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Duan Y, Xu Y, Dou Y, Xu D. Helicobacter pylori and gastric cancer: mechanisms and new perspectives. J Hematol Oncol 2025; 18:10. [PMID: 39849657 PMCID: PMC11756206 DOI: 10.1186/s13045-024-01654-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 12/23/2024] [Indexed: 01/25/2025] Open
Abstract
Gastric cancer remains a significant global health challenge, with Helicobacter pylori (H. pylori) recognized as a major etiological agent, affecting an estimated 50% of the world's population. There has been a rapidly expanding knowledge of the molecular and pathogenetic mechanisms of H. pylori over the decades. This review summarizes the latest research advances to elucidate the molecular mechanisms underlying the H. pylori infection in gastric carcinogenesis. Our investigation of the molecular mechanisms reveals a complex network involving STAT3, NF-κB, Hippo, and Wnt/β-catenin pathways, which are dysregulated in gastric cancer caused by H. pylori. Furthermore, we highlight the role of H. pylori in inducing oxidative stress, DNA damage, chronic inflammation, and cell apoptosis-key cellular events that pave the way for carcinogenesis. Emerging evidence also suggests the effect of H. pylori on the tumor microenvironment and its possible implications for cancer immunotherapy. This review synthesizes the current knowledge and identifies gaps that warrant further investigation. Despite the progress in our previous knowledge of the development in H. pylori-induced gastric cancer, a comprehensive investigation of H. pylori's role in gastric cancer is crucial for the advancement of prevention and treatment strategies. By elucidating these mechanisms, we aim to provide a more in-depth insights for the study and prevention of H. pylori-related gastric cancer.
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Affiliation(s)
- Yantao Duan
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yonghu Xu
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yi Dou
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Dazhi Xu
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
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Bhattacharjee A, Sahoo OS, Sarkar A, Bhattacharya S, Chowdhury R, Kar S, Mukherjee O. Infiltration to infection: key virulence players of Helicobacter pylori pathogenicity. Infection 2024; 52:345-384. [PMID: 38270780 DOI: 10.1007/s15010-023-02159-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 12/13/2023] [Indexed: 01/26/2024]
Abstract
PURPOSE This study aims to comprehensively review the multifaceted factors underlying the successful colonization and infection process of Helicobacter pylori (H. pylori), a prominent Gram-negative pathogen in humans. The focus is on elucidating the functions, mechanisms, genetic regulation, and potential cross-interactions of these elements. METHODS Employing a literature review approach, this study examines the intricate interactions between H. pylori and its host. It delves into virulence factors like VacA, CagA, DupA, Urease, along with phase variable genes, such as babA, babC, hopZ, etc., giving insights about the bacterial perspective of the infection The association of these factors with the infection has also been added in the form of statistical data via Funnel and Forest plots, citing the potential of the virulence and also adding an aspect of geographical biasness to the virulence factors. The biochemical characteristics and clinical relevance of these factors and their effects on host cells are individually examined, both comprehensively and statistically. RESULTS H. pylori is a Gram-negative, spiral bacterium that successfully colonises the stomach of more than half of the world's population, causing peptic ulcers, gastric cancer, MALT lymphoma, and other gastro-duodenal disorders. The clinical outcomes of H. pylori infection are influenced by a complex interplay between virulence factors and phase variable genes produced by the infecting strain and the host genetic background. A meta-analysis of the prevalence of all the major virulence factors has also been appended. CONCLUSION This study illuminates the diverse elements contributing to H. pylori's colonization and infection. The interplay between virulence factors, phase variable genes, and host genetics determines the outcome of the infection. Despite biochemical insights into many factors, their comprehensive regulation remains an understudied area. By offering a panoramic view of these factors and their functions, this study enhances understanding of the bacterium's perspective, i.e. H. pylori's journey from infiltration to successful establishment within the host's stomach.
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Affiliation(s)
- Arghyadeep Bhattacharjee
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, 713209, India
- Department of Microbiology, Kingston College of Science, Beruanpukuria, Barasat, West Bengal, 700219, India
| | - Om Saswat Sahoo
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, 713209, India
| | - Ahana Sarkar
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, 713209, India
| | - Saurabh Bhattacharya
- Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, The Hebrew University of Jerusalem, P.O.B. 12272, 9112001, Jerusalem, Israel
| | - Rukhsana Chowdhury
- School of Biological Sciences, RKM Vivekananda Educational and Research Institute Narendrapur, Kolkata, India
| | - Samarjit Kar
- Department of Mathematics, National Institute of Technology Durgapur, Durgapur, West Bengal, 713209, India
| | - Oindrilla Mukherjee
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, 713209, India.
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Ding SZ, Du YQ, Lu H, Wang WH, Cheng H, Chen SY, Chen MH, Chen WC, Chen Y, Fang JY, Gao HJ, Guo MZ, Han Y, Hou XH, Hu FL, Jiang B, Jiang HX, Lan CH, Li JN, Li Y, Li YQ, Liu J, LI YM, Lyu B, Lu YY, Miao YL, Nie YZ, Qian JM, Sheng JQ, Tang CW, Wang F, Wang HH, Wang JB, Wang JT, Wang JP, Wang XH, Wu KC, Xia XZ, Xie WF, Xie Y, Xu JM, Yang CQ, Yang GB, Yuan Y, Zeng ZR, Zhang BY, Zhang GY, Zhang GX, Zhang JZ, Zhang ZY, Zheng PY, Zhu Y, Zuo XL, Zhou LY, Lyu NH, Yang YS, Li ZS. Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition). Gut 2022; 71:238-253. [PMID: 34836916 PMCID: PMC8762011 DOI: 10.1136/gutjnl-2021-325630] [Citation(s) in RCA: 107] [Impact Index Per Article: 35.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 11/03/2021] [Indexed: 02/05/2023]
Abstract
OBJECTIVE Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.
