Jirong Huo

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

BackgroundInvasion 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.AimsThis 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.MethodsZEB2 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.ResultsThe 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.ConclusionsZEB2 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.

Effect of ligustrazine on mice model of hepatic veno-occlusive disease induced by Gynura segetum.

Background and Aim:  To investigate the therapeutic effect of ligustrazine on hepatic veno‐occlusive disease (HVOD) induced by Gynura segetum and the possible mechanism of it.

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.

Effect of prednisone on transforming growth factor-β1, connective tissue growth factor, nuclear factor-κBp65 and tumor necrosis factor-α expression in a murine model of hepatic sinusoidal obstruction syndrome induced by Gynura segetum.

Aim:  One major cause of hepatic sinusoidal obstruction syndrome (HSOS) is the consumption of products containing pyrrolizidine alkaloids (PA). As the use of herbal preparations has increased in China, so has the number of reports of HSOS induced by ingesting PA‐containing herbs. The aim of the present study was to investigate the mechanisms by which prednisone and the related factors, transforming growth factor (TGF)‐β1 and connective tissue growth factor (CTGF), prevent liver fibrosis and the pathogenesis of HSOS.

MicroRNA-375 suppresses esophageal cancer cell growth and invasion by repressing metadherin expression

Accumulating evidence indicates that aberrant expression of microRNAs is involved in tumorigenesis, tumor progression and response to therapy. MicroRNA-375 (miR-375) is an important cancer-associated RNA that is downregulated in multiple types of cancer. In the present study, the potential effects of and underlying molecular mechanism for miR-375 in esophageal cancer were investigated. The expression of miR-375 in paired esophageal squamous cell carcinoma (ESCC) and non-tumor tissues from 10 patients was quantified using the reverse transcription-quantitative polymerase chain reaction. The miR-375 levels in the ESCC cell line EC109 and a normal esophageal epithelial cell line, Het-1A, were also detected. The effect of miR-375 on ESCC cell growth and invasion was determined using Cell Counting kit-8, flow cytometry and invasion assays. A luciferase assay was conducted for target identification. The results of the present study revealed that miR-375 was downregulated in ESCC tumor tissue and EC109 cells compared with normal tissue and Het-1A cells (P<0.01). Overexpression of miR-375 inhibited EC109 cell growth and invasion, and induced cell cycle arrest. In addition, metadherin (MTDH) was demonstrated to be a direct target of miR-375 (P<0.01). The overexpression of miR-375 downregulated MTDH (P<0.01), cyclin D1 (P<0.05) and vascular endothelial growth factor (P<0.01) expression, while upregulating epithelial cadherin (P<0.01) expression, which may account for its effect on ESCC cell proliferation and invasion. The results of the present study suggest that the miR-375/MTDH axis represents a target for the treatment of ESCC.

Comparison of peroral endoscopic myotomy and endoscopic balloon dilation for primary treatment of pediatric achalasia

BACKGROUND Both peroral endoscopic myotomy (POEM) and endoscopic balloon dilation (EBD) are effective method for pediatric achalasia, however little is known about the comparison between them. Herein we compare the safety and efficacy of them for primary treatment of pediatric achalasia. METHODS We retrospectively reviewed the medical records of pediatric patients who received POEM or EBD for their primary therapy of achalasia at our hospital from January 2007 to June 2015, they were divided into the POEM group and EBD group. Demographics, and data about safety and efficacy were retrospectively collected and compared between the two groups. RESULTS A total of 21 patients (Female/male: 11/10, aged 6~17year-old) were enrolled, 12 of them received POEM, while the other 9 received EBD. As for the short-term efficacy, the treatment success (Eckardt score≤3) rate of POEM and EBD 3, 6 and 12months after the primary treatment were comparable (100% vs 100%, 100% vs 88.9%, 100% vs 66.7%, P>0.05). As for the medium to long-term efficacy, the treatment success rate of POEM 24 and 36months after the primary treatment was higher than that of EBD (100% vs 44.4%, 100% vs 33.3%, P<0.05). Two cases in the POEM group suffered from esophagitis, and there was no significant difference between POEM and EBD (P>0.05). No severe complications were observed during operation and periodical follow-up. CONCLUSIONS Short-term efficacy of POEM and EBD for primary treatment of pediatric achalasia was comparable, however POEM could result in a better intermediate and long-term efficacy. Large scale, randomized study is necessary for a confirmed conclusion.

