Cancer Research - Europa

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Coordinator John A. Foekens Dept. of Medical Oncology Erasmus MC Josephine Nefkens Institute Rotterdam, The Netherlands j.foekens@erasmusmc.nl Partners John W.M. Martens Dept. of Medical Oncology Erasmus MC Rotterdam, The Netherlands j.martens@erasmusmc.nl Manfred Schmitt Nadia Harbeck Dept. of Obstetrics and Gynaecology Technische Universität München Klinikum rechts der Isar München, Germany manfred.schmitt@lrz.tu-muenchen.de; nadia.harbeck@lrz.tu-muenchen.de Nils Brünner Royal Danish Veterinary and Agriculture University Institute of Pharmacology and Pathobiology Frederiksberg C, Denmark nbr@kvl.dk 122 Fred C.G.J. Sweep Dept. of Chemical Endocrinology University Medical Center Nijmegen Nijmegen, The Netherlands f.sweep@ace.umcn.nl Sabine Maier Epigenomics AG Berlin, Germany sabine.maier@epigenomics.com Tanja Cufer Dept. of Medical Oncology Institute of Oncology Ljubljana, Slovenia tcufer@onko-i.si Frédérique Spyratos Centre René Huguenin Laboratoire d’Oncobiologie St-Cloud, France f.spyratos@stcloud-huguenin.org Joe Duffy Nuclear Medicine Department National University of Ireland St.Vincent’s University Hospital Dublin, Ireland michael.j.duffy@ucd.ie Serenella Eppenberger-Castori Urs Eppenberger Stiftung Tumorbank Basel Riehen, Switzerland s.eppenberger@oncoscore.com Binary epigenetic predictor: Predictive DNA methylation patterns identifi ed during this project and indicated by the barcode here can guide the clinician to decide whether or not to treat and to determine the best type of treatment for the individual patient. © Epigenomics AG, Berlin. Project number LSHC-CT-2003-504586 EC contribution € 2 533 758 Duration 36 months Starting date 01/01/2004 Instrument STREP Project website www.erasmusmc.nl/ interne_oncologie/ FP6/index.htm CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME
Keywords | Urology | clinical analysis | anticancer therapy | prognonsis | microarray | Drop-Top Integration of DNA, RNA and protein markers in a tool for the prognosis and diagnosis of human disease Summary The management of patients with superfi cial bladder cancer is diffi cult. No reliable means exists to determine whether a tumour will progress towards an infi ltrative form, which requires radical surgery (cystectomy), or whether it will remain superfi cial, which requires only conservative surgery (resection). In addition, no dependable marker exists to predict whether a primary tumour will reappear or not during the years following surgical resection, forcing patients to undergo constant revisions that reduce their quality of life and overburden health care systems. Numerous markers of various types (genes, transcripts and proteins) have been analyzed in bladder cancer studies. Some of them have been found to harbor potential for the prognosis (progression and recurrence) of superfi cial tumours. However, analyses have often been limited to a single type of marker or even to a single marker. To the best of our knowledge, no study has attempted to integrate diff erent types of markers for an increased predictive power. The main scientifi c goal of Drop-Top is to identify a set of markers with high predictive power for tumour progression and recurrence. To this end, we propose to collect tumour and urine samples from bladder cancer patients with a detailed clinical record, to measure in them markers of diff erent types, to fi nd statistically signifi cant correlations between measurements and clinical records, and to select a predictor set. In addition, Drop-Top pursues an ambitious technological challenge: the development of a prognosis microarray for the detection of said predictor set. In order to achieve this we propose to measure all three types of marker biomolecules by means of a single type of probe: oligonucleotides. Specifi cally, we propose to use short, long and aptamer oligonucleotides for the detection of gene, transcript and protein markers respectively. Problem <strong>Cancer</strong> is the second cause of death in the Western world and its incidence is increasing due to the overall aging of the population. Although advances in our understanding of the mechanisms of tumour onset and progression have been EARLY DETECTION, DIAGNOSIS AND PROGNOSIS enormous, major impact on survival has been restricted to haematopoietic malignancies, some pediatric tumours, and very few solid tumours. Improvement in survival can be attributed not only to advances in standard chemo- and radio-therapy and to the recent implementation of targeteddrug therapy, but also to advances in diagnosis and the identifi cation of high-risk groups, which allow for earlier and better treatment selection. In contrast, the overall prognosis of the most common cancers, such as lung, colon, prostate, breast and bladder cancers remains poor, specially when the tumour cannot be cured by surgery. One limitation is that the pathologist’s interpretation of the tumour’s histological features remains the ‘gold standard’. Recent advances in microarray technology together with information derived from the sequencing of the human genome have raised hopes that this situation will change dramatically in the coming years. For these hopes to be realized, it is essential to make appropriate use of information, technology and clinical resources. We believe that resources are often wasted because of inappropriate approaches and inadequate collaboration between clinical, academic and industrial partners. Transcriptome analysis by DNA microarrays has been successfully used for the identifi cation of biomarkers of tumour progression. However, and due to the use of diff erent microarray platforms and patient selection strategies, among others, the biomarkers identifi ed for a given clinical condition vary from study to study. Therefore, their application to common clinical practice has not yet taken place, and requires prospective studies. The Drop-Top proposal intends to overcome the above limitations by a double approach: • prospective validation of the information acquired through retrospective studies. For this, a collaborative multicentre eff ort is essential; • integration of biomarkers from genome, transcriptome and proteome analysis in a single predictor set. Even though each of these three analyses by itself will likely contribute, it is expected that the combination of biomarker types will result in an enhanced predictive power. This type of strategy has scarcely been used due to: • the high cost of microarray technology; • the need to have access to diff erent platforms for the detection of diff erent biomolecules; • the fragmentary nature of most of the published work (multiple DNA, mRNA and protein markers studied, but only individually and in most cases weakly associated to disease phenotype); • the lack of bioinformatics and biostatistics tools to handle heterogeneous data; • the limited amount of clinical and follow-up information usually available. In addition, most of these studies are performed without taking into consideration potential bias in the patient population under study (i.e. large tumour cases are more likely to be studied than small tumour cases for sample availability reasons). 123
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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
Page 73 and 74: Coordinator Ewa Sikora Nencki Insti
Page 75 and 76: Expected results The SIROCCO consor
Page 77 and 78: Keywords | Epigenetics | gene regul
Page 79 and 80: Keywords | Hereditary | tricarboxyl
Page 81 and 82: Keywords | HSV-1 | hepatocellular c
Page 83 and 84: Keywords | Apoptosis | autophagy |
Page 85 and 86: Keywords | Tumour | host | signalli
Page 87 and 88: 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 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 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
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descriptors of the molecules to be
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Keywords | Therapeutic vaccine | im
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Keywords | Cancer chemotherapy | dr
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Keywords | Children | cancer | leuk
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Chimaeric TCR shown in context of n
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Andrea Splendiani Leaf Bioscience s
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Coordinator Anne O’Garra The Medi
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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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