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Background/aim Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-tumor agent. However, resistance to TRAIL has been reported in a number of clinical trials. In this study, we investigated the molecular mechanisms by which a novel histone deacetylase (HDAC) inhibitor, CBUD-1001, sensitizes colorectal cancer (CRC) cells to TRAIL-induced apoptosis. Materials and methods Apoptotic cell death induced by CBUD-1001 and/or TRAIL was assessed on human CRC cells using the MTT assay, FACS analysis and nuclei staining. The involved molecular mechanisms were explored through western blotting analysis. Results We demonstrated that combined with CBUD-1001, TRAIL significantly enhanced TRAIL-induced apoptosis in CRC cells via mitochondria-mediated pathways. We also found that hyper-acetylation of histone by CBUD-1001 treatment leads to up-regulation of death receptor (DR) 5 in a dose- and time-dependent manner. Furthermore, we identified that enhanced sensitivity to TRAIL by combination with CBUD-1001 depends on the MAPK/CHOP axis, being a key mediator of DR5. Conclusion A novel HDAC inhibitor CBUD-1001 sensitizes TRAIL-induced apoptosis via up-regulation of DR5, and that CBUD-1001 and TRAIL combination treatment offers an effective strategy to overcome TRAIL resistance in CRC cells.

Fexuprazan, a novel potassium-competitive acid blocker, reversibly suppresses the KTo compare fexuprazan to esomeprazole and establish its efficacy and safety in patients with erosive esophagitis (EE).Korean adult patients with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg or esomeprazole 40 mg once daily for eight weeks. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy at week 8. The secondary endpoints included the healing rate of EE at week 4, symptom response, and quality of life assessment. Safety profiles and serum gastrin levels were compared between the groups.Of the 263 randomized, 218 completed the study per protocol (fexuprazan 40 mg,Fexuprazan 40 mg is non-inferior to esomeprazole 40 mg in EE healing at week 8. We suggest that fexuprazan is an alternative promising treatment option to PPIs for patients with EE.

Tegoprazan is a novel potassium-competitive acid blocker used to treat acid-related disorders.To compare tegoprazan 25 mg with lansoprazole 15 mg as maintenance therapy in healed erosive oesophagitis (EE) METHODS: In this phase 3, double-blind, multi-centre study, patients with endoscopically confirmed healed EE were randomised 1:1 to receive tegoprazan 25 mg or lansoprazole 15 mg once daily for up to 24 weeks. The primary efficacy endpoint was the endoscopic remission rate after 24 weeks. The secondary efficacy endpoint was the endoscopic remission rate after 12 weeks. Safety endpoints included adverse events, clinical laboratory results and serum gastrin and pepsinogen I/II levels.We randomised patients to tegoprazan 25 mg (n = 174) or lansoprazole 15 mg (n = 177). Most had mild EE (Los Angeles (LA) grade A: 57.3%, LA grade B: 37.3%). The endoscopic remission rate after 24 weeks was 90.6% with tegoprazan and 89.5% with lansoprazole. Tegoprazan was not inferior to lansoprazole for maintaining endoscopic remission at 24 weeks and 12 weeks. In subgroup analysis, tegoprazan 25 mg showed no significant difference in maintenance rate according to LA grade (p = 0.47). The maintenance effect of tegoprazan was consistent in CYP2C19 extensive metabolisers (p = 0.76). Increases in serum gastrin were not higher in tegoprazan-treated than lansoprazole-treated patients.Tegoprazan 25 mg was non-inferior to lansoprazole 15 mg in maintenance of healing of mild EE. In this study, tegoprazan had a similar safety profile to lansoprazole.

Background/aimsThis study aimed to investigate the factors associated with prolonged hospital stay and in-hospital mortality in patients with pyogenic liver abscess.MethodsWe retrospectively reviewed data from patients with pyogenic liver abscess who were admitted between 2005 and 2018 at three tertiary hospitals in Jeonbuk province, South Korea. Prolonged hospital stay was defined as a duration of hospital admission of more than 21 days.ResultsA total of 648 patients (406 men and 242 women) diagnosed with pyogenic liver abscess were enrolled in the study. The mean maximal diameter of the liver abscess was 5.4 ± 2.6 cm, and 74.9% of the lesions were single. The three groups were divided according to the maximal diameter of the abscess. Laboratory parameters indicated a more severe inflammatory state and higher incidence of complications and extrahepatic manifestations with increasing abscess size. Rates of percutaneous catheter drainage (PCD) insertion, multiple PCD drainage, and salvage procedures as well as duration of drainage were also higher in the large liver abscess group. Of note, the duration of hospitalization and in-hospital mortality were significantly higher in the large hepatic abscess group. A multivariate analysis revealed that underlying diabetes mellitus, hypoalbuminemia, high baseline high-sensitivity C-reactive protein (hs-CRP) and procalcitonin levels, and large maximal abscess diameter were independent factors associated with prolonged hospital stay. Regarding in-hospital mortality, acute kidney injury at admission and maximal diameter of the abscess were independent factors associated with in-hospital mortality.ConclusionsA large maximal diameter of the liver abscess at admission indicated prolonged hospitalization and poor prognosis. More aggressive treatment strategies with careful monitoring are warranted in patients with large liver abscesses.

