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)

Work begun more than 30 years ago at Children's Hospital in Boston led to the publication of an article on the antiangiogenic properties of two compounds, endostatin and angiostatin (J. Folkman, Nature 1997; 390:404-7). It only took weeks for the medias in the US and then in France and the rest of Europe to stimulate the fervor of patients for this new 'cure' for cancer. Insight into the fundamental role of angiogenesis in locoregional and metastatic development of cancer has been accumulated over the last decades. Factors stimulating tumoral angiogenesis include aFGF, bFGF, VEGF, angiogenin, and other more recently discovered substances. Likewise, factors inhibiting tumoral angiogenesis, including angiostatin, have been identified. Angiostatin is a specific inhibitor of endothelial cell growth that migh appear rapidly in the serum of patients with a primary tumor. Angiostatin could have both local and systemic effects and possibly protect against metastatic dissemination in vivo. The importance of angiogenesis inhibitors was emphasized at the recent meeting of the American Association for Cancer Research (New Orleans March 28-April 1, 1998). To date, at least eleven compounds are being tested. Currently, most are in phase 1 or 2; for the few in phase 3, marketing approval will undoubtedly require several years. It is interesting to note that neither endostatin nor angiostatin are among the list of drugs under clinical assessment, first because these small human proteins are not available in sufficient quantity for therapeutic trials and secondly, because the processes necessary to produce pure and safe compounds remain to be developed. Even after these steps have been accomplished, preclinical evaluations will have to be performed before the first clinical trials could be envisaged. For the time being, antiangiogenesis remains a promising avenue of anti-cancer research but neither endostatin nor angiostatin will be available for human research for several months at least.
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PMID:[Tumor angiogenesis inhibitors: media and scientific aspects]. 976 82

A number of clinical studies have demonstrated the prognostic significance of angiogenesis and angiogenic growth factors in solid tumours; however, very little is known about the relevance of these parameters in haematological malignancies. We evaluated circulating levels of angiogenic growth factors and endostatin in 36 non-Hodgkin's lymphoma (NHL) patients. Baseline vascular endothelial growth factor (VEGF) levels of patients in complete remission (CR) after a median follow-up of 21 months were significantly lower than those of patients with progressive disease (P = 0.016). Event-free survival (EFS) rate was significantly higher in patients who had baseline VEGF and basic-fibroblast growth factor (b.FGF) levels below the median values of 147 and 19.5 pg/ml (P = 0.018 and 0.039 by log-rank test, respectively). Conversely, the levels of endostatin, angiogenin and leptin were not different in CR patients compared to relapsed patients and did not correlate with EFS. Our data suggest that b-FGF and, particularly, VEGF might be considered prognostic factors in NHL staging and management.
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PMID:Angiogenic growth factors and endostatin in non-Hodgkin's lymphoma. 1084 4

INTRODUCTION: Angiogenesis is critical for tumour growth and dissenmination. Some angiogenic cytokines can be detected in the serum/plasma, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiogenin (ANG) and endostatin. VEGF, bFGF and ANG are pro-angiogenic cytokines implicated in tumour angiogenesis. Endostatin is antiangiogenic and arises from tumour-induced porteolysis. The purpose of this study was to ascertain whether there are differences between healthy controls and patients head and neck squamous cell carcinoma (HNSCC) for each cytokine; and whether there is any association with clinico-pathological variables or prognosis. METHODS: Serum/plasma was assayed by ELISA in the following numbers of patients and controls: serum VEGF (80 : 80); plasma VEGF (32 : 15); serum bFGF and ANG (25 : 15); and plasma endostatin (26:15). RESULTS: Serum VEGF is raised in patients with HNSCC (P < 0.001) but there were no associations with clinico-pathological variables or outcome. Serum VDGF correlated with platelet count (P = 0.05) and plasma VDGF (P = 0.02) although the latter is substantially lower (P < 0.001). bFGF and ANG were not raised in patients with HNSCC. Plasma endostatin was lower in patients with HNSCC than controls (P = - 0.02). However, with the HNSCC group endostatin was positively associated with disease recurrence (P = 0.008). CONCLUSIONS: These data suggest that plasma endostatin may be a clinically useful prognostic marker in patients with HNSCC. Serum VDGF arises from platelet aggregation and does not reflect tumour load, dissemination or prognosis. bFGF and ANG are not raised in patients with HNSCC.
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PMID:Angiogenic cytokines in serum and plasma of patients with head and neck squamous cell carcimona 1112 75

