Xuegang Guo

MiR-218 Inhibits Invasion and Metastasis of Gastric Cancer by Targeting the Robo1 Receptor

MicroRNAs play key roles in tumor metastasis. Here, we describe the regulation and function of miR-218 in gastric cancer (GC) metastasis. miR-218 expression is decreased along with the expression of one of its host genes, Slit3 in metastatic GC. However, Robo1, one of several Slit receptors, is negatively regulated by miR-218, thus establishing a negative feedback loop. Decreased miR-218 levels eliminate Robo1 repression, which activates the Slit-Robo1 pathway through the interaction between Robo1 and Slit2, thus triggering tumor metastasis. The restoration of miR-218 suppresses Robo1 expression and inhibits tumor cell invasion and metastasis in vitro and in vivo. Taken together, our results describe a Slit-miR-218-Robo1 regulatory circuit whose disruption may contribute to GC metastasis. Targeting miR-218 may provide a strategy for blocking tumor metastasis.

miR-206 inhibits gastric cancer proliferation in part by repressing cyclinD2.

In this study, we detected miR-206 expression in gastric cancer (GC) and further investigated its effects on GC cell growth in vitro and in vivo. miR-206 expression was found to be significantly decreased in 30 GC samples and GC cell lines by real time-PCR. Restoration of miR-206 reduced cell growth and colony forming ability in GC cells with G0/G1 cell cycle arrest. Further studies demonstrated that miR-206 could suppress GC cells proliferation at least partially through targeting the cyclinD2 (CCND2). Therefore, we provided evidence that miR-206 was a potential tumor suppressor and may be used as a therapeutic target for gastric cancer.

Telephone-based re-education on the day before colonoscopy improves the quality of bowel preparation and the polyp detection rate: a prospective, colonoscopist-blinded, randomised, controlled study

Background Despite advances in bowel preparation methods, the quality of bowel preparation in some patients undergoing colonoscopy remains unsatisfactory. The effect of telephone re-education (TRE) on the day before colonoscopy on the quality of bowel preparation and other outcome measures had not been studied. Methods A prospective colonoscopist-blinded study was conducted. All patients received regular instructions during a visit to discuss colonoscopy. Those scheduled for colonoscopy were randomly assigned to receive TRE on the day before colonoscopy (TRE group) for bowel preparation or no TRE (control group). The primary outcome was the rate of adequate bowel preparation. The secondary outcomes included polyp detection rate (PDR), non-compliance with instructions, and willingness to repeat bowel preparation. Results A total of 605 patients were randomised, 305 to the TRE group and 300 to the control group. In an intention-to-treat analysis of the primary outcome, adequate preparation was found in 81.6% vs 70.3% of TRE and control patients, respectively (p=0.001). PDR was 38.0% vs 24.7% in the TRE and control group, respectively (p<0.001). Among patients with successful colonoscopy, the Ottawa scores were 3.0±2.3 in the TRE group and 4.9±3.2 in the control group (p<0.001). Fewer patients who showed non-compliance with instructions were found in the TRE group (9.4% vs 32.6%, p<0.001). No significant differences were observed between the two groups with regard to willingness to have a repeat bowel preparation (p=0.409). Conclusions TRE about the details of bowel preparation on the day before colonoscopy significantly improved the quality of bowel preparation and PDR.

Cellular prion protein promotes proliferation and G1/S transition of human gastric cancer cells SGC7901 and AGS

The function of cellular prion protein (PrPC), the essential protein for the pathogenesis and transmission of prion diseases, is still largely unknown. The putative roles of PrPC are thought to be related to cell signaling, survival, and differentiation. In a previous study, we showed that PrPC was overexpressed in gastric cancer tissues. In the present report, we show that ectopic expression of PrPC could promote tumor‐igenesis, proliferation, and G1/S transition in gastric cancer cells. Furthermore, CyclinD1, a protein related to cell cycle, was shown to be significantly up‐regulated by PrPC at both mRNA and protein levels. PI3K/Akt pathway mediated above PrPC signal since PrPC increased the expression of phosphorylated Akt, and the specific inhibitor of Akt, LY294002, could markedly suppress growth of SGC7901 and transactivation of CyclinD1 induced by PrPC. Octapeptide repeat region played a vital role in this function, as deletion of this region abolished or reduced these effects. Collectively, this study demonstrates that overexpression of PrPC might promote the tumorigenesis and proliferation of gastric cancer cells at least partially through activation of PI3K/Akt pathway and subsequent transcriptional activation of CyclinD1 to regulate the G1/S phase transition, in which octapeptide repeat region might be an indispensable region.–Liang, J., Pan, Y., Zhang, D., Guo, C., Shi, Y., Wang, J., Chen, Y., Wang, X., Liu, J., Guo, X., Chen, Z., Qiao, T., Fan, D. Cellular prion protein promotes proliferation and G1/S transition of human gastric cancer cells SGC7901 and AGS. FASEB J. 21, 2247–2256 (2007)

Routine pre-procedural rectal indometacin versus selective post-procedural rectal indometacin to prevent pancreatitis in patients undergoing endoscopic retrograde cholangiopancreatography: a multicentre, single-blinded, randomised controlled trial.

