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首页> 外文期刊>British Journal of Cancer >Demonstration of vincristine resistance in primary intestinal neoplasms in the rat by the 'post-metaphase index'
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Demonstration of vincristine resistance in primary intestinal neoplasms in the rat by the 'post-metaphase index'

机译：通过“中期后指数”证明大鼠原发性肠肿瘤中长春新碱的耐药性

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摘要

A method is described enabling the direct measurement of vincristine resistance in intact tissues in vivo by morphological study. Using the metaphase arresting properties of the drug, counts were made of escaping anaphase and telophase mitotic figures at a range of doses. The proportion of post-metaphase mitotic figures is called the post-metaphase index (PMI). In 95 primary intestinal tumours induced by dimethylhydrazine (DMH) in rats, an increase in resistance to vincristine was shown over normal mucosa (P less than 0.001). The data were analysed by computer modelling and a linear relationship is demonstrated between the logit of the post-metaphase index, and log dose of vincristine. To achieve a PMI of 1% the fitted lines show an enhanced vincristine dose requirement over normal mucosa of 6 times in colonic tumours, and 8 times in small intestinal tumours. Non-neoplastic mucosa from the DMH-treated animals requires an enhanced dose of vincristine of 1.5 times, compared with normal mucosa, to achieve a PMI of 1%. Given current interest in the mechanism of vincristine resistance in cell lines this new approach provides a technique for assessing the resistance of solid tumours, both in vivo and in vitro, and for subsequent experimental manipulation.
机译：描述了一种能够通过形态学研究在体内完整组织中直接测量长春新碱抗性的方法。利用药物的中期停滞特性，在一定剂量范围内对逃逸的后期和末期有丝分裂数进行计数。中期后有丝分裂图的比例称为中期后指数（PMI）。在大鼠中由二甲基肼（DMH）诱发的95个原发性肠肿瘤中，对长春新碱的耐药性高于正常粘膜（P小于0.001）。通过计算机建模分析数据，并证明中期中期指数的对数与长春新碱的对数剂量之间存在线性关系。为使PMI达到1％，拟合线显示长春新碱的剂量要求比正常粘膜增加了6倍（结肠癌）和8倍（小肠肿瘤）。与正常粘膜相比，DMH处理动物的非肿瘤性粘膜需要长春新碱的剂量增加1.5倍，以达到1％的PMI。鉴于当前对细胞系中长春新碱抗性机制的兴趣，这种新方法提供了一种在体内和体外评估实体瘤抗性以及随后的实验操作的技术。

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