SET7 interacts with HDAC6 and suppresses the development of colon cancer through inactivation of HDAC6.

SET7 is the first lysine methyltransferase and plays vital roles in tumorigenesis. This study aims to seek clinical value of SET7 in colorectal cancer (CRC) patients, along with its biological impact on cell proliferation and migration. In patients with CRC, the expression of SET7 in cancer tissue was significantly lower than that in adjacent tissue, and down-regulated SET7 was closely correlated with poor prognosis. Loss-of-function and gain-of-function studies indicated that SET7 inhibited cell proliferation and migration by acting on HDAC6 substrate in colon cancer cells. Besides, the co-immunoprecipitation assay showed that SET7 and HDAC6 can interact reciprocally. The interaction effect between SET7 and HDAC6 could significantly reduce cell viability, scratch healing rate, and migrated cells in colon cancer cells. Instead of acting on each endogenous expression, the results demonstrated that the level of acetylated α-tubulin was greatly decreased in HDAC6 overexpression group, while significantly increased in SET7 overexpressed group. However, changes were partly restored in both SET7 and HDAC6-transfected group. On the contrary, the expression of acetylated α-tubulin protein was significantly increased in HDAC6 knockdown group, but higher in both HDAC6 and SET7 silencing group. These results indicated that SET7 played a role in tumor suppression via increasing levels of acetylated-α-tubulin mediated by HDAC6. In addition, the interaction effect significantly decreased the ratios of p-ERK/ERK, which indicated that it may partly suppress ERK signaling pathway. In conclusion, SET7 is a promising therapeutic target for preventing metastasis and improving prognosis in colon cancer.

Pancreatic and duodenal homeobox-1 in pancreatic ductal adenocarcinoma and diabetes mellitus.

Diabetes mellitus and pancreatic ductal adenocarcinoma are two common diseases worldwidely which are both derived from different components of pancreas. The pancreatic and duodenal homeobox-1 (PDX1) is an essential transcription factor for the early development of pancreas that is required for the differentiation of all pancreatic cell lineages. Current evidence suggests an important role of PDX1 in both the origin and progression of pancreatic diseases. In this review, we discussed recent studies of PDX1 in diabetes mellitus and pancreatic cancer, and the therapeutic strategies derived from this transcription factor.

Clinical outcomes of endoscopic submucosal tunnel dissection compared with conventional endoscopic submucosal dissection for superficial esophageal cancer: a systematic review and meta-analysis.

BACKGROUND: Endoscopic submucosal dissection (ESD) is the standard treatment for superficial esophageal cancer. However, it has limitations in case of large superficial esophageal squamous cell neoplasms (SESCNs), in which submucosal injection cannot attain satisfactory lifting effects. Thus, endoscopic submucosal tunnel dissection (ESTD) was introduced as a new treatment for SESCNs presenting satisfying results. Many studies have tried to verify the efficacy of ESTD, yet no meta-analysis has been published until now. METHODS: We searched the databases of PubMed, Cochrane Library, Web of Science, SinoMed, Wanfang, and CNKI dating up to February 1, 2019. Studies comparing the clinical outcomes of ESTD and ESD for superficial esophageal cancers were enrolled. The Newcastle-Ottawa Quality Assessment Scale was used to evaluate the quality of these studies. Eight articles were included that involved a total of 625 superficial esophageal cancer patients. RESULTS: Our analysis revealed that ESTD is superior to ESD as it has higher en bloc resection rate, shorter operation time, and lower recurrence rate 1 year after operation. The R0 resection rate and postoperative adverse event rate of ESTD group is comparable with ESD group. CONCLUSIONS: Our study implicates that ESTD is a potentially superior treatment to ESD for superficial esophageal cancer.

Histone deacetylase 6 is overexpressed and promotes tumor growth of colon cancer through regulation of the MAPK/ERK signal pathway.

