Study of anti-angiogenesis enhanced radiotherapy

描述(由申请人提供)：需要补充治疗策略来摧毁实体肿瘤并抑制转移或残留原发肿瘤的再生长。从理论上讲，放射治疗和抗血管生成治疗的结合完全符合这些要求。我们使用一种有效的抗血管生成设计的多肽Anginex获得了初步数据，表明肿瘤优先结合、抑制肿瘤生长和协同抗肿瘤效果与放射治疗相当或优于Angiostatin或SUGEN 6668和放射治疗我们的肿瘤模型。Anginex是明尼苏达大学开发的一种形成33-聚体的无毒和稳定的β-折叠。我们和其他人最近证明了各种抗血管或抗血管生成化合物的潜力，通过改变现有的肿瘤生理学或肿瘤内皮放射敏感性来影响放射治疗的成功。因此，使用Anginex来增强辐射反应是开发更好的癌症治疗方法的一种理性和谨慎的方法。该项目旨在最大限度地了解Anginex对肿瘤生理和辐射反应的影响，以及循环内皮细胞对这些过程的影响。这项工作的三个具体目标将(1)扩大我们的初步观察，即应用Anginex可以延缓肿瘤生长并增强放射反应(2)评估Anginex与肿瘤-内皮细胞的结合和放射增敏的机制以及Anginex对内皮祖细胞的影响(3)阐明Anginex治疗和分次放疗相互之间的影响以及循环内皮细胞在分次治疗中的作用。这项研究将获得的信息将是设计和实施大型动物和人类临床试验的重要部分。

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.