Taiqian Gong

miRNA-223 Promotes Gastric Cancer Invasion and Metastasis by Targeting Tumor Suppressor EPB41L3

Traditional research modes aim to find cancer-specific single therapeutic target. Recently, emerging evidence suggested that some micro-RNAs (miRNA) can function as oncogenes or tumor suppressors. miRNAs are single-stranded, small noncoding RNA genes that can regulate hundreds of downstream target genes. In this study, we evaluated the miRNA expression patterns in gastric carcinoma and the specific role of miR-223 in gastric cancer metastasis. miRNA expression signature was first analyzed by real-time PCR on 10 paired gastric carcinomas and confirmed in another 20 paired gastric carcinoma tissues. With the 2-fold expression difference as a cutoff level, we identified 22 differential expressed mature miRNAs. Sixteen miRNAs were upregulated in gastric carcinoma, including miR-223, miR-21, miR-23b, miR-222, miR-25, miR-23a, miR-221, miR-107, miR-103, miR-99a, miR-100, miR-125b, miR-92, miR-146a, miR-214 and miR-191, and six miRNAs were downregulated in gastric carcinoma, including let-7a, miR-126, miR-210, miR-181b, miR-197, and miR-30aa-5p. After examining these miRNAs in several human gastric originated cell lines, we found that miR-223 is overexpressed only in metastatic gastric cancer cells and stimulated nonmetastatic gastric cancer cells migration and invasion. Mechanistically, miR-223, induced by the transcription factor Twist, posttranscriptionally downregulates EPB41L3 expression by directly targeting its 3′-untranslated regions. Significantly, overexpression of miR-223 in primary gastric carcinomas is associated with poor metastasis-free survival. These findings indicate a new regulatory mode, namely, specific miRNA, which is activated by its upstream transcription factor, could suppress its direct targets and lead to tumor invasion and metastasis. Mol Cancer Res; 9(7); 824–33. ©2011 AACR.

Prevention and management of complications after colon interposition for corrosive esophageal burns

We present our experience in the management of complications after a colon interposition for corrosive esophageal burns. From April 1976 to December 2006, 85 patients with caustic esophageal burns were included in this study. The superior belly median incision with an anterior border incision of the left sternocleidomastoid was used. Anastomosis between the colon and the cervical esophagus was performed in 68 and between the colon and pharyngeal portion in 14 patients. An esophageal scar part resection and gastric-esophageal anastomosis was performed in one patient who had been given an unsuccessful colon and jejunum interposition at another institute. An anastomotic modeling operation was performed in one patient with anastomotic stricture who had been managed with colon interposition at another institute. Exploratory thoracotomy and gastrostomy was performed in one patient who had an unsuccessful colon interposition at another institute. Seven of 14 patients (8.5% of 17.1%) died with serious complications such as aspirated pneumonia, interposition colon necrosis, abdominal wound dehiscence and degradation of swallowing and concordance function. However, others with such serious complications survived and were discharged for rehabilitation after corresponding treatment. The 25 patients (30.1%) with other mild complications were discharged for rehabilitation and corresponding management. Two patients from other institutes were discharged for rehabilitation and one was lost to follow-up. The most dangerous complication of this procedure is colon necrosis, and the stomach is the best organ for re-operation. Otherwise, aspiration in infants due to hypoplasia and degradation of swallowing co-ordination needs attention. Peri-operative management is very important, including the control of mediastinal and pulmonary infection and systemic nutritional support to avoid abdominal wound dehiscence. The platysma flap is an excellent method for the treatment of anastomotic stricture.

Management of delayed intrathoracic esophageal perforation with modified intraluminal esophageal stent

In this article, we reviewed our experience of treatment of the delayed intrathoracic nonmalignant esophageal perforation employing modified intraluminal esophageal stent. Between February 1990 and August 2006, eight patients were included in this study. Five patients experienced sepsis. The interval time between perforation and stent placement ranged from 36 h to 27 days (average, 8.6 days). Esophageal stenting and throracotomy for foreign body removal were performed in four patients. The remaining four patients underwent stent placement and thoracostomy. Nutrition was initiated through gastrostomy after 7 to 10 days after the stenting. The stent was removed after the patients resumed oral intake of food and the esophagogram showed that perforation was closed. There was no death in this group. Signs of sepsis remitted 1 week after stent placement. Complications included stress ulcer, stimulative cough, and pneumonia each. Stent removal ranged 32 to 120 days (average 66.7) after its placement. The stent was kept in place for 4 months to prevent formation of esophageal stricture in one patient with caustic esophageal burns. The follow-up was completed in all the patients. The mean follow-up period was 59 months (range 12-180). One patient with caustic esophageal burn underwent cicatricial esophagectomy and gastric transposition 3 years later due to the esophageal stricture. Barium swallow demonstrated that there was a diverticulum-like outpouching in one patient and slight esophageal stricture at T2 and T3 level in another. One patient developed reflux esophagitis 5 years after stent removal. All the patients finally had a normal intake of food. Modified esophageal stenting is an effective method to manage the delayed intrathoracic esophageal perforation. Prevention of stent migration and its convenient adjustment might be the major advantages of this method.

