studies 

contributed to a better understanding of the specific 

NK cell-leukaemia interactions and to the development of 

novel approaches towards curing human leukaemia. 


Prof. Dr. Aleksandra Wodnar-Filipowicz 

Basel Stem Cell Center of Competence 



Klingelbergstrasse 61 

CH-4056 Basel 

Phone +41 (0)61 265 33 87 

aleksandra.wodnar-filipowicz@unibas.ch 

Zaman Khalil | Monitoring of angiogenesis-related 

molecules during first line chemotherapy with 

bevacizumab and pegylated liposomal doxorubicin 

for advanced stage breast cancer: A substudy of 

the SAKK 24/06 trial (OCS 02029-02-2007) 

The anti-angiogenic drug Avastin ® is currently used in the 

treatment of different malignancies including breast cancer. 

Until now, no identified factor had been identified 

predicting benefit from Avastin ® . Many angiogenesis associated 

molecules are detectable in the blood of patients 

with cancer. We monitored prospectively six angiogenesis 

related factors in patients with advanced stage breast 

cancer treated with a combination of Avastin ® and pegylated 

liposomal doxorubicin (PLD) in a phase II trial of 

the Swiss Group for Clinical Cancer Research (SAKK). 

Methods 

Patients received Caelyx ® and Avastin ® every 2 weeks for 

a maximum of 12 administrations, followed by Avastin ® 

monotherapy until progression or severe toxicity. Blood 

samples were collected at baseline, after 2 months of 

therapy, then every 3 months and at treatment discontinuation. 

Enzyme-linked immunosorbent assays were used 

to measure vascular endothelial growth factor (VEGF), 

placental growth factor (PlGF), matrix metalloproteinase-9 

(MMP-9) and soluble VEGF receptors, sVEGFR-1, 

sVEGFR-2 and sVEGFR-3. The natural log transformed (ln) 

data for each factor was analyzed by analysis of variance 

(ANOVA) model to investigate differences between the 

mean values of the subgroups of interest (where a=0.05), 

based on the best tumour response. 

Results 

132 samples were collected in 41 patients. The mean 

of baseline MMP-9 levels was significantly higher in patients 

with tumour response (p=0.0202, log fold change= 

0.8786) or disease control (p=0.0035, log fold change= 

0.8427) compared to those with disease progression. 

Higher MMP-9 level was also a predictor of better progression-free 

survival (p=0.0417, hazard ratio=0.574, 

95 % CI=0.336–0.979), even when other prognostic factors 

were considered in a multivariate cox proportional 

hazards model (p=0.0266). MMP-9 level allows to distinguish 

two groups in the treated population, one with 

higher levels and longer progression-free survival and the 

other with lower levels and rapidly progressing cancer 

during treatment (p=0.0408). 

The mean level of baseline sVEGFR-1 was significantly 

lower in patients with disease control than those with progression 

(p-value=0.0008, log fold change=–1.0289). 

No strong correlation was shown for the other factors 

measured. 

Conclusions 

Higher baseline levels of MMP-9 could predict better efficacy 

of the combination of Avastin ® and Caelyx ® and a 

longer progression free survival. 

Clinical implications for the patients 

Only a limited number of patients with breast cancer benefit 

from the association of Avastin ® with their chemotherapy. 

If our exploratory results are confirmed in the future, 

MMP-9 could allow a better selection of the patients 

who will benefit from Avastin ® and consequently improve 

the benefit/risk ratio of this controversial treatment. 


Dr Khalil Zaman 





Phone +41 (0)79 556 78 01 

Secrétariat +41 (0)21 314 01 68 

Fax +41 (0)21 314 02 00 

khalil.zaman@chuv.ch 

Zhong Xiao Yan | Investigating tumour-derived 

methylation DNA in circulation as markers for non- 

invasive screening, early diagnosis, monitoring and 

determination of the prognosis of breast cancer 

(OCS 01993-02-2007) 

The discovery of cell-free DNA in plasma and serum samples 

offers new diagnostic possibilities in two crucial areas 

– prenatal genetic diagnosis and cancer detection. 

In the prenatal area, we have recently shown that both 

cell-free foetal DNA and foetal cells in maternal blood 

could be used for non-invasive prenatal diagnosis regarding 

genetic diseases and pathological pregnancies. We 

were able to detect cell-free foetal DNA earlier, more frequently 

and in greater amounts than foetal cells in the 

maternal circulation. In the cancer area, we have found 

that a high level of cell-free DNA in plasma was elevated 

in breast cancer and was related to tumour size and distant 

metastases, suggesting a potential for clinical applications. 

In order to develop a non-invasive blood test, we intend 

to identify breast cancer-related DNA methylation 

changes in tumour tissues as tumour biomarkers. DNA 

methylation analysis is a rapidly developing field. However, 

studies demonstrating its usefulness are still limited 

due to the fact that no one technique is superior. A new 

quantitative high-throughput MassCLEAVE TM assay (Sequenom) 

based on MALDI-TOF MS system enables dis-

covering of methylation, discriminating between methylated 

and non-methylated DNA and quantifying the 

methylation levels of DNA. 

We were able to use the MALDI-TOF MS-based assay to 

analyze DNA methylation status of 22 genes (APC, BIN1, 

BMP6, BRCA1, BRCA2, CADHERIN 1, CST6, DAPK1, 

EGFR, ESR2, GSTP1, NES1, Nm23-H1, P16, P21, PR, 

Prostasin, RAR-b, RASSF1, SRBC, TIMP3, TP53) in breast 

cancer (BC). They are mostly tumour suppressor genes 

(TSGs) involved in cancerogenesis, metastasis, drug resistance 

and response to hormone therapy in BC. We analyzed 

the methylation status of a total of 42,528 CpG dinucleotides 

on 22 genes in 96 different paraffin-embedded 

tissues (48 breast cancerous tissues and 48 paired normal 

tissues). A two-way hierarchical cluster analysis was used 

to classify methylation profiles. In this study, 10 hypermethylated 

genes (APC, BIN1, BMP6, BRCA1, CST6, 

ESRb, GSTP1, P16, P21 and TIMP3) were identified to distinguish 

between cancerous and normal tissues according 

to the extent of methylation. Individual assessment of the 

methylation status for each CpG dinucleotide indicated 

that cytosine hypermethylation in the cancerous tissue 

samples was mostly located near the consensus sequences 

of the transcription factor binding sites. These hypermethylated 

genes may serve as biomarkers for developing 

a non-invasive blood test for management of patients 

with breast cancer. 


Prof. Dr. Xiao Yan Zhong 

Forschungsgruppe pränatale Medizin und 

gynäkologische Onkologie 




CH-4031 Basel 

Phone +41 (0)61 328 69 86 

Fax +41 (0)61 265 93 99 

xzhong@uhbs.ch

152 

Zucca Emanuele | A prospective clinico-pathologic 

study of primary mediastinal B-cell lymphoma 

(PMBCL) (OCS 01709-04-2005) 

The need for radiotherapy in patients with primary mediastinal 

B-cell lymphoma (PMBCL) treated with the modern 

immunochemotherapy regimens is an unresolved issue 

that is becoming more and more controversial. The 

IELSG-26 study (International Extranodal Lymphoma 

Study Group) aims to obtain data on treatment outcomes 

following anthracycline-containing immunochemotherapy 

regimens, with or without mediastinal radiotherapy, 

the latter depending upon the practice of the participating 

institutions. Main endpoint of the study is to determine the 

response rate evaluated by positron emission tomography 

scans (18FDG PET-CT) following chemo-immunotherapy. 

The study enrolled 125 patients with PMBCL treated using 

either the R-CHOP or the R-MACOP-B chemotherapeutic 

regimen; 123 received consolidation radiotherapy. 

The recruitment ended in November 2010. Treatment 

results were monitored using 18-F-FDG PET-CT scan performed 

baseline, at 3– 4 weeks after the end of chemotherapy 

and 2 months post-radio-therapy, respectively. 

The PET CR was defined according to the criteria of the 

International Harmonization Project (Cheson et al., Journal 

of Clinical Oncology 2007). 

The central PET images qualitative review by an expert 

nuclear medicine specialist is ongoing and has included 61 

patients up to now. The PET-CT scan became negative at 

the end of chemotherapy in only 49 % of patients. The 

agreement between central review and “on site” reporting 

was 70 % (43/61) with increase on central review of 

the positive cases (from 39 % to 51 %) due mainly to the 

“on site” underestimation of the minimal residual 18FDG 

activity at the end of treatment. The rate of patients with 

persistent PET-positive scans at the end of immunotherapy 

in this study seems higher than in the non-mediastinal 

large cell lymphoma. This might partly depend on the 

relatively short interval between end of chemotherapy 

and imaging (which may affect the rate of false positive 

scans). Analysis of the PET response and its correlation 

with clinical outcome in the entire study population is 

awaited. It will be of paramount importance for the design 

of future clinical trials aimed at defining the increasingly 

debated role of radiotherapy. 


PD Dr. Emanuele Zucca 

International Extranodal Lymphoma 

Study Group (IELSG) 




Phone +41 (0)91 811 90 40 

Fax +41 (0)91 811 91 82 

emanuelezucca@yahoo.com 

Further completed research projects from July 2008 to December 2010 

Cozzi Luca | OCS 01821-02-2006 | CHF 80,800.– 

Servizio di fisica medica, Istituto oncologico della Svizzera italiana (IOSI), Ospedale regionale di Bellinzona 

e valli, Bellinzona 

Heterogeneity management in advanced algorithms for photon dose calculation and the clinical impact on 

breast and lung cancer radiotherapy. Validation of existing models against experimental studies, Monte Carlo 

simulations and determination of potential 

Garayoa Elisa Garcia | KLS 02040-02-2007 | CHF 150,700.– 

Zentrum für radiopharmazeutische Wissenschaften, Paul Scherrer Institut (PSI), Villigen 

Development of new bombesin-based radiopharmaceuticals with improved pharmacokinetics as potential 

imaging and therapeutic agents for bombesin receptor-positive tumours 

Hoek Keith | OCS 01927-08-2006 | CHF 145,500.– 


Zürich 

Clinical implications of Wnt signal-driven regulation of melanoma metastatic potential 

Stahel Rolf A. | OCS 01915-08-2006 | CHF 148,800.– 

Klinik und Poliklinik für Onkologie, Medizinbereich Innere Medizin-Onkologie, UniversitätsSpital Zürich, Zürich 

SAKK trial 17/04 on neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural 

mesothelioma (MPM) with or without hemithoracic radiotherapy, including translational research



Total funds allocated CHF 7,097,850.– 

Aebi Stefan | KFS 02689-08-2010 | CHF 260,300.– 

Medizinische Onkologie, Luzerner Kantonsspital, Luzern 

IBCSG 39-10 / MA.32: A phase III randomized trial of the effect of metformin versus placebo on recurrence 

and survival in early stage breast cancer 

Anderle Pedone Pascale | OCS 02303-08-2008 | CHF 195,000.– 

Institut für Biochemie und molekulare Medizin, Universität Bern, Bern 

Exploiting transporters in the tumor-stroma interface to aim for a more efficient chemotherapy 

Bertoni Francesco | KLS 02403-02-2009 | CHF 150,000.– 



Anaplastic large cell lymphoma: One or more entities? 



Pre-clinical evaluation of a new pharmacological approach using obatoclax for chemosensitization of drug 




Comprehensive analysis of the cell surface proteome of childhood refractory ALL for identification of new 

diagnostic and therapeutic targets 

Carbone Giuseppina | KFS 02573-02-2010 | CHF 305,100.– 


Deregulated ETS transcriptional network and clinical implications for prostate cancer progression 

Cathomas Gieri | KLS 02392-02-2009 | CHF 248,550.– 

Kantonales Institut für Pathologie, Kantonsspital Liestal, Liestal 

The role of polyomavirus in the development of Merkel cell and epithelial skin carcinomas 

Cavalli Franco | KLS 02399-02-2009 | CHF 157,550.– 


A randomised phase II trial on primary chemotherapy with high-dose methotrexate (HD-MTX) and high-dose 

cytarabine (HD-AraC) with or without thiotepa and with or without rituximab, followed by brain irradiation 

vs. high-dose chemotherapy supported by autologous stem cell transplantation (ASCT) for immunocompetent 

patients with newly diagnosed primary central nervous system lymphoma (PCNSL) 

Foti Michelangelo | KFS 02502-08-2009 | CHF 307,400.– 

Département de physiologie cellulaire et métabolisme, Faculté de médecine, Centre médical universitaire (CMU), 


Role of dietary free fatty acids, microRNA-21 and PTEN in liver cancer 

Gruber Günther | KFS 02527-02-2010 | CHF 150,700.– 

Institut für Radiotherapie Zürich, Klinik Hirslanden, Zürich 

BIG 3-07: A randomised phase-III study of radiation doses and fractionation schedules for ductal carcinoma 

in situ (DCIS) of the breast 

Hegi Monika E. | KFS 02670-08-2010 | CHF 198,300.– 

Laboratoire de biologie et génétique des tumeurs, Service de neurochirurgie, Centre hospitalier universitaire 

vaudois (CHUV), Lausanne 

Targeting the EGFR/PI3K pathway in glioblastoma, what matters? 

Heim Markus Hermann | KLS 02522-02-2010 | CHF 218,300.– 



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Heinimann Karl | KFS 02489-08-2009 | CHF 133,000.– 

Forschungsgruppe Humangenetik, Abteilung für medizinische Genetik UKBB, Departement Biomedizin, 

Universität Basel, Basel 

miRNA expression profiling in Lynch syndrome-associated colorectal cancer 

Körner Meike | OCS 02349-02-2009 | CHF 108,500.– 

Abteilung für Zellbiologie und experimentelle Krebsforschung, Institut für Pathologie, Universität Bern, Bern 

In vitro evaluation of the glucagon-like peptide 2 receptor expression in human cancer: molecular basis for 

in vivo tumor radiotargeting 

Kristiansen Glen | KFS 02465-08-2009 | CHF 171,200.– 

Institut für klinische Pathologie, UniversitätsSpital Zürich, Zürich 

Identification of a clinically applicable prognostic RNA signature of prostate cancer 

Mermod Nicolas | KFS 02446-08-2009 | CHF 360,100.– 

Laboratoire de biotechnologie moléculaire, Institut de biotechnologie, Université de Lausanne, Lausanne 

Evaluation of AP2 protein-binding microarrays for breast tumor profiling and for the prognosis of the response 

to chemotherapies 

Moeckli Raphaël | KFS 02637-08-2010 | CHF 107,200.– 

Institut de radiophysique, Département de radiologie, Centre hospitalier universitaire vaudois (CHUV), Lausanne 

Evaluation of second cancer risk models in radiotherapy for average and high dose levels 

Müller Beatrice U. | KFS 02449-08-2009 | CHF 297,900.– 

Departement für allgemeine Innere Medizin und klinische Forschung, Inselspital, Bern 

Transcriptional dysregulation during myeloid transformation in acute myeloid leukemia (AML) 

Nadal David | KLS 02375-02-2009 | CHF 227,900.– 

Abteilung Infektiologie und Spitalhygiene, Medizinische Klinik, Kinderspital Zürich, Universitäts-Kinderkliniken, 

Zürich 

Is endemic Burkitt’s lymphoma really promoted by chronic innate immunity triggering by malaria infection? 

Niggli Felix | KLS 02578-02-2010 | CHF 298,300.– 

Onkologielabor, Kinderspital Zürich, Universitäts-Kinderkliniken, Zürich 

Constitution of a national study centre for the European acute lymphoblastic leukaemia trial (AIEOP-BFM 

ALL 2009) on behalf of the Swiss paediatric oncology group (BFM-CH) 

Ozsahin Hulya | KLS 02656-08-2010 | CHF 155,300.– 

Unité d’onco-hématologie pédiatrique, Hôpitaux universitaires de Genève (HUG), Genève 

SIOPEL International Childhood Liver Tumour Strategy Group – a comprehensive research program and a 

randomized trial for standard risk hepatoblastoma 

Pabst Thomas | KLS 02520-02-2010 | CHF 349,100.– 

Institut für medizinische Onkologie, Inselspital, Bern 

Transcriptional dysregulation of the myeloid key transcription factor CEBPA in human acute myeloid leukemia 

Petignat Patrick | KFS 02691-08-2010 | CHF 230,600.– 

Unité d’oncogynécologie chirurgicale, Hôpitaux universitaires de Genève (HUG), Genève 

Self-sampling for HPV in women who do not undergo routine cervical cancer screening: A randomized trial 

Renevey Philippe | KFS 02681-08-2010 | CHF 138,400.– 

Centre suisse d’électronique et de microtechnique (CSEM), Neuchâtel 

Automatic vocal aid system for laryngectomees with improved voice quality 

Resink Theresa | KFS 02447-08-2009 | CHF 343,000.– 

Forschungsgruppe Signaltransduktion, Departement Biomedizin, Universität Basel, Basel 

T-cadherin: a functional determinant and early prognostic marker for malignant transformation of squamous 

cell carcinomas 

Roth Arnaud | KFS 02697-08-2010 | CHF 202,700.– 

Unité d’oncochirurgie, Hôpitaux universitaires de Genève (HUG), Genève 

Molecular heterogeneity and prognostic markers in colon cancer by analysis of gene expression and gene 

mutation data

Rothermundt Christian | KFS 02641-08-2010 | CHF 76,500.– 

Fachbereich Onkologie/Hämatologie, Kantonsspital St. Gallen, St. Gallen 

Metformin in castration resistant prostate cancer. A multicenter phase II trial of the SAKK (Swiss Group for 

Clinical Cancer Research) (SAKK08/09) 

Rufer Nathalie | KFS 02635-08-2010 | CHF 210,300.– 

Centre Ludwig de recherche sur le cancer, Université de Lausanne, Lausanne 

Structural and functional studies of T-cell receptors specific for tumor antigens: Implications for immunotherapy 

in cancer patients 

Schwaller Jürg | OCS 02357-02-2009 | CHF 232,000.– 

Forschungsgruppe Kinder-Leukämie, Departement Biomedizin, Universitätsspital Basel, Basel 

Exploring new molecular therapeutic targets in MLL-X acute leukemia 

Skoda Radek | KLS 02398-02-2009 | CHF 324,100.– 

Forschungsgruppe experimentelle Hämatologie, Departement Biomedizin, Universität Basel, Basel 

The pathogenesis of myeloproliferative disorders 

Stenner-Liewen Frank | KFS 02423-04-2009 | CHF 216,700.– 

Medizinische Onkologie, UniversitätsSpital Zürich, Zürich 

Establishment of GOLPH2 as a serum marker in hepatocellular carcinoma (within the SAKK 77/08 trial) and 

in bile duct cancer for routine clinical use 

Zeller Rolf | OCS 02368-02-2009 | CHF 360,350.– 

Forschungsgruppe Entwicklungsgenetik, Departement Biomedizin, Universität Basel, Basel 

Functional analysis of modulators of SHH pathway activity during the formation of medulloblastomas: 

a mechanistic study with clinical relevance 

Approved bursaries in 2009/2010 

Total funds allocated: CHF 621,250.– 

Arber Barth Caroline | BIL KFS 02506-08-2009 | CHF 109,300.– 

Targeting B acute lymphoblastic leukemia by adoptive transfer of leukemia-specific T-cells after cord blood 

transplantation 

Zielort: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, USA 

Baumann Michael | BIL KLS 02589-02-2010 | CHF 28,750.– 

Treatment of naive and fludarabine-refractory CLL in the TCL-1 mouse model with IPI-926 and other hedgehog 

pathway inhibitors 

Zielort: Labor für molekulare Biologie und Immunologie der CLL, Klinik I für Innere Medizin, Universität Köln, 

Köln, Deutschland 

Bohanes Pierre | BIL KLS 02591-02-2010 | CHF 53,500.– 

Intratumoral gene expression and germline polymorphism of patients with gastric cancer treated with chemoradiation 

in the Southwest Oncology Group protocol (SWOG) 9008 

Zielort: USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, USA 

Dedes Konstantin | BIL KLS 02406-02-2009 | CHF 60,000.– 

Identification of therapeutic targets for invasive ductal carcinomas of no special type 

Zielort: Breakthrough Breast Cancer Research Center, Institute of Cancer Research and the Royal Marsden 

Hospital, London, United Kingdom 

Omlin Aurelius | BIL KFS 02592-02-2010 | CHF 136,000.– 

A prospective comparison of three different methods of circulating tumor cell (CTC) isolation and characterization 

utilizing multi-colour immunofluorescence (IF) and fluorescent in-situ hybridization (FISH) in advanced 

cancer patients 

Zielort: Drug Development Unit, Royal Marsden Hospital, Sutton Surrey, United Kingdom 

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Riggi Nicolò | BIL KFS 02717-08-2010 | CHF 88,400.– 

The role of microRNAs in Ewing’s sarcoma cancer stem cells 

Zielort: Institut universitaire de pathologie de Lausanne (IUP), Centre hospitalier universitaire vaudois (CHUV), 

Lausanne 

Sùva Mario | BIL KFS 02590-02-2010 | CHF 104,300.– 

Role of the polycomb group protein EZH2 in glioblastoma cancer stem cells 

Zielort: Harvard Medical School, Massachusetts General Hospital, Boston, USA 

Wirth Johann Gregory | BIL KLS 02593-02-2010 | CHF 41,000.– 

Apoptosis resistance in prostate cancer, with a focus on the use of patient tissue samples 

Zielort: Harvard Medical School, Massachusetts General Hospital, Boston, USA 



Aebi Stefan | IBCSG39-10/MA.32: A phase III randomized 

trial of the effect of metformin versus placebo 

on recurrence and survival in early stage breast cancer 

(KFS 02689-08-2010) 

Duration: 01.09.2010 – 01.09.2013 

A large clinical trial is investigating whether metformin, a 

drug used for the treatment of diabetes, diminishes the 

risk of recurrence in patients with early breast cancer. The 

trial was organized by the National Cancer Institute of 

Canada (NCIC) Clinical Trials Group. Swiss patients can 

participate through the International Breast Cancer Study 

Group. 

