MiR-196a promotes the proliferation and migration of esophageal cancer via the UHRF2/TET2 axis.

The aim of this study was to investigate the functions and molecular mechanism of miR-196a in esophageal cancer (EC). miR-196a as well as UHRF2 and TET2 mRNA and protein levels in EC tissues and cells were detected using quantitative real-time PCR or western blot, respectively. Cell proliferation was evaluated via MTT assay. Transwell assays were used to detect cell migration. In addition, the targeted relationship between miR-196a and UHRF2 was assessed through a dual luciferase reporter assay. Enzyme-linked immunosorbent assay was performed to detect the levels of the cytosine intermediates 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). We found increased miR-196a expression in EC tissues and cells but decreased UHRF2 and TET2 expression. Next, functional experiments showed that knockdown of miR-196a or UHRF2 overexpression suppress EC cell proliferation and migration. miR-196a negatively regulates TET2 expression by directly targeting UHRF2. UHRF2 overexpression decreased 5mC levels but increased 5hmC levels. Furthermore, TET2 downregulation reversed the functions of miR-196a inhibition on EC cell proliferation and migration. Collectively, our study suggested that miR-196a was closely related to the progression of EC possibly by regulating the UHRF2/TET2 axis. Thus, miR-196a represents a potential new EC therapeutic target.

The effect of Salvia miltiorrhiza in a mouse model of hepatic sinusoidal obstruction syndrome induced by Gynura segetum.

BACKGROUND AND AIMS: to investigate the potential effect and mechanism of Salvia miltiorrhiza in Gynura segetum-induced hepatic sinusoidal obstruction syndrome (HSOS). METHODS: the mice were gavaged with PBS, Gynura segetum or Gynura segetum, along with 100 or 200 mg/kg Salvia miltiorrhiza. Histological scoring and liver function were performed. The expression of tumor necrosis factor-alpha (TNF-α), vascular cellular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and nuclear transcription factor P65 (NF-κBp65) were determined by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot. RESULTS: liver function were effectively improved in the Salvia miltiorrhiza groups. The levels of TNF-α, VCAM-1, ICAM-1 and NF-κBp65 were significantly lower in the Salvia miltiorrhiza groups than in the Gynura segetum group. CONCLUSIONS: Salvia miltiorrhiza has a therapeutic effect on Gynura segetum-induced HSOS.

Overexpression of F-box only protein 31 predicts poor prognosis and deregulates p38α- and JNK-mediated apoptosis in esophageal squamous cell carcinoma.

F-box only protein 31 (FBXO31), a subunit of the Skp1-Cul1-F box ubiquitin ligase, plays a crucial role in DNA damage response and tumorigenesis. Yet its expression and function vary in different types of human cancer. The expression of FBXO31 in esophageal squamous cell carcinoma (ESCC) and its association with clinicopathological features is not well studied. The underlying mechanism by which deregulated FBXO31 contributes to ESCC tumorigenesis is largely unknown. By immunohistochemical analysis of a tissue microarray containing 85 cases of ESCC and matched adjacent noncancerous tissue and an additional 10 cases of ESCC tissue samples, we found that FBXO31 was overexpressed in ESCC, and that its expression was significantly correlated with histological grade (p = 0.04) and clinical stage (p = 0.022). Higher expression of FBXO31 was associated with poor prognosis in univariate (p = 0.013) and multivariate (p = 0.014) analyses. We found that FBXO31 functioned as an antiapoptotic molecule in ESCC cells exposed to different types of genotoxic stress. Knockdown of FBXO31 inhibited serum-starved cell viability and decreased tumorigenicity of ESCC cells. In addition, the antiapoptotic effects of FBXO31 were associated with deactivation of stress-induced MAPK p38α and JNK. Furthermore, in vitro and in vivo data showed that silencing of FBXO31-sensitized ESCC cells and tumors to cisplatin treatment. Taken together, in addition to revealing that FBXO31 is an independent prognostic marker for ESCC, our findings substantiate a novel regulatory role of FBXO31 in tumorigenesis and drug resistance of ESCC.

