Mir-21-Sox2 Axis Delineates Glioblastoma Subtypes with Prognostic Impact.

UNLABELLED: Glioblastoma (GBM) is the most aggressive human brain tumor. Although several molecular subtypes of GBM are recognized, a robust molecular prognostic marker has yet to be identified. Here, we report that the stemness regulator Sox2 is a new, clinically important target of microRNA-21 (miR-21) in GBM, with implications for prognosis. Using the MiR-21-Sox2 regulatory axis, approximately half of all GBM tumors present in the Cancer Genome Atlas (TCGA) and in-house patient databases can be mathematically classified into high miR-21/low Sox2 (Class A) or low miR-21/high Sox2 (Class B) subtypes. This classification reflects phenotypically and molecularly distinct characteristics and is not captured by existing classifications. Supporting the distinct nature of the subtypes, gene set enrichment analysis of the TCGA dataset predicted that Class A and Class B tumors were significantly involved in immune/inflammatory response and in chromosome organization and nervous system development, respectively. Patients with Class B tumors had longer overall survival than those with Class A tumors. Analysis of both databases indicated that the Class A/Class B classification is a better predictor of patient survival than currently used parameters. Further, manipulation of MiR-21-Sox2 levels in orthotopic mouse models supported the longer survival of the Class B subtype. The MiR-21-Sox2 association was also found in mouse neural stem cells and in the mouse brain at different developmental stages, suggesting a role in normal development. Therefore, this mechanism-based classification suggests the presence of two distinct populations of GBM patients with distinguishable phenotypic characteristics and clinical outcomes. SIGNIFICANCE STATEMENT: Molecular profiling-based classification of glioblastoma (GBM) into four subtypes has substantially increased our understanding of the biology of the disease and has pointed to the heterogeneous nature of GBM. However, this classification is not mechanism based and its prognostic value is limited. Here, we identify a new mechanism in GBM (the miR-21-Sox2 axis) that can classify ∼50% of patients into two subtypes with distinct molecular, radiological, and pathological characteristics. Importantly, this classification can predict patient survival better than the currently used parameters. Further, analysis of the miR-21-Sox2 relationship in mouse neural stem cells and in the mouse brain at different developmental stages indicates that miR-21 and Sox2 are predominantly expressed in mutually exclusive patterns, suggesting a role in normal neural development

Avaliação do padrão de recuperação nutricional de crianças desnutridas atendidas no centro de recuperação e educação nutricional Pattern of nutritional recovery in malnourished children

Estudo de acompanhamento do padrão de recuperação nutricional de crianças desnutridas atendidas no Centro de Recuperação e Educação Nutricional (CREN), entre setembro de 1995 e novembro de 1996. OBJETIVO: Avaliar a recuperação nutricional das crianças em termos de velocidade de ganho anual de peso/idade e estatura/idade e identificar variações do processo de recuperação de acordo com o sexo e a idade. MÉTODOS: Foram estudadas 38 crianças, utilizando-se os valores do incremento de peso/idade e estatura/idade em unidades de desvio padrão ou escore Z, em relação à mediana de peso e estatura do padrão NCHS, pelo método da velocidade de crescimento por incremento. RESULTADOS: Houve uma relação significante entre ganhos de peso/idade (P=0,012) e estatura/idade (P=0,001) e tempo de internação. Os pré-escolares tiveram uma velocidade de ganho de peso/idade significantemente maior (0,684 escores Z/ano) que os lactentes (0,299 escores Z/ano), excluídas as crianças com menos de seis meses de internação. Em relação à velocidade de ganho de estatura/idade, os lactentes apresentaram um ganho maior (0,794 escores Z/ano) em relação aos pré-escolares( 0,506 escores Z/ano), embora a diferença não tenha sido estatisticamente significante. Entre os sexos, a velocidade de ganho de peso/idade foi 0,540 e 0,524 escores Z/ano para meninos e meninas, respectivamente. Quanto à velocidade de ganho de estatura/idade as meninas apresentaram um ganho significantemente maior (0,856 escores Z/ano) que os meninos (0,485 escores Z/ano). CONCLUSÃO: O presente trabalho evidenciou que existem diferenças no padrão de velocidade de recuperação nutricional de acordo com a idade e sexo.<br>PURPOSE: To assess the pattern of nutritional recovery in malnourished children. This prospective analysis was conducted between September 1995 and November 1996 at the Center for Recovery and Nutrition Education (CREN) in São Paulo, Brazil. Of the thirty-eight children studied, 47.4% were infants (nine girls and nine boys) and 52.6% preschool children (twelve boys and eight girls). METHOD: Thirty eight children were studed by velocity of W/A and H/A gain in standard deviation or Z score, according to weight and height median of NCHS. RESULTS: There was a statistically significant increase in the weight-for-age (W/A)(p=0.012), height-for-age (H/A) ( p=0.001) from the time of admission.The difference in the velocity of W/A gain between infants (0.299-Z/year) and preschool children (0.684-Z/year) with more than six months of treatment, was found to be statistically significant (p=0.038). The difference in the velocity of H/A gain for infants (0.794-Z/year) and for preschool chidren (0.506-Z/year), was not statistically significant (p=0.166). In regards to gender, there was not a statistically significant difference between boys and girls in the velocity of W/A gain (0.540 and 0.524-Z/year, respectively). The difference in velocity of H/A gain was statisically significant, 0.485-Z/year for boys and 0.856-Z/year for girls (p=0.043). CONCLUSION: These findings show that there are differences in the nutritional recovery patterns between gender and age groups