RESUMO
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.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Antineoplásicos/uso terapêutico , Ciclofosfamida/análogos & derivados , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Interleucina-3/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Fatores de Tempo , Células Tumorais CultivadasAssuntos
Otopatias/veterinária , Cobaias , Hematoma/veterinária , Doenças dos Roedores/patologia , Animais , Otopatias/patologia , Otopatias/cirurgia , Cobaias/cirurgia , Hematoma/complicações , Hematoma/patologia , Hematoma/cirurgia , Masculino , Otite Externa/complicações , Otite Externa/veterinária , Doenças dos Roedores/cirurgiaRESUMO
BACKGROUND: Resistance of tumor cells to cytotoxic agents can be due to the overexpression of the mdr 1 gene, which encodes a plasma membrane protein (P-glycoprotein). To understand the molecular basis of multidrug resistance, several laboratories have isolated cell lines resistant to doxorubicin, actinomycin D, vinca alkaloids and related agents. Many months or years of culture with gradually increasing concentrations of cytotoxic agents are necessary to obtain a resistant cell line. METHODS: We selected a new multidrug resistant cell line (MELC-DRTL) by 24-hour cycles of exposure to relatively high concentrations of daunorubicin from sensitive Friend Leukemia cells. After each cycle, the residual live cells were expanded up to the density of 1 x 10(6) cells/ml. RESULTS: The assay conducted with MoAb C-219 showed a high expression on the membrane surface of P-glycoprotein in the MELC-DRTL line, but the fact that it was impossible to obtain a complete reversal of the resistance, even when using high concentrations of verapamil, suggests the presence of other mechanisms unrelated to the presence of P-glycoprotein. CONCLUSIONS: The kind of cellular resistance induction used in this experiment enabled us to obtain an MDR cell line in three months of culture.
Assuntos
Daunorrubicina/farmacologia , Vírus da Leucemia Murina de Friend , Leucemia Eritroblástica Aguda/patologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Animais , Resistência a Medicamentos , Citometria de Fluxo , Glicoproteínas de Membrana/análise , Glicoproteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/análise , Camundongos , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/patologiaRESUMO
A preliminary screening of 511 persons at risk for AIDS living in southeastern Italy disclosed 20 cases of seroreactivity to human T lymphotropic viruses (HTLV). To verify and type the HTLV infection among these subjects, confirmatory serologic tests, polymerase chain reaction (PCR), and virus culture were done. No evidence of HTLV-I infection was found. HTLV-II infection was confirmed in 8 cases by HTLV-specific, synthetic peptide EIAs and PCR on uncultured cells; restriction analysis of the PCR-amplified env regions revealed the presence of HTLV-II/b strains in all 8 cases. Four sera were nontypeable by EIA. The finding of such indeterminate reactivities in a geographic area in which HTLV variants were previously described indicates the need for more extensive surveys among the healthy population. HTLV-II was isolated in 5 cases, and virus isolation was mostly dependent on the presence of an actively replicating human immunodeficiency virus type 1 in culture.