Inaba M, Tashiro T, Kobayashi T, Fujimoto S, Sakurai Y, Maruo K, Ohnishi Y, Ueyama Y, Nomura T
Jpn J Cancer Res. 1986 Feb;77(2):190-6.
To ascertain the clinical predictability and, in the long run, the usefulness of the human tumor/nude mouse model as a screening tool for antitumor agents, it seems particularly important to use as many tumor lines as possible and to evaluate the therapeutic effectiveness of antitumor agents in terms of the overall response rate of a range of tumors. In this study, using 11 strains of established human gastric tumor xenografts with various histological characteristics and proliferation behavior, the experimental response rates to 8 typical antitumor drugs (mitomycin C, cyclophosphamide, ACNU, cisplatin, adriamycin, vincristine, vinblastine and 5-fluorouracil) were determined and compared with the clinical values. The experimental response rates to adriamycin, vincristine and 5-fluorouracil were in good accordance with the clinical results. However, with the other drugs, significantly higher response rates were observed with the nude mouse model as compared to clinical therapy, indicating that this model tends to overestimate the responsiveness of human tumor to a number of antitumor agents. These results strongly suggest the importance of using appropriate dose levels in the nude mouse to reproduce clinically equivalent effects in this model.
为了确定人类肿瘤/裸鼠模型作为抗肿瘤药物筛选工具的临床可预测性以及长期的实用性,尽可能多地使用肿瘤细胞系,并根据一系列肿瘤的总体反应率评估抗肿瘤药物的治疗效果似乎尤为重要。在本研究中,使用11株具有不同组织学特征和增殖行为的已建立的人胃肿瘤异种移植模型,测定了对8种典型抗肿瘤药物(丝裂霉素C、环磷酰胺、嘧啶亚硝脲、顺铂、阿霉素、长春新碱、长春花碱和5-氟尿嘧啶)的实验反应率,并与临床值进行比较。对阿霉素、长春新碱和5-氟尿嘧啶的实验反应率与临床结果高度一致。然而,对于其他药物,与临床治疗相比,裸鼠模型观察到的反应率显著更高,这表明该模型倾向于高估人类肿瘤对多种抗肿瘤药物的反应性。这些结果强烈表明在裸鼠中使用适当剂量水平以在该模型中重现临床等效效果的重要性。