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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。

相似文献

1
[Effects of 5'-deoxy-5-fluorouridine on human gastrointestinal and breast cancers xenografted to nude mice].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
Gan To Kagaku Ryoho. 1984 Aug;11(8):1635-43.
2
[Combination chemotherapy with 3 or 4 drugs on human breast and gastrointestinal cancer xenografts in nude mice (II)].[裸鼠人乳腺癌和胃肠道癌异种移植瘤的三药或四药联合化疗(II)]
Gan To Kagaku Ryoho. 1987 May;14(5 Pt 1):1252-9.
3
[Experimental chemotherapy of human gastrointestinal and breast cancers in nude mice and its correlation to clinical effect].人胃肠道癌和乳腺癌裸鼠实验性化疗及其与临床疗效的相关性
Gan No Rinsho. 1984 Jul;30(9 Suppl):1168-74.
4
[Effects of alternating chemotherapy with 2 non-cross-resistant drug combinations on human alimentary and breast cancer xenografts in nude mice].[两种非交叉耐药药物联合交替化疗对裸鼠人消化道和乳腺癌异种移植瘤的影响]
Gan To Kagaku Ryoho. 1987 May;14(5 Pt 1):1297-304.
5
[Clinical phase II study of 5'-DFUR for cancer of the digestive organs by a cooperative study group].5'-脱氧氟尿苷用于消化器官癌的临床II期合作研究组研究
Gan To Kagaku Ryoho. 1985 Dec;12(12):2358-64.
6
Antitumor activity of a new fluoropyrimidine derivative, 5'-deoxy-5-fluorouridine, against murine and human experimental tumors.一种新型氟嘧啶衍生物5'-脱氧-5-氟尿苷对小鼠和人类实验性肿瘤的抗肿瘤活性。
Jpn J Cancer Res. 1985 Jul;76(7):644-50.
7
[Phase II study of 5'-DFUR (5'-deoxy-5-fluorouridine) by the Cooperative Study Group].协作研究组关于5'-去氧-5-氟尿苷(5'-DFUR)的II期研究
Gan To Kagaku Ryoho. 1985 Nov;12(11):2179-84.
8
[Phase II study of 5'-DFUR in gastrointestinal and breast cancer].5'-脱氧氟尿苷用于胃肠道癌和乳腺癌的II期研究
Gan To Kagaku Ryoho. 1985 Nov;12(11):2172-8.
9
A comparative study of the antitumor activities of 5'-deoxy-5-fluorouridine and its prodrug trimethoxybenzoyl-5'-deoxy-5-fluorocytidine (Ro09-1390) on human digestive organ cancer xenograft lines transplanted into nude mice.
Anticancer Drugs. 1992 Aug;3(4):387-93. doi: 10.1097/00001813-199208000-00012.
10
[Clinical effect of 5'-deoxy-5-fluorouridine (5'-DFUR)].5'-脱氧-5-氟尿苷(5'-DFUR)的临床疗效
Gan No Rinsho. 1985 May;31(6 Suppl):746-50.

引用本文的文献

1
The antiproliferative effects of fluoropyrimidine derivatives against human tumor xenografts in a subrenal capsule assay.氟嘧啶衍生物在肾包膜下试验中对人肿瘤异种移植的抗增殖作用。
Jpn J Surg. 1988 Nov;18(6):725-8. doi: 10.1007/BF02471537.