Background/aim The mouse diarrhea score is usually determined by evaluating stool consistency and shape. Thus, defecated stools should be collected without damage or contamination. The study aimed to develop improved mouse stool collection methods and diarrhea-scoring criteria. Materials and methods We developed improved stool collection methods (paper towel methods) and compared them with previously used ones (stool collection using regular cages containing bedding chips or filter paper and metabolic cages). Results Compared to previously used methods, paper towel methods collected stools without bedding chips-induced contamination, mouse body/foot-induced damage, or sampling errors. When using paper towel methods, wet stools create water marks (diarrhea marks) on paper towels with strong water absorption capacity, by which diarrheal severity can be analyzed semi-quantitatively. To improve the objectivity in determining diarrhea scores, practical diarrhea-scoring criteria were also proposed. Conclusion These results would be helpful to researchers facing difficulties in evaluating the mouse diarrhea score.

Background/aim Intestinal mucositis with diarrhea is a dose-limiting toxicity of 5-fluorouracil (5-FU). M40403, a superoxide dismutase mimetic, was evaluated on whether it improves the mucositis with diarrhea. Materials and methods BALB/c mice were treated with daily intraperitoneal injections of 5-FU±M40403 for five consecutive days. Following treatment, light microscopy (apoptosis), electron microscopy (autophagy), and analyses for the expression of apoptosis/autophagy-related proteins were performed in analysing small intestinal samples. Body weight, diarrhea score, blood cytokine levels, complete blood count, and blood chemistries were measured. The in vivo anti-tumor activity of 5-FU±M40403 was also evaluated. Results M40403 improved 5-FU-induced intestinal mucositis (apoptosis and autophagy) and attenuated 5-FU-induced changes in the expression of apoptosis/autophagy-related proteins, weight loss, diarrhea score, and serum TNF-α levels. M40403 neither added further adverse effects nor compromised the anti-tumor activity during 5-FU treatment. Conclusion M40403 can be useful in improving 5-FU-induced intestinal mucositis with diarrhea.

This study was aimed at investigating the clinical efficacy of probiotics in pneumonia patients. To this end, we enrolled 80 participants diagnosed with pneumonia at Naval Pohang Hospital, Pohang, Korea, from May 2016 to January 2017. The participants were randomly assigned to the control and probiotic groups depending on whether they received probiotics. All participants clinically improved but 22.6% of the participants complained of abnormal stool habits after pneumonia treatment. In comparison, fever duration was significantly shorter in the probiotic group, and the group exhibited an improved general condition. The probiotic group also showed better stool characteristics according to the Bristol stool scale (P = 0.009). Notably, the serum hs-CRP levels were significantly lower in the probiotic group at 2 weeks of treatment (P = 0.015), and all participants in the probiotic group achieved their levels within the normal range. Flow cytometry was used to analyze T-helper 17 (Th17) cells and regulatory T cells (Tregs). Tregs were promoted and the Th17 cell/Treg ratio was suppressed after 2 weeks of treatment in the probiotic group (P = 0.007 and 0.037, respectively). This study demonstrated that probiotics improved clinical symptoms and normalized inflammatory biomarker levels in patients with pneumonia. Early infection and inflammation recovery may be due to the immunomodulatory effects of probiotics by facilitating the subset of Tregs and suppressing the Th17 cell/Treg ratio.

