Publications (13)19.49 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: The 5-lipoxygenase (5-LOX) pathway has been associated with a variety of inflammatory diseases including asthma, atherosclerosis, rheumatoid arthritis, cancer and liver fibrosis. Several classes of 5-LOX inhibitors have been identified, but only one drug, zileuton, a redox inhibitor of 5-LOX, has been approved for clinical use. In the present study, 5-LOX was found to be overexpressed not only in pancreatic cancer cell lines but also in tissue samples of patients suffering from pancreatic adenocarcinoma. There was a close correlation between the tumor expression levels of 5-LOX mRNA and protein and the clinicopathological patient characteristics including lymph node metastasis and TNM stage. Zileuton suppressed the proliferation of SW1990 cells in a concentration- and time‑dependent manner. In addition, zileuton induced SW1990 cells to undergo apoptosis and significantly decreased 5-LOX expression. The number of apoptotic cells, estimated by flow cytometry, Annexin V/PI assay, TUNEL staining and sub‑diploid population was significantly higher than that of the control. These results suggest that the level of 5-LOX expression was increased in pancreatic cancer tissues and may be related to lymph node metastasis and TNM stage.
- [Show abstract] [Hide abstract] ABSTRACT: Hepatitis B virus (HBV) infection remains a challenging global health problem, with more than 350 million people chronically infected and at risk of developing hepatocellular carcinoma (HCC). Interactions that occur among host, environmental, and viral factors determine the natural course and predict the prognosis of patients with chronic HBV infection. In the past decades, several important viral factors of predictive of HCC have been identified, such as high hepatitis B surface antigen level, seropositivity of hepatitis B e antigen, high viral load, viral genotype, and specific viral sequence mutations. Identification of certain viral risk factors for HCC development and stratification of patient risk are very important to perform future surveillance programs. In this article, we thus reviewed the risk of viral factors involved in hepatocarcinogenesis.
- [Show abstract] [Hide abstract] ABSTRACT: Aim: The impact of viral status on recurrence of hepatitis B-related hepatocellular carcinoma (HCC) after curative therapy remains controversial. This meta-analysis aimed to determine whether the presence of viral load, genotype, specific mutation and antiviral therapy influenced HCC recurrence after curative therapy. Methods: We performed a meta-analysis including 20 studies to assess the effect of viral status and antiviral therapy with nucleoside analog on recurrence of HCC after curative therapy. The pooled odds ratios (OR) were calculated using a random or fixed effects model. PUBMED, MEDLINE, EMBASE and the Cochrane Database were searched for articles published from 1990 to December 2012. Results: Our results showed that the presence of high viral load significantly increased overall HCC recurrence risk after curative therapy. Pooled data from four studies on the recurrence rate among patients with genotype C infection compared with genotype B showed an increased risk of recurrence. Basal core promoter (BCP) mutation was associated with a significant risk in the recurrence of HCC. The pooled estimate of treatment effect was significantly in favor of a preventive effectiveness of antiviral therapy. Conclusion: The present study suggested that HCC patients with high viral load, genotype C and BCP mutation had a significantly higher risk of recurrence. Antiviral therapy has potential beneficial effects after the curative treatment of HCC in terms of tumor recurrence.
- [Show abstract] [Hide abstract] ABSTRACT: Severe acute pancreatitis (SAP) is a serious systemic disease with high mortality. This study aims to investigate the role of the chemokine, fractalkine (FKN), in the pathogenesis of SAP and the effects of intervention by ulinastatin on FKN expression in an SAP rat model. We randomly divided 72 Sprague Dawley rats into the following groups: SAP, ulinastatin treatment (UT), and control (C). The SAP model was induced by retrograde infusion of 4% sodium taurocholate into the bili-pancreatic ducts of the rats. Rats in the UT group were injected with ulinastatin immediately after establishment of the SAP model. Serum FKN levels were detected by ELISA at various time points. Histopathological analyses of the pancreas and lung were performed. Expressions of FKN mRNA in the tissues of the pancreas and lung were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) at various time points for each group. Serum levels of FKN at 3 h after surgery in the SAP subgroup were significantly higher than those in the C group (P < 0.05). There were no significant differences between the UT and C groups observed at various time points. Expression levels of FKN mRNA in the pancreatic tissues of the SAP group increased gradually. Although we observed no difference between the SAP and C groups (P > 0.05) at 1 hour h after surgery, mRNA levels of FKN in the lung tissues at 3, 6, and 12 h post-surgery in the SAP subgroups were significantly higher than those in the C group for the same time points (P < 0.05). Pathological injury of the pancreatic tissues was more remarkable in the SAP group compared to the UT group. FKN may play an important role in the pathogenesis of SAP and SAP-related acute lung injury (ALI). Ulinastatin efficiently interferes with SAP and SAP-related ALI and may be related to inhibition of FKN expression.
