Cancer Research - Europa

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Coordinator Anna Maria Teti Dept. of Experimental Medicine University of L’Aquila L’Aquila, Italy info@metabre.org Partners Roberto Buccione Consorzio Mario Negri Sud Italy Rosette Lidereau Centre René Huguenin Saint-Cloud, France Philippe Clezardin INSERM U664 Paris, France 50 Image of a bone metastasis obtained by 3 dimensional computerised micro-tomodensitometry. Philippe Clement-Lacroix ProSkelia SAS Romainville, France Gabri van der Pluijm Leiden University Medical Center Leiden, The Netherlands Ben-Tsion Williger CancerTek Pharmaceuticals Ltd Kiriat-Oro, Israel Maciej Ugorski Wroclaw University of Environmental and Life Sciences Wroclaw, Poland Suzanne Eccles Institute of Cancer Research United Kingdom Angels Sierra Fundació Privada Institut d’Investigació Biomèdica de Bellvitge Barcelona, Spain Marc Bracke Ghent University Ghent, Belgium Vincent Castronovo University of Liège Liège, Belgium Project number LSHC-CT-2004-503049 EC contribution € 4 005 295 Duration 48 months Starting date 01/01/2004 Instrument STREP Project website www.metabre.org CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME
Keywords | Mitosis | phosphorylation | RNAi | mass spectrometry | chemical inhibitors | MitoCheck Regulation of Mitosis by Phosphorylation – A Combined Functional Genomics, Proteomics and Chemical Biology Approach Summary The proliferation of cells depends on the duplication and segregation of their genomes. The latter is an immensely complex process that remains poorly understood at a molecular level. Mistakes during mitosis contribute to cancer, whereas mistakes during meiosis that cause aneuploidy are the leading cause of infertility and mental retardation. During mitosis, sister DNA molecules are dragged towards opposite poles of the cell due to their prior attachment to microtubules with opposite orientations (bi-orientation). Bi-orientation involves dissolution of the nuclear membrane, changes in chromosome organisation, and re-organisation of the spindle apparatus. How mitotic cells coordinate these disparate but inter-locking processes is poorly understood. One thing, however, is certain – protein kinases like Cdk1 have fundamental roles. Nevertheless, Cdk1’s actual function remains mysterious, despite recognition of its importance by a Nobel Prize. The same is true for other mitotic kinases, such as Plk1 and Aurora A and B. We need to know what set of proteins are phosphorylated, what their functions are, or how phosphorylation changes their activity. Identifi cation of kinase substrates has been hampered by diffi culties in mapping phosphorylation sites, in experimentally controlling protein kinase activity, and in evaluating the physiological consequences of defi ned phosphorylation sites. The premise behind this proposal is that all three hurdles can be overcome by new technologies, namely the use of RNA interference to identify, in a systematic (functional genomics) manner, potential substrates, iTAP-tagging to purify protein complexes, small molecules to inhibit specifi c kinases in a controlled fashion, and mass spectrometry to identify phosphorylation sites on complex subunits. Because the concept behind this project could be applied to other areas, it will have an impact on European cell biology far beyond the cell cycle community. BIOLOGY Problem Better understanding of mitotic process in mammalian cells. Aim The objectives of this project are: • to identify all human protein complexes required for mitosis; • to analyse how these complexes are regulated through phosphorylation by mitotic kinases; • to evaluate the potential of mitotic kinases as diagnostic or prognostic markers in clinical oncology. Expected results • A list of mammalian proteins that have important roles during mitosis. • Subunit composition of the mitotic protein complexes and their mitosis-specifi c phosphorylation sites. • Expression profi les of mitotic kinases in tumour samples and the potential of the mitotic kinases as diagnostic or prognostic markers in clinical oncology. • A web-based database. Potential applications Our basic understanding of the cell division process at a molecular level will be advanced. The project will generate knowledge relevant for diagnostics and biomarker research as well as for target identifi cation for new antiproliferative pharmaceuticals. We will develop genomics and proteomics technology, applicable not only to mitosis research but also to other research areas, and we will contribute to the integration and international visibility of the European research area. 51
