CISPLATIN INCREASES SENSITIVITY OF HUMAN LEUKEMIC BLASTS TO TRIAZENE COMPOUNDS

被引:35
作者
PICCIONI, D [1 ]
DATRI, S [1 ]
PAPA, G [1 ]
CARAVITA, T [1 ]
FRANCHI, A [1 ]
BONMASSAR, E [1 ]
GRAZIANI, G [1 ]
机构
[1] UNIV ROMA TOR VERGATA,DIPARTIMENTO MED SPERIMENTALE & SCI BIOCHIM,I-00133 ROME,ITALY
关键词
CISPLATIN; DACARBAZINE; LEUKEMIA; O-6-ALKYL-GUANINE-DNA-ALKYLTRANSFERASE; TEMOZOLOMIDE;
D O I
10.1179/joc.1995.7.3.224
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
High levels of O-6-alkylguanine-DNA-alkyltransferase (OGAT) can, at least in part, account for tumor cell resistance to O-6-alkylguanine alkylating agents, including triazene compounds. A pilot clinical study indicates that dacarbazine can induce a marked decrease of leukemic blasts in patients affected by acute myelogenous leukemia (AML) with low pretreatment levels of OGAT activity. In this study we show a synergistic antitumor effect between cisplatin (CDDP) and temozolomide (an in vitro active analog of dacarbazine), following combined in vitro treatment of leukemic blasts. Synergistic effect appears to be CDDP-dose dependent. In vivo treatment of leukemic patients with CDDP was followed by a reduction of OGAT activity in 2 out 3 cases. These data point out that CDDP could be a good candidate for depleting OGAT protein of leukemic cells, thus reversing tumor cell resistance to dacarbazine.
引用
收藏
页码:224 / 229
页数:6
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