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Query: UMLS:C1519670 (tumor angiogenesis)
 6,052 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Physiologically, angiogenesis in adults is a controlled process which plays a role, for example, in wound healing. Pathological angiogenesis is observed in tumor formation and represents a multifactorial process, in which specific angiogenic factors, as well as growth factors, extracellular matrix proteins and cell adhesion molecules are involved. Tumor growth is characterized by an imbalance in favor of angiogenic over angiogenesis-inhibiting factors. Some of the most frequently examined angiogenic factors are vascular endothelial growth factor, acidic/basic fibroblast growth factors and the platelet-derived endothelial cell growth factor. The most important angiogenesis inhibitors are angiostatin and thrombospondin. To date, the clinical relevance of tumor angiogenesis has been shown for several human tumors. For most urological tumors, the grade of tumor vessel formation, measured as microvessel density, has been associated with metastases, tumor growth and clinical course. The prognostic value of this feature of malignant growth seems to be higher than that of most of the classical and newer prognostic factors. Systematic investigations of tumor angiogenesis are becoming increasingly relevant for diagnostic and therapeutic strategies and offer opportunities for the development of new specific therapeutic approaches in clinical oncology.
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PMID:[Angiogenesis--principles and significance in urologic tumors]. 899 26

The switch from a quiescent tumor to an invasive tumor is accompanied by the acquisition of angiogenic properties. This phenotypic change likely requires a change in the balance of angiogenic stimulators and angiogenic inhibitors. The nature of the angiogenic switch is not known. Here, we show that introduction of activated H-ras into immortalized endothelial cells is capable of activating the angiogenic switch. Angiogenic switching is accompanied by up-regulation of vascular endothelial growth factor and matrix metalloproteinase (MMP) bioactivity and downregulation of tissue inhibitor of MMP. Furthermore, we show that inhibition of phosphatidylinositol-3-kinase leads to partial inhibition of tumor angiogenesis, thus demonstrating that activated H-ras activates tumor angiogenesis through two distinct pathways. Finally, we show evidence for two forms of tumor dormancy.
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PMID:Oncogenic H-ras stimulates tumor angiogenesis by two distinct pathways. 902 47

Marked neovascularization is a hallmark of many neoplasms in the nervous system. Recent reports indicate that the endothelial mitogen vascular endothelial growth factor (VEGF) may play a critical role in the regulation of vascular endothelial proliferation in malignant gliomas. Using novel monoclonal antibodies to the VEGF polypeptide we have determined the expression and cellular distribution of VEGF protein in a representative series of 171 human central nervous system (CNS) tumors by immunohistochemistry and immunoblotting. In agreement with previous in situ hybridization data, 19 out of 20 glioblastomas (95%) showed immunoreactivity for VEGF, whereas both the percentage of immunoreactive tumors and the extent of immunoreactivity for VEGF were significantly lower in astrocytomas. Of the pilocytic astrocytomas (WHO grade I) 44% were immunoreactive for VEGF, but we observed several cases with pronounced vascular proliferates in the absence of VEGF. In ependymomas, meningiomas, hemangioblastomas, and primitive neuroectodermal tumors, there was no correlation between VEGF expression, vascular endothelial proliferation and the grade of malignancy. Oligodendrogliomas and the oligodendroglial component of mixed gliomas lacked immunoreactive VEGF, indicating that endothelial growth factors other than VEGF may regulate tumor angiogenesis in these neoplasms. Western blot analysis showed a predominant VEGF protein species of 23 kDa and confirmed the immunohistochemical data in all cases. Our findings demonstrate that VEGF is expressed in a wide spectrum of brain tumors in which it may induce neovascularization. However, other angiogenic factors also appear to contribute to the vascularization of CNS neoplasms.
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PMID:Expression and distribution of vascular endothelial growth factor protein in human brain tumors. 903 57

MRI enhanced with a macromolecular contrast medium (MMCM) has previously been shown to estimate tumor microvascular characteristics that correlate closely with histologic microvascular density, an established surrogate of tumor angiogenesis. A similar MMCM-enhanced MRI technique has now been used to investigate the acute tumor microvascular effects of antibody-mediated inhibition of vascular endothelial growth factor (VEGF), a well-studied and potent angiogenesis stimulator. Athymic rats xenografted with a human breast carcinoma (MDA-MB-435) were imaged after administration of albumin-gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA30) using a heavily T1-weighted three dimensional-spoiled gradient-refocused acquisition in a steady-state pulse sequence before and 24 hours after treatment with anti-VEGF antibody (single dose of 1 mg). Changes in longitudinal relaxivity (delta R1) were analyzed using a bidirectional two-compartment kinetic model to estimate tumor fractional blood volume (fBV) and permeability surface area product (PS). Data showed a significant decrease (P < 0.05) of tumor PS with respect to macromolecular contrast medium at 24 hours after treatment with anti-VEGF antibody. No significant change was observed in fBV. Suppression of tumor microvascular permeability induced by anti-VEGF antibody can be detected and quantified by MMCM-enhanced MRI. MRI grading of tumor angiogenesis and monitoring of anti-angiogenesis interventions could find wide clinical application.
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PMID:Assessing tumor angiogenesis using macromolecular MR imaging contrast media. 903 95

