Cancer Research - Europa

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OVCAD Ovarian Cancer – Diagnosis of a Silent Killer Summary In Europe each year, 63 000 ovarian cancer cases are diagnosed and 41 000 ovarian cancer patients die. Seventy-fi ve per cent of patients are diagnosed at advanced stages due to an asymptomatic course and 75 % of these patients die within fi ve years. Treatment involves surgery followed by chemotherapy. However, 25 % of patients relapse within six months after initial treatment and there is doubt as to whether these patients benefi t from this therapy at all. Recurrent disease is diagnosed by clinical evidences or by CA125 dynamics. But detection is limited due to a lack of sensitivity and specifi city, as is the case with primary diagnosis. Currently, there is no method to detect minimal disease, the fi rst indicator of therapy failure and a precursor of recurrence, which inevitably leaves specifi c traces throughout the body. There is a strong need for molecular-oriented research to detect minimal disease in order to disburden patients from an ineffi cient and toxic therapy. 144 Keywords | Ovarian cancer | molecular diagnosis | minimal disease | chemotherapy | gene expression | signature | proteomics | CGH | mutation | methylation | targeted therapy | Ovarian carcinoma – immunohistochemical staining of L1on ovarian carcinoma and its metastases in adjacent organs (Source: J. Sehouli, Berlin; M. Fogel, Rehovot and P. Altevogt, Heidelberg). Problem Diagnosis at advanced stages and a high mortality rate is the tragedy of ovarian cancer. After initial surgical therapy, 25 % of patients relapse within six months and 75 % die within fi ve years, mainly due to resistance to chemotherapy. Available methods for the detection of recurrent disease lack both sensitivity and specifi city and usually miss minimal disease as a fi rst sign of therapy resistance. Aim The aim of this project is to defi ne clinically useful molecular-orientated early detection of minimal residual disease (MRD) in ovarian cancer that can identify patients not responding to the standard (state-of-theart) therapy at the time of surgery. This will disburden the patients from the very toxic and ineffi cient standard chemotherapy and eventually lead to alternative therapy modalities, which can really bring benefi ts to this group of patients. ‘Signatures’ that signal the presence of MRD will be investigated at various molecular levels (DNA, RNA and protein) and in a broad spectrum of biological materials (tumour tissue, disseminated tumour cells, sera, white blood cells, ascites) from ovarian cancer patients. Specifi cally, the project is aiming at: • development and/or validation of several molecular diagnostic methods to identify MRD in ovarian cancer patients; • defi nition of a new ‘diagnostic state-of-the-art’ by correlating the diagnostic results with the clinically-defi ned response of the patients to standard therapy, consisting of primary surgery, followed by standard platinum/Taxolbased chemotherapy; • early discovery and characterisation of MRD by molecular diagnostics leading to additional therapeutic interventions, ultimately improving patients’ prognosis and quality of life; • better understanding of the mechanisms that cause MRD and therapy failure; • identifi cation and evaluation of new potential therapy targets. Expected results Defi nition of a diagnostic method consisting of one or several molecular tests for early detection of minimal disease as an early indicator of therapy failure. Potential applications Diagnostic molecular tests and immunotherapy. CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME
Immunohistochemical staining of disseminated tumour cells isolated from blood • Comparative genomic hybridisation to detect genomic loss and gain. • GeneStiX Imager for analysis of gene methylation (Sources: G. Hager and R. Zeillinger, Vienna; C. Theillet, Montpellier; Biofocus GmbH, Recklinghausen). Coordinator Robert Zeillinger Medizinische Universität Wien Dept. of Obstetrics and Gynaecology Vienna, Austria robert.zeillinger@meduniwien.ac.at Partners Jalid Sehouli Dominique Koensgen Alexander Mustea Charité Universitätsmedizin Berlin Berlin, Germany Ignace B. Vergote Toon van Gorp Katholieke Universiteit Leuven Leuven, Belgium Jean-Paul Borg Anthony Gonçalves Institut Paoli-Calmettes Institut de Recherches sur le Cancer de Marseille Marseille, France Peter Altevogt German Cancer Research Centre Heidelberg, Germany EARLY DETECTION, DIAGNOSIS AND PROGNOSIS Mina Fogel Kaplan Medical Centre Institute of Pathology Rehovot, Israel Lothar Prix Andreas Schuetz Biofocus GmbH Recklinghausen, Germany Charles Theillet Centre Régional de Lutte contre le Cancer de Montpellier Montpellier, France Viktoria Weber Centre for Biomedical Technology Danube University Krems Krems, Austria Bernd Mayer Emergentec biodevelopment GmbH Vienna, Austria Fritz Kury Labordiagnostika GmbH Vienna, Austria Els Berns Erasmus Medical Center Rotterdam, The Netherlands Hans Dieplinger Vitateq Biotechnology GmbH Innsbruck, Austria Burkhard Brandt Universitätsklinikum Hamburg-Eppendorf Institute of Tumour Biology Hamburg, Germany Project number LSHC-CT-2005-018698 EC contribution € 4 259 625 Duration 36 months Starting date 15/12/2005 Instrument STREP Project website www.ovcad.org 145
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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
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Coordinator Rosalind Eeles Reader i
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The parallelogram approach in CARCI
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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 140 and 141: Tumor initiation, progression to ma
Page 142 and 143: MolDiag-Paca Novel Molecular Diagno
Page 144 and 145: NEMO Nano based capsule-Endoscopy w
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
Page 191 and 192: Structure Driven Drug Design The in
Page 193 and 194: • acquire fundamental knowledge a
Page 195 and 196: 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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