Anti-angiogenic therapy for malignant gliomas using hypoxia-responsive soluble VEGF receptor

使用缺氧反应性可溶性 VEGF 受体对恶性胶质瘤进行抗血管生成治疗

基本信息

批准号：
14571299
负责人：
TAKANO Shingo
金额：
$ 1.86万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571299/
关键词：
glioma VEGF hypoxia inducible factor angiogenesis CPT-11 metronomic chemotherapy soluble VEGF receptor Juzen Taiho To グリオーマ VEGF 血管新生十全大補湯可溶性VEGFレセプター分子標的治療 angiopietin

项目摘要

Soluble form of VEGF receptor, sFlt1 and hypoxia indutible factor(HIF) were focused on the key molecules of antiangiogenic therapy for malignant gliomas.1.The role of sFlt1 and HIF in glioma tissues : The VEGF/sFlt1 ration over than 1 and high expression of HIF were bad prognostic factors in the patients with gliomas.2.Anti-glioma effect of over expression of sFlt1 : sFlt1 gene transfection into U87 human malignant glioma cell lines resulted in 30% decrease of tumor volume compared to control.3.Anti-angiogenic effect of CPT-11 : CPT-11 had potent angiosuppressive agent by inhibiting HIF and VEGF expression of glioma cells and inhibiting endothelial cell proliferation and tube formation.4.The effect of metronomic schedule of CPT-11 for glioma growth : Low dose (1mg/kg) and long term (77 days) administration of CPT-11 resulted in glioma growth which was similar to moderate dose (40mg/kg) and short term (10 days) administration without systemic side effect.5.JTT treatment caused to not only enhance immune function but also inhibit angiogenesis in mouse bearing glioma.Metronomic chemotherapy using CPT-11 is effective for glioma growth by inhibiting HIF and VEGF expression and by inhibiting endothelial cell proliferation and tube formation. sFlt1 and JTT are also candidates as angiosuppressive agent for glioma.

VEGF受体，SFLT1和低氧原谅因子（HIF）的可溶形式集中在恶性神经膜瘤的抗血管生成疗法的关键分子上。1。SFLT1和HIF在神经膜瘤组织中的作用：VEGFF/SFEGF/SFLT1的作用超过1和高度表达。胶质瘤患者的HIF是不良的预后因素。2。sflt1：Sflt1基因转染到U87人类恶性神经胶质瘤细胞系的抗糖瘤作用，与对照相比导致肿瘤量减少30％。 CPT-11：CPT-11的血管生成作用通过抑制胶质瘤细胞的HIF和VEGF表达并抑制内皮细胞增殖和管形成具有有效的血管抑制剂。 1mg/kg）和长期（77天）给药CPT-11导致神经胶质瘤的生长，类似于中等剂量（40mg/kg）和短期（10天）给药而没有全身副作用。5.JTT治疗。不仅可以增强免疫功能，而且还抑制了使用CPT-11的水合化疗中的小鼠轴承化学疗法，通过抑制HIF和VEGF表达并抑制内皮细胞增殖和管形成，对神经胶质瘤生长有效。 SFLT1和JTT也是候选人作为神经胶质瘤的血管抑制剂。