All patients will receive prophylactic (adjuvant) therapy 

according to current standards; this study aims to compare 

the frequency of relapses of patients on additional 

metformin with patients on standard therapy. Patients 

who consent will be randomly allocated to the control 

group or to the metformin group. In addition to the number 

of relapses, biological properties of the tumours will 

be studied (e. g. presence of insulin receptors) to find out 

which patients are most likely to respond to therapy. This 

trial will include 3,500 patients worldwide. It is being conducted 

by academic researchers without any funding from 

the pharmaceutical industry. This clinical trial will demonstrate 

whether a simple therapy with a well-known drug 

improves the prognosis of women with breast cancer. 


Prof. Dr. Stefan Aebi 


Luzerner Kantonsspital 

CH-6000 Luzern 16 

Phone +41 (0)41 205 58 60 

Fax +41 (0)41 205 58 62 

Anderle Pedone Pascale | Exploiting transporters in 

the tumor-stroma interface to aim for a more efficient 

chemotherapy (OCS 02303-08-2008) 

Duration: 01.06.2009 – 01.06.2012 

Tumour cells within the same carcinoma are heterogeneous 

and contribute to different aspects of tumour progression. 

Whereas some are mainly responsible for tumour 

growth and are in a proliferating state, others at the 

invasive front are responsible for invasion into the surrounding 

tissue. It has become clear in recent years that 

the behaviour of a tumour does not solely depend on the 

tumour cells alone but also on the interaction of the tumour 

cells with the surrounding tissue. However, still little 

is known on how tumour cells respond to their microenvironment. 

A better understanding of the underlying processes 

could eventually lead to improved therapy. 

In this project we are studying the expression and functions 

of membrane transporters that are known or very 

likely to be involved in tumour progression and may also 

serve as drug carriers. Using laser-dissection microscopy 

of tumour and healthy colon tissue from freshly operated 

patients, we will extract RNA to perform genome-wide 

profiling. Microarray expression data will be further validated 

with RT-PCR and protein expression patterns with 

immunofluorescence in human colon sections. Appropriate 

cell lines will be selected based on the gene expression 

profile and used for drug sensitivity and resistance testing. 

Eventually, we will test the effect of selected chemotherapeutics 

in vivo in mouse tumour models. 

In general, studying the tumour-stroma interaction is still 

an emerging field. In particular, the expression of transporters 

has hardly been studied in the context of tumourstroma 

interaction or in the context of the heterogeneity 

of a solid tumour. Thus, a better understanding of the role

of transporters with respect to chemosensitivity and 

chemoresistance in the various tumour cell subpopulations 

will contribute to a more efficient chemotherapy. 


Dr. Pascale Anderle Pedone 

Institut für Biochemie und molekulare Medizin 


Bühlstrasse 28 

Postfach 

CH-3000 Bern 9 

Phone +41 (0)31 631 47 39 

Fax +41 (0)31 631 37 37 

pascale.anderle@mci.unibe.ch 

Bertoni Francesco | Anaplastic large cell lymphoma: 

One or more entities? (KLS 02403-02-2009) 

Duration: 01.08.2009 – 01.08.2011 

The recent 2008 World Health Organization (WHO) classification 

divides anaplastic large cell lymphoma (ALCL) 

into two distinct subgroups based mainly on the presence 

or absence of translocations affecting the anaplastic lymphoma 

kinase (ALK) gene. It is well accepted that patients 

with ALK positive ALCL are a distinct group sharing 

unique phenotypic and well-defined genetic and clinical 

features. Although the general clinical presentations and 

peculiar translocations and/or genetic events differ in the 

ALK positive and ALK negative ALCL subgroups, the question 

as to how related the two types of ALCL are and 

whether ALK negative ALCL may represent a subset of 

‘peripheral T-cell lymphomas, not otherwise specified 

(PTCL, NOS)’ remains open. 

The aim of this project is to focus on the genetic events 

underlying the pathogenesis of ALCL. The dual aim is to 

provide better tools to differentiate the individual lymphoma 

types and to identify genes that might represent 

new therapeutic targets. 


The study is being performed on a large series of ALK positive 

and ALK negative ALCL clinical samples; this has 

been made possible thanks to an international network of 

collaborating investigators. For genomic profiles we are 

using Affymetrix Human Mapping SNP6 Arrays and for 

gene expression profiling Affymetrix U133 plus 2.0. We 

are also data mining a very large dataset of proprietary 

and public T-cell NHL gene expression profiles. 

Results 

Ongoing are: data mining, validation of regions of interests 

and characterization of a gene identified by data mining 

of the gene expression profiles. The project is proceeding 

according to plan. 







Phone +41 (0)91 820 03 67 

Fax +41 (0)91 820 03 97 


Bourquin Jean-Pierre | Pre-clinical evaluation of a 

new pharmacological approach using obatoclax for 

chemosensitization of drug resistant childhood 

acute lymphoblastic leukemia (KFS 02453-08-2009) 

Duration: 01.03.2010 – 01.03.2011 

Using a preclinical model that is based on representative 

cases with highly resistant disease, we have established 

a new rationale for chemosensitization in acute lymphoblastic 

leukaemia (ALL). A small molecule that is thought 

to act as an antagonist of critical regulators of programmed 

cell death, obatoclax mesylate, very effectively 

restored the response to conventional chemotherapeutic 

agents in ALL cells that were otherwise completely refractory 

to these conventional chemotherapeutic agents. Unexpectedly, 

combination of obatoclax with dexamethasone, 

one of the most important drugs for ALL treatment, 

triggered a new type of programmed cell death specifically 

in resistant leukaemia cells but not in chemosensitive 

ALL cells, providing a strong rationale for a selective therapeutic 

targeting of resistant leukaemia cells. Interestingly, 

combination of obatoclax with other cytotoxic 

agents triggered a classical cell death pathway, the mitochondrial 

apoptotic pathway, suggesting that this agent 

interferes with critical mechanisms at the interface of two 

cell death pathways. 

Based on our work, which is in part published in the Journal 

of Clinical Investigation, a proposal for a clinical 

phase I trial was developed under the auspices of the 

leading group of experts in Europe, regrouped in the resistant 

disease committee of the international BFM Study 

Group (BFM stands for Berlin-Frankfurt-Münster to credit 

the important contribution of the first founders who 

paved the way to successful chemotherapy regimen for 

ALL). The aim of this study is to evaluate toxicity and gain 

first evidence for activity of the combination of obatoclax 

and dexamethasone in patients with relapsed or refractory 

ALL. This approach would then be taken forward as 

an investigational phase II window for high risk patients in 

first relapse to evaluate clinical activity. This trial will also 

contribute to designing an experimental therapy with several 

chemotherapeutic agents for patients with refractory 

disease. This proposal has received a lot of attention in the 

field and was declared as one of the priorities for drug development 

for refractory ALL by IBFM. 

To further improve and accelerate the clinical development 

of obatoclax as chemosensitizer, we established a 

larger number of cases with relapsed and refractory B-cell 

precursor (BCP) and T-cell ALL using our leukaemia xenograft 

model. The aim was to understand whether resistance 

to chemosensitization with obatoclax could occur in 

this patient population and to identify biomakers that 

would help predict a response to the drug. Interestingly, 

we could not find any case that would not respond to the 

combination of obatoclax with chemotherapeutic agents 

in BCP-ALL but detected several resistant cases in T-ALL. 

Sensitization activity to the glucocorticoid drug dexamethasone 

using obatoclax was clearly associated with 

inhibition of mTOR kinase activity, an important signalling 

node that integrates signals from different pathways to 

promote tumour growth. We used our leukaemia xenograft 

model to test the possibility to follow mTOR kinase 

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activity at the single cell level in the peripheral blood of 

treated animals, using flow cytometry. We consistently 

detected reduction of mTOR kinase activity in leukaemias 

that respond to treatment but not in leukaemias that were 

resistant to this approach. We will therefore include this 

method in the planned clinical trial to obtain evidence for 

biological activity of this approach in patients under treatment 

with obatoclax and dexamethasone. Furthermore, 

the identification of independent ALL cases that were resistant 

to obatoclax-mediated chemosensitization provides 

a strong basis to better understand the molecular 

mechanisms that are involved for drug activity. Finally, 

having first shown that we could prevent disease progression 

with a combination of obatoclax and dexamethasone 

in an in vivo mouse xenograft model, we now showed 

that we can induce remissions in mice with very high disease 

burden with a treatment that corresponds to the type 

of exposition patients will receive as treatment. 

Taken together, we have been able to establish a new rationale 

to achieve chemosensitization using a preclinical 

model that is representative of the patient population at 

need. We will continue to work on improving our understanding 

of the complex underlying mechanisms that are 

involved to achieve this type of treatment response, in 

order to provide a better methodology to predict which 

patients will benefit from this treatment approach. Our 

study illustrates how such a platform will be used to accelerate 

and improve the preclinical evaluation of new therapeutic 

options. We hope that this type of approach will 

contribute to improving the dismal outcome of patients 

with refractory disease and serve to reduce treatment in 

general. 


PD Dr. Jean-Pierre Bourquin 






Phone +41 (0)44 266 73 04 

jean-pierre.bourquin@kispi.uzh.ch 

Bourquin Jean-Pierre | Comprehensive analysis of 

the cell surface proteome of childhood refractory ALL 

for identification of new diagnostic and therapeutic 

targets (KFS 02583-02-2010) 

Duration: 01.08.2010 – 01.08.2012 

Acute lymphoblastic leukaemia (ALL) of childhood is a 

deadly disease for which salvage of therapy-resistant 

cases remains challenging. Leukaemia-associated cell surface 

markers have been very useful for leukaemia classification 

and may provide better possibilities for selective 

therapeutic intervention. Here we exploit the power of 

combining two experimental platforms to generate an unprecedented 

view at the cell surface landscape in childhood 

ALL. We have established a reliable methodology to 

expand small amounts of leukaemia cells directly from patient 

samples, while keeping the dominant genetic and 

phenotypic features of the original leukaemia. We are 

now in a unique position to perform biomedical studies 

that were previously deemed impossible due to limiting 

material. 

In collaboration with the Institute of Molecular Systems 

Biology at the ETH Zurich, we have mapped hundreds of 

cell surface proteins on leukaemia cells from patients with 

highly resistant or very chemosensitive disease. We took 

advantage of a proteomic technology that relies on the 

specific tagging of cell surface proteins on specific sugar 

structures on the protein backbone directly on the surface 

of intact living cells. Small peptide fragments can then be 

purified based on the presence of such a tag and analyzed 

simultaneously using mass spectrometry, a technique that 

enables us to determine the protein composition in a large 

mixture that is obtained from cellular preparations after 

the identification of these protein fragments. The proteomics-based 

approach completely recapitulated the typical 

pattern of leukaemia-associated markers for ALL classification, 

as it is usually analyzed by multicolour flow 

cytometry at diagnosis in the clinical setting. Importantly, 

we can detect proteins that are universally expressed in 

ALL or in contrast overrepresented in resistant cases. 

Different clinically relevant research questions are being 

pursued based on this dataset. Firstly, we identified a cell 

surface marker that is characteristic for a previously unrecognized 

subtype of ALL. Because expression at the 

protein level corresponds to gene expression levels for this 

marker, we have been able to expand this analysis to different, 

very large collections of patient samples that were 

available from two European clinical studies. We thereby 

identified a rare leukaemia subgroup, which could be consistently 

found at the same frequency in independent 

large cohorts of patients and only in groups with a higher 

risk of relapse. This new subtype carries a characteristic 

gene expression signature that is characteristic for an inflammatory 

response. We are now evaluating the effect 

of a large number of therapeutic agents to target the corresponding 

pathways. Second, we are exploring the importance 

of candidate cell surface proteins for the interaction 

of leukaemia cells with their microenvironment in the 

bone marrow, providing new targets to dislodge ALL cells 

from their protective niche. 

Taken together, the combination of the mouse xenograft 

model of ALL with modern proteomic technologies provides 

a view of the leukaemia cell surface with an unprecedented 

resolution. A number of applications will be derived 

from this knowledge base. A significant contribution 

will be the identification of a new biologic subgroup in ALL 

that will provide new insights in disease pathogenesis and 

may be amenable to alternative, less toxic therapeutic approaches. 


PD Dr. Jean-Pierre Bourquin 






Phone +41 (0)44 266 73 04 

jean-pierre.bourquin@kispi.uzh.ch

Carbone Giuseppina | Deregulated ETS transcriptional 

network and clinical implications for prostate cancer 

(KFS 02573-02-2010) 

Duration: 01.08.2010 – 01.08.2013 

ETS transcription factors have emerged as important elements 

in the pathogenesis of prostate cancer, and chromosomal 

translocations involving ETS genes are very frequent. 

We recently showed that multiple ETS alterations 

coexist in prostate cancers, resulting in potential transcriptional 

and phenotypic synergistic effects that can influence 

the clinical behaviour of the tumour. 

Objectives 

In this application we plan to investigate the clinical and 

functional impact of aberrantly expressed ETS factors 

alone and in combination. We will evaluate ETS expression 

patterns at different stages of disease, the effects of 

deregulated ETS genes on the prostate cancer cell phenotype 

and transcriptome in vitro and in vivo and the impact 

of selected ETS factors and ETS target genes on tumour 

clinical behaviour. 

Methods 

To reach our goal, we will integrate data from clinical 

prostate cancer samples with molecular and functional 

studies in multiple ETS cell models. We will analyze patient 

samples from benign prostate from different stages 

of prostate cancer progression in archival formalin-fixed 

paraffin-embedded tissue specimens and in a large collection 

of tissue microarray (TMA). Correlation of ETS expression 

and clinical parameters will be also assessed. 

Potential patient benefit 

These studies will lead to a better understanding of the 

role of the ETS factors in prostate cancer initiation and 

progression and may have important implications for prevention, 

prognosis and treatment of this disease. 


Dr. Giuseppina Carbone 





Phone +41 (0)91 820 03 66 

Fax +41 (0)91 820 03 97 

pina.carbone@irb.unisi.ch 

Cathomas Gieri | The role of polyomavirus in 

the development of Merkel cell and epithelial skin 

carcinomas (KLS 02392-02-2009) 

Duration: 01.07.2009 – 01.07.2011 

About 20 % of all malignant tumours are induced by infectious 

agents, namely, by viruses. Recently, a new virus 

called Merkel cell polyomavirus (MCV) has been detected 

in a rare aggressive skin tumour. We could show that 

MCV DNA can also be detected in about one-third of 

other epithelial skin tumours, tumours which are very 

common in the general population. In the present study, 

we are analyzing the type of MCV presence in these epithelial 

skin tumours using highly sensitive detection methods, 

including methods that allow the visualization of integrated 

virus within the cellular gene of the individual 

tumour cells. In addition, mutations in the viral genome 

will be analyzed, mutations which may be crucial for the 

malignant potential of this virus. The knowledge concerning 

tumour-inducing viruses is important, as contact with 

the virus can be omitted and a vaccine for prophylaxis 

may be developed. 


Prof. Dr. Gieri Cathomas 

Kantonales Institut für Pathologie 

Mühlemattstrasse 11 

CH-4410 Liestal 

Phone +41 (0)61 925 26 21 

Fax +41 (0)61 925 20 94 

gieri.cathomas@ksli.ch 

Cavalli Franco | A randomised phase II trial on primary 

chemotherapy with high-dose methotrexate (HD-MTX) 

and high-dose cytarabine (HD-AraC) with or without 

thiotepa and with or without rituximab, followed 

by brain irradiation vs. high-dose chemotherapy supported 

by autologous stem cells transplantation 

(ASCT) for immunocompetent patients with newly 

diagnosed primary central nervous system lymphoma 

(PCNSL) (KLS 02399-02-2009) 

Duration: 01.01.2009 – 01.01.2013 

Still as of recently, there was practically no possibility of 

cure for patients with PCNSL. In the last years, results 

have improved, however. In an earlier study, the International 

Extranodal Lymphoma Study Group (IELSG) demonstrated 

that the combination of two cytotoxic agents 

(methotrexate with Ara-C) represents the best currently 

available treatment. In this study, this standard chemotherapy 

with or without the addition of thiotepa and 

rituximab is used in the induction treatment. Thereafter, 

patients are randomised in two different modalities of 

consolidation: either radiotherapy of the brain or highdose 

chemotherapy followed by reinfusion of autologous 

stem cells. The aim of the study is to further improve the 

outcome in the treatment of this lymphoma and concomitantly 

to clarify the role of the brain irradiation. Should 

it be possible in future to avoid this latter treatment, it 

would represent an important improvement, since patients 

could be spared a lot of side effects. 


Prof. Dr. Franco Cavalli 




Phone +41 (0)91 811 86 66 

Fax +41 (0)91 922 20 84 

franco.cavalli@eoc.ch 

Foti Michelangelo | Role of dietary free fatty acids, 

microRNA-21 and PTEN in liver cancer 

(KFS 02502-08-2009) 

Duration: 01.01.2010 – 01.01.2013 

Diabetes and obesity represent important risk factors for 

the development of hepatocellular carcinoma (HCC). In 

particular, high levels of circulating fatty acids play an important 

role in the development of this cancer by stimulating 

an aberrant growth of hepatocytes. Fatty acids 

seem to act by inducing the expression of a specific microRNA, 

miR-21, which inhibits the function of the tumour 

suppressor PTEN. 

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160 

Our research projects aim at understanding the role of 

fatty acids, miR-21 and PTEN in the development of hepatic 

precancerous lesions and HCC. Experimental approaches 

using mouse genetic models fed special diets, 

and proteomic analyses to identify new factors modulated 

by miR-21/PTEN, are undertaken to reach this goal. 

Our research should allow us to better understand the 

molecular basis of liver cancer, in particular in the setting 

of metabolic diseases. In addition, the pertinence of future 

therapeutic interventions restoring normal miR-21 

and PTEN activities in hepatocytes to prevent or treat liver 

cancer should also be evaluated. 


Dr Michelangelo Foti 

Département de physiologie cellulaire et 

métabolisme 

Centre médical universitaire (CMU) 



1, rue Michel-Servet 


Phone +41 (0)22 379 52 04 

Fax +41 (0)22 379 52 60 

michelangelo.foti@unige.ch 

Gruber Günther | BIG 3-07: A randomised phase III 

study of radiation doses and fractionation schedules 

for ductal carcinoma in situ (DCIS) of the breast 

(KFS 02527-02-2010) 

Duration: 01.02.2010 – 01.02.2013 

Patients with ductal carcinoma in situ (DCIS) (precursor 

for breast cancer) are normally treated with breast-conserving 

surgery and postoperative radiotherapy (RT). This 

worldwide ongoing phase III trial is testing the influence 

of RT duration (different fractionation) and RT dose (+/– 

tumour bed boost) on local failure rates and quality of life 

(QoL). 


Individualization of postoperative RT for patients with 

DCIS after breast-conserving surgery for optimal tumour 

control and less toxicity. 

Methods 

Patients will be randomised into 4 treatment arms: 1) 

ARM A (25x whole breast RT) or 2) ARM B (16x whole 

breast RT) or 3) ARM C (ARM A + 8x boost) or 4) ARM D 

(ARM B + 8x boost). Clinical and biological parameters 

for local failure will be evaluated. QoL will be measured. 

Potential gain for the patients 

Radiotherapeutic individualization and optimization of 

different RT schemes in regard to local control and influence 

on QoL in patients with DCIS. 


PD Dr. Günther Gruber 

Institut für Radiotherapie 

Klinik Hirslanden 

Witellikerstrasse 40 


Phone +41 (0)44 387 25 50 

Fax +41 (0)44 387 25 51 

guenther.gruber@hirslanden.ch 

Hegi Monika E. | Targeting the EGFR/PI3K pathway 

in glioblastoma, what matters? (KFS 02670-08-2010) 

Duration: 01.02.2011– 01.02.2014 

Glioblastoma is the most aggressive and most common 

tumour of the brain, with a median survival of only 15 

months despite modern therapies. New cancer drugs specifically 

target aberrantly modified or activated molecules 

in the tumour cells that are thought to be essential for aggressive 

growth and thus, may represent the molecular 

“Achilles heel”. We are investigating the regulatory network 

associated with the growth-promoting effect of the 

epidermal growth factor receptor (EGFR) that is highly 

amplified in 50 % of all glioblastoma. 

We will combine molecular data of glioblastoma tissue 

from patients treated with an inhibitor of the EGFR, with 

data from experimental investigations of the EGFR network 

in glioblastoma cell lines and mouse models. The 

aim is to identify critical molecular “hubs” of the network 

that need to be targeted for inactivation of its growthpromoting 

mechanisms. The goal is to propose effective 

combination therapies, adapted to the molecular makeup 

of glioblastoma. 


Prof. Dr Monika E. Hegi 

Laboratoire de biologie et génétique des tumeurs 

Service de neurochirurgie 


(BH19-110) 



Phone +41 (0)21 314 25 82/81 

Fax +41 (0)21 314 25 87 

monika.hegi@chuv.ch 

Heim Markus Hermann | Hepatocarcinogenesis in 

chronic hepatitis C (KLS 02552-02-2010) 

Duration: 01.07.2010 – 01.07.2012 

Hepatocellular carcinoma is usually the consequence of 

chronic liver inflammation, for example chronic viral hepatitis 

C. The mechanisms responsible for carcinogenesis 

are not known. The aim of the study is to identify molecular 

mechanisms that are involved in hepatocarcinogenesis 

in chronic hepatitis C. 

We study liver cells that we infect with hepatitis C virus. 

We specifically investigate if important cellular processes 

such as DNA repair are impaired in cells infected with hepatitis 

C virus. We showed that an important phosphatase 

(PP2A) is induced by hepatitis C. PP2A inhibits another 

enzyme, PRMT1, which regulates histones through methylation 

of arginine amino acids. Histones are proteins that 

are important for the correct packaging of DNA in the nucleus. 

