MODIFICATION OF TUMOR RESPONSE TO LOCAL IRRADIATION

改变肿瘤对局部辐射的反应

• 批准号: 3163745
• 负责人: JAY Steven LOEFFLER
• 金额: $ 35.14万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1975
• 资助国家: 美国
• 起止时间: 1975-10-01 至 1990-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3163745
• 关键词: Corynebacterium; astrocytoma; breast neoplasms; cellular oncology; combination cancer therapy; fibrosarcoma; gamma radiation; hamsters; histopathology; human subject; hyperbaric oxygen therapy; hypoxia; laboratory mouse; macrophage; metastasis; neoplasm /cancer immunotherapy; neoplasm /cancer radiation therapy; neoplasm /cancer remission /regression; neoplasm /cancer transplantation; neoplastic growth; radiation related neoplasm /cancer; radiation sensitivity; radiation therapy dosage; relative biological effectiveness; skin neoplasms

A major research effort is to study the response to fractionated irradiation of xenografts of human astrocytoma (high grade), squamous cell carcinoma, and mammary adenocarcinoma growing in nude mice. The end-point is to be the dose which achieves a specified growth delay. Radiation is to be given in 1, 2, 4, and 10 equal doses under clamp hypoxic conditions. To decrease the level of immune rejection against the xenografts, the nude mice will be prepared by procedures to immune suppress and to induce specific tolerance (partial or hopefully complete). An important component of this work will be to evaluate several procedures, alone and in combination, designed to immune suppress and to induce specific tolerance in the nude mouse. Evaluation of the radiation response data will be in terms of Alpha/Beta and Alpha/e ratios derived from plots of the reciprocal of dose which produces a specified delay in tumor growth against dose per fraction (an Fe plot). An additional set of experiments will be to examine for the extent of PLDR (potentially lethal damage repair) by comparing the cell number to transplant the tumor for tumor excised immediately or 6 hours after single dose irradiation. In addition Alpha/Beta amd Alpha/e are to be determined for a spontaneous fibrosarcoma two spontaneous squamous cell carcinoma and an ovarian carcinoma using early generation isotransplants in the C3Hf/Sed mouse. Another major area of research will be the examination for correlations between tumor response and biochemically determined levels of lactate, the Krebs cycle intermediates, and the adenylate nucleotides from small biopsy samples (less than 20mg) before and at mid-point during fractionated irradiation (Upsilon=10). The determination will be made using HPLC techniques. Parallel experiments will be made for polarographically estimated tissue P02 (using a simple electrode system, measurements at 3-4 points. A similar experiment will determine intertumor variation in adriamycin concentration (HPLC technique, small biopsy specimen) and also examine for correlation between tumor response to adriamycin alone or with radiation. This series is to be made on isotransplants and spontaneous autochthonous tumors. Also, a study will be made of effect of procedures to suppress Q02 to modify tumor response to radiation given to Air or 023ATA respiring mice.

一个主要的研究工作是研究对分离的反应 人类星形细胞瘤异种移植物的辐照（高级），鳞状细胞 癌中癌和乳腺癌癌中生长的乳腺癌。 终点 是实现特定生长延迟的剂量。 辐射是 在夹具低氧条件下以1、2、4和10相等的剂量给予。 到 降低针对异种移植物的免疫排斥水平，裸色 小鼠将通过免疫抑制和诱导的程序准备 特定的容忍度（部分或希望完成）。 一个重要的组成部分 这项工作将是单独评估几个程序 组合，旨在免疫抑制和诱导特定的公差 在裸鼠中。 辐射响应数据的评估将在 来自倒数图的α/beta和α/e比的术语 剂量产生特定的肿瘤生长延迟针对剂量 分数（FE图）。 另一组实验将是检查 通过比较PLDR（潜在的致命损害修复）的程度 细胞编号，以立即切除肿瘤的肿瘤或6个 单剂量照射后数小时。 此外，alpha/beta amd alpha/e 为自发纤维肉瘤确定两个自发的 鳞状细胞癌和卵巢癌使用早期 C3HF/SED小鼠中的各向同植物。 研究的另一个主要领域将是检查相关性 在肿瘤反应和生化确定的乳酸水平之间， KREBS循环中间体和小活检的腺苷酸核苷酸 分数之前和中点处的样品（小于20mg） 辐照（Upsilon = 10）。 该决定将使用HPLC做出 技术。 将对抛石线进行平行实验 估计的组织P02（使用简单的电极系统，在3-4处进行测量 点。 类似的实验将确定肿瘤的变化 阿霉素浓度（HPLC技术，小型活检标本），也是 检查单独或与阿霉素的肿瘤反应之间的相关性或与 辐射。 该系列将在各向同载体和自发上制作 自肿瘤。 此外，将对程序的效果进行研究 抑制Q02以改变对空气给予辐射的反应或 023ATA呼吸小鼠。