Membrane transport of antifolates as a critical determinant of drug cytotoxicity.
Membrane transport of antifolates as a critical determinant of drug cytotoxicity.
复制标题
抗叶酸剂的膜转运是药物细胞毒性的关键决定因素。
DOI：
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发表时间：
1977
影响因子：
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通讯作者：
I. Goldman
中科院分区：
文献类型：
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作者：
I. Goldman
在治疗学领域中，很少有像用细胞毒性药物治疗恶性疾病那样对药物的膜转运进行如此深入的研究。与可以选择性地抑制细菌或真菌生物体特有的生化过程的抗菌剂或抗真菌剂不同，构成癌症化学治疗师当前武器的药剂对肿瘤和易感宿主组织产生毒性作用。由于缺乏对正常细胞和恶性细胞之间基本生化差异的了解，需要利用微妙的技术（通常是经验性的）来实现药物的“选择性”效果，以尽量减少对易感宿主组织的毒性，同时最大限度地提高对肿瘤的毒性。更好地理解这些技术通常利用肿瘤与宿主细胞速率的定量而非定性差异：(a)细胞增殖，(b)药物激活或失活，(c)药物跨细胞膜转运，以及(d)药物与细胞内靶位点的相互作用。
There are few areas in therapeutics in which membrane transport of pharmacologic agents has been subjected to as intense study as in the treatment of malignant diseases with cytotoxic agents. Unlike the antibacterial or antifungal agents, which may selectively inhibit biochemical processes unique to the bacterial or fungal organism, the agents which comprise the current armamentarium of the cancer chemotherapist produce toxic effects on both tumor and susceptible host tissues. The lack of understanding of the basic biochemical differences between normal and malignant cells require the utilization of subtle techniques, often empirical, to achieve “selective” effects of the agents in an attempt to minimize toxicity to susceptible host tissues while maximizing toxicity to the tumor. The better understood of these techniques usually exploit quantitative rather than qualitative differences in the tumor vs. host cell rates of (a) cellular proliferation, (b) drug activation or inactivation, (c) drug transport across the cell membrane, and (d) drug interaction with target sites within the cell.