RESUMO
BACKGROUND: Transcription factor STAT3 has a prominent innate immunity effect on cancer progression. We determined the regulation of STAT3 in the immunophenotype modulation of macrophages from M1 into M2 induced by the cell-culture supernatant of the Prostate-Cancer line PC3. METHODS: Monocytes-macrophages from healthy donors were cultured in the supernatant of PC3 cells, membrane proteins, and intracytoplasmic and phosphorylated STAT3 were measured using flow cytometry, while cytokines and growth factors were studied using luminescence. Cytotoxicity and nitric oxide were evaluated via colorimetric assays. RESULTS: The supernatant of PC3 prostate-tumor cells effectively induced macrophages toward an M2 profile, and the expression of phosphorylated STAT3 in the monocytes-macrophages notably increased, and mainly related to IL-10. In the group of monocytes-macrophages treated with a STAT3 inhibitor, the macrophages were induced toward an M1 phenotype. CONCLUSIONS: In this study, we showed that the secretion profile of PC3 prostate-cancer cells induces a change in macrophage phenotype from M1 into M2, and that the phenomenon is related to phosphorylation of transcription factor STAT3 and IL-10.
Assuntos
Meios de Cultivo Condicionados/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Monócitos/imunologia , Fator de Transcrição STAT3/imunologia , Células Cultivadas , Humanos , Imunofenotipagem , Interleucina-10/imunologia , Interleucina-10/metabolismo , Macrófagos/metabolismo , Masculino , Células PC-3 , Fosforilação/efeitos dos fármacos , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Fator de Transcrição STAT3/metabolismoRESUMO
PURPOSE: Pentoxifylline (PTX) has been shown to increase chemotherapy-induced apoptosis. A clinical trial was developed to evaluate the effect of the addition of PTX to the induction steroid window phase in children with acute lymphoblastic leukemia (ALL). METHODS: Thirty-two children were enrolled on this study. Children with a new diagnosis of ALL were randomly assigned to receive prednisone (PRD) 40 mg/m(2)/day only during the 7-day treatment pre-phase (PRD group, 11 patients) or to receive PRD with PTX (10 mg/kg/day) (PTX group, 11 patients); the control group included children with normal bone marrow (10 patients). Bone marrow aspiration (BMA) was performed at diagnosis (day -7) in all groups, and at day 0 (end of PRD window) for patients with ALL (PRD and PTX groups). Apoptosis was evaluated by flow cytometry (FC) using Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) stains. Statistical analysis was performed using the Mann-Whitney U test. RESULTS: Apoptotic index at day -7 was similar in all groups. However, at day 0 post-treatment, apoptosis was significantly higher in the PTX group than in the PRD group (p < 0.001). There were no serious adverse effects associated with PTX. CONCLUSIONS: PTX potentiates blast apoptosis induced by PRD in children with ALL during steroid window phase.
Assuntos
Apoptose/efeitos dos fármacos , Pentoxifilina/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prednisona/uso terapêutico , Adolescente , Anti-Inflamatórios/uso terapêutico , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Citometria de Fluxo , Seguimentos , Sequestradores de Radicais Livres/uso terapêutico , Humanos , Lactente , Masculino , Estadiamento de Neoplasias , Projetos Piloto , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Indução de RemissãoRESUMO
Several studies have demonstrated that the serum of patients with cancer contains antibodies that react with a group of autoantigens denominated tumor-associated antigens (TAA). TAA can be detected prior to clinical diagnosis; thus, they would be ideal biomarkers for early detection of cancer, using only a few microliters of a patient's serum. In the current study, we used an immune proteomic approach, combining two-dimensional (2D) electrophoresis, Western blot, and matrix-associated laser desorption/ionization-mass spectrometry (MALDI-MS) methods to identify TAA in the sera of patients diagnosed with breast cancer. Sera were obtained from 36 newly diagnosed patients with stage II breast cancer and those from 36 healthy volunteers were evaluated for the presence of the TAA. Alpha 2HS-glycoprotein (AHSG) antibodies were detected in 33 of 36 patients with breast cancer (91.7%) and in only 3 of 36 healthy patients (controls, 8.3%). Sensitivity of detection of autoantibodies against AHSG in patients with breast cancer was 91.7%. AHSG was detected in cancer tissue by immunohistochemistry. Our results strongly suggest that the presence of serum autoantibodies against AHSG protein may be useful as serum biomarkers for early-stage breast cancer screening and minimally invasive diagnosis in Mexican populations. BIOLOGICAL SIGNIFICANCE: In the present study, 2D immunoblot analysis was used to make a screening in samples of sera from patients with a diagnosis of early-stage breast cancer, in order to identify some autoantibodies that react against TAA. Proteins identified in the present study, particularly alpha 2HS-glycoprotein (AHSG), might be useful as potential biomarkers for breast cancer in early stages for Mexican populations.