Abstract:
:Tumors provide an extremely abnormal microenvironment that stimulates neovascularization from surrounding vessels and causes altered gene expression within vascular cells. Up-regulation of vascular endothelial growth factor (VEGF) receptors has allowed selective destruction of tumor vessels by administration of a chimeric protein consisting of VEGF121 coupled to the toxin gelonin (VEGF/rGel). We sought to determine whether there is sufficient up-regulation of VEGF receptors in endothelial cells participating in ocular neovascularization to permit a similar strategy. After intravenous injection of 45 mg/kg VEGF/rGel, but not uncoupled recombinant gelonin (rGel), there was immunofluorescent staining for rGel within choroidal neovascularization in mice and regression of the neovascularization occurred, demonstrating successful vascular targeting via the systemic circulation. Intraocular injection of 5 ng of VEGF/rGel also caused significant regression of choroidal neovascularization and regression of retinal neovascularization in two models, transgenic mice with expression of VEGF in photoreceptors and mice with ischemic retinopathy, whereas injection of 5 ng of rGel had no effect. These data suggest that the strategy of vascular targeting can be applied to nonmalignant neovascular diseases and could serve as the basis of a new treatment to reduce established ocular neovascularization.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Akiyama H,Mohamedali KA,E Silva RL,Kachi S,Shen J,Hatara C,Umeda N,Hackett SF,Aslam S,Krause M,Lai H,Rosenblum MG,Campochiaro PAdoi
10.1124/mol.105.015628keywords:
subject
Has Abstractpub_date
2005-12-01 00:00:00pages
1543-50issue
6eissn
0026-895Xissn
1521-0111pii
mol.105.015628journal_volume
68pub_type
杂志文章abstract::KARs, new semisynthetic antitumor bis-indole derivatives, were found to be inhibitors of tubulin polymerization with lower toxicity than vinblastine or vincristine, used in chemotherapy. Here, we compare the effect of KARs with those of vinblastine and vincristine on cell viability, cell proliferation, and cell cycle ...
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:1986-11-01 00:00:00
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-10-01 00:00:00
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pub_type: 杂志文章
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:1990-10-01 00:00:00
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-06-01 00:00:00
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journal_title:Molecular pharmacology
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doi:
更新日期:1999-03-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-04-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:2002-04-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:2003-11-01 00:00:00
abstract::A nonnaturally occurring L-configuration nucleoside analog, L-beta-5-bromovinyl-(2-hydroxymethyl)-1,3-(dioxolanyl)uracil (L-BVOddU) selectively inhibited varicella-zoster virus growth in human embryonic lung (HEL) 299 cell culture with an EC(50) of 0.055 microM, whereas no inhibition of CEM and HEL 299 cell growth or ...
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pub_type: 杂志文章
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更新日期:2000-11-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1984-09-01 00:00:00
abstract::We show here that arsenite (As(3+)) elicits multiple effects on gene control, such as the interruption of cell cycle control by initiating G(2)/M arrest as well as inhibiting the aryl hydrocarbon (Ah) receptor-mediated 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible expression of CYP1A1. This raises the question ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.006130
更新日期:2005-04-01 00:00:00