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Zhao SQ, Zheng HL, Zhong XT, Wang ZY, Su Y, Shi YY. Effects and mechanisms of Helicobacter pylori infection on the occurrence of extra-gastric tumors. World J Gastroenterol 2024; 30:4090-4103. [DOI: 10.3748/wjg.v30.i37.4090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 08/23/2024] [Accepted: 09/12/2024] [Indexed: 09/26/2024] Open
Abstract
Helicobacter pylori (H. pylori) colonizes the human stomach and many studies have discussed the mechanisms of H. pylori infection leading to gastric diseases, including gastric cancer. Additionally, increasing data have shown that the infection of H. pylori may contribute to the development of extra-gastric diseases and tumors. Inflammation, systemic immune responses, microbiome disorders, and hypergastrinemia caused by H. pylori infection are associated with many extra-gastric malignancies. This review highlights recent discoveries; discusses the relationship between H. pylori and various extra-gastric tumors, such as colorectal cancer, lung cancer, cholangiocarcinoma, and gallbladder carcinoma; and explores the mechanisms of extra-gastric carcinogenesis by H. pylori. Overall, these findings refine our understanding of the pathogenic processes of H. pylori, provide guidance for the clinical treatment and management of H. pylori-related extra-gastric tumors, and help improve prognosis.
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Affiliation(s)
- Shi-Qing Zhao
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
- Health Science Center, Peking University, Beijing 100191, China
| | - Hui-Ling Zheng
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Xiao-Tian Zhong
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
- Health Science Center, Peking University, Beijing 100191, China
| | - Zi-Ye Wang
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
- Health Science Center, Peking University, Beijing 100191, China
| | - Yi Su
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
- Health Science Center, Peking University, Beijing 100191, China
| | - Yan-Yan Shi
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
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Dan W, Peng L, Yan B, Li Z, Pan F. Human Microbiota in Esophageal Adenocarcinoma: Pathogenesis, Diagnosis, Prognosis and Therapeutic Implications. Front Microbiol 2022; 12:791274. [PMID: 35126331 PMCID: PMC8815000 DOI: 10.3389/fmicb.2021.791274] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 12/23/2021] [Indexed: 11/29/2022] Open
Abstract
Esophageal adenocarcinoma (EAC) is one of the main subtypes of esophageal cancer. The incidence rate of EAC increased progressively while the 5-year relative survival rates were poor in the past two decades. The mechanism of EAC has been studied extensively in relation to genetic factors, but less so with respect to human microbiota. Currently, researches about the relationship between EAC and the human microbiota is a newly emerging field of study. Herein, we present the current state of knowledge linking human microbiota to esophageal adenocarcinoma and its precursor lesion—gastroesophageal reflux disease and Barrett’s esophagus. There are specific human bacterial alternations in the process of esophageal carcinogenesis. And bacterial dysbiosis plays an important role in the process of esophageal carcinogenesis via inflammation, microbial metabolism and genotoxicity. Based on the human microbiota alternation in the EAC cascade, it provides potential microbiome-based clinical application. This review is focused on novel targets in prevention, diagnosis, prognosis, and therapy for esophageal adenocarcinoma.