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Affiliation(s)
- Song-Ze Ding
- Department of Gastroenterology and Hepatology, People's Hospital, Zhengzhou University, Zhengzhou, Henan, China .,Department of Gastroenterology and Hepatology, People's Hospital, Henan University, Kaifeng, Henan, China
| | - Yi-Qi Du
- Gastroenterology Division, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Hong Lu
- GI Division, Renji Hospital, Shanghai Institution of Digestive Diseas, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei-Hong Wang
- Department of Gastroenterology and Hepatology, Peking University First Hospital, Beijing, China
| | - Hong Cheng
- Department of Gastroenterology and Hepatology, Peking University First Hospital, Beijing, China
| | - Shi-Yao Chen
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Min-Hu Chen
- Division of Gastroenterology and Hepatology, Sun Yat-Sen University First Affiliated Hospital, Guangzhou, Guangdong, China
| | - Wei-Chang Chen
- Department of Gastroenterology and Hepatology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Ye Chen
- Department of Gastroenterology and Hepatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Jing-Yuan Fang
- Renji Hospital, Gastroenterology Division, Shanghai Jiao Tong University, Shanghai, China
| | - Heng-Jun Gao
- Department of Gastroenterology and Hepatology, School of Medicine, Tongji University, Shanghai, China
| | - Ming-Zhou Guo
- Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, China
| | - Ying Han
- Department of Gastroenterology and Hepatology, The Seventh Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Xiao-Hua Hou
- Department of Gastroenterology and Hepatology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Fu-Lian Hu
- Department of Gastroenterology and Hepatology, Peking University First Hospital, Beijing, China
| | - Bo Jiang
- Department of Gastroenterology and Hepatology, Changgeng Hospital, Tsinghua University, Beijing, China
| | - Hai-Xing Jiang
- Department of Gastroenterology and Hepatology, First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China
| | - Chun-Hui Lan
- Department of Gastroenterology and Hepatology, Daping Hospital, Army Medical University, Chongqing, China
| | - Jing-Nan Li
- Department of Gastroenterology and Hepatology, Peking Union Medical College Hospital, Beijing, China
| | - Yan Li
- Department of Gastroenterology and Hepatology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yan-Qing Li
- Department of Gastroenterology and Hepatology, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Jie Liu
- Department of Gastroenterology and Hepatology, Huashan Hospital, Fudan University, Shanghai, China
| | - You-Ming LI
- Department of Gastroenterology and Hepatology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Bin Lyu
- Department of Gastroenterology and Hepatology, First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - You-Yong Lu
- Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital, Beijing, China
| | - Ying-Lei Miao
- Department of Gastroenterology and Hepatology, First Affilliated Hospital, Kunming Medical University, Kunming, Yunnan, China
| | - Yong-Zhan Nie
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Air Force Medical University, Xian, Shaanxi, China
| | - Jia-Ming Qian
- Department of Gastroenterology and Hepatology, Peking Union Medical College Hospital, Beijing, China
| | - Jian-Qiu Sheng
- Department of Gastroenterology, The Seventh Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Cheng-Wei Tang
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Fen Wang
- Department of Gastroenterology and Hepatology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China,Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan, China
| | - Hua-Hong Wang
- Department of Gastroenterology and Hepatology, Peking University First Hospital, Beijing, China
| | - Jiang-Bin Wang
- Department of Gastroenterology and Hepatology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Jing-Tong Wang
- Department of Gastroenterology and Hepatology, Peking University Third Hospital, Beijing, China
| | - Jun-Ping Wang
- Department of Gastroenterology and Hepatology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Xue-Hong Wang
- Department of Gastroenterology and Hepatology, Qinghai University Hospital, Qinghai University, Xining, Qinghai, China
| | - Kai-Chun Wu
- Department of Gastroenterology and Hepatology, Xijing Hospital, Air Force Medical University, Xian, Shaanxi, China
| | - Xing-Zhou Xia
- Department of Gastroenterology and Hepatology, The Fifth Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China
| | - Wei-Fen Xie
- Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Yong Xie
- Department of Gastroenterology and Hepatology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Jian-Ming Xu
- Department of Gastroenterology and Hepatology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Chang-Qing Yang
- Division of Gastroenterology and Hepatology, Tongji Hospital, Tongji University, Shanghai, China
| | - Gui-Bin Yang
- Department of Gastroenterology and Hepatology, Aerospace Central Hospital, Beijing, China
| | - Yuan Yuan
- Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Zhi-Rong Zeng
- Department of Gastroenterology and Hepatology, First Affiliated Hospital, Zhongshan University, Guangzhou, Guangdong, China
| | - Bing-Yong Zhang
- Department of Gastroenterology and Hepatology, People's Hospital, Zhengzhou University, Zhengzhou, Henan, China
| | - Gui-Ying Zhang
- Department of Gastroenterology and Hepatology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Guo-Xin Zhang
- Department of Gastroenterology and Hepatology, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jian-Zhong Zhang
- Department of Communicable Disease Diagnostics(DCDD), National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Zhen-Yu Zhang
- Department of Gastroenterology and Hepatology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Peng-Yuan Zheng
- Department of Gastroenterology and Hepatology, The Fifth Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China
| | - Yin Zhu
- Department of Gastroenterology, First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
| | - Xiu-Li Zuo
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Li-Ya Zhou
- Department of Gastroenterology and Hepatology, Peking University Third Hospital, Beijing, China
| | - Nong-Hua Lyu
- Department of Gastroenterology and Hepatology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yun-Sheng Yang
- Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, China
| | - Zhao-Shen Li
- Department of Gastroenterology and Hepatology, Changhai Hospital, Naval Medical University, Shanghai, China
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Ding SZ. Global whole family based- Helicobacter pylori eradication strategy to prevent its related diseases and gastric cancer. World J Gastroenterol 2020; 26:995-1004. [PMID: 32205991 PMCID: PMC7080999 DOI: 10.3748/wjg.v26.i10.995] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Revised: 12/14/2019] [Accepted: 02/11/2020] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) infects approximately 50% of the world population. The multiple gastrointestinal and extra-gastrointestinal diseases caused by H. pylori infection pose a major healthcare threat to families and societies; it is also a heavy economic and healthcare burden for countries that having high infection rates. Eradication of H. pylori is recommended for all infected individuals. Traditionally, “test and treat” and "screen and treat" strategies are available for various infected populations. However, clinical practice has noticed that these strategies have some shortfalls and may need refinement, mostly due to the fact that they are not easily manageable, and are affected by patient compliance, selection of treatment population and cost-benefit estimations. Furthermore, it is difficult to control infections from the source, therefore, development of additional, compensative strategies are encouraged to solve the above problems and facilitate bacteria eradication. H. pylori infection is a family-based disease, but few studies have been performed in a whole family-based approach to curb its intra-familial transmission and the development of related diseases. In this work, a third, novel whole family-based H. pylori eradication strategy is introduced. This approach screens, identifies, treats and follows up on all H. pylori-infected individuals in entire families to control H. pylori infection among family members, and reduce its long-term complications. This strategy is high-risk population-oriented, and able to reduce H. pylori spread among family members. It also has good patient-family compliance and, importantly, is practical for both high and low H. pylori-infected communities. Future efforts in these areas will be critical to initiate and establish healthcare policies and management strategies to reduce H. pylori-induced disease burden for society.
