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Dong H.-W.,Harbin Medical University | Zhang S.,Harbin Medical University | Sun W.-G.,Harbin Medical University | Liu Q.,Gannan Medical University | And 8 more authors.
Archives of Toxicology | Year: 2013

β-Ionone is an end ring analog of β-carotenoid which has been shown to possess potent anti-proliferative activity both in vitro and in vivo. To investigate the possible inhibitory effects of β-ionone, we studied cell growth characteristics, DNA synthesis, cell cycle progression, as well as mitogen-activated protein kinases (MAPKs) pathways in the human gastric adenocarcinoma cancer cell line (SGC-7901). Our results show that cell growth and DNA synthesis were inhibited, and the cell cycle was arrested at the G0/G1 phase in a dose-dependent manner in cells treated with β-ionone (25, 50, 100 and 200 μmol/L) for 24 h. We found that the β-ionone significantly decreased the extracellular signal-regulated kinase protein expression and significantly increased the levels of p38 and Jun-amino-terminal kinase protein expression (P < 0.01). β-Ionone also inhibited cell cycle-related proteins of Cdk4, Cyclin B1, D1 and increased p27 protein expression in SGC-7901 cells. These results suggested that the cell cycle arrest observed may be regulated through a MAPK pathway by transcriptional down-regulation of cell cycle proteins. These results demonstrate potent ability of β-ionone to arrest cell cycle of SGC-7901 cells and decrease proliferation. © 2013 Springer-Verlag Berlin Heidelberg.


Liu Q.,Gannan Medical University | Dong H.-W.,Harbin Medical University | Sun W.-G.,Harbin Medical University | Liu M.,Harbin Medical University | And 8 more authors.
Archives of Toxicology | Year: 2013

β-ionone has been shown to hold potent anti-proliferative and apoptosis induction properties in vitro and in vivo. To investigate the effects of β-ionone on apoptosis initiation and its possible mechanisms of action, we qualified cell apoptosis, proteins related to apoptosis and a phosphatidylinositol 3-kinase (PI3K) - AKT pathway in human gastric adenocarcinoma cancer SGC-7901 cells. The results demonstrated that β-ionone-induced apoptosis in a dose-dependent manner in SGC-7901 cells treated with β-ionone (25, 50, 100 and 200 μmol/L) for 24 h. β-ionone was also shown to induce the expression of cleaved-caspase-3 and inhibit bcl-2 expression in SGC-7901 cells in a dose-dependent manner. The significantly decreased levels of p-PI3K and p-AKT expression were observed in SGC-7901 cells after β-ionone treatments in a time- and dose-dependent manner (P < 0.01). Thus, the apoptosis induction in SGC-7901 cells by β-ionone may be regulated through a PI3K-AKT pathway. These results demonstrate a potential mechanism by which β-ionone to induce apoptosis initiation in SGC-7901 cells. © 2012 Springer-Verlag Berlin Heidelberg.


Wang J.,Southern Medical University | Wang J.,Guangdong Provincial Key Laboratory of Gastroenterology | Wang X.,Southern Medical University | Wang X.,Guangdong Provincial Key Laboratory of Gastroenterology | And 8 more authors.
PLoS ONE | Year: 2013

Background:Serum markers represent potential tools for the detection of colorectal cancer (CRC). The aim of this study was to obtain proteomic expression profiles and identify serum markers for the early detection of CRC.Methods:Proteomic profiles of serum samples collected from 35 healthy volunteers, 35 patients with advanced colorectal adenoma (ACA), and 40 patients with CRC were compared using Clinprot technology. Using enzyme-linked immunosorbent assays (ELISAs), 366 sera samples were additionally analyzed, and immunohistochemistry studies of 400 tissues were used to verify the expression of kininogen-1 and its value in the early detection of CRC.Results:Predicting models were established among the three groups, and kininogen-1 was identified as a potential marker for CRC using Clinprot technology. ELISAs also detected significantly higher serum kininogen-1 levels in ACA and CRC patients compared to controls (P<0.05). Furthermore, the area under the receiver operating characteristic curve (AUC) for serum kininogen-1 in the diagnosis of ACA was 0.635 (P = 0.003), and for serum carcinoembryonic antigen (CEA) was 0.453 (P = 0.358). The sensitivity, specificity, and accuracy of serum kininogen-1 for diagnosing Duke's stage A and B CRC was 70.13%, 65.88%, and 67.90%, respectively, whereas serum CEA was 38.96%, 85.88%, and 63.58%, respectively. Moreover, immunohistochemistry showed that expression of kininogen-1 was significantly higher in CRC and ACA tissues than in normal mucosa (48.39% vs. 15.58% vs. 0%, P<0.05).Conclusions:These results suggest that Clinprot technology provides a useful tool for the diagnosis of CRC, and kininogen-1 is a potential serum biomarker for the early detection of advanced colorectal adenoma and CRC. © 2013 Wang et al.