Efficacy of anterior versus posterior per-oral endoscopic myotomy for treating achalasia: a randomized, prospective study.

BACKGROUND AND AIMS: Per-oral endoscopic myotomy (POEM) has been demonstrated to be safe and effective for treating achalasia. Two approaches-anterior myotomy and posterior myotomy-are used during POEM. However, little is known about the comparison between the 2 different approaches. The objective of the study is to compare the safety and short-term efficacy of the 2 approaches for treating achalasia. METHODS: From October 2015 to December 2016, 63 consecutive patients with achalasia without prior treatment or sigmoid-type esophagus were prospectively recruited. They were randomly assigned to an anterior or posterior myotomy group. Clinical data about general characteristics, operative parameters, pre- and postoperative Eckardt score, esophageal manometry results, 24-hour pH test, and adverse events were recorded and compared between the 2 groups. RESULTS: The anterior group included 31 patients and the posterior group 32 patients. All patients underwent POEM successfully, and treatment success (defined as an Eckardt score ≤3) was achieved in all patients during a mean follow-up of 15.5 months. Mean Eckardt score, lower esophageal sphincter pressure, and 4-second integrated relaxation pressure were significantly decreased (6.2 ± 1.3, 37.5 ± 6.7 mm Hg, and 27.3 ± 4.9 mm Hg vs .70 ± .70, 12.8 ± 2.8 mm Hg, and 11.1 ± 2.3 mm Hg, respectively; P < .01). There was no significant difference between the 2 groups in terms of general characteristics, treatment success, pre- and postoperative esophageal manometry, Eckardt score, and adverse events (P > .05). CONCLUSIONS: The short-term treatment efficacy, manometry outcomes, and adverse events were comparable between the anterior and posterior myotomy groups. Large-scale studies with long-term follow-up are warranted for a more definitive conclusion. (Clinical trial registration number: ChiCTR-ICR-15007211.).

[Clinicopathological differences in laterally spreading tumors between rectum and colon].

OBJECTIVE: To investigate the clinicopathological differences in laterally spreading tumor (LST) from the rectum and colon.
 Methods: Clinicopathological records of 198 patients with LST (116 cases in rectum, 82 cases in colon) from the Second Xiangya Hospital of Central South University between January 2012 and January 2017 were evaluated.
 Results: A total of 198 colorectal LST were included. According to the endoscopic classification, nodular mixed type (LST-GM), homogeneous type (LST-GH), flat elevated type(LST-FE) and pseudodepressed type (LST-PD) were 127(64.1%), 13(6.6%), 41(20.7%) and 17(8.6%), respectively. LST-GM was predominant in the rectum (71.7%), while LST-FE was predominant in the colon (78.0%), with significant difference (P<0.01). The mean size of LST was (52.03±35.62) mm or (25.37±11.56) mm in the rectum or the colon, with significant difference between them (P<0.01). High grade intraepithelial neoplasia frequency was higher in the rectum than that in the colon (31.0% vs 18.3%), while the low grade intraepithelial neoplasia frequency was lower in the rectum than that in the colon (61.2% vs 75.6%) (both P<0.05). The mean size of LST-GM and LST-GH diameter were larger in the rectum than that in the colon, and the malignant potential of LST-GM was higher in the rectum than that in the colon. The percentage of high grade intraepithelial neoplasia + invasive carcinoma was 41.8% and 22.2%, respectively (both P<0.05). LST in colon was mostly treated with endoscopic mucosal resection, while LST in rectum was treated by endoscopic submucosal dissection predominantly.
 Conclusion: LSTs from the rectum and colon show different clinicopathological characteristics to some extent. LST-GM is predominant in the rectum, while LST-FE is predominant in the colon. The malignant potential of LST-GM is higher in the rectum than that in the colon.

Comparison between submucosal tunneling endoscopic resection and endoscopic full-thickness resection for gastric stromal tumors originating from the muscularis propria layer.