MicroRNA library-based functional screening identified miR-137 as a suppresser of gastric cancer cell proliferation

AbstractPurposesUncontrolled proliferation is a key characteristic of gastric carcinogenesis and the precise mechanisms underlying the altered proliferation behaviors of GC cells have not been clearly elucidated. miRNAs has been suggested to play a crucial role in the pathogenesis and development of various cancers. In the present study, we employed an impedance-based real-time cell electronic sensing (RT-CES) system to detect the effects of ectopically expressed miRNAs on GC cell proliferation.MethodsmiRNA mimics were transfected into gastric cancer cell line SGC7901 and the effect of individual miRNA on the proliferation rate of the cells was measured by the RT-CES system. The screening results were validated with qRT-PCR and miR-137 was selected for further research. The effects of ectopically expressed miR-137 on GC cell growth and cell cycle progress were measured using MTT assay and flow cytometry. The target gene of miR-137 was predicted using different bioinformatics tools and the direct interaction between miR-137 and the 3’-UTR was confirmed with a luciferase reporter assay. The in vivo effect of miR-137 on GC cell proliferation was examined with a tumor-bearing nude mouse model. The correlation between miR-137 expression and patients’ prognosis was explored in a cohort of 38 patients. Prognosis was explored in a cohort of 38 patients.ResultsEctopic expression of miR-137 was sufficient to inhibit GC cell proliferation both in vitro and in vivo. Bioinformatics prediction and luciferase reporter assay revealed CDK6 as a target gene through which miR-137 exerted an inhibitory function. Moreover, miR-137 expression positively correlated with better prognosis.ConclusionOur data indicated an important regulatory role of miR-137 in GC cell proliferation and that it may be explored as a prognostic marker for GC.

Decreased expression of CIAPIN1 is correlated with poor prognosis in patients with esophageal squamous cell carcinoma.

BackgroundCIAPIN1, a newly identified antiapoptotic molecule, is a downstream effector of the receptor tyrosine kinase–Ras signaling pathway in the mouse Ba/F3 pro-B cell line. Neither CIAPIN1 expression nor its clinical significance has been previously examined in esophageal squamous cell carcinoma (ESCC), and the present immunohistochemical analysis is the first study on CIAPIN1 distribution in ESCC.AimsTo investigate the relationships between the expression of CIAPIN1 and clinicopathological characteristics of ESCC, and evaluate the relationship between the expression of this gene and prognosis in ESCC patients.MethodsThe expression of CIAPIN1 was investigated in 112 surgically resected specimens of ESCC by immunohistochemistry using a specific monoclonal antibody. The relations of CIAPIN1 expression with clinicopathological characteristics and the postoperative survival rate were statistically analyzed.ResultsWe found that the expression of CIAPIN1 was statistically correlated with the degree of differentiation, depth of invasion, and lymph node metastasis of ESCC. Consistently, the survival rates of patients with CIAPIN1-negative tumors tended to be statistically lower than those with CIAPIN1-positive tumors. However, no significant difference was observed between CIAPIN1 expression and the patient age, sex, tumor location, and distant metastasis. Furthermore, multivariate analysis was performed by using Cox’s proportional hazards model, and the results showed that lymph node metastases and CIAPIN1 expression were two independent prognostic factors.ConclusionsCIAPIN1 might play an important role in esophageal carcinogenesis, and it could be considered as a valuable prognostic indicator in ESCC. Finally, functional enhancement of CIAPIN1 might lead to a novel strategy for the treatment of SCC in the esophagus.

SDR9C7 Promotes Lymph Node Metastases in Patients with Esophageal Squamous Cell Carcinoma

Background The major reason for the poor prognosis of esophageal squamous cell carcinoma (ESCC) patients is lymph node (LN) metastases. Methodology/Principal In the present study, gene expression profiling assay (GEP) was performed to identify the differences in gene expression profiles between primary ESCC tumors that were with LN metastases (N+) and those without LN metastases (N-). Conclusions/Significance A total of 23 genes were identified as being significantly elevated, and 30 genes were sharply decreased in ESCC tumors that were N+ compared with N- tumors. Among these genes, two transcripts of the short chain dehydrogenase/reductase family 9C, member 7 (SDR9C7) were observed 7 times more frequently in N+ compared with N- tumors. Immunohistochemical staining showed that SDR9C7 expression closely correlated with metastasis, and would be a prognostic marker for ESCC patients. To investigate the role of SDR9C7 in the ESCC metastasis, repeated transwell assays were adopted to establish highly and non-invasive ESCC sublines, and western blot showed that SDR9C7 expression was markedly higher in highly invasive cells compared with non-invasive ones. Down-regulation of SDR9C7 dramatically inhibited the metastatic abilities in vitro and in vivo, and repressed the expression of MMP11 in highly invasive cells, indicating that SDR9C7 promotes ESCC metastasis partly through regulation of MMP11, and might be a potential prognostic and therapeutic marker for ESCC patients.