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Affiliation(s)
- Wanyue Dan
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
- Medical School of Nankai University, Tianjin, China
| | - Lihua Peng
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Bin Yan
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Zhengpeng Li
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Fei Pan
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
- *Correspondence: Fei Pan,
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Du YL, Duan RQ, Duan LP. Helicobacter pylori infection is associated with reduced risk of Barrett's esophagus: a meta-analysis and systematic review. BMC Gastroenterol 2021; 21:459. [PMID: 34876031 PMCID: PMC8650239 DOI: 10.1186/s12876-021-02036-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 11/16/2021] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Helicobacter pylori (Hp) is a class I carcinogen in gastric carcinogenesis, but its role in Barrett's esophagus (BE) is unknown. Therefore, we aimed to explore the possible relationship. METHODS We reviewed observational studies published in English until October 2019. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for included studies. RESULTS 46 studies from 1505 potential citations were eligible for inclusion. A significant inverse relationship with considerable heterogeneity was found between Hp (OR = 0.70; 95% CI, 0.51-0.96; P = 0.03) and BE, especially the CagA-positive Hp strain (OR = 0.28; 95% CI, 0.15-0.54; P = 0.0002). However, Hp infection prevalence was not significantly different between patients with BE and the gastroesophageal reflux disease (GERD) control (OR = 0.99; 95% CI, 0.82-1.19; P = 0.92). Hp was negatively correlated with long-segment BE (OR = 0.47; 95% CI, 0.25-0.90; P = 0.02) and associated with a reduced risk of dysplasia. However, Hp had no correlated with short-segment BE (OR = 1.11; 95% CI, 0.78-1.56; P = 0.57). In the present infected subgroup, Hp infection prevalence in BE was significantly lower than that in controls (OR = 0.69; 95% CI, 0.54-0.89; P = 0.005); however, this disappeared in the infection history subgroup (OR = 0.88; 95% CI, 0.43-1.78; P = 0.73). CONCLUSIONS Hp, especially the CagA-positive Hp strain, and BE are inversely related with considerable heterogeneity, which is likely mediated by a decrease in GERD prevalence, although this is not observed in the absence of current Hp infection.
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Affiliation(s)
- Yan-Lin Du
- Department of Gastroenterology, Peking University Third Hospital, No. 49 North Garden Rd., Haidian District, Beijing, 100191, China
| | - Ru-Qiao Duan
- Department of Gastroenterology, Peking University Third Hospital, No. 49 North Garden Rd., Haidian District, Beijing, 100191, China
| | - Li-Ping Duan
- Department of Gastroenterology, Peking University Third Hospital, No. 49 North Garden Rd., Haidian District, Beijing, 100191, China.
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Riahi Rad Z, Riahi Rad Z, Goudarzi H, Goudarzi M, Mahmoudi M, Yasbolaghi Sharahi J, Hashemi A. MicroRNAs in the interaction between host-bacterial pathogens: A new perspective. J Cell Physiol 2021; 236:6249-6270. [PMID: 33599300 DOI: 10.1002/jcp.30333] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 02/04/2021] [Accepted: 02/08/2021] [Indexed: 12/17/2022]
Abstract
Gene expression regulation plays a critical role in host-pathogen interactions, and RNAs function is essential in this process. miRNAs are small noncoding, endogenous RNA fragments that affect stability and/or translation of mRNAs, act as major posttranscriptional regulators of gene expression. miRNA is involved in regulating many biological or pathological processes through targeting specific mRNAs, including development, differentiation, apoptosis, cell cycle, cytoskeleton organization, and autophagy. Deregulated microRNA expression is associated with many types of diseases, including cancers, immune disturbances, and infection. miRNAs are a vital section of the host immune response to bacterial-made infection. Bacterial pathogens suppress host miRNA expression for their benefit, promoting survival, replication, and persistence. The role played through miRNAs in interaction with host-bacterial pathogen has been extensively studied in the past 10 years, and knowledge about these staggering molecules' function can clarify the complicated and ambiguous interactions of the host-bacterial pathogen. Here, we review how pathogens prevent the host miRNA expression. We briefly discuss emerging themes in this field, including their role as biomarkers in identifying bacterial infections, as part of the gut microbiota, on host miRNA expression.
