Abe Takashige, Tada Mitsuhiro, Shinohara Nobuo, Okada Futoshi, Itoh Tomoo, Hamada Jun-Ichi, Harabayashi Toru, Chen Qinzhong, Moriuchi Tetsuya, Nonomura Katsuya
Department of Urology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Int J Urol. 2006 Jan;13(1):47-57. doi: 10.1111/j.1442-2042.2006.01220.x.
To establish and characterize a murine xenograft model of human urothelial cancer in severe combined immunodeficient (SCID) mice for therapeutic simulation.
Pieces of 30 freshly resected urothelial tumors (24 obtained from bladder and 6 from ureter or pelvis) were implanted subcutaneously into SCID mice, and xenograft tumors were passed in tumorigenic cases. At each passage, histopathology, TP53 mutational status assessed by yeast p53 functional assay, and the Ki-67 labeling index (LI) were examined to evaluate the preservation of original features. A growth delay assay after single-dose irradiation was performed in four representative xenografts.
Tumor growth was observed in 18 mice (60%, 18/30). Histologically, 15 of the 18 were epithelial carcinomas similar to the original tumors, whereas the other 3 were Epstein-Barr virus-associated lymphoproliferative disease, resulting in a 50% (15/30) take rate. No correlation was found between the tumor take rate and the clinicopathologic features, TP53 mutational status, or Ki-67 LI of the patients' tumors. Of these 15 xenografts, 11 xenografts were passed from 3 to 10 generations. TP53 mutational status remained stable during the passages, and the Ki-67 LI of eight xenografts was within a range of 50% of the LI of the original tumors, although the other three xenografts increased by over 50%. Specific growth delay after irradiation, independent of the original tumor growth speed and Ki-67 LI, was observed in four xenografts.
SCID mice are useful recipients for investigations of human urothelial cancer with a wide biological range. This easy-to-handle xenograft system can help to develop a better in vivo preclinical evaluation system for therapeutic agents as well as the investigation of tumor pathophysiology.
建立并鉴定一种用于治疗模拟的严重联合免疫缺陷（SCID）小鼠人尿路上皮癌异种移植模型。
将30块新鲜切除的尿路上皮肿瘤组织（24块取自膀胱，6块取自输尿管或肾盂）皮下植入SCID小鼠体内，在致瘤病例中传代异种移植肿瘤。每次传代时，检查组织病理学、通过酵母p53功能分析评估的TP53突变状态以及Ki-67标记指数（LI），以评估原始特征的保留情况。对四个代表性异种移植瘤进行单剂量照射后的生长延迟试验。
18只小鼠（60%，18/30）观察到肿瘤生长。组织学上，18只中有15只为与原始肿瘤相似的上皮癌，而另外3只为爱泼斯坦-巴尔病毒相关的淋巴增殖性疾病，移植成功率为50%（15/30）。未发现肿瘤移植成功率与患者肿瘤的临床病理特征、TP53突变状态或Ki-67 LI之间存在相关性。在这15个异种移植瘤中，11个异种移植瘤传代了3至10代。传代过程中TP53突变状态保持稳定，8个异种移植瘤的Ki-67 LI在原始肿瘤LI的50%范围内，尽管另外3个异种移植瘤增加了50%以上。在四个异种移植瘤中观察到照射后特定的生长延迟，与原始肿瘤生长速度和Ki-67 LI无关。
SCID小鼠是用于广泛生物学范围的人尿路上皮癌研究的有用受体。这种易于操作的异种移植系统有助于开发更好的体内临床前治疗药物评估系统以及肿瘤病理生理学研究。
