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

Talc remains the most effective sclerosing agent for pleurodesis. However, its mechanism of action in resolving pleural malignant disease remains unclear. The present study evaluated the angiogenic balance in the pleural space in patients with malignant pleural effusions (MPE) following talc insufflation. Patient pleural fluid samples were collected both before and after talc insufflation. The ability of pleural mesothelial cells (PMC) and malignant mesothelioma cells (MMC) to produce endostatin in vitro was compared. The biological effects of pleural fluids and conditioned media from talc-activated PMC on endothelial cells were evaluated by performing proliferation, invasion, tube formation and apoptosis assays. Pleural fluids from patients with MPE who received thoracoscopic talc insufflation contained significantly higher levels of endostatin (median 16.75 ng.mL(-1)) compared with pre-talc instillation (1.06 ng.mL(-1)). Talc-activated PMC released significantly greater amounts of endostatin (mean+/-SEM 1052.39+/-38.66 pg.mL(-1)) when compared with a MMC line (134.73+/-8.72 pg.mL(-1)). In conclusion, talc alters the angiogenic balance in the pleural space from a biologically active and angiogenic environment to an angiostatic milieu. Functional improvement following talc poudrage in patients with malignant pleural effusions may, in part, reflect these alterations in the pleural space.
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PMID:Talc mediates angiostasis in malignant pleural effusions via endostatin induction. 1740 Aug 75

Anti-angiogenic gene therapy represents a promising strategy for cancer; however, it has rarely been tested in malignant mesothelioma, a highly aggressive tumor associated with asbestos with poor prognosis. In the present study, we investigated whether anti-angiogenic factors such as angiostatin, endostatin and the soluble form of vascular endothelial growth factor receptor 2 (sFlk1) were able to inhibit endothelial cell proliferation via lentivirus-mediated gene transfer into malignant mesothelioma cells in culture. We also assessed whether a dual-agent strategy had greater therapeutic benefit. Human malignant pleural mesothelioma MSTO-211H cells were transduced using lentiviral vectors that individually expressed angiostatin, endostatin and sFlk1 and linked to enhanced green fluorescent protein (EGFP) marker gene expression via an internal ribosome entry site. The lentivirus expressing EGFP alone was used as a control. The resultant cells designated as MSTO-A, MSTO-E, MSTO-F and MSTO-C were confirmed by western blot analysis and fluorescence microscopy to stably express the corresponding proteins. No differences were observed in the in vitro growth rates between any of these cells. However, co-culture of MSTO-A, MSTO-E and MSTO-F showed significant suppression of human umbilical endothelial cell growth in vitro compared with that of MSTO-C. Furthermore, a combination of any two among MSTO-A, MSTO-E and MSTO-F significantly enhanced efficacy. These results suggest that combinatorial anti-angiogenic gene therapy targeting different pathways of endothelial growth factor signaling has the potential for greater therapeutic efficacy than that of a single-agent regimen.
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PMID:Combinatorial anti-angiogenic gene therapy in a human malignant mesothelioma model. 2608 3