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)

Serum level of endostatin, a natural angiogenesis inhibitor, was measured in 12 patients with hyperthyroidism and 9 patients with hypothyroidism. Control values were obtained from 12 healthy individuals. Hyperthyroidism was shown to be associated with an increased level of endostatin and hypothyroidism with a decreased endostatin level. There was no correlation of serum endostatin with thyroid hormone levels. Endostatin is a fragment of type XVIII collagen, and it is possible that reported changes are related to the effect of thyroid hormones on connective tissue metabolism.
 ...
PMID:Serum level of the circulating angiogenesis inhibitor endostatin in patients with hyperthyroidism or hypothyroidism. 1274 Oct 78

Angiogenesis plays a vital role in the pathology of cancer, ischemic diseases and chronic inflammation, among other conditions. Endostatin, a newly found protein that is distributed in some parts of the human body, has been demonstrated to have a strong inhibitory role in angiogenesis. It specifically inhibits the proliferation of endothelial cells and induces their apoptosis both in vitro and in vivo. Preclinical research has proven its effective role in the treatment of various experimental tumors in rodents. Although endostatin therapy has entered phase II clinical trials in the USA, the exact mechanism and its effects on antiangiogenesis, especially the action on the suppression of endothelial cell proliferation and induction of apoptosis, remain unclear. The treatment modality for malignancies and other angiogenesis-related diseases still requires further analysis.
 ...
PMID:The antiangiogenic and therapeutic implications of endostatin. 1274 27

Endostatin, a proteolytic fragment of collagen XVIII, is a potent inhibitor of angiogenesis and suppresses neovascularization and tumor growth. However, the inhibitory mechanism of endostatin in human endothelial cells has not been characterized yet. Electron microscopic analysis revealed that endostatin induced formation of numerous autophagic vacuoles in endothelial in 6 to 24 h after treatment. Moreover, there was only a 2- to 3-fold increase in intracellular reactive oxygen species after endostatin treatment. Endostatin-induced cell death was not prevented by antioxidants (vitamin C, vitamin E, or propyl gallate) or caspase inhibitors, suggesting that the increase of oxidative stress or the activation of caspases may not be the crucial factors in the anti-angiogenic mechanism of endostatin. However, the cytotoxicity of endostatin was significantly reduced by 3-methyladenine (a specific inhibitor of autophagy) and serine and cysteine lysosomal protease inhibitors (leupeptin and aprotinin). Taken together, these results suggest that in human endothelial cells: (1) endostatin predominantly causes autophagic, rather than apoptotic, cell death, (2) endostatin-induced autophagic cell death occurs in the absence of caspase activation and through an oxidative-independent pathway, and (3) endostatin-induced "autophagic cell death" or "type 2 physiological cell death" is regulated by serine and cysteine lysosomal proteases.
 ...
PMID:Endostatin induces autophagic cell death in EAhy926 human endothelial cells. 1279 83

Endostatin, located in the NC1 domain of the collagen XVIII, is believed to inhibit the migration and proliferation of endothelial cells (Fed. Am. Soc. Exp. Biol. J. 15 (2001) 1044) and to play a role in axon guidance in Caenorhabditis elegans (J. Cell Biol. 152 (2001) 1219). Zebrafish is an attractive vertebrate model to determine the role of endostatin and the entire molecule of collagen XVIII during vertebrate development. Therefore, we have investigated the expression pattern of COL18A1 in zebrafish embryos from the segmentation to the hatching period stages.
 ...
PMID:Sequence and embryonic expression of collagen XVIII NC1 domain (endostatin) in the zebrafish. 1279 84

Endostatin is a fragment of collagen XVIII that acts as an inhibitor of tumor angiogenesis and tumor growth. Anti-tumor effects have been described using both soluble and insoluble recombinant endostatin. However, differences in endostatin structure are likely to cause differences in bioactivity. In the present study, we have investigated the cellular effects of insoluble endostatin. We previously found that insoluble endostatin shows all the hallmarks of amyloid aggregates and potently stimulates tissue plasminogen activator-mediated formation of the serine protease plasmin. We here show that amyloid endostatin induces plasminogen activation by endothelial cells, resulting in vitronectin degradation and plasmin-dependent endothelial cell detachment. Endostatin-mediated stimulation of plasminogen activation, vitronectin degradation, and endothelial cell detachment is inhibited by carboxypeptidase B, indicating an essential role for carboxyl-terminal lysines. Our results suggest that amyloid endostatin may inhibit angiogenesis and tumor growth by stimulating the fibrinolytic system.
 ...
PMID:Amyloid endostatin induces endothelial cell detachment by stimulation of the plasminogen activation system. 1280 3

Endostatin is a naturally occurring proteolytic fragment of the C-terminal domain of collagen XVIII. It inhibits angiogenesis by a mechanism that appears to involve binding to HS (heparan sulphate). We have examined the molecular interaction between endostatin and HS from micro- and macrovessel endothelial cells. Two discrete panels of oligosaccharides were prepared from metabolically radiolabelled HS, using digestion with either heparinase I or III, and then examined for their endostatin affinity using a sensitive filter-binding assay. Two types of endostatin-binding regions were identified: one comprising sulphated domains of five or more disaccharides in length, enriched in 6-O-sulphate groups, and the other contained long heparinase I-resistant fragments. In the latter case, evidence from the present study suggests that the binding region encompasses a sulphated domain fragment and a transition zone of intermediate sulphation. The contribution to binding of specific O-sulphate groups was determined using selectively desulphated HS species, namely HS from Hs2st-/- mutant cells, and by comparing the compositions of endostatin-binding and non-binding oligosaccharides. The results indicate that 6-O-sulphates play a dominant role in site selectivity and 2-O-sulphates are not strictly essential.
 ...
PMID:Binding of endostatin to endothelial heparan sulphate shows a differential requirement for specific sulphates. 1281 20

