Xiangyu Kong

Combination of plasma microRNAs with serum CA19-9 for early detection of pancreatic cancer

This study was performed to identify plasma microRNAs (miRNAs) as diagnostic biomarkers for pancreatic cancer (PCa) and to assess their supplementary role with serum CA19‐9 in early identification of tumors. Plasma RNAs were extracted from 140 PCa patients, 111 chronic pancreatitis (CP) patients and 68 normal controls, and the relative abundances of seven miRNAs (miR‐16, 21, 155, 181a, 181b, 196a and 210) were measured using real‐time PCR. Their diagnostic utility for PCa and correlation with clinical characteristics were analyzed. All seven miRNAs were significantly aberrantly upregulated in the PCa group compared with both the CP and normal groups, between which only four miRNAs (miR‐155, 181a, 181b and 196a) were significantly different. Logistic modeling proved that only miR‐16 and miR‐196a possessed an independent role in discriminating PCa from normal and CP. Furthermore, after including serum CA19‐9 in the logistic model, the combination of miR‐16, miR‐196a and CA19‐9 was more effective for discriminating PCa from non‐PCa (normal+CP) (AUC‐ROC, 0.979; sensitivity, 92.0%; specificity, 95.6%), and for discriminating PCa from CP (AUC‐ROC, 0.956; sensitivity, 88.4%; specificity, 96.3%) compared with the miRNA panel (miR‐16+miR‐196a) or CA19‐9 alone. Most significantly, the combination was effective at identification of tumors in Stage 1 (85.2%). In conclusion, plasma miRNAs were effective for distinguishing PCa from non‐PCa (normal+CP). The combination of miR‐16, miR‐196a and CA19‐9 was more effective for PCa diagnosis, especially in early tumor screening.

Aberrant expression miR-196a is associated with abnormal apoptosis, invasion, and proliferation of pancreatic cancer cells.

Objectives MiR-196a levels inversely correlated with survival in pancreatic adenocarcinoma patients. However, the functional contributions of miR-196a to pancreatic cancer remain unclear. Methods Three lentiviral vectors encoding microRNA miR-196a precursor, inhibitor, and scrambled microRNA oligomer were transfected into Panc-1 cells, respectively. Then we explored the regulation of inhibitor of growth 5 (ING5) expression by miR-196a and its impact on apoptosis, invasion, and growth of pancreatic cancer cells. The lentiviral transfected Panc-1 cells were surgically implanted into the pancreas of mice. In vivo tumor growth and ING5 expression were measured. Results Down-regulation of ING5 expression was detected in cells transfected with miR-196a precursor (P < 0.01), accompanied by less apoptosis, increased invasion, and proliferation compared with control cells (P < 0.05). Cells transfected with miR-196a inhibitor revealed an opposite trend. Smaller detectable tumors were found in only 60% of mice after implantation of Lenti.miR-196a inhibitor–transfected Panc-1 cells compared with controls (360.7 ± 303.6 mm3 vs 511.58 ± 365.9 mm3 in controls; P < 0.01). Conclusion Our results provide experimental evidence to support aberrant expression of miR-196a is associated with abnormal apoptosis, invasion, and proliferation of pancreatic cancer cells.

Targeted destruction of the orchestration of the pancreatic stroma and tumor cells in pancreatic cancer cases: molecular basis for therapeutic implications.

Pancreatic cancer is one of the most lethal malignancies, with a prominent desmoplastic reaction as its defining hallmark. The past several decades have seen dramatic progress in understanding of pancreatic cancer pathogenesis, including identification of precursor lesions, sequential transformation from normal pancreatic tissue to invasive pancreatic cancer and corresponding signature genetic events, and the biological impact of these events on malignant behavior. However, the currently used therapeutic strategies for epithelial tumor cells, which have exhibited potent antitumor activity in cell culture and animal models, have failed to produce significant effects in the clinic. The desmoplastic stroma surrounding pancreatic cancer cells, which accounts for about 90% of a tumors mass, clearly is not a passive scaffold for cancer cells but an active contributor to carcinogenesis. Improved understanding of the dynamic interaction between cancer cells and the stroma will be important to designing effective therapeutic strategies for pancreatic cancer. This review focuses on the origin of stromal molecular and cellular components in pancreatic tumors, their biological effects on pancreatic cancer cells, and the orchestration of these two components.