We plan to further investigate whether the changes 

induced by hepatitis C virus could be corrected by drugs 

such as S-adenosyl-L-methionine (SAMe) that correct the 

enzyme activity of PRMT1. 






CH-4031 Basel 

Phone +41 (0)61 265 51 74 

markus.heim@unibas.ch

Heinimann Karl | miRNA expression profiling in Lynch 

syndrome-associated colorectal cancer 

(KFS 2489-08-2009) 

Duration: 01.02.2010 – 01.02.2012 

Colorectal cancer (CRC) is among the most common cancer 

types in the Western world. Up to 20 % of CRCs have 

a hereditary basis, with Lynch syndrome representing the 

most common cancer predisposition worldwide. Although 

the genetic basis of Lynch syndrome is well known, medical 

management of carriers remains difficult, in particular 

with regard to disease development, prognosis and cancer 

prevention. 

Our study aims to assess how CRC development in Lynch 

syndrome is influenced by microRNA (miRNA) expression. 

miRNAs are short RNA molecules that control about 30 % 

of all genes in man. Because of their diagnostic, prognostic 

and therapeutic potential, miRNA research is topical. 

Our study wants to make a substantial contribution to the 

field, investigating a cohort of 260 clinically well-documented 

Lynch syndrome carriers and 145 CRC samples 

and comparing selected miRNAs with their expression in 

sporadic colon cancer. 


PD Dr. Karl Heinimann 

Forschungsgruppe Humangenetik 




CH-4058 Basel 

Phone +41 (0)61 267 07 73 

karl.heinimann@unibas.ch

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Körner Meike | In vitro evaluation of the glucagon- 

like peptide 2 receptor expression in human cancer: 

Molecular basis for in vivo tumor radiotargeting 

(OCS 02349-02-2009) 

Duration: 01.07.2009 – 01.07.2011 

Peptide receptors that are highly overexpressed in human 

tumours represent potential molecular targets for important 

clinical applications, namely, in vivo peptide receptor 

targeting of tumours. Radioactively labelled peptide analogues 

that bind specifically to tumoural receptors can be 

used for imaging or radiotherapy of tumours. Moreover, 

cold, long-acting peptide analogues may interfere with 

biologic functions of tumour cells regulated by peptide 

receptors, such as hormone release or proliferation. 

The glucagon-like peptide 2 (GLP-2) receptor represents 

a potential new candidate for such applications. It is closely 

related to the glucagon-like peptide 1 (GLP-1) receptor, 

which was recently identified as an important clinical target 

in insulinomas. The GLP-2 receptor had been of interest 

because of its stimulatory role in intestinal growth 

and, consequently, potential therapeutic use in short 

bowel syndrome. Lately, evidence has emerged on its possible 

role in cancer. The GLP-2 receptor was identified 

in tumours in single instances. Moreover, in vitro data indicate 

that it may stimulate tumour cell migration and 

growth. These preliminary results call for an in-depth 

evaluation of the GLP-2 receptor for its suitability as tumour 

target. 

The aim of our project was to perform the first step in that 

evaluation, namely, to assess the GLP-2 receptor expression 

quantitatively in a large spectrum of human tumours. 

We analyzed approximately 200 different human tissue 

samples for their GLP-2 receptor expression with in vitro 

receptor autoradiography. This method identifies receptor 

binding sites, i.e. the actual clinical target, in tissues. It allows 

specific receptor identification based on receptor 

pharmacology as well as quantification of receptor levels 

in tissues. We found a marked GLP-2 receptor expression 

in several tumour types mostly of gastrointestinal origin, 

in particular in gastrointestinal stromal tumours (GIST). 

The binding data were confirmed by RT-PCR. This tumoural 

GLP-2 receptor expression represents the molecular 

basis for an in vivo GLP-2 receptor targeting of GIST. 

In future studies it has to be investigated whether therapy 

with long-acting GLP-2 analogues of short bowel syndrome 

may affect the biologic behaviour of GIST. 


PD Dr. Meike Körner 

Abteilung für Zellbiologie und 

experimentelle Krebsforschung 




Postfach 62 

CH-3010 Bern 

Phone +41 (0)31 632 99 60 

Fax +41 (0)31 632 89 99 

meike.koerner@pathology.unibe.ch 

Kristiansen Glen | Identification of a clinically 

applicable prognostic RNA signature of prostate 

cancer (KFS 2465-08-2009) 

Duration: 01.01.2010 – 01.01.2012 

A major problem in the treatment of prostate cancer relates 

to the difficulty in estimating tumour aggressiveness. 

This probably leads to over-treatment in up to 35 % of 

prostate cancer patients. Unfortunately, current clinical or 

histopathological approaches are still unsatisfactory with 

regard to predicting the aggressiveness of prostate cancer. 

The aim of our study is to develop and validate novel, 

mRNA-based methods that will allow estimation of prostate 

cancer prognosis. In previous studies the applicant 

identified several mRNA-based markers that are prognostically 

relevant. Modern high-throughput technologies allow 

their measurement simultaneously in many tumours. 

By comparing expression profiles in retrospective samples 

representing both aggressive and indolent tumours, combinations 

of markers or profiles will be developed that aid 

estimation of the risk of individual prostate cancers to 

progress and eventually lead to the patient’s death or stay 

benign. In future, this approach may become an important 

tool for physicians that would allow them to apply 

tailored therapies to each patient based on a personal risk 

profile. 


Prof. Dr. Glen Kristiansen 

Institut für klinische Pathologie 


Schmelzbergstrasse 12 


Phone +41 (0)44 255 34 57 

glen.kristiansen@usz.ch 

Mermod Nicolas | Evaluation of AP2 protein-binding 

microarrays for breast tumor profiling and for 

the prognosis of the response to chemotherapies 

(KFS 02446-08-2009) 

Duration: 01.01.2010 – 01.01.2013 

In Switzerland, about 5,000 new cases of breast cancer 

are recorded each year, and despite significant progress, 

about 1,500 patients still die of this pathology. This is a 

very heterogeneous disease whose accurate classification 

remains difficult. Although the diagnosis makes it possible 

to tailor treatment to individual cases, some tumours do 

not respond to the therapy, and it is generally difficult to 

predict with certainty whether a treatment will be effective 

for a given patient. With the ability to predict the lack 

of therapeutic response in case of neoadjuvant therapy 

(chemotherapy before surgery), unnecessary treatments 

could be avoided and the patient could be operated on 

without undue delays. Most molecular methods investigating 

tumour biology are exploring solely DNA, mRNAs 

or proteins, and they are often unaware of the activity or 

functional interaction of proteins with each other and 

with target genes. In this project, we hope to develop an 

approach based on analyzing the interactions of proteins 

from the tumour with the genes responsible for tumour 

progression and resistance to chemotherapy, so as to provide 

a more comprehensive analysis of the tumour type 

and to potentially better predict its treatment response 

potential.

Study Objective 

To develop a new molecular diagnostic method to better 

predict the response to various therapeutic approaches 

available, especially focusing on neoadjuvant chemotherapy. 

Methods and Procedures 

Breast cancer chemotherapy resistance has been linked to 

the activity of transcription factor AP-2a, whose role in 

development and in various breast carcinogenesis has 

been well documented. However, the activity of AP-2a 

and its interaction with other oncogenic proteins are not 

easily detected by conventional techniques. This requires 

the establishment of innovative approaches to molecular 

diagnostics. Our previous results showed that a new approach 

based on the use of DNA chips called “proteinbinding 

microarrays” (PBM) allows detection of the activity 

and gene-binding specificity of the protein AP-2a from 

breast cancer biopsies and the distinguishing between 

healthy and cancer tissues. In this project proposal, we 

wish to use this technique to measure the activity of AP- 

2a on a PBM covering 6,000 human gene sequences 

to identify molecular interaction signatures that may be 

indicative of the tumour resistance or sensitivity to chemotherapy. 

Potential benefits to patients 

The application of this technique to study the response to 

chemotherapy could lead to the development of a new 

predictive tool for the choice of the most appropriate 

treatment for each patient, according to the type of cancer, 

and thus to further increase the success of these therapies. 


Prof. Dr Nicolas Mermod 

Laboratoire de biotechnologie moléculaire 

Institut de biotechnologie 


CH-1015 Lausanne 15 

Phone +41 (0)21 693 61 51 

Fax +41 (0)21 693 76 10 

nicolas.mermod@unil.ch 

Moeckli Raphaël | Evaluation of second cancer risk 

models in radiotherapy for average and high dose 

levels (KFS 02637-08-2010) 

Duration: 01.01.2011– 01.01.2013 

Cancer survival rates have increased over the last decades 

due to improvement in treatment quality and earlier detection 

of the disease through screening programs. However, 

the price of this success is a higher probability of a 

radiation-induced second cancer later in life. Modern 

high-level radiotherapy techniques yield different types of 

dose distribution, which may have an impact on second 

cancer risk. Presently, the impact of these techniques on 

second cancer risk is not clear. 

The objective of this study is to better understand the impact 

on risk estimation of non-linear risk models applied 

to inhomogeneous dose distributions. 

Non-linear dose-risk models will first be applied in simple 

and well-known irradiation conditions. Then, the impact 

of realistic organ shape and size will be investigated. 

Finally, modern high-level treatment techniques will be 

investigated. The study will yield a better understanding 

of the response of non-linear risk models for different 

types of dose distributions. It will also give some insight 

into the discrepancies between different epidemiological 

studies in dose/risk estimations. 


Dr Raphaël Moeckli 

Institut de radiophysique 

Département de radiologie 


Rue du Grand-Pré 1 


Phone +41 (0)21 314 46 18 

raphael.moeckli@chuv.ch 

Müller Beatrice U. | Transcriptional dysregulation 

during myeloid transformation in acute myeloid leukemia 

(AML) (KFS-02449-08-2009) 

Duration: 01.01.2010 – 01.01.2013 

Blood cancer, especially leukaemia, is a common disease, 

and improved therapeutic strategies are desperately 

needed, since the majority of patients with acute myeloid 

leukemia (AML) still die of their disease. In leukaemic 

cells, the normal development of white blood cells is typically 

blocked at a particular stage. In fact, blocked differentiation 

is the hallmark of acute leukaemia. Timely regulation 

of key transcription factors is crucial for normal 

haematopoiesis. In particular, the transcription factor 

CEBPA plays a key role in the differentiation of white 

blood cells. Disrupted CEBPA function leads to a block in 

differentiation at the myeloblast stage, whereas mature 

granulocytes are absent. Various alterations may lead ultimately 

to suppressed CEBPA function, thereby mediating 

the differentiation block in these leukaemias. What is 

missing so far is an unbiased comprehensive assessment 

of CEBPA transcription factor function among all subtypes 

of AML patients. 

Here we evaluate a method to reliably assess CEBPA function 

in AML patient samples at diagnosis. The hypothesis 

would be that suppressed CEBPA function is associated 

with favourable clinical outcome. We hope that this study 

will allow the identification of subgroups of AML patients 

that might benefit from therapeutic approaches targeting 

restoration of CEBPA function and thereby overcoming 

the differentiation block in these leukaemias. 


Dr. Beatrice U. Müller 

Departement für allgemeine Innere Medizin 

und klinische Forschung 

Inselspital 

CH-3010 Bern 

Phone +41 (0)31 632 03 78 

Fax +41 (0)31 632 0514 

beatrice.mueller@insel.ch 

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Nadal David | Is endemic Burkitt’s lymphoma really 

promoted by chronic innate immunity triggering by 

malaria infection? (KLS 02375-02-2009) 

Duration: 01.10.2009 – 01.10.2011 

Endemic Burkitt’s lymphoma (BL) is a type of lymph node 

cancer in Africa. The cancer cells harbour Epstein-Barr 

virus (EBV), which infects over 90 % of children for a lifetime. 

Malaria is thought to contribute to the formation of 

this cancer type. We have shown that stimulation of the 

innate immunity, as malaria does, pushes EBV into a form 

that enables lymphocytes to continuously proliferate. 

We will study the impact of immune stimulation on the 

preservation of EBV’s form, leading to survival and unrestricted 

proliferation of cells. Newly gained insights into 

the interaction between chronic stimulation of the innate 

immunity and the behaviour of EBV-infected cells towards 

cancer will hopefully allow the engineering of novel modalities 

for prevention and treatment of EBV-harbouring 

lymphomas. 


Prof. Dr. David Nadal 

Abteilung Infektiologie und Spitalhygiene 





Phone +41 (0)44 266 72 50 

Fax +41 (0)44 266 80 72 

david.nadal@kispi.uzh.ch 

Niggli Felix | Constitution of a national study centre 

for the European acute lymphoblastic leukaemia trial 

(AIEOP-BFM ALL 2009) on behalf of the Swiss Paediatric 

Oncology Group (BFM-CH) (KLS 02578-02-2010) 

Duration: 01.06.2010 – 01.06.2013 

Acute lymphoblastic leukaemia (ALL) is the most common 

malignancy of childhood. Remarkable progress has been 

made in the past decades. Combination treatment with intensive 

multi-agent chemotherapeutic regimens, adapted 

to biological factors like response to treatment, cytogenetic 

changes in leukaemic cells and minimal residual disease 

after initial treatment phase has raised the cure rate 

of the disease to over 80 %. However, treatment burden 

is still considerable. An international consortium established 

a new treatment protocol (AIEOP-BFM ALL 2009 

trial) with risk adapted treatment application, taking also 

into account early response assessment. Within the Swiss 

Paediatric Oncology Group we will establish a national 

study centre for ALL to coordinate relevant diagnostic 

procedures and to perform reference investigation, data 

collection and coordination of research. We hope to further 

improve the survival rate for childhood ALL and to 

decrease side effects, at least in subgroups of patients. 


Prof. Dr. Felix Niggli 

Onkologielabor 





Phone +41 (0)44 266 71 11 

felix.niggli.@kispi.uzh.ch 

Ozsahin Hulya | SIOPEL International Childhood Liver 

Tumour Strategy Group – a comprehensive research 

program and a randomized trial for standard risk 

hepatoblastoma (KLS 02656-08-2010) 

Duration: 01.10.2010 – 01.10.2013 

SIOPEL (Société internationale d’oncologie pédiatrique – 

Epithelial Liver Tumour Study Group) is a trials group for 

research on the diagnosis, treatment and long-term outcome 

of childhood hepatoblastoma (HB) and hepatocellular 

carcinoma. These cancers are extremely rare, with 

about 1.5 cases per million per year. The Swiss Paediatric 

Oncology Group (SPOG) has participated in SIOPEL trials 

1– 4 and is activating SIOPEL 6 in Switzerland. SIOPEL 6 is 

a multi-centre randomised phase III trial of the efficacy of 

sodium thiosulphate in reducing hearing loss with cisplatin 

chemotherapy for standard risk HB. The continued 

participation of SPOG in SIOPEL activities and research 

will result in optimal treatment of children with HB. 


Prof. Dr Hulya Ozsahin 

Unité d’onco-hématologie pédiatrique 


6, rue Willy-Donzé 


Phone +41 (0)22 382 46 20 

Fax +41 (0)22 382 47 20 

ayse.h.ozsahin@hcuge.ch 

Pabst Thomas | Transcriptional dysregulation of 

the myeloid key transcription factor CEBPA in human 

acute myeloid leukemia (KLS 02520-02-2010) 

Duration: 01.07.2010 – 01.07.2013 

Despite intensive chemotherapy, more than 50 % of patients 

with acute myeloid leukemia (AML) still die of the 

disease. To improve the treatment of patients with AML, 

novel innovative concepts are needed. The concept of differentiation 

therapy offers a possible approach. The block 

in normal differentiation of white blood cells is characteristic 

for AML cells. Importantly, each step during differentiation 

of normal white blood cells is regulated by only a 

handful of transcription factors. In particular, the transcription 

factor CEBPA plays a key role in this process. If 

CEBPA function is deficient, no mature granulocytes are 

observed, and this leads to an accumulation of leukaemic 

blasts. 

In this project, we analyze how CEBPA protein expression 

is regulated in leukaemic cells. Further, we aim to elucidate 

how CEBPA controls a new class of regulating molecules 

called microRNAs. Through specific reconstitution 

of CEBPA function, we intend finally to develop a novel 

therapeutic approach for patients with AML. 


Prof. Dr. Thomas Pabst 

Institut für medizinische Onkologie 


Inselspital 

CH-3010 Bern 

Phone +41 (0)31 632 41 15 

Fax +41 (0)31 632 41 19 

thomas.pabst@insel.ch

Petignat Patrick | Self-sampling for HPV in women 

who do not undergo routine cervical cancer screening: 

A randomized trial (KFS 02691-08-2010) 

Duration: 01.09.2011– 01.09.2013 

In Switzerland, 250 to 300 women are diagnosed with 

cervical cancer each year, and 100 die of the disease. 

Some 30–40 % of Swiss women do not have cervical cancer 

screening and are therefore at higher risk of developing 

cervical cancer. The study will include 1,100 women 

aged 25 to 69 years who have not participated in routine 

screening in the last three years. They will be invited 

to the screening procedure, a Pap smear (control group), 

or HPV self-sampling (study group). In the latter group, 

women will be able to take the sample themselves at 

home, using a kit that will be sent to them. The results of 

this study could provide women not screened by Pap tests 

with a simple alternative form of screening. This could 

overcome barriers to presentation for screening, such as 

difficulty in reaching a doctor, reluctance to undergo gynaecological 

examination and cost. Interviews will be 

conducted in order to gain a better understanding of the 

reasons for non-attendance and to gauge the acceptability 

of self-sampling. 


Prof. Dr Patrick Petignat 

Unité d’oncogynécologie chirurgicale 


Boulevard de la Cluse 30 


Phone +41 (0)22 382 68 16 

patrick.petignat@hcuge.ch 

Renevey Philippe | Automatic vocal aid system for 

laryngectomees with improved voice quality 

(KFS 02681-08-2010) 

Duration: 01.01.2011– 01.01.2013 

Medical rehabilitation techniques allow laryngectomees 

to partially recover vocal function, but it results in poor 

voice quality and insufficient speech intensity. 

The ultimate goal of the project is the improvement of existing 

speech processing algorithms for laryngectomees, 

which would increase laryngectomees’ quality of life by 

improving their communicational abilities. 

The approach is to further improve and refine the algorithms 

for speech restoration developed in a previous project. 

Special attention will be devoted to enhancing the 

perceived natural characteristics and speaker-specific artefacts. 

High perceptual performance will be aimed at, such 

as improving speech quality and intelligibility, through 

combined state-of-the-art parametric and statistical signal 

processing methods. 

The expected result is to obtain a sufficient quality of the 

restored speech so as to be integrated in a usable system 

(e. g. vocal aid, improvement of telephone calls, public audience 

amplification). 


Dr Philippe Renevey 

Centre suisse d’électronique et 

de microtechnique (CSEM) 

Rue Jaquet-Droz 1 

CH-2007 Neuchâtel 

Phone +41 (0)32 720 55 27 

prv@csem.ch 

Resink Therese | T-cadherin: a functional determinant 

and early prognostic marker for malignant transformation 

of squamous cell carcinomas 

(KFS 02447-08-2009) 

Duration: 01.01.2010–01.01.2013 

Skin cancer is a disease in which cancer cells are found in 

the outer layers of the skin. It occurs in different forms. 

Melanoma is highly metastatic and deadly. Basalioma 

(basal cell carcinoma) and spinalioma (squamous cell carcinoma) 

are relatively benign, but they occur much more 

frequently and cause major disfigurement. Whereas basalioma 

growth is locally restricted, spinalioma can transform 

into malignant metastatic cancers with fatal results. 

We want to understand the whys and hows of this transformation, 

and focus on T-cadherin, a molecule that 

seems important for integrity of skin. Too much or too 

little of T-cadherin has been found in many skin diseases, 

including skin cancers. We are studying tissue from spinalioma 

patients to see if particular changes in T-cadherin 

can predict malignant transformation. We use cells isolated 

from healthy skin and spinalioma to study how 

changes in T-cadherin affects growth and metastatic potential. 

Given that Switzerland has one of the highest 

rates of skin cancers in Europe, our results will aid better 

identification and treatment of those patients at risk of 

developing metastatic spinalioma. 


Prof. Dr. Therese Resink 

Forschungsgruppe Signaltransduktion 




CH-4031 Basel 

Phone +41 (0)61 265 24 22 

therese-j.resink@unibas.ch 

Roth Arnaud | Molecular heterogeneity and prognostic 

markers in colon cancer by analysis of gene expression 

and gene mutation data (KFS 02697-08-2010) 

Duration: 01.01.2011– 01.01.2013 

Prognostic markers allowing better determination of 

which patients operated on for colon cancer could benefit 

from additional treatment are missing. PETACC-3, a 

clinical trial in postoperative treatment of colon cancer, 

enrolled 3,278 patients and collected the pathologic material 

of 1,564 of them for the study of new molecular 

prognostic factors. In addition to the ability to validate 

some already known potential prognostic molecular markers, 

we performed new tests to insulate mutations of the 

genome of the tumour and to study their genomic expression. 

These tests provided us with large sets of data 

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166 

(> 50.000/patient). For their analysis, the Swiss Group for 

Clinical Cancer Research (SAKK) obtained the assistance 

of the Swiss Institute of Bioinformatics (SIB), which is specialized 

in the analysis of this type of biological data, with 

the financial support of the Swiss Cancer League. 


Dr Arnaud Roth 

Unité d’oncochirurgie 


4, rue Gabrielle-Perret-Gentil 

1211 Genève 14 

Phone +41 (0)22 372 77 44 

Fax +41 (0)22 372 98 50 

arnaud.roth@hcuge.ch 

Rothermundt Christian | Metformin in castration 

resistant prostate cancer. A multicenter phase II trial 

of the SAKK (Swiss Group for Clinical Cancer Research) 

(SAKK08/09) (KFS 02641-08-2010) 

Duration: 01.01.2011– 01.07.2012 

Patients with prostate cancer receiving androgen deprivation 

therapy (orchiectomy or GnRH analogue) develop 

hyperglycaemia and hyperinsulinaemia. There is a suggestion 

that high insulin concentrations promote progression 

of prostate cancer. 

