MX2011005851A - Composiciones y metodos para la inhibicion selectiva de isoformas vegf proangiogenicas. - Google Patents
Composiciones y metodos para la inhibicion selectiva de isoformas vegf proangiogenicas.Info
- Publication number
- MX2011005851A MX2011005851A MX2011005851A MX2011005851A MX2011005851A MX 2011005851 A MX2011005851 A MX 2011005851A MX 2011005851 A MX2011005851 A MX 2011005851A MX 2011005851 A MX2011005851 A MX 2011005851A MX 2011005851 A MX2011005851 A MX 2011005851A
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- seq
- sirna
- vegf
- rna
- human
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| US17157109P | 2009-04-22 | 2009-04-22 | |
| US21980809P | 2009-06-24 | 2009-06-24 | |
| PCT/US2009/066741 WO2010065834A1 (en) | 2008-12-04 | 2009-12-04 | Compositions and methods for selective inhibition of pro-angiogenic vegf isoforms |
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| MX2011005851A true MX2011005851A (es) | 2011-07-29 |
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| MX2011005851A MX2011005851A (es) | 2008-12-04 | 2009-12-04 | Composiciones y metodos para la inhibicion selectiva de isoformas vegf proangiogenicas. |
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| US (1) | US8470792B2 (https=) |
| EP (1) | EP2361306A1 (https=) |
| JP (1) | JP5832293B2 (https=) |
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| MX (1) | MX2011005851A (https=) |
| NZ (1) | NZ593743A (https=) |
| SG (1) | SG171952A1 (https=) |
| WO (1) | WO2010065834A1 (https=) |
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| EP2342340A1 (en) | 2008-09-22 | 2011-07-13 | Rxi Pharmaceuticals Corporation | Rna interference in skin indications |
| US9745574B2 (en) | 2009-02-04 | 2017-08-29 | Rxi Pharmaceuticals Corporation | RNA duplexes with single stranded phosphorothioate nucleotide regions for additional functionality |
| US8227444B2 (en) * | 2009-12-04 | 2012-07-24 | Opko Ophthalmics, Llc | Compositions and methods for inhibition of VEGF |
| CN103200945B (zh) | 2010-03-24 | 2016-07-06 | 雷克西制药公司 | 眼部症候中的rna干扰 |
| RU2615143C2 (ru) | 2010-03-24 | 2017-04-04 | Адвирна | Самодоставляющие PHKi соединения уменьшенного размера |
| MX2013000986A (es) * | 2010-07-28 | 2013-07-03 | Alcon Res Ltd | Sirna dirigido al vegfa y metodos de tratamiento in vivo. |
| EP2628482A1 (en) * | 2012-02-17 | 2013-08-21 | Academisch Medisch Centrum | Rho kinase inhiitors for use in the treatment of neuroblastoma |
| CA2879597C (en) * | 2012-08-21 | 2021-01-12 | Opko Pharmaceuticals, Llc | Ophthalmic liposome formulations for treating posterior segment disease |
| KR20150103280A (ko) * | 2013-01-08 | 2015-09-09 | 베니텍 바이오파마 리미티드 | 연령-관련 황반 변성 치료 |
| CN106061488B (zh) | 2013-12-02 | 2021-04-09 | 菲奥医药公司 | 癌症的免疫治疗 |
| WO2015168108A2 (en) | 2014-04-28 | 2015-11-05 | Rxi Pharmaceuticals Corporation | Methods for treating cancer using nucleic targeting mdm2 or mycn |
| CN104267188B (zh) * | 2014-08-28 | 2015-12-30 | 汪建平 | 针对msk1基因的相关制剂在制备5-fu耐药性检测试剂及5-fu耐药逆转剂方面的应用 |
| US10900039B2 (en) | 2014-09-05 | 2021-01-26 | Phio Pharmaceuticals Corp. | Methods for treating aging and skin disorders using nucleic acids targeting Tyr or MMP1 |
| US12544344B2 (en) | 2017-04-19 | 2026-02-10 | Phio Pharmaceuticals Corp. | Topical delivery of nucleic acid compounds |
