Tibbetts L M, Chu M Y, Hager J C, Dexter D L, Calabresi P
Cancer. 1977 Nov;40(5 Suppl):2651-9. doi: 10.1002/1097-0142(197711)40:5+<2651::aid-cncr2820400939>3.0.co;2-v.
An in vivo model is described for assessing the antitumor activity of chemotherapeutic agents. Tumors derived from human colon carcinoma cell lines injected into antithymocyte serum (ATS) immunosuppressed mice were used. In this system, both antitumor effects and host toxicity can be quantitated, permitting calculation of a Therapeutic Index. Compared with other xenograft models, the present system is simple, experiments are completed in less than 2 weeks, and the use of cultured cell lines allows in vitro studies to be performed. The in vitro sensitivities of one colon cell line to 22 chemotherapeutic agents and of four cell lines to three agents is reported. Four drugs used in treating colon cancer (Mitomycin C, 5-FU, BCNU, and methyl-CCNU) show antitumor activity in vivo in this system. Each has a low therapeutic index. Further work with this model is indicated, with the goal of finding new drugs with high Therapeutic Indices.
描述了一种用于评估化疗药物抗肿瘤活性的体内模型。使用将源自人结肠癌细胞系的肿瘤注射到抗胸腺细胞血清(ATS)免疫抑制小鼠体内所形成的肿瘤。在该系统中,抗肿瘤作用和宿主毒性均可进行定量,从而能够计算治疗指数。与其他异种移植模型相比,本系统简单,实验可在不到2周内完成,并且使用培养的细胞系可进行体外研究。报告了一种结肠癌细胞系对22种化疗药物以及四种细胞系对三种药物的体外敏感性。用于治疗结肠癌的四种药物(丝裂霉素C、5-氟尿嘧啶、卡莫司汀和甲基环己亚硝脲)在该系统中显示出体内抗肿瘤活性。每种药物的治疗指数都较低。表明需要对该模型进行进一步研究,目标是找到具有高治疗指数的新药。