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1
Comparative effect of 6S, 6R and 6RS leucovorin on methotrexate rescue and on modulation of 5-fluorouracil.6S、6R和6RS亚叶酸对甲氨蝶呤解救及5-氟尿嘧啶调节的比较效果
Br J Cancer. 1991 Jun;63(6):885-8. doi: 10.1038/bjc.1991.194.
2
Pharmacokinetics and in vitro studies of l-leucovorin. Comparison with the d and d,l-leucovorin.
Ann Oncol. 1993;4 Suppl 2:1-5. doi: 10.1093/annonc/4.suppl_2.s1.
3
Lack of interference by the unnatural isomer of 5-formyltetrahydrofolate with the effects of the natural isomer in leucovorin preparations.5-甲酰四氢叶酸的非天然异构体对亚叶酸制剂中天然异构体的作用无干扰。
J Natl Cancer Inst. 1989 Aug 2;81(15):1175-8. doi: 10.1093/jnci/81.15.1175.
4
Effects of diastereoisomers of 5-formyltetrahydrofolate on cellular growth, sensitivity to 5-fluoro-2'-deoxyuridine, and methylenetetrahydrofolate polyglutamate levels in HCT-8 cells.5-甲酰四氢叶酸非对映异构体对HCT-8细胞的细胞生长、对5-氟-2'-脱氧尿苷的敏感性及亚甲基四氢叶酸多聚谷氨酸水平的影响
Cancer Res. 1991 Jul 1;51(13):3476-81.
5
Influence of dose of [6RS]leucovorin on reduced folate pools and 5-fluorouracil-mediated thymidylate synthase inhibition in human colon adenocarcinoma xenografts.[6RS]亚叶酸剂量对人结肠腺癌异种移植瘤中还原型叶酸池及5-氟尿嘧啶介导的胸苷酸合成酶抑制作用的影响。
Cancer Res. 1990 Jul 1;50(13):3940-6.
6
Relationship between dose rate of [6RS]Leucovorin administration, plasma concentrations of reduced folates, and pools of 5,10-methylenetetrahydrofolates and tetrahydrofolates in human colon adenocarcinoma xenografts.[6RS]亚叶酸钙给药剂量率、还原型叶酸的血浆浓度以及人结肠腺癌异种移植瘤中5,10-亚甲基四氢叶酸和四氢叶酸池之间的关系。
Cancer Res. 1990 Jun 15;50(12):3493-502.
7
Role of folylpolyglutamates in biochemical modulation of fluoropyrimidines by leucovorin.亚叶酸钙介导的叶酰聚谷氨酸在氟嘧啶类药物生化调节中的作用
Cancer Res. 1991 Feb 1;51(3):789-93.
8
Cellular interactions between the natural and unnatural isomers of 5-formyltetrahydrofolate.5-甲酰基四氢叶酸天然和非天然异构体之间的细胞相互作用。
Adv Exp Med Biol. 1993;339:23-30; discussion 41-2. doi: 10.1007/978-1-4615-2488-5_3.
9
Interactions of carboxypeptidase G2 with 6S-leucovorin and 6R-leucovorin in vitro: implications for the application in case of methotrexate intoxications.羧肽酶G2与6S-亚叶酸和6R-亚叶酸的体外相互作用：对甲氨蝶呤中毒应用的启示。
Cancer Chemother Pharmacol. 2005 Apr;55(4):347-353. doi: 10.1007/s00280-004-0910-2. Epub 2004 Oct 21.
10
Interaction between 5-fluorouracil, [6RS]leucovorin, and recombinant human interferon-alpha 2a in cultured colon adenocarcinoma cells.
Cancer Commun. 1991 Jul;3(7):225-31. doi: 10.3727/095535491820873236.

引用本文的文献

1
New recommendations for reversal of high-dose methotrexate cytotoxicity with folinic acid.用亚叶酸钙逆转大剂量甲氨蝶呤细胞毒性的新建议。
Cancer Chemother Pharmacol. 2025 Mar 13;95(1):41. doi: 10.1007/s00280-025-04749-w.
2
The role of l-leucovorin uptake and metabolism in the modulation of 5-fluorouracil efficacy and antifolate toxicity.左亚叶酸摄取和代谢在调节5-氟尿嘧啶疗效及抗叶酸毒性中的作用。
Front Pharmacol. 2024 Aug 21;15:1450418. doi: 10.3389/fphar.2024.1450418. eCollection 2024.
3
Pharmacokinetic comparison of leucovorin and levoleucovorin.
Eur J Clin Pharmacol. 1993;44(6):569-73. doi: 10.1007/BF02440861.
4
Effect of cisplatin in advanced colorectal cancer resistant to 5-fluorouracil plus (S)-leucovorin.顺铂对耐5-氟尿嘧啶加（S）-亚叶酸钙的晚期结直肠癌的疗效。
J Cancer Res Clin Oncol. 1995;121(8):474-7. doi: 10.1007/BF01218364.
5
New targets for pyrimidine antimetabolites in the treatment of solid tumours. 1: Thymidylate synthase.嘧啶抗代谢物在实体瘤治疗中的新靶点。1：胸苷酸合成酶。
Pharm World Sci. 1994 Apr 15;16(2):84-103. doi: 10.1007/BF01880660.
6
Biomodulation of 5-Fu cytotoxicity by folinic acid and its stereoisomers: in vitro experiments with different cell lines of prostatic cancer.亚叶酸及其立体异构体对5-氟尿嘧啶细胞毒性的生物调节作用：前列腺癌不同细胞系的体外实验
Urol Res. 1995;23(3):163-7. doi: 10.1007/BF00389568.