Purpose: To investigate the expression of histone deacetylase 6 (HDAC6) in colon cancer and its role in colon cancer cell growth and migration. Materials and methods: We detected the expression of HDAC6 in a colon cancer tissue chip using immunochemical staining, and analyzed the difference in HDAC6 expression between cancer and adjacent noncancerous tissues. Then, we explored the relationship between HDAC6 expression and patients' clinicopathological characteristics and prognoses. In adidition, the role of HDAC6 in colon cancer cell growth and migration, as well as its potential related signal pathway, through HDAC6 knockdown was explored. Results: The immunochemical score of HDAC6 expression was higher in cancer tissue than in the adjacent noncancerous tissue (4.54 vs 3.08, P<0.005); similarly, as well as the rate of high HDAC6 expression was higher in cancer tissue than in the adjacent noncancerous tissue (71.1% vs 40.9%, P<0.001). Patients showing high HDAC6 expression had a shorter overall survival time. Additionally, Cox regression analysis showed that high HDAC6 expression was an independent risk factor for poor prognosis. HDAC6 knockdown decreased cell viability, colony formation, and number of migrated colon cancer cells (HCT116 and HT29); the expression of p-MEK, p-ERK, and p-AKT was also decreased, but had no influence on MEK, ERK, and AKT expression. Conclusion: HDAC6 is highly expressed in colon cancer and associated with a poor prognosis. HDAC6 knockdown inhibits colon cancer cell growth and migration, partly through the MAPK/ERK pathway.

A comparison of submucosal tunneling endoscopic resection and endoscopic full-thickness resection for gastric fundus submucosal tumors

Aim: Both submucosal tunneling endoscopic resection (STER) and endoscopic full-thickness resection (EFTR) are effective methods for gastric fundus submucosal tumors (SMTs). However, there is little data that compares the two methods. The aim of this study was to compare the safety and efficacy of STER and EFTR for the treatment of SMTs in the gastric fundus. Methods: Clinical data was retrospectively collected from patients with gastric fundus SMTs who underwent STER or EFTR at our hospital from April 2011 to May 2016. Epidemiological data (gender, age), tumor size, procedure-related parameters, complications, postoperative hospital stay, cost and follow-up data were compared. Results: A total of 43 patients were enrolled: 15 underwent STER and the remaining 28 cases underwent EFTR. There were no significant differences between the two groups with regard to gender, age, tumor size, en bloc resection rate, operation time, pathohistological results and cost (p > 0.05). However, patients who underwent EFTR had a longer suture time, required a larger number of clips for closure and a prolonged postoperative hospital stay (p < 0.05). No recurrence was noted in either the STER or the EFTR group during a mean follow-up of 12.1 and 22.8 months, respectively. Conclusions: The treatment efficacy of STER and EFTR for the treatment of gastric fundus SMTs was comparable. However, STER has some advantages over EFTR in terms of suture time, the number of clips required for closure and postoperative hospital stay (AU)

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A comparison of submucosal tunneling endoscopic resection and endoscopic full-thickness resection for gastric fundus submucosal tumors.

AIM: Both submucosal tunneling endoscopic resection (STER) and endoscopic full-thickness resection (EFTR) are effective methods for gastric fundus submucosal tumors (SMTs). However, there is little data that compares the two methods. The aim of this study was to compare the safety and efficacy of STER and EFTR for the treatment of SMTs in the gastric fundus. METHODS: Clinical data was retrospectively collected from patients with gastric fundus SMTs who underwent STER or EFTR at our hospital from April 2011 to May 2016. Epidemiological data (gender, age), tumor size, procedure-related parameters, complications, postoperative hospital stay, cost and follow-up data were compared. RESULTS: A total of 43 patients were enrolled: 15 underwent STER and the remaining 28 cases underwent EFTR. There were no significant differences between the two groups with regard to gender, age, tumor size, en bloc resection rate, operation time, pathohistological results and cost (p > 0.05). However, patients who underwent EFTR had a longer suture time, required a larger number of clips for closure and a prolonged postoperative hospital stay (p < 0.05). No recurrence was noted in either the STER or the EFTR group during a mean follow-up of 12.1 and 22.8 months, respectively. CONCLUSIONS: The treatment efficacy of STER and EFTR for the treatment of gastric fundus SMTs was comparable. However, STER has some advantages over EFTR in terms of suture time, the number of clips required for closure and postoperative hospital stay.

Full-thickness myotomy is associated with higher rate of postoperative gastroesophageal reflux disease.