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Affiliation(s)
- Song-Ze Ding
- Department of Gastroenterology and Hepatology, People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital, and Henan University School of Medicine, Zhengzhou 450003, Henan Province, China
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Howard R, Al Diffalha S, Pimiento J, Mejia J, Enderling H, Giuliano A, Coppola D. CD133 Expression as a Helicobacter pylori-independent Biomarker of Gastric Cancer Progression. Anticancer Res 2018; 38:4443-4448. [PMID: 30061208 PMCID: PMC7771274 DOI: 10.21873/anticanres.12746] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Revised: 06/22/2018] [Accepted: 06/28/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND/AIM Gastric adenocarcinoma is the fourth most common cancer worldwide. While gastric cancer prevalence varies globally and incidence rates are decreasing in the West, many cases continue to be diagnosed at an advanced stage and the 5-year survival rate still falls below 30%. Early treatment of gastric cancer by endoscopic and/or surgical therapy may decrease mortality; yet reliable, universally applicable biomarkers for early detection of gastric cancer have still not been established. MATERIALS AND METHODS The present work compares the expression of CD133 (prominin-1), a potential biomarker of disease progression in gastric cancer, between independent cohorts of H. pylori (+) and H. pylori (-) patients at each respective stage of carcinogenesis. H. pylori (-) patients (N=45) who underwent gastric biopsy at the Moffitt Cancer Center (MCC) in Tampa, Florida, and H. pylori (+) patients (N=59) who underwent gastric biopsy at the Instituto de Patologia Mejia Jimenez (IPMJ) in Cali, Colombia were evaluated and immunostained for CD133. RESULTS A statistically significant increase in CD133 expression (in terms of the Allred score) was observed between all stages of progression (normal mucosa, inflammation/metaplasia, low-grade dysplasia and gastric adenocarcinoma) for each respective patient cohort. No statistically significant difference in CD133 expression at each respective stage of disease was observed between the H. pylori-positive and negative-cohorts. CONCLUSION The observation of distinct stepwise increases in CD133 expression in both patient cohorts, and the lack of any significant difference between groups, suggests that CD133 expression may serve as a biomarker for early detection of gastric cancer independent of bacterial status and strain, and corresponding differences in disease histomorphology and classification. This warrants further validation on larger independent cohorts across multiple geographic regions and incorporating multiple bacterial strain types.
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Affiliation(s)
- Rachel Howard
- Department of Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, U.S.A
| | - Sameer Al Diffalha
- Pathology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, U.S.A
| | - Jose Pimiento
- Surgical Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, U.S.A
| | - Jaime Mejia
- Department of Pathology, Instituto de Patología Mejía Jiménez in Cali, Pathology, Valle del Cauca, Colombia
| | - Heiko Enderling
- Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, U.S.A
| | - Anna Giuliano
- Center for Infection Research in Cancer, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, U.S.A
| | - Domenico Coppola
- Pathology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, U.S.A.
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The Double Face of Mucin-Type O-Glycans in Lectin-Mediated Infection and Immunity. Molecules 2018; 23:molecules23051151. [PMID: 29751628 PMCID: PMC6100456 DOI: 10.3390/molecules23051151] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Revised: 05/03/2018] [Accepted: 05/07/2018] [Indexed: 02/07/2023] Open
Abstract
Epithelial human blood group antigens (HBGAs) on O-glycans play roles in pathogen binding and the initiation of infection, while similar structures on secretory mucins exert protective functions. These double-faced features of O-glycans in infection and innate immunity are reviewed based on two instructive examples of bacterial and viral pathogens. Helicobacter pylori represents a class 1 carcinogen in the human stomach. By expressing blood group antigen-binding adhesin (BabA) and LabA adhesins that bind to Lewis-b and LacdiNAc, respectively, H. pylori colocalizes with the mucin MUC5AC in gastric surface epithelia, but not with MUC6, which is cosecreted with trefoil factor family 2 (TFF2) by deep gastric glands. Both components of the glandular secretome are concertedly up-regulated upon infection. While MUC6 expresses GlcNAc-capped glycans as natural antibiotics for H. pylori growth control, TFF2 may function as a probiotic lectin. In viral infection human noroviruses of the GII genogroup interact with HBGAs via their major capsid protein, VP1. HBGAs on human milk oligosaccharides (HMOs) may exert protective functions by binding to the P2 domain pocket on the capsid. We discuss structural details of the P2 carbohydrate-binding pocket in interaction with blood group H/Lewis-b HMOs and fucoidan-derived oligofucoses as effective interactors for the most prevalent norovirus strains, GII.4 and GII.17.