- [Show abstract] [Hide abstract] ABSTRACT: Aim: The role of interferon (IFN) therapy on prevention of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related cirrhosis remains controversial. This meta-analysis aimed to determine whether IFN therapy reduced the incidence of HCC in HCV-related cirrhotic patients. Methods: We performed a meta-analysis including eight randomized controlled trials (RCT) (a total of 1505 patients) to assess the effect of IFN therapy on prevention of HCC in patients with HCV-related cirrhosis. The pooled odds ratios (OR) were calculated using a random or fixed effects model. Results: Our results showed that IFN therapy significantly decreased the overall HCC incidence in HCV-related cirrhotic patients (OR, 0.29; 95% confidence interval [CI], 0.10-0.80; P = 0.02). HCC risk in patients who failed to achieve sustained virological response (SVR) in the initial IFN-based treatment was also reduced by maintenance IFN therapy (OR, 0.54; 95% CI, 0.32-0.90; P = 0.02). Subgroup analysis indicated that IFN therapy decreased HCC incidence in HCV-related cirrhotic patients during long-term follow up (>48 months) evidently (OR, 0.25; 95% CI, 0.09-0.67; P = 0.006). However, subgroup analysis of four RCT with short-term follow up (≤48 months) did not demonstrate the significant difference in HCC incidence between IFN-treated cirrhotic patients and controls (OR, 0.78; 95% CI, 0.39-1.55; P = 0.48). Conclusion: The present study suggested that IFN therapy could efficiently reduce HCC development in patients with HCV-related cirrhosis; this effect was more evident in the subgroup of patients with long-term follow up (>48 months). Patients who received maintenance IFN therapy had a lower risk of HCC than controls.
- [Show abstract] [Hide abstract] ABSTRACT: Chemokines and their receptors play key roles in the pathogenesis of acute pancreatitis. This study aimed to establish a rat model of severe acute pancreatitis (SAP) for investigating monocyte chemotactic protein-1 (MCP-1) expression in the pathogenesis of the disease. We assessed the effects of the inhibitor of MCP-1, Bindarit, on SAP and explored the mechanisms underlying SAP. Seventy-two Sprague-Dawley rats were randomly divided into a saline control group (group S), an SAP group (group P), and a Bindarit group (group T). The SAP model was induced by retrograde infusion of 4% sodium taurocholate into the biliopancreatic duct. Based on the SAP model, Bindarit was injected intraperitoneally in group T, and 0.5% methyl cellulose was injected intraperitoneally in groups S and P. In group S, saline was retrogradely infused into the bilipancreatic duct. Serum amylase levels and the histological changes in the pancreas were assessed at different time-points in each group. Expression of MCP-1 in serum was measured by enzyme-linked immunoadsorbent assay (ELISA). MCP-1 protein and mRNA expression levels were detected by immunohistochemistry, Western blotting, and semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Serum amylase levels in groups P and T were higher than those in group S. Serum amylase levels were significantly lower in group T than in group P at 6 and 12 hours after operation. The levels of MCP-1 in serum at 6 and 12 hours after operation in group P were significantly higher than in group S, and significantly lower in group T than in group P at 6 and 12 hours after operation. The pathological damage in the pancreas was milder in group T than in group P. MCP-1 protein and mRNA expression levels in the pancreas were higher in groups P and T than in group S. These expression levels were positively correlated with the pathological damage of pancreatic tissues. The activity of MCP-1 in group T was significantly lower than in group P. MCP-1 may play important roles in the pathogenesis of SAP. The data suggest that Bindarit ameliorates SAP by inhibiting the activity of MCP-1 in vivo.