This pilot study investigated the potential use of three circulating angiogenesis-related cytokines, basic fibroblast growth factor (bFGF), angiogenin (ANG) and endostatin, as tumour markers and prognostic factors in patients with head and neck squamous cell carcinoma (HNSCC). A total of 30 patients with HNSCC treated with curative intent and 15 healthy controls were studied. Serum (bFGF and ANG) and plasma (endostatin) was assayed by enzyme-linked immunoabsorbance assay (ELISA). None of the cytokines was raised in HNSCC patients when compared with controls. Serum bFGF was not associated with any clinico-pathological or outcome parameters, although there was a trend towards higher levels in more advanced and aggressive tumours. Lower serum angiogenin (sANG) levels were associated with loco-regional disease recurrence (P = 0.036). Using a cut-off level of 400 pg/mL, a low level of sANG predicted tumour recurrence with a relative risk of 4.0 (95% CI: 0.7-24.0). Plasma endostatin was associated with higher histological grade (P = 0.01) and with both disease recurrence (P = 0.045) and death from disease (P = 0.021). Plasma endostatin above a cut-off point of 70 ng/mL could predict tumour recurrence with a relative risk of 4.7 (95% CI: 1.1-19.7). These data suggest that plasma endostatin and sANG have potential roles as prognostic factors and require further investigation.
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PMID:Circulating angiogenic cytokines as tumour markers and prognostic factors in head and neck squamous cell carcinoma. 1190 69

The process of new capillary formations from previously existing mature vessels in healthy individuals has been mainly studied during cycles of the female reproductive tract. This new capillary formation, known as angiogenesis is related to endogenous regulators that both stimulates or inhibits it. Knowledge on the role of both stimulators and inhibitors under physiological and pathological conditions accentuates a main role of VEGF, FGF, angiogenin and angiopoietics among the formers; and main role of angiostatin and endostatin among the latters. In recent years, angiogenesis in the ovaries that leads to follicular and luteal growth and development has been extensively studied. Whether a number of endogenous stimulators and inhibitors have been identified, the molecular link between the endocrine and vascular system is not fully understood. Therefore, efforts to formulate questions that need answers must be made.
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PMID:[Angiogenesis in reproductive physiology. Follicular development, formation and maintenance of the corpus luteum]. 1191 46

The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor microvessel density (MVD) have been evaluated and found to be of prognostic significance. Body fluid (particularly blood and urinary) testing for biomarkers is easily accessible and useful in clinical patients. The prognostic significance of circulating DNA in plasma or serum, and its genetic alterations in HCC are other important trends. More attention should be paid to these two areas in future. As the progress of the human genome project advances, so does a clearer understanding of tumor biology, and more and more new prognostic markers with high sensitivity and specificity will be found and used in clinical assays. However, the combination of some items, i.e., the pathological features and some biomarkers mentioned above, seems to be more practical for now.
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PMID:The prognostic molecular markers in hepatocellular carcinoma. 1204 56

Angiogenesis seems to be important both in the pathogenesis of acute myelogenous leukemia (AML) and for the susceptibility of AML blasts to chemotherapy. Recent clinical studies even suggest that antiangiogenic therapy can induce disease control in patients with AML relapse. In this context we have investigated the profile of the systemic component of angiogenic regulation in AML by characterizing the serum levels of (i) the angiogenic regulators angiogenin, basic fibroblast growth factor (bFGF) and endostatin; (ii) the endothelial cell marker soluble (s) E-selectin. Patients with untreated AML had increased levels of angiogenin, endostatin and sE-selectin, whereas the levels of bFGF were not significantly altered. The systemic levels of the proangiogenic bFGF, the antiangiogenic endostatin and the endothelial cell marker sE-selectin showed significant correlations, whereas angiogenin and sE-selectin levels were not correlated. Furthermore, intensive chemotherapy resulted in decreased systemic levels of the 2 proangiogenic mediators angiogenin and bFGF, whereas endostatin levels remained high after treatment. Although angiogenin normally is a part of the acute phase reaction, its systemic levels were not altered when patients with chemotherapy-induced cytopenia developed complicating bacterial infections. Our results suggest that intensive chemotherapy can modulate the systemic component of angiogenic regulation in AML patients.
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PMID:Serum levels of angiogenin, basic fibroblast growth factor and endostatin in patients receiving intensive chemotherapy for acute myelogenous leukemia. 1220 93

