Cancer Research in Switzerland - Krebsliga Schweiz

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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. Project coordinator Prof. Dr. Anne Müller Institut für molekulare Krebsforschung Universität Zürich Winterthurerstrasse 190 CH8057 Zürich 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. Project coordinator Prof. Dr. Christian Münz Institut für experimentelle Immunologie Universität Zürich Winterthurerstrasse 190 CH8057 Zürich 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. Project coordinator Prof. Dr. Adrian F. Ochsenbein Universitätsklinik für medizinische Onkologie Inselspital Freiburgstrasse 10 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. Project coordinator Prof. Dr. Olivier Pertz Institut für Biochemie und Genetik Departement Biomedizin Universität Basel Mattenstrasse 28 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. Project coordinator Prof. Dr Tatiana Petrova Centre pluridisciplinaire d’oncologie (CePO) Centre hospitalier universitaire vaudois (CHUV) et Université de Lausanne Chemin des Boveresses 155 CH1066 Epalinges 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. Project coordinator Prof. Dr. Andreas Plückthun Biochemisches Institut Universität Zürich Winterthurerstrasse 190 CH8057 Zürich 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. Project coordinator Prof. Dr. Martin Pruschy Labor für molekulare Radiobiologie Klinik für RadioOnkologie UniversitätsSpital Zürich Rämistr. 100 CH8091 Zürich Phone +41 (0)44 255 85 49 martin.pruschy@usz.ch 107
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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
Page 58 and 59: 56 “hierarchical structure” of
Page 60 and 61: 58 the attempt should be made to st
Page 62 and 63: 60 Gönczy Pierre | KLS 0202402
Page 64 and 65: 62 Romero Pedro | OCS 020110220
Page 66 and 67: 64 Beermann Friedrich | In vivo scr
Page 68 and 69: 66 Christofori Gerhard | Podoplanin
Page 70 and 71: 68 Frei Christian | The function of
Page 72 and 73: 70 cell, this novel mechanism serve
Page 74 and 75: 72 Results The induction of viral p
Page 76 and 77: 74 Hübscher Ulrich | Repair of oxi
Page 78 and 79: 76 Methods and experimental approac
Page 80 and 81: 78 of cMyc and/or NMyc and demo
Page 82 and 83: 80 In summary, this work improves o
Page 84 and 85: 82 Pruschy Martin | Microtubule int
Page 86 and 87: 84 Renner Christoph | Selective inh
Page 88 and 89: 86 Goal Here we build on these obse
Page 90 and 91: 88 by TDG prevents efficient downst
Page 92 and 93: 90 To address these questions, we a
Page 94 and 95: 92 Translational relevance The resu
Page 96 and 97: 94 Grünberg Jürgen | KFS 025460
Page 98 and 99: 96 Tschan Mario P. | KFS 0248608
Page 100 and 101: 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 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 152 and 153: 150 recurrence of the disease, we a
Page 154 and 155: 152 Zucca Emanuele | A prospective
Page 156 and 157: 154 Heinimann Karl | KFS 02489-08-2
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156 Riggi Nicolò | BIL KFS 02717-0
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158 activity at the single cell lev
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160 Our research projects aim at un
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162 Körner Meike | In vitro evalua
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164 Nadal David | Is endemic Burkit
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166 (> 50.000/patient). For their a
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168 Zeller Rolf | Functional analys
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170
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172 area of health services researc
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174 The financing of palliative car
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176 National Strategy for Palliativ
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178 Psychosocial research List of c
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180 Within the patient group, level
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182 Further, the results suggest th
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184 It is in this context that the
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186 Recommendation Female spouses o
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188 Psychosocial research Presentat
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190 rates communication skills rema
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Epidemiological research Epidemiolo
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data from cancer registries. In the
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The importance of cancer registries
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Ess Silvia | Patterns of care and s
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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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