LOW DOSE IRRADIATION AND HYPERTHERMIA IN HUMAN TUMOURS

近距离放射治疗(腔内或腔内插入放射性同位素照射 间质)现在被广泛用于癌症的治疗 由于剂量分布的改善和正常组织的增加 节俭。在常规方法中达到的有效剂量率 近距离放射治疗(0.1-3.09 Cgy/分钟)广泛的组织保留发生在 从亚致死剂量辐射中恢复的正常和肿瘤组织 损坏(SLD)。我们的体外实验结果表明，热疗可以 抑制这种恢复。该项目的目标是评估 局部热疗(41-45摄氏度)改善预后的可能性 近距离放射治疗在癌症治疗中的应用。 具体目标： 1)评估热疗和低剂量率辐射反应 5个人类细胞系(1个正常和4个肿瘤来源)，它们有 对亚致死性辐射损伤的恢复能力不同。 2)测定低辐射下的热辐射增敏程度 剂量率及其与SLD修复能力和抑制作用的关系 这5个人细胞系。 3)确定接触等单元格条件的修改效果 以及Ph对高温和辐射的反应。 4)评估DNA聚合酶的活性作为热指标 放射增敏，目的是可以使用这些指示剂 临床上确定近距离放射治疗的潜在热增强作用。 目前还没有关于低剂量热强化的数据报道。 在人体肿瘤细胞中的率照射。临床试验显示不同 药效程度和我们评估时间、温度和 测序关系及其对聚合酶活性与辐射的影响 敏化将为组合的优化提供指导 治疗和预测临床疗效的潜力。有待改进的技术 用途：细胞存活、低剂量率照射、热疗、流量 细胞计数、聚合酶分析、Ph调节。

Brachytherapy (irradiation by inserted radioisotopes interacavitary or interstitial) is now being extensively used in the treatment of cancer because of improved dose distribution and increased normal tissue sparing. At the effective dose rates achieved in conventional brachytherapy (0.1 - 3.09 Cgy/min) extensive tissue sparing occurs in both normal and tumor tissues due to recovery from sublethal radiation damage (SLD). our in vitro results have shown that hyperthermia can inhibit such recovery. The goal of this project is to evaluate the potential for localized hyperthermia (41-45C) to improve the outcome of brachytherapy in cancer treatment. Specific Aims: 1) Evaluate the hyperthermia and low dose rate radiation responses of five human cell lines (1 normal and 4 tumor derived) which have different capacities for recovery of sublethal radiation damage. 2) Determine the degree of thermal radiosensitization at low radiation dose rates and relate this to SLD repair capacity and its inhibition in the 5 human cell lines. 3) Determine the modifying effects of cell conditions such as contact and Ph on the responses to hyperthermia and radiation. 4) Assess the activity of DNA polymerases as indicators of thermal radiosensitization with the objective that these indicators may be used clinically to determine potential thermal enhancement of brachytherapy. Presently no data has been reported on thermal enhancement of low dose rate irradiation in human tumor cells. Clinical trials show varying degrees of efficacy and our experiments evaluating time temperature and sequencing relationships and effect on polymerase activity vs. radiation sensitization will provide guidance to optimization of combination therapy and potential for predicting clinical efficacy. Techniques to be used: cell survival, low dose rate irradiation, hyperthermia, flow cytometry, polymerase analysis, Ph modulation.