Zi-Man Zhu

Prognostic significance of microRNA-141 expression and its tumor suppressor function in human pancreatic ductal adenocarcinoma

Increasing evidence shows that dysregulation of microRNAs is correlated with tumor development. This study was performed to determine the expression of miR-141 and investigate its clinical significance in pancreatic ductal adenocarcinoma (PDAC). Taqman quantitative RT-PCR was used to detect miR-141 expressions in 94 PDAC tissues and 16 nontumorous pancreatic tissues. Correlations between miR-141 expression and clinicopathologic features and prognosis of patients were statistically analyzed. The effects of miR-141 expression on growth and apoptosis of PDAC cell line (PANC-1) were determined by MTT, colony formation, and flow cytometry assays. Potential target genes were identified by luciferase reporter and Western blot assays. The expression level of miR-141 in PDAC tissues was significantly lower than that in corresponding nontumorous tissues. Downregulation of miR-141 correlated with poorer pT and pN status, advanced clinical stage, and lymphatic invasion. Also, low miR-141 expression in PDAC tissues was significantly correlated with shorter overall survival, and multivariate analysis showed that miR-141 was an independent prognostic factor for PDAC patients. Further, functional researches suggested that miR-141 inhibits growth and colony formation, and enhances caspase-3-dependent apoptosis in PANC-1 cells by targeting Yes-associated protein-1 (YAP1). Therefore, miR-141 is an independent prognostic factor for PDAC patients, and functions as a tumor suppressor gene by targeting YAP1.

Expression of microRNA‐218 in human pancreatic ductal adenocarcinoma and its correlation with tumor progression and patient survival

Our aim was to analyze clinicopathologic and prognostic values of microRNA (miR)‐218 in pancreatic ductal adenocarcinima (PDAC).

Impact of mesocaval shunt on safe minimal liver remnant: Porcine model

AIM To investigate the capacity of shunts to relieve portal hypertension and decrease the safe minimal liver remnant in pigs. METHODS A subtotal hepatectomy with < 60 mL blood loss and without hepatic pedicle occlusion was performed. The mesenteric venous inflow was diverted through a mesocaval shunt (MCS) constructed using the prepared left renal vein with an end-to-side running suture of 5-0 proline. All 21 animals that underwent subtotal hepatectomy and/or MCS were divided into three groups. In the 15% group, the residual volume was 14%-19% of total liver volume (TLV); in the 15%+ S group, the residual volume was also 14%-19% of TLV with a mesocaval shunt (MCS); and in the 10%+ S group, the residual volume was 8%-13% of TLV with an MCS. In the three groups, the intraoperative portal vein pressure (PVP) and portal vein flow (PVF) were monitored and compared at laparotomy and 1 h post-hepatectomy. The survival rate, sinusoidal endothelial damage, tissue analysis, and serum analysis were investigated among the three groups. RESULTS The percentage residual liver volume was 15.9%, 16.1% and 11.8% in the 15%, 15%+ S, 10%+ S groups, respectively. After hepatectomy, PVF and portal-to-arterial flow ratio in the 15%+ S group significantly decreased and hepatic artery flow (HAF) per unit volume significantly increased, compared to those in the 15% group. The PVP in the 15%+ S group and 10%+ S group increased slightly from that measured at laparotomy; however, in the 15% group, the PVP increased immediately and significantly above that observed in the other two groups. The 14-d survival rates were 28.5%, 85.6%, and 14.2% in the 15%, 15%+ S, and 10%+ S groups, respectively. In the 15%+ S group, the shunts effectively attenuated injury to the sinusoidal endothelium, and the changes in the serum and tissue analysis results were significantly reduced compared to those in the 15% and 10%+ S groups. CONCLUSION MCS can decompress the portal vein and so attenuate liver injury from hyperperfusion, and make extreme or marginal hepatectomy safer.

Effects of intensive insulin therapy combined with low molecular weight heparin anticoagulant therapy on severe pancreatitis.

