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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.

可溶性VEGF受体、sFlt 1和缺氧诱导因子（hypoxia inductible factor，HIF）是恶性胶质瘤抗血管生成治疗的关键分子。1. sFlt 1和HIF在胶质瘤组织中的作用：VEGF/sFlt 1比值大于1和HIF高表达是胶质瘤患者预后不良的因素。2. sFlt 1过表达的抗胶质瘤作用：sFlt 1基因转染U87人恶性胶质瘤细胞系后，肿瘤体积比对照组缩小30%。3. CPT-11的抗血管生成作用：CPT-11通过抑制胶质瘤细胞HIF和VEGF的表达，抑制内皮细胞增殖和管腔形成，具有较强的血管抑制作用。CPT-11用于胶质瘤生长的节拍时间表：低剂量（1 mg/kg）和长期（77天）给予CPT-11导致胶质瘤生长，这与中等剂量（40 mg/kg）和短期（10天）给药相似。JTT治疗不仅增强了荷瘤小鼠的免疫功能，而且抑制了血管生成。使用CPT-11的化疗通过抑制HIF和VEGF表达以及通过抑制内皮细胞增殖和管形成而对胶质瘤生长有效。sFlt 1和JTT也是胶质瘤血管抑制剂的候选者。