KIDNEY RESPONSE TO RADIATION AND CHEMOTHERAPY

这个项目的目标是研究肾脏对 分次辐照及其相互作用 用化疗药物。晚期对非扩散的损害 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 分割放射治疗及其对药物照射效果的影响 在这类组织中的相互作用。放射性肾炎已有报道 在儿童和成人放射治疗中，以及在全身放疗后 照射(TBI)和骨髓移植。数据来自 这些肾脏耐受性研究将为全面的 放化疗晚期正常组织效应模型的建立 放射治疗。 该项目的具体目标可以分为三组。 1)分次外照射的研究。 A)肾脏对多次小剂量辐射的耐受性如何？ 每天的分数，并且该关系是否与 线性-二次模型？ B)小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是多少？ 辐射？ D)肾脏耐受性如何取决于照射时的年龄？ 2)颅脑损伤及骨髓移植后放射性肾炎。 A)颅脑损伤后放射性肾炎与骨骼的关系 骨髓移植取决于分割和剂量率 是TBI的？ B)这种肾炎如何依赖于用于治疗的药物 条件反射和免疫抑制？ 3)肾照射与辐射相互作用的研究 化疗。 A)药物-脑损伤联合用药如何造成器官损害 影响后使用药物的药代动力学 移植？ B)如何治疗肾毒性化疗 药物会影响对后续肾脏辐射的耐受性吗？ C)使用肾毒性药物治疗如何影响 既往肾放射治疗导致肾炎的发展？

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?