Family Cites Families (115)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
| US4394448A (en) | 1978-02-24 | 1983-07-19 | Szoka Jr Francis C | Method of inserting DNA into living cells |
| US4670388A (en) | 1982-12-30 | 1987-06-02 | Carnegie Institution Of Washington | Method of incorporating DNA into genome of drosophila |
| US4501728A (en) | 1983-01-06 | 1985-02-26 | Technology Unlimited, Inc. | Masking of liposomes from RES recognition |
| US5019369A (en) | 1984-10-22 | 1991-05-28 | Vestar, Inc. | Method of targeting tumors in humans |
| US5550289A (en) | 1985-01-07 | 1996-08-27 | Syntex (U.S.A.) Inc. | N-(1,(1-1)-dialkyloxy)-and N-(1,(1-1)-dialkenyloxy alk-1-yl-N-N,N-tetrasubstituted ammonium lipids and uses therefor |
| US5139941A (en) | 1985-10-31 | 1992-08-18 | University Of Florida Research Foundation, Inc. | AAV transduction vectors |
| US4837028A (en) | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US4920016A (en) | 1986-12-24 | 1990-04-24 | Linear Technology, Inc. | Liposomes with enhanced circulation time |
| US5712257A (en) | 1987-08-12 | 1998-01-27 | Hem Research, Inc. | Topically active compositions of mismatched dsRNAs |
| US5683986A (en) | 1987-08-12 | 1997-11-04 | Hemispherx Biopharma Inc. | Elaboration of host defense mediators into biological fluids by systemic dsRNA treatment |
| IE72103B1 (en) | 1987-08-12 | 1997-03-12 | Hem Res Inc | Promotion of host defense by systemic dsRNA treatment |
| US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
| US5498521A (en) | 1990-01-24 | 1996-03-12 | President And Fellows Of Harvard College | Diagnosis of hereditary retinal degenerative diseases |
| US5843738A (en) | 1990-08-14 | 1998-12-01 | Isis Pharmaceuticals, Inc. | Oligonucleotide modulation of cell adhesion |
| US5252479A (en) | 1991-11-08 | 1993-10-12 | Research Corporation Technologies, Inc. | Safe vector for gene therapy |
| US5322933A (en) | 1992-05-07 | 1994-06-21 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Crystal structure of TGF-β-2 |
| US5587308A (en) | 1992-06-02 | 1996-12-24 | The United States Of America As Represented By The Department Of Health & Human Services | Modified adeno-associated virus vector capable of expression from a novel promoter |
| ATE404683T1 (de) | 1992-09-25 | 2008-08-15 | Aventis Pharma Sa | Adenovirus vektoren für die übertragung fremder gene in zellen des zentralen nervensystems, insbesondere im gehirn |
| US6177401B1 (en) | 1992-11-13 | 2001-01-23 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften | Use of organic compounds for the inhibition of Flk-1 mediated vasculogenesis and angiogenesis |
| US5478745A (en) | 1992-12-04 | 1995-12-26 | University Of Pittsburgh | Recombinant viral vector system |
| GB9308271D0 (en) | 1993-04-21 | 1993-06-02 | Univ Edinburgh | Method of isolating and/or enriching and/or selectively propagating pluripotential animal cells and animals for use in said method |
| JP3626187B2 (ja) | 1993-06-07 | 2005-03-02 | バイカル インコーポレイテッド | 遺伝子治療に適するプラスミド |
| US6410322B1 (en) | 1993-07-27 | 2002-06-25 | Hybridon Inc | Antisense oligonucleotide inhibition of vascular endothelial growth factor expression |
| US5731294A (en) | 1993-07-27 | 1998-03-24 | Hybridon, Inc. | Inhibition of neovasularization using VEGF-specific oligonucleotides |
