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)

Patients with metastatic neuroblastoma are rarely curable with currently available therapy, and the search for new treatment options, which include the use of inhibitors of tumor angiogenesis, is warranted. Here, we have evaluated the efficacy of one of the most promising natural inhibitors of angiogenesis described to date, endostatin, in a human neuroblastoma xenograft model in nude mice. Murine endostatin cDNA was cloned in a bacterial expression vector, expressed as a polyHis-Endostatin fusion protein and purified on Ni2+-NTA beads. The in vitro activity of soluble endostatin was confirmed on bovine capillary endothelial cells and human umbilical vein endothelial cells. The human neuroblastoma cell line SKNAS was injected subcutaneously in the flank of nude mice and administration of the recombinant angiogenesis inhibitor started when tumors reached the size of 100 microm3. Twenty mg/kg of recombinant precipitated endostatin or PBS was subcutaneously injected daily for 12 days. Serum endostatin levels were measured using a competitive enzyme immunoassay. Tumor growth was only slowed down in endostatin-treated mice when compared to control mice, and no statistically significant difference in serum levels of endostatin was observed between endostatin-treated and control groups. The lack of correlation between serum concentration and tumor response raises concern regarding the mechanism of action of endostatin.
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PMID:Lack of antitumor activity of recombinant endostatin in a human neuroblastoma xenograft model. 1134 75

OBJECTIVE: To evaluate the inhibitory effect of recombinant human endostatin on tumor growth and metastasis of adenocarcinoma LA795 in mice. METHODS: Recombinant human endostatin was purified rom endostadin-expressing pCX clones. LA795 cells were inoculated subcutaneously on the back of T739 mice, which were randomized into 2 groups. From the tenth day on, treatment group was given 20 mg/kg recombinant human endostatin subcutaneously daily for 14 consecutive days, and the control group received PBS in the same manner. The sizes of the subcutaneous tumors, lung weights, the number of metastases over the lung surface and the survival time of the mice were observed. RESULTS: The tumor sizes of the treatment group in creased slowly from (650+/-201) mm3 to (1 642+/-21) mm3 when compared with those of the control group which showed and increase from (623+/-248) mm3 to (9 194+/-952) mm3. The lung weight of the 2 groups was (190+/-25) mg and (324+/-43) mg respectively, and the number of lung sung surface metastases was 8+/-2 and 22+/-8 for each. The average survival time of the rats in the 2 groups was 48 d and 27 d, respectively. All parameters measured between the 2 groups showed significant differences (P<0.01). CONCLUSION: Recom binent human endostatin has strong inhibitory effect on both the growth of primary tumor and metastasis of lung adenocarcinoma LA795 cells, and prolongs the survival time of the tumor-bearing mice.
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PMID:Inhibition of lung adenocarcinoma LA795 in mice by recombinant human endostatin. 1242 65

This study aims to investigate the role of angiogenic factors in the pathogenesis of experimental strongyloidiasis. Two complementary approaches were used: Firstly, CD1 mice were treated with endostatin, an angiogenesis inhibitor, and infected with Strongyloides venezuelensis. Also, the mechanisms involved in this process were studied. Parasitological examination revealed a significant decrease in egg per gram of faeces, number of collected larvae from lung tissue and number of collected adult females in mice treated with endostatin. Direct mechanisms with diminution of angiogenesis factors and an indirect mechanism with increase of eosinophil perhaps produced their effect. Secondly, the effect of the antigens responsible for stimulation of angiogenic factors [vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2)] from alveolar macrophages and the mechanisms involved in their production were investigated. Alveolar macrophage cells obtained by bronchoalveolar lavage were incubated at different concentrations of somatic and excretory/secretory antigens of S. venezuelensis. Also, mRNA levels of VEGF and FGF2 in macrophage cells were detected by RT-PCR. L3-PBS larvae antigens induced angiogenic factors. The relationship between angiogenesis factors and nitric oxide has been observed using nitric oxide synthase inhibitors.
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PMID:Role of angiogenic factors in acute experimental Strongyloides venezuelensis infection. 2050 Jun 74

Salmonella typhimurium (hereafter S. typhimurium), as Gram-negative facultative anaerobic bacteria, are good candidates for cancer therapy and delivering therapeutic antitumor agents. However, it is necessary to reduce the virulence of such bacteria and enhance their tumor-targeting ability, and their immunostimulatory ability to induce tumor cell apoptosis. In this study, we constructed a S. typhimurium mutant named S634 harboring aroA mutation and additional mutations involved in modifications of lipid A. Upon intraperitoneal infection in mice, the aroA-deficient strain S634 showed greatly attenuated virulence and preferential accumulation within tumor tissue. We next investigated the ability of S636, the asd mutant derivative of S634, to deliver the anti-angiogenic agent "endostatin" (S636/pES) and to inhibit tumor growth in mouse CT26 colon carcinoma and B16F10 melanoma models. S636/pES-treated tumor-bearing mice showed suppressed tumor growth and prolonged survival, compared to mice treated with either the bacteria carrying empty plasmids or PBS intraperitoneally. Immunohistochemical studies demonstrated that, when tumor-bearing mice were infected with S636/pES, Salmonella colonization and endostatin expression were accompanied by the increase of apoptosis level and suppression of tumor angiogenesis within tumor tissues. Our findings showed that endostatin gene therapy delivered by attenuated S. typhimurium displays therapeutic antitumor effects in murine tumor models.
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PMID:Endostatin gene therapy delivered by attenuated Salmonella typhimurium in murine tumor models. 2975 10