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[人癌/裸鼠系统中抗肿瘤作用评价的实验研究]

[Experimental study on the evaluation of antineoplastic effects in the human cancer/nude mouse system].

作者信息

Tashiro T, Fujimoto S, Kobayashi T, Inaba M

出版信息

Gan To Kagaku Ryoho. 1983 Apr;10(4 Pt 1):973-80.

PMID:6408993
Abstract

Human tumor/nude mouse system is expected to be an antitumor screening system with higher predictability of the clinical effect. To establish this, it is quite necessary to fundamentally investigate the optimal treatment regimen in this new model, nevertheless few papers related to these subjects are currently, available. In this preliminary report, we examined the effect of several known antitumor agents against human breast tumor xenograft, MX-1, with reference to the dose, route and schedule of administration of drugs in comparison with the clinical regimens. As a result, the treatment regimens were desirable to be similar to that clinically done: the route of administration should be IV or PO, instead of IP often used in usual animal experiments. The selection of dose would be the most important factor, that is, the maximum tolerated doses (MTD) of mitomycin C, vincristine, etc. were higher than the clinical doses, even in terms of dose per square meter. Thus, for these drugs the risk to overestimate the effect might exist. On the other hand, the case was opposite as for 5-fluorouracil, because its MTD in the nude mouse was lower than the clinical dose. To evaluate the effect of a drug, it appeared to be reasonable to make account of not only the average percentage of tumor growth inhibition but also the statistical means such as Mann-Whitney's U-test.

摘要

人肿瘤/裸鼠系统有望成为一种对临床疗效具有更高预测性的抗肿瘤筛选系统。为建立该系统,从根本上研究这种新模型中的最佳治疗方案是非常必要的,然而目前很少有关于这些主题的论文。在这份初步报告中,我们参照药物的剂量、给药途径和给药方案,并与临床方案进行比较,研究了几种已知抗肿瘤药物对人乳腺肿瘤异种移植瘤MX - 1的作用。结果表明,治疗方案应与临床方案相似:给药途径应为静脉注射或口服,而不是通常在动物实验中常用的腹腔注射。剂量的选择将是最重要的因素,也就是说,丝裂霉素C、长春新碱等的最大耐受剂量(MTD)高于临床剂量,即使按每平方米计算也是如此。因此,对于这些药物可能存在高估疗效的风险。另一方面,5 - 氟尿嘧啶的情况则相反,因为其在裸鼠中的MTD低于临床剂量。为评估药物的效果,不仅考虑肿瘤生长抑制的平均百分比,还考虑诸如曼 - 惠特尼U检验等统计方法似乎是合理的。

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