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Song Y, Li X, Zeng Z, Li Q, Gong Z, Liao Q, Li X, Chen P, Xiang B, Zhang W, Xiong F, Zhou Y, Zhou M, Ma J, Li Y, Chen X, Li G, Xiong W. Epstein-Barr virus encoded miR-BART11 promotes inflammation-induced carcinogenesis by targeting FOXP1. Oncotarget 2017; 7:36783-36799. [PMID: 27167345 PMCID: PMC5095039 DOI: 10.18632/oncotarget.9170] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2016] [Accepted: 04/16/2016] [Indexed: 12/23/2022] Open
Abstract
Epstein-Barr virus (EBV) infection and chronic inflammation are closely associated with the development and progression of nasopharyngeal carcinoma (NPC) and gastric cancer (GC), and the infiltration of inflammatory cells, including tumor-associated macrophages (TAMs), is often observed in these cancers. EBV encodes 44 mature micro RNAs (miRNAs), but the roles of only a few EBV-encoded miRNA targets are known in cancer development, and here, our aim was to elucidate the effects of EBV-miR-BART11 on FOXP1 expression, and potential involvement in inflammation-induced carcinogenesis. We constructed an EBV miRNA-dependent gene regulatory network and predicted that EBV-miR-BART11 is able to target forkhead box P1 (FOXP1), a key molecule involved in monocyte to macrophage differentiation. Here, using luciferase reporter assay, we confirmed that EBV-miR-BART11 directly targets the 3′-untranslated region of FOXP1 gene, inhibits FOXP1 induction of TAM differentiation, and the secretion of inflammatory cytokines into the tumor microenvironment, inducing the proliferation of NPC and GC cells. FOXP1 overexpression hindered monocyte differentiation and inhibited NPC and GC cells growth. Our results demonstrated that EBV-miR-BART11 plays a crucial role in the promotion of inflammation-induced NPC and GC carcinogenesis by inhibiting FOXP1 tumor-suppressive effects. We showed a novel EBV-dependent mechanism that may induce the carcinogenesis of NPC and GC, which may help define new potential biomarkers and targets for NPC and GC diagnosis and treatment.
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Affiliation(s)
- Yali Song
- The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.,The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Xiaoling Li
- The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.,The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China.,Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zhaoyang Zeng
- The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.,The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China.,Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Qiao Li
- The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Zhaojian Gong
- The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Qianjin Liao
- Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Xiayu Li
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Pan Chen
- Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Bo Xiang
- The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.,The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China.,Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Wenling Zhang
- The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Fang Xiong
- The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yanhong Zhou
- The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Ming Zhou
- The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Jian Ma
- The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Yong Li
- The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China.,Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Xiang Chen
- The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Guiyuan Li
- The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.,The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China.,Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Wei Xiong
- The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.,The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China.,Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
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8
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Sekar D, Krishnan R, Thirugnanasambantham K, Rajasekaran B, Islam VIH, Sekar P. Significance of microRNA 21 in gastric cancer. Clin Res Hepatol Gastroenterol 2016; 40:538-545. [PMID: 27179559 DOI: 10.1016/j.clinre.2016.02.010] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2015] [Revised: 02/01/2016] [Accepted: 02/17/2016] [Indexed: 02/04/2023]
Abstract
Despite promising developments of treatment, the mortality due to gastric cancer remains high and the mechanisms of gastric cancer initiation and the development also remains elusive. It has been reported that patients with positive serologic tests for H. pylori have a higher risk of the development of gastric cancer. microRNAs (miRNAs) are short non-coding RNA molecules consisting of 21-25 nucleotides (nt) in length. The miRNAs silence their cognate target genes by inhibiting mRNA translation or degrading the mRNA molecules by binding to their 3'-untranslated (UTR) regions and plays a very important role in cancer biology. Recent evidences indicate that miR-21 is overexpressed in tumour tissue, including gastric cancer and plays a vital role in tumour cell proliferation, apoptosis, invasion and angiogenesis. Elevated levels of miR-21 is associated with downregulation of tumour suppressor genes, such as programmed cell death 4 (PDCD4), tissue inhibitor of metalloproteinase 3, phosphatase and tensin homolog (PTEN), tropomyosin 1, ras homolog gene family member B, and maspin. Silencing of miR-21 through the use of a miR-21 inhibitor affected cancer cell viability, induced cell cycle arrest and increased chemosensitivity to anticancer agents indicating that miR-21 functions as an oncogene. Although an increased expression level of miR-21 has been observed in gastric cancer, studies related to the role of miR-21 in gastric cancer progression is very limited. The main thrust of this mini review is to explain the potency of miR-21 as a prognostic and/or diagnostic biomarker and as a new target for clinical therapeutic for interventions of gastric cancer progression.
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Affiliation(s)
- Durairaj Sekar
- Narayana Medical College and Hospital, Chintha Reddy Palem, Nellore 524002, India; Stem Cell Division, Cryovault Biotech India Pvt. Ltd, Bangalore 560016, India.
| | - Ramalingam Krishnan
- Narayana Medical College and Hospital, Chintha Reddy Palem, Nellore 524002, India
| | | | - Baskaran Rajasekaran
- Biochemistry and Molecular Biology, Pondicherry University, RV Nagar, Pondicherry 6-5014, India
| | | | - Punitha Sekar
- Stem Cell Division, Cryovault Biotech India Pvt. Ltd, Bangalore 560016, India
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9
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Helicobacter pylori vacA and cagA genotype diversity and interferon gamma expression in patients with chronic gastritis and patients with gastric cancer. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2016; 79:220-8. [PMID: 25432406 DOI: 10.1016/j.rgmx.2014.10.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2014] [Revised: 10/22/2014] [Accepted: 10/23/2014] [Indexed: 01/09/2023]
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is the main risk factor for the development of chronic gastritis, gastric ulcer, and gastric cancer. In H. pylori-infected individuals, the clinical result is dependent on various factors, among which are bacterial components, the immune response, and environmental influence. AIMS To compare IFN-γ expression with the H. pylori vacA and cagA genotypes in patients with chronic gastritis and patients with gastric cancer. METHODS Ninety-five patients diagnosed with chronic gastritis and 20 with gastric cancer were included in the study. Three gastric biopsies were taken; one was used for the molecular detection and genotyping of H. pylori; another was fixed in absolute alcohol and histologic sections were made for determining IFN-γ expression through immunohistochemistry. RESULTS No differences were found in the cells that expressed IFN-γ between the patients with chronic gastritis (median percentage of positive cells: 82.6% in patients without H. pylori and 82% in infected persons) and those with gastric cancer (70.5% in H. pylori-negative patients and 78.5% in infected persons). IFN-γ expression was 69% in chronic gastritis patients infected with H. pylori vacAs2m2/cagA⁻ it was 86.5% in patients infected with H. pylori vacAs1m2/cagA⁻, 86.5% in vacAs1m1/cagA⁻, and 82% in vacAs1m1/cagA⁺. Similar data were found in the patients with gastric cancer. CONCLUSIONS IFN-γ expression varied depending on the H. pylori vacA and cagA genotype, but not in accordance with the presence of chronic gastritis or gastric cancer.