Angiogenesis seems to be important in the pathogenesis of acute myelogenous leukemia (AML). The endothelial cell proliferation and microvessel formation are regulated by a wide range of soluble mediators, including angiogenin, angiopoietin-2, basic fibroblast growth factors, vascular endothelial growth factor (VEGF), VEGF-D, angiostatin and endostatin. In the present study, it has been investigated whether these mediators have an additional direct effect on the proliferation and cytokine release by native human AML blasts. AML cells derived from a large group of consecutive patients were investigated. All these mediators could alter the proliferation and cytokine release [interleukin (IL) 1beta, IL6, IL8, tumor necrosis factor alpha] for a minority of patients. Alteration of spontaneous proliferation by at least one mediator was detected in five of 38 patients; whereas, altered cytokine (Flt3-ligand, granulocyte-macrophage colony-stimulating factor, stem cell factor)-dependant proliferation was observed for 10 patients. Growth enhancement was most frequently observed, whereas growth inhibition was uncommon. The effects on AML blast proliferation were often dependant on or were modulated by the presence of the three hematopoietic growth factors. Based on the present results, it is concluded that angioregulatory mediators have additional growth-enhancing effects directly on the AML blasts for certain patients. However, based on the results from this investigation and previous studies it is suggested that their major contribution to the pathogenesis of AML is through their effects on regulation of bone marrow angiogenesis, and future studies of these mediators in AML should probably focus on these effects.
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PMID:Effects of angiogenic regulators on in vitro proliferation and cytokine secretion by native human acute myelogenous leukemia blasts. 1280 Dec 93

The vascular system that ensures an adequate blood flow is required to provide the cells with sufficient supply of nutrients and oxygen. Two different mechanisms of the formation of new vessels can be distinguished: vasculogenesis, the formation of the first primitive vascular plexus de novo and angiogenesis, the formation of new vessels from preexisting ones. Both processes are regulated by a delicate balance of pro- and anti-angiogenic factors. Physiologically, angiostatic mediators outweigh the angiogenic molecules and angiogenesis does not occur. Under certain conditions such as tumor formation or wound healing, the positive regulators of angiogenesis predominate and the endothelium becomes activated. Angiogenesis is initiated by vasodilatation and an increased permeability. After destabilization of the vessel wall, endothelial cells proliferate, migrate and form a tube, which is finally stabilized by pericytes and smooth muscle cells. Numerous soluble growth factors and inhibitors, cytokines and proteases as well as extracellular matrix proteins and adhesion molecules strictly control this multi-step process. The properties and interactions of angiogenic molecules such as VEGFs, FGFs, angiopoietins, PDGF, angiogenin, angiotropin, HGF, CXC chemokines with ELR motif, PECAM-1, integrins and VE-cadherin as well as angiostatic key players such as angiostatin, endostatin, thrombospondin, CXC chemokines without ELR motif, PEDF are discussed in this review with respect to their molecular impact on angiogenesis.
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PMID:Angiogenic and angiostatic factors in the molecular control of angiogenesis. 1289 7

Vascular endothelial growth factor (VEGF), an established angiogenesis factor, is expressed in allografts undergoing rejection, but its function in the rejection process has not been defined. Here, we initially determined that VEGF is functional in the trafficking of human T cells into skin allografts in vivo in the humanized SCID mouse. In vitro, we found that VEGF enhanced endothelial cell expression of the chemokines monocyte chemoattractant protein 1 and IL-8, and in combination with IFN-gamma synergistically induced endothelial cell production of the potent T cell chemoattractant IFN-inducible protein-10 (IP-10). Treatment of BALB/c (H-2d) recipients of fully MHC-mismatched C57BL/6 (H-2b) donor hearts with anti-VEGF markedly inhibited T cell infiltration of allografts and acute rejection. Anti-VEGF failed to inhibit T cell activation responses in vivo, but inhibited intragraft expression of several endothelial cell adhesion molecules and chemokines, including IP-10. In addition, whereas VEGF expression was increased, neovascularization was not associated with acute rejection, and treatment of allograft recipients with the angiogenesis inhibitor endostatin failed to inhibit leukocyte infiltration of the grafts. Thus, VEGF appears to be functional in acute allograft rejection via its effects on leukocyte trafficking. Together, these observations provide mechanistic insight into the proinflammatory function of VEGF in immunity.
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PMID:Proinflammatory functions of vascular endothelial growth factor in alloimmunity. 1466 Jul 42


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