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Proc Am Assoc Cancer Res ; 40 : 68a. Inhibitors of protein kinases: CGP , a protein kinase inhibitor with potential as an anticancer agent. This Article doi: Services E-mail this article to a colleague Alert me when this article is cited Alert me if a correction is posted Alert me when eletters are published Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager.
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The activation of VEGF receptors is considered one of the most critical events in angiogenesis 3. VEGF has activity in diverse cell types, such as muscle 4 and neuronal cells 5 , however its main actions are on endothelial cells 6.
Family members play key roles in orchestrating the formation of new blood vessels, such as induction of gene expression, regulation of vascular permeability, and promotion of cell migration, proliferation and survival. As a consequence, disruption of VEGF pathways in mice increases embryonic lethality due to circulatory problems 8.
Expression of VEGF decreases significantly after birth. However, localized levels can be up-regulated in tissues undergoing wound healing or fracture repair 2.
Recent studies have emphasized the role VEGF plays in pathological conditions involving the formation of new blood vessels, such as cancer, rheumatoid arthritis and age-related macular degeneration 3 ,9, Once the angiogenic switch is induced to promote the formation of new blood vessels, a complex and highly regulated sequence of events takes place. By activating multiple proteases, this pathway promotes the degradation of the basement membrane surrounding the existing vessel. This is followed by increased proliferation of endothelial cells, the formation of a lumen and a new basement membrane, and the fusion of newly formed vessels 2.