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

VEGF 受体或炎症细胞因子参与肿瘤血管生成作为癌症治疗

基本信息

批准号：
10557014
负责人：
ONO Mayumi
金额：
$ 4.48万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

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.

血管生成与肿瘤，糖尿病性视网膜病和类风湿关节炎等身体状况密切相关。为了了解这些血管生成疾病中产生的分子机制导致了一种新的疗法。A）血管生成是宿主中环境刺激和基质细胞的串扰中的一个复杂过程。据观察，单核细胞/巨噬细胞的浸润与肿瘤血管生成状态密切相关。我们发现1）巨噬细胞的浸润与人黑色素瘤中的恶性肿瘤和微血管密度密切相关； 2）浸润的巨噬细胞表达胸苷磷酸化酶（TP）和血红素氧酶-1（HO-1），这可能是肿瘤浸润巨噬细胞的生物标记； 3）在糖尿病性视网膜病患者中，最有效地，在TP基因启动子区域中，TP通过气体元件在TP区域中表达TP的各种细胞因子干扰素-γ（IFN-γ），我们发现VEGF围绕残留视频的表达增加，而高级糖化最终产物的积累（AGES）。我们观察到，年龄是VEGF表达的主要刺激，糖症控制剂可以通过抑制糖尿病眼睛中残留的内皮细胞的信号传导转导的信号传导来减少新血管形成的发生。吸收破骨细胞。我们发现血管生成抑制剂可预防实验性关节炎的骨骼和关节破坏。血管生成抑制剂可能是RA治疗的新策略之一。