One year of treatment with entecavir (0.5 mg daily) in nucleoside-naive patients with hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic hepatitis B (CHB) resulted in significantly improved liver histology and virological and biochemical endpoints in comparison with lamivudine. Patients who received at least 3 years of cumulative entecavir therapy in phase 3 studies and a long-term rollover study and underwent long-term liver biopsy were evaluated for improvements in histological appearance. Sixty-nine patients [50 HBeAg-positive and 19 HBeAg-negative] receiving entecavir therapy underwent longterm liver biopsy (median time of biopsy 5 6 years, range 5 3-7 years). Histological improvement was analyzed for 57 patients who had adequate baseline biopsy samples, baseline Knodell necroinflammatory scores !2, and adequate long-term biopsy samples. At the time of long-term biopsy, all patients in the cohort had a hepatitis B virus DNA level <300 copies/mL, and 86% had a normalized alanine aminotransferase level. Histological improvement (!2-point decrease in the Knodell necroinflammatory score and no worsening of the Knodell fibrosis score) was observed in 96% of patients, and a !1-point improvement in the Ishak fibrosis score was found in 88% of patients, including all 10 patients with advanced fibrosis or cirrhosis at the phase 3 baseline. Conclusion: The majority of nucleoside-naive patients with CHB who were treated with entecavir in this longterm cohort achieved substantial histological improvement and regression of fibrosis or cirrhosis. (HEPATOLOGY 2010;52:886-893)

Cancer cells preferentially metabolize glucose through aerobic glycolysis, a phenomenon known as the Warburg effect. Emerging evidence has shown that long non-coding RNAs (lncRNAs) act as key regulators of multiple cancers. However, it remains largely unexplored whether and how lncRNA regulates glucose metabolism in cancer cells. In this study, we show that lncRNA UCA1 promotes glycolysis in bladder cancer cells, and that UCA1-induced hexokinase 2 (HK2) functions as an important mediator in this process. We further show that UCA1 activates mTOR to regulate HK2 through both activation of STAT3 and repression of microRNA143. Taken together, these findings provide the first evidence that UCA1 plays a positive role in cancer cell glucose metabolism through the cascade of mTOR–STAT3/microRNA143–HK2, and reveal a novel link between lncRNA and the altered glucose metabolism in cancer cells.

Etiological variations in hepatocellular carcinoma (HCC) exist across different geographic areas. To gain better control of HCC, we retrospectively studied the secular trends and geographic variations in hepatitis B virus (HBV)-related and hepatitis C virus (HCV)-related HCCs in Taiwan. A total of 18,423 HCC cases enrolled in 8 medical centers from 1981 to 2001 were reviewed. Overall, 67% of male HCC in Taiwan was related to HBV infection whereas 55.2% of female HCC in Taiwan was related to HCV infection. The mean age of patients with HBV-related HCC was 53.2 6 13.6 years, while the mean age of patients with HCV-related HCC was 65.1 6 9.1 years (p < 0.001). The male/female ratio was 6.4 for HBV-related HCC, while it was 1.7 for the HCV-related HCC (p < 0.001). The percentage of HBV-related HCC progressively decreased from 81.5 to 66.2% in males, and from 66.7 to 41.4% in females over the study period. Our study demonstrates that the percentage of HBV-related HCC has progressively decreased over the last 20 years. The relative decrease in HBV-related HCC was not due to a decrease in HBV-related HCC death. Instead, it was caused by an increase in HCV-related HCC. Prevention of new HCV infection and the treatment of chronic hepatitis C should be the primary goals, which will result in better control of HCC in the future, even in an HBV-endemic area like Taiwan. ' 2006 Wiley-Liss, Inc.Key words: hepatocellular carcinoma; hepatitis B virus; hepatitis C virus; secular trend; geographic variation; Taiwan Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, especially in sub-Saharan Africa and Southeast Asia. Since 1984, it has been the leading cause of cancer death in Taiwan, 1 accounting for approximately 7,000 death annually. In addition, around 8,000 new HCC cases are diagnosed each year. 2 High-risk groups for HCC include patients chronically infected with hepatitis B virus (HBV) or hepatitis C virus (HCV), liver cirrhosis patients, and people with a family history of HCC. Chronic HBV and HCV infections are the 2 major etiologies of HCC in Taiwan. 3 About 15-20% of the general population in Taiwan are chronic carriers of hepatitis B surface antigen (HBsAg). 4 HBV carriers have a 20-to 98-fold increased risk of HCC, 5,6 especially among the hepatitis B e antigen (HBeAg)-positive group. 7 A recent prospective study has further confirmed that positivity for HBeAg is associated with an increased risk of HCC. 8 To combat HBV infection in Taiwan, a mass immunization program has been launched on July 1, 1984, aiming first at the prevention of perinatal mother-to-infant, chronic HBV infection. 9 This nationwide vaccination program has markedly decreased the HBV carrier rate 10 and childhood HBVrelated HCCs (B-HCCs). 11 An 80-85% decrease in HCC among Taiwanese adults up to 3-4 decades later is anticipated. 12 The prevalence of anti-HCV antibody (anti-HCV) is 2-4% among the general population of Taiwan, 13 while it ranges from 0.95 to 2.2% in Taiwanese blood donors. 13,14 The anti-HCV prevalen...

Macrophages have been linked to tumor initiation, progression, metastasis, and treatment resistance. However, the transcriptional regulation of macrophages driving the protumor function remains elusive. Here, we demonstrate that the transcription factor c-Maf is a critical controller for immunosuppressive macrophage polarization and function in cancer. c-Maf controls many M2-related genes and has direct binding sites within a conserved noncoding sequence of the Csf-1r gene and promotes M2-like macrophage-mediated T cell suppression and tumor progression. c-Maf also serves as a metabolic checkpoint regulating the TCA cycle and UDP-GlcNAc biosynthesis, thus promoting M2-like macrophage polarization and activation. Additionally, c-Maf is highly expressed in tumor-associated macrophages (TAMs) and regulates TAM immunosuppressive function. Deletion of c-Maf specifically in myeloid cells results in reduced tumor burden with enhanced antitumor T cell immunity. Inhibition of c-Maf partly overcomes resistance to anti-PD-1 therapy in a subcutaneous LLC tumor model. Similarly, c-Maf is expressed in human M2 and tumor-infiltrating macrophages/monocytes as well as circulating monocytes of human non-small cell lung carcinoma (NSCLC) patients and critically regulates their immunosuppressive activity. The natural compound β-glucan downregulates c-Maf expression on macrophages, leading to enhanced antitumor immunity in mice. These findings establish a paradigm for immunosuppressive macrophage polarization and transcriptional regulation by c-Maf and suggest that c-Maf is a potential target for effective tumor immunotherapy.

If we encountered a young HCC patient, the patient will probably be a male HBV carrier. He would probably have larger tumor and is more likely to expire within 1 year than the older HCC patients. However, if the young HCC patient can survive for more than 1 year, he would probably have better survival in the following years than the older patients.