RESUMO
We examined postoperative material from 28 patients aged 39-61 years with gliomas of different degrees of anaplasia (the diagnosis was histologically verified according to the WHO classification of CNS tumors) who had not previously received antitumor treatment. In glioma tissue, the glucose concentration was significantly higher than in the brain tissue of subjects dead from traumas (control), while lactate concentration did not differ from that in the control group or was lower. Hexokinase activity demonstrated a tendency to an increase in grade I and significant elevation in grades II and III, while in grade IV gliomas, this parameter did not differ from the control. Activities of the pentose-phosphate pathway enzymes glucose-6-phosphate dehydrogenase and transketolase increased with increasing of tumor anaplasia. Activity of glycogen synthase 3ß kinase was significantly higher than in the control group. IDH1 mutation was discovered in 40% cases, the MGMT promoter methylation was detected in more than 50%, the Ki-67 level increased with increasing tumor anaplasia. The most significant correlations with glioma markers were detected for glucose-6-phosphate dehydrogenase and glycogen synthase 3ß kinase. Activities of the studied enzymes of carbohydrate metabolism significantly correlated with Ki-67 marker.
Assuntos
Química Encefálica/fisiologia , Neoplasias Encefálicas/patologia , Glioma/genética , Glioma/patologia , Glucosefosfato Desidrogenase/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Adulto , Anaplasia/patologia , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Metabolismo dos Carboidratos/genética , Metabolismo dos Carboidratos/fisiologia , Metilação de DNA/genética , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Glucose/análise , Hexoquinase/metabolismo , Humanos , Isocitrato Desidrogenase/genética , Ácido Láctico/análise , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , Transcetolase/metabolismo , Proteínas Supressoras de Tumor/genéticaRESUMO
The presence of mutations in the gene encoding isocitrate dehydrogenase (IDH1), parameters of pro- and antioxidant activity in glioma tumor tissue, and their correlation were studied using bioinformatic analysis using STRING, IntAct, BioGrid, UniProt, SwissProt databases. The rate of detection of IDH1 gene mutations varied in different degree of anaplasia, being maximum in grade III gliomas. The intensity of free radical oxidation and activities of superoxide dismutase and catalase in the tumor tissue were significantly higher than in the control. The dependence of these parameters on the degree of anaplasia was shown. Mutations in IDH1 are associated with a decrease in antioxidant activity in the tissues of gliomas, which is critically important for the initial diagnosis, the choice of treatment options, and prediction of patient survival.