BACKGROUND: Both submucosal tunneling endoscopic resection (STER) and endoscopic full-thickness resection (EFTR) are effective method for treating gastric gastrointestinal stromal tumors (GISTs); however, little is known about the comparison between STER and EFTR. The aim of the study was to compare the safety and efficacy of STER and EFTR for treating gastric GIST. METHODS: We retrospectively collected the clinical data about patients with gastric GISTs who received STER or EFTR at our hospital from April 2011 to June 2016. Epidemiological data (gender, age), tumor size, procedure-related parameters, complications, length of stay, cost and follow-up data were compared between STER and EFTR. RESULTS: A total of 52 patients were enrolled, and 20 of them received STER, while the other 32 cases received EFTR. There was no significant difference between the two groups in terms of gender, age, concomitant diseases, tumor size, en bloc resection rate, operation time, complications, pathohistological grade of GIST, hospital stay and cost (P > 0.05). However, patients who received EFTR had a longer suture time and needed more clips to close the gastric-wall defect (STER vs EFTR, 291.5 ± 68.7 vs 380.6 ± 96.9s and 6.0 ± 1.2 vs 7.6 ± 1.6, P < 0.05). No recurrence was noted in the STER and EFTR groups during a mean follow-up of 10.9 and 23.8 months, respectively. CONCLUSIONS: The treatment efficacy between STER and EFTR for treating gastric GISTs was comparable, and a large-scale, randomized study is necessary for a more confirmed conclusion.

Endoscopic full-thickness resection for a gastric angioleiomyoma.

Angioleiomyoma (ALM) is a rare benign tumor, which is generally occurs on extremity, particularly the lower legs. It is composed of varied smooth muscle bundles and vascular channels. In this letter to editor, we describe the first case report of gastric ALM.

[Research progress in endoscopic incision in treating gastrointestinal benign stricture].

Gastrointestinal benign stricture is a common disease with symptoms of dysphagia, abdominal pain and difficult defecation, which severely impair the quality of life for patients. Endoscopic intervention is the first-line treatment, and the available methods include balloon dilation, local drug injection and stent insertion, etc. Endoscopic incision was first used for the treatment of Schatzki's rings, and later it was used for the treatment of other gastrointestinal benign strictures, and the promising results were achieved.

Rupture of esophagus by compressed air.

Currently, beverages containing compressed air such as cola and champagne are widely used in our daily life. Improper ways to unscrew the bottle, usually by teeth, could lead to an injury, even a rupture of the esophagus. This letter to editor describes a case of esophageal rupture caused by compressed air.

Submucosal tunneling endoscopic resection for simultaneous esophageal and cardia submucosal tumors originating from the muscularis propria layer (with video).

Submucosal tunneling endoscopic resection (STER) is a new treatment technique for upper gastrointestinal submucosal tumors (SMT) originating from the muscularis propria (MP) layer. In contrast to conventional endoscopic resection, the new therapy can maintain the mucosal integrity of the digestive tract, which effectively prevents mediastinitis and peritonitis. STER, although a known method, has not been widely adopted because of technical difficulties. Here, we describe the case of a 30-year-old patient presenting with two separate SMT originating from the esophageal and cardia MP layer. A 2-cm longitudinal mucosal incision was made approximately 5 cm proximal to the esophageal SMT, and the esophageal and cardia SMT were dissected successively in the same submucosal tunnel. In the relevant literature, this is the first case of STER for resecting esophageal and cardia SMT using the same submucosal tunnel.

[Current status and clinical progress of capsule retention].

Small bowel capsule endoscopy has been now widely applied for patients who are highly suspected of small bowel disease with occult bleeding and unexplained abdominal pain. Capsule retention is a major complication, with an overall incidence of 1%-2%, commonly seen in the detection of Crohn's disease and small bowel tumors. Most cases run asymptomatically after retention, while intestinal obstruction or perforation can occur ralely. Conservative methods, endoscopic or surgical interventions are performed to deal with the retention. Patency capsule is currently used as a novel tool to reduce the risk of capsule retention.

Down-regulation of miR-138 promotes colorectal cancer metastasis via directly targeting TWIST2.

