Cancer Research in Switzerland - Krebsliga Schweiz

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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. Project coordinator Prof. Dr. Aleksandra Wodnar-Filipowicz Basel Stem Cell Center of Competence Medizinische Fakultät Universität Basel 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. Project coordinator Dr Khalil Zaman Centre pluridisciplinaire d’oncologie (CePO) Centre hospitalier universitaire vaudois (CHUV) Rue du Bugnon 46 CH-1011 Lausanne 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. Project coordinator Prof. Dr. Xiao Yan Zhong Forschungsgruppe pränatale Medizin und gynäkologische Onkologie Departement Biomedizin Universität Basel Hebelstrasse 20 CH-4031 Basel Phone +41 (0)61 328 69 86 Fax +41 (0)61 265 93 99 xzhong@uhbs.ch
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Cancer Research in Switzerland A pu
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Cancer Research in Switzerland
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Basic biomedical research 55 Cancer
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policy work and was in charge of de
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The main focus of the research fund
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gramme research funding decreased b
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Table 2 Distribution of funds for i
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Funding patient-centred research Pa
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value was not clearly discernible.
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New organization of the Foundation
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The board of the Foundation Cancer
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The president of the Scientific Com
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Prof. Martin Pruschy, PhD Departmen
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Swartz wants to find out how tumour
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The scientific and medical research
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3. The original order/sequence of t
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As a federation, the Cancer League
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List of funded research projects, i
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Zippelius Alfred | 2009: CHF 100,00
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Kridel Robert | 2010: CHF 100,000.-
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Thurgau Cancer League Biotechnologi
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Weller Michael | 2010: CHF 65,828.-
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manageable funding of individual pr
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enhances breast cancer cell motilit
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Rüegg Curzio et al. | Tumor-mediat
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International Clinical Cancer Resea
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in PHIV were shown for Hodgkin’s
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Zucca Emanuele et al. | Internation
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56 “hierarchical structure” of
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58 the attempt should be made to st
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60 Gönczy Pierre | KLS 0202402
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62 Romero Pedro | OCS 020110220
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64 Beermann Friedrich | In vivo scr
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66 Christofori Gerhard | Podoplanin
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68 Frei Christian | The function of
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70 cell, this novel mechanism serve
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72 Results The induction of viral p
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74 Hübscher Ulrich | Repair of oxi
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76 Methods and experimental approac
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78 of cMyc and/or NMyc and demo
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80 In summary, this work improves o
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82 Pruschy Martin | Microtubule int
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84 Renner Christoph | Selective inh
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86 Goal Here we build on these obse
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88 by TDG prevents efficient downst
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90 To address these questions, we a
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92 Translational relevance The resu
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94 Grünberg Jürgen | KFS 025460
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96 Tschan Mario P. | KFS 0248608
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98 Boyman Onur | Preclinical testin
Page 102 and 103: 100 Constam Daniel | Role of activi
Page 104 and 105: 102 this study we will examine the
Page 106 and 107: 104 Janscak Pavel | Study of the ro
Page 108 and 109: 106 Müller Anne | The molecular pa
Page 110 and 111: 108 Radtke Freddy | The role of Not
Page 112 and 113: 110 Schär Primo | DNA repair, epig
Page 114 and 115: 112 In this project we will investi
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Page 118 and 119: 116 and Research). Other financial
Page 120 and 121: 118 be totally unaffordable for aca
Page 122 and 123: 120 Clinical research List of compl
Page 124 and 125: 122 Hunger Robert E. | OCS 02262-08
Page 126 and 127: 124 Clinical research Presentation
Page 128 and 129: 126 Benhattar Jean | Identification
Page 130 and 131: 128 Bertoni Francesco | Genome-wide
Page 132 and 133: 130 Interpretation ESA treatment in
Page 134 and 135: 132 Our results could pave the way
Page 136 and 137: 134 new drugs that specifically tar
Page 138 and 139: 136 slides in two different concent
Page 140 and 141: 138 Conclusions A strong network of
Page 142 and 143: 140 tions introduced to ARE motifs
Page 144 and 145: 142 Müller Beatrice U. | The maste
Page 146 and 147: 144 A novel method was developed fo
Page 148 and 149: 146 (SAKK 35-98) the Swiss Group fo
Page 150 and 151: 148 Timmermann Beate | Prospective
Page 154 and 155: 152 Zucca Emanuele | A prospective
Page 156 and 157: 154 Heinimann Karl | KFS 02489-08-2
Page 158 and 159: 156 Riggi Nicolò | BIL KFS 02717-0
Page 160 and 161: 158 activity at the single cell lev
Page 162 and 163: 160 Our research projects aim at un
Page 164 and 165: 162 Körner Meike | In vitro evalua
Page 166 and 167: 164 Nadal David | Is endemic Burkit
Page 168 and 169: 166 (> 50.000/patient). For their a
Page 170 and 171: 168 Zeller Rolf | Functional analys
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Page 174 and 175: 172 area of health services researc
Page 176 and 177: 174 The financing of palliative car
Page 178 and 179: 176 National Strategy for Palliativ
Page 180 and 181: 178 Psychosocial research List of c
Page 182 and 183: 180 Within the patient group, level
Page 184 and 185: 182 Further, the results suggest th
Page 186 and 187: 184 It is in this context that the
Page 188 and 189: 186 Recommendation Female spouses o
Page 190 and 191: 188 Psychosocial research Presentat
Page 192 and 193: 190 rates communication skills rema
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Page 197 and 198: data from cancer registries. In the
Page 199 and 200: The importance of cancer registries
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Epidemiological research List of ap
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Impact This work will serve as the
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Thürlimann Beat | Management of br
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