DUOX2 As a Potential Prognostic Marker which Promotes Cell Motility and Proliferation in Pancreatic Cancer.

DUOX2 has been reported to highly express in several types of cancers. However, the prognostic significance and the biological function of DUOX2 expression with pancreatic cancer (PC) still remain unclear. The present study is aimed at investigating whether DUOX2 could act as a novel biomarker of prognosis and evaluating its effect on PC cell progression. The mRNA and protein expression of DUOX2 in PC cells and tissues were assessed by quantitative real-time PCR (RT-qPCR) and immunohistochemistry. The effect of DUOX2 expression on PC cell motility and proliferation was evaluated in vitro. The correlation between DUOX2 mRNA expression and clinicopathological features and its prognostic significance were analyzed according to the Gene Expression Profiling Interactive Analysis (GEPIA) website based on The Cancer Genome Atlas (TCGA) and the GTEx databases combined with our clinical information. According to bioinformatics analysis, we forecasted the upstream transcription factors (TFs) and microRNA (miRNA) regulatory mechanism of DUOX2 in PC. The expression of DUOX2 at transcriptional and protein level was dramatically increased in PC specimens when compared to adjacent nontumor specimens. Functionally, DUOX2 knockdown inhibited cell motility and proliferation activities. Our clinical data revealed that the patients had better postoperative overall survival (OS) with lower expression of DUOX2, which is consistent with GEPIA data. Multivariate analysis revealed that high DUOX2 expression was considered as an independent prognostic indicator for OS (P = 0.031). Based on Cistrome database, the top 5 TFs of each positively and negatively association with DUOX2 were predicted. hsa-miR-5193 and hsa-miR-1343-3p targeting DUOX2 were forecasted from TargetScan, miRDB, and DIANA-TarBase databases, which were negatively correlated with OS (P = 0.043 and P = 0.0088, respectively) and DUOX2 expression (P = 0.0093 and P = 0.0032, respectively) in PC from TCGA data. These findings suggest that DUOX2 acts as a promising predictive biomarker and an oncogene in PC, which could be a therapeutic target for PC.

Activation of pancreatic stellate cells involves an EMT-like process.

Pancreatic adenocarcinoma (PDAC) and chronic pancreatitis (CP) are characterized by a desmoplastic reaction involving activated pancreatic stellate cells (PSCs). However, the mechanisms of PSC activation remain poorly understood. We examined whether the epithelial-mesenchymal transition (EMT) process might play a role in PSC activation. PSCs were isolated from a rat pancreas and characterized using immunofluorescence and immunocytochemistry. We evaluated changes in cell motility and in the expression levels of a panel of EMT-related genes during the PSC activation process. Activation of PSCs occurred after 48 h of in vitro culture, as indicated by a morphological change to a myofibroblastic shape and a decrease in the number of cytoplasmic lipid droplets. After activation, PSCs showed enhanced cell migration ability compared to quiescent cells. In addition, the expression of epithelial markers (E-cadherin, BMP7 and desmoplakin) decreased, while expression of mesenchymal markers (N-cadherin, vimentin, fibronectin1, collagen1α1 and S100A4) increased in activated PSCs. EMT-related transcription factors (Snail and Slug) were also upregulated after PSC activation. The concurrent increase in cell migration ability and alterations in EMT-related gene expression suggests that the activation of PSCs involves an EMT-like process. The knowledge that PSC activation involves an EMT­like process may help to identify potential new therapeutic targets to alleviate pancreatic fibrosis in diseases like CP and PDAC.

Role of CXCL12/CXCR4 signaling axis in pancreatic cancer.

OBJECTIVE: This review focuses on the state-of-the-art of CXCL12/CXCR4 signaling axis in pancreatic cancer and its role in tumor progression. DATA SOURCES: Relevant articles published in English were identified by searching in Pubmed from 1997 to 2013, with keywords "CXCL12", "CXCR4" and "pancreatic cancer". Important references from selected articles were also retrieved. STUDY SELECTION: Articles about CXCL12/CXCR4 signaling axis in pancreatic cancer and relevant mechanisms were selected. RESULTS: Pancreatic cancer has been one of the most lethal human malignancies, with median survival less than one year and overall 5-year survival only 6%. Tumor cells from pancreatic cancer express high level of CXCR4. CXCL12, the ligand for CXCR4, is extensively secreted by neighboring stromal cells and other distant organs. CXCL12 primarily binds to CXCR4, induces intracellular signaling through several divergent pathways, which are involved in progression and metastasis of pancreatic cancer. CONCLUSIONS: CXCL12/CXCR4 signaling axis may play an important role in the communication between pancreatic cancer cells and their microenvironment, which may have effect on tumor proliferation, invasion, angiogenesis, metastasis and chemoresistance. CXCL12/CXCR4 signaling axis may serves as a novel therapeutic target for pancreatic cancer.

Palliative treatment for incurable malignant colorectal obstructions: a meta-analysis.

AIM: To perform a meta-analysis of palliative stent placement vs palliative surgical decompression for management of incurable malignant colorectal obstructions. METHODS: The databases of Medline, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials were searched from their inception to July 2012 for studies (prospective, retrospective, randomized controlled trials, and case-control trials) designed as comparative analyses of patients with incurable malignant colorectal obstructions treated by self-expanding metallic stents (SEMS) or palliative surgery. No language restrictions were imposed. The main outcome measures were hospital stay, intensive care unit admission, clinical success rate, 30-d mortality, stoma formation, complications, and overall survival time. The data extraction was conducted by two investigators working independently and using a standardized form. The Mantel-Haenszel χ² method was used to estimate the pooled risk ratios with 95%CI under a fixed-effects model; when statistical heterogeneity existed in the pooled data (as evaluated by Q test and I² statistics, where P < 0.10 and I² < 25% indicated heterogeneity), a random-effects model was used. RESULTS: Thirteen relevant articles, representing 837 patients (SEMS group, n = 404; surgery group, n = 433), were selected for analysis. Compared to the surgery group, the SEMS group showed lower clinical success (99.8% vs 93.1%, P = 0.0009) but shorter durations of hospital stay (18.84 d vs 9.55 d, P < 0.00001) and time to initiation of chemotherapy (33.36 d vs 15.53 d, P < 0.00001), and lower rate of stoma formation (54.0% vs 12.7%, P < 0.00001). Additionally, the SEMS group experienced a significantly lower rate of 30-d mortality (4.2% vs 10.5%, P = 0.01). Stent-related complications were not uncommon and included perforation (10.1%), migration (9.2%), and occlusion (18.3%). Surgery-related complications were slightly less common and included wound infection (5.0%) and anastomotic leak (4.7%). The rate of total complications was similar between these two groups (SEMS: 34.0% vs surgery: 38.1%, P = 0.60), but the surgery-related complications occurred earlier than stent-related complications (rate of early complications: 33.7% vs 13.7%, P = 0.03; rate of late complications: 32.3% vs 12.7%, P < 0.0001). The overall survival time of SEMS- and surgery-treated patients was not significantly different (7.64 mo vs 7.88 mo). CONCLUSION: SEMS is less effective than surgery for palliation of incurable malignant colorectal obstructions, but is associated with a shorter time to chemotherapy and lower 30-d mortality.