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10
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Laird-Fick HS, Saini S, Hillard JR. Gastric adenocarcinoma: the role of Helicobacter pylori in pathogenesis and prevention efforts. Postgrad Med J 2016; 92:471-7. [PMID: 27222587 DOI: 10.1136/postgradmedj-2016-133997] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2016] [Accepted: 04/24/2016] [Indexed: 12/20/2022]
Abstract
Gastric cancer is the third most common cause of cancer deaths in the world, prompting high-risk countries like South Korea and Japan to establish nationwide screening programmes. Helicobacter pylori is linked to the majority of gastric adenocarcinoma cases and to the vast majority of non-cardia gastric adenocarcinomas. Several studies have demonstrated the effectiveness of 'test-and-treat' programmes for H. pylori infection to prevent gastric cancer in high-risk populations. While this strategy has gained momentum, providers in low-risk developed countries may be unaware of the risk individual patients face, particularly those who have emigrated from high-risk regions and members of economically disadvantaged minority groups. Rapidly evolving science in recent years has made it difficult for clinicians to keep up with the current best practices. This article reviews the epidemiology of H. pylori and gastric cancer, screening and diagnostic tests and the current treatment regimens for clinicians.
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Affiliation(s)
- Heather S Laird-Fick
- Department of Medicine, Michigan State University, East Lansing, Michigan, USA Department of Medicine, EW Sparrow Hospital, Lansing, Michigan, USA
| | - Shivani Saini
- Department of Medicine, Michigan State University, East Lansing, Michigan, USA
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11
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Craven CJ. A hypothesis of couplet molecules and couplet cells in gastric function and an association with Helicobacter pylori. BMC Gastroenterol 2016; 16:16. [PMID: 26879837 PMCID: PMC4754955 DOI: 10.1186/s12876-016-0429-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Accepted: 02/09/2016] [Indexed: 11/21/2022] Open
Abstract
Background Gastrin, from G-cells, and histamine, from enterochromaffin-like (ECL) cells, are two of the hormones that regulate gastric activity. Discussion It is proposed that the G-cells and the ECL cells are coupled by the couplet molecules gastrin and histamine and by a prior asymmetrical cell division. The gastrin (from G-cells) stimulates the ECL cells to produce and secrete histamine while, in a reciprocal way, this histamine (from ECL cells), stimulates the G-cells to produce and secrete gastrin. These molecules would also stimulate cell division – the gastrin would stimulate cell division of ECL cells while histamine would stimulate that of G-cells. A chemical complex of gastrin and histamine is postulated as is also the asymmetric cell divisions of precursor cells to produce the coupled G-cells and ECL cells. Conclusion There is sufficient evidence to support the feasibility of the model in general, but more direct experimental evidence is required to validate the model as applied here to gastric function.
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12
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Lee SH, Park JM, Han YM, Ko WJ, Hahm KB. [Unpleasant Journey from Helicobacter pylori-associated Gastritis to Gastric Cancer: Cancer Prevention by Taking a Detour]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2015; 66:303-11. [PMID: 26691187 DOI: 10.4166/kjg.2015.66.6.303] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
As a commensal or a pathogen, Helicobacter pylori can change the balance of a complex interaction that exists among gastric epithelial cells, microbes, and their environment. Therefore, unraveling this complex relationship of these mixtures can be expected to help prevent cancer as well as troublesome unmet medical needs of H. pylori infection. Though gastric carcinogenesis is a multi-step process, precancerous lesion can be reversible in the early phase of mucosal damage before reaching the stage of no return. However, biomarkers to predict rejuvenation of precancerous atrophic gastritis have not been identified yet and gastric cancer prevention is still regarded as an impregnable fortress. However, when we take the journey from H. pylori-associated gastritis to gastric cancer, it provides us with the clue for prevention since there are two main preventive strategies: eradication and anti-inflammation. The evidence supporting the former strategy is now ongoing in Japan through a nation-wide effort to eradicate H. pylori in patients with chronic gastritis, but suboptimal apprehension to increasing H. pylori resistance to antibiotics and patient non-compliance still exists. The latter strategy has been continued in the author'sresearch center under siTRP (short-term intervention to revert premalignant lesion) strategy. By focusing on the role of inflammation in the development of H. pylori-associated gastric carcinogenesis, this review is intended to explain the connection between inflammation and gastric cancer. Strategies on H. pylori eradication, removal of inflammation, and reverting preneoplastic lesion will also be introduced. In the end, we expect to be able to prevent gastric cancer by take a detour from the unpleasant journey, i.e. from H. pylori-associated gastritis to gastric cancer.