Background/Aims: The proper handling of antithrombotics is critical, and this study aimed to assess guideline adher ence in the management of antithrombotics before and after endoscopy. Methods: A survey questionnaire was developed. The respondents’ demographic information was included, and the questionnaire was divided into the first section for forceps biopsy, the second for polypectomy, and the third for endoscopic submucosal dissection (ESD) in which aspirin, clopidogrel, combination therapy (aspirin and clopidogrel), warfarin, and direct oral anticoagulants (apixaban) were prescribed to imaginary patients. Results: A total of 415 endoscopists completed this survey (response rate of 6.2%, 415/6,673). The percentage of respondents who chose to proceed with biopsy for patients taking aspirin, those tak ing clopidogrel, those under combination therapy, those taking warfarin, and those taking apixaban was 89.4%, 74.2%, 61.0%, 38.6%, and 50.4%, respectively. Most re spondents answered that they would discontinue aspirin, clopidogrel, and a combination of both drugs for 5 days before polypectomy or ESD (69.4%/76.9%, 83.6%/83.9%, and 53.3%/65.8%, respectively). The answers indicated that warfarin should be discontinued with heparin bridge therapy in high thromboembolic risk patients (polypectomy 70.1%, ESD 73.5%). Regarding apixaban use in polypectomy and ESD, 63.9% and 58.1% of respondents, respectively, chose answers consistent with the guidelines. Conclusions: The gap between the guidelines and clinical practice in the man agement of antithrombotics before and after endoscopy is considerable and should be addressed via educational strat egies. (Gut Liver 2020;14:316-322)

Endoscopic ultrasound (EUS)-guided tissue acquisition of pancreatic solid tumor requires a strict recommendation for its proper use in clinical practice because of its technical difficulty and invasiveness. The Korean Society of Gastrointestinal Endoscopy (KSGE) appointed a task force to draft clinical practice guidelines for EUS-guided tissue acquisition of pancreatic solid tumor. The strength of recommendation and the level of evidence for each statement were graded according to the Minds Handbook for Clinical Practice Guideline Development 2014. The committee, comprising a development panel of 16 endosonographers and an expert on guideline development methodology, developed 12 evidence-based recommendations in eight categories intended to help physicians make evidence-based clinical judgments with regard to the diagnosis of pancreatic solid tumor. This clinical practice guideline discusses EUS-guided sampling in pancreatic solid tumor and makes recommendations on circumstances that warrant its use, technical issues related to maximizing the diagnostic yield (e.g., needle type, needle diameter, adequate number of needle passes, sample obtaining techniques, and methods of specimen processing), adverse events of EUS-guided tissue acquisition, and learning-related issues. This guideline was reviewed by external experts and suggests best practices recommended based on the evidence available at the time of preparation. This guideline may not be applicable for all clinical situations and should be interpreted in light of specific situations and the availability of resources. It will be revised as necessary to cover progress and changes in technology and evidence from clinical practice. (Gut Liver 2021;15:354-374)

Introduction: Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is an alternative treatment option for patients with acute cholecystitis, especially for those who are unsuitable for cholecystectomy. Recently used luminal apposing metal stents (LAMS) in EUS-GBD has several advantages over standard metal stents. However, there is no current guideline on where to locate the LAMS when transgastric approach is required. This study reports a case of gastric outlet obstruction (GOO) by placing LAMS too close to the pyloric ring. Patient concerns: A 79-year-old female patient was referred to our department for evaluation of a large hepatic mass on abdominal ultrasound. Abdominal pain on right upper quadrant and spiking fever up to 38 °C appeared after liver biopsy. Abdominal ultrasound showed thickened GB wall and positive sonographic Murphy sign. Diagnoses: Intrahepatic cholangiocarcinoma with multiple lung and intrahepatic metastasis, acute cholecystitis, and pyloric ring obstruction caused by flange of LAMS in EUS-GBD. Interventions: EUS-GBD via transgastric approach was performed with LAMS. After complete deployment of stent, esophagogastroduodenoscopy showed complete GOO by flange of LAMS. A gastroduodenal metal stent was inserted to relieve the GOO. Outcomes: The patient recovered well. She did not complain about obstruction induced symptom such as vomiting or abdominal fullness after gastroduodenal stent insertion. Conclusion: To the best of our knowledge, this is the first case report of EUS-GBD induced GOO. If physicians use LAMS as a transgastric approach in EUS-GBD, the puncture site should be carefully selected considering the size of the flange.

Background/Aims: To investigate the treatment efficacy and renal safety of long-term tenofovir disoproxil fumarate (TDF) therapy in chronic hepatitis B (CHB) patients with preserved renal function. Methods: The medical records of 919 CHB patients who were treated with TDF therapy were reviewed. All patients had preserved renal function with an estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m2. Results: A total of 426 patients (184 treatment-naive and 242 treatment-experienced) were included for analysis. A virologic response (VR) was defined as achieving an undetectable serum hepatitis B virus (HBV) DNA level, and the overall VR was 74.9%, 86.7%, and 89.4% at the 1, 2, and 3-year follow-ups, respectively. Achieving a VR was not influenced by previous treatment experience, TDF combination therapy, or antiviral resistance. In a multivariate analysis, being hepatitis B e antigen positive at baseline and having a serum HBV DNA level ≥2,000 IU/mL at 12 months were associated with lower VR rates during the long-term TDF therapy. The overall renal impairment was 2.9%, 1.8%, and 1.7% at the 1, 2, and 3-year follow-ups, respectively. With regard to renal safety, underlying diabetes mellitus (DM) and an initial eGFR of 60 to 89 mL/min/1.73 m2 were significant independent predictors of renal impairment. Conclusions: TDF therapy appears to be an effective treatment option for CHB patients with a preserved GFR. However, patients with underlying DM and initial mild renal dysfunction (eGFR, 60 to 89 mL/min/1.73 m2) have an increased risk of renal impairment. (Gut Liver 2019;13:93-103.)

