Steinberg G D, Brendler C B, Squire R A, Isaacs J T
James Buchanan Brady Urological Institute, Department of Urology Oncology and Comparative Medicine, Johns Hopkins Hospital, Baltimore, Maryland 21205.
J Urol. 1991 Mar;145(3):647-53. doi: 10.1016/s0022-5347(17)38413-6.
A rodent bladder cancer model that is induced by intravesical instillation of N-methyl-N-nitrosourea (MNU) was characterized. Cohorts of four to five week old female Fisher 344 rats received four biweekly 1.5 mg. doses of intravesical MNU and were sacrificed at various intervals. By week 13 all animals had flat atypia and/or papillary transitional cell tumors, and 67% of the lesions were moderately (grade II) or poorly differentiated (grade III). By week 20, 83% had gross muscle invasive tumors that eventually killed the host. A cohort of 40 MNU treated animals was subsequently treated commencing at week 17 after initiation of MNU with one of three intravesical six week regimens: 1) saline; 2) BCG (Tice strain); or 3) recombinant human tumor necrosis factor (RTNF) plus adriamycin. There was no difference in animal survival or tumor growth in any group of animals commencing therapy at week 17. A second cohort of 107 animals commenced therapy at 13 weeks after initiation of MNU with one of five intravesical six week regimens: 1) intravesical BCG (Tice strain); 2) adriamycin; 3) recombinant human tumor necrosis factor (RTNF); 4) RTNF plus adriamycin; or 5) BCG plus adriamycin. BCG, RTNF or adriamycin alone had no effect on tumor growth; however, BCG plus adriamycin and RTNF plus adriamycin commencing at week 13 significantly inhibited tumor growth and progression. In conclusion, this autochthonous intravesical rodent transitional cell carcinoma model appears useful for the following reasons: 1) it closely resembles human transitional cell carcinoma histologically and biologically in that all animals develop neoplastic changes in-situ that progress to muscle invasion and kill the host; 2) as with human bladder cancer these tumors do not respond to intravesical therapy if treated when tumor burden is large; however, tumor growth is inhibited when treated early; and 3) this model appears appropriate for screening and developing new intravesical treatments for superficial bladder cancer.
对通过膀胱内灌注N-甲基-N-亚硝基脲（MNU）诱导的啮齿动物膀胱癌模型进行了特征描述。将4至5周龄的雌性Fisher 344大鼠分成若干组，每两周接受4次1.5毫克剂量的膀胱内MNU，并在不同时间点处死。到第13周时，所有动物均出现扁平异型增生和/或乳头状移行细胞肿瘤，67%的病变为中度（II级）或低分化（III级）。到第20周时，83%的动物出现肉眼可见的肌层浸润性肿瘤，最终导致宿主死亡。随后，对一组40只接受MNU治疗的动物在开始MNU治疗后的第17周开始采用以下三种膀胱内六周治疗方案之一进行治疗：1）生理盐水；2）卡介苗（Tice株）；或3）重组人肿瘤坏死因子（RTNF）加阿霉素。在第17周开始治疗的任何一组动物中，动物存活率或肿瘤生长均无差异。第二组107只动物在开始MNU治疗后的第13周开始采用以下五种膀胱内六周治疗方案之一进行治疗：1）膀胱内卡介苗（Tice株）；2）阿霉素；3）重组人肿瘤坏死因子（RTNF）；4）RTNF加阿霉素；或5）卡介苗加阿霉素。单独使用卡介苗、RTNF或阿霉素对肿瘤生长没有影响；然而，在第13周开始使用卡介苗加阿霉素和RTNF加阿霉素可显著抑制肿瘤生长和进展。总之，这种自发性膀胱内啮齿动物移行细胞癌模型似乎有以下用途：1）在组织学和生物学上它与人类移行细胞癌非常相似，因为所有动物都会原位发生肿瘤性变化，进而发展为肌层浸润并导致宿主死亡；2）与人类膀胱癌一样，如果在肿瘤负荷较大时进行治疗，这些肿瘤对膀胱内治疗无反应；然而，早期治疗可抑制肿瘤生长；3）该模型似乎适合用于筛选和开发针对浅表性膀胱癌的新的膀胱内治疗方法。