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Affiliation(s)
- Sang Hwan Lee
- Digestive Disease Center, CHA University Bundang Medical Center, Seongnam, Korea
| | - Jong Min Park
- CHA Bio Complex, CHA Cancer Prevention Research Center, Seongnam, Korea
| | - Young Min Han
- CHA Bio Complex, CHA Cancer Prevention Research Center, Seongnam, Korea
| | - Weon Jin Ko
- Digestive Disease Center, CHA University Bundang Medical Center, Seongnam, Korea
| | - Ki Baik Hahm
- Digestive Disease Center, CHA University Bundang Medical Center, Seongnam, Korea.,CHA Bio Complex, CHA Cancer Prevention Research Center, Seongnam, Korea
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13
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Ahmadzadeh A, Ghalehnoei H, Farzi N, Yadegar A, Alebouyeh M, Aghdaei HA, Molaei M, Zali MR, Pour Hossein Gholi MA. Association of CagPAI integrity with severeness of Helicobacter pylori infection in patients with gastritis. ACTA ACUST UNITED AC 2015; 63:252-7. [PMID: 26530303 DOI: 10.1016/j.patbio.2015.09.004] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Accepted: 09/29/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM The Helicobacter pylori cag pathogenicity island (cagPAI) is involved in delivery of CagA effector protein and peptidoglycan into host cells and also in IL-8 induction in the human gastric tissue. Diversity of cagPAI may affect disease status and clinical outcome of the infected patients. Our study was aimed to investigate diversity of this island and its intactness in Iranian patients to investigate possible associations between cagPAI integrity and pathological changes of the infected tissue. MATERIAL/PATIENTS AND METHODS Out of the 75 patients, H. pylori strains were obtained from 30 patients with severe active gastritis (SAG) (n=11), moderate chronic gastritis (CG) (n=14) and intestinal metaplasia/dysplasia (IM) (n=5). Intactness of the cagPAI was determined using 12 sets of primer pairs specific for functionally important loci of cagPAI by polymerase chain reaction (PCR). RESULTS The cagPAI positive strains were significantly observed in patients with SAG (52.4%) in comparison to those presenting CG (33.3%) and IM (14.3%). In addition, the presence of intact cagPAI was 87.5% in H. pylori strains isolated from patients with SAG, which was higher than those obtained from patients with CG (12.5%) or IM (0%). A significant increase in the frequency of cagα-cagY and cagW-cagT segments, as exterior proteins of the CagPAI, was illustrated in strains from SAG patients compared with those from patients with CG. CONCLUSIONS Overall, these results strongly proposed an association between the severity of histopathological changes and intactness of cagPAI in the gastric tissue of patients infected with H. pylori.
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Affiliation(s)
- A Ahmadzadeh
- Molecular Medicine, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Faculty of Medicine, Ilam University of Medical Sciences, Tehran, Iran
| | - H Ghalehnoei
- Molecular Medicine, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - N Farzi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - A Yadegar
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - M Alebouyeh
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - H A Aghdaei
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - M Molaei
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - M R Zali
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - M A Pour Hossein Gholi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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14
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Durham AL, Adcock IM. The relationship between COPD and lung cancer. Lung Cancer 2015; 90:121-7. [PMID: 26363803 PMCID: PMC4718929 DOI: 10.1016/j.lungcan.2015.08.017] [Citation(s) in RCA: 300] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Revised: 08/24/2015] [Accepted: 08/27/2015] [Indexed: 02/07/2023]
Abstract
COPD is a risk factor for lung cancer beyond their shared aetiology. Both are driven by oxidative stress. Both are linked to cellular aging, senescence and telomere shortening. Both have been linked to genetic predisposition. Both show altered epigenetic regulation of gene expression. Both COPD and lung cancer are major worldwide health concerns owing to cigarette smoking, and represent a huge, worldwide, preventable disease burden. Whilst the majority of smokers will not develop either COPD or lung cancer, they are closely related diseases, occurring as co-morbidities at a higher rate than if they were independently triggered by smoking. Lung cancer and COPD may be different aspects of the same disease, with the same underlying predispositions, whether this is an underlying genetic predisposition, telomere shortening, mitochondrial dysfunction or premature aging. In the majority of smokers, the burden of smoking may be dealt with by the body’s defense mechanisms: anti-oxidants such as superoxide dismutases, anti-proteases and DNA repair mechanisms. However, in the case of both diseases these fail, leading to cancer if mutations occur or COPD if damage to the cell and proteins becomes too great. Alternatively COPD could be a driving factor in lung cancer, by increasing oxidative stress and the resulting DNA damage, chronic exposure to pro-inflammatory cytokines, repression of the DNA repair mechanisms and increased cellular proliferation. Understanding the mechanisms that drive these processes in primary cells from patients with these diseases along with better disease models is essential for the development of new treatments.
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Affiliation(s)
- A L Durham
- Airway Disease Section, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London, UK.
| | - I M Adcock
- Airway Disease Section, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London, UK
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15
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Barooei R, Mahmoudian RA, Abbaszadegan MR, Mansouri A, Gholamin M. Evaluation of thymic stromal lymphopoietin (TSLP) and its correlation with lymphatic metastasis in human gastric cancer. Med Oncol 2015; 32:217. [DOI: 10.1007/s12032-015-0653-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2015] [Accepted: 06/10/2015] [Indexed: 12/28/2022]
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16
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Curcio C, Lanzini M, Calienno R, Mastropasqua R, Marchini G. The expression of LGR5 in healthy human stem cell niches and its modulation in inflamed conditions. Mol Vis 2015; 21:644-8. [PMID: 26097379 PMCID: PMC4455891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2015] [Accepted: 06/02/2015] [Indexed: 11/29/2022] Open
Abstract
PURPOSE The aims of this study are to investigate the expression of leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) protein in the normal human cornea and limbus and to analyze modifications of this expression under inflammatory conditions. METHODS The expression of LGR5 was evaluated in seven limbal epithelial crypts (LECs), collected from healthy cadaver donors, and five inflamed LECs obtained from enucleated eyes. Central corneal buttons were used as controls. LGR5 protein distribution was determined by immunohistochemistry staining analysis. RESULTS The cytoplasmic expression of LGR5 protein was observed in 100% of healthy LECs. Three out of five inflamed tissues analyzed were completely negative, while in the two remaining cases, we observed a moderate positivity in the basal cells of LECs. No relation was found between the expression of LGR5 and the grade of inflammatory cells. CONCLUSIONS These findings demonstrate the presence of LGR5-positive cells in human LECs and their decrease in inflamed conditions, which suggests a critical role of this protein during inflammation and its possible use as a marker in normal crypts.
