Mechanisms for cisplatin-FUra synergism and cisplatin resistance in human ovarian carcinoma cells both in vitro and in vivo.

Mechanisms for cisplatin-FUra synergism and cisplatin resistance in human ovarian carcinoma cells both in vitro and in vivo.
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人卵巢癌细胞体内外顺铂-FUra 协同作用和顺铂耐药机制。

DOI:
10.1007/978-1-4684-5607-3_12
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发表时间:
1988
影响因子:
--
通讯作者:
Newman,E
Newman,E
中科院分区:
医学4区
文献类型:
--
作者:
Scanlon,KJ;Lu,Y;Kashani-Sabet,M;Ma,J;Newman,E

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顺铂和呋喃在人类癌症中的协同作用。FdUMP与胸苷酸合成酶(TS)紧密结合所必需的还原性叶酸的增加有助于增强该药物组合的细胞毒性。对顺铂产生三倍耐药的人卵巢A2780细胞系显示,二氢叶酸还原酶(DHFR)和TS的m-RNA升高了三倍,然而,这种增加不是由于这两种酶基因的扩增。相比之下,来自顺铂和呋喃治疗失败患者的卵巢癌细胞显示DHFR和TS的基因表达增强和基因拷贝数增加。
Cisplatin and FUra act synergisticly in human carcinomas. An increase in the availability of reduced folates necessary for tight binding of FdUMP to thymidylate synthase (TS) contributes to the enhanced cytotoxicity of this drug combination. The human ovarian A2780 cell line made three-fold resistant to cisplatin has been shown to have a three-fold elevation of m-RNA for dihydrofolate reductase (DHFR) and TS. However, this increase did not result from an amplification of the genes for these two enzymes. In contrast, ovarian carcinoma cells from patients who failed treatment with cisplatin and FUra have been shown to have both enhanced gene expression and increased gene copy number for DHFR and TS.
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