title: Brain angiogenesis in developmental and pathological processes: therapeutic aspects of vascular endothelial growth factor.
abstract: The angiogenic process in the central nervous system (CNS) is basically regulated by typical angiogenic signaling systems such as vascular endothelial growth factor (VEGF)-VEGF receptors and angiopoietin-Tie receptors. In addition to regular endothelial-pericyte interaction, the CNS vasculature has a unique system of cell to cell communication between endothelial cells and astrocytes which is known as the blood-brain barrier. Among the pathological conditions of the CNS vascular network, stroke is a major disease in which the supply of blood is decreased. Pro-angiogenic therapy using natural VEGF-A has so far been unsuccessful, indicating the possible need for a new approach related to upstream or downstream regulators involved in the VEGF-signaling pathway, or alternate VEGF family members. By contrast, a pathological increase in the blood supply in the CNS is seen in brain tumors, in particular malignant gliomas. In phase II clinical trials, anti-VEGF therapies have been shown to suppress tumor growth and improve survival rates to some extent. However, tumor invasion and the distant metastasis of gliomas can occur following anti-angiogenic therapy. Further studies are needed to obtain safer clinical outcomes by developing new strategies with combination therapy using known anti-angiogenic drugs or by developing unique medicines specifically targeting the blood vessels in brain tumors.
authors: Department of Molecular Oncology, Tokyo Medical and Dental University, Japan. shibuya@ims.u-tokyo.ac.jp
authors: Masabumi
authors: M
authors: Shibuya
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000502:physiology*; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism; D002450:Cell Communication; D005910:Glioma / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D009046:Motor Neurons / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000502:physiology; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor