RESUMO
Selenium binding protein 1 (SELENBP1) has been known to be reduced in various types cancer, and epigenetic change is shown to be likely to account for the reduction of SELNEBP1 expression. With cDNA microarray comparative analysis, we found that SELENBP1 is markedly decreased in hepatitis B virus-X (HBx)-expressing cells. To clarify the effect of HBx on SELENBP1 expression, we compared the expression levels of SELENBP1 mRNA and protein by semi-quantitative RT-PCR, Northern blot, and Western blot. As expected, SELENBP1 expression was shown to be reduced in cells expressing HBx, and reporter gene analysis showed that the SELENBP1 promoter is repressed by HBx. In addition, the stepwise deletion of 5' flanking promoter sequences resulted in a gradual decrease in basal promoter activity and inhibition of SELENBP1 expression by HBx. Moreover, immunohistochemistry on tissue microarrays containing 60 pairs of human liver tissue showed decreased intensity of SELENBP1 in tumor tissues as compared with their matched non-tumor liver tissues. Taken together, our findings suggest that inhibition of SELENBP1 expression by HBx might act as one of the causes in the development of hepatocellular carcinoma caused by HBV infection.
Assuntos
Regulação para Baixo , Vírus da Hepatite B/metabolismo , Proteínas de Ligação a Selênio/genética , Proteínas de Ligação a Selênio/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Hepatite B , Vírus da Hepatite B/genética , Humanos , Imuno-Histoquímica , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Regiões Promotoras Genéticas , RNA Mensageiro , Transativadores , Proteínas Virais Reguladoras e AcessóriasRESUMO
BACKGROUND AND AIM: Infection of Helicobacter pylori is viewed as a major driver of progression to the precancerous state or to gastric cancer. This study was performed to investigate the effect of H. pylori infection on gastric cancer development and to determine to what extent H. pylori eradication is likely to reduce the prevalence of gastric cancer. METHODS: Gastric cancer development was investigated in 1790 Korean subjects who underwent gastroscopy and H. pylori testing between 1992 and 1998. The effects of H. pylori-positive and eradicated states on gastric cancer development were analyzed. RESULTS: Gastric cancer developed in 5 of the study cohort during a mean follow-up period of 9.4 years. All of these patients were positive for H. pylori infection, and 4 of the 5 had antral intestinal metaplasia (IM) at the time of study enrollment. One of these 5 patients was in an eradicated state when the gastric cancer was diagnosed, and had histologic IM before eradication therapy was performed. Gastric cancer was found to develop 10.9 times more frequently in the presence of IM than in its absence. CONCLUSIONS: The present study shows a close relationship between H. pylori infection and IM, and between IM and the development of gastric cancer. In addition, our finding suggests that chronic H. pylori infection looks like an important risk factor for the development of gastric cancer in Korea, where the prevalence of H. pylori remains high. This study indicates that to prevent gastric cancer H. pylori eradication is best performed before the development of IM.
Assuntos
Mucosa Gástrica/patologia , Infecções por Helicobacter/patologia , Lesões Pré-Cancerosas , Neoplasias Gástricas/patologia , Adulto , Antibacterianos/uso terapêutico , Anticorpos Antibacterianos/análise , Biópsia , Diagnóstico Diferencial , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Mucosa Gástrica/microbiologia , Gastroscopia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/imunologia , Helicobacter pylori/isolamento & purificação , Humanos , Incidência , Coreia (Geográfico)/epidemiologia , Masculino , Metaplasia/patologia , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Fatores de TempoRESUMO
Oxidative stress plays an important role in the pathological processes of a variety of neurodegenerative diseases. The neuroprotective effects of 3,5-diCQA and 3,4-diCQA, two caffeoylquinic acid derivatives present in Dipsacus asper, on hydrogen peroxide (H2O2)-induced neuronal cell damage were evaluated in this study.SH-SY5Y cells treated with H2O2 exhibited a decrease in survival and intracellular glutathione and also an increase in the caspase-3 activity. However, pretreatment of cells with 3,5-diCQA attenuated the neuronal death and caspase-3 activation induced by H2O2. In addition, 3,5-diCQA restored H2O2-induced depletion of intracellular glutathione. 3,5-diCQA showed significant protective effects although it could not completely suppress H2O2-induced cell injury to control levels. The data suggest that 3,5-diCQA might be a potential therapeutic agent for treating or preventing neurodegenerative diseases implicated with oxidative stress.
Assuntos
Ácido Clorogênico/análogos & derivados , Ácido Clorogênico/farmacologia , Magnoliopsida , Doenças Neurodegenerativas/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Fitoterapia , Extratos Vegetais/farmacologia , Caspase 3 , Caspases/metabolismo , Linhagem Celular Tumoral/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ácido Clorogênico/administração & dosagem , Ácido Clorogênico/uso terapêutico , Relação Dose-Resposta a Droga , Glutationa/metabolismo , Humanos , Peróxido de Hidrogênio , Neuroblastoma/patologia , Doenças Neurodegenerativas/induzido quimicamente , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/uso terapêutico , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêuticoRESUMO
PURPOSE: Oxidative stress has been implicated in the pathogenesis of various diseases. Catalase is one of the main defense mechanisms against oxidative stress. To examine the possible relationship between oxidative stress, and gastric and hepatocellular carcinomas, HinfI restriction length polymorphism (RFLP) in the human catalase gene was assessed. MATERIALS AND METHODS: The genotype and allele frequencies in the promoter region of the catalase gene were studied by PCR-RFLP in 108 Korean controls, 80 Korean gastric carcinoma (GC) and 106 Korean hepatocellular carcinoma (HCC) patients. RESULTS: No statistically significant differences were found in the genotypic distribution and allelic frequencies between the controls and both types of carcinoma patient. CONCLUSION: To address the possible contribution of oxidative stresses to the pathogenesis of gastric and hepatocellular carcinomas, the associations between the catalase gene polymorphism and GC and HCC susceptibilities were studied. As a result, the catalase gene polymorphism was found not to be determinant of GC and HCC susceptibilities. Further studies are required on various other oxidative stress related genes to elucidate the mechanisms of GC and HCC.