Metformin is a biguanide and is being used in the treatment 

for diabetes. Metformin can potentially revert the 

above-mentioned negative effects of androgen deprivation 

in patients with metastatic prostate cancer. Additionally, 

metformin has an inhibitory effect on cell proliferation. 

We conduct a multicenter phase II trial with metformin in 

patients with slowly progressing castration resistant prostate 

cancer. The research question is whether metformin 

can stabilize the disease with tolerable side effects. We 

also measure metabolic changes due to metformin, and 

we aim to identify pharmacogenetic markers for a favourable 

treatment response. 


Dr. Christian Rothermundt 

Fachbereich Onkologie/Hämatologie 

Kantonsspital St. Gallen 


Phone +41 (0)71 494 11 63 

christian.rothermundt@kssg.ch 

Rufer Nathalie | Structural and functional studies 

of T-cell receptors specific for tumor antigens: 

Implications for immunotherapy of cancer patients 

(KLS 02635-08-2010) 

Duration: 01.04.2011– 01.04.2013 

Although tumour-reactive T lymphocytes can be detected 

in cancer patients, these immune responses often fail to 

control or eliminate the disease. Adoptive transfer of Tcells 

engineered with T-cell receptors (TCRs) has been 

recently developed with the aim to induce immune reactivity 

towards defined tumour-associated antigens to 

which the endogenous T-cell repertoire is non-responsive. 

An attractive approach to improve this strategy is to optimize 

the TCR sequence to increase its affinity for cognate 

tumour antigen. We recently generated tumour-specific T 

lymphocytes expressing sequence-optimized TCRs, and 

we showed that T-cell immune responses against cancer 

cells could be specifically improved. However, our study 

also revealed the presence of an affinity window for optimal 

T-cell function. The objectives of our current project 

are to characterize some of the parameters involved in 

regulation of TCR function. Identifying rationally optimized 

TCRs and expressing such tumour-specific receptors 

in T lymphocytes represents one of the most promising 

approaches to improving adoptive T-cell therapy 



Dr Nathalie Rufer 



c/o CHUV 

HO 05/1532 

Avenue Pierre-Decker 4 


Phone +41 (0)21 314 01 99 

nathalie.rufer@unil.ch 

Schwaller Jürg | Exploring new molecular therapeutic 

targets in MLL-X acute leukemia 

(OCS 02357-02-2009) 

Duration: 01.07.2009 – 01.07.2011 

Expression of mixed lineage leukaemia/lymphoma fusions 

(MLL-X) is a hallmark for a significant group of paediatric, 

adult and therapy-related acute leukaemias with a poor 

prognosis. Previous work suggested that the MLL fusion is 

essential to induce and probably maintain the disease. 

Genetic studies identified potential functional co-factors 

as well as downstream effectors of MLL-X leukaemogenesis 

including protein kinases like PIM1. We propose to: 

1) address the role of PIM kinases as biomarkers and therapeutic 

targets in haematological malignancies including 

MLL leukaemia; 2) search for potentially druggable novel 

protein kinases by performing an RNA interference screen 

in cells from conditional transgenic MLL models; and 3) to 

explore possibilities to block MLL leukaemia by targeting 

the fusion or critical co-factors of the MLL-X complex. 

Our project will provide important insights for potential 

molecular targeting, setting new landmarks for future 

therapeutic intervention. 


Prof. Dr. Jürg Schwaller 

Forschungsgruppe Kinder-Leukämie 




CH-4031 Basel 

Phone +41 (0)61 265 35 04 

Fax +41 (0)61 265 23 50 

j.schwaller@unibas.ch

Skoda Radek C. | The pathogenesis of myeloproliferative 

disorders (KLS 02398-02-2009) 

Duration: 01.10.2009 – 01.10.2012 

Myeloproliferative disorders (MPD) are chronic blood diseases 

characterized by overproduction of blood cell precursors 

in the bone marrow. Patients with MPD bear an 

increased risk (5–20 %) to develop an acute leukaemia after 

a variable latency. Therefore, MPD is often considered 

a “pre-leukaemia“. We found that in about 70–80 % of 

MPD patients, the blood stem cells carry a mutation in the 

gene “Janus kinase 2” (JAK2). JAK2 is an enzyme that 

transmits signals coming from the outside into the cell and 

the mutation (JAK2-V617) amplifies the growth-promoting 

effect of these signals, so that more blood cells are 

formed. The aim of our studies is to better understand 

how the JAK2-V617F mutation causes MPD, with which 

partner genes it collaborates in this process and what the 

predisposing events are that can favour the acquisition of 

MPD. 

To address these questions, we are combining detailed 

analysis of cells and tissues from patients with MPD with 

mouse models of MPD. Our studies in patients revealed 

that JAK2-V617F may be preceded by as yet unknown 

mutations. To follow up on this observation, we studied 

patients with MPD that in addition to JAK2-V617F have 

deletions of chromosome 20q (del20q) or carry mutations 

in a gene called TET2, and we determined the temporal 

order in which these mutations were acquired. Our studies 

showed that there is no fixed order of events, and 

some patients acquire JAK2-V617F first, followed by 

del20q or TET2 mutations, whereas in other patients with 

MPD the inverse order can be observed. Thus, deletions 

of chromosome 20 and mutations in TET2 are unlikely to 

represent pre-disposing events for JAK2-V617F, and we 

are examining other candidate genes for such a function 

in familial forms of MPD. 

A second question that we are addressing is why the 

JAK2-V617F mutation can cause 3 different subtypes of 

MPD, namely, essential thrombocythemia (ET) with elevated 

platelet levels, polycythemia vera (PV) with increased 

numbers of red cells and in some cases primary 

myelofibrosis (PMF) with fibrosis of the bone marrow and 

blood formation in the spleen and liver. We generated a 

mouse model of MPD that expresses the mutant JAK2- 

V617F and displays all 3 types of MPD. We found that ET 

develops when the mutant human JAK2-V617F is expressed 

at lower levels, while at higher levels PV phenotype 

can be observed. Myelofibrosis occurred later in 

these mice and appears to correlate with the platelet 

counts. Interestingly, when we made a mutation in a different 

position in JAK2 that is associated with a pure red 

cell phenotype in patients (JAK2 exon 12 mutation), we 

observed a pure red cell elevation in the mice, i.e. the 

same phenotype as in patients. Thus, in addition to expression 

levels, the different JAK2 mutations may also 

cause different quality of signals that favour the expansion 

of specific blood cell types. 

Finally, inhibitors have been developed that can reduce 

the enzymatic activity of JAK2 and are undergoing clinical 

trials in patients with MPD. Our mouse models have 

proven to be valuable in testing such compounds. 

Our projects on JAK2 have contributed to changing the 

diagnostic and therapeutic approach to patients with 

MPD. We are now examining how other known gene mutations 

collaborate with JAK2 mutations and are searching 

for as yet unknown new gene mutations in MPD. 


Prof. Dr. Radek C. Skoda 

Forschungsgruppe experimentelle Hämatologie 

Departement Biochemie 



4031 Basel 

Phone +41 (0)61 265 22 72 

Fax +41 (0)61 265 32 72 

radek.skoda@unibas.ch 

Stenner-Liewen Frank | Establishment of GOLPH2 

as a serum marker in hepatocellular carcinoma 

(within the SAKK 77/08 trial) and in bile duct cancer 

for routine clinical use (KFS 02423-04-2009) 

Duration: 01.11.2009 – 01.11.2011 

Malignant tumours of the liver are often detected in advanced 

stages, thus having a poor prognosis. Strategies 

for detection and surveillance of hepatocellular carcinoma 

(HCC) are urgently warranted. We recently described a 

novel marker GOLPH2 in HCC and bile duct cancer (BDC). 

Validation of our data and meanwhile other conformational 

data will be validated prospectively within the setting 

of a randomised clinical trial. 

Purpose 

Within the HCC trial SAKK 77/08 serial GOLPH2 measurements 

will be performed to investigate the prognostic 

and predictive value of this tumour marker. 

Methods 

Serum-GOLPH2 will be quantified using a sandwich 

ELISA, or enzyme-linked immunosorbent assay. Specific 

antibodies against GOLPH2 and purified GOLPH2 will be 

employed. Further, by screening phage libraries novel antibodies 

for therapeutic and testing purposes will be defined. 

Descriptive statistical analysis will be performed 

correlating GOLPH2 values with disease progression and 

overall survival. 

Benefit for patients 

A new marker for diagnostics and monitoring of HCC and 

BDC could be established. This has the potential to simplify 

clinical routine and clinical trials. 


PD Dr. Frank Stenner-Liewen 





Phone +41 (0)44 255 22 14 

Fax +41 (0)44 255 45 48 

frank.stenner@usz.ch 

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Zeller Rolf | Functional analysis of modulators of SHH 

pathway activity during the formation of medulloblastomas: 

A mechanistic study with clinical relevance 

(OCS 02368-02-2009) 

Duration: 01.01.2010 – 01.01.2013 

Medulloblastomas are among the most common and aggressive 

childhood brain tumours. Currently, the only 

therapy involves surgery in combination with radio- and 

chemotherapy. However, this often results in long-term 

negative side effects, as postnatal brain development is 

not yet completed at the time of treatment. The mechanisms 

underlying medulloblastoma development are analyzed 

using Ptch1 heterozygous mice, which are an excellent 

animal model. 

We showed that the protease inhibitor PN-1 is upregulated 

in 95 % of all biopsies of human medulloblastoma 

patients and overexpressed in mouse medulloblastomas. 

Genetic reduction of PN-1 in the mouse model reduces 

the tumour frequency by about two-thirds, and the remaining 

medulloblastomas are less aggressive. Therefore, 

we hope that our studies will not only provide insights into 

tumour formation but also pave the way to molecular 

therapy strategies of medulloblastomas. 


Prof. Dr. Rolf Zeller 

Forschungsgruppe Entwicklungsgenetik 




CH-4058 Basel 

Phone +41 (61) 695 30 33 

Fax +41 (0)61 695 30 90 

rolf.zeller@unibas.ch

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Palliative care research in Switzerland 

The National Strategy for Palliative Care 2010–2012 

[1] declared the promotion of research in the field of 

palliative care an urgent task. This prioritization is 

correct and important. Each year the European Association 

for Palliative Care (EAPC) holds a World Research 

Congress, at which important research activities 

in all European countries and also other countries 

are presented. Switzerland has been a participant at 

the congress for many years; however, it is worth 

noting that the same group of people present their 

work year after year. This indicates that Switzerland 

has unfortunately not succeeded in significantly 

strengthening and expanding this group of researchers. 

In international comparison, it is also noticeable 

that most of the research on palliative care in Switzerland 

is in the medical area, with clearly fewer 

studies being conducted in the areas of care, sociology, 

public health, and psychology. 

Current topics in palliative care research 

in Switzerland 

The working group for research of the Schweizerische 

Gesellschaft für Palliative Medizin, Pflege und 

Begleitung (abbreviated as “palliative ch”) lists the 

current research focal points in Switzerland [2]: end 

of life issues, including decision-making processes 

and patients’ living wills, care of the dying, palliative 

aspects, and aspects of assisted suicide. In addition, 

there is a lot of research activity in the area of 

frequent symptoms, especially fatigue, significant 

weight loss, and pain, and there are some projects on 

specific topics in the areas of neurology, cardiology, 

intensive care, paediatrics, and different types of dementia. 

Much less research activity is found in the 

Steffen Eychmüller, MD 

Medical director and head of the Center for Palliative Care at the Cantonal Hospital of St. Gallen 

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area of health services research. 1 This is mostly due 

to the fact that with the health system organized by 

the cantons, making it difficult to track patients’ 

paths, there are definite limitations to conducting 

this kind of research in Switzerland. Countries with 

national health systems are much more active in such 

areas of research. 

Regarding patient groups, the research activities on 

patients diagnosed with cancer continue to be the 

most frequent. This accords only in part with the international 

trend. In recent years, other countries 

have put much more emphasis on integrating patient 

groups with cardiovascular disease and pulmonary 

disease, and research interest has also focused on 

neurological diseases and especially dementia. 

Based on the World Health Organization’s definition 

of palliative care [3] it follows that palliative care research 

should not be restricted to medical issues but 

should instead include research topics from other 

areas, such as ethics, sociology, and economics. But 

the non-medical area has been underrepresented in 

the research up to now. However, there is hope that 

this will change through the National Research Programme 

“End of Life” (NRP 67), which was launched 

in 2011 and covers a wide range of topics. 

Attractiveness of palliative care research, 

1 Health services research is a research area within health care system research at the microlevel of 

the health care system, in particular hospitals, doctors’ practices, or specific technologies in the health 

system. The subject of health services research is sickness and wellness services. Other factors, such 

as the intermediary institutions (health insurance companies, medical associations, etc.) and the national 

health policy that shapes services in the long term are not the direct subjects of research. But they 

are taken into consideration in the scientific studies as framework conditions of certain health services. 

especially for junior scientists 

In the field of palliative care, there is a demand for 

research projects that are highly practice-oriented 

and need-oriented. Researchers are supposed to give 

greater heed to the soft voice of the seriously ill and 

dying and their caregivers. The idea of bottom-up or 

grassroots research impresses people, but it is not 

usually feasible in practice. Due to a lack of time and 

a lack of research resources, specialists working in 

clinical practice are often hardly in a position to submit 

research proposals that have a chance of being 

approved for a grant and to conduct research. Partners 

in academia as “engines” are urgently needed 

here and could, at least theoretically, join with specialists 

to become successful duos of practical orientation 

and academic competency and to be brilliant 

in a joint effort. With regard to these prospects, 

Switzerland has definitely fallen behind in international 

comparison. So far, there has been only one 

single chair in palliative care at the universities (an 

endowed chair at the University of Lausanne), and 

for years, no one could be appointed to it. At present, 

no further professorships are foreseen. At the 

universities of applied sciences, too, there are no 

specialized institutes or specialists for research in 

palliative care focusing on research topics in this 

field. In the professional curricula, in particular in 

medicine and nursing, there are still no specialized 

programmes leading to nationally recognized titles. 

But in the end, this type of specialized postgraduate

programme is needed – not only to interest young 

specialists in a new field but also to offer them 

attractive professional development. Ultimately, in 

view of the definition of palliative care, it would be 

important to set up inter-professional professorships, 

such as a joint academic position for persons in nursing 

and medicine, or also in public health and other 

areas. They would then collaborate on the broad and 

varied spectrum of palliative care and promote joint 

research. 

Palliative care research in different language 

regions of Switzerland 

When embarking upon a new field of study (such as 

research in the field of palliative care), it is an advantage 

when it can be done in one’s native language. 

Trying to understand the research methodology and 

dealing with statistics and research designs works 

best when one thoroughly understands the contents. 

For this reason, English as the “research language” is 

not always appropriate, and it is very understandable 

that members from the different language regions of 

Switzerland are joining together for these first steps 

in palliative care research. For instance, the Plateforme 

latine de recherche en soins palliatifs et fin de 

vie (www.plrsp.ch) was established in 2010. In an 

exemplary manner, this platform not only brings together 

researchers at different academic institutions 

but also, and most importantly, people interested in 

research at institutions in clinical practice, from hospitals 

to Spitex home care to nursing homes. This is a 

first step: not only to overcome barriers between academic 

institutions and the world of clinical practice 

and patient care but also as the researchers’ attempt 

to communicate together in their own language efficiently 

and understandably. The Plateforme latine de 

recherche for the French-speaking region of Switzerland 

is also open to Italian-speaking colleagues in Ticino. 

A similar platform is planned to be established 

for the German-speaking region of Switzerland in 

September 2011. 

International cooperation 

Another way to strengthen the national research capacity 

in the field of palliative care is to co-operate 

with international partners. Here in Switzerland, we 

already have many contacts. They range from the 

Euro-Sentinella collaboration between the Swiss 

Sentinel Surveillance Network (general practitioners) 

and European countries to cooperation with the 

University of Ottawa in Canada (Lausanne), but 

there are also contacts within EU projects. Here, 

in particular two projects in St Gallen, EPCRC and 

OPCARE9, profited greatly and have expanded their 

own research capacities in recent years [4, 5]. In the 

European Palliative Care Research Collaborative 

(EPCRC), research topics such as genetic disposition 

and the administering of opiates were examined. In 

Optimizing Care of the Dying in 9 Countries (OP 

CARE9), the aim was to set up a research collaboration 

on events in the dying process and their effects 

on support, monitoring, and treatment. These projects, 

funded through the EU 7th Framework are 

lucky chances, since they boost intensive collaboration 

with clear objectives and capacity building for 

several years to come. At the international level, this 

has led to additional projects. Furthermore, it has 

become clear that if palliative care research in Switzerland 

does not become firmly anchored in the 

academic sector, it is unlikely to remain competitive 

in the future. The phase of pioneers, also in research, 

must now become consolidated through a phase of 

implementation and integration of palliative care in 

the national research landscape. This is the only way 

that Switzerland’s continued participation in larger 

international projects with considerable potential 

synergies for national research can be ensured. 

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The financing of palliative care research 

in Switzerland 

In my experience, the pioneering phase is also over 

with regard to funding. In past years, first research 

projects could still find financial support outside of 

competitive research funds, based on goodwill. Now, 

this has clearly changed. Our research projects in all 

areas must bear critical evaluation in the form of the 

internationally established and common peer review 

system. With respect to quality, this is surely welcomed, 

but on the other hand, there are few reviewers 

who know and recognize the specific aspects of 

palliative care, from its inter-professional nature to 

multidisciplinarity and the specific methodology and 

its restrictions in the research. Special funding programmes 

could be an important step here. Another 

issue concerns the extent to which private foundations 

show commitment and interest in this much neglected 

area of research. 

What is palliative care? 

Palliative care is the care and treatment of persons with terminal, life-threatening 

and/or chronic, progressive illnesses. Palliative care begins early on, 

but its main emphasis is during the time when curing the disease is no longer 

considered possible and is therefore no longer the primary objective. Patients 

are ensured an optimal quality of life, adapted to their situation, up to the 

end of life, and their loved ones are offered appropriate support. Palliative 

care prevents suffering and complications. It encompasses medical pain and 

symptom relief and psychological, social, and spiritual support [7]. 

In 2009 the Council of Europe adopted a resolution 

on palliative care, assessing palliative care as “a 

model for innovative health and social policies” [6]. 

This could and should also serve as a model for the 

future development of palliative care research in 

Switzerland: an innovative model for inter-professional 

research and research in the related areas of 

health system, sociology, public health, economics, 

ethics, philosophy, and many other areas. With regard 

to the broad orientation of this research, the 

National Research Programme “End of Life” (NRP 67), 

launched in 2011, is a significant milestone. It remains 

to be seen whether this measure will suffice to firmly 

anchor this wide range of research in Switzerland.

Conclusion 

Palliative care is a broad and an interesting topic. In 

the light of the sociodemographic development in 

Switzerland and other Western countries, the social 

and political relevance of palliative care research is 

very high. Research efforts show that results cannot 

simply be “imported” from elsewhere but instead 

must be adapted to the cultural context of a country, 

or must be gained in the country itself. For this reason, 

an important objective over the years to come 

will be the establishment of a broad research community 

in the field of palliative care in Switzerland. 

This should represent and revitalize the various axes: 

from clinical practice research to philosophical issues, 

from various regional foci in the sense of a virtual 

national research institute to international collaboration 

– and all of this supported and solidly 

anchored within the academic world. This objective 

could best be reached in Switzerland by establishing 

modern, inter-professional professorships in palliative 

care. In this way, palliative care could be further 

developed as an innovative model also in research. 

Steffen Eychmüller, MD 

Steffen Eychmüller has been 

medical director and head of 

the Center for Palliative Care 

at the Cantonal Hospital of 

St Gallen since 2006. He studied 

medicine and completed his residency 

in Germany and Switzerland. 

He then conducted research 

in Sydney and Perth, Australia. 

Eychmüller specializes in palliative care, psycho-oncology, 

and pain. He is a co-investigator in the European research 

project OPCARE9. From 2005 to 2009 he was co-president 

of the Schweizerische Gesellschaft für Palliative Medizin, 

Pflege und Begleitung (palliative ch). 

Phone +41 (0)71 494 35 51 

steffen.eychmueller@kssg.ch 

www.palliativ-sg.ch 

References 

1. BAG/GDK (Federal Office of Public Health/Swiss 

Conference of the Cantonal Ministers of Public 

Health). Nationale Strategie Palliative Care 2010–2012 

[National Strategy for Palliative Care 2010–2012]. 

Available in German, French, and Italian at 

www.bag.admin.ch/palliativecare. A summary in 

English is available at http://www.bag.admin.ch/ 

themen/medizin/06082/10907/index.html?lang=de 

2. “palliative ch” working group for research (Arbeitsgruppe 

Forschung): www.palliative.ch/index. 

php?id=126 

3. WHO Definition of Palliative Care (2002): 

www.who.int/cancer/palliative/definition/en/ 

4. European Palliative Care Research Collaborative 

EPCRC: www.epcrc.org 

5. OPCARE9, a European collaboration to improve care 

of the dying: www.opcare9.eu 

6. Council of Europe Resolution 1649 (2009): Palliative 

care: a model for innovative health and social policies: 

http://assembly.coe.int/Mainf.asp?link=/Documents/ 

AdoptedText/ta09/ERES1649.htm 

7. BAG/GDK (Federal Office of Public Health/ 

Swiss Conference of the Cantonal Ministers of Public 

Health). (2010). Nationale Leitlinien Palliative 

Care [National guidelines for palliative care] (p. 8). 