Li B.-S.,Southern Medical University | Li B.-S.,Guangdong Provincial Key Laboratory of Gastroenterology | Wang X.-Y.,Southern Medical University | Wang X.-Y.,Guangdong Provincial Key Laboratory of Gastroenterology | And 6 more authors.
PLoS ONE | Year: 2011

Background: High Resolution Melting Analysis (HRMA) is becoming the preferred method for mutation detection. However, its accuracy in the individual clinical diagnostic setting is variable. To assess the diagnostic accuracy of HRMA for human mutations in comparison to DNA sequencing in different routine clinical settings, we have conducted a meta-analysis of published reports. Methodology/Principal Findings: Out of 195 publications obtained from the initial search criteria, thirty-four studies assessing the accuracy of HRMA were included in the meta-analysis. We found that HRMA was a highly sensitive test for detecting disease-associated mutations in humans. Overall, the summary sensitivity was 97.5% (95% confidence interval (CI): 96.8-98.5; I 2 = 27.0%). Subgroup analysis showed even higher sensitivity for non-HR-1 instruments (sensitivity 98.7% (95%CI: 97.7-99.3; I 2 = 0.0%)) and an eligible sample size subgroup (sensitivity 99.3% (95%CI: 98.1-99.8; I 2 = 0.0%)). HRMA specificity showed considerable heterogeneity between studies. Sensitivity of the techniques was influenced by sample size and instrument type but by not sample source or dye type. Conclusions/Significance: These findings show that HRMA is a highly sensitive, simple and low-cost test to detect human disease-associated mutations, especially for samples with mutations of low incidence. The burden on DNA sequencing could be significantly reduced by the implementation of HRMA, but it should be recognized that its sensitivity varies according to the number of samples with/without mutations, and positive results require DNA sequencing for confirmation. © 2011 Li et al.


Yang H.,Southern Medical University | Yang H.,Guangdong Provincial Key Laboratory of Gastroenterology | Xia B.-Q.,Southern Medical University | Xia B.-Q.,Guangdong Provincial Key Laboratory of Gastroenterology | And 14 more authors.
Canadian Journal of Gastroenterology | Year: 2013

Background and objectives: The diagnostic value of stool DNA (sDNA) testing for colorectal neoplasms remains controversial. To compensate for the lack of large-scale unbiased population studies, a meta-analysis was performed to evaluate the diagnostic value of sDNA testing for multiple markers of colorectal cancer (CRC) and advanced adenoma. Methods: The PubMed, Science Direct, Biosis Review, Cochrane Library and Embase databases were systematically searched in January 2012 without time restriction. Meta-analysis was performed using a random-effects model using sensitivity, specificity, diagnostic OR (DOR), summary ROC curves, area under the curve (AUC), and 95% CIs as effect measures. Heterogeneity was measured using the X2 test and Q statistic; subgroup analysis was also conducted. Results: A total of 20 studies comprising 5876 individuals were eligible. There was no heterogeneity for CRC, but adenoma and advanced adenoma harboured considerable heterogeneity influenced by risk classification and various detection markers. Stratification analysis according to risk classification showed that multiple markers had a high DOR for the high-risk subgroups of both CRC (sensitivity 0.759 [95% CI 0.711 to 0.804]; specificity 0.883 [95% CI 0.846 to 0.913]; AUC 0.906) and advanced adenoma (sensitivity 0.683 [95% CI 0.584 to 0.771]; specificity 0.918 [95% CI 0.866 to 0.954]; AUC 0.946) but not for the average-risk subgroups of either. In the methylation subgroup, sDNA testing had significantly higher DOR for CRC (sensitivity 0.753 [95% CI 0.685 to 0.812]; specificity 0.913 [95% CI 0.860 to 0.950]; AUC 0.918) and advanced adenoma (sensitivity 0.623 [95% CI 0.527 to 0.712]; specificity 0.926 [95% CI 0.882 to 0.958]; AUC 0.910) compared with the mutation subgroup. There was no significant heterogeneity among studies for subgroup analysis. Conclusion: sDNA testing for multiple markers had strong diagnostic significance for CRC and advanced adenoma in high-risk subjects. Methylation makers had more diagnostic value than mutation markers. © 2013 Pulsus Group Inc. All rights reserved.