Reconstruction of hypopharyngeal and cervical esophageal defect after resection of hypopharyngeal carcinoma: a new technique based on the use of bilateral platysma myocutaneous flaps

Commonly used procedures for reconstructing hypopharyngeal and cervical esophageal defects resulting from total laryngopharyngectomy (TL) are the gastric conduit or colon transposition as well as microvascularized free flaps. Herein we designed an alternative procedure utilizing bilateral platysma myocutaneous flaps (PMCFs) for the reconstruction of hypopharyngeal and cervical esophageal defects. This report summarizes the technical description of this procedure. TL and cervical esophagectomy were performed and bilateral PMCFs were harvested for reconstruction of hypopharyngeal and cervical esophageal defects in 25 patients aged between 46 and 73 years (mean 58.7 ± 16.2 years). All these patients had advanced-stage (IV) cancer with involvement of the cervical esophagus. Operative time ranged from 176 to 382 minutes (average 243 ± 91 minutes) and the mean intraoperative blood loss was 294 ± 119mL. There were six cases of anastomotic leak (24.0%) and two of them (8.0%) developed anastomotic stricture. Neither flap necrosis nor postoperative death was observed. The majority of our patients (68.0%) were restored to a normal unrestricted oral diet after surgery. The 3-year and 5-year actuarial survival rates were approximately 54.7% and 26.1%, respectively. We conclude that reconstruction of the cervical esophagus with bilateral PMCFs is a valuable method for treating advanced hypopharyngeal carcinoma.

Prevention of stricture development after corrosive esophageal burn with a modified esophageal stent in dogs

OBJECTIVE We sought to test the feasibility and technical ease of a newly designed nitinol-based modified esophageal stent and its effects on preventing postcaustic stricture in mongrel dogs and to try to explain the result at the molecular level. METHODS Twenty-four dogs were included in this controlled study. Stenosis index (wall thickness/intraluminal diameter), pathologic features, hydroxyproline quantities, esophageal compliance, and biomechanics were compared between the injured but unstented and stented dogs. Transforming growth factor beta1, Sma/Mad (Smad)3, and Smad7 mRNA expression and protein levels in esophageal tissue were detected by means of reverse transcriptase-polymerase chain reaction and Western blotting, respectively. RESULTS The modified esophageal stent was able to be placed and retrieved successfully and conveniently and was not only intact but there was also no macroscopic esophageal mucosal injury after the stent removal 4 months later. In comparison with the injured but unstented group, esophageal compliance, biomechanics, and the stenosis index were significantly better in the stented group. Histopathologic study revealed that collagen bundles were thinner and its orientation tended toward a regular and parallel pattern. Transforming growth factor beta1 and Smad3 mRNA expression and protein levels increased and Smad7 mRNA expression and protein levels decreased significantly in esophageal tissue in the stented group. These variables showed no statistically significant difference 2 months after stent removal. CONCLUSIONS The modified esophageal stent might be a promising stent in preventing stricture formation after corrosive esophageal burns clinically.

Thoracoscopic and laparoscopic radical esophagectomy with lateral-prone position

With 20 years of development, minimally-invasive treatment for esophageal cancer has been widely spread. However, surgeons have not reached consensus about the optimal minimally-invasive operation method, or whether the effect of radical lymph nodes dissection is comparable to the traditional open procedure. Thoracoscopic esophagectomy with lateral-prone position combines the advantages of both lateral position (allowing quick conversion to open procedure) and prone position (good visual area and complete lymphadenectomy). Together with laparoscopic abdominal lymphadenectomy, gastric tube formation and jejunostomy, this approach provides an easier way for minimally-invasive radical esophagectomy. In this article, approaches for thoracoscopic esophagectomy with lateral-prone position and total mediastinal lymphadenectomy, combined with totally laparoscopic gastric mobilization, abdominal lymphadenectomy, gastric tube formation and jejunostomy, will be presented by video instructions. All the procedures were under the rule of radical lymphadenectomy. Cervical lymph nodes dissection and esophago-gastrostomy were the same as those in open procedure, which will not be discussed here.

Human Leukocyte Antigen-ABDR Genes in Pulmonary Adenocarcinoma Cell Lines

2008;134;890 Chest Jing-Hai Zhou, Yun-Ping Zhao, Tai-Qian Gong and Zheng Ma Bo Deng, Ru-Wen Wang, Yao-Guang Jiang, Yi-Dan Lin, Qun-You Tan, Pulmonary Adenocarcinoma Cell Lines Human Leukocyte Antigen-ABDR Genes in http://chestjournal.chestpubs.org/content/134/4/890.1.full.html services can be found online on the World Wide Web at: The online version of this article, along with updated information and ISSN:0012-3692 ) http://chestjournal.chestpubs.org/site/misc/reprints.xhtml ( written permission of the copyright holder. this article or PDF may be reproduced or distributed without the prior Dundee Road, Northbrook, IL 60062. All rights reserved. No part of Copyright2008by the American College of Chest Physicians, 3300 Physicians. It has been published monthly since 1935. is the official journal of the American College of Chest Chest