Vulvar intraepithelial neoplasia (VIN) has been reported to be a precursor of invasive vulvar cancer. Switching to the angiogenic phenotype is considered a key step in tumor growth. Microvessel density (MVD) and vascular endothelial growth factor (VEGF), a highly angiogenic peptide, are important parameters of tumor angiogenesis. Forty-three histologic slides with 38 VIN I-III lesions were immunohistochemically stained for factor VIII-related antigen (F8-RA) and 44 slides with 37 VIN I-III for VEGF, since F8-RA reliably highlights tumor microvessels. Determination of MVD and VEGF expression was done by counting microvessels and VEGF-positive cells at a magnification of 200x and 400x. The highest concentration of F8-RA-stained MVD and VEGF expression was found at a small subepithelial area at the border of the VIN lesion to the stroma underneath but concentrations were low in all specimens of normal epithelium. High VEGF expression was significantly correlated to high MVD. For both MVD and VEGF expression the differences between VIN I and VIN III and between VIN II and VIN III were statistically significant (P < 0.0001). VIN III lesions are the clinical relevant precursors of invasive cancer of the vulva, as outlined by intense expression of VEGF protein and a highly dense network of microvessels underlying the dysplastic epithelium.
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PMID:Angiogenesis in vulvar intraepithelial neoplasia. 906 59

Scatter factor (SF) (also known as hepatocyte growth factor) is a plasminogen-related growth factor that induces tumor cell motility, invasion, and angiogenesis. Its receptor is a tyrosine kinase encoded by c-met, a protooncogene. Human breast cancer cells express SF and c-met in vivo; but human breast cancer cell lines do not produce SF in vitro. To determine whether SF can modulate the in vivo growth of human breast cancers within a natural mammary environment, we studied the orthotopic growth of SF-transfected (SF+) versus control (SF-) clones of MDAMB231 human mammary carcinoma cells in the mammary fat pads of athymic nude mice. SF+ clones expressed SF mRNA and produced very high titers of SF protein, whereas SF- clones did not express SF mRNA or produce detectable SF protein. Two SF+ clones (21 and 29) showed significantly increased tumor growth rates, reaching 3- to 4-fold larger primary tumor volumes and weights by time of killing (p < 0.001), as well as higher rates of axillary lymph node metastasis (p < 0.02), as compared with two SF- clones (32 and 34). In contrast, in vitro proliferation rates, two-dimensional colony formation, and soft agar colony formation were no greater in SF+ than in SF- clones. We performed further studies to investigate the discrepancy between the in vivo and in vitro growth results. Tumor extracts from SF+ clone (21 + 29) tumors had 50-fold higher SF content than did SF- clone (32 + 34) tumors, confirming high-level SF expression in vivo in SF+ tumors. Immunostaining of tumor sections for proliferating cell nuclear antigen revealed only a modest increase in the proportion of cycling cells in SF+ versus SF- tumors (70% versus 60%, respectively). The terminal deoxytransferase-labeling index was equally low (approximately 1%) in SF+ and SF- tumors, suggesting that apoptosis was not responsible for the slower growth of SF- tumors. However, SF+ tumors had significantly higher tumor microvessel densities than SF- tumors (p < 0.001). Moreover, there were much higher titers of chemotactic activity for microvascular endothelial cells in cell-conditioned media and primary tumor extracts from SF+ clones as compared with SF- clones. As demonstrated using the rat cornea assay, there was more angiogenic activity in SF+ tumor extracts than in SF- extracts. The increased chemotactic and angiogenic activities in SF+ tumor extracts were not explained by secondary alterations in the content of the angiogenic mediator, vascular endothelial growth factor, or the antiangiogenic glycoprotein, thrombospondin-1; and those activities were neutralized using an anti-SF monoclonal antibody. These findings suggest that SF promotes the orthotopic growth of human breast cancers, at least in part, by stimulating tumor angiogenesis.
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PMID:Scatter factor stimulates tumor growth and tumor angiogenesis in human breast cancers in the mammary fat pads of nude mice. 912 Nov 17

Systemic administration of the nitric oxide (NO) synthase inhibitor Nomega-nitro--arginine methyl ester (L-NAME) to rabbits bearing a corneal implant blocked vascular endothelial growth factor (VEGF), but not basic fibroblast growth factor (bFGF)-induced angiogenesis. L-NAME completely blocked angiogenesis induced by VEGF-transfected MCF-7 breast carcinoma cells and the cells remained dormant in the cornea. Postcapillary endothelial cell migration and growth induced by VEGF were blocked by both the NO synthase inhibitor Nomega-mono-methyl--arginine and by the guanylate cyclase inhibitor LY 83583. We conclude that NO is a downstream imperative of VEGF-, but not bFGF-induced angiogenesis, and propose that the NO synthase/guanylate cyclase pathway is a potential target for controlling tumor angiogenesis in response to VEGF. Our studies support recent evidence that VEGF and bFGF induce angiogenesis by different mechanistic pathways using the alphavbeta5 and alphavbeta3 integrins, respectively.
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PMID:Nitric oxide synthase lies downstream from vascular endothelial growth factor-induced but not basic fibroblast growth factor-induced angiogenesis. 1130 96

