伊曲康唑对婴幼儿血管瘤增殖和血管生成的作用及其分子机制研究

项目名称： 伊曲康唑对婴幼儿血管瘤增殖和血管生成的作用及其分子机制研究

项目编号： No.81472539

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 冉玉平

作者单位： 四川大学

项目金额： 80万元

中文摘要： 血管瘤是婴幼儿最常见肿瘤，治疗具挑战性。伊曲康唑在治疗和预防婴幼儿真菌病有效且安全。研究表明伊曲康唑能抑制血管生成和肿瘤生长。我们在临床上发现伊曲康唑对婴幼儿血管瘤有效；体外实验证实对血管瘤内皮细胞的增殖和血管生成也有抑制作用；将伊曲康唑与血管瘤内皮细胞作用后提取RNA做基因芯片分析筛选出能抑制血管瘤增殖和血管生成相关的候选蛋白DDIT4L、ADM2、HDAC9。以DDIT4L为例，本课题拟体内外实验解决以下科学问题：1）进一步明确伊曲康唑对婴幼儿血管瘤内皮细胞增殖和血管生成的作用；2）筛选并验证与血管瘤增殖和血管生成相关的关键调控蛋白DDIT4L；3）明确DDIT4L在伊曲康唑抑制血管瘤增殖和血管生成过程中的调控作用；4）研究DDIT4L在伊曲康唑抑制血管瘤增殖和血管生成过程中的作用机制及关键效应分子；5）从组织病理学角度探讨DDIT4L表达水平与血管瘤增殖和血管生成相关性。

中文关键词： C25_其它肿瘤；信号通路；血管瘤；伊曲康唑

英文摘要： Hemangioma, the most common tumor for infants, can present as a therapeutic challenge to the clinicians. Itraconazole is effective and safe in the treatment and prevention of fungal disease in infants. We occasionally found that itraconazole have a therapeutic effect for infantile hemangiomas accompanied with Candia albicans infection in the clinical, and later successfully repeated full therapeutic course in another 5 cases of infantile hemangiomas. We also found that itraconazole inhibits vascular endothelial cell proliferation and angiogenesis of infantile hemangiomas in vitro. The RNA was extracted to do microarray after itraconazole treated hemangioma endothelial cells, by which we selected a group of candidate proteins, DDIT4L, ADM2 and HDAC9, closely associated with vascular proliferation and tumor angiogenesis. Taking DDIT4L as a key regulatory protein for example, this study intends to use cell culture and animal models to address the following scientific queries: 1) Further clarifying the effects of itraconazole on cell proliferation and angiogenesis in infantile hemangioma; 2) Screening and verification of a key regulatory protein DDIT4L related with hemangioma proliferation and angiogenesis; 3) Regulatory role of protein DDIT4L in itraconazole inhibiting vascular proliferation and tumor angiogenesis of hemangioma; 4) Mechanism and key effector molecules of protein DDIT4L in itraconazole inhibiting vascular proliferation and tumor angiogenesis of hemangioma； 5） Investigating correlations between protein DDIT4L and tumor vascular proliferation and angiogenesis of hemangioma from the perspective of histopathology.

英文关键词： itraconazole;hemangiomas;infants