Noso Y, Niimi K, Nishiyama M, Hirabayashi N, Toge T, Niimoto M, Hattori T
Department of Surgery, Hiroshima University, Japan.
Cancer Res. 1987 Dec 1;47(23):6418-22.
A new screening assay for anticancer agents was established using an in vivo nude mouse model. Assessment of the chemosensitivity of individual human tumors was determined by [3H]thymidine incorporation by the treated tumors. Three hundred and thirty tumors derived from cancer patients were transplanted into nude mice s.c. and treated with anticancer agents. Mitomycin C, 5-fluorouracil, cyclophosphamide, and doxorubicin were used in the present studies. In 270 of 330 cancers, chemosensitivity was evaluated by this method (evaluable rate, 81.8%). The rate of positive sensitivity against all tumors was 21.9% in mitomycin C, 12.2% in 5-fluorouracil, 27.4% in cyclophosphamide, and 23.6% in doxorubicin, respectively. The tumor sensitivity to anticancer agents varied according to the type of cancer. Retrospective and prospective clinical studies were performed to determine the usefulness of the nude mouse-isotope assay for the prediction of tumor sensitivity. The 24-month survival rates of 24 gastric cancer patients treated with tumor-sensitive agents was significantly higher than that of 28 patients treated with tumor-resistant agents. The end results after chemotherapy in far-advanced and inoperable terminal cases of gastrointestinal cancers was also investigated, prospectively. Out of 19 cases, the 50% survival time of 11 patients treated with tumor-sensitive agents was longer than that of eight patients treated with tumor-resistant agents. From prospective correlative studies carried out on 25 patients, this assay correlated with clinical responses (overall agreement, 76.0%; P less than 0.05) with specific agreements of sensitivity and resistance of 37.5 and 94.1%, respectively. From these results, it seems reasonable to conclude that nude mouse-isotope assay is a screening assay to identify appropriate agents for the treatment of patients with cancer. However, there is still a need to develop a better protocol in this assay, especially for antimetabolites, and to continue research in order to find more sufficient assays to predict clinical sensitivity to anticancer agents.
利用体内裸鼠模型建立了一种新的抗癌药物筛选试验。通过处理后肿瘤的[3H]胸腺嘧啶核苷掺入来确定个体人类肿瘤的化学敏感性评估。将330例癌症患者来源的肿瘤移植到裸鼠皮下，并用抗癌药物进行治疗。本研究使用了丝裂霉素C、5-氟尿嘧啶、环磷酰胺和阿霉素。在330例癌症中的270例中，通过该方法评估了化学敏感性（可评估率为81.8%）。丝裂霉素C对所有肿瘤的阳性敏感率分别为21.9%，5-氟尿嘧啶为12.2%，环磷酰胺为27.4%，阿霉素为23.6%。肿瘤对抗癌药物的敏感性因癌症类型而异。进行了回顾性和前瞻性临床研究，以确定裸鼠-同位素试验对预测肿瘤敏感性的有用性。24例接受肿瘤敏感药物治疗的胃癌患者的24个月生存率显著高于28例接受肿瘤耐药药物治疗的患者。还对晚期和无法手术的胃肠道癌症终末期病例化疗后的最终结果进行了前瞻性研究。在19例病例中，11例接受肿瘤敏感药物治疗的患者的50%生存时间长于8例接受肿瘤耐药药物治疗的患者。对25例患者进行的前瞻性相关性研究表明，该试验与临床反应相关（总体一致性为76.0%；P小于0.05），敏感性和耐药性的具体一致性分别为37.5%和94.1%。从这些结果来看，得出裸鼠-同位素试验是一种筛选试验以确定适合癌症患者治疗药物的结论似乎是合理的。然而，在该试验中仍需要制定更好的方案，特别是对于抗代谢物，并继续进行研究以找到更充分的试验来预测对抗癌药物的临床敏感性。
