[Potentiation of the antiblastic activity of mafosfamide by GM-CSF and interleukin-3: a possible use in the treatment of acute myeloblastic leukemia].
The low activity of antiblastic drugs on tumor cells in the G0 phase is an important limitation in the therapy of malignancies. Cells in the G0 phase are able to enter in cycle any time after chemotherapy treatment, causing relapse of the disease. The use of colony stimulating factors (for example granulocyte-macrophage stimulating factor-GM-CSF and interleukin 3-IL-3) permits the recruitment in cycle of myeloblastic leukemic cells in the G0 phase and thus a cellular population sensitive to chemotherapy. We evaluated the in vitro activity of GM-CSF and IL-3 in fresh myeloblastic leukemic cells: after 96 h of incubation with GM-CSF (500 U/mL), IL-3 (500 U/mL), and GM-CSF + IL-3 (500 + 500 U/mL), 10(6) cells were treated with mafosfamide (30 microgram/mL x 30 min); 10(6) cells were simultaneously treated with mafosfamide without preincubation with colony stimulating factors. The sensitivity of leukemic cells preincubated with GM-CSF and IL-3 to the cytotoxic action of mafosfamide was greater than that of the control cells treated with mafosfamide alone. No enhancement of cytotoxic activity of mafosfamide was observed with GM-CSF + IL-3 combined treatment. The use of colony stimulating factors may effectively increase the number of leukemic cells sensitive to alkylating drugs.
Tolomeo
M
M
Clinica Medica Generale e Terapia Medica R, Università degli Studi di Palermo.
Luparello
M
M
Caravello
E
E
Musso
M
M
Abbadessa
V
V
Perricone
R
R
Cajozzo
A
A
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007377:Interleukin-3 / Q000008:administration & dosage*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D007377:Interleukin-3; C048341:mafosfamide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide
Potenziamento dell'attività antiblastica della mafosfamide mediante GM-CSF e interleuchina-3: una possibile applicazione nel trattamento delle leucemie acute mieloblastiche.