Initial experience from the transgastric endoscopic peritoneoscopy and biopsy: a stepwise approach from the laboratory to clinical application.

Background and Aim:  Natural‐orifice translumenal endoscopic surgery (NOTES) is a newly minimally invasive technique that gives access to the abdominal cavity via transgastric, transcolonic, transvaginal or transvesical routes. The aim of the present study was to evaluate the safety and feasibility of transgastric endoscopic peritoneoscopy and biopsy from laboratory to clinical application.

STK33 promotes growth and progression of pancreatic cancer as a critical downstream mediator of HIF1a

The serine/threonine kinase STK33 has been implicated in cancer cell proliferation. Here, we provide evidence of a critical role for STK33 in the pathogenesis and metastatic progression of pancreatic ductal adenocarcinoma (PDAC). STK33 expression in PDAC was regulated by the hypoxia-inducible transcription factor HIF1α. In human PDAC specimens, STK33 was overexpressed and associated with poor prognosis. Enforced STK33 expression promoted PDAC proliferation, migration, invasion, and tumor growth, whereas STK33 depletion exerted opposing effects. Mechanistic investigations showed that HIF1α regulated STK33 via direct binding to a hypoxia response element in its promoter. In showing that dysregulated HIF1α/STK33 signaling promotes PDAC growth and progression, our results suggest STK33 as a candidate therapeutic target to improve PDAC treatment. Cancer Res; 77(24); 6851-62. ©2017 AACR.

VDR signaling inhibits cancer-associated-fibroblasts’ release of exosomal miR-10a-5p and limits their supportive effects on pancreatic cancer cells

We read with great interest the recent publication by Ferrer-Mayorga et al ,1 concerning Vitamin D receptor (VDR) signalling’s impacts on cancer-associated fibroblasts (CAFs) in colorectal cancer (CRC). In line with one previous publication regarding VDR in pancreatic cancer (PC),2 activation of VDR signalling in stromal fibroblasts predicts a favourable clinical outcome in CRC. Both reports set the concept in principle that VDR agonists can be explored as a therapy against tumor-associated stroma in PC and CRC. However, detailed mechanisms involved in VDR’s regulation of tumor-stroma crosstalk remained to be elucidated. Recent publications identified exosomal miRNAs as critical mediators for cellular communication. In this study, we aimed to investigate whether exosomal miRNAs were implicated in VDR’s regulation against the protumoural activity of CAFs. Three immortalised CAF cell lines were generated from PC patients following the protocol reported previously.3 Exosomes released by CAFs were labelled with fluorescent dye 1,1’-dioctadecyl-3,3,3’,3’-tetramethylindocarbocyanine perchlorate (DiI) and incubated with PC cell lines (PANC-1 and SW1990) for 24 hours. Analysis using fluorescence microscopy (figure 1A) and flow cytometry (figure …

Lumen-apposing metal stent acted as an interim role in walled-off necrosis drainage

Recently, Bang et al 1 conducted the first randomised trial on lumen-apposing metal stents (LAMS) versus plastic stents for endoscopic ultrasonography (EUS)-guided drainage of walled-off necrosis (WON), which provided significant information for the clinical application of LAMS. We agree with Bang et al 1 that the wider diameter of LAMS facilitates more rapid drainage of necrotic contents leading to faster WON resolution, and we agree that LAMS must be removed at 3 weeks postprocedure if the WON resolved. Our endoscopy centre observed LAMS-related adverse events, including stent buried in tissue2 and cardia occlusion,3 at more than 3 weeks postprocedure. Bang et al 1 stated that disconnected pancreatic duct …