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Hepatocellular carcinoma (HCC) is a common cancer associated with chronic hepatitis B virus (HBV) infection. Conventional interferon-α (IFN-α) and pegylated IFNs (PEG-IFNs) approved for chronic HBV infection treatment can reduce the risk of HCC but are not suitable for the majority of patients and cause significant side effects. IFN-λ1 is a type III IFN with antiviral, antiproliferative, and immunomodulatory functions similar to type I IFNs but with fewer side effects. However, the tolerability and antitumor activity of PEG-IFN-λ1 in HCC xenograft mice are unknown. In vitro IFN-λ1 treatment of Hep3B and Huh7 human hepatoma cell lines increased MHC class I expression, activated JAK-STAT signaling pathways, induced IFN-stimulated gene expression, and inhibited hepatitis B surface antigen (HBsAg) expression. IFN-λ1 treatment also caused 23.2 and 19.9% growth inhibition of Hep3B and Huh7 cells, respectively, and promoted cellular apoptosis. PEG-IFN-λ1, but not IFN-λ1 treatment, significantly suppressed tumor growth (P= 0.002) and induced tumor cell apoptosis in a Hep3B cell xenograft mouse model without significant weight loss or toxicity. PEG-IFN-λ1 also significantly inhibited (P= 0.000) serum HBsAg secretion from Hep3B xenograft tumors in vivo. Thus, PEG-IFN-λ1 can suppress Hep3B xenograft tumor growth and inhibit HBsAg production and may be a potential treatment for HBV-related HCC. [ABSTRACT FROM AUTHOR]

Elevated serum heat shock protein 27 (HSP27) levels are atheroprotective; however, the role of HSP27 after arterial injury is unknown. Human endothelial progenitor cells (EPCs) were treated with recombinant (r)HSP27 (50 μg/ml) or its inactive C1 terminus, and gene expression was characterized before functional studies were performed in vitro and in vivo. Vascular endothelial growth factor (VEGF) was markedly up-regulated by rHSP27 (10- and 6-fold increases in mRNA and secretion, respectively). Pretreat-ment of EPCs with rHSP27 resulted in a 60% reduction hi reendothelialization (RE) time in a scratch assay, an effect diat was blocked with VEGF-neutralizing antibodies. Mice overexpressing HSP27 demonstrated more robust mobilization of EPCs at the time of arterial injury, as well as a 67% increase in RE and a 45% reduction in neointima (NI) formation at 28 d. Implantation of rHSP27-eluting stents in rabbit carotid arteries resulted in a marked improvement in RE at 7 and 28 d and transient attenuation of NI formation by 42% at 7 d. Hence, extracellular HSP27 up-regulated VEGF and improved EPC migration in vitro. Augmented systemic or local levels of HSP27 markedly unproved RE after vascular injury, an effect that is of particular relevance to the safety profile of vascular stents. [ABSTRACT FROM AUTHOR]