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)

Angiogenesis is necessary for growth and the spread of human tumors. Animal studies also suggest that angiogenesis is an important interspecies biological mechanism of tumor development. Angiogenesis is a complex multistep cascade modulated by both positive soluble factors, such as vascular endothelial growth factor, thymidine phosphorylase, basic-fibroblast growth factor and negative soluble factors such as angiostatin and endostatin. From the imbalance of the above angiogenesis regulators, tumor endothelial cells may divide up to 50 times more frequently than endothelial cells of normal tissue. Published studies have suggested that the assessment of microvessel density (MVD) or endothelial area (EA) can be considered as surrogate markers of angiogenesis with biological and prognostic relevance. Literature data on angiogenesis of mesothelioma are inconclusive, with only a few studies performed in primary peritoneal mesothelioma (PPM) due to the rarity of the disease. We assessed immunohistochemically MVD and EA and their biological and clinical significance in a consecutive series of 23 PPM cases. MVD and EA were detected in "hot spots" by a computerized image analyzer. The mean value of MVD and EA was 27 +/- 14 and 26.04 +/- 8.35 x10(-2) micro(2) per field (400x), respectively. Patients with a high MVD or EA tumors showed a more clinical aggressiveness due to the presence of ascites and a shorter overall survival. Our results suggest that PPM is an angiogenesis-dependent neoplasia. Therefore, antiangiogenic compounds should be tested particularly in those patients with highly vascularized PPM.
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PMID:Drug targets to pro-angiogenetic factors with special reference to primary peritoneal mesothelioma. 1701 78

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