Esophageal squamous cell carcinoma cell proliferation induced by exposure to low concentration of cigarette smoke extract is mediated via targeting miR-101-3p/COX-2 pathway.

Cigarette smoke has been implicated as a major risk factor for esophageal squamous cell carcinoma (ESCC). Several lines of evidence have suggested that the promoting effect of cigarette smoking extract (CSE) on ESCC is mediated by upregulation of cyclooxygenase-2 (COX-2) expression. Yet, the underlying molecular and cellular mechanisms of how CSE stimulates COX-2 expression and facilitates ESCC development are largely unknown. In the present study, we revealed microRNA (miR)-101-3p expression was downregulated upon exposure to low concentration of CSE in Eca109 cancer cells, and suppression of miR-101-3p was required for low CSE-induced cell proliferation, presenting as overexpression of miR-101-3p reversing CSE stimulated cancer cell growth. Luciferase assay revealed that COX-2 was a direct target for miR-101-3p and overexpression of miR-101-3p decreased cellular COX-2 protein expression. Furthermore, we found that COX-2 inhibitor and knockdown of COX-2 by siRNA interference could abolish CSE-induced cell proliferation, indicating that promotion of cancer cell proliferation by low concentration of CSE was dependent on COX-2 activity. Finally, downregulation of miR-101-3p expression and upregulation of COX-2 was found in ESCC specimens from patients with smoking history. Taken together, our findings revealed a new post-transcriptional mechanism by which CSE regulated COX-2 expression to favor cancer cell proliferation, suggesting miR-101-3p as a potential biomarker and therapeutic target for smoke-related ESCC.

Current status of submucosal tunneling endoscopic resection for gastrointestinal submucosal tumors originating from the muscularis propria layer (Review)

Gastrointestinal submucosal tumors (SMTs) have been increasingly identified via the use of endoscopic ultrasonography, and removal is often recommended for SMTs that are >2 cm in diameter or symptomatic. Submucosal tunneling endoscopic resection (STER), also known as submucosal endoscopic tumor resection, endoscopic submucosal tunnel dissection or tunneling endoscopic muscularis dissection, is a novel endoscopic technique for treating gastrointestinal SMTs originating from the muscularis propria layer, and has been demonstrated to be effective in the removal of SMTs with a decreased rate of recurrence by clinical studies. STER may be performed for patients with esophageal or cardia SMTs, and its application has expanded beyond these types of SMTs due to modifications to the technique. The present study reviewed the applications, procedure, efficacy and complications associated with STER.

Involvement of F-box proteins in esophageal cancer (Review)

The F-box proteins (FBPs) in esophageal tumorigenesis are pivotal as they govern a broad array of basic physiological responses including cell growth, cell death and DNA damage repair. Esophageal cancer (EC) is a common and highly aggressive cancer worldwide. Aberrant stabilization of crucial proteins participates in esophageal tumorigenesis. Recently, growing evidence has shown that FBPs play a critical role in oncogenesis, invasion, metastasis and prognosis assessment of EC. In this review we summarized published data on the roles of known FBPs, their respective substrates and the key signaling pathways, in the development of EC, aiming to uncover new ways for the rational design of targeted therapies in EC.

The way to calculate the heart rate

We have read with great interest the article by Bang et al entitled “Intraprocedural increase in heart rate during EUS-guided celiac plexus neurolysis: clinically relevant or just a physiological change?” In this study, the authors found that an intraprocedural increase in heart rate can serve as a predictor of treatment outcome, and this simple indicator may have the potential to guide EUSguided celiac plexus neurolysis. We have 2 questions regarding the method to calculate the heart rate. First, the baseline heart rate was recorded immediately before the alcohol injection, that is, a rate at an exact time point. The human heart rate varies with times, and fluctuation could be seen even under deep sedation; thus, we wonder whether an average heart rate 30 seconds or 1 minute before the alcohol injection would better represent the baseline heart rate. Second, it remains unclear how the time “a minimum of 30 seconds” in the definition of “heart rate change” was calculated. Is it an accumulative time during the 90 seconds of alcohol injection or a continuous one? The authors think that the increased heart rate is mainly caused by the inhibition of reflex sympathetic vasoconstriction after celiac plexus neurolysis. If the time is an accumulative one, what is the meaning of the interval between 2 increased stages of heart rates? Does this suggest dislocation of the needle?