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BackgroundNicotinamide (NAM), the precursor for the synthesis of NAD+ and also an inhibitor of SIRT1, has been discovered to inhibit some types of cancer. However, little is known about the effects of NAM on pancreatic cancer cells. Since previous research showed that SIRT1 and K-Ras/Akt signaling acted as a promoter in tumorigenesis of pancreatic cancer, our present research set out to explore whether NAM inhibits proliferation and facilitates chemosensitivity in pancreatic cancer cells as well as the potential mechanisms involving SIRT1 and K-Ras/Akt pathway.MethodsCell viability was assessed by MTT assay, and apoptosis and cell cycle were measured by flow cytometry. Cell invasive ability was evaluated by matrigel invasion assays. The activity of SIRT1 was measured by the Fluor de Lys deacetylation assay. Expression levels of SIRT1, K-Ras, Phosphated Akt (P-Akt, Ser-473) and Akt were measured using western blot. In vivo tumor growth was performed in pancreatic cancer cells xenografts.ResultsNAM inhibited the proliferation of pancreatic cancer cells in a dose-dependent manner, and significantly induced apoptosis and cell cycle arrest in G2/M phase. Moreover, NAM obviously restrained cell invasive ability and increased the chemosensitivity. NAM significantly inhibited the activity of SIRT1 and decreased expression of SIRT1, K-Ras and P-Akt. Further, NAM prohibited proliferation and enhanced GEM antitumor activity in vivo.ConclusionsOur results implied that NAM might be a potential therapeutic agent for human pancreatic cancer treatment through downregulating SIRT1, K-Ras and P-Akt expression.  相似文献   
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BackgroundAn increasing number of patients with hepatolithiasis were diagnosed at an early stage in China. Laparoscopic surgery has introduced new methods of treating this condition.AimTo investigate the patient selection, operative technique, and efficacy of laparoscopic hepatectomy with bile duct exploration for the treatment of hepatolithiasis.Patients and methodsThe clinical data of 116 patients who underwent laparoscopic hepatectomy (laparoscopic group) and 78 patients who underwent open hepatectomy (open group) for hepatolithiasis were retrospectively analyzed, and were compared with the recent reports.ResultsThe laparoscopic group had a longer duration of operation (323.3 ± 103.0 min vs. 272.8 ± 66.8 min, p < 0.05) and shorter postoperative hospital stay (13.1 ± 5.6 days vs. 16.5 ± 8.4 days, p < 0.05) than the open group. There were no significant differences between the two groups in intraoperative blood loss or transfusion rate, postoperative complications, calculus clearance, calculus recurrence, or recurrent cholangitis (p > 0.05 for all). Efficacy in the laparoscopic group was similar to that in other recently reported studies.ConclusionsLaparoscopic hepatectomy with bile duct exploration is safe and feasible for early stage localized hepatolithiasis, with an efficacy similar to that of open surgery. Anatomic hepatectomy is important for achieving good therapeutic outcomes.  相似文献   
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