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)

Serum concentrations of three angiogenic cytokines: vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukin-18 (IL-18) and antiangiogenic factor endostatin in the serum of 52 patients with systemic lupus erythematosus (SLE) and 20 healthy subjects were investigated. The possible association between serum levels of these proteins and SLE activity as well as correlation between the concentrations of angiogenic cytokines and the level of endostatin was also analyzed. VEGF and IL-18 were detectable in all SLE patients and healthy control group. bFGF was measurable in 71.2% of patients with SLE and 65% of healthy persons. Endostatin was detectable in 94.2% of SLE patients and 95% of normal subjects. The serum levels of endostatin and bFGF were not significantly different in SLE and healthy control (P > 0.05). The median concentration of VEGF was higher in active SLE (238.4 pg/ml) than in inactive disease (118.1 pg/ml, P < 0.05) or in control group (133.5 pg/ml, P < 0.04). The median serum level of IL-18 was higher in the SLE patients (595.2 pg/ml) than in the control group (252.7 pg/ml) (P < 0.001). The correlations between the levels of angiogenic cytokines and endostatin with clinical features, laboratory abnormalities and also with the type of treatment were analysed. We found a positive correlation between VEGF serum concentration and SLE activity according to SLAM score (p = 0.275, P < 0.05). The significant positive correlation was also found between IL-18 and endostatin (p = 0.289, P < 0.04). In contrast, the correlation between bFGF and endostatin was significantly negative (p = - 0.299, P < 0.04). In conclusion, serum levels of the angiogenic and antiangiogenic factors may play an important role in SLE pathogenesis.
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PMID:Circulating angiogenesis inhibitor endostatin and positive endothelial growth regulators in patients with systemic lupus erythematosus. 1213 72

Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. To gain insight into ES-mediated signaling, we studied the effects of ES RNA on Xenopus embryogenesis and observed developmental abnormalities consistent with impaired Wnt signaling. ES RNA blocked the axis duplication induced by beta-catenin, partially suppressed Wnt-dependent transcription, and stimulated degradation of both wild-type and "stabilized" forms of beta-catenin, the latter suggesting that ES signaling does not involve glycogen synthase kinase 3. Moreover, ES uses a pathway independent of the Siah1 protein in targeting beta-catenin for proteasome-mediated degradation. ES failed to suppress the effects of T cell-specific factor (TCF)-VP16 (TVP), a constitutive downstream transcriptional activator that acts independently of beta-catenin. Importantly, these data were replicated in endothelial cells and also in the DLD-1 colon carcinoma cells with the mutated adenomatous polyposis coli protein. Finally, suppression of endothelial cell migration and inhibition of cell cycle by ES were reversed by TVP. Though high levels of ES were used in both the Xenopus and endothelial cell studies and the effects on beta-catenin signaling were modest, these data argue that at pharmacological concentrations ES may impinge on Wnt signaling and promote beta-catenin degradation.
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PMID:Endostatin is a potential inhibitor of Wnt signaling. 1214 76

Human endostatin is a novel antiangiogenic molecule, which can inhibit the proliferation and development of new blood vessels, and experimentally can cause nearly complete regression of established tumors. In this paper, the cDNA encoding human endostatin was cloned into a baculovirus shuttle vector pBacPAK8 and co-infected with linearized Bm-BacPAK6 DNA into and BmN cells. The recombinant virus was screened and identified by PCR, DNA and RNA dot hybridization, and ELISA assay. The recombinant endostatin was expressed in culture cells, and the larvae and pupa of silkworm by inoculation of recombinant virus. The biological activity assay showed that the expression product in larvae was over 150 microg/ml, about 50-fold higher than that expressed in cultured cells. SDS-PAGE and Western blotting analysis showed a pattern of molecular weight of about 20 kDa. The bio-activity of the protein product was determined by human umbilical vein endothelial cells (ECV304) proliferation test in vitro and the chick chorioallantoic membrane (CAM) vascular inhibition test. Endostatin showed significant inhibitory effect on endothelial cells in a dose-dependent manner. Silkworm-produced endostatin induced apoptosis of endothelial cells and also inhibited angiogenesis in the CAM assay. Combination regimen using angiostatin and endostatin showed more than additive effect in angiogenic inhibition and increasing apoptosis when compared with treatment with the individual antiangiogenic protein.
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PMID:Expression of human endostatin in larvae of silkworm (Bombyx mori) and in vitro activity assays. 1218 48

