RESUMEN
Protein phosphatase 2A (PP2A) is a tumor suppressor gene, that has been frequently deactivated in many types of cancer. However, its molecular and clinical relevance in oral squamous cell carcinoma (OSCC) remain unclear. Here we show that, PP2A deactivation is a common event in oral cancer cells and hyperphosphorylation in its tyrosine-307 (Y307) residue contributes to PP2A deactivation. PP2A restoration by FTY720 treatment reduced cell growth and decreased GSK-3ß phosphorylation without significantly altering other PP2A targets. We further detected PP2A phosphorylation in 262 OSCC tissues. Increased expression of p-PP2A in the tumor tissues was significantly correlated with higher N2/N3-stage (aOR = 2.1, 95%CI: 1.2-3.8). Patients with high p-PP2A expression had lower overall survival rates than those with low expression. Hazard ratio analysis showed that, high p-PP2A expression was significantly associated with mortality density (aOR = 2.2, 95%CI: 1.2-4.0) and lower 10-year overall survival (p = 0.027) in lymph node metastasis. However, no interaction was observed between p-PP2A expression and lymph node metastasis. All our results suggest that PP2A is frequently deactivated in oral cancer and determines poor outcome, restoring its expression by FTY720 can be an alternative therapeutic approach in OSCC.
Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Células Escamosas/tratamiento farmacológico , Clorhidrato de Fingolimod/farmacología , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de la Boca/tratamiento farmacológico , Proteína Fosfatasa 2/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/enzimología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Activación Enzimática , Activadores de Enzimas/farmacología , Femenino , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Neoplasias de Cabeza y Cuello/enzimología , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/enzimología , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Análisis Multivariante , Estadificación de Neoplasias , Oportunidad Relativa , Fosforilación , Modelos de Riesgos Proporcionales , Factores de Riesgo , Transducción de Señal/efectos de los fármacos , Carcinoma de Células Escamosas de Cabeza y Cuello , Factores de Tiempo , TirosinaRESUMEN
UNLABELLED: Direct decompositions of nitric oxide (NO) by La0.7Ce0.3SrNiO4, La0.4Ba0.4Ce0.2SrNiO4, and Pr0.4Ba0.4Ce0.2SrNiO4 are experimentally investigated, and the catalysts are tested with different operating parameters to evaluate their activities. Experimental results indicate that the physical and chemical properties of La0.7Ce0.3SrNiO4 are significantly improved by doping with Ba and partial substitution with Pr. NO decomposition efficiencies achieved with La0.4Ba0.4Ce0.2SrNiO4 and Pr0.4Ba0.4Ce0.2SrNiO4 are 32% and 68%, respectively, at 400 °C with He as carrier gas. As the temperature is increased to 600 °C, NO decomposition efficiencies achieved with La0.4Ba0.4Ce0.2SrNiO4 and Pr0.4Ba0.4Ce0.2SrNiO4, respectively, reach 100% with the inlet NO concentration of 1000 ppm while the space velocity is fixed at 8000 hr(-1). Effects of O2, H2O(g), and CO2 contents and space velocity on NO decomposition are also explored. The results indicate that NO decomposition efficiencies achieved with La0.4Ba0.4Ce0.2SrNiO4 and Pr0.4Ba0.4Ce0.2SrNiO4, respectively, are slightly reduced as space velocity is increased from 8000 to 20,000 hr(-1) at 500 °C. In addition, the activities of both catalysts (La0.4Ba0.4Ce0.2SrNiO4 and Pr0.4Ba0.4Ce0.2SrNiO4) for NO decomposition are slightly reduced in the presence of 5% O2, 5% CO2, or 5% H2O(g). For durability test, with the space velocity of 8000 hr(-1) and operating temperature of 600 °C, high N2 yield is maintained throughout the durability test of 60 hr, revealing the long-term stability of Pr0.4Ba0.4Ce0.2SrNiO4 for NO decomposition. Overall, Pr0.4Ba0.4Ce0.2SrNiO4 shows good catalytic activity for NO decomposition. IMPLICATIONS: Nitrous oxide (NO) not only causes adverse environmental effects such as acid rain, photochemical smog, and deterioration of visibility and water quality, but also harms human lungs and respiratory system. Pervoskite-type catalysts, including La0.7Ce0.3SrNiO4, La0.4Ba0.4Ce0.2SrNiO4, and Pr0.4Ba0.4Ce0.2SrNiO4, are applied for direct NO decomposition. The results show that NO decomposition can be enhanced as La0.7Ce0.3SrNiO4 is substituted with Ba and/or Pr. At 600 °C, NO decomposition efficiencies achieved with La0.4Ba0.4Ce0.2SrNiO4 and Pr0.4Ba0.4Ce0.2SrNiO4 reach 100%, demonstrating high activity and good potential for direct NO decomposition. Effects of O2, H2O(g), and CO2 contents on catalytic activities are also evaluated and discussed.