| US5639872A (en) | 1993-07-27 | 1997-06-17 | Hybridon, Inc. | Human VEGF-specific oligonucleotides |
| US5624803A (en) | 1993-10-14 | 1997-04-29 | The Regents Of The University Of California | In vivo oligonucleotide generator, and methods of testing the binding affinity of triplex forming oligonucleotides derived therefrom |
| US6037329A (en) | 1994-03-15 | 2000-03-14 | Selective Genetics, Inc. | Compositions containing nucleic acids and ligands for therapeutic treatment |
| US5728068A (en) | 1994-06-14 | 1998-03-17 | Cordis Corporation | Multi-purpose balloon catheter |
| US5505700A (en) | 1994-06-14 | 1996-04-09 | Cordis Corporation | Electro-osmotic infusion catheter |
| US6057119A (en) | 1994-06-17 | 2000-05-02 | Vertex Pharmaceuticals, Incorporated | Crystal structure and mutants of interleukin-1β converting enzyme |
| US6150092A (en) | 1994-06-27 | 2000-11-21 | Taogosei Company, Ltd. | Antisense nucleic acid compound targeted to VEGF |
| US5882914A (en) | 1995-06-06 | 1999-03-16 | The Johns Hopkins University School Of Medicine | Nucleic acids encoding the hypoxia inducible factor-1 |
| CA2225460A1 (en) | 1995-06-23 | 1997-01-09 | Winston Campbell Patterson | Transcriptional regulation of genes encoding vascular endothelial growth factor receptors |
| WO2002096927A2 (en) | 2001-05-29 | 2002-12-05 | Ribozyme Pharmaceuticals, Incorporated | Ribozyme based treatment of female reproductive diseases |
| US20030216335A1 (en) | 2001-11-30 | 2003-11-20 | Jennifer Lockridge | Method and reagent for the modulation of female reproductive diseases and conditions |
| WO1997018855A1 (en) | 1995-11-21 | 1997-05-29 | Eduard Naumovich Lerner | Device for enhanced delivery of biologically active substances and compounds in an organism |
| GB9524807D0 (en) | 1995-12-05 | 1996-02-07 | Smithkline Beecham Plc | Novel compounds |
| US5843016A (en) | 1996-03-18 | 1998-12-01 | Physion S.R.L. | Electromotive drug administration for treatment of acute urinary outflow obstruction |
| DE59703449D1 (de) | 1996-11-01 | 2001-05-31 | Christian Stern | Spritzgussdüse |
| US7033598B2 (en) | 1996-11-19 | 2006-04-25 | Intrabrain International N.V. | Methods and apparatus for enhanced and controlled delivery of a biologically active agent into the central nervous system of a mammal |
| WO1998022132A1 (en) | 1996-11-20 | 1998-05-28 | Yissum Res Dev Co | A method and composition for enabling passage through the blood-brain barrier |
| WO2001052904A2 (en) | 2000-01-19 | 2001-07-26 | Gill Parkash S | Pharmaceutical compositions and methods of treatment based on vegf antisense oligonucleotides |
| US6165709A (en) | 1997-02-28 | 2000-12-26 | Fred Hutchinson Cancer Research Center | Methods for drug target screening |
| WO1998048009A2 (en) | 1997-04-21 | 1998-10-29 | University Of Florida | Materials and methods for ribozyme treatment of retinal diseases |
| US20050096282A1 (en) | 1997-04-21 | 2005-05-05 | Lewin Alfred S. | Adeno-associated virus-delivered ribozyme compositions and methods for the treatment of retinal diseases |
| CA2295177C (en) | 1997-06-13 | 2007-01-09 | Medinova Medical Consulting Gmbh | Drug targeting system, method of its preparation and its use |
| US5902598A (en) | 1997-08-28 | 1999-05-11 | Control Delivery Systems, Inc. | Sustained release drug delivery devices |
