RESUMO
Histone deacetylase inhibitors (HDACis) are epigenetic agents that display antitumor activities in experimental medulloblastoma (MB). Fingolimod (FTY720), an immunosuppressant agent currently used in the treatment of multiple sclerosis, also has anticancer actions and can act as an HDACi. Here we examined whether fingolimod can inhibit human MB cell viability and survival, and if the effects are accompanied by increased histone acetylation. D283 and DAOY MB cells were treated with different doses of fingolimod. Cell viability was assessed by cell counting in a hemocytometer, and cell survival was analyzed with a colony formation assay. Histone H3 acetylation was measured with an enzyme-linked immunosorbent assay (ELISA). Fingolimod at 7.5 or 10 µM, but not at 5 µM, induced a significant reduction in cell viability in D283 and DAOY cultures, and similar results were observed for inhibition of cell survival. In both cell lines, fingolimod also led to a significant increase in the levels of acetylated H3. These findings provide preliminary evidence indicating that fingolimod induces antitumor activities in MB, possibly through a mechanism which increases H3 histone acetylation.
Assuntos
Cloridrato de Fingolimode/uso terapêutico , Imunossupressores/uso terapêutico , Meduloblastoma/tratamento farmacológico , Acetilação , Cloridrato de Fingolimode/farmacologia , Humanos , Imunossupressores/farmacologiaRESUMO
BACKGROUND: Headache has been described as a factor with significant negative impact on the quality of life of school-aged children with a high risk of developing in chronic and persistent form in adulthood. Among other headache associated triggers or aggravating factors, lifestyle and obesity has been investigated, but results are still conflicting. OBJECTIVE: To evaluate the prevalence of headache in school-aged children and its relationship to anthropometric characteristics, lifestyle, and quality of life. METHODS: A cross-sectional study was conducted in six schools located in two cities in southern Brazil, involving 750 students aged 7 to 14 years. Information was collected on sociodemographic characteristics, clinical variables (presence of headache and menarche), anthropometric data, lifestyle, and quality of life. RESULTS: A total of 185 (24.7%) students reported having headache crises in the last 3 months. Among students aged 10 to 14 years, presence of headache was associated with female sex, affecting 32.2% of girls vs. 23.3% of boys (p = 0.042, chi-square test). Anthropometric parameters (data on overweight/obesity) were consistent with national prevalence rates, and there was no association between Body Mass Index (BMI) and headache. Regarding lifestyle, 2.0% of students reported smoking and 1.6% consuming alcohol occasionally, and neither was associated with headache. Quality of life, especially aspects of social life, appeared to be affected by the presence of headache. CONCLUSION: This study found a high prevalence of headache in school-aged children, which was associated with female students aged 10-14 years and quality of life.
Introducción: Dolor de cabeza se ha descrito como un factor con impacto negativo significativo en la calidad de vida de los niños en edad escolar, con alto riesgo de desarrollar la forma crónica y persistente en la edad adulta. Entre otros factores desencadenantes o agravantes asociados, se ha investigado el estilo de vida y la obesidad, pero los resultados siguen siendo contradictorios. Objetivo: Evaluar la prevalencia de dolor de cabeza en niños en edad escolar y su relación con las características antropométricas, estilo de vida y calidad de vida. Métodos: Un estudio transversal se llevó a cabo en seis escuelas ubicadas en dos ciudades del sur de Brasil, con la participación de 750 estudiantes de 7 a 14 años. Se obtuvo información sobre características sociodemográficas, variables clínicas (presencia de dolor de cabeza y la menarquia), datos antropométricos, estilo de vida y calidad de vida. Resultados: Un total de 185 (24,7%) estudiantes reportaron tener crisis de dolor de cabeza en los últimos 3 meses. Entre los estudiantes de 10 a 14 años, presencia de dolor de cabeza se asoció con el sexo femenino, que afecta a un 32,2% de niñas frente a un 23,3% de los varones (p = 0,042, chi-cuadrado). Parámetros antropométricos (datos de sobrepeso/ obesidad) fueron consistentes con las tasas nacionales de prevalencia, y no hubo asociación entre el Índice de Masa Corporal (IMC) y dolor de cabeza. En cuanto a estilo de vida, 2,0% de los estudiantes reportaron fumar y un 1,6% el consumo de alcohol de vez en cuando, y no se asoció con dolor de cabeza. La calidad de vida, especialmente los aspectos de la vida social, parece estar afectada por la presencia de dolor de cabeza. Conclusión: Este estudio encontró una alta prevalencia de dolor de cabeza en niños en edad escolar, que se asoció con estudiantes de 10-14 años y la calidad de vida.