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)

Blood transfusions are associated with recurrence of solid cancers. Angiogenesis is essential for cancer growth. Our aim was to determine for the first time in a prospective cohort study the effect of prestorage allogeneic leucodepleted SAGM (saline, adenine, glucose, mannitol) red cell transfusion on angiogenic factor levels and in vitro angiogenesis. Forty pretransfusion adult hospital inpatients were selected consecutively. Serum vascular endothelial growth factor (VEGF) and endostatin were measured in each patient before and after prestorage allogeneic leucodepleted SAGM red cell transfusion. All samples were exposed to an in vitro endothelial cell proliferation assay and 10 sample groups were also exposed to an in vitro whole angiogenesis assay. The median number of units transfused was 2 (minimum-maximum, 2-4). Twenty-nine (73%) patients had a rise in VEGF, with an overall increase of 118 pg/ml (quartiles -5, 306; P < 0.01). Twenty-eight (70%) patients had a decrease in endostatin, with an overall reduction of 1.2 ng/ml (quartiles 4.0, 0.0; P = 0.017). There was an overall 33% increase in endothelial cell proliferation (P < 0.01) and a 9.4% increase in in vitro whole assay angiogenesis (P < 0.01). Prestorage allogeneic leucodepleted SAGM red cell transfusions are associated with a favourable angiogenic factor imbalance and an elevation in in vitro angiogenesis.
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PMID:Enhanced angiogenesis following allogeneic blood transfusion. 1505 7

Previous experiments have shown that a vascular endothelial growth factor (VEGF)-DT385 toxin conjugate inhibits endothelial cell proliferation, angiogenesis and solid tumor growth in a xenotransplant model system. Here, we report that VEGF-DT385 toxin conjugate effectively inhibits spontaneous tumorigenesis. The C3(1)/SV40 TAg transgenic mouse model of mammary gland carcinogenesis was used to determine the effectiveness of VEGF-DT385 toxin conjugate in delaying the onset of disease and the development of solid tumors. Animals were treated daily with conjugate for a period of 7 days. Therapy was initiated at week 14 of development before any visible adenocarcinomas were evident. Treatment of mice with VEGF-DT385 toxin conjugate significantly delayed the onset of tumorigenesis and inhibited solid tumor growth by more than 92%. Furthermore, conjugate treated animals showed less than twice the number of tumor nodules when compared to control mice. Finally, this vascular targeting agent significantly increased survival time of animals by 5 weeks. VEGF-DT385 toxin conjugate resulted in temporary weight loss and no long-lasting toxicity was seen. More importantly, using this established tumor model, VEGF-DT385 toxin conjugate appeared to be as effective as a similar treatment schedule with recombinant human endostatin. Our results suggest that VEGF-DT385 toxin conjugate is a potent inhibitor of mammary adenocarcinoma growth and might be useful in breast cancer therapy.
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PMID:VEGF-DT385 toxin conjugate inhibits mammary adenocarcinoma development in a transgenic mouse model of spontaneous tumorigenesis. 1511 74

Tumour associated neovascularisation has been characterised as chaotic and insufficient. This report details the results of the analysis of angiogenic factors in tumour cyst fluid, pleural fluid, and blood from a patient with a gastrointestinal autonomic nerve tumour. The tumour produced vascular endothelial growth factor and endostatin in large quantities, which may explain the dysfunctional angiogenesis and tendency to bleeding seen in this tumour type.
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PMID:A patient with a VEGF and endostatin producing gastrointestinal autonomic nerve tumour. 1511 63

Endostatin, a 20-kDa fragment of collagen XVIII, is a potent angiogenesis inhibitor. E-selectin, an inducible leukocyte adhesion molecule specifically expressed by endothelial cells, has also been implicated in angiogenesis. By using in vivo, ex vivo, and in vitro angiogenic assays, we investigated the functional relationship between endostatin and E-selectin. In corneal micropocket assays, recombinant endostatin administered i.p. by osmotic pump inhibited basic fibroblast growth factor-induced angiogenesis in WT, but not E-selectin-deficient, mice. Similarly, endostatin inhibited vascular endothelial growth factor-stimulated endothelial sprout formation from aortic rings dissected from WT but not from E-selectin-deficient mice. To further explore this apparent requirement for E-selectin in endostatin action, we manipulated E-selectin expression in cultured human endothelial cells. When E-selectin was induced by IL-1beta, or lipopolysaccharide, human umbilical vein endothelial cells and human dermal microvascular endothelial cells each became markedly more sensitive to inhibition by endostatin in a vascular endothelial growth factor-induced cell migration assay. To dissociate E-selectin expression from other consequences of endothelial activation, human umbilical vein endothelial cells were transduced with an adenoviral human E-selectin expression construct; these cells also showed increased sensitivity to endostatin, and this effect required the E-selectin cytoplasmic domain. Taken together, these results indicate that E-selectin is required for the antiangiogenic activity of endostatin in vivo and ex vivo and confers endostatin sensitivity to nonresponsive human endothelial cells in vitro. E-selectin may be a useful predictor and modulator of endostatin efficacy in antiangiogenic therapy.
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PMID:E-selectin is required for the antiangiogenic activity of endostatin. 1514 73

