Cancer Research - Europa

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ENLIGHT New molecular methods and image analysis tools for analysis of cancer biomarkers in situ Summary The ENLIGHT project has the purpose to develop analytical procedures with the sensitivity and specifi city required to study individual nucleic acid and protein molecules, and also interacting molecules, in their normal context in cells and tissues (in situ) and in tissue lysate microarrays. A spectrum of reagents will be developed for the analysis of specifi c markers of particular interest in oncology. Furthermore, we will establish software and algorithms for automatic user-independent in situ image analysis of single molecule-events. These methods and algorithms will be applied to evaluate candidate biomarkers of special relevance for tumour biology and cancer pathology. Problem In situ analysis of cells and tissues has been an essential part of pathological research and diagnosis primarily within cancer for many years, and a number of specifi c biomarkers of predictive and prognostic value for various cancers have been identifi ed. In situ analysis of nucleic acid sequences is dominated by in situ hybridization, while in situ analysis of proteins is dominated by immunohistochemistry where sections of tissues are tested for the presence of proteins by specifi c antibodies. Due to limitations in these technologies there is a signifi cant need in the scientifi c community for new effi cient techniques and procedures for more advanced analyses. A major challenge is to develop improved means for more detailed studies of biomolecules in situ, in order to determine their abundance, sub-cellular localization, and secondary modifi cations, as well as how they interact with other molecules and participate in signalling and control of cellular function. Aims The fi rst aim is to develop new molecular methods and assays for the analysis of individual DNA and protein molecules in situ. The project is based on two fundamental technological inventions, padlock probing and proximity ligation. These are the fi rst technologies to off er the sensitivity and specifi city required for studies of single bio-molecules in situ. The padlock probe technology is used to interrogate 30 Keywords | Cancer | biomarker | in situ analysis | technology development | proximity ligation | padlock probing | nucleic acids and to distinguish closely similar sequence variants, while the proximity ligation assay (PLA) is applied to analyze individual proteins, interactions between proteins, and post-translational protein modifi cations. As a second aim we will develop automated image analysis procedures to complement the molecular methods. The objective is to achieve quantitative information about what molecules or molecule complexes are present in the sample and their tissue or sub-cellular localization (i.e. in which cellular substructures). The third aim is to use the new methods and image analysis procedures to clarify the role of molecular biomarkers in tumourigenesis, primarily concerning the AP-1 and HER protein families and for mitochondrial DNA. The methods will also be tested in a high-throughput microarray analysis system. The cancer biomarker will primarily be investigated in a research setting, but we will also explore the utility of the markers for diagnostic analyses. Expected results This project is expected to provide new means to study biomarkers for oncogenesis, and to generate novel insights in cancer biology. We expect that the in situ techniques developed in this project, and the scientifi c knowledge created, in the longer run will lead to improved disease prevention, more rapid and accurate cancer diagnosis, and better treatment opportunities. New analytical means will be developed to analyse cancer biomarkers in situ. Relative to state-of-the-art procedures, these methods are expected to provide signifi cantly improved in situ analyses in terms of specifi city, sensitivity (single molecule detection), possibility to study biomarker localisation, analysis of protein interactions and protein modifi cations, and an opportunity for simultaneous analysis of multiple markers (multiplex analysis). Automated image analysis procedures will be developed, i.e. software-based classifi cation of molecules and their localisation in tissues or cells. The software will provide a rapid way to analyse many samples as well as user-independent, unbiased data classifi cation. The results from this project are furthermore expected to provide new commercial opportunities for products addressing signifi cant market needs, thereby allowing the participating European SMEs to build sustainable businesses at the forefront of biotechnology. Potential applications Cancer biology and diagnosis. CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME
Microscopic examination of tissue sections. Coordinator Björn Ekström Anders Alderborn Olink AB Uppsala, Sweden bjorn.ekstrom@olink.com anders.alderborn@olink.com Partners Mats Gullberg Olink AB Uppsala, Sweden mats.gullberg@olink.com Ulf Landegren Ewert Bengtsson Uppsala University Uppsala, Sweden ulf.landegren@genpat.uu.se ewert.bengtsson@cb.uu.se Henrik Winther Dako Denmark A/S Glostrup, Denmark henrik.winther@dako.com Anders Larsson Immunsystem I.M.S. AB Uppsala, Sweden anders.larsson@akademiska.se Niels Foged Visiopharm A/S Hørsholm, Denmark ntf@visiopharm.com Olli Kallioniemi VTT Technical Research Centre of Finland Turku, Finland olli.kallioniemi@vtt.fi John Bartlett The University of Edinburgh Edinburgh, United Kingdom jbartlet@staffmail.ed.ac.uk Anton Raap Hans van Dam Leiden University Medical Center Leiden, The Netherlands a.k.raap@lumc.nl J.A.F.van_Dam@lumc.nl Project number LSHB-CT-2006-037545 EC contribution € 2 978 810 Duration 36 months Starting date 01/08/2006 Instrument STREP Project website www.olink.com/ enlight.html BIOLOGY 31
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: Potential applications Our DNA is u
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 and 52: Keywords | Breast cancer | metastas
Page 53 and 54: Keywords | Mitosis | phosphorylatio
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
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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
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Keywords | Melanoma | genetics | na
Page 95 and 96:
Keywords | Virus | bacteria | HPV |
Page 97 and 98:
Keywords | Breast | prostate | gene
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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
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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
Page 265 and 266:
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:
HOW TO OBTAIN EU PUBLICATIONS Our p
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