Experimental Design: A total of 114 consecutive patients with hepatocellular carcinoma receiving combination therapy were retrospectively enrolled. The therapy CHIR-99021 chemical structure response at different time points was assessed using RECIST, EASL, and mRECIST. Cox
regression analysis and Kaplan-Meier curves were used to assess overall survival (OS) in the responders and nonresponders. Results: At the third follow-up (median, 94 days; range, 89-102 days) after therapy, the response rates obtained using EASL (50.6%) and mRECIST (51.6%) were greater than that obtained using RECIST (16.5%). The agreement was strong between the mRECIST and EASL results (k = 0.9) but weak between mRECIST and RECIST (k = 0.3). The EASL and mRECIST responses significantly correlated with survival. Risk reductions of 52% and 50% were observed for EASL and mRECIST responders, respectively, compared with nonresponders. However, no significant association between the treatment
response and survival was observed using RECIST. Conclusions: The earliest time to evaluate the response to combination therapy is 3 months (median, 94 days) after therapy. EASL and mRECIST responses are independent predictors for OS at this early time point. (C)2014 AACR.”
“Recently, dual-specificity phosphatase 16 (DUSP16) emerged as a promising therapeutic GW786034 in vitro target protein for the development of anti-atherosclerosis and anticancer medicines. The present study was undertaken to identify the novel inhibitors of DUSP16 based on the structure-based virtual screening. We have been able to find seven novel inhibitors of DUSP16 through the drug design protocol involving homology modeling of the target protein, docking simulations between DUSP16 and its putative inhibitors with the modified scoring function, and in vitro enzyme assay. These inhibitors revealed good potency, with IC50 values ranging from 1 to 22 mu M, and they were also screened computationally for having desirable physicochemical
properties as drug candidates. Therefore, they deserve consideration for further development by structure-activity relationship studies to optimize the inhibitory activity against DUSP16. Structural features relevant to the stabilization of the newly identified selleck kinase inhibitor inhibitors in the active site of DUSP16 are addressed in detail.”
“The circadian clock controls daily rhythms in many physiologic processes, and the clock oscillation is regulated by external time cues such as light, temperature, and feeding. In mammals, the transcriptional regulation of clock genes underlies the clock oscillatory mechanism, which is operative even in cultured fibroblasts. We previously demonstrated that glucose treatment of rat-1 fibroblasts evokes circadian expression of clock genes with a rapid induction of Tieg1 transcript encoding a transcriptional repressor. Here, we found diurnal variation of both Tieg1 mRNA and nuclear TIEG1 protein levels in the mouse liver with their peaks at day/night transition and midnight, respectively.