Vascular endothelial growth factor: basic science and clinical progress.
TLDR
Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen in vitro and an angiogenic inducer in a variety of in vivo models and is implicated in intraocular neovascularization associated with diabetic retinopathy and age-related macular degeneration.Abstract:
Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen in vitro and an angiogenic inducer in a variety of in vivo models. Hypoxia has been shown to be a major inducer of VEGF gene transcription. The tyrosine kinases Flt-1 (VEGFR-1) and Flk-1/KDR (VEGFR-2) are high-affinity VEGF receptors. The role of VEGF in developmental angiogenesis is emphasized by the finding that loss of a single VEGF allele results in defective vascularization and early embryonic lethality. VEGF is critical also for reproductive and bone angiogenesis. Substantial evidence also implicates VEGF as a mediator of pathological angiogenesis. In situ hybridization studies demonstrate expression of VEGF mRNA in the majority of human tumors. Anti-VEGF monoclonal antibodies and other VEGF inhibitors block the growth of several tumor cell lines in nude mice. Clinical trials with various VEGF inhibitors in a variety of malignancies are ongoing. Very recently, an anti-VEGF monoclonal antibody (bevacizumab; Avastin) has been approved by the Food and Drug Administration as a first-line treatment for metastatic colorectal cancer in combination with chemotherapy. Furthermore, VEGF is implicated in intraocular neovascularization associated with diabetic retinopathy and age-related macular degeneration.read more
Citations
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Ranibizumab for Neovascular Age-Related Macular Degeneration
Philip J. Rosenfeld,David M. Brown,Jeffrey S. Heier,David S. Boyer,Peter K. Kaiser,Carol Chung,Robert Y. Kim +6 more
TL;DR: Intravitreal administration of ranibizumab for 2 years prevented vision loss and improved mean visual acuity, with low rates of serious adverse events, in patients with minimally classic or occult (with no classic lesions) choroidal neovascularization secondary to age-related macular degeneration.
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Angiogenesis as a therapeutic target
TL;DR: Therapeutic angiogenesis (promoting new vessel growth to treat ischaemic disorders) is an exciting frontier of cardiovascular medicine, but further understanding of the mechanisms of vascular morphogenesis is needed first.
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Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer
TL;DR: The recent approval of bevacizumab by the US FDA as a first-line therapy for metastatic colorectal cancer validates the ideas that VEGF is a key mediator of tumour angiogenesis and that blockingAngiogenesis is an effective strategy to treat human cancer.
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Wound repair and regeneration: Mechanisms, signaling, and translation
TL;DR: In this review, emerging concepts in tissue regeneration and repair are highlighted, and some perspectives on how to translate current knowledge into viable clinical approaches for treating patients with wound-healing pathologies are provided.
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Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis
Mats Hellström,Li-Kun Phng,Jennifer J. Hofmann,Elisabet Wallgard,Leigh Coultas,Per Lindblom,Per Lindblom,Jackelyn A. Alva,Ann Katrin Nilsson,Linda Karlsson,Nicholas Gaiano,Keejung Yoon,Janet Rossant,M. Luisa Iruela-Arispe,Mattias Kalén,Holger Gerhardt,Christer Betsholtz +16 more
TL;DR: Evidence is presented that delta-like 4 (Dll4)–Notch1 signalling regulates the formation of appropriate numbers of tip cells to control vessel sprouting and branching in the mouse retina, and modulators of Dll4 or Notch signalling, such as γ-secretase inhibitors developed for Alzheimer's disease, might find usage as pharmacological regulators of angiogenesis.
References
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The biology of VEGF and its receptors.
TL;DR: Vascular endothelial growth factor (VEGF) is a key regulator of physiological angiogenesis during embryogenesis, skeletal growth and reproductive functions and is implicated in pathologicalAngiogenesis associated with tumors, intraocular neovascular disorders and other conditions.
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Takayuki Asahara,Toyoaki Murohara,Alison Sullivan,Marcy Silver,Rien van der Zee,Tong Li,Bernhard Witzenbichler,Gina C. Schatteman,Jeffrey M. Isner +8 more
TL;DR: It is suggested that EC progenitors may be useful for augmenting collateral vessel growth to ischemic tissues (therapeutic angiogenesis) and for delivering anti- or pro-angiogenic agents, respectively, to sites of pathologic or utilitarianAngiogenesis.
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Angiogenesis in cancer, vascular, rheumatoid and other disease
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