Background/aims Parthenolide (PT), a principle component derived from feverfew (Tanacetum parthenium), is a promising anticancer agent and has been shown to promote apoptotic cell death in various cancer cells. In this study, we focused on its functional role in apoptosis, migration, and invasion of human colorectal cancer (CRC) cells. Methods SW620 cells were employed as representative human CRC cells. We performed the MTT assay and cell cycle analysis to measure apoptotic cell death. The wound healing, Transwell migration, and Matrigel invasion assays were performed to investigate the effect of PT on cell migration/invasion. Western blotting was used to establish the signaling pathway of apoptosis and cell migration/invasion. Results PT exerts antiproliferative effect and induces apoptotic cell death of SW620 cells. In addition, PT prevents cell migration and invasion in a dose-dependent manner. Moreover, PT markedly suppressed migration/invasion-related protein expression, including E-cadherin, β-catenin, vimentin, Snail, cyclooxygenase-2, matrix metalloproteinase-2 (MMP-2), and MMP-9 in SW620 cells. PT also inhibited the expression of antiapoptotic proteins (Bcl-2 and Bcl-xL) and activated apoptosis terminal factor (caspase-3) in a dose-dependent manner. Conclusions Our results suggest that PT is a potential novel therapeutic agent for aggressive CRC treatment.

Background/Aims: With recent changes in the treatment of pancreatic cancer, patients’ active decision-making has become more important. Nevertheless, it is difficult to give patients proper insights into the disease. The purpose of this study was to determine associated factors between pancreatic cancer awareness and treatment decisions as well as how cancer awareness affects the timing of treatment decisions and the desired treatment method. Methods: This is a retrospective study that reviewed and analyzed the electronic medical records of 110 patients who were diagnosed with pancreatic cancer from January 2013 to April 2016. A "patient with pancreatic cancer awareness" means that the patient was informed of their disease state before making the first treatment decision. Results: Of all, only 63.6% of patients (n=70) were shown to have pancreatic cancer awareness before making their first treatment decision. Compared to patients without pancreatic cancer awareness, patients with pancreatic cancer awareness were younger (65.00 vs. 76.98, t=6.70, p

Background/Aims: Transforming growth factor-β1 (TGF-β1) induction of epithelial-mesenchymal transition (EMT) is one of the mechanisms by which colorectal cancer (CRC) cells acquire migratory and invasive capacities, and subsequently me tastasize. Parthenolide (PT) expresses multiple anti-cancer and anti-inflammatory activities that inhibit nuclear factor κB by targeting the IκB kinase complex. In the present study, we aimed to investigate whether PT can inhibit TGF-β1-induced EMT in CRC cell lines. Methods: HT-29 and SW480 cell lines were used in the experiment. Cell viability was detected by 3-(4,5-dimeth ylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and sub-G1 analysis was measured by flow cytometry. The in duction of EMT by TGF-β1 and inhibition of the process by PT was analyzed by phase contrast microscopy, wounding healing, cellular migration and invasion assays, and Western blotting. Results: TGF-β1 inhibits HT-29 cell proliferation, but has no effect on SW480 cell proliferation; different concentrations of TGF-β1 did not induce apoptosis in HT-29 and SW480 cells. PT attenu ates TGF-β1-induced elongated, fibroblast-like shape changing in cells. PT inhibits TGF-β1-induced cell migration and cell invasion. In addition, other EMT markers such as β-catenin, Vimentin, Snail, and Slug were suppressed by PT, while E-cadherin was increased by PT. Conclusions: Our findings show that PT inhibits TGF-β1-induced EMT by suppressing the expression of the mesenchymal protein and increasing expression of the epithelial protein. These findings suggest a novel approach for CRC treatment by suppression of TGF-β1-induced EMT. (Intest Res 2019;17:527-536)