| WO1999012572A1 (en) | 1997-09-10 | 1999-03-18 | University Of Florida | Compounds and method for the prevention and treatment of diabetic retinopathy |
| US6506559B1 (en) | 1997-12-23 | 2003-01-14 | Carnegie Institute Of Washington | Genetic inhibition by double-stranded RNA |
| US6479729B1 (en) * | 1998-02-06 | 2002-11-12 | The Johns Hopkins University | Mouse model for ocular neovascularization |
| US20030096775A1 (en) | 2001-10-23 | 2003-05-22 | Isis Pharmaceuticals Inc. | Antisense modulation of complement component C3 expression |
| US6433145B1 (en) | 1998-07-21 | 2002-08-13 | Human Genome Sciences, Inc. | Keratinocyte derived interferon |
| EP0979869A1 (en) | 1998-08-07 | 2000-02-16 | Hoechst Marion Roussel Deutschland GmbH | Short oligonucleotides for the inhibition of VEGF expression |
| US6219557B1 (en) | 1998-12-11 | 2001-04-17 | Ericsson Inc. | System and method for providing location services in parallel to existing services in general packet radio services architecture |
| CA2361201A1 (en) | 1999-01-28 | 2000-08-03 | Medical College Of Georgia Research Institute, Inc. | Composition and method for in vivo and in vitro attenuation of gene expression using double stranded rna |
| DE19956568A1 (de) | 1999-01-30 | 2000-08-17 | Roland Kreutzer | Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens |
| WO2000046147A2 (en) | 1999-02-03 | 2000-08-10 | Biosante Pharmaceuticals, Inc. | Therapeutic calcium phosphate particles and methods of manufacture and use |
| US6121000A (en) | 1999-02-11 | 2000-09-19 | Genesense Technologies, Inc. | Antitumor antisense sequences directed against R1 and R2 components of ribonucleotide reductase |
| KR20070118315A (ko) | 1999-04-21 | 2007-12-14 | 와이어쓰 | 폴리뉴클레오티드 서열의 기능을 억제하기 위한 조성물 |
| US6331313B1 (en) | 1999-10-22 | 2001-12-18 | Oculex Pharmaceticals, Inc. | Controlled-release biocompatible ocular drug delivery implant devices and methods |
| GB9927444D0 (en) | 1999-11-19 | 2000-01-19 | Cancer Res Campaign Tech | Inhibiting gene expression |
| DE10100586C1 (de) | 2001-01-09 | 2002-04-11 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines Ziegens |
| DE10160151A1 (de) | 2001-01-09 | 2003-06-26 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines vorgegebenen Zielgens |
| WO2001057206A2 (en) | 2000-02-03 | 2001-08-09 | Ribozyme Pharmaceuticals, Inc. | Method and reagent for the inhibition of checkpoint kinase-1 (chk 1) enzyme |
| EP1272630A2 (en) | 2000-03-16 | 2003-01-08 | Genetica, Inc. | Methods and compositions for rna interference |
| ES2336887T5 (es) | 2000-03-30 | 2019-03-06 | Whitehead Inst Biomedical Res | Mediadores de interferencia por ARN específicos de secuencias de ARN |
| AU2001253255A1 (en) | 2000-04-07 | 2001-10-23 | Large Scale Biology Corporation | Compositions and methods for inhibiting gene expression |
| US6372250B1 (en) | 2000-04-25 | 2002-04-16 | The Regents Of The University Of California | Non-invasive gene targeting to the brain |
| US6375972B1 (en) | 2000-04-26 | 2002-04-23 | Control Delivery Systems, Inc. | Sustained release drug delivery devices, methods of use, and methods of manufacturing thereof |
| AU2001295193A1 (en) | 2000-05-01 | 2001-11-12 | Novartis Ag | Vectors for ocular transduction and use thereof for genetic therapy |
