ZEB1 is a Subgroup-Specific Marker of Prognosis and Potential Drug Target in Medulloblastoma.

Medulloblastoma (MB) is a malignant brain tumor that afflicts mostly children and adolescents and presents four distinct molecular subgroups, known as WNT, SHH, Group 3, and Group 4. ZEB1 is a transcription factor that promotes the expression of mesenchymal markers while restraining expression of epithelial and polarity genes. Because of ZEB1 involvement in cerebellum development, here we investigated the role of ZEB1 in MB. We found increased expression of ZEB1 in MB tumor samples compared to normal cerebellar tissue. Expression was higher in the SHH subgroup when compared to all other MB molecular subgroups. High ZEB1 expression was associated with poor prognosis in Group 3 and Group 4, whereas in patients with WNT tumors poorer prognosis were related to lower ZEB1 expression. There was a moderate correlation between ZEB1 and MYC expression in Group 3 and Group 4 MB. Treatment with the immunomodulator and histone deacetylase (HDAC) inhibitor fingolimod (FTY720) reduced ZEB1 expression specifically in D283 cells, which are representative of Group 3 and Group 4 MB. These findings reveal novel subgroup-specific associations of ZEB1 expression with survival in patients with MB and suggest that ZEB1 expression can be reduced by pharmacological agents that target HDAC activity.

Body mass index, abdominal obesity, body fat and migraine features in women.

BACKGROUND: Studies seeking to establish an association between migraine and anthropometric parameters have thus far been inconclusive. Furthermore, drugs used for migraine prophylaxis may be associated with changes in body weight. OBJECTIVE: To investigate the potential association of anthropometric parameters and body fat percentage with attack patterns and use of prophylactic medication in migraineurs. METHODS: Cross-sectional study that assessed the body mass index, waist circumference, body fat percentage and related clinical variables (characteristics of attacks and the use of prophylactic medication) in female outpatients with migraine. RESULTS: 166 female migraineurs aged ≥18 years (mean age, 45 ± 14 years) were included in the study. Migraine without aura was most prevalent (71.7%). Mean body mass index and body fat percentage were 27.8±6.0 kg/m² and 36.4 ± 8.3% respectively. Body mass index and waist circumference were weakly correlated with frequency of attacks over 6 months (rs = 0.162, p < 0.05 and rs = 0.187, p < 0.05 respectively). These correlations remains weak considering only premenopausal women, but disappear in the older women. Stratification of analysis by migraine type field shows a moderate correlation between migraine with aura and frequency of attacks over 6 months and body mass index (rs = 0.369, p < 0.05), as well as waist circumference (rs = 0.423, p < 0.01). Patients who were on prophylactic medication had higher body mass index, waist circumference, and body fat percentage values (p < 0.01, Student t-test). CONCLUSION: This study revealed a potential, though tenuous association between migraine and anthropometric parameters and frequency of attacks, which does not reflect on the duration, severity, and disability of attacks, with patterns differing by migraine type, reproductive age and prophylactic medication.

Introducción: Los estudios que tratan de establecer una asociación entre la migraña y los parámetros antropométricos hasta ahora han sido poco concluyentes. Además, los fármacos utilizados para la profilaxis de la migraña pueden estar asociados con cambios en el peso corporal. Objetivos: Investigar la posible asociación de los parámetros antropométricos y el porcentaje de grasa corporal con patrones de ataque y el uso de la profilaxis en los pacientes con migraña. Métodos: Estudio transversal que evaluó el índice de masa corporal, circunferencia de cintura, porcentaje de grasa corporal y las variables clínicas (características de los ataques y uso de medicación) en mujeres con migraña. Resultados: 166 mujeres con migraña ≥18 años (edad media, 45 ± 14 años) fueron incluidos en el estudio. Migraña sin aura era más frecuente (71,7%). La media del índice de masa corporal y porcentaje de grasa corporal fueron 27,8 ± 6,0 kg/m2 y 36,4 ± 8,3%, respectivamente. Índice de masa corporal y la circunferencia de cintura se correlacionaron débilmente con la frecuencia de los ataques durante 6 meses (rs = 0,162, p < 0,05 y r = 0,187, p < 0,05, respectivamente). Estas correlaciones se mantiene débil considerando sólo las mujeres premenopáusicas, pero desaparecen en las mujeres mayores. La estratificación de los análisis por tipo migraña muestra una correlación moderada entre la migraña con aura y la frecuencia de los ataques de más de 6 meses y el índice de masa corporal (rs = 0,369, p < 0,05), así como la circunferencia de cintura (rs = 0,423, p < 0,01) . Los pacientes que estaban tomando medicamentos profilácticos tuvieron un mayor índice de masa corporal, circunferencia de la cintura, y los valores de porcentaje de grasa corporal (p < 0,01, prueba t de Student). Conclusiones: Este estudio reveló un potencial, aunque débil asociación entre la migraña y los parámetros antropométricos y la frecuencia de ataques, que no refleja la duración, la gravedad y la incapacidad de los ataques, que tienen diferentes modelos según el tipo de migraña, la edad reproductiva y la medicación profiláctica.