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.

一项主要的研究工作是研究对分馏的反应 人星形细胞瘤（高级别）、鳞状细胞异种移植物的照射 裸鼠体内生长的癌和乳腺癌。 终点 是达到特定生长延迟的剂量。 辐射是为了 在钳夹缺氧条件下以1、2、4和10等剂量给药。 到 降低对异种移植物、裸鼠的免疫排斥水平 小鼠将通过免疫抑制和诱导程序进行准备 特定容差（部分或希望完全）。 重要组成部分 这项工作的重点是单独评估几个程序 组合，旨在免疫抑制和诱导特异性耐受 在裸鼠中。 辐射响应数据的评估将在 从倒数图导出的 Alpha/Beta 和 Alpha/e 比率项 相对于每剂量的剂量，产生特定的肿瘤生长延迟的剂量 分数（Fe 图）。 一组额外的实验将检查 通过比较 PLDR（潜在致命损伤修复）的程度 立即切除的肿瘤移植肿瘤的细胞数或6 单剂量照射后数小时。 此外，Alpha/Beta 和 Alpha/e 自发性纤维肉瘤需确定两种自发性 使用早期一代的鳞状细胞癌和卵巢癌 C3Hf/Sed 小鼠的同种移植。 另一个主要研究领域是相关性检查 在肿瘤反应和生化测定的乳酸水平之间， 克雷布斯循环中间体和来自小活检的腺苷酸核苷酸 分馏前和中点时的样品（少于 20mg） 辐照（Upsilon=10）。 将使用 HPLC 进行测定 技术。 将进行极谱平行实验 估计组织 P02（使用简单的电极系统，在 3-4 时测量 点。 类似的实验将确定肿瘤间的变异 阿霉素浓度（HPLC 技术，小活检标本）以及 检查肿瘤对单独使用阿霉素或联合使用阿霉素的反应之间的相关性 辐射。 该系列是在同种移植和自发的基础上制作的 本土肿瘤。 此外，还将研究程序的效果 抑制 Q02 改变肿瘤对空气或辐射的反应 023ATA 正在呼吸的小鼠。