Estrogens, which have been associated with several types of human and animal cancers, can induce tumor angiogenesis in the pituitary of Fischer 344 rats. The mechanistic details of tumor angiogenesis induction, during estrogen carcinogenesis, are still unknown. To elucidate the role of estrogen in the regulation of tumor angiogenesis in the pituitary of female rats, the density of blood vessels was analysed using factor VIII related antigen (FVIIIRAg) immunohistochemistry and the expression of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) was examined by Western blot and immunohistochemical analysis. The expression of VEGF receptor (VEGFR-2/Flk-1/KDR) was also examined by immunohistochemistry. The results demonstrated that 17beta-estradiol (E2) induces neovascularization, as well as the growth and enlargement of blood vessels after 7 days of exposure. The high tumor angiogenic potential was associated with an elevated VEGF/VPF protein expression in the E2 exposed pituitary of ovariectomized (OVEX) rats. VEGF/VPF and FVIIIRAg immunohistochemistry and endothelial specific lectin (UEA1) binding studies, indicate that the elevation of VEGF protein expression initially occurred in both blood vessels and non-endothelial cells. After 15 days of E2 exposure, VEGF/VPF protein expression, in the non-endothelial cell population, sharply declined and was restricted to the blood vessels. The function of non-endothelial-derived VEGF is not clear. Furthermore, immunohistochemical studies demonstrated that VEGFR-2 (flk-1/KDR), expression was elevated significantly in the endothelial cells of microblood vessels after 7 days of E2 exposure. These findings suggest that over expression of VEGF and its receptor (VEGFR-2) may play an important role in the initial step of the regulation of estrogen induced tumor angiogenesis in the rat pituitary.
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PMID:Over expression of vascular endothelial growth factor and its receptor during the development of estrogen-induced rat pituitary tumors may mediate estrogen-initiated tumor angiogenesis. 921 97

Tumor specimens from 84 patients with untreated epidermoid lung carcinomas were analysed immunohistochemically for the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), tumor cell proliferation (PCNA index) and tumor vascularity (vessel density). The purpose of this study was to find out whether differences in tumor cell proliferation and tumor vascularity might be associated with differential angiogenic growth factor expression. The present results indicate that the proliferation of the tumors is closely related to their expression of VEGF, but not for bFGF. The PCNA labelling index in VEGF positive tumors (VEGF+/bFGF- or VEGF+/bFGF+) was significantly higher than that in VEGF negative tumors (VEGF-/bFGF- or VEGF-/bFGF+; Wilcaxon rank sum test, p < 0.0001). To investigate whether VEGF or bFGF is involved in lung tumor angiogenesis, the data of VEGF and bFGF expression were correlated with vessel density. It was found that the expression of VEGF and bFGF were associated with increment of vessel density, however, vessel density was significantly increased only when VEGF and bFGF were coexpressed (p < 0.02). It is suggested that VEGF and bFGF might act cooperatively in the neovascularization of human epidermoid lung carcinomas.
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PMID:Coexpression of VEGF and bFGF in human epidermoid lung carcinoma is associated with increased vessel density. 921 96

Recent studies of tissue culture cells have defined a widespread system of oxygen-regulated gene expression based on the activation of a heterodimeric transcription factor termed hypoxia-inducible factor-1 (HIF-1). To determine whether the HIF-1 transcriptional response is activated within solid tumors and to define the consequences, we have studied tumor xenografts of a set of hepatoma (Hepa-1) cells that are wild type (wt), deficient (c4), and revertant (Rc4) for an obligatory component of the HIF-1 heterodimer, HIF-1beta. Because HIF-1beta is also essential for the xenobiotic response (in which it is termed the aryl hydrocarbon receptor nuclear translocator), we also studied c31 cells, which have a different defect in the xenobiotic response and form the HIF-1 complex normally. Two genes that show different degrees of HIF-1-dependent hypoxia-inducible expression in cell culture were selected for analysis-the glucose transporter, GLUT3, and vascular endothelial growth factor (VEGF). In situ hybridization showed intense focal induction of gene expression in tumors derived from wt, Rc4, and c31 cells, which was reduced (VEGF) or not seen (GLUT3) in those derived from c4 cells. In association with these changes, tumors of c4 cells had reduced vascularity and grew more slowly. These findings show that HIF-1 activation occurs in hypoxic regions of tumors and demonstrate a major influence on gene expression, tumor angiogenesis, and growth.
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PMID:Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. 922 22


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