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Nano4Drugs An Innovative Protein-Based Drug Delivery Device using Fluorescent Diamond Nano-Particles Summary Advances in genomics have resulted in the development of new protein-based drugs and this trend will increase in the next decade. However, delivery technologies for these drugs must be designed to surmount biochemical and anatomical barriers to safely permit their passage to an intended site. The targeted delivery of protein-based drugs is limited by a series of barriers and advances made to overcome these barriers will lead to the development of new, safer and more eff ective drugs by reducing undesirable side eff ects. To this end, the Nano4drugs consortium has integrated top-level teams across Europe to develop an innovative, challenging, frontier biotechnology device ideally suited for the targeted delivery of protein-based drugs. The device consists of biocompatible non-bleachable fl uorescent diamond nano-particles that can be grafted with both cell-penetrating peptides and protein-based drugs. As a proof of concept, Nano4drugs will target microtubules in two diff erent biological contexts, neuron and cancer. The protein-based drugs will consist of anti-microtubules peptides recently discovered by one team in Nano4Drug, and of new ones that will be tested during the project with the help of a post-genomic computer-based system of choices designed to guide and improve the development of proteinbased drugs. At the end of this STREP, Nano4Drugs will provide Europe with a better understanding of ways to overcome proteinbased drug delivery barriers. In achieving its objectives, Nano4Drugs will also deliver new potential treatments for societal health diseases such as neurological degenerative diseases and cancer. 60 Keywords | Vector | nano-sciences | protein-based drugs | Problem A series of barriers limits the targeted delivery of newly developed protein-based drugs, of which three are of critical importance: • transport of protein-based drugs across the cell membrane; • understanding the inter and intra-cellular routes taken by protein-based drugs; • exploitation of the 3D structure of the target, to narrow the protein-based drug specifi city, a condition to develop new, safer and more eff ective drugs by reducing undesirable side eff ects. Aim Nano4Drugs intends to exploit the exceptional properties of diamond nano-particles to develop a novel delivery technology that should overcome these barriers. Expected results The cargo will be made of a stable, biocompatible traceable diamond nano-particle of a small size (< 25 nm) with selected surface functional groups able to form an oriented covalent or reversible complex with the protein-based drugs. As a proof of concept, we will use this new vector to target microtubules which are main critical intra-cellular components involved in major biological processes, such as cell proliferation or neuronal axonal transport. Potential applications Protein-based drug delivery in the context of cancer therapy (microtubules are key components for chromosome segregation at the end of mitosis) and neurodegenerative diseases that imply microtubules (for example Alzheimer and spastic paralysis). CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME
Coordinator Patrick A. Curmi INSERM Paris, France pcurmi@univ-evry.fr Partners Solange Lavielle JP Boudou Université Pierre et Marie Curie Laboratoire Synthèse Structure et Fonctionnement de Molécules Bioactives Paris, France lavielle@ccr.jussieu.fr boudou@ccr.jussieu.fr François Treussart École Normale Supérieure de Cachan Laboratoire de Photonique Quantique et Moléculaire Cachan, France treussar@physique.ens-cachan.fr Alain Thorel École Nationale Supérieure des Mines de Paris Centre des matériaux Evry, France alain.thorel@ensmp.fr Isabelle Geahel Inserm Transfert Laboratoire – Projets Européens Paris, France isabelle.geahel@tolbiac.inserm.fr BIOLOGY Diane Braguer Université d’Aix-Marseille 2 Marseille, France diane.braguer@pharmacie.univ-mrs.fr Anke Krueger Christian-Albrechts-University of Kiel Kiel, Germany akrueger@oc.uni-kiel.de Fedor Jelezko University of Stuttgart Stuttgart, Germany f.jelezko@physik.uni-stuttgart.de Marco Fragai Consorzio Interuniversitario Risonanze Magnetiche di Metalloproteine paramagnetiche Florence, Italy fragai@cerm.unifi.it Stéphane Legastellois Indicia Biotechnology Oullins, France slegastelois@indicia.fr Rebecca del Conte ProtEra s.r.l. Florence, Italy delconte@cerm.unifi.it Project number LSHC-CT-2005-019102 EC contribution € 2 453 000 Duration 36 months Starting date 01/01/2006 Instrument STREP Project website www.nano4drugs.com 61
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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
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 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: Development of eff ective anti-canc
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
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These centres of excellence will in
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Expected results Optimise the benef
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114 Cell proliferation and apoptosi
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COBRED Colon and Breast cancer Diag
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DASIM Diagnostic Applications of Sy
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Expected results Primarily, the res
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Coordinator John A. Foekens Dept. o
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124 Aim Drop-Top has two major obje
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Coordinator Gorka Ochoa Progenika B
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Expected results The E.E.T.-Pipelin
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e developed by eTUMOUR is likely to
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Coordinator Angel Porgador Ben-Guri
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• the design of a compact assembl
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Potential applications We believe t
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Tumor initiation, progression to ma
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MolDiag-Paca Novel Molecular Diagno
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NEMO Nano based capsule-Endoscopy w
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OVCAD Ovarian Cancer - Diagnosis of
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P-MARK Validation of recently devel
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POC4life Multiparametric quantum do
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PROMET Prostate cancer molecular-or
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Micrometastasis in the bone marrow.
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and pharmaco-kinetics studies. This
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Coordinator Raffaella Giavazzi Isti
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• Development of tools for diagno
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Treatment Two major problems when t
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Coordinator Lluis M. Mir UMR 8121 C
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Potential applications ANGIOSTOP ha
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Green-fl uorescence protein- expres
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Coordinator Robert Hawkins Universi
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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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