RESUMO
BACKGROUND: Sox11 is a transcription factor expressed in foetal and neoplastic brain tissue, including gliomas. It has been shown to suppress the tumourigenicity of glioma stem cells in vivo, thereby being hypothesised to function as a tumour suppressor. METHODS: We investigated the expression of Sox11 in 132 diffuse astrocytomas in relation to the regulator cell marker nestin, c-Met and IDH1-R132H, which have shown to be differentially expressed among the molecular subgroups of malignant gliomas, as well as to an inducer of astrocytic differentiation, that is, signal transducer and activator of transcription (p-STAT-3), clinicopathological features and survival. RESULTS: Sox11 immunoreactivity was identified in all tumours irrespective of grade, but being correlated with p-STAT-3. Three out of seven cases showed partial Sox11 promoter methylation. In >50% of our cases neoplastic cells coexpressed Sox11 and nestin, a finding further confirmed in primary glioblastoma cell cultures. Furthermore, nestin, c-Met and IDH1-R132H expression differed among grade categories. Cluster analysis identified four groups of patients according to c-Met, nestin and IDH1-R132H expression. The c-Met/nestin high-expressor group displayed a higher Sox11 expression. Sox11 expression was an indicator of favourable prognosis in glioblastomas, which remained in multivariate analysis and validated in an independent set of 72 cases. The c-Met/nestin high-expressor group was marginally with shorter survival in univariate analysis. CONCLUSIONS: We highlight the importance of Sox11 expression as a favourable prognosticator in glioblastomas. c-Met/nestin/IDH1-R132H expression phenotypes recapitulate the molecular subgroups of malignant glioma.
Assuntos
Astrocitoma/genética , Neoplasias Encefálicas/genética , Proteínas de Filamentos Intermediários/genética , Isocitrato Desidrogenase/genética , Proteínas do Tecido Nervoso/genética , Proteínas Proto-Oncogênicas c-met/genética , Fatores de Transcrição SOXC/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , Arginina/genética , Astrocitoma/diagnóstico , Astrocitoma/metabolismo , Astrocitoma/mortalidade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Estudos de Coortes , Feminino , Regulação Neoplásica da Expressão Gênica , Histidina/genética , Humanos , Proteínas de Filamentos Intermediários/metabolismo , Isocitrato Desidrogenase/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/metabolismo , Nestina , Fenótipo , Fosforilação , Prognóstico , Proteínas Quinases/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Fatores de Transcrição SOXC/metabolismo , Fator de Transcrição STAT3/metabolismo , Análise de Sobrevida , Células Tumorais Cultivadas , Adulto JovemRESUMO
INTRODUCTION: The aim of the presented study was to investigate nerve regeneration after application of C3-Toxin, a Rho-GTPase inhibitor and to correlate morphometry, neurophysiology, and function in an end-to-side peroneal/tibial nerve repair model of the rat. MATERIALS AND METHODS: Twenty rats with a peroneal to tibial end-to-side neurorrhaphy were divided into two groups: 1) control group, 2) C3 fusion toxin group with intrafascicular application of 1 µg/100 µl C3 fusion toxin. Survival time was 8 weeks. Nerve conduction velocities and motor function were analyzed and histomorphological evaluation consisting of measurement of intraneural collagen level, axon count, total nerve area, myelination index, and N-ratio followed. RESULTS: Evaluation of motor function and nerve conduction did not show any statistical differences. Histological analysis revealed higher axon count, thicker myelin sheaths, and higher myelination index in the C3 fusion toxin group (P < 0.001). Comparison of N-ratio and intraneural collagen level were without statistical significance. CONCLUSION: The current study shows that application of C3 fusion toxin leads to higher myelination and increases axonal sprouting.