Page 1 and 2: PROJECT SYNOPSES CANCER RESEARCH PR
Page 3 and 4: CANCER RESEARCH PROJECTS FUNDED UND
Page 5 and 6: TABLE OF CONTENTS FOREWORD - CANCER
Page 7 and 8: Prevention 97 EPIC 98 EUROCADET 100
Page 9 and 10: CANCER: COMBATING A COMPLEX DISEASE
Page 11 and 12: Biology Cancer is a disease ethat t
Page 13 and 14: p53 activators ASPP Partner 5 NFkap
Page 15 and 16: Keywords | Angiogenesis | vasculoge
Page 17 and 18: Keywords | Tumour-host interactions
Page 19 and 20: Keywords | Breast | metastasis | ge
Page 21 and 22: Keywords | Identifi cation of novel
Page 23 and 24: Keywords | Systems biology | modell
Page 25 and 26: Keywords | Oncology | anticancer th
Page 27 and 28: • public health research coupled
Page 29 and 30: Expected results We will construct
Page 31 and 32: Potential applications Our DNA is u
Page 33 and 34: Microscopic examination of tissue s
Page 35 and 36: Pluripotent embryonic stem cells ar
Page 37 and 38: • Decryption of the leukaemia cel
Page 39 and 40: • identifi cation of molecular ta
Page 41 and 42: A B C LT-HSC CSC The Cancer Stem Ce
Page 43 and 44: X-ray diff raction of target drug c
Page 45 and 46: using pathway-specifi c reporter ce
Page 47 and 48: Keywords | Kinases | pediatric panc
Page 49 and 50: Keywords | Lymphangiogenesis | angi
Page 51: Keywords | Breast cancer | metastas
Page 55 and 56: Keywords | Therapy | genome | telom
Page 57 and 58: Keywords | Multiple myeloma | cance
Page 59 and 60: Keywords | p53 tumour suppressor |
Page 61 and 62: Development of eff ective anti-canc
Page 63 and 64: Coordinator Patrick A. Curmi INSERM
Page 65 and 66: Drosophila as a model system for tu
Page 67 and 68: Normal cell growth and epithelial l
Page 69 and 70: effi ciently with cancer cell proli
Page 71 and 72: 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 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
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Tumor initiation, progression to ma
Page 142 and 143:
MolDiag-Paca Novel Molecular Diagno
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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
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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
Page 197 and 198:
Potential applications The use of t
Page 199 and 200:
groups and management structures. T
Page 201 and 202:
T. Barbui Azienda Ospedaliera-Osped
Page 203 and 204:
Keywords | Mantle cell lymphoma | t
Page 205 and 206:
Keywords | Hypoxia | HIF | pericell
Page 207 and 208:
Keywords | Radiation-induced compli
Page 209 and 210:
Keywords | Gene therapy | adenoviru
Page 211 and 212:
Keywords | Dependence receptors | a
Page 213 and 214:
Keywords | Photodynamic therapy | a
Page 215 and 216:
Keywords | Ovarian cancer | thymidy
Page 217 and 218:
Keywords | Quality assurance | clin
Page 219 and 220:
Keywords | Circadian | clocks | cel
Page 221 and 222:
Keywords | Anticancer therapy | onc
Page 223 and 224:
Coordinator Monika Lusky Transgene
Page 225 and 226:
6 000 women over a three-year perio
Page 227 and 228:
Keywords | Solid tumours | apoptosi
Page 229 and 230:
Keywords | Lymphoma | leukaemia | v
Page 231:
Coordinator Riccardo Dolcetti Centr
Page 234 and 235:
CCPRB Cancer Control using Populati
Page 236 and 237:
EPCRC The European Palliative Care
Page 238 and 239:
EUROCAN+PLUS Feasibility Study for
Page 240 and 241:
EUSTIR A European strategy for the
Page 242 and 243:
NORMOLIFE Development of new therap
Page 245 and 246:
Scientifi c Model Systems The compl
Page 247 and 248:
Performance of benchmarking exercis
Page 249 and 250:
• markers correlating with the im
Page 251 and 252:
Indices - Keywords Indices - Partne
Page 253 and 254:
● disease markers 131 ● DNA dam
Page 255 and 256:
● renal 77 ● replication 219
Page 257 and 258:
Bos, Nico A. 56 Boskovic, Darinka 2
Page 259 and 260:
Geley, Stephan 159 Georgopoulos, Li
Page 261 and 262:
Lingner, Joachim 54 Linial, Michal
Page 263 and 264:
Ragno, Pia 115 Rainford, Martyn 92
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Vernos, Isabelle 22 Veronesi, Umber
Page 267 and 268:
● Centre Hospitalier Universitair
Page 269 and 270:
● IFOM - Fondazione Istituto FIRC
Page 271 and 272:
● National University of Ireland
Page 273 and 274:
● University of Bari 174 ● Univ
Page 275 and 276:
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