Study of anti-angiogenesis enhanced radiotherapy

抗血管生成强化放射治疗的研究

• 批准号: 7215160
• 负责人: Robert James Griffin
• 金额: $ 21.94万
• 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/7215160
• 关键词: Adverse effects; Affect; Angiogenesis Inhibitors; Angiogenic Peptides; Angiostatins; Animals; Binding; Blood Vessels; Cancer Model; Cell physiology; Characteristics; Clinical Trials; Combined Modality Therapy; Data; Dose; Endothelial Cells; Endothelium; Fractionation; Future; Goals; Human; Individual; Institution; Lead; Mediating; Methods; Minnesota; Modeling; Modification; Molecular and Cellular Biology; Mus; Neoplasm Metastasis; Normal tissue morphology; Peptides; Physiology; Primary Neoplasm; Principal Investigator; Process; Production; Property; Radiation; Radiation Tolerance; Radiation therapy; Radiobiology; Radiosensitization; Research; Residual state; Role; Schedule; Solid Neoplasm; Stem cells; Testing; Therapeutic; Time; Universities; Work; antiangiogenesis therapy; base; beta pleated sheet; cancer therapy; design; experience; improved; innovation; novel; progenitor; radiation effect; research clinical testing; response; size; success; synergism; theories; therapeutic angiogenesis; tumor; tumor growth; tumor xenograft

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）：需要互补的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。从理论上讲，放射治疗和抗血管生成疗法的结合完全满足了这些要求。我们使用有效的抗血管生成设计的肽Anginex拥有初步数据，表明优先的肿瘤结合，肿瘤生长抑制和协同抗肿瘤作用，与放射疗法相等或更好地等于或更好的是Angiostatin或SUGEN或SUGEN 6668，以及针对我们的肿瘤模型的放射线。 Anginex是在明尼苏达大学开发的33-mer的无毒且稳定的β-元折叠。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，从而通过修饰现有的肿瘤生理学或肿瘤内皮放射线敏感性来影响辐射疗法的成功。因此，使用Anginex来增强辐射反应是一种理性且谨慎的方法，可以开发出更好的癌症治疗方法。该项目旨在最大程度地了解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。这项工作的三个特定目的将（1）扩展我们最初的观察结果，即延迟肿瘤的生长障碍，并随着Anginex的应用增强辐射反应（2）评估anginex结合的机制，肿瘤 - 内皮和Anginex对anginex祖细胞的影响（3）对循环的影响（3）对循环的作用（3），这是循环的作用（3）在分馏过程中。在这项研究中获得的信息将是大型动物和人类临床试验设计和实施的重要组成部分。