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Affiliation(s)
- Zohreh Riahi Rad
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Riahi Rad
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Goudarzi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Goudarzi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Mahmoudi
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Javad Yasbolaghi Sharahi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Hashemi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Association Between Helicobacter pylori Infection and Short-segment/Long-segment Barrett's Esophagus in a Japanese Population: A Large Cross-Sectional Study. J Clin Gastroenterol 2020; 54:439-444. [PMID: 31524650 DOI: 10.1097/mcg.0000000000001264] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
GOAL The goal of this study was to investigate the relationship between Helicobacter pylori (H. pylori) infection and short-segment and long-segment Barrett's esophagus (SSBE and LSBE). BACKGROUND H. pylori infection is reported to be inversely associated with Barrett's esophagus (BE) in western countries. However, the impact of BE segment length on the association between BE and H. pylori infection has scarcely been investigated. MATERIALS AND METHODS The study subjects were 41,065 asymptomatic Japanese individuals who took medical surveys between October 2010 and September 2017. Using this large database of healthy Japanese subjects, we investigated the association between H. pylori infection and SSBE/LSBE. We used multivariable logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Among the study subjects, 36,615 were eligible for the analysis. H. pylori seropositivity was significantly associated with a lower rate of LSBE (OR: 0.42; 95% CI: 0.16-0.91) and a higher rate of SSBE (OR: 1.66; 95% CI: 1.56-1.78) after multivariate adjustment. In the subgroup analysis, H. pylori seropositivity was significantly associated with a high rate of SSBE in subjects without reflux esophagitis (RE) (OR: 1.73; 95% CI: 1.61-1.85). However, H. pylori seropositivity was not associated with SSBE in subjects with RE (OR: 1.07; 95% CI: 0.84-1.37). CONCLUSION In a Japanese population, H. pylori infection was inversely associated with LSBE but significantly associated with SSBE only in subjects without RE. H. pylori may be a risk factor for SSBE, especially in individuals without RE.
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Aguilar C, Mano M, Eulalio A. Multifaceted Roles of microRNAs in Host-Bacterial Pathogen Interaction. Microbiol Spectr 2019; 7:10.1128/microbiolspec.bai-0002-2019. [PMID: 31152522 PMCID: PMC11026079 DOI: 10.1128/microbiolspec.bai-0002-2019] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Indexed: 02/06/2023] Open
Abstract
MicroRNAs (miRNAs) are a well-characterized class of small noncoding RNAs that act as major posttranscriptional regulators of gene expression. Accordingly, miRNAs have been associated with a wide range of fundamental biological processes and implicated in human diseases. During the past decade, miRNAs have also been recognized for their role in the complex interplay between the host and bacterial pathogens, either as part of the host response to counteract infection or as a molecular strategy employed by bacteria to subvert host pathways for their own benefit. Importantly, the characterization of downstream miRNA targets and their underlying mechanisms of action has uncovered novel molecular factors and pathways relevant to infection. In this article, we review the current knowledge of the miRNA response to bacterial infection, focusing on different bacterial pathogens, including Salmonella enterica, Listeria monocytogenes, Mycobacterium spp., and Helicobacter pylori, among others.
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Affiliation(s)
- Carmen Aguilar
- Host RNA Metabolism Group, Institute for Molecular Infection Biology (IMIB), University of Würzburg, Würzburg, Germany
| | - Miguel Mano
- Functional Genomics and RNA-Based Therapeutics Group, Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal
| | - Ana Eulalio
- Host RNA Metabolism Group, Institute for Molecular Infection Biology (IMIB), University of Würzburg, Würzburg, Germany
- RNA & Infection Group, Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal
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Teng G, Dai Y, Chu Y, Li J, Zhang H, Wu T, Shuai X, Wang W. Helicobacter pylori induces caudal-type homeobox protein 2 and cyclooxygenase 2 expression by modulating microRNAs in esophageal epithelial cells. Cancer Sci 2018; 109:297-307. [PMID: 29215765 PMCID: PMC5797820 DOI: 10.1111/cas.13462] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Revised: 11/02/2017] [Accepted: 11/16/2017] [Indexed: 12/17/2022] Open
Abstract