| AU784561B2 (en) | 2000-06-23 | 2006-05-04 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Positively-charged peptide nucleic acid analogs with improved properties |
| AU2001271614B2 (en) | 2000-07-03 | 2007-05-31 | Catalent Pharma Solutions, Llc | Host cells containing multiple integrating vectors |
| AU2001277094A1 (en) | 2000-07-21 | 2002-02-05 | The Trustees Of Columbia University In The City Of New York | Nucleic acids comprising regions of the rat peg-3 promoter and uses thereof |
| US20020132788A1 (en) | 2000-11-06 | 2002-09-19 | David Lewis | Inhibition of gene expression by delivery of small interfering RNA to post-embryonic animal cells in vivo |
| US20020173478A1 (en) | 2000-11-14 | 2002-11-21 | The Trustees Of The University Of Pennsylvania | Post-transcriptional gene silencing by RNAi in mammalian cells |
| CA2429814C (en) | 2000-12-01 | 2014-02-18 | Thomas Tuschl | Rna interference mediating small rna molecules |
| CA2369944A1 (en) | 2001-01-31 | 2002-07-31 | Nucleonics Inc. | Use of post-transcriptional gene silencing for identifying nucleic acid sequences that modulate the function of a cell |
| US20020165158A1 (en) | 2001-03-27 | 2002-11-07 | King George L. | Methods of modulating angiogenesis |
| JP2002305193A (ja) | 2001-04-05 | 2002-10-18 | Sony Corp | 半導体装置とその製造方法 |
| US20030045830A1 (en) | 2001-04-17 | 2003-03-06 | De Bizemont Therese | Gene therapy with chimeric oligonucleotides delivered by a method comprising a step of iontophoresis |
| US20050159380A1 (en) | 2001-05-18 | 2005-07-21 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of angiopoietin gene expression using short interfering nucleic acid (siNA) |
| US20050187174A1 (en) | 2001-05-18 | 2005-08-25 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of intercellular adhesion molecule (ICAM) gene expression using short interfering nucleic acid (siNA) |
| US7517864B2 (en) * | 2001-05-18 | 2009-04-14 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| US20050148530A1 (en) | 2002-02-20 | 2005-07-07 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| US20050048529A1 (en) | 2002-02-20 | 2005-03-03 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of intercellular adhesion molecule (ICAM) gene expression using short interfering nucleic acid (siNA) |
| WO2003070910A2 (en) | 2002-02-20 | 2003-08-28 | Ribozyme Pharmaceuticals, Incorporated | INHIBITION OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) AND VEGF RECEPTOR GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| EP1401884A1 (en) | 2001-05-29 | 2004-03-31 | Union Carbide Chemicals & Plastics Technology Corporation | Olefin polymerization catalyst compositions and method of preperation |
| US20040028613A1 (en) | 2001-06-25 | 2004-02-12 | Nastech Pharmaceutical Company Inc | Dopamine agonist formulations for enhanced central nervous system delivery |
| DK2280070T3 (en) | 2001-07-23 | 2015-08-24 | Univ Leland Stanford Junior | Methods and compositions for use in RNAi-mediated inhibition of gene expression in mammals |
| DE60235761D1 (de) | 2001-08-01 | 2010-05-06 | Univ Bristol Clifton | Isoform des vegfs |
| AU2002348163A1 (en) | 2001-11-02 | 2003-05-19 | Intradigm Corporation | Therapeutic methods for nucleic acid delivery vehicles |
