KIDNEY RESPONSE TO RADIATION AND CHEMOTHERAPY

肾脏对放射和化疗的反应

• 批准号: 3166530
• 负责人: JOHN E MOULDER
• 金额: $ 13.9万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-01-01 至 1992-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3166530
• 关键词: X ray; antineoplastics; azathioprine; blood chemistry; bone marrow transplantation; carmustine; cis platinum compound; combination cancer therapy; combination chemotherapy; cyclophosphamide; cytosine arabinoside; drug adverse effect; human therapy evaluation; immunosuppression; ionizing radiation; laboratory rat; methotrexate; mitomycin C; neoplasm /cancer chemotherapy; neoplasm /cancer radiation therapy; nephritis; physical chemical interaction; radiation dosage; radiation recovery; radiation sensitivity; radiobiology; urinalysis; vincristine; whole body irradiation effect

The goal of this project is to study the response of the kidney to fractionated irradiation, and the interaction of this irradiation with chemotherapy agents. Late damage to nonproliferating normal tissues is a major limiting factor in radiotherapy, but there is a paucity of information on late tissue damage from fractionated radiotherapy and on the effects of drug-radiation interaction in such tissues. Radiation nephritis has been reported in both pediatric and adult radiotherapy, and after total body irradiation (TBI) and bone marrow transplantation. The data from these renal tolerance studies will provide the basis for a general model for the late normal tissue effects of radiation and chemo- radiotherapy. The specific aims of the project can be divided into three groups. 1) Studies of fractionated external beam radiotherapy. a) What is the tolerance of the kidney to multiple small radiation fractions per day, and is the relationship compatible with the linear-quadratic model? b) What is the rate of repair of sublethal damage after small radiation fractions? c) What is the radiation tolerance of the kidney for low dose rate irradiation? d) How does renal tolerance depend on age at irradiation? 2) Radiation nephritis after TBI and bone marrow transplant. a) How does the radiation nephritis seen after TBI and bone marrow transplantation depend on the fractionation and dose rate of the TBI? b) How does this nephritis depend on the drugs used for conditioning and immunosuppression? 3) Studies of the interaction of renal irradiation and chemotherapy. a) How does organ damage caused by drug-TBI combinations affect the pharmacokinetics of drugs that are used after transplantation? b) How does treatment with nephrotoxic chemotherapeutic agents affect tolerance to subsequent renal radiation? c) How does treatment with nephrotoxic agents affect the development of nephritis from previous renal irradiation?

这个项目的目标是研究肾脏对 分次照射，这种照射的相互作用 化疗药物。 晚期非增殖性损伤 正常组织是放射治疗的主要限制因素，但 关于晚期组织损伤的信息很少， 分次放射治疗和药物放射治疗的影响 这些组织中的相互作用。 放射性肾炎已有报道 在儿童和成人放疗中，以及全身放疗后， 照射（TBI）和骨髓移植。 的数据 这些肾耐受性研究将为一般的 模型的放射和化疗的晚期正常组织效应， 放疗 该项目的具体目标可分为三组。 1)分割外照射放射治疗的研究。 a）肾脏对多次小剂量辐射的耐受性如何 每天的分数，并且与 线性二次模型 B）小剂量损伤后亚致死损伤的修复率是多少？ 辐射分数？ c）肾脏对低剂量率的辐射耐受性如何 辐射？ d）肾耐受性如何取决于照射时的年龄？ 2)TBI和骨髓移植后的放射性肾炎。 一、TBI后放射性肾炎与骨 骨髓移植依赖于分次和剂量率 TBI的？ B）这种肾炎是如何依赖于药物用于 调节和免疫抑制 3)肾照射与放射性核素相互作用的研究 化疗 a）药物-TBI组合如何引起器官损伤 影响药物的药代动力学， 移植？ B）肾毒性化疗如何治疗 药物影响对后续肾放射的耐受性？ c）肾毒性药物治疗如何影响 既往肾放射导致肾炎？