Previous in vivo studies have suggested that nucleic acid polymers (NAPs) may reduce circulating levels of HBsAg in the blood by blocking its release from infected hepatocytes and that this effect may have clinical benefit. NAP treatment, was evaluated in two clinical studies in patients with HBeAg positive chronic HBV infection. The REP 101 study examined REP 2055 monotherapy in 8 patients and the REP 102 study examined REP 2139-Ca, in monotherapy in 12 patients, 9 of which transitioned to short term combined treatment with pegylated interferon alpha 2a or thymosin alpha 1. In both studies NAP monotherapy was accompanied by 2–7 log reductions of serum HBsAg, 3–9 log reductions in serum HBV DNA and the appearance of serum anti-HBsAg antibodies (10–1712 mIU / ml). Eight of the 9 patients transitioning to combined treatment with immunotherapy (pegylated interferon or thymosin alpha 1) in the REP 102 study experienced HBsAg loss and all 9 patients experienced substantial increases in serum anti-HBsAg antibody titers before withdrawal of therapy. For 52 weeks after removal of REP 2055 therapy, rebound of serum viremia (HBV DNA > 1000 copies / ml, HBsAg > 1IU / ml) was not observed in 3 / 8 patients. Suppression of serum virema was further maintained for 290 and 231 weeks in 2 of these patients. After withdrawal of all therapy in the 9 patients that transitioned to combination therapy in the REP 102 study, 8 patients achieved HBV DNA < 116 copies / ml after treatment withdrawal. Viral rebound occurred over a period of 12 to 123 weeks in 7 patients but was still absent in two patients at 135 and 137 weeks of follow-up. Administration tolerability issues observed with REP 2055 were rare with REP 2139-Ca but REP 2139-Ca therapy was accompanied by hair loss, dysphagia and dysgeusia which were considered related to heavy metal exposure endemic at the trial site. These preliminary studies suggest that NAP can elicit important antiviral responses during treatment which may improve the effect of immunotherapy. NAPs may be a potentially useful component of future combination therapies for the treatment of chronic hepatitis B.Trial Registration: ClinicalTrials.gov NCT02646163 and NCT02646189
The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on ''APASL consensus statements and recommendations for management of hepatitis C'' in March 2015 to revise the ''APASL consensus statements and management algorithms for hepatitis C virus infection'' (Hepatol Int 6:409-435, 2012). The working party consisted of expert hepatologists from the Asian-Pacific region gathered at the Istanbul Congress Center, Istanbul, Turkey on 13 March 2015. New data were presented, discussed, and debated during the course of drafting a revision. Participants of the consensus meeting assessed the quality of the cited studies. The finalized recommendations for hepatitis C prevention, epidemiology, and laboratory testing are presented in this review.
Background: Hepatitis C virus is encountered sporadically in Bangladesh. It results in a wide range liver diseases, with asymptomatic acute hepatitis rarely at one end to HCC at the other end of the spectrum. Methods: 1018 individuals of different age groups and sex with varied religious, educational and social backgrounds were tested for anti-HCV by ELISA. Before testing, blood samples were preserved at -20°C. The study was conducted in a semi-urban location on the outskirts of Dhaka. Results: 0.88% tested positive for anti HCV. None of them tested positive for HBsAg. There was a male predominance and those who tested positive were mostly between 17 and 50 years of age. Major risk factors for exposure to HBV appeared to be injudicious use of injectable medications, treatment by unqualified, traditional practitioners, mass-vaccination against cholera and smallpox, barbers and body piercing. Conclusion: HCV remains an important cause of morbidity and mortality in Bangladesh.Key words: HCV, prevalence, general population, Bangladesh. [BSMMU J 2009; 2(1): 14-17]Correspondence to : Dr. Mamun-Al-Mahtab, Assistant Professor, Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka-1000, Bangladesh, Email: shwapnil@agni.com Materials and methodsThe study was conducted in the Savar area on the outskirts of Dhaka in May 2007. The area has a large industrial base. The leading export processing zone of the country is also situated here. People from all over the country stay and work in different industrial and other installations in this area. Moreover, due to its proximity and excellent communication with Dhaka city, many people from different parts of the country reside here and commute to Dhaka daily for work and business. It was therefore assumed that the study population was representative of the Bangladeshi population.
Purpose: We utilized whole-genome mapping of promoters that are activated by DNA hypomethylation in hepatocellular carcinoma (HCC) clinical samples to shortlist novel targets for anticancer therapeutics. We provide a proof of principle of this approach by testing six genes short-listed in our screen for their essential role in cancer growth and invasiveness.Experimental Design: We used siRNA-or shRNA-mediated depletion to determine whether inhibition of these genes would reduce human tumor xenograft growth in mice as well as cell viability, anchorageindependent growth, invasive capacities, and state of activity of nodal signaling pathways in liver, breast, and bladder cancer cell lines.Results: Depletion of EXOSC4, RNMT, SENP6, WBSCR22, RASAL2, and NENF effectively and specifically inhibits cancer cell growth and cell invasive capacities in different types of cancer, but, remarkably, there is no effect on normal cell growth, suggesting a ubiquitous causal role for these genes in driving cancer growth and metastasis. Depletion of RASAL2 and NENF in vitro reduces their growth as explants in vivo in mice. RASAL2 and NENF depletion interferes with AKT, WNT, and MAPK signaling pathways as well as regulation of epigenetic proteins that were previously demonstrated to drive cancer growth and metastasis.Conclusion: Our results prove that genes that are hypomethylated and induced in tumors are candidate targets for anticancer therapeutics in multiple cancer cell types. Because these genes are particularly activated in cancer, they constitute a group of targets for specific pharmacologic inhibitors of cancer and cancer metastasis. Clin Cancer Res; 20(12); 3118-32. Ó2014 AACR.
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