Balsalazide is a colon-specific prodrug of 5-aminosalicylate that is associated with a reduced risk of colon cancer in patients with ulcerative colitis. Parthenolide, a strong NF-κB inhibitor, has recently been demonstrated to be a promising therapeutic agent, promoting apoptosis of cancer cells. In the current study, the antitumor effect of balsalazide combined with parthenolide in human colorectal cancer cells and colitis-associated colon cancers (CAC) was investigated. The results demonstrate that the combination of balsalazide and parthenolide markedly suppress proliferation, nuclear translocation of NF-κB, IκB-α phosphorylation, NF-κB DNA binding, and expression of NF-κB targets. Apoptosis via NF-κB signaling was confirmed by detecting expression of caspases, p53 and PARP. Moreover, treatment of a CAC murine model with parthenolide and balsalazide together resulted in significant recovery of body weight and improvement in histologic severity. Administration of parthenolide and balsalazide to CAC mice also suppressed carcinogenesis as demonstrated by uptake of 18F-fluoro-2-deoxy-D-glucose (FDG) using micro-PET/CT scans. These results demonstrate that parthenolide potentiates the efficacy of balsalazide through synergistic inhibition of NF-κB activation and the combination of dual agents prevents colon carcinogenesis from chronic inflammation. Implications: This study represents the first evidence that combination therapy with balsalazide and parthenolide could be a new regimen for colorectal cancer treatment. Mol Cancer Res; 15(2); 141–51. ©2016 AACR.

AIM To assess the effect of long-term oral nucleos(t)ide analogues (NUCs) therapy on liver volume change in patients with suppress hepatitis B virus (HBV)-related liver cirrhosis. METHODS We reviewed the data of naïve patients with HBV-related liver cirrhosis, who had taken oral NUCs therapy, between 2003 and 2007 at Chonbuk University Hospital. We analyzed two consecutive sets of abdominal computerized tomography scans-one at the time of treatment initiation and another at the second-year follow-up. Liver volume was calculated by 3-dimensional liver extraction volumetry program. RESULTS A total of 55 patients (34 males) were included. There was 114.3 mL ± 167.8 mL (12.9% ± 17.9%) of increase in liver volume during the two years of NUCs therapy (993.8 mL ± 242.8 mL at baseline vs 1108.1 mL ± 263.3 mL at two-year follow-up, P < 0.001). The ratio of the measured baseline liver volume to the estimated standard liver volume was improved from 70.8% to 78.0%. An increase in liver volume was shown not only in patients with compensated cirrhosis (P = 0.046) but also in those with decompensated cirrhosis (P < 0.001). Significant factors for volume increases were Child-Turcotte-Pugh grade and model for end-stage liver disease score improvement without virological breakthrough. In multiple linear regression analysis, delta albumin and delta alanine aminotransferase levels showed a significant association with the increase in liver volume (P = 0.002 and 0.005, respectively). CONCLUSION Long-term oral NUCs therapy in patients with HBV-related liver cirrhosis lead to significant increase in liver volume assessed with 3-dimensional liver extraction volumetry program.

Genome-wide association study in diffusely infiltrating type cholangiocarcinoma (CC) can be limited due to the difficulty of obtaining tumor tissue. We aimed to evaluate the genomic alterations of diffusely infiltrating type CC using next-generation sequencing (NGS) of bile and to compare the variations with those of mass-forming type CC. A total of 24 bile samples obtained during endoscopic retrograde cholangiopancreatography (ERCP) and 17 surgically obtained tumor tissue samples were evaluated. Buffy coat and normal tissue samples were used as controls for a somatic mutation analysis. After extraction of genomic DNA, NGS analysis was performed for 48 cancer related genes. There were 27 men and 14 women with a mean age of 65.0±11.8years. The amount of extracted genomic DNA from 3cm(3) of bile was 66.0±84.7μg and revealed a high depth of sequencing coverage. All of the patients had genomic variations, with an average number of 19.4±2.8 and 22.3±3.3 alterations per patient from the bile and tumor tissue, respectively. After filtering process, damaging SNPs (8 sites for each type of CC) were predicted by analyzing tools, and their target genes showed relevant differences between the diffusely infiltrating and mass-forming type CC. Finally, in somatic mutation analysis, tumor-normal paired 14 tissue and 6 bile samples were analyzed, genomic alterations of EGFR, FGFR1, ABL1, PIK3CA, and CDKN2A gene were seen in the diffusely infiltrating type CC, and TP53, KRAS, APC, GNA11, ERBB4, ATM, SMAD4, BRAF, and IDH1 were altered in the mass-forming type CC group. STK11, GNAQ, RB1, KDR, and SMO genes were revealed in both groups. The NGS analysis was feasible with bile sample and diffusely infiltrating type CC revealed genetic differences compared with mass-forming type CC. Genome-wide association study could be performed using bile sample in the patients with CC undergoing ERCP and a different genetic approach for accurate diagnosis, pathogenesis study, and targeted therapy will be needed in diffusely infiltrating type CC.

TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis through death receptors (DRs)4 and/or 5 expressed on the cell surface. Multiple clinical trials are underway to evaluate the antitumor activity of recombinant human TRAIL and agonistic antibodies to DR4 or DR5. However, their therapeutic potential is limited by the high frequency of cancer resistance. In this study, we provide evidence demonstrating the role of lipocalin 2 (LCN2) in the TRAIL-mediated apoptosis of human colorectal cancer (CRC). By analyzing the mRNA expression data of 71 CRC tissues from patients, we found that DR5 was preferentially expressed in CRC tissues with a low LCN2 expression level compared to tissues with a high LCN2 expression level. Moreover, we analyzed the association between DR5 and LCN2 expression and this analysis revealed that DR5 expression in CRC tended to be inversely associated with LCN2 expression. By contrast, no association was found between the DR4 and LCN2 expression levels. The expression patterns of LCN2 in human CRC cell lines also exhibited an inverse association with DR5 expression. The knockdown of LCN2 by siRNA in the TRAIL‑resistant CRC cells expressing high levels of LCN2 led to a significant increase in TRAIL-induced apoptosis through the upregulation of DR5 protein and mRNA expression. The mechanism through which LCN2 silencing sensitized the CRC cells to TRAIL was dependent on the extrinsic pathway of apoptosis. In addition, we identified that the knockdown of LCN2 enhanced the sensitivity of the cells to TRAIL through the p38 MAPK/CHOP-dependent upregulation of DR5. Taken together, the findings of this study suggest that LCN2 is responsible for TRAIL sensitivity and LCN2 may thus prove to be a promising target protein in DR-targeted CRC therapy.

MicroRNA-9 (miR-9) has been reported to play a suppressive or promoting role according to cancer type. In this study, we investigated the effects of anoctamin-1 (ANO1) and miR-9 on colorectal cancer (CRC) cell proliferation, migration, and invasion and determined the underlying molecular mechanisms. Thirty-two paired CRC tissues and adjacent normal tissues were analyzed for ANO1 expression using quantitative real-time PCR (qRT-PCR). HCT116 cells were transiently transfected with miR-9 mimic, miR-9 inhibitor, or si-ANO1. Cell proliferation was determined by MTT, and flow cytometric analysis, while cell migration and invasion were assayed by trans-well migration and invasion assay in HCT116 cells. ANO1 was validated as a target of miR-9 using luciferase reporter assay and bioinformatics algorithms. We found that ANO1 expression was up-regulated in CRC tissues compared with adjacent normal tissues. ANO1 expression was associated with advanced tumor stage and lymph node metastasis, and there was an inverse relationship between miR-9 and ANO1 mRNA expression in CRC specimens, but no significant difference was found between miR-9 and ANO1 expression. ANO1 is a direct target of miR-9, and overexpression of miR-9 suppressed both mRNA and protein expression of ANO1 and inhibited cell proliferation, migration, and invasion of HCT116 cells. We also showed that overexpression of miR-9 suppressed expression of p-AKT, cyclin D1, and p-ERK in HCT116 cells. We conclude that miR-9 inhibits CRC cell proliferation, migration, and invasion by directly targeting ANO1, and miR-9/ANO1 could be a potential therapeutic target for CRC.

MiRNA (miR)-206 plays a tumor suppressor role in various cancer types. Here, we investigated whether miR-206 is involved in prostaglandin E2 (PGE2)-induced epithelial–mesenchymal transition (EMT) in colorectal cancer (CRC) cells through the targetting of transmembrane 4 L six family member 1 (TM4SF1).The effect of PGE2 on growth and apoptosis of CRC cells was evaluated using the MTT assay and flow cytometry analysis, respectively. TM4SF1 and miR-206 expression levels were determined with quantitative polymerase chain reaction (qRT-PCR) in CRC tissues and cell lines. The concentration of PGE2 in the serum of CRC patients and healthy controls was measured with an ELISA kit. A miR-206 or TM4SF1 construct was transfected into cells with PGE2. Transwell migration and invasion assays were used to examine cell migration and invasion properties. Additionally, a luciferase assay was performed to determine whether TM4SF1 was directly targetted by miR-206.We found that miR-206 was down-regulated and TM4SF1 was up-regulated in human CRC tissues and cell lines. Moreover, miR-206 was negatively correlated with TM4SF1 expression. Bioinformatics analysis and a luciferase reporter assay revealed that miR-206 directly targetted the 3′-untranslated region (UTR) of TM4SF1, and TM4SF1 expression was reduced by miR-206 overexpression at both the mRNA and protein levels. Additionally, PGE2 significantly suppressed the expression of miR-206 and increased the expression of TM4SF1 in CRC cells. PGE2 induction led to enhanced CRC cell proliferation, migration, and invasion. Moreover, the overexpression of miR-206 decreased CRC cell proliferation, migration, and invasion compared with control group in PGE2-induced cells, and these effects could be recovered by the overexpression of TM4SF1. Overexpression of miR-206 also suppressed the expression of β-catenin, VEGF, MMP-9, Snail, and Vimentin and enhanced E-cadherin expression in PGE2-induced cells. These results could be reversed by the overexpression of TM4SF1. At last, up-regulation of miR-206 suppressed expression of p-AKT and p-ERK by targetting TM4SF1 in PGE2-induced cells.Our results provide further evidence that miR-206 has a protective effect on PGE2-induced colon carcinogenesis.