Head and neck cancers are significant due to their high morbidity and associated complications. We report, for the first time, that endostatin directly affects epithelial lineage human cells derived from tumors of patients with head and neck squamous cell carcinoma (HNSCC). This study investigated endostatin's effects on several HNSCC cellular functions that are essential for tumor progression. We determined that exposure of HNSCC cells to endostatin activated the transcription-activating factors, NF-xB and AP-1 in a cell-line-dependent fashion. Endostatin also down-regulated the gene expression of several pro-migratory molecules. Migration and invasion assays showed that endostatin significantly inhibited these functions that are essential for tumor progression. Fluorescent labeling studies showed endostatin co-localized to tropomysin-binding HNSCC the microfilaments, suggesting endostatin's suppression of HNSCC cell migration and invasion may reflect perturbation of the microfilament function. Our data imply that endostatin's clinical efficacy extends beyond angiostatic properties to encompass a direct anti-tumorigenic effect against HNSCC cells.
 ...
PMID:Endostatin inhibits migration and invasion of head and neck squamous cell carcinoma cells. 1282 Mar 85

Endostatin is a 20 kDa carboxyl-terminal fragment of collagen XVIII that, when added exogenously, inhibits endothelial proliferation and migration in vitro and angiogenesis and tumor growth in vivo. Previous results showed endostatin/collagen XVIII labeling in few endothelial cells in human glioblastoma multiforme. We have now observed constitutive release of endostatin from one of four endothelial cell lines. Induction of endostatin release was observed after H2O2, an in vitro model of cell stress, CoCl2, a model of hypoxia, and by IFN-gamma challenge. Endostatin expression and release was reduced by the nitric oxide synthase inhibitors aminoguanidine and L-NAME and induced by the NO synthase-independent NO donors sodium nitroprusside (SNP) and spermine-NONO-ate. SNP-mediated endostatin induction was abrogated by the soluble guanylate cyclase inhibitor 1H-(1.2.4) oxadiazolo (4,3-A) quinoxalin-1-one. Adenoviral endostatin transduction resulted in the release of endostatin from endothelial cells and in down-regulation of iNOS (NOS2) and eNOS (NOS3), and surprisingly in a 10% induction of PCNA. These results describe the modulation of endostatin release by the NO signaling cascade and provide important new pharmacological information for the systemic induction of endogenous endostatin release by common NO donor pharmacotherapy.
 ...
PMID:Endothelial endostatin release is induced by general cell stress and modulated by the nitric oxide/cGMP pathway. 1283 91

Endostatin, the C-terminal fragment of collagen XVIII, is a potent inhibitor of angiogenesis. Observations that endostatin inhibits endothelial cell migration and induces disassembly of the actin cytoskeleton provide putative cellular mechanisms for this effect. To understand the mechanisms of endostatin-induced intracellular signaling, we analyzed the association of recombinant endostatin with endothelial cell lipid rafts and the roles of its heparin- and integrin-binding properties in this interaction. We observed that a fraction of cell surface-bound endostatin partitioned in low density membrane raft fractions together with caveolin-1. Heparinase treatment of cells prevented the recruitment of endostatin to the lipid rafts but did not affect the association of endostatin with the non-raft fraction, whereas preincubation of endostatin with soluble alpha5beta1 integrin prevented the association of endostatin with the endothelial cell membrane. Endostatin treatment induced recruitment of alpha5beta1 integrin into the raft fraction via a heparan sulfate proteoglycan-dependent mechanism. Subsequently, through alpha5beta1 integrin, heparan sulfate, and lipid raft-mediated interactions, endostatin induced Src-dependent activation of p190RhoGAP with concomitant decrease in RhoA activity and disassembly of actin stress fibers and focal adhesions. These observations provide a cell biological mechanism, which plausibly explains the anti-angiogenic mechanisms of endostatin in vivo.
 ...
PMID:Endostatin associates with lipid rafts and induces reorganization of the actin cytoskeleton via down-regulation of RhoA activity. 1285 10

Endostatin, the C-terminal part of collagen XVIII, has been shown to inhibit blood vessel formation in different pathological conditions characterized by increased angiogenesis, such as growing tumors. Subcutaneous injection of endostatin in tumor-bearing mice leads to decreased tumor growth, and even in some cases, cure of tumor disease. Endostatin has been tested in a clinical phase I study and shown not to be toxic. Whether the finding in mice that endostatin treatment does not result in development of resistance will hold true in humans is too early to tell. Endostatin binds to a specific motif in heparan sulfate, which may serve a co-receptor function. The structure of a potential primary receptor is not known. The mechanism of action of endostatin in inhibition of angiogenesis and thereby, inhibition of tumor growth, involves apoptosis of tumor cells. The most consistent effect of endostatin on endothelial cells in vitro is inhibition of endothelial cell migration, which may be due to disturbed cell-matrix interactions. An interesting candidate for transducing endostatin's effect on apoptosis and cell migration is beta-catenin, an intracellular protein which participates both in cell adhesion and in transcriptional regulation.
 ...
PMID:Endostatin action and intracellular signaling: beta-catenin as a potential target? 1286 Feb 82


<< Previous 1 2 3 4 5 6 7 8 9 10