PRECLINICAL EVALUATION OF INTERMEDIATE ENDPOINTS

中间终点的临床前评估

• 批准号: 6356785
• 负责人: MING YOU
• 金额: $ 24.27万
• 依托单位: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2001-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6356785
• 关键词: angiogenesis; biomarker; cancer prevention; chemoprevention; diagnosis design /evaluation; diagnostic tests; disease /disorder model; gene expression; ischemia; laboratory mouse; neoplasm /cancer blood supply; neoplasm /cancer diagnosis; neoplastic process; polymerase chain reaction; proliferative vitreoretinopathy; technology /technique development

An experimental model of proliferative retinopathy produced in response to ischemia-induced retinal neovascularization in mice (Smith et al, 1994) lends itself as an ideal system in which to quantitate angiogenesis. The system is well characterized and highly reproducible generating a quantifiable neovascular response in 100% of animals (Pierce et al, 1995). It has been shown that VEGF expression is upregulated during retinal neovascularization and that its inhibition by VEGF antagonists leads to suppression of ischemia-induced neovascularization (Aiello et al, 1995). Besides VEGF, this model system can also be used to measure the levels of expression of several genes such as VEGF, VEGFR, Tie 2, E-Selectin, Collagen IV, and AC133 etc, which are known to be upregulated during angiogenesis and play an essential role during various phases of angiogenesis in multiple cancers. A quantitative RT-PCR model is being standardized and tested to measure the angiogenic response . The goal of the study is to develop a molecular technique(s) to quantitate angiogenesis, which is highly sensitive and less labor-intensive than the existing biological assays or staining procedures and can be used to monitor angiogenic changes in early neoplastic lesions. This project is a) developing a quantitative angiogenesis assay in the mouse model of proliferative retinopathy and b) validating its sensitivity and usefulness in human tumor model system(s) as well as in clinical specimens.

增殖性视网膜病变的实验模型， 对缺血诱导的小鼠视网膜新生血管的反应 （Smith等人，1994）是一个理想的系统， 定量血管生成。 该系统具有良好的特性， 可重现，100%产生可量化的新生血管反应 （Pierce et al，1995）。 研究表明，VEGF 在视网膜新生血管形成过程中表达上调， VEGF拮抗剂对其的抑制导致 缺血诱导的新血管形成（Aiello等，1995）。 除了 VEGF，该模型系统也可用于测量 几种基因如VEGF、VEGFR、Tie 2、E-选择素、 胶原蛋白IV和AC 133等，已知其在哺乳动物中上调。 血管生成，并发挥重要作用，在各个阶段， 多种癌症中的血管生成。 定量RT-PCR模型是 被标准化和测试以测量血管生成反应。 这项研究的目标是开发一种分子技术， 定量血管生成，这是高度敏感， 比现有的生物测定或染色更劳动密集 并且可以用于监测早期的血管生成变化。 肿瘤性病变 该项目是a）开发一个定量的 增殖性视网膜病小鼠模型中的血管生成测定 和B）验证其在人肿瘤模型中的灵敏度和有用性 系统以及临床标本中。