Dysregulation of microRNAs (miRNAs) has been linked to virulence factors of Helicobacter pylori. The role of H. pylori in esophageal disease has not been clearly defined. We previously reported that H. pylori esophageal colonization promotes the incidence of Barrett's esophagus and esophageal adenocarcinoma in vivo. Here, we studied the direct effects of H. pylori on the transformation of esophageal epithelial cells, with particular focus on whether H. pylori exerts its effects by modulating miRNAs and their downstream target genes. The normal human esophageal cell line HET‐1A was chronically exposed to H. pylori extract and/or acidified deoxycholic acid for up to 36 weeks. The miRNA profiles of the esophageal epithelial cells associated with H. pylori infection were determined by microarray analysis. We found that chronic H. pylori exposure promoted acidified deoxycholic acid‐induced morphological changes in HET‐1A cells, along with aberrant overexpression of intestinal metaplasia markers and tumorigenic factors, including caudal‐type homeobox protein 2 (CDX2), mucin 2, and cyclooxygenase 2 (COX2). Helicobacter pylori modified the miRNA profiles of esophageal epithelial cells, particularly aberrant silencing of miR‐212‐3p and miR‐361‐3p. Moreover, in biopsies from Barrett's esophagus patients, esophageal H. pylori colonization was associated with a significant decrease in miR‐212‐3p and miR‐361‐3p expression. Furthermore, we identified COX2 as a target of miR‐212‐3p, and CDX2 as a target of miR‐361‐3p. Helicobacter pylori infection of esophageal epithelial cells was associated with miRNA‐mediated upregulation of oncoprotein CDX2 and COX2. Our observations provide new evidence about the molecular mechanisms underlying the association between H. pylori infection and esophageal carcinogenesis.
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Affiliation(s)
- Guigen Teng
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Yun Dai
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Yunxiang Chu
- Department of Gastroenterology, Peking University First Hospital, Beijing, China.,Department of Gastroenterology, China Meitan General Hospital, Beijing, China
| | - Jing Li
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Hongchen Zhang
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Ting Wu
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Xiaowei Shuai
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Weihong Wang
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
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Lin B, Xie F, Xiao Z, Hong X, Tian L, Liu K. Basal progenitor cells bridge the development, malignant cancers, and multiple diseases of esophagus. J Cell Physiol 2017; 233:3855-3866. [PMID: 28777465 DOI: 10.1002/jcp.26136] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Accepted: 08/03/2017] [Indexed: 12/19/2022]
Abstract
The esophagus is a pivotal organ originating from anterior foregut that links the mouth and stomach. Moreover, its development involves precise regulation of multiple signal molecules and signal transduction pathways. After abnormal regulation of these molecules in the basal cells of the esophagus occurs, multiple diseases, including esophageal atresia with or without tracheoesophageal fistula, Barrett esophagus, gastroesophageal reflux, and eosinophilic esophagitis, will take place as a result. Furthermore, expression changes of signal molecules or signal pathways in basal cells and the microenvironment around basal cells both can initiate the switch of malignant transformation. In this review, we highlight the molecular events underlying the transition of normal development to multiple esophageal diseases. Additionally, the animal models of esophageal development and related diseases, challenges, and strategies are extensively discussed.
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Affiliation(s)
- Baoshun Lin
- Institute for Laboratory Medicine, Fuzhou General Hospital, PLA, Fuzhou, Fujian, P. R. China
| | - Fuan Xie
- Institute for Laboratory Medicine, Fuzhou General Hospital, PLA, Fuzhou, Fujian, P. R. China
| | - Zhangwu Xiao
- Emergency Department of the 476 Hospital, Fuzhou General Hospital, PLA, Fuzhou, Fujian, P. R. China
| | - Xiaoqian Hong
- Dong fang Hospital, Xiamen University, Fuzhou, Fujian, P. R. China
| | - Liming Tian
- Dong fang Hospital, Xiamen University, Fuzhou, Fujian, P. R. China
| | - Kuancan Liu
- Institute for Laboratory Medicine, Fuzhou General Hospital, PLA, Fuzhou, Fujian, P. R. China.,Dong fang Hospital, Xiamen University, Fuzhou, Fujian, P. R. China.,Department of Medicine, Columbia University Medical Center, New York, New York
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10
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Herrera-Goepfert R, Oñate-Ocaña LF, Mosqueda-Vargas JL, Herrera LA, Castro C, Mendoza J, González-Barrios R. Methylation of DAPK and THBS1 genes in esophageal gastric-type columnar metaplasia. World J Gastroenterol 2016; 22:4567-4575. [PMID: 27182166 PMCID: PMC4858638 DOI: 10.3748/wjg.v22.i18.4567] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Revised: 01/19/2016] [Accepted: 01/30/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore methylation of DAPK, THBS1, CDH-1, and p14 genes, and Helicobacter pylori (H. pylori) status in individuals harboring esophageal columnar metaplasia.
