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)

Angiostatin and endostatin are potent endothelial cell growth inhibitors and have been carefully evaluated for antiangiogenic cancer therapy. Previously, we have shown that subcutaneous administration of angiostatin K1-3 and endostatin genes complexed with liposomal vectors is a more practical treatment procedure than administration of angiostatin and endostatin proteins. This study provides additional conclusive evidence supporting the effectiveness of antiangiogenic cancer gene therapy employing angiostatin K1-3 and endostatin genes. Plasmids encoding a mouse angiostatin K1-3 gene (pFLAG-AngioK1/3) and an endostatin gene (pFLAG-Endo) were introduced by the hydrodynamic transduction method into mice carrying Matrigel plugs or B16BL6 mouse melanoma tumors. A single systemic injection of the two genes exhibited potent antiangiogenic and antitumor activity in the mouse model. Hydrodynamic coadministration of the genes inhibited the B16BL6 mouse melanoma growth and pulmonary metastasis more effectively than administration of either gene alone. Compared with the untreated control group, the mice cotreated with pFLAG-AngioK1/3 and pFLAG-Endo exhibited 75% reduction of tumor growth while those treated with pFLAG-AngioK1/3 or pFLAG-Endo showed 46% and 52% reduction, respectively. The cotreatment inhibited B16BL6 pulmonary metastasis formation by 80% while the inhibition induced by individual treatment with pFLAG-AngioK1/3 or pFLAG-Endo was 68% and 71%, respectively. These results provide additional evidence that systemic expression of angiostatin K1-3 and/or endostatin genes is a viable alternative procedure for antiangiogenic cancer therapy.
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PMID:Antitumor effects of angiostatin K1-3 and endostatin genes coadministered by the hydrodynamics-based transfection method. 1649 52

Angiostatin(AS) and endostatin(ES) are both potent endogenous angiogenesis inhibitors, and the combination of AS and ES has been shown to have synergistic antiangiogenic effects. Here we report the fusion protein AS-ES expressed in E. coli which has antiangiogenic effects. At first, AS and ES genes were cloned respectively through RT-PCR, then fusion gene was made through gene splicing ,finally pET-42 (b)/AS-ES expression plasmid was constructed and transduced in E. coli BL21 (DE3). Target protein was in form of inclusion body,the rate of expression was about 14%, and MW about 65KD. Western blotting assay showed expressed protein had specific immune reaction to both the antibodies of AS and ES. The expressed protein which was refolded and purified through heparin affinity chromatography had antiangiogenic effect to vessels on chicken embryo chorioallantoic membrane. The results show that fusion protein AS-ES was expressed successfully in E. coli, and the expressed protein,which was renatured and purified, had immuno-reactivity to anti-AS and anti-ES in Western blotting and angiogenesis inhibition activity.
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PMID:[Fusion expression and identification of angiostatin and endostatin in E. coli BL21(DE3)]. 1712 60

Coronary artery disease (CAD) is the leading cause of mortality in diabetic patients. Because of the diffuse nature of their disease, diabetic patients may be at risk for incomplete revascularization, highlighting a potential role for proangiogenic therapy in this group. This study investigates molecular mechanisms of angiogenesis in diabetic patients. Myocardial tissue was harvested from patients undergoing coronary artery bypass grafting [nondiabetic (ND) 11, type 2 diabetic (DM) 10]. Expression of angiostatin, endostatin, their precursors (plasminogen and collagen XVIII, respectively), enzymes leading to their production [matrix metalloprotease (MMP)-2 and -9, cathepsin L], and an inhibitor of MMPs (tissue inhibitor of metalloproteinase) was assessed with Western blotting. MMP activity was assessed. Coronary collateralization was graded by Rentrop scoring of angiograms. Plasminogen and collagen XVIII expression were similar between groups. Angiostatin expression trended to increase 1.24-fold (P = 0.07), and endostatin expression increased 2.02-fold in DM patients relative to ND (P = 0.02). MMP-9 expression was no different between groups, whereas MMP-2 expression decreased 1.8-fold in diabetics (P = 0.003). MMP-2 and -9 activity decreased 1.33-fold (P = 0.03) and 1.57-fold (P = 0.04), respectively, in diabetic patients. Cathepsin L expression was 1.38-fold higher in diabetic patients (P = 0.02). Coronary collateralization scores were ND 2.1 +/- 0.37 vs. DM 1.0 +/- 0.4 (P = 0.05). Myocardial endostatin expression correlated strongly with the percentage of hemoglobin A(1c) (r = 0.742, P = 0.0001). Myocardial expression of angiostatin and endostatin demonstrated significant negative linear correlations with coronary collateralization (angiostatin r = -0.531, P = 0.035, endostatin r = -0.794, P = 0.0002). Diabetic patients with CAD exhibit increased levels of the antiangiogenic proteins angiostatin and endostatin and differential regulation of the enzymes governing their production relative to ND patients. Myocardial levels of these proteins show significant correlation to coronary collateralization. These findings offer potential new therapeutic targets for enhancing proangiogenic therapy and insight into the angiogenic impairments seen in diabetes.
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PMID:Endostatin and angiostatin are increased in diabetic patients with coronary artery disease and associated with impaired coronary collateral formation. 1907 76

