Involvement of VEGF receptors or inflammatory cytokines in tumor angiogenesis as a cancer therapy

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Angiogenesis is closely associated with physiolocical condition such as tumor, diabetic retinopathy and rheumatoid arthritis. To understand the molecular mechanism invoived in these angiogenesis disease leads to a new therapy.A) Angiogenesis is a complex process in cross-talks with environmental stimuli and stroma cells in host. It was observed that infiltration of monocytes/macrophages are closely associated with tumor angiogenesis status. We found that 1) infiltration of macrophages was closely associated with malignancy and microvessel density in human melanoma ; 2) infiltrated macrophage express thymidine phosphorylase (TP) and heme oxygenase-1 (HO-1), which could be the biological markers of tumor infiltrating macrophage ; 3) of various cytokines interferon-γ(IFN-γ) most effectively the expression of TP through GAS element in the promoter region of TP gene.B) In patients with diabetic retinopathy, we have found increased expression of VEGF around retinal vessels and accumulation of advanced glycation end products (AGES). We observed that AGES were the major stimulus for expression of VEGF and that glycemic control agents could reduce the incidence of neovascularization through inhibition of signaling transduction of retinal endothelial cells in diabetic eyes.C) Rheumatoid arthritis (RA) is an arthritic disease characterized by extensive neovascularization in synovial tissue leading to pannus formation with large number of newly-formed blood vessels and bone resorbing osteoclasts. We found that angiogenesis inhibitor prevented bone and joint destruction in experimental arthritis. Angiogenesis inhibitor might be one of the new strategy for treatment of RA.