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Affiliation(s)
- Claudia Curcio
- Biological Eye Center Research, CeSI, University “G. d'Annunzio” of Chieti and Pescara, Italy
| | - Manuela Lanzini
- Department of Medicine and Ageing Science, Opthalmology Clinic, University “G. d'Annunzio” of Chieti and Pescara, Italy
| | - Roberta Calienno
- Department of Medicine and Ageing Science, Opthalmology Clinic, University “G. d'Annunzio” of Chieti and Pescara, Italy
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17
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Tornesello ML, Buonaguro L, Buonaguro FM. An overview of new biomolecular pathways in pathogen-related cancers. Future Oncol 2015; 11:1625-1639. [PMID: 26043216 DOI: 10.2217/fon.15.87] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Cancer molecular pathways are combinations of metabolic processes deregulated in neoplastic cells. Besides pathways specific to tissues from which cancers originate, common neoplastic traits are present among most tumors. Hanahan and Weinberg have described the most critical 'hallmarks' shared by many cancer types. In recent years, cancer stem cell specific properties and pathways have also been identified. Other altered pathways are peculiar of cancer type and cancer stage, even in different cancer stem cell types. In pathogen-related tumors, the alteration of inflammatory and immunologic response along with impairment of cell cycle control represents key molecular events of tumor progression. This article summarizes the recent discoveries of new altered pathways in cancer and their importance in cancer diagnosis and tailored therapies.
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18
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Le X, Gu Q, Xu J. Identifying MurI uncompetitive inhibitors by correlating decomposed binding energies with bioactivity. RSC Adv 2015. [DOI: 10.1039/c5ra03079j] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
MurI uncompetitive inhibitors can be virtually identified by a new method that correlates decomposed binding free energies with the bioactivity.
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Affiliation(s)
- Xiu Le
- Research Center for Drug Discovery
- School of Pharmaceutical Sciences
- Sun Yat-Sen University
- Guangzhou 510006
- China
| | - Qiong Gu
- Research Center for Drug Discovery
- School of Pharmaceutical Sciences
- Sun Yat-Sen University
- Guangzhou 510006
- China
| | - Jun Xu
- Research Center for Drug Discovery
- School of Pharmaceutical Sciences
- Sun Yat-Sen University
- Guangzhou 510006
- China
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19
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Martínez-Carrillo D, Atrisco-Morales J, Hernández-Pando R, Reyes-Navarrete S, Betancourt-Linares R, Cruz-del Carmen I, Illades Aguiar B, Román-Román A, Fernández-Tilapa G. Helicobacter pylori vacA and cagA genotype diversity and interferon gamma expression in patients with chronic gastritis and patients with gastric cancer. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2014. [DOI: 10.1016/j.rgmxen.2014.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
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20
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Craven CJ. A model to explain specific cellular communications and cellular harmony:- a hypothesis of coupled cells and interactive coupling molecules. Theor Biol Med Model 2014; 11:40. [PMID: 25218581 PMCID: PMC4237941 DOI: 10.1186/1742-4682-11-40] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2014] [Accepted: 09/02/2014] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The various cell types and their relative numbers in multicellular organisms are controlled by growth factors and related extracellular molecules which affect genetic expression pathways. However, these substances may have both/either inhibitory and/or stimulatory effects on cell division and cell differentiation depending on the cellular environment. It is not known how cells respond to these substances in such an ambiguous way. Many cellular effects have been investigated and reported using cell culture from cancer cell lines in an effort to define normal cellular behaviour using these abnormal cells.A model is offered to explain the harmony of cellular life in multicellular organisms involving interacting extracellular substances. METHODS A basic model was proposed based on asymmetric cell division and evidence to support the hypothetical model was accumulated from the literature. In particular, relevant evidence was selected for the Insulin-Like Growth Factor system from the published data, especially from certain cell lines, to support the model. The evidence has been selective in an attempt to provide a picture of normal cellular responses, derived from the cell lines. RESULTS The formation of a pair of coupled cells by asymmetric cell division is an integral part of the model as is the interaction of couplet molecules derived from these cells. Each couplet cell will have a receptor to measure the amount of the couplet molecule produced by the other cell; each cell will be receptor-positive or receptor-negative for the respective receptors. The couplet molecules will form a binary complex whose level is also measured by the cell. The hypothesis is heavily supported by selective collection of circumstantial evidence and by some direct evidence. The basic model can be expanded to other cellular interactions. CONCLUSIONS These couplet cells and interacting couplet molecules can be viewed as a mechanism that provides a controlled and balanced division-of-labour between the two progeny cells, and, in turn, their progeny. The presence or absence of a particular receptor for a couplet molecule will define a cell type and the presence or absence of many such receptors will define the cell types of the progeny within cell lineages.
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Affiliation(s)
- Cyril J Craven
- Queensland University of Technology (QUT), Brisbane, Australia.
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21
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Park SS, Izadjoo MJ. Wound infections and healing: are they contributing factors for carcinogenesis? J Wound Care 2014; 23:314, 316-9, 321-2 passim. [PMID: 24920202 DOI: 10.12968/jowc.2014.23.6.314] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The link between inflammation and tumourisation has long been considered as a key event in clinical cancer development. Inflammation and inflammatory diseases can be caused by many factors including infectious agents, altered genetics and various degrees of injuries from simple cuts to traumatic wounds, such as those suffered in battlefield. Improved management of all wound types is critical in protecting affected individuals against the development of tumourisation cues, which may potentially lead to cancer development. There have been numerous studies on the mechanism of inflammation-induced tumourisation. Thus, in this mini review, we summarised evidence demonstrating the potential link between infectious agents and their moonlight proteins, wounding, trauma, overactive repair mechanisms, and carcinogenesis.
