AIM： To clarify the significance of JC virus （JCV） T-antigen （T-Ag） expression in human gastric cancer. METHODS： We investigated the relationship between TAg detected by immunohistochemistry and Epstein- Barr vi...AIM： To clarify the significance of JC virus （JCV） T-antigen （T-Ag） expression in human gastric cancer. METHODS： We investigated the relationship between TAg detected by immunohistochemistry and Epstein- Barr virus （EBV） infection, microsatellite instability （MSI）, and genetic and epigenetic alterations in gastric cancers. Mutations in the p53,β-catenin, K/MS, BRAF, PIK3CA genes were analyzed by PCR- single strand conformation polymorphism and DNA sequencing. Allelic losses were determined by PCR at 7 microsatellite loci. Aberrant DNA methylation was analyzed by MethyLight assay. RESULTS： JCV T-Ag protein expression was found in 49% of 90 gastric cancer tissues. TAg positivity was not correlated with clinicopathological characteristics. TAg expression was detected in a similar percentage of EBV positive cancers （4 of 9, 44%） and EBV negative cancers （35 of 73, 48%）. TAg expression was detected in a significantly lower percentage of MSI-H cancers （14%） than in non MSI-H cancers （55%, P = 0.005）. TAg expression was detected in a significantly higher percentage of cancers with nuclear/cytoplasmic localization of β-catenin （15 of 21, 71%） than in cancers without （42%, P = 0.018）. p53 mutations were detected in a significantly lower percentage of T-Ag positive cancers （32%） than in TAg negative cancers （57%, P = 0.018）. TAg positive gastric cancers showed a significant increase in the allelic losses and aberrant methylation compared with T-Ag negative gastric cancers （P = 0.008 and P = 0.003）. CONCLUSION： The results suggest that JCV T-Ag is involved in gastric carcinogenesis through multiple mechanisms of genetic and epigenetic alterations.展开更多
Hepatitis D virus(HDV)infection is associated with severe liver-related morbidity and mortality.The prevalence of HDV is rising especially among people who abuse drugs and immigrants from endemic areas.Reliable diagno...Hepatitis D virus(HDV)infection is associated with severe liver-related morbidity and mortality.The prevalence of HDV is rising especially among people who abuse drugs and immigrants from endemic areas.Reliable diagnostic assays with enhanced sensitivity and specificity are essential for screening at-risk populations.Until recently,interferon has been the only treatment for hepatitis D.Its efficacy is,however,limited and it is associated with significant side effects.A number of novel antiviral agents that target various stages of the HDV life cycle show promising results.They are currently in different phases of clinical development.This review focuses on the changing epidemiology,novel therapeutic agents,and updated management of chronic hepatitis delta.展开更多
基金Supported by Grants-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology of Japan(Yamamoto H,Imai K and Shinomura Y)Grants-in-Aid for Cancer Research from the Ministry of Health,Laborand Welfare of Japan(Yamamoto H)
文摘AIM： To clarify the significance of JC virus （JCV） T-antigen （T-Ag） expression in human gastric cancer. METHODS： We investigated the relationship between TAg detected by immunohistochemistry and Epstein- Barr virus （EBV） infection, microsatellite instability （MSI）, and genetic and epigenetic alterations in gastric cancers. Mutations in the p53,β-catenin, K/MS, BRAF, PIK3CA genes were analyzed by PCR- single strand conformation polymorphism and DNA sequencing. Allelic losses were determined by PCR at 7 microsatellite loci. Aberrant DNA methylation was analyzed by MethyLight assay. RESULTS： JCV T-Ag protein expression was found in 49% of 90 gastric cancer tissues. TAg positivity was not correlated with clinicopathological characteristics. TAg expression was detected in a similar percentage of EBV positive cancers （4 of 9, 44%） and EBV negative cancers （35 of 73, 48%）. TAg expression was detected in a significantly lower percentage of MSI-H cancers （14%） than in non MSI-H cancers （55%, P = 0.005）. TAg expression was detected in a significantly higher percentage of cancers with nuclear/cytoplasmic localization of β-catenin （15 of 21, 71%） than in cancers without （42%, P = 0.018）. p53 mutations were detected in a significantly lower percentage of T-Ag positive cancers （32%） than in TAg negative cancers （57%, P = 0.018）. TAg positive gastric cancers showed a significant increase in the allelic losses and aberrant methylation compared with T-Ag negative gastric cancers （P = 0.008 and P = 0.003）. CONCLUSION： The results suggest that JCV T-Ag is involved in gastric carcinogenesis through multiple mechanisms of genetic and epigenetic alterations.
文摘Hepatitis D virus(HDV)infection is associated with severe liver-related morbidity and mortality.The prevalence of HDV is rising especially among people who abuse drugs and immigrants from endemic areas.Reliable diagnostic assays with enhanced sensitivity and specificity are essential for screening at-risk populations.Until recently,interferon has been the only treatment for hepatitis D.Its efficacy is,however,limited and it is associated with significant side effects.A number of novel antiviral agents that target various stages of the HDV life cycle show promising results.They are currently in different phases of clinical development.This review focuses on the changing epidemiology,novel therapeutic agents,and updated management of chronic hepatitis delta.