BACKGROUND Rectal indometacin decreases the occurrence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). However, the population most at risk and the optimal timing of administration require further investigation. We aimed to assess whether pre-procedural administration of rectal indometacin in all patients is more effective than post-procedural use in only high-risk patients to prevent post-ERCP pancreatitis. METHODS We did a multicentre, single-blinded, randomised controlled trial at six centres in China. Eligible patients with native papilla undergoing ERCP were randomly assigned in a 1:1 ratio (with a computer-generated list) to universal pre-procedural indometacin or post-procedural indometacin in only high-risk patients, with stratification by trial centres and block size of ten. In the universal indometacin group, all patients received a single dose (100 mg) of rectal indometacin within 30 min before ERCP. In the risk-stratified, post-procedural indometacin group, only patients at predicted high risk received rectal indometacin, immediately after ERCP. Investigators, but not patients, were masked to group allocation. The primary outcome was overall ocurrence of post-ERCP pancreatitis. The analysis followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT02002650. FINDINGS Between Dec 15, 2013, and Sept 21, 2015, 2600 patients were randomly assigned to universal, pre-procedural indometacin (n=1297) or risk-stratified, post-procedural indometacin (n=1303). Overall, post-ERCP pancreatitis occurred in 47 (4%) of 1297 patients assigned to universal indometacin and 100 (8%) of 1303 patients assigned to risk-stratified indometacin (relative risk 0·47; 95% CI 0·34-0·66; p<0·0001). Post-ERCP pancreatitis occurred in 18 (6%) of 305 high-risk patients in the universal group and 35 (12%) of 281 high-risk patients in the risk-stratified group (p=0·0057). Post-ERCP pancreatitis was also less frequent in average-risk patients in the universal group (3% [29/992]), in which they received indometacin, than in the risk-stratified group (6% [65/1022]), in which they did not receive the drug (p=0·0003). Other than pancreatitis, adverse events occurred in 41 (3%; two severe) patients in the universal indometacin group and 48 (4%; one severe) patients in the risk-stratified group. The most common adverse events were biliary infection (22 [2%] patients vs 33 [3%] patients) and gastrointestinal bleeding (13 [1%] vs ten [1%]). INTERPRETATION Compared with a risk-stratified, post-procedural strategy, pre-procedural administration of rectal indometacin in unselected patients reduced the overall occurrence of post-ERCP pancreatitis without increasing risk of bleeding. Our results favour the routine use of rectal indometacin in patients without contraindications before ERCP. FUNDING National Key Technology R&D Program, National Natural Science Foundation of China.

Gankyrin promotes the proliferation of human pancreatic cancer

Previous studies in our laboratory have suggested that gankyrin expression is correlated with a malignant phenotype in colorectal cancer. Here, we investigated the possible role of gankyrin in pancreatic carcinogenesis. Gankyrin expression was significantly increased in pancreatic cancer compared to non-cancerous tissues. This expression significantly enhanced cancer cell proliferation and growth in vitro and in vivo. Suppression of gankyrin downregulated cyclin A, cyclin D1, cyclin E, CDK2, CDK4, PCNA and p-Rb but upregulated p27, Rb and p53. However, gankyrin overexpression led to opposite results. Thus, gankyrin could enhance pancreatic cancer cell proliferation by promoting cell cycle progression and p53 degradation.

Distinguishing pancreatic cancer from chronic pancreatitis and healthy individuals by 1H nuclear magnetic resonance-based metabonomic profiles

OBJECTIVES To develop a noninvasive and accessible diagnostic method for pancreatic cancer (PC). DESIGN AND METHODS We presented a metabolomic method, pattern recognition techniques applied to (1)H nuclear magnetic resonance ((1)H NMR) spectra, to investigate the plasma metabolites obtained from 19 patients with PC, 20 patients with chronic pancreatitis (CP) and 20 healthy individuals. RESULTS Metabolic changes associated with PC included abnormal amino acid and lipid metabolism, and possible multiple metabolic syndrome. PC elevated plasma levels of N-acetyl glycoprotein (NAG), dimethylamine (DMA), very low density lipoprotein (VLDL), and acetone, and reduced levels of 3-hydroxybutyrate, lactate, high density lipoprotein (HDL), low density lipoprotein (LDL), citrate, alanine, glutamate, glutamine, histidine, isoleucine, lysine, and valine. These metabolites could be a biomarker group for PC that distinguishes between PC and CP patients and healthy individuals. CONCLUSIONS NMR-based metabonomic strategy appears as a promising approach for distinguishing pancreatic cancer and identifying new strategies for prevention or therapy in the clinical practice.

