High levels of O6-alkylguanine-DNA-alkyltransferase (OGAT) can, at least in part, account for tumor cell resistance to O6-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.

Piccioni, D., D'Atri, S., Papa, G., Caravita, T., Franchi, A., Bonmassar, E., et al. (1995). Cisplatin increases sensitivity of human leukemic blasts to triazene compounds. JOURNAL OF CHEMOTHERAPY, 7(3), 224-229.

Cisplatin increases sensitivity of human leukemic blasts to triazene compounds

FRANCHI, ANNIBALE;BONMASSAR, ENZO;GRAZIANI, GRAZIA
1995-06-01

Abstract

High levels of O6-alkylguanine-DNA-alkyltransferase (OGAT) can, at least in part, account for tumor cell resistance to O6-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.
giu-1995
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/14 - FARMACOLOGIA
English
Con Impact Factor ISI
Blast Crisis; Dacarbazine; O(6)-Methylguanine-DNA Methyltransferase; Dose-Response Relationship, Drug; Humans; Aged; Pilot Projects; Leukemia, Megakaryoblastic, Acute; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Leukemia; Triazenes; Cisplatin; Adult; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols; Middle Aged; Methyltransferases; Drug Synergism; Male; Female; Remission Induction
Piccioni, D., D'Atri, S., Papa, G., Caravita, T., Franchi, A., Bonmassar, E., et al. (1995). Cisplatin increases sensitivity of human leukemic blasts to triazene compounds. JOURNAL OF CHEMOTHERAPY, 7(3), 224-229.
Piccioni, D; D'Atri, S; Papa, G; Caravita, T; Franchi, A; Bonmassar, E; Graziani, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/68031
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