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  • 1
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    Role of Raf in vascular protection from distinct apoptotic stimuli (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-07-05
    Description: Raf kinases have been linked to endothelial cell survival. Here, we show that basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) differentially activate Raf, resulting in protection from distinct pathways of apoptosis in human endothelial cells and chick embryo vasculature. bFGF activated Raf-1 via p21-activated protein kinase-1 (PAK-1) phosphorylation of serines 338 and 339, resulting in Raf-1 mitochondrial translocation and endothelial cell protection from the intrinsic pathway of apoptosis, independent of the mitogen-activated protein kinase kinase-1 (MEK1). In contrast, VEGF activated Raf-1 via Src kinase, leading to phosphorylation of tyrosines 340 and 341 and MEK1-dependent protection from extrinsic-mediated apoptosis. These findings implicate Raf-1 as a pivotal regulator of endothelial cell survival during angiogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alavi, Alireza -- Hood, John D -- Frausto, Ricardo -- Stupack, Dwayne G -- Cheresh, David A -- CA45726/CA/NCI NIH HHS/ -- CA50286/CA/NCI NIH HHS/ -- CA75924/CA/NCI NIH HHS/ -- P01 CA78045/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2003 Jul 4;301(5629):94-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12843393" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Cell Survival ; Cells, Cultured ; Chick Embryo ; Endothelial Growth Factors/pharmacology ; Endothelium, Vascular/*cytology/drug effects ; Enzyme Activation ; Enzyme Inhibitors/pharmacology ; Fibroblast Growth Factor 2/pharmacology ; Flavonoids/pharmacology ; Humans ; Intercellular Signaling Peptides and Proteins/pharmacology ; Lymphokines/pharmacology ; MAP Kinase Kinase 1 ; Mitochondria/metabolism ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/metabolism ; Mitogen-Activated Protein Kinases/metabolism ; Neovascularization, Pathologic ; *Neovascularization, Physiologic/drug effects ; Phosphorylation ; Point Mutation ; Protein Transport ; Protein-Serine-Threonine Kinases/antagonists & inhibitors/metabolism ; Proto-Oncogene Proteins B-raf ; Proto-Oncogene Proteins c-raf/chemistry/genetics/*metabolism ; Signal Transduction ; Umbilical Veins ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; p21-Activated Kinases ; src-Family Kinases/antagonists & inhibitors/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Tumor regression by targeted gene delivery to the neovasculature (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-06-29
    Description: Efforts to influence the biology of blood vessels by gene delivery have been hampered by a lack of targeting vectors specific for endothelial cells in diseased tissues. Here we show that a cationic nanoparticle (NP) coupled to an integrin alphavbeta3-targeting ligand can deliver genes selectively to angiogenic blood vessels in tumor-bearing mice. The therapeutic efficacy of this approach was tested by generating NPs conjugated to a mutant Raf gene, ATPmu-Raf, which blocks endothelial signaling and angiogenesis in response to multiple growth factors. Systemic injection of the NP into mice resulted in apoptosis of the tumor-associated endothelium, ultimately leading to tumor cell apoptosis and sustained regression of established primary and metastatic tumors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hood, John D -- Bednarski, Mark -- Frausto, Ricardo -- Guccione, Samira -- Reisfeld, Ralph A -- Xiang, Rong -- Cheresh, David A -- CA50286/CA/NCI NIH HHS/ -- P41 RR09784/RR/NCRR NIH HHS/ -- T32 CA09696/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Jun 28;296(5577):2404-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12089446" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Animals ; Apoptosis ; Cations ; Endothelium, Vascular/cytology/metabolism/pathology ; Gene Targeting ; Gene Transfer Techniques ; Genetic Therapy/*methods ; Genetic Vectors ; Humans ; In Situ Nick-End Labeling ; Ligands ; Lipids ; Melanoma, Experimental/blood supply/pathology/therapy ; Mice ; Mice, Inbred BALB C ; Mutation ; *Nanotechnology ; Neoplasm Metastasis ; Neoplasm Transplantation ; Neoplasms, Experimental/blood supply/pathology/*therapy ; Neovascularization, Pathologic/pathology/*therapy ; Proto-Oncogene Proteins c-raf/*genetics/metabolism ; Random Allocation ; Receptors, Vitronectin/*metabolism ; Tumor Cells, Cultured
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Definition of two angiogenic pathways by distinct alpha v integrins (1995)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1995-12-01