BACKGROUND: Colorectal cancer (CRC) is the most common digestive system malignancy. The molecular events involved in the development and progression of CRC remain unclear. Recently, more and more evidences have showed that deregulated miRNAs participate in colorectal carcinogenesis. METHODS: The expression levels of miR-138 were first examined in CRC cell lines and tumor tissues by real-time PCR. The in vitro and in vivo functional effects of miR-138 were examined further. Luciferase reporter assays were conducted to confirm the targeting associations. Kaplan-Meier analysis and log-rank tests were performed to estimate the overall survival and disease free survival rate. RESULTS: miR-138 was found to be down-regulated in human colorectal cancer tissues and cell lines. Ectopic expression of miR-138 resulted in a dramatic inhibition of CRC migration and invasion in vitro and in vivo. Twist basic helix-loop-helix transcription factor 2 gene (TWIST2) was identified as one of the functional target. Restoration of miR-138 resulted in a dramatic reduction of the expression of TWIST2 at both mRNA and protein levels by directly targeting its 3'-untranslated region (3'UTR). Up-regulation of TWIST2 was detected in CRC tumors compared with adjacent normal tissues (P < 0.001) and is inversely correlated with miR-138 expression. We also identified that down-regulation of miR-138 was associated with lymph node metastasis, distant metastasis, and always predicted poor prognosis. CONCLUSION: These data highlight a pivotal role for miR-138 in the regulation of CRC metastasis by targeting TWIST2, and suggest a potential application of miR-138 in prognosis prediction and CRC treatment.

Large gastric folds arising in polyposis syndromes.

Large gastric folds (LGF) can be caused by benign conditions as well as malignancies. Unfortunately, endoscopic features and biopsy results are often equivocal, making the diagnosis and management of large gastric folds difficult. Polyposis syndromes encompass a group of conditions in which multiple gastrointestinal polyps occur in the lumen of the gut. Large gastric folds are extremely rare in these syndromes. We present the case of a patient with polyposis who was found to have large gastric folds in the entire gastric fundus and body, mimicking malignancy. The patient's medical history and endoscopic ultrasonography (EUS) with mucosal resection confirmed the diagnosis of a pre-malignant disease. The lesion was monitored by serial endoscopic ultrasonography and biopsy, abdominal computed tomography (CT), and positron emission and computed tomography (PET-CT) for 6 years. The lesion remained stable, with the exception of abnormal fluorodeoxyglucose uptake on PET-CT in the gastric folds, which was determined to be a false-positive sign. To date, the patient remains healthy. We further discuss the mechanisms underlying the formation of large gastric folds caused by polyposis syndromes. Helicobacter pylori (H. pylori) or cytomegalovirus (CMV) is unnecessary for this progression. Immunohistochemistry (IHC) staining suggested that overexpression of transforming growth factor alpha (TGF-alpha) and down-regulation of myocyte enhancer-binding factor 2 (MEF2) may be involved in this case.

ZEB2 promotes the metastasis of gastric cancer and modulates epithelial mesenchymal transition of gastric cancer cells.

BACKGROUND: Invasion and metastasis are the hallmarks of advanced gastric cancer progression. Therefore, it is urgent to overcome metastasis in order to improve the survival of gastric cancer patients. AIMS: This study aimed to examine the expression of ZEB2 in gastric cancer samples and analyze its correlation with clinicopathologic features. In addition, the molecular mechanism by which ZEB2 contributes to gastric cancer metastasis will be explored. METHODS: ZEB2 expression in clinical gastric cancer samples was evaluated by immunohistochemical analysis. ZEB2 was knocked-down in HGC27 gastric cancer cells by shRNA and the effects on cell invasion and migration were examined by in vitro cell invasion and migration assays. The expression of epithelial marker E-cadherin, mesenchymal markers fibronecin and vimentin, and MMPs was detected by western blot analysis. RESULTS: The expression of ZEB2 was positively correlated with the depth of invasion, lymph node metastasis and TNM stage. In addition, patients with positive ZEB2 expression showed a significantly shorter overall survival time than did patients with negative ZEB2. shRNA mediated knockdown of ZEB2 resulted in reduced invasion and migration of HGC27 cells, along with the upregulation of E-cadherin and downregulation of fibronecin, vimentin, MMP2, and MMP9. CONCLUSIONS: ZEB2 expression is closely associated with the clinicopathological parameters of gastric cancer. ZEB2 promotes gastric cancer cell migration and invasion at least partly via the regulation of epithelial-mesenchymal transition. ZEB2 is a potential target for gene therapy of aggressive gastric cancer.

