OLIGONUCLEOTIDE MANIPULATION OF TUMOR CELL RADIORESISTANCE

寡核苷酸调控肿瘤细胞辐射抗性

• 批准号: 6334986
• 负责人: Usha N. Kasid
• 金额: $ 34.88万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6334986
• 关键词: SDS polyacrylamide gel electrophoresis; antisense nucleic acid; athymic mouse; autoradiography; cell cycle; cell line; cellular oncology; confocal scanning microscopy; densitometry; flow cytometry; gamma radiation; gene expression; genetic manipulation; genetic regulation; genetic strain; neoplasm /cancer pharmacology; neoplasm /cancer radiation therapy; neoplastic cell; oligonucleotides; pharmacokinetics; protooncogene; radiation resistance; radiosensitizer

Radiation Therapy is an important treatment modality of cancer. However, its effectiveness is limited due to the resistance of certain tumors to ionizing radiation. Although diverse factors dictate the cellular response to radiation, this study will focus on the importance of the product of the human proto-oncogene c-raf-1 (Raf-1) in the in vitro and in vivo tumor responses to gamma radiation. We have previously demonstrated the potential of antisense raf oligo as a sequence-specific inhibitor of Raf-1 expression and activity, as well as in vitro radiosensitizer. We will extend these observations to further investigate the potential of free and liposome-encapsulated antisense oligos (bFgf, ras, raf) as sequence- specific inhibitors of gene expression and as radiosensitizers. In addition, we will test the hypothesis that antisense raf oligonucleotide inhibits Raf-1 protein expression in vivo, and enhances the response of solid tumors to radiation. Overall, these studies should (i) generate a better understanding of the novel radiosensitizing property of antisense raf oligonucleotide, for the first time in a rodent system, and (ii) advance technological and scientific bases for the future translational application of antisense raf oligonucleotide.

放射疗法是癌症的重要治疗方式。然而， 由于某些肿瘤对 电离辐射。尽管各种因素决定了细胞反应 在辐射中，这项研究将重点介绍 体外和体内肿瘤中的人类原始癌基因C-RAF-1（RAF-1） 对伽马辐射的反应。我们以前已经证明了 反义RAF寡核作为RAF-1的序列特异性抑制剂的潜力 表达和活性以及体外放射敏剂。我们将 扩展这些观察结果，以进一步研究自由的潜力和 脂质体封装的反义寡寡寡做（BFGF，RAS，RAF）作为序列 - 基因表达的特定抑制剂和作为放射激素的抑制剂。在 此外，我们还将检验反义RAF寡核苷酸的假设 抑制RAF-1蛋白在体内的表达，并增强 实体瘤辐射。总体而言，这些研究应（i）产生 更好地理解反义的新型放射敏化特性 RAF寡核苷酸，第一次在啮齿动物系统中，（ii） 未来翻译的高级技术和科学基础 反义RAF寡核苷酸的应用。