    Description: Angiogenesis depends on cytokines and vascular cell adhesion events. Two cytokine-dependent pathways of angiogenesis were shown to exist and were defined by their dependency on distinct vascular cell integrins. In vivo angiogenesis in corneal or chorioallantoic membrane models induced by basic fibroblast growth factor or by tumor necrosis factor-alpha depended on alpha v beta 3, whereas angiogenesis initiated by vascular endothelial growth factor, transforming growth factor-alpha, or phorbol ester depended on alpha v beta 5. Antibody to each integrin selectively blocked one of these pathways, and a cyclic peptide antagonist of both integrins blocked angiogenesis stimulated by each cytokine tested. These pathways are further distinguished by their sensitivity to calphostin C, an inhibitor of protein kinase C that blocked angiogenesis potentiated by alpha v beta 5 but not by alpha v beta 3.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Friedlander, M -- Brooks, P C -- Shaffer, R W -- Kincaid, C M -- Varner, J A -- Cheresh, D A -- New York, N.Y. -- Science. 1995 Dec 1;270(5241):1500-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Robert Mealey Laboratory for the Study of Macular Degenerations, Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7491498" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal ; Chick Embryo ; Cornea/*blood supply ; Endothelial Growth Factors/pharmacology ; Enzyme Inhibitors/pharmacology ; Fibroblast Growth Factor 2/pharmacology ; Integrins/immunology/*physiology ; Lymphokines/pharmacology ; Naphthalenes/pharmacology ; Neovascularization, Pathologic ; *Neovascularization, Physiologic/drug effects ; Peptides, Cyclic/pharmacology ; Protein Kinase C/antagonists & inhibitors/metabolism ; Rabbits ; Receptors, Vitronectin/immunology/*physiology ; Tetradecanoylphorbol Acetate/pharmacology ; Transforming Growth Factor alpha/pharmacology ; Tumor Necrosis Factor-alpha/pharmacology ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    Requirement of vascular integrin alpha v beta 3 for angiogenesis (1994)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1994-04-22
    Description: Angiogenesis depends on the adhesive interactions of vascular cells. The adhesion receptor integrin alpha v beta 3 was identified as a marker of angiogenic vascular tissue. Integrin alpha v beta 3 was expressed on blood vessels in human wound granulation tissue but not in normal skin, and it showed a fourfold increase in expression during angiogenesis on the chick chorioallantoic membrane. In the latter assay, a monoclonal antibody to alpha v beta 3 blocked angiogenesis induced by basic fibroblast growth factor, tumor necrosis factor-alpha, and human melanoma fragments but had no effect on preexisting vessels. These findings suggest that alpha v beta 3 may be a useful therapeutic target for diseases characterized by neovascularization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brooks, P C -- Clark, R A -- Cheresh, D A -- CA45726/CA/NCI NIH HHS/ -- CA50286/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1994 Apr 22;264(5158):569-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7512751" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal ; Blood Vessels/metabolism ; Chick Embryo ; Fibroblast Growth Factor 2/pharmacology ; Granulation Tissue/*blood supply/metabolism ; Humans ; Integrins/biosynthesis/immunology/*physiology ; Laminin/analysis ; Melanoma/blood supply/metabolism ; Neovascularization, Pathologic/*metabolism ; Receptors, Cytoadhesin/biosynthesis/immunology/*physiology ; Receptors, Vitronectin ; Skin/blood supply/metabolism ; Tumor Necrosis Factor-alpha/pharmacology ; von Willebrand Factor/analysis
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 5
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    O-acetylation of disialoganglioside GD3 by human melanoma cells creates a unique antigenic determinant (1984)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1984-08-24
    Description: Monoclonal antibody Mab D1.1 recognizes on human melanoma cells a ganglioside antigen characterized by an alkali-labile O-acetylated sialic acid residue. Immunochemical analysis showed that this molecule is an O-acetylated product of the neuroectoderm-associated disialoganglioside GD3. Controlled chemical O-acetylation of purified GD3 resulted in the generation of this same epitope. Lysates of human melanoma cells were found to contain O-acetyltransferase activity capable of generating the antigenic epitope recognized by Mab D1.1. Thus, the addition of a single O-acetyl group to a common cell surface-associated ganglioside can create a potentially tumor-specific antigen.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheresh, D A -- Reisfeld, R A -- Varki, A P -- CA 07544/CA/NCI NIH HHS/ -- CA 28420/CA/NCI NIH HHS/ -- GM32373/GM/NIGMS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1984 Aug 24;225(4664):844-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6206564" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Acetyltransferases/metabolism ; Antibodies, Monoclonal ; Antigens, Neoplasm/*immunology ; Cell Line ; Epitopes/immunology ; Gangliosides/analysis/*immunology/metabolism ; Humans ; Melanoma/enzymology/*immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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