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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
1996-7-15
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pubmed:abstractText |
Inhibition of tumor neovascularization has profound effects on the growth of solid tumors. An endothelial cell-specific cytotoxic conjugate was prepared by chemically linking recombinant vascular endothelial growth factor (VEGF165) and a truncated diphtheria toxin molecule (DT385). The treatment of subconfluent cultures of human umbilical vein endothelial cells and human microvascular endothelial cells with the VEGF165-DT385 conjugate resulted in a selective, dose-dependent inhibition of growth. Parallel experiments with either the free toxin or a mixture of VEGF and the toxin polypeptide did not affect proliferation (DNA synthesis) of these cells. The selective cytotoxicity correlated with the appropriate receptor expression (KDR/flk-1 positive) on the target cells. VEGF-toxin conjugate inhibited the growth of a murine hemangioma-derived endothelial cell line (Py-4-1), which was positive for flk-1 expression. Under similar conditions, the conjugate did not affect the proliferation of a receptor-negative ovarian cancer cell line in vitro. In an in vivo model of angiogenesis, the VEGF165-DT385 conjugate blocked basic fibroblast growth factor-induced neovascularization of the chick chorioallantoic membrane. These studies demonstrate the successful targeting of a cytotoxic polypeptide to proliferating vascular endothelial cells (normal and tumorigenic) and the potential utility of such conjugates in blocking tumor neovascularization.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Diphtheria Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelial Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Fibroblast Growth Factor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Immunotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphokines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Vascular Endothelial...,
http://linkedlifedata.com/resource/pubmed/chemical/VEGFA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0008-5472
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
56
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1324-30
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:8640821-Animals,
pubmed-meshheading:8640821-Cell Division,
pubmed-meshheading:8640821-Cells, Cultured,
pubmed-meshheading:8640821-DNA,
pubmed-meshheading:8640821-Diphtheria Toxin,
pubmed-meshheading:8640821-Dose-Response Relationship, Drug,
pubmed-meshheading:8640821-Drug Screening Assays, Antitumor,
pubmed-meshheading:8640821-Endothelial Growth Factors,
pubmed-meshheading:8640821-Endothelium, Vascular,
pubmed-meshheading:8640821-Female,
pubmed-meshheading:8640821-Fibroblast Growth Factor 2,
pubmed-meshheading:8640821-Hemangioma,
pubmed-meshheading:8640821-Humans,
pubmed-meshheading:8640821-Immunotoxins,
pubmed-meshheading:8640821-Lymphokines,
pubmed-meshheading:8640821-Mice,
pubmed-meshheading:8640821-Neovascularization, Pathologic,
pubmed-meshheading:8640821-Neovascularization, Physiologic,
pubmed-meshheading:8640821-Ovarian Neoplasms,
pubmed-meshheading:8640821-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:8640821-Receptors, Growth Factor,
pubmed-meshheading:8640821-Receptors, Vascular Endothelial Growth Factor,
pubmed-meshheading:8640821-Tumor Cells, Cultured,
pubmed-meshheading:8640821-Umbilical Cord,
pubmed-meshheading:8640821-Vascular Endothelial Growth Factor A,
pubmed-meshheading:8640821-Vascular Endothelial Growth Factors
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pubmed:year |
1996
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pubmed:articleTitle |
Vascular endothelial growth factor-toxin conjugate specifically inhibits KDR/flk-1-positive endothelial cell proliferation in vitro and angiogenesis in vivo.
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pubmed:affiliation |
Department of Pharmacology, University of Minnesota, Minneapolis, 55455, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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