ASSAYS OF TUMOR RESPONSE TO RADIOTHERAPY

放射治疗是现代癌症治疗的核心组成部分。 确定最可能从以下治疗中受益的患者 电离辐射将极大地提高个人治疗的成功率。 我们建议调查这样一种假设，即 人类肿瘤中辐射抵抗或修复熟练的细胞预测 放射治疗失败。因此，我们将建立早传文化 放射治疗前患者来源的肿瘤细胞的研究 人肿瘤放射敏感性及放射损伤的修复 细胞。我们的研究将包括：1)D-O，N-和 这些肿瘤指数培养物中亚致死性X射线损伤的修复 细胞；2)确定潜在致命性损伤的修复 平台期培养；3)DNA诱导和修复的测量 DNA洗脱和染色体畸变法测定DNA链断裂 指数期和平台期培养；4)多聚体的测量 (ADP-核糖)活性和烟酰胺腺嘌呤二核苷酸(NAD)含量 在照射前后肿瘤细胞中的指数和 平台期培养。这些细胞、染色体和生化分析 将与患者的预后相关，通过局部控制进行评估 以及患者的总生存时间和无病间隔 放射治疗。预计这些生物检测中的一种或多种 将预测接受放射治疗的患者的放射治疗能力。

Radiotherapy is a central component of modern cancer treatment. Identification of patients most likely to benefit from treatment with ionizing radiation would greatly improve individual therapeutic success. We propose to investigate the hypothesis that the presence of radioresistant or repair-proficient cells in human tumors predicts radiotherapy failure. Therefore, we will establish early-passage cultures of human tumor cells derived from patients prior to radiotherapy and study the radiosensitivity and repair of radiation damage in these human tumor cells. Our studies will include: 1) determination of D-o, n- and the repair of sublethal x-ray damage in exponential cultures of these tumor cells; 2) determination of the repair of potentially lethal damage in plateau-phase cultures; 3) measurement of the induction and repair of DNA strand breaks employing DNA elution and chromosome aberration assays in both exponential and plateau-phase cultures; and 4) measurement of poly (ADP-ribose) activity and nicotinamide adenine dinucleotide (NAD+) content in the tumor cells before and after irradiation in exponential and plateau-phase cultures. These cellular, chromosomal and biochemical assays will be correlated with patient outcome, assessed in terms of local control as well as total patient survival time and disease-free interval following radiotherapy. It is expected that one or more of these biological assays will predict radiocurability in patients receiving radiotherapy.