The current study explored the effects of intensive insulin therapy (IIT) combined with low molecular weight heparin (LMWH) anticoagulant therapy on severe acute pancreatitis (SAP). A total of 134 patients with SAP that received treatment between June 2008 and June 2012 were divided randomly into groups A (control; n=33), B (IIT; n=33), C (LMWH; n=34) and D (IIT + LMWH; n=34). Group A were treated routinely. Group B received continuous pumped insulin, as well as the routine treatment, to maintain the blood sugar level between 4.4 and 6.1 mmol/l. Group C received a subcutaneous injection of LMWH every 12 h in addition to the routine treatment. Group D received IIT + LMWH and the routine treatment. The white blood cell count, hemodiastase, serum albumin, arterial partial pressure of oxygen and prothrombin time were recorded prior to treatment and 1, 3, 5, 7 and 14 days after the initiation of treatment. The intestinal function recovery time, incidence rate of multiple organ failure (MOF), length of hospitalization and fatality rates were observed. IIT + LMWH noticeably increased the white blood cell count, hemodiastase level, serum albumin level and the arterial partial pressure of oxygen in the patients with SAP (P<0.05). It markedly shortened the intestinal recovery time and the length of stay and reduced the incidence rate of MOF, the surgery rate and the fatality rate (P<0.05). It did not aggravate the hemorrhagic tendency of SAP (P>0.05). IIT + LMWH had a noticeably improved clinical curative effect on SAP compared with that of the other treatments.

The ubiquitin ligase RNF43 downregulation increases membrane expression of frizzled receptor in pancreatic ductal adenocarcinoma

RNF43 is a novel tumor suppressor protein and known to be expressed in a multitude of tissue and dysregulated in cancers of these organs including ovarian and colorectal tissues. RNF43 expression has been shown to be expressed in mutated forms in several pancreatic cell lines. RNF43, by virtue of being an ubiquitin ligase, has the potential to ubiquitinylate membrane receptors like frizzled that subserves sensing Wnt soluble signals at the cell membrane. Thus, normally, RNF43 downregulates Wnt signaling by removing frizzled receptor from the membrane. In the present study, the expression of the tumor suppressor RNF43 was examined in human patient samples of pancreatic ductal adenocarcinoma (PDAC). Reduced levels of expression of RNF43 in PDAC were demonstrated by Western blotting. We incorporated membrane biotinylation assay to examine the expression of frizzled6 receptor in the membrane and demonstrated that it is significantly increased in PDAC tissues. This may be responsible for enhanced Wnt/beta-catenin signaling and provides the first level of evidence of a possible role of this well-known pathway in pancreatic exocrine carcinogenesis. We have utilized appropriate controls to ensure the true positivity of the findings of the present study. The contribution of Wnt/beta-catenin/RNF43 pathway in pancreatic carcinogenesis may provide for utilization of pharmacologic resources for precision-based approaches to treat pancreatic ductal adenocarcinoma.

Modified hepatic vascular occlusion facilitates hepatectomy for malignant hepatic tumor in laparoscopy.

Purpose: The parenchymal transection and bleeding are important problems in laparoscopic hepatectomy (LH). The study aimed to evaluate the feasibility and safety of LH for a malignant hepatic tumor (MHT) with hepatic vascular occlusion (HVO) only using a monopolar electrocautery. Methods: A total of 31 patients’ profiles, operative data, clinical outcomes, pathologic findings, and follow-up information were collected who underwent LH with HVO. Results: The median operative time was 176 minutes and the median postoperative hospital stay was 9 days. The median estimated blood loss was 310 mL. The median tumor size was 4.6 cm and the median surgical margin was 12 mm.The ischemia injury to the liver in patients subjected to selective HVO was less than that in patients subjected to the Pringle maneuver. Conclusions: HVO facilitates LH in transecting liver parenchyma and reduces bleeding, making LH safe and feasible only using monopolar electrocautery in selected patients with malignancies. Moreover, the selective HVO have more advantages over the Pringle maneuver in decreasing ischemic injury.

CCND1 rs9344 polymorphism is associated with the risk of hepatocellular carcinoma in Caucasian population

Aims: Some studies investigated the association between CCND1 rs9344 polymorphism and hepatocellular carcinoma (HCC) risk. However, the results were inconclusive. Thus, we did a meta-analysis to determine this relationship. Materials and Methods: Relevant studies were systematically searched using the PubMed, CNKI, and EMBASE databases. The strength of the association was calculated with the odds ratio (OR) and respective 95% confidence intervals (Cis). Results: We investigated the association between CCND1 rs9344 polymorphism and HCC risk in the dominant models. The result of this meta-analysis showed that CCND1 rs9344 polymorphism did not significantly associated with HCC risk (OR = 1.09; 95% CI 0.88–1.34). In the stratified analysis by ethnicity, we found that this polymorphism was significantly associated with HCC risk in Caucasians (OR = 1.55; 95% CI, 1.05–2.29). However, we did not find any significant association between this polymorphism and HCC risk in Asians (OR = 0.91; 95% CI, 0.71–1.18). Conclusions: This meta-analysis suggested that CCND1 rs9344 polymorphism might be associated with the risk of HCC among Caucasians.