The purpose of this research was to evaluate if withdrawal time is a useful index in spite of differences in gastroenterologists’ ability and if there are other quality indicators of colonoscopy. A total of 665 consecutive, asymptomatic individuals of average risk between 50 and 75 years of age who underwent screening colonoscopies performed by 12 gastroenterologists were included in this study. The endoscopists were classified to either the experienced group (group A, N = 6) or the under-experienced group (group B, N = 6). The endoscopists were unaware that they were being studied during the two-month study period. In group A, adenoma detection rate was 0.56, while in group B it was 0.43 (P = 0.048). The mean withdrawal time ranged widely from 4.2 to 10.3 min per patient with a mean value of 6.83 for group A and 6.54 for group B. There was a significantly positive relationship between the number of adenomas detected and the withdrawal time for group B (r = 0.827, P = 0.005), but not for group A (r = −0.152, P = 0.584). In the case of group A, the ratio of cecal intubation time to withdrawal time (I/E ratio) less than 1 showed significantly correlated adenoma detection rate compared to I/E ratio greater than 1 (r = −0.308, P = 0.036). In the case of group B, mean I/E ratio was 1.7 and all endoscopists' I/E ratios were greater than 1. For experienced endoscopists, a useful supplementary quality indicator of colonoscopy is to keep intubation/withdrawal time ratio less than 1 and it is necessary for under-experienced endoscopists to try to keep enough withdrawal time.

Background/Aims: To evaluate the efficacy and safety of a controlled release, once-daily formulation of mosapride (UI05MSP015CT) in patients with functional dyspepsia (FD). Methods: Patients with FD were randomly assigned (1:1) to receive either UI05MSP015CT (15 mg once a day, study group) or mosapride (5 mg three times a day, control group) and corresponding placebo for 4 weeks. The primary endpoint was a change in the gastrointestinal symptom score (GIS) evaluated at enrollment and after 4 weeks. Secondary endpoints were changes in the Nepean Dyspepsia Index-Korean version (NDI-K), rate of satisfactory symptom relief, and rate of adverse events. Results: A total of 138 patients were enrolled (female, 73.9%; mean age, 44.0±15.4 years). After excluding patients who violated the study protocol, 59 and 58 patients from the study and control groups, respectively, were included in the per-protocol analysis. No difference was observed in drug compliance between the control and study groups (97.07%±4.52% vs 96.85%±6.05%, p=0.870). Changes in GIS scores were -9.69±6.44 and -10.01±5.92 in the study and control groups. The mean difference in GIS change between groups was 0.33 (95% confidence interval, -1.75 to 2.41), demonstrating non-inferiority of UI- 05MSP015CT (p=0.755). The rate of satisfactory symptom relief was not different between the study and control groups (39.0% vs 56.9%, p=0.053). No differences in change in NDI-K score (14.3 vs 16.9, p=0.263) or rates of adverse events (12.9% vs. 4.4%, p=0.062) were observed between the study and control groups. Conclusions: Once-daily mosapride is not inferior to conventional mosapride in efficacy and is safe in patients with FD. (Gut Liver 2018;12:516-522)