Concomitant antitumoral resistance (CAR), the phenomenon by which the growth of distant secondary tumor implants or metastases in some tumor-bearing hosts is inhibited by the presence of a primary tumor, has been previously ascribed to an antiangiogenic process. Here, we investigated vascular endothelial growth factor (VEGF) and endostatin serum levels in nude or BALB/c mice bearing human lung tumors (Calu-6 and H460) or murine mammary tumors (M3MC, M-234p and M-234m), respectively. In these experimental models we previously found an association between in vivo generation of CAR and in vitro conversion of plasminogen into angiostatin. Serum endostatin level in CAR+ Calu-6-bearing mice was significantly higher than in CAR- H460 counterpart. Sera from mammary tumor-bearing mice showed similar levels of endostatin, regardless of their ability to induce CAR. Conversely, serum VEGF levels in mice bearing CAR+ tumors were lower than those found in CAR- tumor-bearing hosts. Immunostaining with an anti-CD31 antibody revealed that secondary tumors subjected to CAR were significantly less vascularized than primary tumors, while this difference was not observed in CAR- tumors. In vitro studies showed an inhibitory effect of sera from CAR-inducing tumors on endothelial cell proliferation as compared to normal sera, whereas sera from non-CAR-inducing tumors did not alter endothelial proliferation and, in some instances, even caused stimulation of endothelial proliferation. These data suggest that the antiangiogenic mechanism operating in concomitant antitumoral resistance is the result of an increase in the ratio of antiangiogenic/proangiogenic regulators. The levels of the factors involved in this phenomenon can vary in the different tumor models, but the trend favoring the inhibition of angiogenesis is always conserved.
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PMID:Angiogenic and antiangiogenic balance regulates concomitant antitumoral resistance. 1516 35

Angiogenesis, the growth of new capillaries from pre-existing vessels, contributes to the development and progression of a variety of physio-pathological conditions. There is growing evidence that anti-angiogenic drugs will improve future therapies of diseases like cancer, rheumatoid arthritis and ocular neovascularisation. Conversely, therapeutic angiogenesis is an important homeostatic response contributing to limit the damage to ischemic tissues. Molecular processes involved in angiogenesis include stimulation of endothelial growth by cytokine production (i.e. vascular endothelial growth factor, VEGF; fibroblast growth factor-2, FGF-2), degradation of extracellular matrix proteins by matrix metalloproteinases (MMPs), and migration of endothelial cells mediated by integrins (cell membrane adhesion molecules). Drugs targeting pathologic angiogenesis have been designed to interfere with any of these steps and are currently undergoing evaluation in early clinical studies. Important therapeutic strategies are: suppression of activity and signaling pathways activated by the major angiogenic regulators like VEGF and FGF-2; inhibition of function of alphav-integrins and MMPs; exploitation of endogenous anti-angiogenic molecules like angiostatin and endostatin. The strategy to "silence" endothelium with antiangiogenic drugs to starve tumors, provides a novel approach for cancer treatment. The unique targets of these drugs (endothelium) make them distinct from traditional cytotoxic chemotherapeutic agents. Conversely, gene transfer of angiogenesis inducers is the new approach for therapeutic neovascularization, which is under investigation using a variety of growth factors and a wide array of potential delivery systems, including the application of the gene as naked DNA or by viral vector. The status of pro- and anti-angiogenic therapies is here presented and discussed.
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PMID:Development of new drugs in angiogenesis. 1521 14

We have studied the antiangiogenic property of berberine. We showed that berberine could directly inhibit in vitro human umbilical vein endothelial cell (HUVEC) tube formation and migration. In addition, to determine whether berberine could influence the cross-talk between the gastric adenocarcinoma cell line SC-M1 and vascular endothelial cells, we performed modified confrontation culture experiments and showed that berberine (7.5 microM, 16 h) could inhibit the capacity of hypoxic SC-M1 cells to stimulate HUVEC migration. These results demonstrated berberine's antiangiogenic property and its clinical potential as an inhibitor of tumor angiogenesis. Parallel Western blot analyses revealed that berberine prevented hypoxic SC-M1 cultures from expressing vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1alpha, two key factors in mediating tumor angiogenesis. However, overexpression of HIF-1alpha in SC-M1 cells dramatically reversed the inhibitory effect of berberine on SC-M1-induced in vitro HUVEC migration. These data indicated that HIF-1alpha repression is a critical step in the inhibitory effect of berberine on tumor-induced angiogenesis. Northern blot analyses plus pulse-chase assays revealed that berberine did not down-regulate HIF-1alpha mRNA but destabilized HIF-1alpha protein. We found that berberine-induced HIF-1alpha degradation was blocked by a 26S proteasome inhibitor. Moreover, immunoprecipitation and Western blot analyses showed that berberine increased the lysine-acetylated HIF-1alpha in hypoxic SC-M1 cultures. These data indicated that a proteasomal proteolytic pathway and lysine acetylation were involved in berberine-triggered HIF-1alpha degradation. In conclusion, our data provided molecular evidence to support berberine as a potent antiangiogenic agent in cancer therapy.
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PMID:Berberine inhibits HIF-1alpha expression via enhanced proteolysis. 1532 53

Angiogenesis, the development of new vessels from a pre-existing vasculature, accompanies the growth and malignant transformation of astrocytic brain tumors. Neovascularization is essential for sustained tumor growth, and with increasing grade, astrocytic tumors undergo an, angiogenic switch, manifested by marked increases in vessel density and changes in vascular morphology. In the quiescent state, endogenous anti-angiogenic factors including endostatin, thrombospondin, and soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) balance the actions of pro-angiogenic stimuli and restrain the angiogenic switch. Once activated, pro-angiogenic factors including most notably basic fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF-A), and platelet-derived growth factor (PDGF) incite robust astrocytoma neovascularization. Recent studies have also explored the expression patterns and functional importance of the angiopoietins, Tie2 and neuropilin receptors, and hepatocyte growth factor/scatter factor (HGF). Together these angiogenic factors have diverse actions on endothelium and perivascular supporting cells that engender tumor neovessels with a unique phenotype, distinct from normal vessels. Properties of the astrocytoma neovasculature contribute to tumor growth, malignant progression, invasion, hemorrhage, and edema formation. Thus, the mechanistic actions of angiogenic factors on cerebral microvessels and the nature of the resultant tumor neovasculature establish a framework for understanding many of the characteristic behaviors of astrocytoma tumors.
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PMID:Angiogenesis and its role in the behavior of astrocytic brain tumors. 1535 41

Hypoxia downregulated the concentration of endostatin in the culture media of human endometrial stromal cells but did not affect the messenger (m)RNA expression of collagen XVIII. Both mRNA and protein expression of vascular endothelial growth factor were upregulated in a hypoxic condition.
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PMID:Hypoxia simultaneously inhibits endostatin production and stimulates vascular endothelial growth factor production by cultured human endometrial stromal cells. 1537 30

The recent discovery of several molecules that negatively modulate the migration and growth of endothelial cells, collectively referred to as inhibitors of angiogenesis, has made it possible to test the hypothesis that control of angiogenesis might be an effective strategy in controlling tumor growth, as well as ameliorating the course of other life-threatening diseases. Angiogenesis inhibitors are heterogeneous in origin and potency, and their growing list includes products of the proteolysis of larger molecules with a different function, such as angiostatin and endostatin, natural modulators of vascular endothelial growth factor activity, such as sFLT-1, and some cytokines with a marked anti-endothelial activity, such as IL-12 and interferon-alpha. Pre-clinical studies have clearly indicated that most of these factors exert cytostatic rather than cytotoxic effects, thus implying the need for long-term administration in order to obtain a prolonged therapeutic effect. This feature of angiostatic therapy and the difficulty in synthesizing large amounts of recombinant functional proteins have prompted several studies, which have investigated their delivery by a gene therapy approach. This review addresses the several experimental approaches attempted to date, points out the constraints that have delayed clinical application, and envisions possible areas of integration between antiangiogenic gene therapy and other established therapeutic options against cancer.
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PMID:Undermining tumor angiogenesis by gene therapy: an emerging field. 1538 43


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