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ANGIOSKIN DNA Electrotransfer of Plasmids Coding for Antiangiogenic Factors as a Proof of Principle of Non-Viral Gene Therapy for the Treatment of Skin Disease Summary Keywords | Gene therapy | non-viral gene therapy | dermatology | biomedical engineering | electropermeabilisation | electroporation | DNA electrotransfer | antiangiogenesis | cancer treatment | new therapies | electric pulses | skin diseases | naked DNA | medical instrumentation | The Angioskin consortium wants to bring the proof of concept that therapeutic genes can be safely delivered to skin by DNA electrotransfer (electrogenetherapy) in order to prevent or to treat acquired or inherited skin diseases. The Angioskin proposal is based on the results of the Fifth Framework Programme’s (FP5) Cliniporator project (the analysis of the mechanisms of DNA electrotransfer and elaboration of a CE labelled pulse generator) and of the FP5’s ESOPE project (the preparation of the standard operating procedures of Electrogenetherapy, electrotransferring a reporter gene in humans), and on a gene coding for a potent human antiangiogenic factor. This factor specifi cally binds to the αvβ3 and α5β1 integrins involved in angiogenic processes. Problem Non-viral gene transfer for the treatment of acquired or inherited skin diseases. Aim • To electrotransfer proprietary therapeutic antiangiogenesis genes to cutaneous metastases in humans, using the procedures validated in the ESOPE project, to show its clinical effi cacy; non-invasive biophysical methods will be used to monitor the antiangiogenic eff ects. • To develop new specifi c electrodes for the treatment of skin lesions. • To validate the electrodes (safety, effi cacy) on normal skin in animals, and analyse the eff ects of the electrotransfer of the antiangiogenetic factor on models of skin disease related to excessive angiogenesis, using noninvasive biophysical as well as histological methods to follow changes in the vascularisation of the lesion. • Finally, to electrotransfer the therapeutic gene to a benign lesion in humans as a proof of concept of the use of non-viral gene therapy to treat acquired or inherited skin diseases. Expected results Electrodes, pulse generators, procedures, proof of concept of a new therapeutic approach, clinical validation of an antiangiogenic factor. Potential applications • <strong>Research</strong> • Biotechnologies • Medicine 162 CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME
Coordinator Lluis M. Mir UMR 8121 CNRS – IGR Villejuif, France luismir@igr.fr Partners Ruggero Cadossi IGEA S.r.l. Carpi (MO), Italy cadossi@igea.it Jean Rémi Garbay Caroline Robert Institut Gustave-Roussy Villejuif, France garbay@igr.fr crobert@igr.fr Véronique Préat Université Catholique de Louvain Unité de Pharmacie galénique Brussels, Belgium preat@farg.ucl.ac.be Julie Gehl Herlev Hospital Department of Oncology Herlev, Denmark juge@herlevhosp.kbhamt.dk Michael P. Schön University of Würzburg Würzburg, Germany michael.schoen@med.uni-goettingen.de TREATMENT Gilles Avenard BioAlliance Pharma SA, Paris, France gilles.avenard@bioalliancepharma.com Damijan Miklavcic University of Ljubljana Ljubljana, Slovenia damijan@svarun.fe.uni-lj.si Lone Skov Gentofte Hospital Department of Dermatology Hellerup, Denmark Losk@geh.regionh.dk Project number LSHB-CT-2005-512127 EC contribution € 2 780 683 Duration 48 months Starting date 01/05/2005 Instrument STREP Project website www.cliniporator.com 163
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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
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Keywords | Virus | bacteria | HPV |
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Keywords | Breast | prostate | gene
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Prevention The fact that preventing
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Coordinator Elio Riboli Imperial Co
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Coordinator Jan Willem Coebergh Joh
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Coordinator Jose M a Benlloch Conse
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BAMOD Breath-Gas Analysis for Molec
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BioCare Molecular Imaging for Biolo
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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 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: Treatment Two major problems when t
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
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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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HOW TO OBTAIN EU PUBLICATIONS Our p
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