- [Show abstract] [Hide abstract] ABSTRACT: Objective: To investigate the expression of chemokine MIP-3α and its receptor CCR6 in ulcerative colitis(UC) and to explore its relationship with the involvement and severity of UC, so as to asses their expression in the pathogenesis of UC. Methods: The expression of MIP-3α and CCR6 protein in the colon mucosa was detected by immunohistochemistry method in 35 UC patients and 20 normal controls. Results: MIP-3α and CCR6 were both positive in the UC group and negative or only weakly expressed in the normal control group. The expression of MIP-3α and CCR6 in the UC group was significantly higher than that in normal controls (P<0.01). The expression of MIP-3α and CCR6 was related to the severity and involvement of UC. The expression of MIP-3α was significantly correlated with that of CCR6(r=0.765,P<0.01). Conclusion: The expression of MIP-3α and CCR6 is positively correlated with each other, and both of them participate in the development and progression of UC. The interaction between the 2 may play an important role in the local damage and pathological changes in UC.
- [Show abstract] [Hide abstract] ABSTRACT: Arachidonic acid (AA), one of the essential fatty acids, refers to icosa-5, 8, 11, 14-tetraenoic acid constituting 20 carbon atoms and 4 double bonds. There are two major pathways including the lipoxygenase (LOX) pathway to hydroxy derivatives and leukotrienes and the cyclooxygenase (COX) pathway to prostaglandins. Members of the AA metabolizing enzymes have been reported to play a significant role in carcinogenesis, because the modulation of these pathways results in suppression of tumor growth. The both pathways were reported recently to be important in the growth regulation of human pancreatic cancer cells, and COX and LOX metabolic pathways are emerging as key regulators of cell proliferation and neo-angiogenesis. COX and LOX inhibitors are being investigated as potential anticancer drugs and results from clinical trials seem to be encouraging.
- [Show abstract] [Hide abstract] ABSTRACT: To investigate apoptosis in human pancreatic cancer cells induced by Triptolide (TL), and the relationship between this apoptosis and expression of caspase-3' bcl-2 and bax. Human pancreatic cancer cell line SW1990 was cultured in DMEM media for this study. MTT assay was used to determine the cell growth inhibitory rate in vitro. Flow cytometry and TUNEL assay were used to detect the apoptosis of human pancreatic cancer cells before and after TL treatment. RT-PCR was used to detect the expression of apoptosis-associated gene caspase-3' bcl-2 and bax. TL inhibited the growth of human pancreatic cancer cells in a dose-and time-dependent manner. TL induced human pancreatic cancer cells to undergo apoptosis with typically apoptotic characteristics. TUNEL assay showed that after the treatment of human pancreatic cancer cells with 40 ng/mL TL for 12 h and 24 h, the apoptotic rates of human pancreatic cancer cells increased significantly. RT-PCR demonstrated that caspase-3 and bax were significantly up-regulated in SW1990 cells treated with TL while bcl-2 mRNA was not. TL is able to induce the apoptosis in human pancreatic cancer cells. This apoptosis may be mediated by up-regulating the expression of apoptosis-associated caspase-3 and bax gene.
- [Show abstract] [Hide abstract] ABSTRACT: Telomerase activity is reported to be specific and frequent in human pancreatic cancer. We conducted this study to assess the usefulness of monitoring telomerase activity in exfoliated cells obtained by pancreatic duct brushing during endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis of pancreatic cancer. Exfoliated cells obtained by pancreatic duct brushing during ERCP from 21 patients (18 with pancreatic cancer, 3 with chronic pancreatitis) were examined. Telomerase activity was detected by polymerase chain reaction and telomeric repeat amplification protocol assay (PCR-TRAP-ELISA). D450 values of telomerase activity were 0.446+/-0.2700 in pancreatic cancer and 0.041+/-0.0111 in chronic pancreatitis. 77.8% (14/18) of patients with pancreatic cancer had cells with telomerase activity. None of the samples from patients with chronic pancreatitis showed telomerase activity, when the cutoff value of telomerase activity was set at 2.0. Cytological examination showed cancer cells in 66.7% (12/18) of the patients. Telomerase activity may be an early malignant event in pancreatic cancer development. Cytology and telomerase activity in cells obtained by pancreatic duct brushing may complement each other for the diagnosis of pancreatic cancer.
