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- W2149249942 abstract "Cisplatin (cis-diammine dichloroplatinum, CDDP) is an established square planar coordination compound, which is effective against ovarian cancer (1). The antitumour activity of CDDP is the result of formation of adducts within the DNA (2). Resistance against CDDP treatment may be related to an increased DNA repair. Like CDDP, Gemcitabine (2’,2’-difluorodeoxycytidine, dFdC) is active against human ovarian carcinoma (3, 4). After entering the cell, dFdC requires activation catalyzed by deoxycytidine kinase (dCK), and can be inactivated by the action of deoxycytidine deaminase (dCDA)(5). The active metabolite dFdCTP can be incorporated into both DNA and RNA (6). For both 1-ß-D-arabinofuranosylcytosine (ara-C) and 2’-deoxy-5-azacytidine (DAC) two other deoxycytidine analogues, synergy with CDDP has already been described (7, 8). The next logical step was to combine dFdC with CDDP. Both agents have a different mechanism of action. A combination is also attractive from a clinical point of view, since both drugs have different side effects. We tested this combination in different concentrations and schedules in the human ovarian cancer cell line A2780, its 50 fold CDDP resistant variant ADDP (9), its 150,000 fold dFdC resistant variant AG6000 (10), and in the murine colon cancer cell line C26-10, which has an inherent lower sensitivity to both drugs compared to A2780 (11). These results were related to both dCK and dCDA activities and the effect of CDDP on dFdCTP accumulation." @default.
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- W2149249942 date "1995-01-01" @default.
- W2149249942 modified "2023-10-06" @default.
- W2149249942 title "Synergistic Interaction between Cisplatin and Gemcitabine in Ovarian and Colon Cancer Cell Lines" @default.
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- W2149249942 doi "https://doi.org/10.1007/978-1-4615-2584-4_32" @default.
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