Based on our data, we propose a model in which the superior antiviral efficacy of pegIFN-�� is the result of continuous stimulation of immune cells and is not due to continuous stimulation selleck chemical of the Jak/STAT pathway in HCV-infected hepatocytes. A large body of fundamental knowledge about the key signaling pathways and the biological role of IFN-�� has been acquired through cell culture experiments and mouse models with genetic deletions of IFNs, IFN receptors, or components of the Jak/STAT pathway (38). On the other hand, the IFN-���Cinduced effects in target organs of human pathogens have been little investigated. Not surprisingly, the molecular mechanisms responsible for the antiviral activity of (peg)IFN-�� against HCV are still not known.

In the Huh7 cell�Cbased HCV replicon system, overexpression and siRNA interference screens identified several ISGs involved in the inhibition of replication, among them: IRF1, IRF2, IRF7, IFN-induced helicase C domain�Ccontaining protein 1 (IFIH1, also known as MDA5), retinoic acid�Cinducible gene 1 (R
Given the poor prognosis of advanced pancreatic cancer and the symptom burden, symptom palliation and balancing the trade-offs between quality of life (QOL) and survival are of paramount importance in these patients. This is particularly the case when discussing palliative chemotherapy. Quality of life as perceived by the patient is not only an important treatment outcome but also a prognostic factor (Gotay et al, 2008; Montazeri, 2009; Quinten et al, 2009). Prognostic factors are especially valuable in this situation.

Pre-treatment concentration of the tumour marker carbohydrate antigen (CA) 19-9 is a strong independent prognostic factor for survival in advanced pancreatic cancer (Micke et al, 2003; Maisey et al, 2005; Hess et al, 2008). Quality of life also predicts survival in these patients (Gupta et al, 2006; Robinson et al, 2008). The contribution of QOL relative to CA 19-9, that is, its clinical significance as an independent prognostic factor, is not known. An early decrease in CA 19-9 concentration during chemotherapy (i.e., a CA 19-9 response) might not only serve as prognostic marker but also as an early marker of tumour response. This would discriminate patients likely to benefit from continued treatment from those who would not. However, in our recent phase III trial (Herrmann et al, 2007) a decrease in CA 19-9 concentration during chemotherapy was not significantly associated with lengthened survival compared with those patients who did not have a corresponding decrease (Hess Brefeldin_A et al, 2008). Whether a decrease in CA 19-9 concentration is associated with palliation as perceived by the patient is not known.