Activation of hypoxia-inducible factor 1α (HIF‑1α) is frequently observed in solid tumors and it has been associated with various pathophysiological processes, including epithelial‑mesenchymal transition (EMT). Previously, we reported that parthenolide (PT), an inhibitor of nuclear factor-κB (NF-κB), is a promising anticancer agent because it promotes apoptosis of human colorectal cancer (CRC). Here, we investigated a new molecular mechanism by which PT acts on HIF‑1α and hypoxia contributing to EMT by NF‑κB inhibition. Cell viability, DNA binding activity, vascular cell tube formation and cell motility were studied after treatment of PT in hypoxic or normoxic condition. Moreover, effects of PT on hypoxia signaling and hypoxia-induced EMT signaling were investigated. We also examined the inhibitory effect of PT on CRC progression in xenografts. We demonstrated that PT markedly inhibits hypoxia dependent HIF‑1α activity and angiogenesis by preventing NF-κB activation. We also report that PT decreases the level of proteins associated with glucose metabolism, angiogenesis, development and survival that are regulated by HIF‑1α. Furthermore, we verified that PT protects the morphological change from epithelial to mesenchymal state, inhibits matrix metalloproteinase (MMP) enzyme activity and decreases cell motility involved in the -regulation of the hypoxia-induced EMT markers. In addition, PT inhibits growth in CRC xenograft models and regulates NF‑κB, HIF‑1α and EMT specific marker in tissue specimens. Our data demonstrated that PT can inhibit HIF‑1α signaling and hypoxia-induced EMT, suggesting a novel molecular mechanism for HIF‑1α mediated cancer progression and metastasis.

There has been no study on the efficacy of lafutidine for patients with reflux esophagitis in Korea. To evaluate the efficacy of a new-generation histamine-2 receptor antagonist, lafutidine, in comparison with famotidine in patients with reflux esophagitis. This was a randomized, double-blind, non-inferiority trial enrolling patients with erosive esophagitis. The efficacy and safety of 20 mg lafutidine (treatment group) were compared with those of 40 mg famotidine (control group) and 20 mg omeprazole (reference group). The primary endpoint was the complete healing rates of reflux esophagitis on endoscopy after 8 weeks of treatment. The non-inferiority margin was assumed to be −15 %. The healing rates of reflux esophagitis on endoscopy after 8 weeks of treatment were 70.14 % (101/144) in the lafutidine, 63.45 % (92/145) in the famotidine, and 85.71 % (126/147) in the omeprazole group. The difference in healing rates between the lafutidine and famotidine groups was 6.69 % (95 % confidence interval = [−4.14 to 17.52]). In addition, lafutidine was superior to famotidine in clinical improvement (53.73 % vs. 39.55 %, P = 0.0200). Lafutidine was non-inferior to famotidine in healing of reflux esophagitis. Lafutidine, however, was superior to famotidine in terms of symptom relief of reflux esophagitis.

BACKGROUND/AIM Delayed bleeding is a serious complication that occurs after polypectomy. Many risk factors for delayed bleeding have been suggested, but there is little analysis of procedure-related risk factors. The purpose of this study is to identify a wide range of risk factors for delayed postpolypectomy bleeding (DPPB) and analyze the correlations of those potential DPPB risk factors. MATERIALS AND METHODS In this retrospective cohort study, 5981 polypectomies in 3788 patients were evaluated between January 2010 and February 2012. Patient-related, polyp-related, and procedure-related factors were evaluated as potential DPPB risk factors. RESULTS Delayed bleeding occurred in 42 patients (1.1%). Multivariate analysis revealed that polyp size >10 mm [odds ratio (OR), 2.785; 95% confidence interval (CI), 1.406-5.513; P=0.003], location in the right hemi-colon (OR, 2.289; 95% CI, 1.117-4.693; P=0.024), and endoscopist's experience (

Background Objective evaluation tools for assessing the effectiveness of stenting in palliative treatment of malignant biliary obstruction are not satisfactory. Effects of biliary stenting on liver volume change have never been studied. Objective We aimed to use volumetry to analyze liver volume changes after endoscopic stenting in bile duct cancer according to the location and number of stents. Design Retrospective review. Setting University hospital. Patients Patients with a diagnosis of hilar or distal bile duct cancer and who underwent biliary metal stenting. Interventions ERCP with self-expandable metal stent placement. Main Outcome Measurements Liver volume change after biliary stenting and its comparison according to the location (hilar vs distal common bile duct) and number (hilar bilateral vs hilar unilateral). Results There were 60 patients; 31 were treated for hilar bile duct cancer (13 for bilateral stent and 18 for unilateral stent) and 29 for distal bile duct cancer. Overall mean follow-up duration was 11.7 ± 4.9 weeks. Liver volume increased 17.4 ± 24.1%. The rate of liver growth was rapid during the early period from 4 to 8 weeks. Stenting in hilar bile duct cancer tended to increase liver volume more than distal biliary stents (22.5% vs 11.9%, P = .091). In hilar bile duct cancer, unilateral and bilateral stents showed similar liver volume increases (20.1% and 25.8%, respectively; P = .512). Limitations Single center, retrospective. Conclusions Biliary stenting markedly increased liver volume in both hilar and distal bile duct cancer. Our data suggest that liver volume assessment could be a useful tool for evaluating stent efficacy.