METHODS: Distal esophageal mucosal samples obtained by endoscopy and histologically diagnosed as gastric-type (non-specialized) columnar metaplasia, were studied thoroughly. DNA was extracted from paraffin blocks, and methylation status of death-associated protein kinase (DAPK), thrombospondin-1 (THBS1), cadherin-1 (CDH1), and p14 genes, was examined using a methyl-sensitive polymerase chain reaction (MS-PCR) and sodium bisulfite modification protocol. H. pylori cagA status was determined by PCR.
RESULTS: In total, 68 subjects (33 females and 35 males), with a mean age of 52 years, were included. H. pylori cagA positive was present in the esophageal gastric-type metaplastic mucosa of 18 individuals. DAPK, THSB1, CDH1, and p14 gene promoters were methylated by MS-PCR in 40 (58.8%), 33 (48.5%), 46 (67.6%), and 23 (33.8%) cases of the 68 esophageal samples. H. pylori status was associated with methylation of DAPK (P = 0.003) and THBS1 (P = 0.019).
CONCLUSION: DNA methylation occurs in cases of gastric-type (non-specialized) columnar metaplasia of the esophagus, and this modification is associated with H. pylori cagA positive infection.
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Chu YX, Wang WH, Dai Y, Teng GG, Wang SJ. Esophageal Helicobacter pylori colonization aggravates esophageal injury caused by reflux. World J Gastroenterol 2014; 20:15715-15726. [PMID: 25400455 PMCID: PMC4229536 DOI: 10.3748/wjg.v20.i42.15715] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2014] [Revised: 04/22/2014] [Accepted: 05/14/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate esophageal Helicobacter pylori (H. pylori) colonization on esophageal injury caused by reflux and the related mechanisms.
METHODS: An esophagitis model, with acid and bile reflux, was surgically produced in male rats. The rats were randomly divided into either: (1) an esophagogastroduodenal anastomosis (EGDA) group; (2) an EGDA with H. pylori infection group; (3) a pseudo-operation with H. pylori infection group; or (4) a pseudo-operation group. All rats were kept for 36 wk. Based on the location of H. pylori colonization, the EGDA rats with H. pylori infection were subdivided into those with concomitant esophageal H. pylori colonization or those with only gastric H. pylori colonization. The esophageal injuries were evaluated grossly and microscopically. The expressions of CDX2 and MUC2 were determined by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. Ki-67 antigen expression was determined by immunohistochemistry. The mRNA levels of cyclin D1, c-Myc, Bax and Bcl-2 were determined by RT-PCR. Cell apoptosis was evaluated using the TdT-mediated dUTP nick-end labeling method.
