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Vascular endothelial growth factor A

About: Vascular endothelial growth factor A is a research topic. Over the lifetime, 15203 publications have been published within this topic receiving 1271498 citations. The topic is also known as: vascular endothelial growth factor A & vascular endothelial growth factor A165.


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Journal ArticleDOI
Napoleone Ferrara1
TL;DR: Strategies aimed at antagonizing VEGF may form the basis for an effective treatment of tumors and retinopathies, as V EGF-induced angiogenesis is sufficient to achieve a therapeutic endpoint in models of coronary or limb ischemia.
Abstract: Vascular endothelial growth factor (VEGF) is a diffusible endothelial cell-specific mitogen and angiogenic factor that can also increase vascular permeability. By alternative splicing of mRNA, VEGF may exist as one of four different isoforms that have similar biological activities but differ markedly in targeting and bioavailability. The VEGF receptors are specifically expressed in the cell surface of vascular endothelial cells. Recent studies point to VEGF as a major regulator of physiological angiogenesis, such as developmental and reproductive angiogenesis. Furthermore, VEGF appears to be a crucial mediator of blood vessel growth associated with tumors and proliferative retinopathies. The VEGF mRNA is up-regulated in the majority of human tumors and the VEGF protein is increased in the aqueous and vitreous humors of patients with proliferative retinopathies. Anti-VEGF antibodies have the ability to suppress the growth of a variety of tumor cell lines in nude mice and also can inhibit angiogenesis in animal models of intraocular neovascularization. Therefore, strategies aimed at antagonizing VEGF may form the basis for an effective treatment of tumors and retinopathies. Furthermore, VEGF-induced angiogenesis is sufficient to achieve a therapeutic endpoint in models of coronary or limb ischemia.

449 citations

Journal ArticleDOI
TL;DR: Angiogenesis is profoundly affected by several members of the FGF family and their four receptors, and indeed, supplementing the media of endothelial cell cultures with basic FGF (FGF2) and heparin is now well established as a means to obtain optimal growth, migration, and capillary morphogenesis.
Abstract: Without new blood vessels, neoplasms cannot expand beyond a few millimeters, the point at which the diffusion of nutrients and the disposal of waste products become rate-limiting. Regulation of angiogenesis thus must be controlled at multiple levels. For instance, the VEGF family of heparin-binding proteins and their primary receptors, VEGFR-1 and VEGFR-2 (KDR), products of the flt-1 and the flk-1 gene, respectively, are required for angioblast differentiation and vasculogenesis, and specific VEGF isoforms play distinct roles in promoting endothelial growth and migration during angiogenesis. In addition, angiogenesis is profoundly affected by several members of the FGF family and their four receptors, and indeed, supplementing the media of endothelial cell cultures with basic FGF (FGF2) and heparin is now well established as a means to obtain optimal growth, migration, and capillary morphogenesis. In addition to producing proangiogenic factors, tumor cells also directly or indirectly generate negative angiogenic stimuli. The ultimate growth rate of the tumors is thus a fine balance between positive and negative angiogenic cues.

448 citations

Journal ArticleDOI
TL;DR: In this article, the native soluble FLT-1 truncated VEGF receptor was used to inhibit tumor angiogenesis in the lungs of nude mice following i.v. injection and their growth as nodules from cells injected s.c. tumors.
Abstract: Vascular endothelial growth factor (VEGF) is a potent and selective vascular endothelial cell mitogen and angiogenic factor. VEGF expression is elevated in a wide variety of solid tumors and is thought to support their growth by enhancing tumor neovascularization. To block VEGF-dependent angiogenesis, tumor cells were transfected with cDNA encoding the native soluble FLT-1 (sFLT-1) truncated VEGF receptor which can function both by sequestering VEGF and, in a dominant negative fashion, by forming inactive heterodimers with membrane-spanning VEGF receptors. Transient transfection of HT-1080 human fibrosarcoma cells with a gene encoding sFLT-1 significantly inhibited their implantation and growth in the lungs of nude mice following i.v. injection and their growth as nodules from cells injected s.c. High sFLT-1 expressing stably transfected HT-1080 clones grew even slower as s.c. tumors. Finally, survival was significantly prolonged in mice injected intracranially with human glioblastoma cells stably transfected with the sflt-1 gene. The ability of sFLT-1 protein to inhibit tumor growth is presumably attributable to its paracrine inhibition of tumor angiogenesis in vivo, since it did not affect tumor cell mitogenesis in vitro. These results not only support VEGF receptors as antiangiogenic targets but also demonstrate that sflt-1 gene therapy might be a feasible approach for inhibiting tumor angiogenesis and growth.

448 citations

Journal Article
TL;DR: A novel function for the vascular endothelial growth factor (VEGF) in its ability to stimulate an autocrine signaling pathway in metastatic breast carcinoma cells that is essential for their survival is identified.
Abstract: We identify a novel function for the vascular endothelial growth factor (VEGF) in its ability to stimulate an autocrine signaling pathway in metastatic breast carcinoma cells that is essential for their survival. Suppression of VEGF expression in metastatic cells in vitro induced their apoptosis, in addition to inhibiting the constitutively elevated phosphatidylinositol 3'-kinase activity that is characteristic of these cells and important for their survival. Hypoxia enhanced the survival of metastatic cells by increasing VEGF expression. The importance of the VEGF receptor neuropilin was indicated by the ability of a neuropilin-binding VEGF isoform to enhance breast carcinoma survival. Moreover, the expression of neuropilin in neuropilin-deficient breast carcinoma cells protected them from apoptosis. The identification of this VEGF autocrine signaling pathway has important implications for tumor metastasis and therapeutic intervention.

448 citations

Journal ArticleDOI
01 Jan 2000-Blood
TL;DR: NO donors may up-regulate the activity of the human VEGF promoter in normoxic human glioblastoma and hepatoma cells independent of a cyclic guanosine monophosphate-mediated pathway and a difference in sensitivity to guanylate cyclase inhibitors and a different pattern of HIF-1 binding.

447 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202394
2022189
2021293
2020347
2019306
2018333