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Background/Aims: Decreased carboxypeptidase E (CPE) expression is associated with numerous pathophysiological conditions. This study aimed to investigate the potential function of hepatic CPE in cholesterol gallstone formation. Patients and Methods: Patients with cholesterol gallstone (CGS group) and patients without cholesterol gallstones (non-CGS group) were enrolled. The serum total cholesterol, triglyceride, and biliary composition were analyzed. Eight liver samples from two patients without CGS and six patients with CGS were subjected to cDNA microarray analysis. Hepatic CPE expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemical analysis. Plasma CCK level was measured by ELISA. Results: cDNA microarray identified CPE as a gene downregulated in the CGS group. RT-PCR showed that CPE mRNA level was lower in CGS group than in control (P < 0.05, t-test). Moreover, Western blot and immunohistochemistry analysis showed that CPE protein level was significantly lower in CGS group than in the control group. In addition, plasma CCK level was lower in CGS group than in the control group. A positive correlation was found between serum CCK level and hepatic CPE mRNA level (r2 = 0.713, P = 0.003). Conclusions: Down-expression of liver CPE may reduce the secretion of serum CCK and contribute to the formation of cholesterol gallstone.

The present study aimed to investigate the mechanism and the possible approaches of solving drug resistance by silencing hypoxia-inducible factor-1 alpha of human pancreatic cancer cell line Patu8988/5-Fu cultured in hypoxia. The effective jamming fragment screened by RT-PCR for silencing HIF-1α gene was transfected into pancreatic cancer cells Patu8988/5-Fu through lentivirus. RT-PCR results showed that the effective jamming fragments for HIF-1α in lentivirus transfection was Wtl-mus-1202(C546). Combined MTT with JC-1 fluorescence staining flow cytometric analysis, the concentration of 200 μmol/L CoCl2 for 8 h was chosen to mimic hypoxia cell environment. The drug resistance significantly enhanced in response to hypoxia in Patu8988/5-Fu (p0.05), and silence HIF-1α could reverse the multidrug resistance (P0.05). In the Patu8988/5-Fu cells, HIF-1α and MDR1 significantly increased in response to hypoxia (p0.05). The inhibition of HIF-1α expression synergistically downregulated the expression of the MDR1 gene in Patu8988/5-Fu cells (p0.05). HIF-1α expression was positively correlated with the MDR1 expression (p0.05). The upregulation of the HIF-1α and MDR1 gene expression caused by hypoxia was related with the generation of multi-drug resistance of Patu8988/5-Fu, targeted silencing HIF-1α may be a kind of way to reverse the chemotherapy drug resistance.

Objectives Pancreatic cancer remains a lethal disease. In this study, we investigated the efficacy of a combination of gastrin-releasing peptide receptor antagonist RC-3095 and gemcitabine on pancreatic cancer CFPAC-1. Methods The antiproliferation effects of RC-3095, gemcitabine, or the combination on pancreatic cancer were monitored in vitro. Nude mice bearing xenografts of CFPAC-1 cell received injections of the vehicle (control), RC-3095 (20 μg, subcutaneously, daily), gemcitabine (15 mg/kg, intraperitoneally, every 3 days), or the combination of RC-3095 and gemcitabine for 4 weeks. The histological changes and protein expression were tested using immunohistochemistry and Western blotting. Results Treatment with the combination in culture exhibited a powerful inhibition effect on CFPAC-1 cell proliferation. In xenograft mice model, RC-3095 or gemcitabine significantly reduced the volume and weight of tumors after 4 weeks of treatment, as compared with controls. The combination more potently inhibited the tumor growth than either agent used individually. Immunohistochemistry and Western blotting showed gastrin-releasing peptide receptor/bombesin receptor subtype-3 positive cells and protein expression in tumors decreased by treatment with RC-3095 or gemcitabine alone or greater in combination. Conclusions Our data suggested that the combination could be considered for the possible new approaches for treatment of pancreatic cancers.

The effectiveness of an external pancreatic duct stent for reduction of the pancreatic fistula after pancreaticoduodenectomy remains controversial. MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched for eligible randomized controlled trials (RCTs). Reviews of each trial were conducted and data were extracted. The primary outcome was pancreatic fistula. Statistical pooling used the fixed or random effects model and reported as risk ratio (RR) or mean difference (MD) with the corresponding 95 % confidence intervals (CI). Four RCTs including a total of 416 patients were detected. Methodological quality assessment revealed a better quality of all analyzed trials. Placing an external stent across pancreaticojejunal anastomosis could significantly reduce the incidence of pancreatic fistula (RR = 0.57, 95 % CI = 0.41–0.80, P = 0.001, I 2 = 0 %), overall morbidity (RR = 0.79, 95 % CI = 0.64–0.98, P = 0.03), and the length of hospital stay (MD = −3.98 days, 95 % CI = −6.42 to −1.54, P = 0.001, I 2 = 13 %). No significant difference was found in terms of hospital mortality, delayed gastric emptying, operation time, operative blood loss, blood replacement, and reoperation rate. This meta-analysis provides compelling evidence that the application of an external pancreatic duct stent after pancreaticoduodenectomy can decrease the incidence of pancreatic leakage when compared with no stent. Moreover, the external drainage of pancreatic juice is associated with lower postoperative overall morbidity and shorter hospital stay.