AIM: To compare long-term occurrence of gastroesophageal reflux disease (GERD) between two different types of peroral endoscopic myotomy (POEM) for achalasia. METHODS: We included all patients with achalasia who underwent POEM at our hospital from August 2011 to October 2012 and had complete GERD evaluation with ≥ 3 years of follow-up. They were divided into circular or full-thickness myotomy groups according to the depth of myotomy. Demographics, Eckardt score, manometry results, 24-h pH monitoring, and GERD symptoms were recorded and compared between the two groups. RESULTS: We studied 56 patients (32 circular myotomy and 24 full-thickness myotomy) with complete GERD evaluation. There was no significant difference between the two groups in terms of treatment success (defined as Eckardt score ≤ 3), postoperative Eckardt score, mean basal lower esophageal sphincter pressure, and 4-s integrated relaxation pressure (4sIRP). Postoperative abnormal esophageal acid exposure was found in 25 patients (44.6%). A total of 13 patients (23.2%) had GERD symptoms and 12 had esophagitis (21.4%). Clinically relevant GERD (abnormal esophageal acid exposure associated with GERD symptoms and/or esophagitis) was diagnosed in 13 patients (23.2%). Multivariate analysis revealed that full-thickness myotomy and low level of postoperative 4sIRP were predictive factors for clinically relevant GERD. CONCLUSION: Efficacy and manometry are comparable between achalasia patients treated with circular or full-thickness myotomy. But patients with full-thickness myotomy and low postoperative 4sIRP have more GERD.

Peroral endoscopic myotomy for achalasia in patients aged ≥ 65 years.

AIM: To investigate the safety and efficacy of peroral endoscopic myotomy (POEM) for achalasia in patients aged ≥ 65 years. METHODS: From November 2011 to August 2014, 15 consecutive patients (aged ≥ 65 years) diagnosed with achalasia were prospectively recruited and all underwent POEM at our institution. Eckardt score, lower esophageal sphincter (LES) pressure, esophageal diameter, SF-36 questionnaire, and procedure-related complications were used to evaluate the outcomes. RESULTS: All 15 patients were treated successfully by POEM, with a median operation time of 55 min. Median myotomy length was 10 cm. Three patients underwent circular myotomy and 12 full-thickness myotomies. Symptoms remitted in all cases during post-POEM follow-up of 6-39 mo. Eckardt score reduced significantly (pre-operation vs post-operation: 8.0 vs 1.0, P < 0.05). Median LES pressure decreased from 27.4 to 9.6 mmHg (P < 0.05). Median diameter of the esophagus was significantly decreased (pre-operation vs post-operation: 51.0 mm vs 30.0 mm, P < 0.05). Only one patient had reflux, which was resolved with oral proton pump inhibitors. No serious complications related to POEM were found. The quality of life of the 15 patients improved significantly after POEM. CONCLUSION: POEM is a safe and effective technique for treatment of achalasia in patients aged ≥ 65 years, with improvement in symptoms and quality of life.

The Outcomes and Quality of Life of Patients with Achalasia after Peroral Endoscopic Myotomy in the Short-Term.

PURPOSE: To assess the short-term efficacy and quality of life (QOL) of patients with achalasia after peroral endoscopic myotomy (POEM). METHODS: Thirty-five achalasia patients underwent POEM from May 2013 to December 2013. The data on clinical evaluation and QOL before therapy, at 1 month and 6 months postoperation were collected and analyzed. RESULTS: All the thirty-five patients underwent POEM successfully. By comparing the data of the preoperative with that of 1 month and 6 months after POEM respectively, we found that: mean Eckardt score decreased (6.83 vs 0.51, 6.83 vs 0.46, all P <0.05), esophagus diameter reduced (47.97 mm vs 32.00 mm, 47.97 mm vs 28.50 mm, all P <0.05), and esophageal manometry declined (29.5 mmHg vs 11.5 mmHg, 29.5 mmHg vs 10.3 mmHg, all P <0.05). Complications occurred in 14.3% (5/35) of the cases, and no recurrence was observed. At each time point, postoperative QOL scores were higher than those of preoperative (P <0.05). CONCLUSIONS: POEM is safe and effective for treating achalasia in the short-term, it can relieve clinic symptoms as well as improve patients' QOL.