Bern: BAG/GDK. 

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National Strategy for Palliative Care 2010– 2012 

The number of deaths per year in Switzerland will increase in the coming years and decades. 

Today, 60,000 persons of all ages die each year in Switzerland. The Federal Statistical 

Office (FSO) expects the number to reach 90,000 persons annually by the year 2050. 

This is due mainly to the age structure of the population: Predictions show that by 2030 

the number of persons over the age of 80 will more than double. 

In addition, owing to the rising life expectancy and medical advances, chronic illnesses and 

multimorbidity – when persons have several concurrent chronic conditions – have become 

more frequent. This affects not only older persons but also younger, seriously ill patients 

with cancer, neurological disorders or chronic, progressive diseases. 

A future consequence of this development is that, for one, the need for extensive care and 

treatment in the final phase of life will be greater. For another, medical care and treatment 

will become significantly more complex. 

In view of these diverse societal, social and health policy challenges, the Swiss government 

and the cantons decided to join together to promote palliative care in Switzerland. 

To this end, in the context of the National Health Policy Dialogue platform they launched 

the “National Strategy for Palliative Care 2010–2012”. 

With the National Strategy, the Confederation and the cantons established goals towards 

closing the identified gaps in access to care, financing, awareness, training and research. 

The measures will be realized and the means used in a targeted-oriented way in a concerted 

effort by all partners. The National Strategy focuses on increased coordination 

and on better utilization of synergies at the national and cantonal levels. 

Palliative care is the care and treatment of persons with terminal, life-threatening and/or 

chronic, progressive illnesses. Palliative care begins early on, but its main emphasis is 

the time when curing the condition is no longer considered possible and is no longer the 

primary goal. The goal of the National Strategy for Palliative Care is to allow all chronically 

ill and dying persons to receive palliative care that is adapted to their situation in order 

to improve their quality of life. 

Federal Office of Public Health (FOPH) 

Health Policy Directorate 

Daniela Wäfler 

Head, National Strategy for Palliative Care 

P. O. Box 

CH-3003 Bern 

Phone +41 (0)31 325 52 53 

palliativecare@bag.admin.ch 

www.bag.admin.ch/palliativecare

National Research Programme “End of Life” (NRP 67) 

The NRP 67 “End of life” aims to gain new insights into the last phase of life. The knowledge 

useful to guiding decisions and practices during the last stage of life will be made 

available to decision-makers in the health care system, as well as to politicians and professionals 

involved in the care of persons at the end of life. “Persons at the end of life” 

refers to persons – whether newborn infants, children, young people, middle-aged, elderly 

or very elderly people – who in all likelihood will live no more than a few months. 

Perceptions and frameworks regarding the end of life in a state of flux 

Perceptions and frameworks regarding the end of life are currently in a state of flux. New 

institutions, such as palliative care services or suicide assistance organizations, dedicate 

themselves to the needs of persons reaching the end of life. Demographic changes and 

new forms of family life challenge traditional models for support and provision of care 

to persons at the end of life. Living wills, the practice of suicide assistance, diverse expectations 

towards medical care, and high health care costs, have become the subject of heated 

public debate. 

Most people in Switzerland currently die in old age. Medical decisions influence the dying 

process in many cases. The focus of these decisions is to ensure a “good dying”, and no 

(longer) to fight impending death. The discourse on “good” and “bad” dying has become 

increasingly pluralistic and intense in recent years. 

Better understanding of dying processes 

New research is needed to understand these developments better. This is the rationale 

for NRP 67, which includes four main research areas: 

– Dying processes and provision of care: The focus here is on the current state of care 

for persons at the end of life in Switzerland, on dying processes, and on attendant 

practices with a special focus on palliative care. 

– Decisions, motives and attitudes: This area centres on decisions made during the dying 

process, and on the motives, convictions and attitudes underlying them. 

– Regulations and proposals for action: The focus here is on normative rules such as legal 

regulation or ethics guidelines, as well as questions regarding distributive justice in 

the health system. 

– Cultural concepts and social ideals: Death and dying have attracted a great deal of public 

interest in recent years. This research area includes questions regarding how death and 

dying are given meaning, cultural representations of death and dying, and relevant social 

normalization processes. 

In February the Federal Council commissioned the Swiss National Science Foundation to 

carry out NRP 67 “End of life”. This research programme is endowed with a budget of 

CHF 15 million. The research projects will be selected after a two-stage procedure in 2011. 

The research projects will start in spring 2012 and will be completed in 2017. 

NRP 67 “End of life” 

Dr. Stephanie Schönholzer 

Swiss National Science Foundation 

Wildhainweg 3 

3001 Bern 

Phone +41 (0)31 308 22 22 

Fax +41 (0)31 305 29 70 

sschoenholzer@snf.ch 

www.nfp67.ch 

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Ansermet François | KLS 01705-04-2005 | CHF 273,000.– 

Service de psychiatrie de l’enfant et de l’adolescent (SPEA), Hôpitaux universitaires de Genève (HUG), Genève 

Biobehavioral responses to stress in adult survivors of a childhood cancer 

Eychmüller Steffen | OCS 01776-08-2005 | CHF 170,000.– 

Palliativzentrum, Kantonsspital St. Gallen, St. Gallen 

Palliative care services in Switzerland: From a national survey to the development of a specific monitoring 

instrument 

Kiss Alexander | KLS 02038-02-2007 | CHF 302,000.– 

Abteilung Psychosomatik, Departement Innere Medizin, Universitätsspital Basel, Basel 

Physical and psychological predictors of patient fatigue 1 to 10 years after human stem cell transplantation 

Lehr Hans-Anton | OCS 02209-02-2008 | CHF 240,400.– 


Biomedical research on human tissues: In the twilight zone between autonomy and data protection. 

What do health professionals, patients and lay persons think about issues of consent and transparency 

in medical research, teaching, and quality control? 

Rüesch Peter | KLS 02198-02-2008 | CHF 155,800.– 

Fachstelle Gesundheitswissenschaften, Departement für Gesundheit, Zürcher Hochschule für Angewandte 

Wissenschaften (ZHAW), Winterthur 

Information needs of patients with curable adenocarcinoma of the prostate and professionals’ opinions: 

An international study (INEPAP) 

Schulz Peter J. | OCS 02101-08-2007 | CHF 150,400.– 

Istituto di comunicazione e sanità, Università della Svizzera italiana, Lugano 

Cancer and health literacy: Establishing a concept of cancer literacy 

Schwappach David | OCS 02109-08-2007 | CHF 117,200.– 

Stiftung für Patientensicherheit, Zürich 

Involving chemotherapy patients in the prevention of medical errors – a feasibility study 

Stiefel Friedrich | OCS 01847-02-2006 | CHF 184,600.– 

Service de psychiatrie de liaison (PLI), Centre hospitalier universitaire vaudois (CHUV), Lausanne 

Evaluation of individual and group psychotherapy for emotionally distressed cancer patients: A randomized 

controlled trial 

Stiefel Friedrich | KLS 02035-02-2007 | CHF 126,300.– 


Effects of communication skills training on oncology clinicians’ communication styles and defense mechanisms 

von der Weid Nicolas | KLS 02215-02-2008 | CHF 285,900.– 

Service de pédiatrie, Centre hospitalier universitaire vaudois (CHUV), Lausanne 

Longterm outcome of childhood cancer: Incidence and spectrum of late effects 

Znoj Hansjörg | OCS 01741-08-2005 | CHF 104,800.– 

Abteilung klinische Psychologie und Psychotherapie, Institut für Psychologie, Universität Bern, Bern 

Posttraumatic personal growth and posttraumatic stress in patients and their partners adapting to cancer



Eychmüller Steffen | Palliative care services in Switzerland: 

From a national survey to the development of a 

specific monitoring instrument (OCS 01776-08-2005) 

Purpose 

In terms of end of life care, Switzerland is known for its legalization 

of physician-assisted suicide but less for excellence 

in palliative care. This study provides the results of a 

national survey on the current situation of palliative care 

in the country. 

Method 

We conducted a national survey on all hospitals, residential 

aged care facilities and cancer networks and on a sample 

of community nursing services stratified by canton, 

addressing the institutions’ directors/head-nurses. 

Results 

In total 2,115 surveys were distributed. Response rate was 

57 % (n=1195), with an equal distribution from all care 

settings all over Switzerland. The overall image of palliative 

care is positive and largely integrated in conceptual 

frameworks, but there is no common definition of service 

characteristics (i. e. for specialist palliative care services), 

and implementation in daily practice varies widely. Geographically, 

the distribution of specialist palliative care 

services shows a predominance of the French-speaking 

part of Switzerland. Use of specific palliative care assessment 

tools or guidelines is best within hospital settings. 

Composition and training of specialist palliative care 

teams in most of the settings may not reach international 

standards. As part of the project, a minimal data set for 

patients in specialist palliative care settings was piloted in 

2008 and presented during the national consensus conference 

for palliative care in December 2008. 

Conclusion 

Palliative care is poorly developed in Switzerland with regionally 

few exceptions due to historic factors. A national 

strategy has been adopted only recently. 

Recommendations for the future 

This national survey was used as a major starting point to 

be built on for the “National Strategy for Palliative Care 

2010–2012” as published at the end of 2009. In addition, 

a first edition of a Swiss Palliative Care Directory was published 

in 2008, followed by a second version planned for 

spring 2011. A national dataset for palliative care patients 

will be established in cooperation with the Federal Statistical 

Office in 2011. 


This project has had an enormous impact on the planning 

and implementation of the national palliative care strategy. 

This strategy is subdivided into five different domains, 

reaching from public awareness and services structures 

to finances, education and research. The results of 

the project will be used for monitoring future service de- 

velopment and regional access to palliative care. Based on 

international data on improvement of patients’ outcomes 

through palliative care services whenever cancer or other 

diseases cannot be cured, we expect to see similar benefit 

for patients in our country. 


Dr. Steffen Eychmüller 

Palliativzentrum 



Phone +41 (0)71 494 3551 

steffen.eychmueller@kssg.ch 

Kiss Alexander | Physical and psychological predictors 

of patient fatigue 1 to 10 years after human stem cell 

transplantation (KLS-02038-02-2007) 

Chronic fatigue is a common, debilitating consequence 

among patients who have undergone haematopoietic 

stem cell transplantation (HSCT) as therapy for malignant 

diseases of the blood-forming system. Fatigue is a major 

source of impairment to quality of life (QoL) among these 

patients, is difficult to treat and is not well understood in 

terms of aetiology or course. 

Aims 

A study was conducted to identify physiological and psychological 

predictors of fatigue among 104 HSCT recipients, 

1-to-10 years post-transplantation. 45 age-andgender-matched 

healthy individuals served as controls. 

Methods 

Cardiovascular, respiratory and activity parameters were 

recorded using the LifeShirt system during a 24-h dailylife 

ambulatory assessment. Participants completed an 

electronic diary (every 50 minutes) on momentary states 

of exhaustion, energy, mood and situation. Retrospective 

self-report questionnaires assessed QoL, fatigue, anxiety, 

depression and HSCT-related complaints. Physical fitness 

was evaluated by bicycle ergometry. Among patients, the 

same procedure was repeated one year later. 

Results 

In comparison with healthy controls, HSCT survivors were 

less physically fit and remained impaired on many dimensions 

of health-related QoL. They also reported significantly 

higher levels of fatigue, anxiety and depression on 

the retrospective questionnaires. Electronic diary data 

partially confirmed these findings, with patients reporting 

substantially more exhaustion over the day than controls. 

On physiological measures, patients manifested significantly 

lower respiratory sinus arrhythmia and higher heart 

rate (HR) across levels of activity and times of day, indicating 

impaired cardiac vagal tone; group differences remained 

significant after adjusting for fitness. On the other 

hand, groups did not differ in daytime physical or metabolic 

activity (as indexed by accelerometry and minute 

ventilation). 

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180 

Within the patient group, level of fatigue was strongly associated 

with anxiety, depression, sleep quality, and pain 

and dyspnea complaints. However, fatigue was weakly 

and inconsistently related to physiological or medical risk 

parameters. 

Conclusions 

Cardiac autonomic functioning may be impaired among 

HSCT survivors, but patterns of daytime activity are similar 

to healthy controls. HSCT fatigue appears to be related 

more to extent of perceived symptoms than to concurrent 

physiological functioning or medical risk indices. The findings 

suggest that psychological processes related to symptom 

perception may be importantly involved in the development 

and maintenance of fatigue. These findings may 

contribute to understanding and treating fatigue in HSCT 

survivors. 


Prof. Dr. Alexander Kiss 

Abteilung Psychosomatik 



CH-4031 Basel 

Contact: 

Dr. Paul Grossmann 

Phone +41 (0)61 265 22 15 

grossmanp@uhbs.ch 

Lehr Hans-Anton | Biomedical research on human 

tissues: In the twilight zone between autonomy and 

data protection. What do health professionals, patients 

and lay persons think about issues of consent and 

transparency in medical research, teaching, and quality 

control? (OCS 02209-02-2008) 

Scientific research is of key importance in the development 

of knowledge on people and their health. This includes 

not only conducting clinical research on individuals 

but also research using human tissues. These tissues, 

taken in the course of treatment, may be used for research. 

Although this is a common practice, progress in 

medical science constantly brings up new issues with regard 

their use. Advances in this field provide new knowledge 

and possibilities for use of the tissues and the data 

thus generated, but the advances also raise new ethical 

problems, such as the possibility to establish a direct link 

between the human tissue and the personal characteristics 

of the patient. In view of these developments, it is imperative 

to understand how the public perceives the use 

of human tissues for research. The present study, conducted 

jointly by the University Institute of Pathology 

(IUP) and the University Institute of Social and Preventive 

Medicine in Lausanne (IUMSP), seeks to analyze the perceptions 

and attitudes of different groups in the Swiss 

population regarding the conservation and use of human 

tissues for research. 

This research project includes the following investigations: 

a systematic review of the literature, an analysis of 

the legal framework surrounding human tissue research, 

consultation of experts in the field, a qualitative study of 

the perceptions and expectations of the general public 

and health professionals regarding the use of human tissues 

for research and the development and testing of an 

instrument for a general population survey. 

Analysis of the scientific literature indicates that current 

debate is on the following questions: 1) What information 

should be given to patients so that they are able to make 

an informed choice? 2) What kind of consent should be 

obtained: broad consent or consent to a specific study; 

explicit or implicit consent? The literature analysis revealed 

that in some countries, studies have been conducted 

on perceptions and wishes of the population with 

regard to consent. It is to be noted that the studies did not 

investigate public expectations regarding what information 

should be given. The main results were the following: 

a) the general public and patients wish to have the opportunity 

to give or withhold consent to use of their tissues; 

b) a large majority of persons interviewed would give consent 

if asked; c) of the different forms of consent possible, 

general consent is favoured by most. 

The literature review and the expert interviews allowed us 

to identify the main issues at stake and to define the 

themes to be discussed in the focus groups. To facilitate 

debate, vignettes describing fictitious situations were presented 

to the participants. The opinions expressed in the 

focus groups, conducted in the Canton of Vaud, indicate 

that certain professionals fear that the need to obtain 

consent from patients to use of their tissues could act as 

a barrier to research. However, the general public and patients 

are generally favourable to research. On the other 

hand, they do express the wish to be explicitly consulted 

and informed of the possibility of such use, perceived 

rather as status-enhancing, or, in severe cases, as a means 

to make sense of one’s illness. 

Patients are ready to consent to use of their tissues for research 

on the condition that they are considered partners 

by health professionals. In this context, consent is seen as 

a means of ensuring that they have been informed rather 

than as an opportunity to withhold consent. 


Prof. Dr Hans-Anton Lehr 

Institut universitaire de pathologie de Lausanne 




Phone +41 (0)21 314 71 20 

Fax +41 (0)21 314 72 05 

hans-anton.lehr@chuv.ch 

Rüesch Peter | Information needs of patients with 

curable adenocarcinoma of the prostate and professionals’ 

opinions: An international study (INEPAP) 

(KLS 02198-02-2008) 

Objectives 

Curable cancer of the prostate can be treated by diverse 

methods of therapy, each of them being defined by specific 

pros and cons. Therefore, treatment decision is challenging, 

because patients have to consider a lot of data to 

understand the practical consequences of different treatment 

options. However, research indicates that men with 

prostate cancer are frequently not satisfied with the information 

offered: Many report not having received sufficient 

data; others complain about redundant, inapt or little 

intelligible information. Therefore, it was the purpose

of this study to ameliorate communication between 

health professionals and patients in the field of prostate 

cancer. 

Methods 

With this purpose in mind, we tried to incorporate both 

the view of patients and the professionals into the design 

of one study. Patients answered a questionnaire developed 

by an international research team and consisting of 

92 questions about prostate cancer and its treatment. Additionally, 

health professionals (urologists, oncologists, 

general practitioners, nurses, etc.) rated the same questions 

with regard to their importance for patients. The 

final sample of the study consisted of 128 patients and 

208 professionals from five clinics in the German-speaking 

part of Switzerland. 

Results 

Patients varied greatly with regard to their judgements of 

prostate cancer topics. Overall, they considered around 

half of the almost 100 provided topics as essential for appropriate 

information. However, some patients considered 

only a few questions as essential, whereas others 

rated almost all of the topics essential. Moreover, participating 

patients agreed only moderately on specific topics. 

This heterogeneity of ratings about what is important to 

know about prostate cancer is not only a patient phenomenon. 

On the contrary, even the health professionals varied 

greatly in judging what might be of significance for patients. 

Conclusions and suggestions 

Information needs with regard to treatment decisions of 

men with curable prostate cancer are broad but very individual, 

too. It seems hardly possible to reduce information 

about this disease to a core set of topics that could then 

be used to print a small booklet. This would still result in a 

substantial number of men with information needs not 

sufficiently covered. The results of this study emphasize 

the function of dialogue between doctor/professional and 

patient in transferring information on a highly individual 

level. However, counselling of prostate cancer patients 

should not be controlled (only) by some standardized 

guidelines but should overall consider the patients’ needs.

182 

Further, the results suggest that health professionals 

counsel men with prostate cancer quite variably. This can 

be confusing for the men concerned. Thus, a good working 

exchange between doctors and other professionals 

caring for patients seems to be of particular importance. 

Case management approaches to the care and coaching 

of patients with cancer could be helpful to reach this goal. 

We also think that the use of e-health, respectively Webbased 

tools, in the field of prostate cancer counselling 

could offer new ways of individually and flexibly tailored 

knowledge transfer from professionals to patients. 


Dr. Peter Rüesch 

Fachstelle Gesundheitswissenschaften 

Departement Gesundheit 

Zürcher Hochschule für Angewandte 

Wissenschaften (ZHAW) 

Technikumstrasse 71 

Postfach 

CH-8400 Winterthur 

Phone +41 (0)58 934 63 09 

peter.rueesch@zhaw.ch 

Schulz Peter J. | Cancer and health literacy: 

Establishing a concept of cancer literacy 

(OCS 02101-08-2007) 

Nowadays, the amount of health information for medical 

laypersons is overwhelming: It is often difficult for them 

to be adequately informed about issues that are essential 

to their health. In the case of cancer this complexity is accompanied 

by many emotions, such as feelings of powerlessness 

and helplessness or even fear of death, inducing 

people to avoid being confronted with information on the 

subject. Consequently, we assume that people lack an adequate 

understanding of cancer and of aspects of cancer 

that could be useful for making fundamental decisions 

regarding their health. The goal of the project was therefore 

to operationalize and to specify a usable and defined 

concept of cancer literacy, i. e. to understand what abilities 

and attitudes make a person cancer literate, what a lay 

person needs to know in order to be considered literate in 

cancer prevention, diagnosis and therapy and, eventually, 

how cancer literate the Ticino population is. 

Methods and results 

To operationally define the concept a Delphi study in 

three consecutive rounds was conducted among a panel 

of Swiss cancer experts (n=47/48/41 oncologists, GPs, 

nurses from oncology wards, social workers, public health 

experts). The result of the Delphi process was a first operational 

definition of the concept of cancer literacy, i. e. 

a list of the aspects of cancer that in the experts’ view laypeople 

should know to be considered cancer literate. 

Afterwards, six in-depth interviews with patients with 

cancer were conducted with the goal to investigate in 

greater depth their views on the cancer literacy concept as 

it emerged from the previous step. In particular, we were 

interested in their perception of experts’ expectations regarding 

people’s knowledge, attitudes and abilities; their 

actual knowledge and learning process; perceived deficits 

in cancer communication; perceived barriers to achieve 

the ideal knowledge proposed by experts; the expected 

role of the health system and health care providers. This 

step yielded a deeper understanding of the value and the 

limits of the concept of cancer literacy and provided some 

hints for its refinement. 

To assess the validity of the resulting concept and to gain 

first insights into the cancer literacy of the Ticino population, 

a survey was developed and administered to a sample 

(n=639) of the general population stratified for 

gender, age and educational level. The survey highlighted 

some major deficiencies as regards knowledge about 

some aspects of cancer. For instance, more than 60 % 

of the respondents were not aware of the relationship 

between overweight and cancer. Moreover, the survey 

revealed some significant knowledge differences between 

people with different education levels: To mention just 

one, almost 20 % of women with a lower education level 

vs. only 2 % of women with a high education level 

(p > 0.01) had never heard of a Pap test. 

Practice implications 

The study helped define the most health illiterate and 

cancer illiterate segments of the Ticino population and 

produced information on the best ways to reach these 

segments in communication campaigns. It also contributed 

to finding out what aspects of health and cancer 

literacy are most in need of improvement. This will aid 

the designing of information campaigns that target the 

deficiencies. 


