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[潜在致死性损伤修复(PLDR)抑制剂的抗肿瘤效应问题——药代动力学]

[Problems of antineoplastic effects by PLDR (potential lethal damage repair) inhibitor--pharmacokinetics].

作者信息

Sougawa M, Akagi K, Yoshii G, Tanaka Y

出版信息

Gan No Rinsho. 1984 Nov;30(14):1787-92.

PMID:6334757
Abstract

PLDR is one known cause of tumor cell radioresistance. Drugs like ara-A have been reported to inhibit PLDR, thus increasing antineoplastic effects. In this research, ara-A concentration was measured by high-pressure liquid chromatography (HPLC) to investigate its metabolism. Ara-A deaminases in vitro in about 30 minutes, but by using a deaminase inhibitor such as 2'-deoxycoformycin, a fixed level of ara-A can be maintained. Furthermore, the new derivative, ara-AMP, does not deaminase. It is hoped that antineoplastic effects can be effectively increased by maintaining the ara-A concentration through the combined use of deaminase inhibitors and through new derivatives.

摘要

潜在致死性损伤修复(PLDR)是肿瘤细胞放射抗性的一个已知原因。据报道,像阿糖腺苷(ara - A)这样的药物可抑制PLDR,从而增强抗肿瘤作用。在本研究中,通过高压液相色谱法(HPLC)测定阿糖腺苷浓度以研究其代谢情况。阿糖腺苷在体外约30分钟内会发生脱氨反应,但使用诸如2'-脱氧助间型霉素这样的脱氨酶抑制剂,可维持阿糖腺苷的固定水平。此外,新衍生物阿糖腺苷一磷酸(ara - AMP)不会发生脱氨反应。希望通过联合使用脱氨酶抑制剂和新衍生物来维持阿糖腺苷浓度,从而有效增强抗肿瘤作用。

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