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5'-脱氧-5-氟尿苷对移植于裸鼠的人胃肠道癌和乳腺癌的作用

[Effects of 5'-deoxy-5-fluorouridine on human gastrointestinal and breast cancers xenografted to nude mice].

作者信息

Fujita F, Fujita M, Taguchi T

出版信息

Gan To Kagaku Ryoho. 1984 Aug;11(8):1635-43.

PMID:6236751
Abstract

As a preclinical secondary screening trial, the efficacy of a new derivative of 5-fluorouracil, 5'-deoxy-5-fluorouridine (5'-DFUR), on 15 human cancers xenografted serially to nude mice of BALB/c background was evaluated in comparison with two other derivatives, tegafur and UFT. Oral administration of 123 mg/kg/day of 5'-DFUR, 25-30 times, produced effective inhibition in 5 out or 7 gastric cancers, 2 out of 3 colorectal cancers, all 3 of breast cancers and 1 out of 2 pancreatic cancers, totalling 11 out of 15 cancer lines (73%) examined. In some cases shrinkage of tumors was noted without any noticeable side effects. Although an increased dose of 185 mg/kg/day of 5'-DFUR resulted in more prominent inhibition on all 9 tumors tested, some animals suffered from severe loss of body weight or diarrhea. Comparative experiments with of equimolac doses of 5'-DFUR(123 mg/kg) and FT-207(100 mg/kg) showed that the inhibition rate of the former was higher than that of the latter in all 8 lines of cancers examined. Six experiments in particular (2 gastric, 1 colorectal, 2 breast and 1 pancreatic cancers), showed that 5'-DFUR statistically sustained more effective suppression. Direct comparisons of 5'-DFUR and UFT were also made in 5 experiments in which 3 cancers were more sensitive to the former drug. Promising results in clinical trials can be expected with the new drug 5'-DFUR for these kinds of cancers.

摘要

作为一项临床前二级筛选试验,将5-氟尿嘧啶的一种新衍生物5'-脱氧-5-氟尿苷(5'-DFUR)与另外两种衍生物替加氟和优福定相比,评估了其对连续移植到BALB/c背景裸鼠体内的15种人类癌症的疗效。每天口服123毫克/千克的5'-DFUR,给药25 - 30次,对7种胃癌中的5种、3种结直肠癌中的2种、所有3种乳腺癌以及2种胰腺癌中的1种产生了有效抑制,在所检测的15种癌症细胞系中共有11种(73%)出现这种情况。在某些情况下,观察到肿瘤缩小且没有明显的副作用。尽管将5'-DFUR的剂量增加到每天185毫克/千克会对所有9种测试肿瘤产生更显著的抑制作用,但一些动物出现了严重的体重减轻或腹泻。用等摩尔剂量的5'-DFUR(123毫克/千克)和替加氟(100毫克/千克)进行的对比实验表明,在所检测的所有8种癌症细胞系中,前者的抑制率高于后者。特别是6项实验(2种胃癌、1种结直肠癌、2种乳腺癌和1种胰腺癌)表明,5'-DFUR在统计学上能持续产生更有效的抑制作用。在5项实验中还对5'-DFUR和优福定进行了直接比较,其中3种癌症对前一种药物更敏感。对于这类癌症,有望通过新药5'-DFUR在临床试验中取得良好结果。

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