Angiogenesis is essential for tumor growth and progression. It has been demonstrated that the expression of angiogenesis stimulators (e.g. basic fibroblast growth factor and vascular endothelial growth factor) correlates to tumor progression in various human tumor types. Furthermore, endogenous angiogenesis inhibitors (e.g. angiostatin and endostatin) have been isolated from human tumor models and have been successfully used to treat tumors in mice and humans. In the present study, the expression of angiostatin, endostatin and thrombospondin-1 in four different human bladder cancer cell lines with different tumorigenic potential (MGH-U4, RT-4, RT-112 and UMUC-3) were investigated. A subset of bladder carcinoma patients demonstrates rapid metastatic progression after removal of the primary tumor, although no evidence of metastasis is diagnosed before the surgical procedure. A potential mechanism to explain this phenomenon is suggested. Angiostatin, endostatin and thrombospondin-1 was detected in the conditioned media of four human bladder cancer cell lines using Western blotting. Angiostatin was purified and amino acid sequenced via mass spectrometry. The biological activity of angiostatin was determined by proliferation assays using endothelial cells, smooth muscle cells and fibroblasts. Tumor characteristics of the four human bladder carcinoma models were investigated in vitro and in vivo. All the bladder carcinoma cell lines employed in this study produced two biologically active variants of the angiostatin molecule (38 and 49 kDa). Endostatin and thrombospondin-1 were only produced by the low malignancy MGH-U4 and RT-4 bladder carcinoma models. This study identified the expression of different antiangiogenic molecules in human bladder carcinoma. The expression of antiangiogenic molecules seems to be a characteristic of low malignancy bladder carcinomas. The sudden lack of expression of antiangiogenic molecules as a consequence of surgical removal of highly malignant bladder carcinomas may explain the rapid metastatic progression of a subset of bladder carcinomas.
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PMID:Expression of angiogenesis inhibitors in human bladder cancer may explain rapid metastatic progression after radical cystectomy. 1914 51

Angiostatin, a proteolytic fragment of plasminogen, is a potent endogenous antiangiogenic agent. The molecular mechanisms governing angiostatin's antiangiogenic and antitumor effects are not well understood. Here, we report the identification of mitochondrial compartment as the ultimate target of angiostatin. After internalization of angiostatin into the cell, at least 2 proteins within the mitochondria bind this molecule: malate dehydrogenase, a member of Krebs cycle, and adenosine triphosphate synthase. In vitro and in vivo studies revealed differential regulation of key prosurvival and angiogenesis-related proteins in angiostatin-treated tumors and tumor-endothelium. Angiostatin induced apoptosis via down-regulation of mitochondrial BCL-2. Angiostatin treatment led to down-regulation of c-Myc and elevated levels of another key antiangiogenic protein, thrombospondin-1, reinforcing its antitumor and antiangiogenic effects. Further evidence is provided for reduced recruitment and infiltration of bone marrow-derived macrophages in angiostatin-treated tumors. The observed effects of angiostatin were restricted to the tumor site and were not observed in other major organs of the mice, indicating unique tumor specific bioavailability. Together, our data suggest mitochondria as a novel target for antiangiogenic therapy and provide mechanistic insights to the antiangiogenic and antitumor effects of angiostatin.
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PMID:Angiostatin regulates the expression of antiangiogenic and proapoptotic pathways via targeted inhibition of mitochondrial proteins. 1971 80

The aim of the study is to investigate the expression of angiogenesis (VEGF and PDGF), angiogenesis inhibitor markers (angiostatin and endostatin), proliferation (Ki67), and apoptosis markers (p53 and p16) of cervical cancer in Indian population and to correlate them with the clinicopathological profile. It is a descriptive study of consecutive cases of cervical cancer from Saveetha Medical College and Hospital between January 2017 and December 2018. The expression of angiogenesis, angiogenesis inhibitor markers, Ki67, p53, and p16 in 60 cases of cervical sections were detected by the immunohistochemical method and analyzed with clinicopathological data. VEGF expression was positive in 16 cases (26.67%) and negative in 20 cases (33.33%). As of PDGF, 3 cases (3.33%) have shown positivity to PDGF and 33 cases have shown negativity. Angiostatin and endostatin expression was reported to be positive in 10 (16.67%) and 21 (35%) cases, respectively. Most of the cases 57 (95%) have shown both p16 and Ki67 positivity. Although p53 expression was positive in 48 cases (80%), the remaining 12 cases (20%) were p53-negative. The PDGF expression was significantly correlated to the stage of tumors. No statistically significant association was observed between angiogenesis inhibitor markers and clinicopathological parameters. A significant positive correlation was noticed between the Ki67 expression and stage of tumors.
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PMID:Prevalence of Angiogenesis, Proliferation, and Apoptosis Markers of Cervical Cancer and Their Correlation with Clinicopathological Parameters. 3327 20


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