ASSAYS OF TUMOR RESPONSE TO RADIOTHERAPY

肿瘤对放射治疗的反应分析

• 批准号: 3184084
• 负责人: RALPH R WEICHSELBAUM
• 金额: $ 23.45万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3184084
• 关键词: DNA repair; NAD nucleosidase; X ray; bioassay; biopsy; carcinoma; complementary DNA; cytogenetics; genetic mapping; head /neck neoplasm; human subject; human therapy evaluation; ionizing radiation; molecular genetics; molecular oncology; neoplasm /cancer radiation therapy; nucleic acid probes; radiation genetics; radiation protection; radiation recovery; radiation sensitivity; radiation therapy dosage; sarcoma; tissue /cell culture

Radiotherapy is an important component of modern cancer treatment. Identification of patients most likely to benefit from treatment with ionizing radiation might improve the therapeutic ratio. We propose to continue to investigate the hypothesis that the presence of radioresistant and/or repair proficient cells in human tumors predicts radiotherapy failure. Therefore, we will establish early-passage cultures of human tumor cell lines from biopsies of head-and-neck carcinomas and soft-tissue sarcomas derived from patients prior to radiotherapy. We will then study the radiosensitivity and repair of radiation damage in these human tumor cells and correlate our in vitro findings with radiocurability measured in terms of local control and total survival. Our studies will include: 1) determination of D0, n, D derived from survival at doses of 100-1100 cGy (3 logs cell kill), survival at 200 cGy; 2) measurement of sublethal damage repair (SLDR) in exponentially-growing cultures of these early-passage tumor cells; determination of the repair of potentially lethal damage (PLDR) employing PLDR survival curves (100-1100 cGy) at 0 and 24 hrs. PLDR time and time course PLDR experiments following a single dose and subculture at various time points from plateau phase cultures; 3) measurement of the induction and rejoining of DNA double-strand breaks in first-passage, exponentially-growing cultures of human head-and-neck and soft-tissue sarcoma cell lines. The radiobiological parameter(s) that is(are) the biological basis of radiotherapy failure or success and predicts clinical outcome may emerge from our investigation.

放射治疗是现代癌症治疗的重要组成部分。 确定最有可能从以下治疗中获益的患者： 电离辐射可提高治愈率。 我们建议 继续研究这种假设， 和/或修复熟练的细胞在人类肿瘤预测放疗 失败 因此，我们将建立早期传代培养的人 来自头颈癌和软组织活检的肿瘤细胞系 来源于放疗前患者的肉瘤。 然后我们将研究 这些肿瘤放射敏感性和放射损伤修复 细胞，并将我们的体外研究结果与 局部控制和总生存期。 我们的研究将包括：1） 确定100-1100 cGy剂量下存活率的D 0、n、D（3 logs细胞杀伤），在200 cGy下存活; 2）亚致死损伤的测量 修复（SLDR）在这些早期传代的指数生长培养物中 肿瘤细胞.潜在致死性损伤修复的测定 在0和24小时使用PLDR存活曲线（100-1100 cGy）的PLDR。 PLDR 单剂量后的时间和时间过程PLDR实验， 从平台期培养物在不同时间点传代培养; 3） DNA双链断裂的诱导和重新连接的测量 第一代，指数增长的人类头颈部和 软组织肉瘤细胞系。 放射生物学参数， 是放射治疗失败或成功的生物学基础， 预测临床结果可能会出现从我们的调查。