Bai Y.,Guangdong Provincial Key Laboratory of Gastroenterology | Bai Y.,Southern Medical University | Qiao W.-G.,Guangdong Provincial Key Laboratory of Gastroenterology | Qiao W.-G.,Southern Medical University | And 9 more authors.
Gastrointestinal Endoscopy | Year: 2014

Background: Natural orifice transluminal endoscopic surgery (NOTES) has been established in animal models and human studies. Objective: The aim of this study was to assess the feasibility and efficacy of applying transgastric NOTES to diagnose patients with ascites of unknown origin. Design: Prospective study. Setting: Two university and teaching hospitals. Patients: Patients with ascites of unknown origin. Interventions: Diagnostic transgastric NOTES. Main Outcome Measurements: Characteristic of ascites cases, conditions of the abdominal cavity, diagnostic accuracy, adverse events, and follow-up time. Results: Transgastric NOTES was performed successfully in 78 patients with ascites of unknown origin, and 72 cases (92.3%) were clearly diagnosed. They included malignant tumors (39 cases), tuberculous peritonitis (28 cases), chronic hepatic inflammation (3 cases), necrotizing lymphadenitis (1 case), and eosinophilic serositis of the small intestine (1 case). In addition, there were 6 nondiagnostic cases, and no severe adverse events were found. Limitations: Nonrandomized control analysis. Conclusion: Transgastric NOTES in combination with biopsy can elucidate the causes of ascites of unknown origin in the majority of cases. Therefore, it is a feasible and effective approach to access the peritoneal cavity and also a valuable modality to detect the cause of diseases with ascites of unknown origin. Copyright © 2014 by the American Society for Gastrointestinal Endoscopy.


Su N.,Southern Medical University | Su N.,Guangdong Provincial key laboratory of Gastroenterology | Peng L.,Southern Medical University | Peng L.,Guangdong Provincial key laboratory of Gastroenterology | And 11 more authors.
Molecular Cancer | Year: 2012

Background and aim: CD24 expression is associated with human colorectal cancer (CRC). Our previous data indicated that CD24 promoted the proliferation and invasion of colorectal cancer cells through the activation of ERK1/2. Since Src family kinases are frequently deregulated in CRC and closely related to the MAPK signaling pathway, we investigated the impact of Lyn, an important member of SFKs, on CD24-induced ERK1/2 activation in CRC.Methods and Results: The interaction of CD24 and Lyn was identified by co-immunoprecipitation (Co-IP) and ectopic expression of CD24-induced Lyn activation. Inhibition of Lyn activation by phosphatase PP2 in SW480CD24cells abrogated CD24-induced invasion. The results of the Co-IP and immunofluorescence assay revealed that overexpression of CD24 enhanced the interaction of Lyn and ERK1/2 and induced the nuclear translocation of Lyn. However, inhibition of Lyn activity attenuated CD24-induced ERK1/2 activation, and depletion of CD24 disrupted Lyn-ERK1/2 interaction. Immunohistochemistry analysis for 202 cases of CRC showed that the expression of both CD24 and Lyn was positively correlated with tumor grade, stage, lymph node and distant metastasis. Patients with lower expression of CD24 or Lyn had a higher survival rate. The Cox multivariate analysis showed that CD24 expression, but not Lyn expression, was an independent prognostic factor of CRC.Conclusions: Our results suggest that Lyn is involved in CD24-induced ERK1/2 activation in CRC. The expression of CD24 is associated with activation of Lyn and ERK1/2, which might be a novel mechanism related to CD24-mediated regulation of CRC development. © 2012 Su et al.; licensee BioMed Central Ltd.


