Fodstad O, Aass N, Pihl A
Int J Cancer. 1980 Apr 15;25(4):453-8. doi: 10.1002/ijc.2910250405.
In attempts to elucidate the factors determining individual differences in response of tumors to chemotherapeutic agents, the sensitivity of six human malignant melanomas growing in athymic, nude mice was studied. Six agents, viz. DTIC, CCNU, vinblastine, procarbazine, as well as the toxic lectins abrin and ricin, were administered in maximum tolerable doses to the tumor-bearing mice. The response to treatment was expressed as tumor growth delay, i.e. the number of volume double times saved by the treatment. The xenografts had very nearly retined the morphology of the parent tumors and were histologically similar. They showed different and characteristic early growth rates and also wide variations in their response to the agents tested. Unexpectedly, in the case of DTIC, CCNU and procarbazine, the response of the xenografts proved to be inversely related to the early growth rates of the tumors. For vinblastine, abrin and ricin, no correlation between response and growth rate of the tumors was apparent. Procarbazine had the best overall effect among the agents here tested. DTIC, CCNU and vinblastine had somewhat less and about equal overall efficiency. The plant toxin abrin, which acts by inhibiting protein synthesis, was at least as effective as DTIC. When abrin was given together with DTIC, the effect on the two xenografts tested was superior to that of each agent given alone. The wide variations observed in the response of the histologically similar xenografts to the different agents demonstrate that testing of the chemosensitivity of human xenografts requires the use of a panel of tumors of each histological tpye. The clear relationship found between the early growth rate of the xenografts and their sensitivity to three of the drugs most commonly used in the treatment of malignant melanomas, may have clinical implications.
为了阐明决定肿瘤对化疗药物反应个体差异的因素，研究了在无胸腺裸鼠体内生长的6个人类恶性黑色素瘤的敏感性。给荷瘤小鼠最大耐受剂量地施用6种药物，即达卡巴嗪、洛莫司汀、长春碱、丙卡巴肼，以及毒性凝集素相思子毒素和蓖麻毒素。治疗反应以肿瘤生长延迟表示，即治疗节省的体积倍增次数。异种移植瘤几乎保留了亲本肿瘤的形态，并且在组织学上相似。它们显示出不同且独特的早期生长速率，并且对所测试药物的反应也有很大差异。出乎意料的是，对于达卡巴嗪、洛莫司汀和丙卡巴肼，异种移植瘤的反应与肿瘤的早期生长速率呈负相关。对于长春碱、相思子毒素和蓖麻毒素，肿瘤反应与生长速率之间没有明显的相关性。在所测试的药物中，丙卡巴肼具有最佳的总体效果。达卡巴嗪、洛莫司汀和长春碱的总体疗效略低且大致相当。通过抑制蛋白质合成起作用的植物毒素相思子毒素至少与达卡巴嗪一样有效。当相思子毒素与达卡巴嗪一起给药时，对所测试的两种异种移植瘤的效果优于单独使用每种药物。在组织学相似的异种移植瘤对不同药物的反应中观察到的广泛差异表明，测试人类异种移植瘤的化学敏感性需要使用每种组织学类型的一组肿瘤。在异种移植瘤的早期生长速率与其对恶性黑色素瘤治疗中最常用的三种药物的敏感性之间发现的明确关系可能具有临床意义。
