Study of anti-angiogenesis enhanced radiotherapy

抗血管生成强化放射治疗的研究

• 批准号: 7350616
• 负责人: Robert James Griffin
• 金额: $ 14.97万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7350616
• 关键词: angiogenesis; angiogenesis inhibitors; antineoplastics; clinical research; combination cancer therapy; host neoplasm interaction; human subject; laboratory mouse; neoplasm /cancer blood supply; neoplasm /cancer radiation therapy; neoplastic growth; nonhuman therapy evaluation; radiation sensitivity

DESCRIPTION (provided by applicant): Complementary therapeutic strategies are required to destroy solid tumors and inhibit regrowth of metastatic or residual primary tumor. In theory, the combination of radiation therapy and antiangiogenesis therapy fully meet these requirements. We have preliminary data using a potent antiangiogenic designed peptide, Anginex, indicating preferential tumor binding, tumor growth inhibition and synergistic anti-tumor effects in combination with radiotherapy equal or better than angiostatin or Sugen 6668 and radiation against our tumor models. Anginex is a non-toxic and stable beta-sheet forming 33-mer, developed at the University of Minnesota. We, and others, have recently demonstrated the potential of various anti-vascular or anti-angiogenic compounds to impact the success of radiation therapy via a modification of the existing tumor physiology or tumor endothelial radiosensitivity. Therefore, the use of Anginex to enhance radiation response represents a rational and prudent approach to develop better methods of cancer therapy. This project aims to maximize our understanding of the effects of Anginex on tumor physiology and radiation response and the influence of circulating endothelial cells on these processes. The three specific aims of this work will (1) expand our initial observations that tumor growth is retarded and radiation response in enhanced with the application of Anginex (2) assess the mechanism of Anginex binding and radiosensitization of tumor-endothelium and anginex effect on endothelial progenitor cells (3) Elucidate the effects of anginex treatment and fractionated radiotherapy on one another and on the role of circulating endothelial cells during fractionated treatment. The information to be obtained in this study will be a vital part of design and implementation of large animal and human clinical trials.

描述（由申请人提供）：需要补充治疗策略来破坏实体瘤并抑制转移性或残留原发性肿瘤的再生长。从理论上讲，放射治疗和抗血管生成治疗的组合完全满足这些要求。我们有初步的数据，使用一种有效的抗血管生成设计的肽，Anginex，表明优先的肿瘤结合，肿瘤生长抑制和协同抗肿瘤作用与放射治疗的组合等于或优于血管抑素或Sugen 6668和辐射对我们的肿瘤模型。Anginex是一种无毒且稳定的β-折叠形成33-mer，由明尼苏达大学开发。我们和其他人最近已经证明了各种抗血管或抗血管生成化合物通过改变现有肿瘤生理学或肿瘤内皮放射敏感性来影响放射治疗成功的潜力。因此，使用Anginex来增强辐射反应代表了开发更好的癌症治疗方法的合理和谨慎的方法。该项目旨在最大限度地了解Anginex对肿瘤生理学和辐射反应的影响以及循环内皮细胞对这些过程的影响。本工作的三个具体目标是：（1）扩大我们的初步观察，即应用Anginex可延缓肿瘤生长并增强辐射反应;（2）评估Anginex结合肿瘤内皮细胞的放射增敏机制以及Anginex对内皮祖细胞的影响;（3）阐明anginex治疗和分次放疗对彼此的影响以及对分次治疗期间循环内皮细胞的作用。本研究中获得的信息将是大型动物和人体临床试验设计和实施的重要组成部分。