Tumor growth and metastasis depend on blood supply and blood vessel formation. Angiogenesis, therefore, represents a promising target for cancer therapy. Endostatin is one of the most potent antiangiogenic factors and has been shown to effectively inhibit angiogenesis and tumor growth in a variety of in vivo models. In this study, we tested the effects of endostatin on xenografted human follicular thyroid carcinoma (FTC) in nude mice. Our result demonstrated that recombinant endostatin significantly inhibited the growth of FTC xenografts. Furthermore, we established an endostatin-expressing FTC cell line (FTC-BmEndo) using retrovirus-mediated gene transfer approach. We found that the in vivo growth of FTC-BmEndo cells was significantly inhibited, compared with the parental FTC cells, whereas both lines grew at the same rate in vitro. High-level expression of endostatin within the FTC-BmEndo tumors was evidenced by immunohistochemical staining, paralleled with a reduced microvessel density. The systemic level of vascular endothelial growth factor was significantly lower in mice bearing the FTC-BmEndo tumors than in those bearing parental FTC tumors. By using two different approaches, namely the recombinant endostatin protein and the gene therapy strategy, our study demonstrated that endostatin could be effective in suppressing the growth of human FTC in immunodeficient mice.
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PMID:Antiangiogenic and antitumor effects of endostatin on follicular thyroid carcinoma. 1219 66

Cancer therapies based on the inhibition of angiogenesis by endostatin have recently been developed. We demonstrate that a mutated form of human endostatin (P125A) can inhibit the angiogenic switch in the C3(1)/Tag mammary cancer model. P125A has a stronger growth-inhibitory effect on endothelial cell proliferation than wild-type endostatin. We characterize the angiogenic switch, which occurs during the transition from preinvasive lesions to invasive carcinoma in this model, and which is accompanied by a significant increase in total protein levels of vascular endothelial growth factor (VEGF) and an invasion of blood vessels. Expression of the VEGF(188) mRNA isoform, however, is suppressed in invasive carcinomas. The VEGF receptors fetal liver kinase-1 (Flk-1) and Fms-like tyrosine kinase-1 (Flt-1) become highly expressed in epithelial tumor and endothelial cells in the mammary carcinomas, suggesting a potential autocrine effect for VEGF on tumor cell growth. Angiopoietin-2 mRNA levels are also increased during tumor progression. CD-31 (platelet-endothelial cell adhesion molecule [PECAM]) staining revealed that blood vessels developed in tumors larger than 1 mm The administration of P125A human endostatin in C3(1)/Tag females resulted in a significant delay in tumor onset, decreased tumor multiplicity and tumor burden and prolonged survival of the animals. Endostatin treatment did not reduce the number of preinvasive lesions, proliferation rates or apoptotic index, compared with controls. However, mRNA levels of a variety of proangiogenic factors (VEGF, VEGF receptors Flk-1 and Flt-1, angiopoietin-2, Tie-1, cadherin-5 and PECAM) were significantly decreased in the endostatin-treated group compared with controls. These results demonstrate that P125A endostatin inhibits the angiogenic switch during mammary gland adenocarcinoma tumor progression in the C3(1)/Tag transgenic model.
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PMID:Inhibition of the mammary carcinoma angiogenic switch in C3(1)/SV40 transgenic mice by a mutated form of human endostatin. 1220 72

We present a heterogeneous non-competitive immunological detection assay for peptide and protein antigens from crude extracts of biological sources. This time-resolved fluoroimmunoassay (TR-FIA) has been designed in a solid-phase mode using 96-well microtiter plates. Using the rare-earth metal europium as a fluorescent marker, a highly sensitive, selective and efficient procedure was developed. This technique prevents from interferences of intrinsic protein fluorescence which is highly important for antigen measurement in complex matrices. The TR-FIA has been applied for the detection of circulating forms of the potential anti-tumor agent endostatin, a C-terminal fragment of collagen XVIII, and its close homolog collagen XV (restin) from hemofiltrate. Endostatin was detected with a limit of detection of 3 ng (150 fmol/well) and a broad dynamic range from 10-1000 ng/well.
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PMID:Time-resolved fluorometric assay for the detection of endostatin in chromatographically separated extracts of natural peptides. 1221 91

