CISPLATIN INCREASES SENSITIVITY OF HUMAN LEUKEMIC BLASTS TO TRIAZENE COMPOUNDS

Citation
D. Piccioni et al., CISPLATIN INCREASES SENSITIVITY OF HUMAN LEUKEMIC BLASTS TO TRIAZENE COMPOUNDS, Journal of chemotherapy, 7(3), 1995, pp. 224-229
Citations number
NO
Categorie Soggetti
Oncology,"Pharmacology & Pharmacy
Journal title
ISSN journal
1120009X
Volume
7
Issue
3
Year of publication
1995
Pages
224 - 229
Database
ISI
SICI code
1120-009X(1995)7:3<224:CISOHL>2.0.ZU;2-7
Abstract
High levels of O-6-alkylguanine-DNA-alkyltransferase (OGAT) can, at le ast in part, account for tumor cell resistance to O-6-alkylguanine alk ylating agents, including triazene compounds. A pilot clinical study i ndicates that dacarbazine can induce a marked decrease of leukemic bla sts in patients affected by acute myelogenous leukemia (AML) with low pretreatment levels of OGAT activity. In this study we show a synergis tic antitumor effect between cisplatin (CDDP) and temozolomide (an in vitro active analog of dacarbazine), following combined in vitro treat ment of leukemic blasts. Synergistic effect appears to be CDDP-dose de pendent. In vivo treatment of leukemic patients with CDDP was followed by a reduction of OGAT activity in 2 out 3 cases. These data point ou t that CDDP could be a good candidate for depleting OGAT protein of le ukemic cells, thus reversing tumor cell resistance to dacarbazine.