Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N-Acetylcysteine (NAC) is a drug bearing multiple preventive properties that can inhibit genotoxicity and carcinogenicity. NAC also inhibits invasion and metastasis of malignant cells, as well as tumor take. We recently demonstrated the effects of NAC on Kaposi's sarcoma cells supernatant-induced invasion in vitro and angiogenesis in vivo. Many anticancer agents act through cytotoxicity of rapidly proliferating cells and several antineoplastic drugs induce apoptosis of cancer cells. Since endothelial cells are the target for the inhibition of angiogenesis, we wanted to verify that NAC, while inhibiting tumor vascularization and endothelial cell invasion would not induce endothelial cell apoptosis. We tested the ability of NAC to modulate apoptosis and cytogenetic damage in vitro and to promote differentiation on a reconstituted basement membrane (matrigel) in two endothelial cell lines (EAhy926 and HUVE). Treatment with NAC protected endothelial cells from TGF-beta-induced apoptosis and paraquat-induced cytogenetic damage. Therefore, NAC acts as an antiangiogenic agent and, at the same time, appears to prevent apoptosis and oxygen-related genotoxicity in endothelial cells.
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PMID:Antiapoptotic and antigenotoxic effects of N-acetylcysteine in human cells of endothelial origin. 1106 41

Gene transfer delivery of endogenous angiogenesis inhibitors such as angiostatin would circumvent problems associated with long-term administration of proteins. Kaposi's sarcoma (KS), a highly vascular neoplasm, is an excellent model for studying tumor angiogenesis and antiangiogenic agent efficacy. We investigated the effects of angiostatin gene transfer in in vitro and in vivo models of KS-induced neovascularization and tumor growth. A eukaryotic expression plasmid and a Moloney leukemia virus-based retroviral vector for expression of murine angiostatin were generated harboring the angiostatin cDNA with cleavable leader signals under the control of either the strong cytomegalovirus promoter/enhancer or the Moloney leukemia virus long terminal repeat. Angiostatin secretion was confirmed by radioimmunoprecipitation and Western blot analysis. Supernatants of angiostatin-transfected cells inhibited endothelial cell migration in vitro. Stable gene transfer of the angiostatin cDNA by retroviral vectors in KS-IMM cells resulted in sustained angiostatin expression and delayed tumor growth in nude mice, which was associated with reduced vascularization. These findings suggest that gene therapy with angiostatin might be useful for treatment of KS and possibly other highly angiogenic tumors.
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PMID:Effects of angiostatin gene transfer on functional properties and in vivo growth of Kaposi's sarcoma cells. 1145 89

Imiquimod (imidazoquinoline 5%) is a topical immune response modifier agent that inhibits angiogenesis, the growth of new blood vessels. In addition to its stimulation of cell-mediated immunity, imiquimod's antiangiogenic activity contributes to its clinical efficacy by interfering with pathological neovascularization that promotes disease progression. The antiangiogenic mechanisms of imiquimod are due to its: 1) induction of cytokines that themselves inhibit angiogenesis (interferons, IL-10, IL-12); 2) local up-regulation of endogenous angiogenesis inhibitors (TIMP, TSP-1); 3) local down-regulation of pro-angiogenic factors (bFGF, MMP-9); and 4) promotion of endothelial cell apoptosis. This report discusses these mechanisms and the rationale for imiquimod's use as an antiangiogenic agent. Key principles of antiangiogenic therapy are presented to describe how imiquimod may be applied in a well-tolerated fashion to treat a broad range of angiogenesis-dependent dermatological conditions, including actinic keratosis (AK), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), lentigo maligna, hemangiomas, Kaposi's sarcoma, pyogenic granuloma, and external genital warts.
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PMID:Imiquimod as an antiangiogenic agent. 1630 56