Endostatin prevents angiogenesis and tumor growth by inhibiting endothelial cell proliferation and migration. The purpose of this study was to determine serum endostatin concentrations in 53 healthy dogs and in 38 dogs with confirmed malignant neoplasms. Endostatin concentration was determined with a competitive enzymatic immunoassay (EIA) with rabbit polyclonal antibody generated against a recombinant canine endostatin protein. Both the presence of cancer and increasing age were associated with increased serum concentration of endostatin. Endostatin concentration in healthy dogs was 87.7 +/- 3.5 ng/mL. Upper and lower limits of the reference range for serum endostatin concentration in healthy dogs were 60 and 113 ng/mL. Dogs with lymphoma (LSA) and hemangiosarcoma (HSA) had endostatin concentrations of 107 +/- 9.3 ng/mL. In conclusion, this study demonstrates that endostatin can be quantified in dogs and that endostatin concentrations are high in dogs with HSA and LSA.
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PMID:Endostatin concentrations in healthy dogs and dogs with selected neoplasms. 1232 7

Endostatin and angiostatin are known as tumor-derived angiogenesis inhibitors, but their mechanisms of action are not yet completely defined. We report here that endostatin and angiostatin, delivered by adenoviral vectors, reduced in vitro the neovessel formation in the mouse aortic ring assay by 85 and 40%, respectively. We also demonstrated in vivo that both endostatin and angiostatin inhibited local invasion and tumor vascularization of transplanted murine malignant keratinocytes, and reduced by 50 and 90% the development of highly vascularized murine mammary tumors. This inhibition of tumor growth was associated with a reduction of tumor vascularization. Expression analysis of vascular endothelial growth factor (VEGF) carried out in the mouse aortic ring model revealed a 3- to 10-fold down-regulation of VEGF mRNA expression in endostatin-treated rings. A similar down-regulation of VEGF expression at both mRNA and protein levels was also observed in the two in vivo cancer models after treatment with each angiogenesis inhibitor. This suggests that endostatin and angiostatin effects may be mediated, at least in part, by their ability to down-regulate VEGF expression within the tumor. This work provides evidence that endostatin and angiostatin act on tumor cells themselves.
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PMID:The antitumoral effect of endostatin and angiostatin is associated with a down-regulation of vascular endothelial growth factor expression in tumor cells. 1235 94

Endostatin, the COOH-terminal fragment of collagen XVIII, is a potent inhibitor of angiogenesis and tumor growth. To understand the mechanisms behind endostatin action, we analyzed the plasma membrane- extracellular matrix interactions of recombinant human endostatin in cultured microvascular endothelial cells. We observed that endostatin induced rapid clustering of alpha5beta1 integrin associated with actin stress fibers and its concomitant colocalization with the membrane anchor protein caveolin-1. Furthermore, endostatin could be coimmunoprecipitated with alpha5beta1 and caveolin-1 from endothelial cell extracts. Endostatin treatment induced phosphatase-dependent activation of caveolin-associated Src family kinases. The disassembly of actin stress fibers and focal adhesions by endostatin was found to occur via activation of Src and in a tyrosyl phosphatase-dependent manner. The endostatin-treated cells void of the focal adhesions had impaired ability to deposit fibronectin into their extracellular matrices and were unable to migrate in response to basic fibroblast growth factor in a wounding experiment. These results indicate that recombinant endostatin interacts with alpha5beta1 integrin and caveolin-1 at the endothelial cell surface. In addition, the antimigratory effect of endostatin involves phosphatase-dependent Src activation and impaired cell-matrix interactions.
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PMID:Endostatin associates with integrin alpha5beta1 and caveolin-1, and activates Src via a tyrosyl phosphatase-dependent pathway in human endothelial cells. 1235 71

The malignant transformation of a normal cell into a cancer cell requires no vasculature. Growth of solid tumors, however, requires angiogenesis to provide oxygen and nutrients to support cell proliferation. The switch from an avascular to a vascular phenotype is typically associated with acceleration of tumor growth. Antiangiogenic therapy, starving a tumor of its blood supply, is an attractive addition to the anticancer armamentarium. Animal tests of antiangiogenic therapy have shown remarkable potential. Initial human trials have proven antiangiogenic therapy to be remarkably nontoxic. Numerous antiangiogenic agents have been isolated as proteolytic fragments of endogenous polypeptides of the extracellular matrix. Endostatin was the first such antiangiogenic protein described and its potent antitumor effects in mice have generated wide interest. This review summarizes recent advances in endostatin biology and highlights new results on the cellular and subcellular mechanisms of endostatin action.
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PMID:Cellular actions and signaling by endostatin. 1244 42


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