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Rapid induction of dog urinary bladder cancer for the human bladder cancer model.

快速诱导狗膀胱癌用于人类膀胱癌模型。

基本信息

批准号：
62570732
负责人：
OKAJIMA Eigoro
金额：
$ 1.34万
依托单位：
Nara Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

Human urinary bladder cancer is wide-spectrum disease ranging from low grade-low stage to high grade-high stage cancer. However, experimental bladder cancer model are restricted to have one type of cancer even induced by various carcinogens. The advantage of dog bladder cancer model is that the dog develop both types of bladder cancer and the clinical examination and treatment is able to perform like a human. The disadvantage of this model is long period needed to induce the bladder cancer. In this experiment, we tried a rapid induction of dog bladder cancer using intravesical instillation of M-metyl-N-nitrosourea(MNU) and oral administration of N-butyl-N-(4-hydroxybutyl) nitrosamine(BBN). 6 female Beagle dogs received MNU 50mg/0.9NaCl 20ml 3 times every 3 weeks followed oral administration of BBN 240mg/day and 2 dogs received MNU instillation alone. Cold cup biopsies at 80 weeks revealed dysplasia but no CIS was observed. At 169 weeks, nodular or non-peduncle papillary tumor were observed cystoscopically, Which were transitional carcinoma, grade 2, pT1b with nodular proliferation into the submucosal layer. Bladder tumor was not observed in the dogs treated MNU alone. These histological findings suggest that these tumor progressed from CIS lesions. This experimental dog model treated with BBN and MNU combined treatment seems to be useful in the study of the natural history of human urinary bladder cancer with close observation for CIS and its development.

膀胱癌是一种从低级别-低阶段到高级别-高阶段的广谱性疾病。然而，实验性膀胱癌模型仅限于一种类型的癌症，甚至是由多种致癌物诱发的。狗膀胱癌模型的优点是，狗发展两种类型的膀胱癌，临床检查和治疗能够像人一样进行。该模型的缺点是诱导膀胱癌需要较长的时间。本实验采用膀胱灌注M-甲基-N-亚硝基脲（MNU）和口服N-丁基-N-（4-羟丁基）亚硝胺（BBN）的方法，尝试了一种快速诱发犬膀胱癌的方法。6只雌性Beagle犬在口服BBN 240 mg/d后，每3周3次给予MNU 50 mg/0.9NaCl 20 ml，2只犬单独滴注MNU。80周时冷杯活检显示发育不良，但未观察到CIS。169周时膀胱镜下可见结节状或无蒂乳头状肿瘤，为移行癌，2级，pT 1b，结节状增生至粘膜下层。在单独给药MNU的犬中未观察到膀胱肿瘤。这些组织学结果表明，这些肿瘤从CIS病变进展。BBN和MNU联合治疗的实验犬模型似乎有助于研究人膀胱癌的自然史，并密切观察CIS及其发展。