Xiong Y.,Southern Medical University | Xiong Y.,Guangdong Provincial Key Laboratory of Gastroenterology | Wang G.-Z.,Southern Medical University | Wang G.-Z.,Guangdong Provincial Key Laboratory of Gastroenterology | And 8 more authors.
European Journal of Gastroenterology and Hepatology | Year: 2014

OBJECTIVES: This meta-analysis evaluated the stratification powers of four well-studied serum antibodies to microbial antigens [ASCA (anti-Saccharomyces cerevisiae), anti-OmpC (anti-outer-membrane protein C), anti-I2 (anti-Pseudomonas fluorescens-associated sequence I2), and anti-CBir1 (anti-bacterial flagellin)] in characterizing progression of Crohn's disease (CD). METHODS: Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence intervals (CI) for individual antibodies and antibody combination were used to evaluate and compare their stratification powers for CD-related complications and the need for surgery. RESULTS: Eleven studies were included in this meta-analysis. In terms of the outcomes for CD complication and surgery, ASCA had the highest sensitivities at 0.66 (CI 0.63-0.69) for complications and 0.66 (CI 0.63-0.68) for surgery, whereas anti-OmpC had the highest specificities at 0.83 (CI 0.80-0.85) for complications and 0.81 (CI 0.79-0.83) for surgery. Anti-OmpC had the highest DORs at 2.61 (CI 2.16-3.15) for complications and 2.93 (CI 2.48-3.47) for surgery, and a combination of at least two antibodies presented pooled DORs at 2.93 (CI 2.42-3.56) for complications and 3.39 (CI 2.73-4.20) for surgery, superior to any single antibody. CONCLUSION: Anti-OmpC had the highest stratification power among the four antibodies screened for the risk of both complications and surgery in CD patients, and the power became stronger when antibodies were assessed in combination. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Liu C.,Guangdong Provincial Key Laboratory of Gastroenterology | Deng H.,Guangdong Province | Zhang Z.,Guangdong Provincial Key Laboratory of Gastroenterology | Bai L.,Southern Medical University
International Journal of Gerontology | Year: 2012

A bezoar is an accumulation of indigestible exogenous matter in the stomach and the intestine. The clinical diagnosis of bezoar is challenging, and initial radiographs are frequently nondiagnostic. Computed tomography (CT) has become a useful method in diagnosing the presence and cause of small bowel obstruction. The most common CT finding of phytobezoars includes a round or ovoid mass containing mottled gas at the obstructed site. We report one case of small bowel obstruction secondary to bezoar that is composed of mushroom, but without a characteristic bezoar CT imaging. Copyright © 2012, Taiwan Society of Geriatric Emergency & Critical Care Medicine. Published by Elsevier Taiwan LLC. All rights reserved.


Liu J.-F.,Guangdong Provincial Key Laboratory of Gastroenterology | Xie H.-J.,Southern Medical University | Cheng T.-M.,Guangdong Provincial Key Laboratory of Gastroenterology
Asian Pacific Journal of Cancer Prevention | Year: 2013

Objective: To investigate the association between the gene polymorphisms of angiotensin-converting enzyme (ACE) and digestive system cancer risk. Method: A search was performed in Pubmed, Medline, ISI Web of Science and Chinese Biomedical (CBM) databases, covering all studies until Sep 1st, 2013. Statistical analysis was performed by using Revman5.2 and STATA 12.0. Results: A total of 15 case-control studies comprising 2,390 digestive system cancer patients and 9,706 controls were identified. No significant association was found between the I/D polymorphism and digestive cancer risk (OR =0.93, 95%CI = (0.75, 1.16), P =0.53 for DD+DI vs. II). In the subgroup analysis by ethnicity and cancer type, no significant associations were found for the comparison of DD+DI vs. II. Results from other comparative genetic models also indicated a lack of associations between this polymorphism and digestive system cancer risks. Conclusions: This meta-analysis suggested that the ACE D/I polymorphism might not contribute to the risk of digestive system cancer.

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