本文引用的文献

1
EFFECT OF DEOXYURIDINE ON INCORPORATION OF TRITIATED THYMIDINE: DIFFERENCE BETWEEN NORMOBLASTS AND MEGALOBLASTS.脱氧尿苷对氚标记胸腺嘧啶掺入的影响：正成红细胞与巨成红细胞的差异
Acta Med Scand. 1964 Apr;175:483-8. doi: 10.1111/j.0954-6820.1964.tb00597.x.
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Entry of malaria parasites into resealed ghosts of human and simian erythrocytes.疟原虫进入人和猿猴红细胞的再封闭血影。
Br J Haematol. 1981 Sep;49(1):97-101. doi: 10.1111/j.1365-2141.1981.tb07201.x.
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Effect of excess folates and deoxyinosine on the activity and site of action of 5-fluorouracil.过量叶酸和脱氧肌苷对5-氟尿嘧啶活性及作用位点的影响。
Cancer Res. 1981 Sep;41(9 Pt 1):3288-95.
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Enzymatic synthesis of folylpolyglutamates. Characterization of the reaction and its products.叶酰聚谷氨酸的酶促合成。反应及其产物的表征。
J Biol Chem. 1980 Jun 25;255(12):5776-88.
5
Relationship of cellular folate cofactor pools to the activity of 5-fluorouracil.细胞叶酸辅助因子库与5-氟尿嘧啶活性的关系。
Mol Pharmacol. 1983 Jan;23(1):190-7.
6
The deoxyuridine suppression test.
Crit Rev Clin Lab Sci. 1984;20(3):205-41. doi: 10.3109/10408368409165775.
7
Deranged DNA synthesis by bone marrow from vitamin B-12-deficient humans.维生素B12缺乏的人类骨髓中DNA合成紊乱。
Br J Haematol. 1968 Jun;14(6):575-92. doi: 10.1111/j.1365-2141.1968.tb00364.x.
8
Treatment of advanced colorectal and gastric adenocarcinomas with 5-fluorouracil and high-dose folinic acid.用5-氟尿嘧啶和高剂量亚叶酸治疗晚期结直肠癌和胃腺癌。
J Clin Oncol. 1986 May;4(5):685-96. doi: 10.1200/JCO.1986.4.5.685.
9
Pharmacokinetics of leucovorin (D,L-5-formyltetrahydrofolate) after intravenous injection and constant intravenous infusion.静脉注射和持续静脉输注后亚叶酸钙（D，L-5-甲酰四氢叶酸）的药代动力学。
NCI Monogr. 1987(5):41-5.
10
The natural and unnatural diastereomers of leucovorin: aspects of their cellular pharmacology.亚叶酸钙的天然和非天然非对映异构体：其细胞药理学方面
Adv Exp Med Biol. 1988;244:13-24. doi: 10.1007/978-1-4684-5607-3_2.

6S、6R和6RS亚叶酸对甲氨蝶呤解救及5-氟尿嘧啶调节的比较效果

Comparative effect of 6S, 6R and 6RS leucovorin on methotrexate rescue and on modulation of 5-fluorouracil.

作者信息

Zittoun J, Marquet J, Pilorget J J, Tonetti C, De Gialluly E

机构信息

Service Central d'Hématologie-Immunologie, Hôpital Henri Mondor Faculté de Médecine, Creteil, France.

出版信息

Br J Cancer. 1991 Jun;63(6):885-8. doi: 10.1038/bjc.1991.194.

DOI:10.1038/bjc.1991.194
PMID:2069845
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1972534/
Abstract

The comparative efficacy of the pure diastereoisomers of leucovorin, the natural (6S) and the unnatural (6R) forms was compared to the racemic form (6RS). A protective effect in methotrexate-treated CCRF-CEM cells was obtained with 6S at concentrations 100-fold higher than those of methotrexate and with 6RS at concentrations 2-fold greater than those of 6S; however, at low concentrations of methotrexate, 6S was more effective than 6RS in preventing the cytotoxicity of methotrexate; on the opposite, 6R exhibited a protective effect at concentrations 10(4) higher than those of methotrexate. On the same cell line, 6S was shown to enhance the cytotoxic effect of 5 Fluorouracil exactly as 6RS while 6R did not exhibit any enhancing effect on cells exposed to 5 Fluorouracil.

摘要

对亚叶酸的纯非对映异构体（天然的(6S)形式和非天然的(6R)形式）与消旋形式(6RS)的比较疗效进行了研究。在甲氨蝶呤处理的CCRF - CEM细胞中，(6S)在浓度比甲氨蝶呤高100倍时具有保护作用，(6RS)在浓度比(6S)高2倍时具有保护作用；然而，在低浓度甲氨蝶呤时，(6S)在预防甲氨蝶呤细胞毒性方面比(6RS)更有效；相反，(6R)在浓度比甲氨蝶呤高10⁴倍时表现出保护作用。在同一细胞系中，(6S)被证明与(6RS)一样能增强5-氟尿嘧啶的细胞毒性作用，而(6R)对暴露于5-氟尿嘧啶的细胞没有任何增强作用。