Cancer Research - Europa

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Tumor initiation, progression to malignancy, and metastasis: the ‘cancer stem cell’ view. Coordinator Riccardo Fodde Erasmus MC/JNI Dept. of Pathology Rotterdam, The Netherlands r.fodde@erasmusmc.nl 138 Partners Alberto Bardelli University of Torino Torino, Italy Thomas Brabletz University of Freiburg Freiburg, Germany Manel Esteller CNIO Madrid, Spain Christoph Klein University of Regensburg Regensburg, Germany Project number LSHC-CT-2006-037297 EC contribution € 2 169 569 Duration 36 months Starting date 01/11/2006 Instrument STREP Project website www.mcscs.eu CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME
Keywords | HNPCC | familial gastric cancer | mismatch repair | MMR-related cancer Prevention, Detection and Molecular Characterisation of Mismatch Repair-Related Hereditary <strong>Cancer</strong>s of the Digestive System Summary This project focuses on hereditary cancers of the digestive system associated with microsatellite instability, hereditary non-polyposis colorectal cancer (HNPCC) and familial gastric cancer (FGC). Microsatellite instability is the result of a defective mismatch repair (MMR) system. Germline mutations in MMR genes are found in families with HNPCC characterised by development of colorectal cancer and extracolonic malignancies, particularly cancer of the endometrium. Evidence is accumulating that also a subset of FGC is MMRrelated as families have been identifi ed with tumours showing microsatellite instability. MMR gene mutations have not yet been identifi ed in these families. Problem In HNPCC, identifi cation of MMR gene mutations has helped in identifying individuals at risk when a clear pathogenic mutation was found. Many families, however, in particular those with less penetrant HNPCC, remain genetically unresolved. Furthermore, in a large proportion of families, mutations are identifi ed whose pathogenic nature is uncertain (unclassifi ed variants). Although we have made great progress in the genetic delineation of this cancer syndrome, it has scarcely improved early diagnosis or treatment of cancer. Aim The objectives are to improve genetic testing by: • determining the role known MMR genes play in both cancer syndromes and identifying new HNPCC or FGC-related genes; • setting up comprehensive functional assays to determine the role of unclassifi ed variants in MMR related genes; • identifying tumour cells at very early stages in faeces by enhancing the sensitivity of MSI determination; • profi ling mutations accumulating in tumours as a consequence of MMR defi ciency, in order to get a better insight in tumour development, which can be instrumental in clinical management/tumour treatment. EARLY DETECTION, DIAGNOSIS AND PROGNOSIS Expected results Our proposal will thus improve genetic testing, improve early detection of polyps/tumours in individuals at risk for these cancer syndromes and improve clinical management of HNPCC and FGC patients. Potential applications The assays and the data generated will be set up and used in diagnostic laboratories and by clinical geneticists all over Europe and the world. Coordinator Robert M.W. Hofstra University Medical Center Groningen Dept. of Medical Genetics Groningen, The Netherlands r.m.w.hofstra@medgen.umcg.nl Partners Lauri A. Aaltonen Haartman Institute Helsinki, Finland Project number LSHC-CT-2005-018754 EC contribution € 2 620 200 Duration 36 months Starting date 01/02/2006 Instrument STREP Project website www.rug.nl/umcg/ onderzoek/internationale projecten/europese projecten/mmr/index Lene Juel Rasmussen Roskilde University Roskilde, Denmark Niels de Wind Leiden University Medical Center Leiden, The Netherlands Raquel Seruca University of Porto, Institute of Molecular Pathology and Immunology <strong>Cancer</strong> Genetics Group Porto, Portugal 139
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PROJECT SYNOPSES CANCER RESEARCH PR
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CANCER RESEARCH PROJECTS FUNDED UND
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TABLE OF CONTENTS FOREWORD - CANCER
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Prevention 97 EPIC 98 EUROCADET 100
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CANCER: COMBATING A COMPLEX DISEASE
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Biology Cancer is a disease ethat t
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p53 activators ASPP Partner 5 NFkap
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Keywords | Angiogenesis | vasculoge
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Keywords | Tumour-host interactions
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Keywords | Breast | metastasis | ge
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Keywords | Identifi cation of novel
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Keywords | Systems biology | modell
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Keywords | Oncology | anticancer th
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• public health research coupled
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Expected results We will construct
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Potential applications Our DNA is u
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Microscopic examination of tissue s
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Pluripotent embryonic stem cells ar
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• Decryption of the leukaemia cel
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• identifi cation of molecular ta
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A B C LT-HSC CSC The Cancer Stem Ce
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X-ray diff raction of target drug c
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using pathway-specifi c reporter ce
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Keywords | Kinases | pediatric panc
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Keywords | Lymphangiogenesis | angi
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Keywords | Breast cancer | metastas
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Keywords | Mitosis | phosphorylatio
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Keywords | Therapy | genome | telom
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Keywords | Multiple myeloma | cance
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Keywords | p53 tumour suppressor |
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Development of eff ective anti-canc
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Coordinator Patrick A. Curmi INSERM
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Drosophila as a model system for tu
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Normal cell growth and epithelial l
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effi ciently with cancer cell proli
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A high-throughput assay of transcri