| AU2002343792A1 (en) | 2001-11-28 | 2003-06-10 | Center For Advanced Science And Technology Incubation, Ltd. | siRNA EXPRESSION SYSTEM AND PROCESS FOR PRODUCING FUNCTIONAL GENE-KNOCKDOWN CELLS AND THE LIKE USING THE SAME |
| US7176303B2 (en) * | 2003-11-06 | 2007-02-13 | Isis Pharmaceuticals, Inc. | Modulation of STAT5 expression |
| AU2003225495B2 (en) | 2002-04-05 | 2009-01-15 | Roche Innovation Center Copenhagen A/S | Oligomeric compounds for the modulation HIF-1alpha expression |
| EP1495120B1 (en) | 2002-04-18 | 2012-10-10 | Acuity Pharmaceuticals, Inc | Means and methods for the specific modulation of target genes in the eye |
| US7199107B2 (en) * | 2002-05-23 | 2007-04-03 | Isis Pharmaceuticals, Inc. | Antisense modulation of kinesin-like 1 expression |
| AU2003237686A1 (en) | 2002-05-24 | 2003-12-12 | Max-Planck Gesellschaft Zur Forderung Der Wissenschaften E.V. | Rna interference mediating small rna molecules |
| US20040115640A1 (en) | 2002-12-11 | 2004-06-17 | Isis Pharmaceuticals Inc. | Modulation of angiopoietin-2 expression |
| US7148342B2 (en) | 2002-07-24 | 2006-12-12 | The Trustees Of The University Of Pennyslvania | Compositions and methods for sirna inhibition of angiogenesis |
| AU2003258100A1 (en) | 2002-08-06 | 2004-02-23 | Intradigm Corporation | Methods of down regulating target gene expression in vivo by introduction of interfering rna |
| NZ540779A (en) | 2002-11-01 | 2008-05-30 | Univ Pennsylvania | Compositions and methods for siRNA inhibition of HIF-1 alpha |
| AU2003295600A1 (en) | 2002-11-14 | 2004-06-15 | Dharmacon, Inc. | Functional and hyperfunctional sirna |
| JP2007524349A (ja) | 2003-01-16 | 2007-08-30 | ザ・トラスティーズ・オブ・ザ・ユニバーシティ・オブ・ペンシルバニア | ＩＣＡＭ−１のｓｉＲＮＡ阻害のための組成物及び方法 |
| AU2004233043A1 (en) | 2003-04-18 | 2004-11-04 | The Trustees Of The University Of Pennsylvania | Compositions and methods for siRNA inhibition of angiopoietin 1 and 2 and their receptor Tie2 |
| US20050019927A1 (en) | 2003-07-13 | 2005-01-27 | Markus Hildinger | DECREASING GENE EXPRESSION IN A MAMMALIAN SUBJECT IN VIVO VIA AAV-MEDIATED RNAi EXPRESSION CASSETTE TRANSFER |
| US7468431B2 (en) * | 2004-01-22 | 2008-12-23 | Isis Pharmaceuticals, Inc. | Modulation of eIF4E-BP2 expression |
| ES2423060T3 (es) | 2004-03-12 | 2013-09-17 | Alnylam Pharmaceuticals, Inc. | Agentes iRNA que tienen como diana al VEGF |
| US20060182783A1 (en) | 2004-04-30 | 2006-08-17 | Allergan, Inc. | Sustained release intraocular drug delivery systems |
| CN101277704A (zh) | 2005-04-12 | 2008-10-01 | 因特拉迪格姆公司 | 用于治疗癌症及其它新血管生成疾病的RNAi治疗剂的组合物和方法 |
| AU2006337093B2 (en) | 2005-12-22 | 2013-03-14 | Opko Pharmaceuticals, Llc. | Compositions and methods for regulating complement system |
| US20090061478A1 (en) | 2006-01-30 | 2009-03-05 | Lene Have Poulsen | High-Speed Quantification of Antigen Specific T-Cells in Whole Blood by Flow Cytometry |
| DK2029746T3 (da) * | 2006-06-12 | 2012-10-08 | Exegenics Inc D B A Opko Health Inc | Sammensætninger og fremgangsmåder til siRNA-hæmning af angiogenese |
| US7872118B2 (en) * | 2006-09-08 | 2011-01-18 | Opko Ophthalmics, Llc | siRNA and methods of manufacture |
| GB0704678D0 (en) | 2007-03-09 | 2007-04-18 | Univ Bristol | Pro- and anti-angiogenic treatments |
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