Giovanella B C, Stehlin J S, Shepard R C, Williams L J
Cancer. 1983 Oct 1;52(7):1146-52. doi: 10.1002/1097-0142(19831001)52:7<1146::aid-cncr2820520704>3.0.co;2-6.
Human tumors serially heterotransplanted in nude mice have been tested for their response to chemotherapeutic agents. Fourteen melanomas, 14 colorectal carcinomas, and 14 breast carcinomas have been used. Each tumor originated in a different patient. The tumors were maintained by serial subcutaneous transplantation in nude mice. For the experiments in this study, each neoplasm was transplanted under the kidney capsule of 60 to 100 adult nude mice. The areas of the individual tumor implants were precisely measured immediately after insertion using a stereo microscope equipped with a micrometric ocular. The animals were then divided into groups of six to ten animals each. One group was injected daily with saline and served as controls. The mice in the remaining groups were injected daily for eight days with one of the following chemotherapeutic agents--Adriamycin (doxorubicin), 5-fluorouracil, methotrexate, Cytoxan (cyclophosphamide), Alkeran (melphalan), vincristine, vinblastine, methyl-CCNU, or BCNU--at optimum doses (the maximum dose tolerated that causes less than 10% weight loss). Treatment was initiated when the implants were well established, having roughly doubled their initial mass. The animals were then sacrificed and the tumors measured again. A drug was rate effective only if it inhibited growth of the tumor by 99% or more. The results so obtained were compared with the published results of various clinical trials. When the sensitivity of the human tumors in the mice was compared with the sensitivity of tumors of the same type that had been treated in human patients, a close correlation was found. The panel study detected nine of ten effective drugs, giving only two false-positive results. Our data strongly support the validity of heterotransplants of human tumors in the nude mouse as a predictive system for testing new anticancer agents and in determining optimal treatment schedules and combinations of known drugs.
已对在裸鼠体内连续异种移植的人类肿瘤对化疗药物的反应进行了测试。使用了14例黑色素瘤、14例结直肠癌和14例乳腺癌。每个肿瘤都起源于不同的患者。这些肿瘤通过在裸鼠体内连续皮下移植得以维持。在本研究的实验中，将每个肿瘤移植到60至100只成年裸鼠的肾包膜下。植入后立即使用配备测微目镜的体视显微镜精确测量各个肿瘤植入物的面积。然后将动物分成每组六至十只动物的组。一组每天注射生理盐水作为对照。其余组的小鼠连续八天每天注射以下化疗药物之一——阿霉素（多柔比星）、5-氟尿嘧啶、甲氨蝶呤、环磷酰胺、美法仑、长春新碱、长春碱、甲基环己亚硝脲或卡莫司汀——以最佳剂量（导致体重减轻少于10%的最大耐受剂量）。当植入物生长良好，其初始质量大致翻倍时开始治疗。然后处死动物并再次测量肿瘤。一种药物只有在抑制肿瘤生长99%或更多时才被认为是有效率的。将如此获得的结果与各种临床试验的已发表结果进行比较。当将小鼠体内人类肿瘤的敏感性与在人类患者中治疗的相同类型肿瘤的敏感性进行比较时，发现了密切的相关性。该小组研究检测出了十种有效药物中的九种，仅产生了两个假阳性结果。我们的数据有力地支持了人类肿瘤在裸鼠体内异种移植作为测试新抗癌药物以及确定已知药物的最佳治疗方案和联合用药的预测系统的有效性。
