Currently, 4% of the world's people are infected with Hepatitis C virus (HCV), and some of them will develop cirrhosis or even hepatocellular carcinoma within 20 to 30 years of infection. Therefore, HCV has become a serious threat to human health. The combination of IFN and ribavirin (RBV) has been the standard treatment for patients with chronic HCV infection. However, it can have a positive effect on only half of the treated individuals, and produce some significant side effects. Thus, it is essential to develop novel and potent agents for the treatment of Hepatitis C. Asmentioned previously, the development of gastric cancer has been closely related to JAK/STAT pathway. Among all STATs, STAT3 played an important role during the activation of JAK/STAT pathway while AG490 (inhibitor of JAK kinase) can block JAK/STAT pathway effectively. The expression of STAT3 were reduced by fucoxanthinat both on mRNA and protein level suggesting the inhibiting effects on JAK/STAT pathway of fucoxanthin. At the presence of AG490, the expressions of p STAT3 and survivin were also reduced to a level slightly lower. With the co treatment of fucoxanthin and AG490, the reduction expressions of STAT3, pSTAT3 and CyclinB1 by fucoxanthin was inhibited. IFN1 (IL29), IFN2 (IL28A). and IFN3 (IL28B), as the members of the type III IFN family, bind to their cognate receptor, consisting of IL28R1 and IL10R2, and then activates the receptor associated protein kinases Jak1 and Tyk2, leading to activation of JAK/STAT signaling pathway. Previously, Robek's group found that IFN1 and 2 inhibited HCV replication in HCV replicon cells [1]. Recent paper by Zhang and his partners reported that IL28B (fty720) inhibited HCV replication in a time and dose dependent manner, confirming that all three IFNs are anti HCV cytokines[2]. Futher study showed that the anti HCV effect of IFNs was decreased in the presence of JAK/STAT pathway inhibitors such as blocking antibodies, a pharmacological inhibitor, and siRNAs[2]. The results indicates that the JAK/STAT pathway is required for the anti GSK1363089 effect of IL28B, IL28A, and IL29. In conclusion, all three IFNs and the mechanisms of their antiviral effect against HCV will provide new approaches in HCV treatment. The paper in Blood by Pardanani A, et al reported that CYT387 had recently undergone Phase I evaluation, demonstrating safe use of low micromolar concentrations, with no relevant haematological toxicities evident [1]. Last month, Monaghan KA's group [2] found that the JAK inhibitor CYT387 could modulate IL6 stimulated signalling within HMCL via JAK/STAT, PI3K/AKT and Ras/MAPK signalling, which can sensitise them to various other anti MM treatments. CYT387 can inhibit proliferation and induces apoptosis of MM cells as a single agent and synergises with melphalan and bortezomi. Despite the existence of tolerance in some patients, the synergy of CYT387 with common myeloma therapies bortezomib and melphalan make it a very attractive compound for further study in the clinic. [1]. Robek M.D., et al. 2005. Lambda interferon inhibits hepatitis B and C virus replication. J Virol. 79, 3851""3854. [2]. Zhang L., et al. 2011. IL28B inhibits hepatitis C virus replication through the JAK""STAT pathway. J Hepatol. 55, 289-298.
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