RESUMO
Thermotherapy has been proven to be effective for the treatment of various tumors, including glioma. We determined whether tumor necrosis factor-alpha (TNF-α) is involved in the regulation of the biological processes of glioma development. Reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry were used to investigate the levels of TNF-α mRNA and heat shock factor-1 (HSF1) protein, respectively, in glioma cells. Radioimmunoassay was used to dynamically monitor the contents of TNF-α in the nutrient fluid of C6 cells after thermotherapy treatment. Crystal violet staining was used to determine glioma invasiveness. The most obvious increases in HSF1 protein and TNF-α mRNA in C6 cells were observed at 30 and 60 min after thermotherapy, respectively. In addition, the radioactivity of TNF-α in the culture fluid of the C6 cells reached a peak after 120 min of thermotherapy. In addition, glioma invasiveness decreased and the concentration of TNF-α reached a maximum after 120 min of thermotherapy. Our results show that the decrease in thermotherapy-mediated glioma invasiveness is due to the accelerated release of TNF-α, which could promote the release of HSF1 from neurospongioma cells.
Assuntos
Neoplasias Encefálicas/terapia , Regulação Neoplásica da Expressão Gênica , Glioma/terapia , Hipertermia Induzida , Fator de Necrose Tumoral alfa/genética , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Glioma/genética , Glioma/metabolismo , Glioma/patologia , Fatores de Transcrição de Choque Térmico , Masculino , Invasividade Neoplásica , Transplante de Neoplasias , Ratos , Ratos Wistar , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
KCNJ11 (potassium inwardly rectifying channel, subfamily J, member 11) and ABCC8 (ATP-binding cassette, subfamily C (CFTR/MRP), member 8) have been studied for association with type 2 diabetes in various ethnic populations with contradictory results. We performed a comprehensive meta-analysis for KCNJ11 rs5219, rs5210, rs5215, and ABCC8 rs757110 to evaluate the effect of these regions on genetic susceptibility for type 2 diabetes. Forty-one case-control association studies of KCNJ11 and ABCC8 polymorphisms with type 2 diabetes, including 61,879 subjects, were identified and used in our meta-analysis. Combined odds ratios (OR) of associations of this disease with the rs5219 T, rs5210 G, rs5215 G, and rs757110 G alleles were 1.15 [95% confidence interval (95%CI) = 1.10-1.21, P < 0.0001], 1.16 (95%CI = 1.08-1.24, P = 0.023), 1.08 (95%CI = 1.02-1.13, P = 0.006), and 1.12 (95%CI = 1.07-1.18, P < 0.0001), respectively. The effect of allele T of rs5219 was similar (OR = 1.16) in Europeans and Japanese. However, rs5219 was not associated with type 2 diabetes in the Chinese Han population. Our meta-analysis demonstrated that KCNJ11 and ABCC8 polymorphisms are associated with risk for type 2 diabetes in the global population. Comparative genomics and bioinformatics analyses revealed that rs5210 is located within a conserved 3'-UTR, and that allele A may abolish the binding site of hsa-miR-1910 that the risk allele G possesses.
Assuntos
Diabetes Mellitus Tipo 2/genética , Estudos de Associação Genética , Canais de Potássio Corretores do Fluxo de Internalização/genética , Receptores de Sulfonilureias/genética , Alelos , Diabetes Mellitus Tipo 2/patologia , Etnicidade/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Polimorfismo Genético , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Uncoupling protein 2 (UCP2) is a mitochondrial transporter protein and can affect the function of ß-cells. We investigated a possible association between functional UCP2 -866G/A and Ala55Val polymorphisms and type 2 diabetes in 715 Hubei Han Chinese. No significant association was found, either for the -866G/A polymorphism (allele, P = 0.254; genotype, P = 0.508) or for the Ala55Val polymorphism (allele, P = 0.250; genotype, P = 0.896). Then, we reviewed the association of UCP2 -866G/A and Ala55Val polymorphisms with type 2 diabetes susceptibility in the Chinese population with a meta-analysis. Our meta-analysis, which included 3643 Chinese, further confirmed a lack of association of -866G/A and Ala55Val with type 2 diabetes (additive model: -866G/A, odds ratio = 1.09, 95% confidence interval = 0.94-1.27, P = 0.25; Ala55Val, odds ratio = 1.21, 95% confidence interval = 0.85-1.72, P = 0.28). Based on our case-control study and meta-analysis, we conclude that UCP2 Ala55Val and -866G/A polymorphisms are not significantly associated with type 2 diabetes risk in the Chinese population.