- [Show abstract] [Hide abstract] ABSTRACT: AIM: To investigate the role of cytokine-induced neutro- phil chemoattractant (CINC) in the pathogenesis of severe acute pancreatitis (SAP). METHODS: The acute pancreatitis model was induced by retrograde injection of 50 g/L sodium taurocholate into the bili-pancreatic duct in SD rats. Forty-eight mas- culinity SD rats were randomly divided into 2 groups: the sodium taurocholate group and the operational control group. The serum amylase level and the histol- ogical pathologic changes of pancreas were measured at different time point in each group. The expression of pancreatic CINC protein and mRNA were determined by immunohistochemistry and semi-quantitative reve- rse transcriptase polymerase chain reaction (RT-PCR), respectively. RESULTS: The level of serum amylase in sodium taur- ocholate group was significantly higher than that in the control group, and its histological pathologic changes were more significant. The expression of CINC protein in the pancreatic acinar cells and the expression of CINC mRNA in the pancreatic tissues in the sodium taurocholate group were higher, and the expression of CINC mRNA in the pancreatic acinar cells in the sodium taurocholate group were significantly higher (0.37±0.10 vs 0.29±0.10, P
- [Show abstract] [Hide abstract] ABSTRACT: To study the value of monitoring K-ras point mutation at codon 12 and telomerase activity in exfoliated cells obtained from pancreatic duct brushings during endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis of pancreatic cancer. Exfoliated cells obtained from pancreatic duct brushings during ERCP were examined in 27 patients: 23 with pancreatic cancers, 4 with chronic pancreatitis. K-ras point mutation was detected with the polymerase chain reaction and restriction fragment-length polymorphism (PCR-RFLP). Telomerase activity was detected by PCR and telomeric repeat amplification protocol assay (PCR-TRAP-ELISA). The telomerase activities in 27 patients were measured in 21 exfoliated cell samples obtained from pancreatic duct brushings. D450 value of telomerase activities in pancreatic cancer and chronic pancreatitis were 0.446+/-0.27 and 0.041+/-0.0111, respectively. Seventy-seven point eight percent (14/18) of patients with pancreatic cancer and none of the patients with chronic pancreatitis showed telomerase activity in cells collected from pancreatic duct brushings when cutoff value of telomerase activity was set at 2.0. The K-ras gene mutation rate (72.2%) in pancreatic cancer was higher than that in chronic pancreatitis (33.3%) (P<0.05). In considering of both telomerase activities and K-ras point mutation, the total positive rate was 83.3%(15/18), and the specificity was 100%. Changes of telomerase activities and K-ras point mutation at codon 12 may be an early event of malignant progression in pancreatic cancer. Detection of telomerase activity and K-ras point mutation at codon 12 may be complementary to each other, and is useful in diagnosis of pancreatic cancer.
- [Show abstract] [Hide abstract] ABSTRACT: To assess the diagnostic value of endoscopic pancreatic duct brushing in detecting mutation of the K-ras gene at codon 12 in cytologic specimens from patients with pancreatic cancer. Thirty-five patients treated at Changhai Hospital, Shanghai between 1999 and 2001 were enrolled. Their cells obtained by pancreatic duct brushing during endoscopic retrograde cholangiopancreatography (ERCP) were suspended with phosphate buffer solution (PBS). DNA of the cells was extracted and mutation of the K-ras gene at codon 12 detected by means of PCR-SSCP. The K-ras gene mutation rate of pancreatic cancer was 70%, which was higher than that of chronic pancreatitis (14%, P<0.05). K-ras gene mutation was not found in patients with pancreatic cystocarcinoma and duodenum carcinoma. As to the location of pancreatic cancer, no significant difference was observed between the head, the body and tail. The sensitivity, specificity, accuracy of pancreatic duct brushing in detecting pancreatic cancer was 70%, 94%, and 83%, respectively. K-ras analysis of pancreatic brushing samples is helpful in the diagnosis of patients with early pancreatic cancer.
Nantong UniversityTungchow, Jiangsu, China