RESULTS: Esophagitis, Barrett’s esophagus (BE), and esophageal adenocarcinoma (EAC) developed in rats that underwent EGDA. When comparing rats with EGDA and concomitant esophageal H. pylori colonization to EGDA-only rats, the severity of injury (87.9 ± 5.2 vs 77.2 ± 8.6, macroscopically, 92.5 ± 8.0 vs 83.8 ± 5.5, microscopically, both P < 0.05) and the incidences of BE (80.0% vs 33.3%, P = 0.055) and EAC (60.0% vs 11.1%, P < 0.05) were increased. These increases were associated with upregulation of CDX2 and MUC2 mRNA (10.1 ± 5.4 vs 3.0 ± 2.9, 8.4 ± 4.6 vs 2.0 ± 3.2, respectively, Ps < 0.01) and protein (8.1 ± 2.3 vs 3.3 ± 3.1, 7.3 ± 4.0 vs 1.8 ± 2.7, respectively, all P < 0.05). The expression of Ki-67 (8.9 ± 0.7 vs 6.0 ± 1.7, P < 0.01) and the presence of apoptotic cells (8.3 ± 1.1 vs 5.3 ± 1.7, P < 0.01) were also increased significantly in rats with EGDA and concomitant esophageal H. pylori colonization compared with rats with EGDA only. The mRNA levels of cyclin D1 (5.8 ± 1.9 vs 3.4 ± 1.3, P < 0.01), c-Myc (6.4 ± 1.7 vs 3.7 ± 1.2, P < 0.01), and Bax (8.6 ± 1.6 vs 5.1 ± 1.3, P < 0.01) were significantly increased, whereas the mRNA level of Bcl-2 (0.6 ± 0.3 vs 0.8 ± 0.3, P < 0.01) was significantly reduced in rats with EGDA and concomitant esophageal H. pylori colonization compared with rats with EGDA only.
CONCLUSION: Esophageal H. pylori colonization increases esophagitis severity, and facilitates the development of BE and EAC with the augmentation of cell proliferation and apoptosis in esophageal mucosa.
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Hsu WY, Lin CH, Lin CC, Sung FC, Hsu CP, Kao CH. The relationship between Helicobacter pylori and cancer risk. Eur J Intern Med 2014; 25:235-40. [PMID: 24485950 DOI: 10.1016/j.ejim.2014.01.009] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2013] [Revised: 01/03/2014] [Accepted: 01/11/2014] [Indexed: 12/18/2022]
Abstract
OBJECTIVES This study investigated the correlation between Helicobacter pylori (HP) and cancer risk. We compared the age, sex, and comorbidity of cancer patients both infected and not infected by HP. METHODS In this study, we compared a comparison cohort (N=24,088) and an HP cohort (N=6022), both taken from the NHI database. We performed a statistical analysis with the multivariable Cox proportional model to estimate the risk of developing cancer for a comparison and the HP cohort. RESULTS Our results showed that the proportion of peptic ulcers in the HP cohort was nearly 4 times higher than that in the comparison cohort. The HP cohort was significantly associated with increased colorectal (HR=1.73, 95% CI=1.08-2.77), stomach (HR=5.21, 95% CI=2.46-11.05) and pancreatic (HR=2.77, 95% CI=1.04-7.39) cancer risks compared to the comparison cohort. In addition, the cancer risk in the HP cohort was considerably higher than that in the comparison cohort when hypertension was absent in both cohorts. CONCLUSIONS In this study, we proposed a method to investigate the correlation between HP infection and cancer risk. We found that HP infection is associated with the development of colorectal, stomach, and pancreatic cancers, and could thus be an independent carcinogenic risk factor.
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Affiliation(s)
- Wan-Yun Hsu
- Comprehensive Cancer Center, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Nursing, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chih-Hung Lin
- Division of Thoracic Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Che-Chen Lin
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
| | - Fung-Chang Sung
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Clinical Medical Science, School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan
| | - Chung-Ping Hsu
- Division of Thoracic Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, National Yang Ming University, Taipei, Taiwan.
| | - Chia-Hung Kao
- Graduate Institute of Clinical Medical Science, School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; Department of Nuclear Medicine, PET Center, China Medical University Hospital, Taichung, Taiwan.