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Coordinator Ewa Sikora Nencki Insti
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Expected results The SIROCCO consor
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Keywords | Epigenetics | gene regul
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Keywords | Hereditary | tricarboxyl
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Keywords | HSV-1 | hepatocellular c
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Keywords | Apoptosis | autophagy |
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Keywords | Tumour | host | signalli
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Aetiology The uncontrolled cell gro
Page 89 and 90: Coordinator Rosalind Eeles Reader i
Page 91 and 92: The parallelogram approach in CARCI
Page 93 and 94: Keywords | Melanoma | genetics | na
Page 95 and 96: Keywords | Virus | bacteria | HPV |
Page 97 and 98: Keywords | Breast | prostate | gene
Page 99 and 100: Prevention The fact that preventing
Page 101 and 102: Coordinator Elio Riboli Imperial Co
Page 103 and 104: Coordinator Jan Willem Coebergh Joh
Page 105: Coordinator Jose M a Benlloch Conse
Page 108 and 109: BAMOD Breath-Gas Analysis for Molec
Page 110 and 111: BioCare Molecular Imaging for Biolo
Page 112 and 113: These centres of excellence will in
Page 114 and 115: Expected results Optimise the benef
Page 116 and 117: 114 Cell proliferation and apoptosi
Page 118 and 119: COBRED Colon and Breast cancer Diag
Page 120 and 121: DASIM Diagnostic Applications of Sy
Page 122 and 123: Expected results Primarily, the res
Page 124 and 125: Coordinator John A. Foekens Dept. o
Page 126 and 127: 124 Aim Drop-Top has two major obje
Page 128 and 129: Coordinator Gorka Ochoa Progenika B
Page 130 and 131: Expected results The E.E.T.-Pipelin
Page 132 and 133: e developed by eTUMOUR is likely to
Page 134 and 135: Coordinator Angel Porgador Ben-Guri
Page 136 and 137: • the design of a compact assembl
Page 138 and 139: Potential applications We believe t
Page 142 and 143: MolDiag-Paca Novel Molecular Diagno
Page 144 and 145: NEMO Nano based capsule-Endoscopy w
Page 146 and 147: OVCAD Ovarian Cancer - Diagnosis of
Page 148 and 149: P-MARK Validation of recently devel
Page 150 and 151: POC4life Multiparametric quantum do
Page 152 and 153: PROMET Prostate cancer molecular-or
Page 154 and 155: Micrometastasis in the bone marrow.
Page 156 and 157: and pharmaco-kinetics studies. This
Page 158 and 159: Coordinator Raffaella Giavazzi Isti
Page 160 and 161: • Development of tools for diagno
Page 163 and 164: Treatment Two major problems when t
Page 165 and 166: Coordinator Lluis M. Mir UMR 8121 C
Page 167 and 168: Potential applications ANGIOSTOP ha
Page 169 and 170: Green-fl uorescence protein- expres
Page 171 and 172: Coordinator Robert Hawkins Universi
Page 173 and 174: Expected results The BACULOGENES pr
Page 175 and 176: descriptors of the molecules to be
Page 177 and 178: Keywords | Therapeutic vaccine | im
Page 179 and 180: Keywords | Cancer chemotherapy | dr
Page 181 and 182: Keywords | Children | cancer | leuk
Page 183 and 184: Chimaeric TCR shown in context of n
Page 185 and 186: Andrea Splendiani Leaf Bioscience s
Page 187 and 188: Coordinator Anne O’Garra The Medi
Page 189 and 190: Coordinator Jacques Bartholeyns IDM
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Structure Driven Drug Design The in
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• acquire fundamental knowledge a
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Terry Jones Victoria University of
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Potential applications The use of t
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groups and management structures. T
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T. Barbui Azienda Ospedaliera-Osped
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Keywords | Mantle cell lymphoma | t
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Keywords | Hypoxia | HIF | pericell
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Keywords | Radiation-induced compli
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Keywords | Gene therapy | adenoviru
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Keywords | Dependence receptors | a
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Keywords | Photodynamic therapy | a
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Keywords | Ovarian cancer | thymidy
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Keywords | Quality assurance | clin
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Keywords | Circadian | clocks | cel
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Keywords | Anticancer therapy | onc
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Coordinator Monika Lusky Transgene
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6 000 women over a three-year perio
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Keywords | Solid tumours | apoptosi
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Keywords | Lymphoma | leukaemia | v
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Coordinator Riccardo Dolcetti Centr
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CCPRB Cancer Control using Populati
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EPCRC The European Palliative Care
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EUROCAN+PLUS Feasibility Study for
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EUSTIR A European strategy for the
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NORMOLIFE Development of new therap
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Scientifi c Model Systems The compl
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Performance of benchmarking exercis
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• markers correlating with the im
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Indices - Keywords Indices - Partne
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● disease markers 131 ● DNA dam
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● renal 77 ● replication 219
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Bos, Nico A. 56 Boskovic, Darinka 2
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Geley, Stephan 159 Georgopoulos, Li
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Lingner, Joachim 54 Linial, Michal
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Ragno, Pia 115 Rainford, Martyn 92
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Vernos, Isabelle 22 Veronesi, Umber
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● Centre Hospitalier Universitair
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● IFOM - Fondazione Istituto FIRC
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● National University of Ireland
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● University of Bari 174 ● Univ
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