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Experimental study of Wilms tumor and its precursor lesion "nephrogenic rest" by using animal models.

肾母细胞瘤及其前驱病变“肾源性休息”动物模型的实验研究。

基本信息

批准号：
07557266
负责人：
YOKOMORI Kinji
金额：
$ 1.92万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557266/
关键词：
Wilms tumor nephrogenic rest animal model renal transplantaion ウイルスム腫瘍 ENU 化学発癌腎癌前駆病変 WT1 腎腫瘍前癌病変癌制御遺伝子 WT1遺伝子

项目摘要

In the first stage of this study, we confirmed histopathologically that transplacental administration of a carcinogenic agent, N-ethyl-N-nitrosourea (ENU) to pregnant rats induced in their F1 generations various renal lesions, such as simple renal cysts, Wilms tumor precursor lesions (nephrogenic rests), renal cell carcinomas, and adenomas. It was also shown that ENU-treated F1 generations inevitably suffered from fatal CNS tumors.In the second stage, we performed renal transplantation experiments. In an attempt to further promote ENU-induced renal carcinogenesis devoid of influence of fatal CNS tumor involvements, we removed the right kidneys of the 15 ENU-treated F1 rats, and transplanted them orthotopically to the healthy F1 rats. Out of 15 kidneys transplanted, 9 were successfully taken as donor kidneys. Following 2 to 5 month long observation period, the transplants were removed and submitted to histopathological analysis for the possible Wilms precursors and tumors perse. Macro-and microscopic studies revealed that the Wilms tumor precursor lesion was found in only one kidney, and marked atrophy of renal parenchyma was observed in 5 kidneys, presumably due to postoperative stenotic process formation at the anastomosed renal vessels. It seemed that further effort to improve technical skills in microscopic surgery is mandatory to obtain higher success rate in renal transplantation procedures.Because of the low success rate obtained in renal transplantation, it was impossible to conduct molecular biological studies for Wilms tumor suppressor genes.

在本研究的第一阶段，我们通过组织病理学证实，对怀孕大鼠经胎盘施用致癌剂N-乙基-N-亚硝基脲（ENU）会在其F1代中诱导各种肾脏病变，例如单纯性肾囊肿、肾母细胞瘤前体病变（肾源性残余物）、肾细胞癌和腺瘤。还表明，ENU处理的F1代不可避免地会罹患致命的中枢神经系统肿瘤。在第二阶段，我们进行了肾移植实验。为了进一步促进 ENU 诱导的肾癌发生，避免致命性 CNS 肿瘤参与的影响，我们切除了 15 只 ENU 治疗的 F1 大鼠的右肾，并将它们原位移植到健康的 F1 大鼠身上。在15个肾移植中，9个成功作为供肾。经过 2 至 5 个月的观察期后，移植物被取出并进行组织病理学分析，以确定可能的肾母细胞瘤前体和肿瘤本身。宏观和微观研究显示，仅在1个肾脏中发现Wilms瘤前体病变，在5个肾脏中观察到肾实质明显萎缩，推测是由于术后吻合肾血管处形成狭窄过程所致。看来，要想获得更高的肾移植成功率，必须进一步提高显微手术技术水平。由于肾移植成功率较低，无法对Wilms抑癌基因进行分子生物学研究。