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13
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Watari J, Oshima T, Fukui H, Tomita T, Miwa H. Carcinogenesis of Barrett's esophagus: a review of the clinical literature. Clin J Gastroenterol 2013; 6:399-414. [PMID: 26182128 DOI: 10.1007/s12328-013-0412-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2013] [Accepted: 07/25/2013] [Indexed: 11/25/2022]
Abstract
Barrett's esophagus (BE) is a premalignant condition of esophageal adenocarcinoma (EAC). Although the incidence of BE has risen rapidly in the West, it is rare in Asia despite a recent increase in the prevalence of gastroesophageal reflux disease. Controversies over the definition of BE are presented because most cases show short-segment BE, especially ultra-short BE, in Asia. Here we review possible risk factors for the development of EAC, particularly possible roles of ethnicity, specialized intestinal metaplasia (SIM), BE length, and environmental factors, such as Helicobacter pylori infection and obesity. Additionally, we summarize recent studies on the effect of chemoprevention including proton pump inhibitors, nonsteroidal anti-inflammatory drugs or aspirin in order to reduce the risk of neoplastic progression in BE patients. Although substantial knowledge of risk factors of dysplasia/EAC in BE is shown, the risk for neoplastic development may be influenced by geographic variation, study population, the presence or absence of SIM or dysplasia at baseline, and the small number of BE patients investigated. Recently, the efficiency of surveillance for BE patients has been discussed from the standpoint of cost-effectiveness. It may be too difficult to draw conclusions because no randomized clinical trials of BE surveillance have been performed.
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Affiliation(s)
- Jiro Watari
- Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
| | - Tadayuki Oshima
- Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Hirokazu Fukui
- Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Toshihiko Tomita
- Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Hiroto Miwa
- Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
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14
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Iwaya Y, Hasebe O, Koide N, Kitahara K, Suga T, Shinji A, Muraki T, Yokosawa S, Yamada S, Arakura N, Tanaka E, Nakayama J. Reduced expression of αGlcNAc in Barrett's oesophagus adjacent to Barrett's adenocarcinoma--a possible biomarker to predict the malignant potential of Barrett's oesophagus. Histopathology 2013; 64:536-46. [PMID: 24117499 DOI: 10.1111/his.12296] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2013] [Accepted: 09/23/2013] [Indexed: 12/17/2022]
Abstract
AIMS Gastric gland mucin contains O-glycans exhibiting terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc). Recently we demonstrated that mice deficient in αGlcNAc in gastric gland mucin develop gastric adenocarcinoma spontaneously, indicating that αGlcNAc is a tumour suppressor for gastric cancer. However, the role of αGlcNAc in Barrett's oesophagus (BO) remains unknown. In this study, we investigated whether reduced αGlcNAc expression in BO is associated with development of Barrett's adenocarcinoma (BAC). METHODS AND RESULTS Thirty-five BO lesions adjacent to BAC were examined by immunohistochemistry for αGlcNAc, MUC6 and CDX2. As controls, 35 BO lesions without BAC obtained from patients with oesophageal squamous cell carcinoma were also analysed. Expression of αGlcNAc relative to its scaffold MUC6 in BO adjacent to BAC was reduced significantly compared to control BO. Decreased αGlcNAc expression in BO adjacent to BAC was particularly significant in patients with smaller tumour size (<20 mm) and minimal invasion of tumour cells to the superficial muscularis mucosae. There was also a significant inverse correlation between αGlcNAc and CDX2 expression in BO adjacent to BAC. CONCLUSIONS Decreased expression of αGlcNAc compared with MUC6 in BO is a possible hallmark in predicting BAC development.
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Affiliation(s)
- Yugo Iwaya
- Department of Molecular Pathology, Shinshu University Graduate School of Medicine, Matsumoto, Japan; Department of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan
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15
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Abstract
These investigators found no significant evidence suggesting a potential role of Helicobacter pylori infection in the development of erosive esophagitis. Background and Objectives: Helicobacter pylori infection represents one of the most common and medically prominent infections worldwide. Gastroesophageal reflux disease (GERD) has a multifactorial etiology. The nature of the relationship between Helicobacter pylori infection (HP) and reflux esophagitis is still not clear. This study is designed to find the influence of HP on GERD. Patients and Methods: The study was conducted retrospectively at Sakarya Newcity Hospital between January 2006 and January 2009. Data were collected on patient's age, sex, weight, the grade of GERD and the severity of HP. Results: There were 1,307 women and 1,135 men in this review with a mean age of 39,54 (range, 17 to 70) years. Helicobacter pylori positive (1 to 3 severity) was frequently seen in patients with GERD. A statistically significant relationship was found between HP positivity and the grade of GERD. The Helicobacter pylori infection (1 to 3 severity) was found in 1,437 (82.5%) of patients with GERD in our series. Conclusions: Controversy still exists about the association between GERD and HP infection. Based on our findings, significant evidence suggests the potential role of HP infection in the development of GERD. Also, the current data provide sufficient evidence to define the relationship between GERD and HP infection.
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Affiliation(s)
- Fatin R Polat
- Department of Surgery, New City State Hospital, Sakarya, Turkey.
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16
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Wang SJ, Wang WH, Teng GG, Dai Y, Chu YX, Li J. Effect of Helicobacter pylori infection on esophageal epithelial cells in vitro. Shijie Huaren Xiaohua Zazhi 2012; 20:3625-3631. [DOI: 10.11569/wcjd.v20.i36.3625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of Helicobacter pylori (H. pylori) exposure on esophageal cell line OE33 in vitro.
METHODS: Human esophageal adenocarcinoma cell line OE33 was cultured and treated with 200 mmol/L acidified deoxycholic acid (pH 6.0) or infected with H. pylori 26695. After treatment or infection, cell viability was tested by CCK-8 assay; cell apoptosis was determined by flow cytometric analysis with Annexin V-FITC/7-AAD; the mRNA expression of CDX2 and MUC2 was assessed by real time-PCR; nuclear factor-kB (NF-kB)-associated proteins were examined by Western blot; and the DNA binding activity of NF-kB was evaluated by electrophoretic mobility shift assay (EMSA).
RESULTS: The viability of OE33 cells was reduced significantly after treatment with acidified deoxycholic acid or infection with H. pylori compared with negative controls (both P < 0.01). Treatment with acidified deoxycholic acid or infection with H. pylori induced apoptosis and increased the mRNA expression of CDX2 and MUC2 (all P < 0.01). Both H. pylori infection and treatment with acidified deoxycholic acid enhanced the DNA binding activity of NF-kB and the protein expression of phosphorylated IkBa and P65 in esophageal epithelial cells.
CONCLUSION: H. pylori infection reduces cell viability, induces apoptosis, and increases the expression of CDX2 and MUC2 and the activation of NF-kB in esophageal epithelial cells.
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17
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Kountouras J, Chatzopoulos D, Zavos C, Polyzos SA, Giartza-Taxidou E, Vardaka E, Molyvas E, Kouklakis G, Tsiaousi E, Klonizakis P. Helicobacter pylori infection might contribute to esophageal adenocarcinoma progress in subpopulations with gastroesophageal reflux disease and Barrett's esophagus. Helicobacter 2012; 17:402-3. [PMID: 22967125 DOI: 10.1111/j.1523-5378.2012.00963.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
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18
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Reply to Letter to the Editor: Re: Comparison of COX-2, Ki-67, and BCL-2 expression in normal esophageal mucosa, Barrett’s esophagus, dysplasia, and adenocarcinoma with postablation mucosa and implications for ablative therapies (Online First). Surg Endosc 2012; 26:291-2. [DOI: 10.1007/s00464-011-1842-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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19
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Kountouras J, Chatzopoulos D, Zavos C, Deretzi G, Polyzos SA, Gavalas E, Klonizakis P, Vardaka E, Katsinelos P, Stergiopoulos C, Moschos J, Giartza-Taxidou E. Ki-67 and Bax expression in esophageal mucosa might have implications in ablative therapies for Barrett’s esophagus, dysplasia, and adenocarcinoma. Surg Endosc 2012; 26:283-4. [DOI: 10.1007/s00464-011-1864-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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