OLIGONUCLEOTIDE MANIPULATION OF TUMOR CELL RADIORESISTANCE

放射治疗是癌症的一种重要治疗方式。然而，在这方面， 由于某些肿瘤对 电离辐射虽然不同的因素决定了细胞的反应， 辐射，这项研究将集中在产品的重要性， 人原癌基因c-raf-1（Raf-1）在体内外肿瘤中的作用 对伽马射线的反应我们之前已经证明了 反义raf oligo作为Raf-1序列特异性抑制剂的潜力 表达和活性，以及体外放射增敏剂。我们将 扩展这些观察结果，以进一步研究自由和 脂质体包裹的反义寡核苷酸（bFgf、ras、raf）作为序列- 基因表达的特异性抑制剂和作为放射增敏剂。在 此外，我们还将检验反义raf寡核苷酸 抑制Raf-1蛋白在体内的表达，并增强 实体瘤的放射治疗总体而言，这些研究应（i）产生 更好地理解反义核酸的放射增敏特性 raf寡核苷酸，首次在啮齿动物系统中，和（ii） 为未来的翻译提供先进的技术和科学基础 反义raf寡核苷酸的应用。

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.