TAILIEUCHUNG - Báo cáo khoa học: Brain angiogenesis in developmental and pathological processes: therapeutic aspects of vascular endothelial growth factor

The angiogenic process in the central nervous system (CNS) is basically regulated by typical angiogenic signaling systems such as vascular endothe-lial growth factor (VEGF)–VEGF receptors and angiopoietin–Tie recep-tors. 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. | MINIREVIEW Brain angiogenesis in developmental and pathological processes therapeutic aspects of vascular endothelial growth factor Masabumi Shibuya1 2 1 Department of Molecular Oncology Tokyo Medicaland DentalUniversity Japan 2 Jobu University Takasaki Japan Keywords macrophage malignant glioma motor neuron tumor angiogenesis vascular hyperpermeability VEGF-A VEGF-B VEGF-E VEGFR-1 VEGFR-2 Correspondence M. Shibuya Department of Molecular Oncology Tokyo Medicaland Dental University 1-5-45 Yushima Bunkyo-ku Tokyo 113-8519 Japan Fax 81 3 5803 0125 Tel 81 3 5803 5086 E-mail shibuya@ Received 19 February 2009 revised 26 May 2009 accepted 15 June 2009 doi 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 .

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