Prof. Dr. Peter J. Schulz 

Istituto di comunicazione e sanità 

Università della Svizzera italiana 

Via Giuseppe Buffi 13 

CH-6900 Lugano 

Phone +41 (0)58 666 47 24 

Fax +41 (0)58 666 46 47 

peter.schulz@usi.ch 

Schwappach David | Involving chemotherapy 

patients in the prevention of medical errors – 

a feasibility study (OCS 02109-08-2007) 

As in all areas of medical care, critical incidents and medical 

errors can occur in oncology, e. g. when administering 

drugs. These events can be of considerable harm to patients. 

In addition to professional activities to improve patient 

safety, patient involvement in safety has been recommended 

internationally. An example is the cooperative 

check of medications. However, this raises the question as 

to whether patients are able and willing to get involved in 

safety, and what conditions need to be satisfied. 

Therefore, the main objective of our study was to investigate 

whether the involvement of patients in the prevention 

of errors would be a promising approach. To answer 

these questions qualitative and quantitative methods 

were used. First, 60 comprehensive semi-structured interviews 

with patients undergoing oncological treatment 

were conducted. In a second step, 4 focus groups (discussion 

groups) with clinical oncology nursing staff were 

conducted and content analysis was performed.

Based on these qualitative results, a sample of 470 oncology 

patients were surveyed using a written questionnaire. 

In the survey, a behavioural model that had been developed 

was tested. This model explains under what conditions 

patients will become involved for their safety in hospital. 

The results show that many patients are concerned 

for their safety and errors in their care. A vast majority 

agrees that they can contribute to the prevention of errors. 

Patients themselves describe their capabilities as developing 

in a learning process alongside the treatment 

course, in which they acquire knowledge and skills concerning 

what aspects of care to monitor, what to communicate 

to care providers and how they can engage for their 

safety. Patients acknowledge the benefit of error monitoring 

and reporting but perceive the process of notifying 

staff of potential errors often as unfamiliar and uncomfortable. 

Behavioural control and subjective norms are the 

key elements that explain whether patients communicate 

their perceptions of safety problems. Oncology nurses 

perceive involvement of patients as their core expertise. 

They share a general positive attitude towards the approach, 

even if communication about safety often is a 

challenge for them. Nurses sensitively apply different 

strategies to get patients involved through information 

and motivation. However, they also see room for improvement, 

particularly in the cultural implementation in hospitals: 

“Patients need to experience from the beginning that 

it is appreciated that they ask questions or notify us that 

something is not correct”. 

Based on these results, distinct recommendations can be 

made to involve patients in the prevention of errors while 

taking their individual situation into account. To be successful, 

it is crucial that clinical staff informs, motivates 

and supports patients. 


PD Dr. David Schwappach, MPH 

Stiftung für Patientensicherheit 

Asylstrasse 77 


Phone +41 (0)43 243 76 70 

schwappach@patientensicherheit.ch 

Stiefel Friedrich | Evaluation of individual psychotherapy 

for emotionally distressed cancer patients: 

A randomized controlled trial (OCS 01847-02-2006) 

In order to evaluate the role psychotherapy can play in the 

oncology setting, in the context of this study psychological 

support was proposed to every new patient treated 

between 2006 and 2009 by the Oncology Service of the 

University Hospital Lausanne (CHUV). 

Among the 2,000 patients approached, about half of 

them had been excluded based on the criteria defined in 

the study, mainly because of organizational reasons (living 

too far away from the hospital, intensive treatments, 

etc.), age > 75, advanced disease or language difficulties. 

A quarter of the patients approached (n=530) refused to 

participate in the study; of participating patients (n=419), 

about half of them (n=190) wished to benefit from psychological 

support, and the other half, who did not desire 

psychological support, agreed to be regularly evaluated 

with regard to their psychological state. Patients who de- 

sired support received either 4 or 16 sessions of brief psychotherapy 

and were regularly evaluated for a period of 

a year with regard to their psychological symptoms and 

quality of life, as this was the case for participating patients 

who did not wish to have this support. 

The results showed that for a lot of patients, it is difficult 

to organize or to accept psychological support; about 

20 % of patients included in the study, or 10 % of the total 

population approached, desired psychological support; 

patients motivated to receive support were in psychological 

distress; two-thirds of participating patients 

showed signs of important emotional detachment with regard 

to the efficacy of psychotherapeutic support. Data 

analysis is still ongoing. 

We conclude 1) that in the oncology setting, psychological 

support should be proposed proactively, for example 

through different modes of communication (telephone, 

e-mail), and more flexibly, for example by consultations at 

a patient’s home; 2) that at least 10 % of patients wish to 

benefit from psychological support at the beginning of 

treatment; 3) that patients in psychological distress were 

also those who desired support and that systematic 

screening of patients in need of support, for example by 

means of a questionnaire, may probably not be necessary; 

and 4) that because of the emotional detachment of patients 

with cancer, evaluation of the effects of psychotherapies 

should use other methods than those utilized up 

to now. 

This study has produced important results that contribute 

to the conceptualization and implementation of psychological 

support in oncology centres and to adjusting scientific 

investigation of this domain. 


Prof. Dr Friedrich Stiefel 

Service de psychiatrie de liaison 


Bugnon 44 


Phone +41 (0)21 314 10 90 

Fax +41 (0)021 314 10 86 

frederic.stiefel@chuv.ch 

Stiefel Friedrich | Effects of communication skills 

training on oncology clinicians’ communication styles 

and defense mechanisms (KLS 02035-02-2007) 

The importance of the quality of exchange between patient 

and physician has been recognised for several decades. 

Concerning the patient, it has been demonstrated 

that efficient communication can influence treatment adherence 

and improve quality of life and satisfaction with 

regard to care. Concerning the physician, it is known that 

efficient communication increases job satisfaction and 

reduces stress and/or burnout. 

Given the call for patient-centred medicine, all domains of 

health care are invited to pay attention to communication 

challenges. This is particularly true of oncology, which implies 

breaking bad news and because of the social representations 

of cancer. 

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184 

It is in this context that the Swiss Cancer League organizes 

Communication Skills Training (CST) with the aim to improve 

the communication skills of oncology clinicians 

(physicians and nurses). Conducted in small groups of 

8–10 participants and with a total duration of 30 hours, 

CST starts with a videotaped interview conducted by each 

participant with a simulated patient and is followed by an 

analysis of and feedbacks on the videos, role-plays and 

transmission of communication theory. CST is completed 

with individual monthly supervision for a period of six 

weeks and a second videotaped interview with a simulated 

patient. 

This study aimed to evaluate the linguistic aspects of CST 

based on the videotaped interviews; the evaluations consisted 

of a comparison of the first and the second videotaped 

interview in CST (pre-/post-comparison) and a comparison 

with interviews of clinicians who did not participate 

in CST and who interviewed the same simulated patients 

with the same scenarios with a six months interval. The 

group of clinicians having participated in CST consisted of 

57 and the control group of 56 oncology physicians and 

nurses. 

Communication skills of clinicians were evaluated and 

measured by means of communication analysis software 

(LaComm) developed at the Institut Jules Bordet (Brussels, 

Belgium) by the team under psycho-oncologist 

Darius Razavi. This software analyzes the logistic content 

(sentences and words) of interviews and categorizes them 

by taking into account the three major functions of a consultation: 

investigation, support and transmission of information. 

In total, the linguistic content of the interviews 

is assigned to 44 specific categories; for example, an utterance 

like “Did you start treatment?” is categorized as 

“closed binary evaluation”, or words like “sad” or “distress” 

are categorized as “psychological information”. 

This study demonstrated that clinicians who participated 

in CST are more inclined than those in the control group 

to break bad news by using precise words without using 

medical jargon and that they focus more on psychosocial 

issues, recognizing the patient as a subject. 

This study demonstrated a positive impact of CST on the 

communication skills of oncology clinicians, since the observed 

changes are in accordance with patient-centred 

communication. 





Bugnon 44 


Phone +41 (0)21 314 10 90 

Fax +41 (0)021 314 10 86 


von der Weid Nicolas | Long-term outcome of childhood 

cancer: Incidence and spectrum of late effects 

(KLS 02215-02-2008) 


The Swiss Childhood Cancer Survivor Study (SCCSS) is a 

common project of the Swiss Childhood Cancer Registry 

and the Swiss Paediatric Oncology Group and is run at the 

Institute for Social and Preventive Medicine of the University 

of Bern. Aim of the SCCSS was to know, in general 

and in many specific aspects, how survivors were doing, 

what kind of late effects they suffered from, to detect 

them as early as possible and to treat or alleviate them. 

Knowledge about long-term toxicities would help to design 

newer treatment strategies with same efficacy and 

less morbidity. 

Methods 

Included in the SCCSS were all children and adolescents 

diagnosed with a malignant disease in Switzerland between 

1976 and 2003. We looked for current addresses 

in the former medical files of the patients and through an 

Internet-based search system. Survivors with established 

addresses received at their home a comprehensive health 

questionnaire in the years 2007–2010. 

Results 

First results are already available in many domains and 

have been or will be published soon. 

Psychological health 

Psychological troubles are not different in frequency or 

severity in survivors of paediatric cancer and in the general 

population. But the proportion of people with severe 

troubles was higher in the survivors, so that in our opinion, 

psychological support should be offered to this population. 

Socio-economic and education status 

Comparing education level reached in survivors and the 

general population, no major differences were found. Initially, 

survivors had more school difficulties, e. g. needed 

to repeat one school year or received teaching support, 

but they eventually achieved the same levels of education 

as the control population. As expected, survivors of brain 

tumours and patients having had a relapse of their primary 

cancer (especially leukaemia) showed more problems 

and often achieved lower education levels. 

Health behaviours (use of alcohol, tobacco, cannabis) 

We found different groups of behaviours in the survivors 

of cancer; compared to the controls, a larger proportion of 

survivors, especially men, engaged in binge drinking (i. e. 

consumption of large amounts of alcohol in a short period 

of time). Survivors were more active than controls in daily 

physical activities but engaged less in sports, especially 

women.

Use of the medical/public health system 

Only a minority (about 20 %) of the survivors of paediatric 

cancer were involved in a systematic follow-up for their 

former disease, and the numbers decreased with time. 

The same was true of the availability of medical files summarizing 

their former disease and therapy and describing 

the needed follow-up examinations and schedule. Many 

survivors found that regular follow-up was unnecessary. 


This prospective cohort study is very important for both 

patients and paediatric oncologists. It shows the spectrum 

of potential late effects and their dynamics and will be 

able to identify what risk factors are associated with what 

late toxicities. In the same way, we think that it will be 

possible also to demonstrate the beneficial effects of 

more recent therapies, which are much more adapted to 

the biological behaviour of the disease, sparing unnecessary 

toxicity in good risk patients (“tailored therapy”, individualized 

oncology). In the last 50 years, paediatric 

cancer moved from an almost always fatal to a usually 

curable disease. It is therefore compulsory to early detect, 

prevent, treat or at least reduce late toxicities in the majority 

of survivors. Another crucial topic is the transition 

from paediatric to adult medical care. This point will be 

the focus of a new study based on the same data and also 

supported by the Foundation Cancer Research Switzerland 

and the Swiss Cancer League. 


PD Dr Nicolas von der Weid 

Service de pédiatrie 




Phone +41 (0)21 314 13 34 

Fax +41 (0)21 314 33 32 

nicolas.von-der-weid@chuv.ch 

Znoj Hansjörg | Posttraumatic personal growth and 

posttraumatic stress in patients and their partners 

adapting to cancer (OCS 01741-08-2005) 

In this longitudinal study, a representative sample of patients 

with a new primary cancer diagnosis was assessed 

within eight weeks of diagnosis, six months after diagnosis 

and 12 months thereafter. Measures included symptoms 

of emotional distress, psychosocial parameters, pain, aim 

of medical treatment and the Posttraumatic Growth Inventory 

(Tedeschi & Calhoun, 1996). In addition, partners 

were also investigated, because gender and role differences 

of couples challenged with cancer have been investigated 

with different results. 


We intended to describe the longitudinal course of posttraumatic 

personal growth and posttraumatic stress in the 

first year post-diagnosis. Second, we intended to identify 

predictors of perceiving posttraumatic personal growth 

vs. posttraumatic stress from cancer at the individual and 

dyadic level for patients and their partners. 

Method 

A total of 346 patient names were provided by their doctors. 

After exclusion based on time since diagnosis and 

other criteria, 296 of the remaining patients were deemed 

eligible, 287 consented to receive the assessment by mail, 

and 218 patients returned a completed questionnaire 

(74 % response rate). No significant differences were 

found between responders and non-responders regarding 

age, stage of disease, ECOG performance status, tumour 

site, curative versus palliative treatment or partners’ 

study participation. 

During the initial phone call, participating patients were 

asked whether they had been living with an intimate partner, 

married or not, for at least six months. If yes and 

where available, spouses were given full study information 

on the phone; 166 spouses were deemed eligible and 

were sent the assessment package together with the 

patient’s and along with full written study information; 

137 spouses returned the completed questionnaire (83 % 

response rate). 

Measures assessed multiple quality of life (QoL) dimensions 

including health-related and dyadic QoL as well as 

symptoms of distress: anxiety, depression, intrusion, 

avoidance and hyperarousal. The main intention of this 

study was to understand in more detail how patients and 

their partners adapt to cancer diagnosis. In order to optimally 

utilize all gathered data, we decided to analyze t1 

and t2 measurements separately and additionally to the 

longitudinal analysis. 

Results of the study 

Multivariate analyses revealed, eight weeks after diagnosis, 

marked symptoms of distress for 25 % of the respondents. 

Twelve months after diagnosis 15 % would still need 

professional help. Most of the patients reported posttraumatic 

growth (PTG) at least in some respect. PTG appeared 

together with emotional and cognitive coping, but 

it was not associated with emotional distress or more progressed 

disease. These results support the findings that 

PTG is not a strategy aimed to deny the seriousness of a 

cancer diagnosis. Moreover, these results indicate that patients 

reporting PTG realize and accept the bad and the 

good of a cancer diagnosis. One-third of the variance of 

PTG is explained by active and target oriented coping, 

seeking social support and emotion regulation. This result 

has important clinical significance, in that these strategies 

can be fostered through psychological interventions. 

Among couples coping with cancer diagnosis, the effects 

of gender, role (patient vs. spouse) and patient relationship 

status (single vs. partnered) on quality of life (QoL) 

have been investigated with inconsistent results. The present 

study examined the impact of gender, role and relationship 

status on male and female patients, their spouses 

and non-partnered patients. Multivariate analyses of covariance 

revealed lower QoL for women versus men, and 

for spouses versus patients on a number of measures 

(health-related QoL, satisfaction with dyadic coping, anxiety 

and intrusions). 

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186 

Recommendation 

Female spouses of patients with cancer are at high risk of 

deteriorated QoL immediately after diagnosis and require 

special attention to their psychosocial care needs. Our results 

show that most patients with a cancer diagnosis cope 

well. However, partners are often overlooked. Especially 

female partners, who take on care-taking burden, suffer 

from detriments in quality of life. Specific psychological 

help and coaching is not only important for patients but is 

also especially important for their life partners. 


Prof. Dr. Hansjörg Znoj 

Institut für Psychologie 

Abteilung für klinische Psychologie und 

Psychotherapie 


Gesellschaftsstrasse 49 

CH-3000 Bern 9 

Phone +41 (0)31 631 45 91 

Fax +41 (0)31 631 82 12 

hansjoerg.znoj@psy.unibe.ch 

Further completed research project from July 2008 to December 2010 

Ansermet François | KLS 01705-04-2005 | CHF 273,000.– 

Service de psychiatrie de l’enfant et de l’adolescent (SPEA), Hôpitaux universitaires de Genève (HUG), Genève 

Biobehavioral responses to stress in adult survivors of a childhood cancer




De Geest Sabina | KFS 02705-08-2010 | CHF 112,900.– 

Institut für Pflegewissenschaften, Universität Basel, Basel 

PROVIVO – patient reported outcomes in view of symptom experience of late effects and selfmanagement 

of adult longterm survivors after allogeneic haematopoietic stem cell transplantation – a mixed methods study 

Despland Jean-Nicolas | OCS 02338-02-2009 | CHF 251,350.– 

Institut universitaire de psychothérapie (IUP), Département de psychiatrie, Centre hospitalier universitaire 

vaudois (CHUV), Prilly 

Communication in cancer care: The relationship between clinician’s defense mechanisms, patient satisfaction 

and information recall 

Ehlert Ulrike | KFS 02662-08-2010 | CHF 173 600.- 

Klinische Psychologie und Psychotherapie, Psychologisches Institut, Universität Zürich, Zürich 

Psychobiological factors influencing the course of HPV infections in young women: a longitudinal study 

Kiss Alexander | OCS 02400-02-2009 | CHF 187,200.– 

Abteilung Psychosomatik, Bereich Medizin, Universitätsspital Basel, Basel 

A cognitivebehavioural mindfulness intervention to improve healthrelated quality of life, depression and 

fatigue among longterm haematopoietic stem cell transplant survivors 

Mueller Michael D. | KFS 02456-08-2009 | CHF 116,500.– 

Gynäkologie und gynäkologische Onkologie, Universitätsklinik für Frauenheilkunde, Inselspital, Bern 

Creating and validating a patientpertinent instrument to assess symptoms experienced related to surgical 

wounds in women with vulvar neoplasms – a mixed methods study (WOMANPRO) 

Stiefel Friedrich | KFS 02353-02-2009 | CHF 124 200.– 


Effects of communication skills training on oncology clinicians’ defense mechanisms, communication 

outcomes and working alliance – extension 

Tschudin Sibil | KLS 02577-02-2010 | CHF 62,800.– 

Gynäkologische Sozialmedizin und Psychosomatik, Frauenklinik, Universitätsspital Basel, Basel 

Fertility preservation in young female cancer patients – assessment of needs regarding decisionmaking and 

development of a decisionaid 

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De Geest Sabina | PROVIVO – patient reported outcomes 

in view of symptom experience of late effects 

and self-management of adult long-term survivors 

after allogeneic haematopoietic stem cell transplantation 

– a mixed methods study (KFS 2705-08-2010) 

Duration: 01.01.2011–01.07.2013 

Long-term survivors after allogeneic haematopoietic stem 

cell transplantation (HSCT) are presumably at a lifelong 

increased risk for developing various adverse side effects, 

also termed ‘late effects’. In addition to objective measures, 

in particular the collection of patient self-report is 

important for the early detection, management and alleviation 

of these symptoms. Moreover, health-promoting 

self-management behaviours might minimize the impact 

of chronic diseases. 

This multicentre study (Basel and Zurich) uses a mixedmethod 

design to develop a self-report instrument assessing 

symptom experience after HSCT. For the development 

of the instrument qualitative and quantitative research 

methods are used, and the content is based on the Patient-Reported 

Outcomes Version of the Common Terminology 

Criteria for Adverse Events (PRO-CTCAE) symptom 

item bank recently developed by the National Cancer 

Institute (USA). Patient interviews, an expert survey and 

a review of the literature will be conducted. 

In a subsequent study phase, the instrument will be validated 

in a sample of 300 patients (≥ 1 year after allogeneic 

HSCT). Additional data will be collected in order to 

investigate the relationship between symptom experience 

and objectively measured late effects, the perception of 

late effects by patients and their self-management 

(i. e. coping with emotions, roles, and medical and healthrelated 

tasks). 

The systematic assessment of patient-reported outcomes 

can be an effective means of secondary prevention in order 

to timely detect, diagnose and manage late effects. 


Prof. Dr. Sabina De Geest 

Institut für Pflegewissenschaften 


Bernoullistrasse 28 

CH-4056 Basel 

Phone +41(0)61 267 30 40 

Fax +41 (0)61 267 09 55 

sabina.degeest@unibas.ch 

Despland Jean-Nicolas | Communication in cancer 

care: The relationship between clinicians’ defense 

mechanisms, patient satisfaction and information 

recall (OCS 02338-02-2009) 

Duration: 01.06.2009–01.12.2011 

Communication has become a key element in oncology 

and has important consequences for both patients’ and 

clinicians’ well-being. Clinicians often need to regulate 

the emotions that occur during the discussion of sensitive 

topics, such as limited life expectancy, which might influence 

the quality of communication. 

Aim 

We wish to better understand how the clinicians’ emotional 

regulation might influence communication in oncology. 

Method 

We analyze discussions between patients and their clinicians 

in several hospitals in the French-speaking part of 

Switzerland. We pay particular attention to the clinicians’ 

defence mechanisms that are used to react to the emotional 

content of the discussions. 

Potential advantages for the patients 

A better understanding of the influence of the clinicians’ 

emotional regulation of communication in oncology will 

allow improvement in patient-clinician communication. 


Prof. Dr Jean-Nicolas Despland 

Institut universitaire de psychothérapie (IUP) 

Département de psychiatrie 


Site de Cery 

Bât. Les Cèdres 

CH-1008 Prilly 

Phone +41 (0)21 643 63 85 

jean-nicolas.despland@chuv.ch 

Kiss Alexander | A cognitive-behavioural mindfulness 

intervention to improve health-related quality of life, 

depression and fatigue among long-term haematopoietic 

stem cell transplant survivors 

(OCS 2400-02-2009) 

Duration: 01.09.2009–01.03.2012 

Haematopoietic stem cell transplantation (HSCT) is a valuable 

treatment employed to cure a variety of malignant 

blood disorders, bone marrow deficiency diseases and 

other diseases. Thanks to this therapy, many patients survive 

disorders that in earlier times were fatal. Nevertheless, 

there are often long-term adverse and challenging 

consequences of treatment, which include immunosuppressive 

conditions, graft-vs.-host disease (GvHD), other 

disorders related to chemotherapy toxicities, chronic fatigue 

and sexual dysfunction. Because these conditions 

can often impair normal physical, professional and recreational 

activities, and social relationships, many patients

eport long-term impairment of sense of well-being, reflected 

by low levels of health-related quality of life 

(HRQoL) and high levels of depression and anxiety. Very 

little effort has been expended in examining whether 

behavioural interventions can serve to improve distinct 

parameters of well-being, e. g. HRQoL, depression, fatigue 

and anxiety. 

Aim 

Mindfulness-based intervention (MBI) is a group behavioural 

program aimed at improving aspects of well-being 

for patients with a broad spectrum of chronic disorders 

(detailed description provided later). The primary goal of 

this investigation is to examine whether MBI is a feasible 

and effective intervention for HSCT survivors in terms of 

enhancing different dimensions of HRQoL (e. g. psychological 

functioning, positive emotions, social contact and 

ability to enjoy life) and decreasing depression, fatigue 

and anxiety. 

Methods 

Using a controlled patient-preference procedure, MBI is 

compared to a comparison intervention of augmented optimal 

medical care, where patients, additional to usual 

medical care, receive brief telephone medical and psychosocial 

consultations twice a month during the intervention 

phase. Feasibility of interventions will be evaluated by 

measuring aspects of acceptability of interventions (percentage 

of invited patients who participate, the dropout 

rate for the program, the average weekly attendance rate 

and the degree to which patients perceive that their personal 

goals for the intervention have been met). Efficacy 

of treatment will be evaluated by validated inventories of 

HRQoL, depression and fatigue as primary outcomes. 

Anxiety, personal growth and physical health status will 

be employed as secondary measures. We plan to include 

100 patients in the study and to examine benefits directly 

after the intervention period and at 3 months follow-up. 

Results 

This study is ongoing, and 51 patients are thus far participating. 

Few patients dropped out of the study before 

completing the intervention (

190 

rates communication skills remains unanswered. To better 

know and understand the mechanism that leads to improvement, 

the filmed interviews before and after CST 

were analyzed and compared with filmed interviews of 

clinicians with simulated patients with a six-month interval 

who did not participate in CST. 

The analysis of the interviews was based on methods utilized 

in psychotherapy, especially the identification of defence 

mechanisms. Defence mechanisms, such as denial 

or intellectualization, are unconscious processes triggered 

by emotions that may emerge during an interview, for example; 

they aim to protect the individual from threatening 

affect. Although defence mechanisms protect the clinicians, 

they also have the effect that the clinician’s 

perception of the patient is coloured by the clinician’s psychological 

state. This hampers the clinician’s capacity to 

adequately perceive the needs of the patient. The results 

of the study show 1) that during an interview of a quarter 

of an hour with a simulated patient, clinicians’ defence 

mechanisms are triggered 15 times, illustrating the affective 

load of such interviews, and 2) that defence mechanisms 

of participants are modified by CST, which increase 

the proportion of mature defence mechanisms, leading to 

more appropriate perception of the patient. 

To conclude, this study demonstrated that patient interviews 

represent an important stressor for the clinician and 

that improvement of communication skills by CST is linked 

to utilization of more mature defence mechanisms. The 

results have increased our knowledge of processes of improvement 

of communication skills by CST and call for a 

modification of teaching with an increased focus on clinicians’ 

emotional experiences and their professional identity. 







Phone +41 (0)21 314 10 90 

Fax +41 (0)021 314 10 86 


Further approved research project 2009/2010 

Tschudin Sibil | Fertility preservation in young female 

cancer patients – assessment of needs regarding 

decision-making and development of a decision-aid 

(KLS 02577-02-2010) 

Duration: 01.07.2010–01.07.2012 

Impaired fertility may be a consequence of successful cancer 

treatment, and the use of one of the fertility preservation 

(FP) techniques being developed currently might 

therefore be an option for all young patients with cancer. 

Decisions on fertility preservation have to be made in the 

short time period after diagnosis and before onset of cancer 

treatment, and the dilemma confronting affected patients, 

their families and their caretakers is considerable. 

The aim of this study is to gain deeper insight into the 

needs and conflicts occurring during this decision-making 

process. The study addresses former and current female 

patients with cancer at young age and consists of two 

parts. Part 1 is an anonymous online survey, which will be 

available via a link on cancer and fertility websites. Part 2 

consists of standardized focus groups facilitated by a psychologist. 

The knowledge gained through this study will 

aid development of a standardized instrument that complements 

and supports shared decision-making in fertility 

issues and FP for young patients with cancer and their 

medical caretakers. 


Dr. Sibil Tschudin 

Gynäkologische Sozialmedizin und Psychosomatik 

Frauenklinik 


Spitalstrasse 21 

CH-4031 Basel 

Phone +41 (0)61 265 90 43 

stschudin@uhbs.ch 

Ehlert Ulrike | KFS 02662-08-2010 | CHF 173 600.- 

Klinische Psychologie und Psychotherapie, Psychologisches Institut, Universität Zürich, Zürich 

Psychobiological factors influencing the course of HPV infections in young women: a longitudinal study

191


Epidemiological studies on mobile telephones and cancer 

Since the introduction and rapid spread of mobile 

telephones in the 1990s, the question as to whether 

the radiofrequency electromagnetic fields of cellular 

phones increase brain tumour risk has become an increasingly 

important public health concern. The use 

of mobile phones is so widespread that even a small 

tumour risk due to exposure to radiofrequency radiation 

emitted by cellular phones would result in increases 

in general population incidence rates. The Interphone 

study is the largest epidemiological study 

of mobile phone use and brain tumours to date. This 

case-control study included 13 countries, with coordination 

by the World Health Organization (WHO). 

Case-control is a retrospective epidemiological study 

design where people with a disease (cases) are 

matched with people who do not have the disease 

(controls). The studies compare the groups with respect 

to past exposure to the potential risk factor and 

look for differences. For example, if it were found that 

persons with brain tumours used their mobile phones 

significantly more often than comparable control 

persons, that would be an indication of increased 

risk. 

The overall evaluation of the Interphone study is 

based on 2,400 cases of meningioma (brain tumours 

that develop from the meninges), 2,700 cases of glioma 

(brain tumours arising from glial cells), and 

5,600 matched controls with no brain cancer, in people 

30–60 years of age [1]. Evaluation of all data revealed 

a 20 % lower risk of meningioma and glioma 

for regular mobile phone users compared to non 

Prof. Martin Röösli, PhD 

Head of the Unit for Environmental Epidemiology and Risk Assessment, Swiss Tropical and 

Public Health Institute, Basel 

Kerstin Hug, MD 

Responsible for the Documentation and Service Database ELMAR – Electromagnetic Radiation and Health, 

Swiss Tropical and Public Health Institute, Basel 

193

194 

regular users. However, in a subset of users – the 

highest users, with a history of at least 1,640 hours of 

call time – the risk of glioma was 40 % higher compared 

to non regular users. These contradictory findings 

raise the question of the explanatory power of 

epidemiological studies. 

The conclusiveness of environmental epidemiological 

studies 

Demonstrating cancer risk due to exposure to environmental 

factors is particularly difficult because the 

negative effects may occur only after a long period 

of exposure. To determine how a potentially harmful 

substance affects the organism and what biological 

processes are involved, experimental studies with 

cells or animals are helpful. However, the extent to 

which the findings can be applied to human beings is 

always uncertain, so that in the end only longitudinal 

studies with people can provide definitive answers. 

The WHO also attaches the most importance to 

these epidemiological studies [2]. 

Studies with human participants present a number of 

practical difficulties. The type of study least prone to 

error would be a very large randomised trial in which 

half of the participants were randomly assigned to 

mobile phone exposure for 10 years and the other 

half were not. Naturally, studying cancer risk in that 

way is not feasible for ethical and practical reasons, 

so we must rely on the findings of observational epidemiological 

studies. The three biggest difficulties 

with these studies are presented in the following taking 

the example of studies on mobile phone use. 

1. The influence of confounders 

In observational study designs, cancer incidence is 

compared in dependency upon mobile phone use. 

Here there is always the question as to how comparable 

the participants with high mobile telephone 

use are with the participants with no or infrequent 

phone use. If there is a difference in cancer rates 

between cellular phone users and non-users, the 

reason is not necessarily mobile phone radiation. The 

two groups may differ in other characteristics or behaviours 

that affect cancer risk. These confounders 

can distort the results of a study. 

This problem became particularly evident in a large 

Danish cohort study [3]. In cohort studies it is examined 

whether a group of persons who are exposed to 

a potential risk factor have a higher incidence of disease 

than persons in a control group that is not exposed 

or less exposed to this factor. In the study in 

Denmark, as compared to the rest of the population 

long-term mobile phone users were found to have a 

lower risk of brain tumours. At the same time, among 

men, long-term cellular phone users were also found 

to have a lower risk of lung cancer. Among women, 

long-term mobile phone users had a higher risk of 

uterine cancer. As it is very unlikely that cellular 

phone radiation affects lung cancer risk or uterine 

cancer risk, this indicated that other lifestyle factors 

could have led to the results. A plausible explanation, 

for example, is that men who started using mobile 

phones shortly after they were first introduced may 

have had higher incomes and may have smoked less. 

2. Distortion of results due to selection bias 

In principle, lifestyle factors that also affect cancer 

risk, such as smoking or alcohol consumption, could 

be captured and taken into consideration in the analysis. 

In the Danish study, however, no such information 

was available because the study was based on

data from cancer registries. In the Interphone study, 

great efforts were undertaken to capture all possible 

confounders by personally surveying all study participants. 

Due to the effort required, willingness to participate 

in such a study can depend on the state of 

health of the participants as well as their mobile 

phone use, and it is generally not very high, especially 

among healthy participants. Already at the 

start a low rate of participation in one of the groups 

can result in systematic differences between the 

groups to be compared and thus lead to a distortion 

of the study results. 

There are indications that this is what happened in 

the Interphone study: Since willingness to take part 

in the study was particularly low in healthy control 

persons who did not use cellular phones, mobile 

phone users came to be overrepresented in the control 

group. Through this, the cellular phone use of 

healthy persons compared to persons with brain 

tumours was overestimated, and the statistical analyses 

yielded a seemingly reduced risk of cancer with 

regular mobile phone use. 

3. Estimating exposure 

The third big difficulty with observational studies in 

epidemiology is estimating and classifying exposure 

correctly. Retrospective studies like the Interphone 

study must frequently rely on participants’ self-reports, 

as no objective exposure data for the past, for 

instance from network providers, are available. Since 

people do not recall the exact number and duration 

of phone calls years or decades ago, their self-reports 

are fraught with great uncertainties. If patients 

and healthy participants make on average the same 

errors in their exposure estimates and if there is a 

correlation between the exposure estimates and actual 

call time, the effect on the results is not dramatic. 

The resulting erroneous classification of the 

participants leads to an underestimate of the associ- 

ation, if there is a connection between exposure and 

disease. And if there is no connection, the study will 

not erroneously compute an association. 

However, it is problematic if self-reports differ be- 

tween patients and control persons. It is known that 

persons with a disease tend to overestimate their 

past exposure to environmental risk factors, because 

they are looking for reasons why they became ill. In 

contrast, persons without a disease tend to underestimate 

their exposure. As a result of this constellation, 

study results can mistakenly indicate an association 

between exposure and disease that in reality 

does not exist. Whether or not this phenomenon is 

the reason for the increased risk of glioma among 

mobile phone users with the highest exposure levels 

in the Interphone study cannot be determined conclusively 

and is a matter of controversy in expert circles. 

Brain tumours caused by mobile phones? 

Epidemiological studies are needed to clarify the 

long-term risks of exposure to potential environmental 

factors such as electromagnetic fields. However, 

due to their non-experimental design the studies are 

prone to errors. For this reason it is necessary to investigate 

a question using different types of studies 

in different contexts. The complementary information 

provided by the different studies yields an overall 

picture that allows us to assess the scientific evidence. 

As mentioned, the Interphone study and other simi- 

lar, previously conducted studies did not conclusively 

determine whether mobile phone use increases brain 

tumour risk. If it did, the widespread and nearly 

global use of mobile communications would lead us 

to expect an increase in brain tumour incidence. 

However, higher incidence rates have not been found 

195

196 

based on evaluations of cancer registry data in Scan- 

dinavia [4], England [5], or the United States [6]. Al- 

though these data tend to speak against an associa- 

tion, it should be noted that long-term risk that would 

become manifest after more than 20 years of exposure 

is not yet discernible in the current incidence 

rates. In summary, the evidence to date does not indicate 

that cellular phone use causes an increase in 

brain tumour risk. But there are still only few studies 

on mobile phone use longer than 15 years and on the 

effects of cellular phone use on children and adolescents. 

References 

1. Interphone Study Group. Brain tumour risk in relation 

to mobile telephone use: results of the Interphone 

international case-control study. Int J Epidemiol. 

2010 Jun;39(3):675-94. 

2. International Agency for Research on Cancer (IARC). 

IARC monographs on the evaluation of carcinogenic 

risks to humans. Non-Ionizing radiation, part 1: 

static and extremely low-frequency (ELF) electric and 

magnetic fields, volume 80. Geneva: World Health 

Organization and IARC Press; 2002. 

3. Schüz J, Jacobsen R, Olsen JH, Boice JD Jr, McLaughlin 

JK, Johansen C. Cellular telephone use and cancer risk: 

update of a nationwide Danish cohort. J Natl Cancer 

Inst. 2006 Dec 6;98(23):1707-13. 

4. Deltour I, Johansen C, Auvinen A, Feychting M, 

Klaeboe L, Schüz J. Time trends in brain tumor 

incidence rates in Denmark, Finland, Norway, and 

Sweden, 1974-2003. J Natl Cancer Inst. 2009 Dec 

16;101(24):1721-4. 

5. de Vocht F, Burstyn I, Cherrie JW. Time trends 

(1998–2007) in brain cancer incidence rates in relation 

to mobile phone use in England. Bioelectromagnetics. 

2011 Jul;32(5):334-9. doi: 10.1002/bem.20648. 

Epub 2011 Jan 28. 

6. Inskip PD, Hoover RN, Devesa SS. Brain cancer incidence 

trends in relation to cellular telephone use in the 

United States. Neuro Oncol. 2010 Nov;12(11):1147-51. 

Prof. Martin Röösli, PhD 

Martin Röösli is an environmental 

epidemiologist with a background 

in atmospheric science. He is 

head of the Unit for Environmental 

Epidemiology and Risk 

Assessment at the Swiss Tropical 

and Public Health Institute. His 

research deals with the effects of 

environmental factors on health, 

such as electromagnetic fields, air pollution, noise, ionizing 

and non-ionizing radiation, and passive smoking. 

Phone +41 (0)61 284 33 88, 

martin.roosli@unibas.ch 

www.swisstph.ch 

Kerstin Hug, MD 

Kerstin Hug is a research assistant 

at the Swiss Tropical and Public 

Health Institute and is responsible 

for the ELMAR Documentation 

Service and Database on electromagnetic 

radiation and health. 

In her work she focuses on systematic 

literature research, methodological 

evaluation of epidemiological 

studies, and writing reviews of the literature on 

non-ionizing radiation. 

Phone +41 (0)61 284 83 66 

kerstin.hug@unibas.ch 

www.elmar.unibas.ch

The importance of cancer registries for health policy 

Cancer is a significant disease in Switzerland: Four out of ten people are diagnosed with 

cancer at some point in their lives, and 16,000 people die of cancer each year. The number 

of cases of cancer in Switzerland is expected to increase in the future due to the ageing 

population. 

Switzerland must have reliable data to monitor the development of cancer, to better understand 

the causes of cancer, and to assess the effectiveness and quality of prevention and 

treatment. These data are systematically collected by cantonal cancer registries and then 

aggregated and analyzed on a national level by the National Institute for Cancer Epidemiology 

and Registration (NICER). In February 2011 NICER, the Swiss Childhood Cancer Registry 

(SCCR), and the Federal Statistical Office (FSO) published the report “Cancer in Switzerland: 

Situation and development from 1983 to 2007”. This report provides an overview 

of the national cancer incidence and many other aspects of cancer, and it is an important, 

evidence-based foundation for decision-making in politics, prevention, and medical practice. 

At present there are 16 cantonal or regional cancer registries, which cover only about twothirds 

of the population of Switzerland. Therefore, for estimates for the whole of Switzerland 

these figures have to be extrapolated. Since it is assumed that there are differences 

in cancer incidence among the different language regions of Switzerland, certain distortions 

of the data are possible. These statistical problems will be solved only once there is full- 

coverage data collection in all cantons. NICER and the cancer registries therefore support 

the continued efforts of the Federal Council to create a basis in federal law for full-coverage, 

nationally coordinated cancer registration in Switzerland. 

National Institute for Cancer Epidemiology 

and Registration (NICER) 

c/o ISPMZ 

University of Zurich 

Seilergraben 49 

CH-8001 Zurich 

Phone +41 (0)44 634 53 74 

info@nicer.org 

www.nicer.org 

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198 



Bouchardy Christine | KLS 01759-08-2005 | CHF 310 600.– 

Registre genevois des tumeurs, Institut national pour l’épidémiologie et l’enregistrement du cancer (NICER), 

Genève 

Epidemiologic research on the impact of genetic factors in breast cancer occurrence among the female 

population of Geneva: A study from the first Familial breast cancer registry in Switzerland 

Ess Silvia | KLS 01766-08-2005 | CHF 259 500.– 

Krebsregister St. Gallen-Appenzell, Kantonsspital St. Gallen, St. Gallen 

Patterns of care and survival in breast cancer patients in Switzerland 

Levi Fabio | OCS 01633-02-2005 | CHF 265 620.– 

Unité d’épidémiologie du cancer et Registres vaudois et neuchâtelois des tumeurs, Institut universitaire 

de médecine sociale et préventive, Centre hospitalier universitaire vaudois (CHUV), Lausanne 

An integrated network of casecontrol studies on cancer: Nutrition, other environmental and genetic factors 

Zwahlen Marcel | OCS 01869-02-2006 | CHF 171 400.– 


Risk of childhood leukemia varies little by familial socioeconomic status – while survival time after a brain 

tumor diagnosis varied considerably by familial socioeconomic status 



Bouchardy Christine | Epidemiologic research on 

the impact of genetic factors in breast cancer occurrence 

among the female population of Geneva: 

A study from the first Familial breast cancer registry 

in Switzerland (KFS 01759-08-2005) 

Breast cancer is a public health priority in Switzerland. 

Family history is one of the major risk factors for breast 

cancer. To perform innovative studies on the effect of 

hereditary factors on breast cancer occurrence and 

outcome, we set up the first and unique Familial breast 

cancer registry in Switzerland, which currently contains 

validated family histories of cancer for more than 6,000 

patients. 

Objectives of the study 

The objectives of our study are to compare pathological 

characteristics of cancers occurring in the same family and 

to evaluate the concordance of prognosis between firstdegree 

relatives with breast cancer. 

Methods 

We will compare tumour characteristics between women 

with breast cancer belonging to the same family, and investigate 

whether the mother or sister’s prognosis influences 

the patient’s prognosis. 


These studies will allow to a better understanding of the 

genetic factors influencing disease prognosis and make it 

possible in the near future to improve surveillance and 

care of women with high risk breast cancer. 


Prof. Dr Christine Bouchardy 

Registre genevois des tumeurs 

Institut de médecine sociale et préventive 

Département de médecine et santé communautaire 


Bd de la Cluse 55 


Phone +41 (0)22 379 49 50 

christine.bouchardymagnin@unige.ch

Ess Silvia | Patterns of care and survival in breast 

cancer patients in Switzerland (KLS 01766-08-2005) 

Background 

Breast cancer is the most common malignancy and the 

first cause of premature mortality for women in Switzerland. 

Two recently published studies described geographical 

disparities in breast cancer mortality and 5-year relative 

survival rates after controlling for prognostic factors 

like tumour size and nodal status, suggesting that other 

factors than stage at diagnosis might influence outcome. 

Although in other countries treatment of breast cancer in 

specialized units has been shown to result in better outcomes, 

there is still much debate as to whether specialization 

in breast cancer care is needed in Switzerland and 

whether differences that matter to the patient exist. 

Aims and Methods 

The aims of this study were to analyze whether differences 

in the implementation of state-of-the-art management 

exist and to find predictors for adequate and poor 

management of early breast cancer in Switzerland. 

We included 4,800 patients newly diagnosed with breast 

cancer in the years 2003–2005. Patients were selected 

from seven population-based cancer registries (Basel, Geneva, 

Grisons-Glaris, St Gallen/Appenzell, Ticino, Valais 

and Zurich). Based on the requirements of the European 

Society of Mastology (EUSOMA) Audit system on Quality 

of Breast Cancer Treatment criteria, a database was 

designed. Items included detailed information on patient 

and tumour characteristics, diagnosis circumstances and 

treatments planned and delivered as part of the first therapeutic 

concept. 

A 10-item score of state-of-the-art management was defined 

based on national and international guideline items. 

The score included five items for surgical management, 

one item for histopathology reporting and four items for 

adjuvant radiotherapy and systemic treatment. 

Results 

Two-thirds of patients were treated with a breast conserving 

surgery. Age, bigger tumours and residence in a rural 

area increased the probability to have a mastectomy. We 

observed geographical disparities regarding the utilization 

of new surgical procedures (sentinel node biopsy, skin 

sparing mastectomy) and pre-treatment diagnosis. On the 

other hand, few differences existed regarding adjuvant radiotherapy 

and systemic therapies. 

In one-third of the patients, management met guidelines 

in all items, whereas in about one-fifth, three or more items 

did not comply. Treatment by a surgeon with a caseload in 

the upper tercile and team involved in clinical research 

were independent predictors of a high score, whereas 

treatment by a surgeon with a caseload in the lower tercile 

was associated with a low score. Socioeconomic characteristics 

such as income and education were not independent 

predictors, but patient’s place of residence and 

age independently predicted management according to 

recommendations. 


In the past few years, increasing awareness of variations 

in the quality of health care across geographic areas as 

well as providers in other countries has helped to propel a 

quality improvement movement. In the Swiss health system, 

characterized by freedom of choice of provider, the 

importance of an informed choice of referring physicians 

and patients is paramount. The introduction of accredited 

breast units in the near future will increase transparency, 

facilitate this informed choice and contribute towards reducing 

disparities. 