Water exchange enhanced cecal intubation in potentially difficult colonoscopy. Unsedated patients with prior abdominal or pelvic surgery: a prospective, randomized, controlled trial

BACKGROUND Colonoscopy is widely used for management of colorectal diseases. A history of abdominal or pelvic surgery is a well-recognized factor associated with difficult colonoscopy. Although water exchange colonoscopy (WEC) was effective in small groups of male U.S. veterans with such a history, its application in other cultural settings is uncertain. OBJECTIVE To investigate the application of WEC in such patients. DESIGN Prospective, randomized, controlled, patient-blinded study. SETTING Tertiary-care referral center in China. PATIENTS Outpatients with prior abdominal or pelvic surgery undergoing unsedated diagnostic, screening, or surveillance colonoscopy. INTERVENTION Patients were randomized to examination by either WEC or conventional air colonoscopy (AC). MAIN OUTCOME MEASUREMENTS Cecal intubation rate. RESULTS A total of 110 patients were randomized to the WEC (n = 55) or AC (n = 55) group. WEC significantly increased the cecal intubation rate (92.7% vs 76.4%; P = .033). The maximum pain scores (± standard deviation) were 2.1 ± 1.8 (WEC) and 4.6 ± 1.7 (AC), respectively (P < .001). Multivariate analysis showed that the colonoscopy method was the only independent predictor of failed colonoscopy (odds ratio 11.44, 95% confidence interval, 1.35-97.09). A higher proportion of patients examined by WEC would be willing to have a repeat unsedated colonoscopy (90.9% vs 72.7%, P = .013). LIMITATIONS Single center; unblinded but experienced endoscopists. CONCLUSION This randomized, controlled trial confirms that the water exchange method significantly enhanced cecal intubation in potentially difficult colonoscopy in unsedated patients with prior abdominal or pelvic surgery. The lower pain scores and higher proportion accepting repeat of the unsedated option suggest that WEC is promising. It may enhances compliance with colonoscopy in specific populations. ( CLINICAL TRIAL REGISTRATION NUMBER NCT01485133.).

Inhibition of PI3K/Akt partially leads to the inhibition of PrP(C)-induced drug resistance in gastric cancer cells.

Cellular prion protein (PrPC), a glycosyl‐phosphatidylinositol‐anchored membrane protein with unclear physiological function, was previous found to be upregulated in adriamycin (ADR)‐resistant gastric carcinoma cell line SGC7901/ADR compared to its parental cell line SGC7901. Overexpression of PrPC in gastric cancer has certain effects on drug accumulation through upregulation of P‐glycoprotein (P‐gp), which is suggested to play an important role in determining the sensitivity of tumor cells to chemotherapy and is linked to activation of the phosphatidylinositol‐3‐kinase/Akt (PI3K/Akt) pathway. In the present study, we further investigate the role of the PI3K/Akt pathway in PrPC‐induced multidrug‐resistance (MDR) in gastric cancer. Immunohistochemistry and confocal microscope detection suggest a positive correlation between PrPC and phosphorylated Akt (p‐Akt) expression in gastric cancer. Using established stable PrPC transfectant cell lines, we demonstrated that the level of p‐Akt was increased in PrPC‐transfected cells. Inhibition of PrPC expression by RNA interference resulted in decreased p‐Akt expression. Inhibition of the PI3K/Akt pathway by one of its specific inhibitors, LY294002, or by Akt small interfering RNA (siRNA) resulted in decreased multidrug resistance of SGC7901 cells, partly through downregulation of P‐gp induced by PrPC. Taken together, our results suggest that PrPC‐induced MDR in gastric cancer is associated with activation of the PI3K/Akt pathway. Inhibition of PI3K/Akt by LY2940002 or Akt siRNA leads to inhibition of PrPC‐induced drug resistance and P‐gp upregulation in gastric cancer cells, indicating a possible novel mechanism by which PrPC regulates gastric cancer cell survival.

Polysaccharide hemostatic system for hemostasis management in colorectal endoscopic mucosal resection

A new polysaccharide hemostatic system (EndoClotTM) was recently developed for bleeding control in gastrointestinal tract endoscopy; however, its efficacy and safety is not yet well established in colorectal endoscopic mucosal resection (EMR). The aim of the present study was to observe the bleeding control effect after EMR in the colorectum.