Decreased expression of T-cadherin is associated with gastric cancer prognosis.

BACKGROUND/AIMS: To investigate the expression status of truncated-cadherin (T-cadherin) and its clinicopathological significance in gastric cancer. METHODOLOGY: Expression status of T-cadherin was detected in a total of 103 surgical specimens of gastric cancer and 34 corresponding normal gastric tissues by real-time qPCR, western blotting and immunohistochemistry. Correlation between the expression of T-cadherin and clinicopathological factors of gastric cancer was analyzed. RESULTS: T-cadherin mRNA levels were significantly reduced in 29 (85.3%) tumor tissue samples, compared with levels in the adjacent normal tissue samples (p<0.01). This finding was confirmed by western blotting analysis (p<0.01) and immunohistochemistry analysis (p<0.01). Larger tumor size (diameter >4cm), lymph node metastasis, invasion into surrounding tissues, poor-differentiation and higher TNM stage of carcinoma were significantly correlated with decreased expression of T-cadherin (p<0.05 or p<0.01). Univariate Cox regression analysis showed that smaller tumor size (diameter =4cm), none lymph node metastasis, none invasion into surrounding tissues, well-differentiation, lower TNM stage and higher expression of T-cadherin were closely associated with increased overall survival (p<0.05 or p<0.01). Multivariate Cox regression analysis showed that positive expression of T-cadherin was a most important independent risk factor in gastric cancer. CONCLUSIONS: Expression of T-cadherin is an important independent prognostic predictor, which can be used as a biomarker of progression and prognosis in gastric cancer.

[5-aza-2'-deoxycytidine-induced inhibition of CDH13 expression and its inhibitory effect on methylation status in human colon cancer cells in vitro and on growth of xenograft in nude mice].

OBJECTIVE: To determine the inhibitory effect of 5-aza-2'-deoxycytidine (5-Aza-CdR) on the growth of human colon carcinoma cells and xenografts in nude mice, to observe its effect on CDH13 gene expression and methylation in the xenografts, and to explore the possible mechanisms. METHODS: Human colon carcinoma cell line HCT116 cells were treated with 5-Aza-CdR, and the cell morphology was observe by phase contrast microscopy. The cell growth was assessed by MTT assay. A tumor-bearing mouse model was generated by subcutaneous inoculation of human colon carcinoma HCT116 cells into nude mice. The tumor growth in the nude mice was observed, the CDH13 gene expression and its methylation status in the tumors were detected using methylation specific PCR (MSP), RT-PCR, Western blotting and immunohistochemistry. RESULTS: After treatment with 5-Aza-CdR, the inhibition rate of the growth of cultured HCT116 cells was increased as the concentration was increasing. The growth of the xenografts in nude mice was significantly inhibited, and the methylated CDH13 gene was reactivated. After 4 weeks of 5-Aza-CdR treatment, no significant difference was found between the body weights of nude mice in the 5-Aza-CdR group [(18.06 ± 1.29) g] and control group [(17.07 ± 0.84) g], (P > 0.10), and the average volume of xenografts of the 5-Aza-CdR group was (907.00 ± 87.29) mm(3), significantly smaller than the (1370.93 ± 130.20) mm(3) in the control group (P < 0.005). No expression of CDH13 gene was found in the control group. The expression of CDH13 gene in the 5-Aza-CdR group was increased along with the increasing concentration of 5-Aza-CdR. CONCLUSIONS: 5-Aza-CdR inhibits the growth of human colon cancer cells in culture and in nude mice, and induces the cancer cells to re-express CDH13 in nude mice. Its mechanism may be that demethylation of the methylated CDH13 promoter induced by 5-Aza-CdR restores CDH13 expression and thus inhibits the tumor growth in nude mice.