Dr. Silvia Ess 

Krebsregister St. Gallen-Appenzell 


Flurhofstrasse 7 


Phone +41 (0)71 494 21 17 

Fax +41 (0)71 494 61 76 

silvia.ess@kssg.ch 

Levi Fabio | An integrated network of case-control 

studies on cancer: Nutrition, other environmental and 

genetic factors (OCS 01633-02-2005) 

This is an integrated epidemiology research scheme, designed 

to identify and better quantify environmental and 

genetic risk factors for several common cancers – including 

head and neck (HNC), breast and colorectal cancers – 

and to estimate the relative and attributable risk in the 

Swiss and other Southern European populations. The program 

originated in the late 1980s and has contributed 

to the definition and quantification of environmental (tobacco, 

alcohol, diet, physical exercise, etc.) and familial 

factors in cancer risk. This project has been included in international 

meta analyses and pooled analyses of various 

neoplasms including head and neck, breast and colon. 

Epidemiological data are collected through interviews of 

patients with cancer and controls admitted to the CHUV 

in Lausanne. At the end of 2010, the overall dataset included 

about: 950 cases of HNC cancers (of oral cavity 

and pharynx, oesophagus and larynx), 600 of colorectal 

cancers, 800 of breast cancers, and over 4,500 controls. 

Our recent findings indicated that citrus fruit has a protective 

role against cancers of the digestive and upper respiratory 

tract. No association was found with breast cancer. 

We were involved in the International Head and Neck 

Cancer Epidemiology (INHANCE) consortium, which includes 

data from 33 HNC studies worldwide, and a total 

of about 25,000 cases of 33,000 controls. The influence 

of family history on HNC risk was investigated, showing 

an increased risk (odds ratio, OR=1.7) in first-degree relatives 

that was higher when the affected relative was 

a sibling rather than a parent and for more distal HNC anatomic 

sites (hypopharynx and larynx). The risk was also 

higher in those exposed to tobacco. The OR rose to 7.2 

among subjects with family history who were alcohol and 

tobacco users. 

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200 

Findings of the INHANCE study also suggested that the 

risks of HNC for beer and liquor are comparable. A greater 

than multiplicative effect between ever tobacco and alcohol 

use was observed for HNC risk. The population attributable 

risk for tobacco or alcohol was 72 % for HNC, 

of which 4 % was due to alcohol alone, 33 % was due to 

tobacco alone and 35 % was due to tobacco and alcohol 

combined. Quitting tobacco smoking resulted in a HNC 

risk reduction in the short term. For alcohol use, a beneficial 

effect on the risk of HNC was only observed after 

≥ 20 years of quitting. 

Additional and more detailed collaborative analyses within 

the INHANCE consortium were conducted on: a) total exposure 

and exposure rate effects of alcohol and smoking 

and risk of HNC; b) cessation of alcohol drinking, tobacco 

smoking and the reversal of HNC; and c) interaction between 

tobacco and alcohol use and risk of HNC. 

The major results of the research are published to increase 

the project impact on various aspects of public health and 

prevention and, in particular, the assessment of the individual 

risks and their public health implications. 


Prof. Dr Fabio Levi 

Unité d’épidémiologie du cancer et 

Registres vaudois et neuchâtelois des tumeurs 

Institut universitaire de médecine sociale et 

préventive 


Chemin des Falaises 1 


Phone +41 (0)21 314 73 11 

fabio.levi@chuv.ch 

Zwahlen Marcel | Risk of childhood leukemia varies 

little by familial socio-economic status – while survival 

time after a brain tumor diagnosis varied considerably 

by familial socio-economic status 

(OCS 1869-02-2006) 

Research on origins and determinants of childhood cancer 

is still important, because the aetiology of childhood cancer 

remains poorly understood. Whether diseases are 

occurring more frequently in persons with lower socioeconomic 

status (SES) is a question that is regularly asked. 

In a nationwide study of the SCCR and the Swiss National 

Cohort (SNC) using data of the 1990 and 2000 census, 

we examined, first, the association of SES level and the 

risk of leukaemia and, second, the association of SES level 

and mortality in childhood cancer patients. 

In the case-control study part we found weak evidence 

for a positive association of childhood leukaemia with 

higher education of mother but no evidence of an association 

with other family indicators of SES. The odds ratio 

for leukaemia and SES, comparing the highest SES category 

with the lowest SES category, was 1.37 (1.00–1.89) 

for mother’s education, 0.95 (95 % CI: 0.71–1.26) for 

father’s education and 0.96 (95 % CI: 0.74–1.25) for 

number of rooms per person. This might imply that childhood 

leukaemia risk is positively associated with a specific 

exposure linked to higher education of the mother. 

When analyzing survival after a cancer diagnosis, SES differentials 

were virtually absent for leukaemia patients but 

existed for other childhood cancers, especially for patients 

with a tumour of the central nervous system. Mortality 

was lower in higher SES groups compared to lower SES 

groups. Depending on the SES measure used, hazard 

ratios ranged from 0.48 (95 % CI: 0.28–0.81) to 0.71 

(95 % CI: 0.44–1.15) when comparing the highest with 

the lowest SES group. This might imply an association of 

SES with access to health care and treatment decisions, 

which in turn would be associated with treatment outcome. 

To improve health conditions and care in all socioeconomic 

groups in high-income countries with mandatory 

health insurance like Switzerland, it is important to understand 

the causes of childhood cancer and the mechanisms 

that are responsible for differences in survival after a cancer 

diagnosis in children. 


Prof. Dr. Marcel Zwahlen 

Institut für Sozial- und Präventivmedizin 



CH-3000 Bern 

Phone +41 (0)31 631 35 11 

zwahlen@ispm.unibe.ch




Bordoni Andrea | KFS 02668-08-2010 | CHF 232,700.– 

Registro cantonale dei tumori, Istituto cantonale di patologia (ICP), Locarno 

Indicators of quality of cancer care in Southern Switzerland 

Bouchardy Christine | KFS 02544-02-2010 | CHF 315,900.– 

Registre genevois des tumeurs, Institut national pour l’épidémiologie et l’enregistrement du cancer (NICER), 

Genève 

Impact of genetic factors in breast cancer occurrence, treatment and outcome using populationbased 

data from the first Familial breast cancer registry in Switzerland 

Clough-Gorr Kerri | KFS 02553-02-2010 | CHF 381,300.– 

NICER, c/o Institut für Sozial- und Präventivmedizin, Universität Zürich, Zürich 

The Swiss National Cohort (SNC) and the National Institute for Cancer Epidemiology and Registration (NICER) – 

cancer epidemiology study, 1990 – 2008 

Keiser Olivia | KFS 02478-08-2009 | CHF 225,700.– 


Changes and determinants of cancer patterns among persons infected with HIV in the era of combined 

antiretroviral therapy in Switzerland 

Levi Fabio | KFS 02437-08-2009 | CHF 270,000.– 

Unité d’épidémiologie du cancer et Registres vaudois et neuchâtelois des tumeurs, Institut universitaire 

de médecine sociale et préventive, Centre hospitalier universitaire vaudois (CHUV), Lausanne 

Modelling, interpretation and forecasting of cancer mortality in Europe 

Michel Gisela | KLS 02631-08-2010 | CHF 283,300.– 


Effectiveness of transition to adult care after childhood cancer 

Mullis Primus-Eugen | KLS 02586-02-2010 | CHF 184,300.– 

Abteilung pädiatrische Endokrinologie, Diabetologie und Stoffwechsel, Universitätsklinik für Kinderheilkunde, 

Inselspital, Bern 

Risk of cancer and longterm mortality in children treated with growth hormone: Swiss participation in the EU 

FP7 project “Safety and Appropriateness of Growth Hormone Treatment in Europe (SAGhE)” 

Thürlimann Beat | KFS 02474-08-2009 | CHF 25,900.– 

Brustzentrum, Kantonsspital St. Gallen, St. Gallen 

Management of breast cancer in the elderly in Switzerland 

Vounatsou Penelope | KLS 02393-02-2009 | CHF 215,850.– 

Biostatistics and Computational Sciences Unit, Departement für Epidemiologie und Gesundheitswesen, 

Schweizerisches Tropen- und Public Health-Institut, Basel 

Spatiotemporal patterns and forecasting of gender specific lung and other tobaccorelated cancer mortality 

and morbidity rates in Switzerland 

201

202 



Bordoni Andrea | Indicators of quality of cancer care 

in Southern Switzerland (KFS 02668-08-2010) 

Duration: 01.01.2011– 01.01.2014 

Study design 

A prospective descriptive population-based study conducted 

in a three-year time period at Ticino Cancer Registry. 

Aims 

To identify a panel of specific quality of cancer care 

(QoCC) indicators concerning three cancers (colorectal, 

prostate, ovary/uterus), so as to assess the quality of the 

diagnostic and therapeutic process offered in Canton 

Ticino; to promote a culture of QoCC among health care 

providers; and to obtain improved patient outcomes in the 

long term. 

Methods 

Specific project research boards will be formed for each 

type of tumour and the indicators identified will refer to 

all incident cases occurring from 2011–2013 in Canton Ticino. 


All incident patients resident in Canton Ticino according 

to the inhabitants control database and diagnosed from 

2011–2013, regardless of age, will be included. We expect 

to collect information for 220, 240 and 70 patients per 

year with colorectal, prostate and ovarian/uterine cancers, 

respectively (for a total number of 1,590 cases for 

the 3-year study period). 


Dr. Andrea Bordoni 

Registro cantonale dei tumori 

Istituto cantonale di patologia (ICP) 

Via in Selva 24 

CH-6601 Locarno 

Phone +41 (0)91 816 08 23 

Fax +41 (0)91 816 08 29 

andrea.bordoni@ti.ch 

Bouchardy Christine | Impact of genetic factors in 

breast cancer occurrence, treatment and outcome using 

population-based data from the first Familial breast 

cancer registry in Switzerland (KFS 02544-02-2010) 

Duration: 01.08.2010 – 01.08.2012 

Breast cancer is a public health priority in Switzerland. 

Family history is one of the major risk factors for breast 

cancer. To perform innovative studies on the effect of hereditary 

factors on breast cancer occurrence and outcome, 

we set up the first and unique Familial breast cancer 

registry in Switzerland, which currently contains 

validated family histories of cancer for more than 6,000 

patients. 

Objectives of the study 

The objectives of our study are to compare pathological 

characteristics of cancers occurring in the same family and 

to evaluate the concordance of prognosis between firstdegree 

relatives with breast cancer. 

Methods 

We will compare tumour characteristics between women 

with breast cancer belonging to the same family, and 

investigate whether the mother or sister’s prognosis influences 

the patient’s prognosis. 


These studies will allow to a better understanding of the 

genetic factors influencing disease prognosis and make it 

possible in the near future to improve surveillance and 

care of women with high risk breast cancer. 


Prof. Dr Christine Bouchardy 

Registre genevois des tumeurs 

Institut de médecine sociale et préventive 

Département de médecine et santé communautaire 


Bd de la Cluse 55 


Phone +41 (0)22 379 49 50 

christine.bouchardymagnin@unige.ch 

Clough-Gorr Kerri | The Swiss National Cohort (SNC) 

and the National Institute for Cancer Epidemiology and 

Registration (NICER) – Cancer Epidemiology Study, 

1990–2008 (KFS 02553-02-2010) 

Duration: 01.10.2010 – 01.10.2013 

Objective 

To answer critical questions related to the burden of cancer 

in Switzerland. 

Methods 

The study population includes the census-based population 

of Swiss adults (≥ age 20) living in NICER cancer registry 

areas (Appenzell, Basel, Geneva, Glarus, Graubünden, 

Neuchâtel, St Gallen, Ticino, Valais, Vaud, Zurich). Participants 

are followed forward in time 1990–2008 with up to 

18 years of follow-up for cancer outcomes. Information 

will be collected on incidence, survival, prevalence of cancer, 

and socio-demographic, lifestyle and geo-cultural 

characteristics. 

Aims: 

1) Examine gender-specific trends in cancer outcomes. 

2) Evaluate gender-specific socio-demographic factors 

associated with cancer outcomes. 

3) Identify gender-specific lifestyle factors associated 

with cancer outcomes. 

4) Create a multi-institution multidisciplinary research 

board to promote cancer epidemiology research based 

on the SNC-NICER study platform.

Impact 

This work will serve as the foundation for the formulation 

of future prevention strategies, healthcare initiatives and 

research agendas based on epidemiological data designed 

to focus on the risk of cancer. 


Dr. Kerri Clough-Gorr 

NICER 

c/o Institut für Sozial- und Präventivmedizin 


Seilergraben 49 

Phone +41 (0)44 634 53 74 

kerri.clough-gorr@nicer.org 

Keiser Olivia | Changes and determinants of cancer 

patterns among persons infected with HIV in the era 

of combined antiretroviral therapy in Switzerland 

(KFS 02478-08-2009) 

Duration: 01.01.2010 – 01.01.2012 

With the introduction of the highly active antiretroviral 

therapy in 1996, life expectancy among persons with HIV 

(PHIV) increased substantially, and AIDS defining conditions 

decreased. However, improving survival also means 

that PHIV are living long enough to develop cancers that 

accompany ageing or are associated with a prolonged immunodeficiency. 

The aim of the project is to understand 

relations between immunodeficiency, ageing and the frequency 

of cancers. This is a collaboration study between 

the cantonal cancer registries, the Swiss HIV Cohort Study 

(SHCS) and the International Agency for Research on 

Cancer (IARC) in Lyon, France. 

Methods 

The anonymous linkage between the patient data of the 

cancer registries and the SHCS allows us to gain an understanding 

of the reasons for the higher cancer incidence in 

PHIV. Cancer incidence in PHIV is compared to incidence 

in the general Swiss population.

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Knowledge about specific risk factors allows earlier diagnosis 

and treatment of cancer. 


Dr. Olivia Keiser 




CH-3012 Bern 

Phone +41 (0)31 631 35 15 

okeiser@ispm.unibe.ch 

Levi Fabio | Modelling, interpretation and forecasting 

of cancer mortality in Europe (KFS 02347-08-2009) 

Duration 01.10.2009 – 01.10.2012 

The main objective of this project, which started in 1993, 

is to maintain and improve the integrated system for analyzing, 

modelling and interpreting mortality statistics in 

Europe created by our international collaborative group 

from the WHO raw mortality database. 

Over the last two decades, total cancer mortality trends 

were favourable, although to a variable degree, in all major 

European countries, including Switzerland. 

The major determinants of these favourable trends were 

the decline of lung and other tobacco-related cancers in 

men, together with the persistent falls in gastric cancer 

and the recent appreciable falls in colorectal cancer. In 

women, relevant contributions came from the persistent 

decline in cervical cancer and the recent falls in breast 

cancer mortality, particularly in Northern and Western 

Europe. Detailed analyses were conducted and published 

on trends for oral and pharyngeal, stomach, biliary tract, 

testis, Hodgkin’s lymphoma and childhood cancer. 

There is ample need to monitor cancer mortality in Europe 

continuously, and the wide diffusion of these statistics 

can have a substantial impact on prevention and public 

health. 


Prof. Dr Fabio Levi 

Unité d’épidémiologie du cancer et Registres 

vaudois et neuchâtelois des tumeurs 

Institut universitaire de médecine sociale et 

préventive 


Chemin des Falaises 1 


Phone +41 (0)21 314 73 11 

fabio.levi@chuv.ch 

Michel Gisela | Effectiveness of transition to adult 

care after childhood cancer (KLS 02631-08-2010) 

Duration: 01.04.2011– 01.04.2014 

Despite improving cure rates, two-thirds of childhood 

cancer survivors experience late effects. Follow-up is thus 

very important. Whereas follow-up is usually well-organized 

in paediatric care, transition to adult care has often 

been lacking in Switzerland. 

We will study clinic documents and medical records to describe 

the organization of follow-up for childhood cancer 

survivors in paediatric care, transition to adult care and 

the information provided to future carers, parents and patients. 

Together with information from two questionnaire 

surveys, organization of follow-up and transition to adult 

care will be described. 

This study will help to develop well-organized transition 

from paediatric to adult care such that long-term followup 

for childhood cancer survivors can be improved. 


Dr. Gisela Michel 




CH-3012 Bern 

Phone +41 (0)31 631 33 47 

michel@ispm.unibe.ch 

Mullis Primus-Eugen | Risk of cancer and long-term 

mortality in children treated with growth hormone: 

Swiss participation in the EU FP7 project “Safety and 

Appropriateness of Growth Hormone Treatment in 

Europe (SAGhE)” (KLS 02586-02-2010) 

Duration: 01.07.2010 – 01.01.2013 

Growth hormone (GH) is crucial for height gain. Diseases 

associated with lack of GH can be treated by GH replacement. 

For example, this GH replacement therapy can be 

applied to children that cannot produce their own GH after 

radiotherapy. Data on the long-term safety of this 

therapy are lacking. A European study, in which Switzerland 

is also contributing, will now investigate these open 

questions. 

This study aims to identify the long-term impact of GH 

therapy on adult height, quality of life, cancer incidence 

and mortality. 

Medical data will be collected from patient files in the 

hospitals. Information about quality of life and current 

health status will be assessed by questionnaires sent to 

the patients. Insights in cancer incidence and mortality 

can be obtained by comparing these data with the mortality 

statistics of the Swiss Federal Statistical Office and 

the national cancer data bases. 

The patients may benefit through an optimization of therapy 

guidelines based on the findings of this study. 


Prof. Dr. Primus-Eugen Mullis 

Abteilung pädiatrische Endokrinologie, 

Diabetologie und Stoffwechsel 

Universitätsklinik für Kinderheilkunde 

Inselspital 

CH-3010 Bern 

Phone +41 (0)31 632 9552 

primus.mullis@insel.ch

Thürlimann Beat | Management of breast cancer 

in the elderly in Switzerland (KFS 02474-08-2009) 

Duration: 01.03.2010 – 01.11.201 

About 40 % of all breast cancer cases are diagnosed in patients 

aged 65 or older. Data on the aging population 

demonstrate an unprecedented expansion of the segment 

of the population aged ≥ 65 years in the last 20 years. 

There is an urgent need to understand the factors influencing 

diagnosis and treatment of breast cancer in the elderly. 

The aim of this study is to examine the patterns of 

breast cancer care in elderly patients and to determine 

predictors for substandard treatment. 

Methods 

We will include a subgroup of 2,049 breast cancer patients 

≥ 65 years of age from the Swiss Breast Cancer Patterns-of-Care 

study. Three age subgroups will be studied: 

the young old (65–74 years), the older old (75–84 years) 

and the oldest old (85 years and older). Patient, tumour 

characteristics and treatment adherence with national 

and international guidelines will be analyzed for each of 

the age subgroups. Predictors for guideline adherence will 

be analyzed using multivariate regression analysis, adjusting 

for known risk factors, type of treatment (surgery, 

radiotherapy, systemic treatment) and age. The potential 

impact of non-adherence to guidelines will be studied 

with appropriate statistical techniques. 


This study is unique in providing very detailed data on the 

quality of breast cancer care in the elderly. Knowledge 

about the patterns of breast cancer care in the elderly will 

be crucial to improving diagnosis and treatment in this 

growing segment of patients. 

Project coordinator: 

Prof. Dr. Beat Thürlimann 

Brustzentrum 


9007 St. Gallen 

Phone +41 (0)71 494 10 83 

Fax +41 (0)71 494 63 68 

beat.thuerlimann@kssg.ch 

Vounatsou Penelope | Spatio-temporal patterns 

and forecasting of gender-specific lung and other 

tobacco-related cancer mortality and morbidity 

rates in Switzerland (KLS 02393-02-2009) 

Duration: 01.09.2009 – 01.09.2012 

In Switzerland, lung cancer is the first cause of cancer 

mortality in men and the second in women. Although 

mortality is declining in men, in women it is steadily increasing. 

The Federal Office of Public Health (FOPH) 

launched the National Program Tobacco 2008–2012, aiming 

to reduce “smoking-related cases of death and disease”. 

Maps of the geographical patterns and trends of 

lung and other tobacco-related cancers as well as estimates 

of the disease burden at different regional scales 

will be important for the design, implementation and 

evaluation of the National Program Tobacco. 

Objectives and goals 

The main objectives of this research are to: 1) produce 

smooth maps of gender, age and site-specific patterns of 

tobacco-related cancer mortality since 1969; 2) produce 

smooth maps of gender, age and site-specific patterns of 

lung cancer mortality over time adjusted for non-smoking 

risk factors to obtain an indirect indicator of space-time 

patterns of smoking hazards; 3) explore differences in 

cancer mortality rates between linguistic regions, urbanisation 

and affluence; and 4) develop models for predictions 

of tobacco-related cancer mortality by region and 

gender for 2009–2018 and other models. 

Methods of investigation 

We propose to accomplish these objectives by employing 

and further developing Bayesian Poisson and negative binomial: 

a) spatio-temporal models for area mortality and 

incidence data; b) shared component models for a joint 

spatio-temporal analysis of the tobacco-related cancers; 

c) age-period-cohort models with spatial and temporal 

random effects to forecast geographical patterns and 

trends of mortality and incidence; and d) back-calculation 

models to estimate incidence from mortality data. 

Significance 

This research will contribute smooth maps of gender, age 

and site-specific patterns of lung and other tobacco-related 

cancer mortality and morbidity over time. The maps 

will identify discrepancies in disease burden and assist 

implementation and evaluation of the National Program 

Tobacco. This information will be useful for planning 

purposes, such as for resource allocation and costing of 

medical supplies for diagnosis and treatment. 


Dr. Penelope Vounatsou 

Biostatistics and Computational Sciences Unit 

Departement für Epidemiologie und 

Gesundheitswesen 

Schweizerisches Tropen- und Public-Health-Institut 

Socinstrasse 57 

CH-4051 Basel 

Phone +41 (0)61 284 81 09 

penelope.vounatsou@unibas.ch 

205

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