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Affiliation(s)
- S S Park
- PhD, Research Scientist, Diagnostics and Translational Research Center, The Henry M. Jackson Foundation for the Advancement of Military Medicine, Gaithersburg, US
| | - M J Izadjoo
- PhD, Senior Distinguished Scientist, Diagnostics and Translational Research Center, The Henry M. Jackson Foundation for the Advancement of Military Medicine, Gaithersburg, US
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22
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Hanisch FG, Bonar D, Schloerer N, Schroten H. Human trefoil factor 2 is a lectin that binds α-GlcNAc-capped mucin glycans with antibiotic activity against Helicobacter pylori. J Biol Chem 2014; 289:27363-75. [PMID: 25124036 DOI: 10.1074/jbc.m114.597757] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Helicobacter pylori infection is the major cause of gastric cancer and remains an important health care challenge. The trefoil factor peptides are a family of small highly conserved proteins that are claimed to play essential roles in cytoprotection and epithelial repair within the gastrointestinal tract. H. pylori colocalizes with MUC5AC at the gastric surface epithelium, but not with MUC6 secreted in concert with TFF2 by deep gastric glands. Both components of the gastric gland secretome associate non-covalently and show increased expression upon H. pylori infection. Although blood group active O-glycans of the Lewis-type form the basis of H. pylori adhesion to the surface mucin layer and to epithelial cells, α1,4-GlcNAc-capped O-glycans on gastric mucins were proposed to inhibit H. pylori growth as a natural antibiotic. We show here that the gastric glycoform of TFF2 is a calcium-independent lectin, which binds with high specificity to O-linked α1,4-GlcNAc-capped hexasaccharides on human and porcine stomach mucin. The structural assignments of two hexasaccharide isomers and the binding active glycotope were based on mass spectrometry, linkage analysis, (1)H nuclear magnetic resonance spectroscopy, glycan inhibition, and lectin competition of TFF2-mucin binding. Neoglycolipids derived from the C3/C6-linked branches of the two isomers revealed highly specific TFF2 binding to the 6-linked trisaccharide in GlcNAcα1-4Galβ1-4GlcNAcβ1-6(Fucα1-2Galβ1-3)GalNAc-ol(Structure 1). Supposedly, lectin TFF2 is involved in protection of gastric epithelia via a functional relationship to defense against H. pylori launched by antibiotic α1,4-GlcNAc-capped mucin glycans. Lectin-carbohydrate interaction may have also an impact on more general functional aspects of TFF members by mediating their binding to cell signaling receptors.
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Affiliation(s)
- Franz-Georg Hanisch
- From the Institute of Biochemistry II, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 52, 50931 Köln, the Center for Molecular Medicine Cologne, University of Cologne, Robert-Koch-Str. 21, 50931 Köln,
| | - David Bonar
- From the Institute of Biochemistry II, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 52, 50931 Köln
| | - Nils Schloerer
- the Institute of Organic Chemistry, University of Cologne, Greinstr. 4, 50939 Köln, and
| | - Horst Schroten
- the University Children's Hospital, Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
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Ansari SA, Devi S, Tenguria S, Kumar A, Ahmed N. Helicobacter pylori protein HP0986 (TieA) interacts with mouse TNFR1 and triggers proinflammatory and proapoptotic signaling pathways in cultured macrophage cells (RAW 264.7). Cytokine 2014; 68:110-7. [DOI: 10.1016/j.cyto.2014.03.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2013] [Revised: 02/09/2014] [Accepted: 03/24/2014] [Indexed: 12/12/2022]
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24
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Chung HW, Lim JB. Role of the tumor microenvironment in the pathogenesis of gastric carcinoma. World J Gastroenterol 2014; 20:1667-1680. [PMID: 24587646 PMCID: PMC3930967 DOI: 10.3748/wjg.v20.i7.1667] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 11/22/2013] [Accepted: 12/06/2013] [Indexed: 02/06/2023] Open
Abstract
Gastric carcinoma (GC) is the 4th most prevalent cancer and has the 2nd highest cancer-related mortality rate worldwide. Despite the incidence of GC has decreased over the past few decades, it is still a serious health problem. Chronic inflammatory status of the stomach, caused by the infection of Helicobacter pylori (H. pylori) and through the production of inflammatory mediators within the parenchyma is suspected to play an important role in the initiation and progression of GC. In this review, the correlation between chronic inflammation and H. pylori infection as an important factor for the development of GC will be discussed. Major components, including tumor-associated macrophages, lymphocytes, cancer-associated fibroblasts, angiogenic factors, cytokines, and chemokines of GC microenvironment and their mechanism of action on signaling pathways will also be discussed. Increasing our understanding of how the components of the tumor microenviroment interact with GC cells and the signaling pathways involved could help identify new therapeutic and chemopreventive targets.
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Xi XL, Jiang BJ, Yu JW. Cancer stem cell-related signaling pathways in development of gastric cancer. Shijie Huaren Xiaohua Zazhi 2014; 22:494-500. [DOI: 10.11569/wcjd.v22.i4.494] [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
Cancer stem cells are a subset of cancer cells with self-renewal and differentiation capacity. They play an important role in gastric carcinogenesis, proliferation, migration, invasion and metastasis and are involved in resistance to chemotherapy. Numerous studies indicate that stem cell-related signaling pathways (such as Wnt, Notch, Hedgehog, PI3K, and BMP) are activated in the occurrence and development of gastric cancer. Inhibition of tumor self-renewal-related signaling pathways can significantly improve the prognosis of patients with gastric cancer. In this paper we will review the roles of these cancer stem cell-related signaling pathways in gastric cancer.
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Park SH, Kangwan N, Park JM, Kim EH, Hahm KB. Non-microbial approach for Helicobacter pylori as faster track to prevent gastric cancer than simple eradication. World J Gastroenterol 2013; 19:8986-95. [PMID: 24379623 PMCID: PMC3870551 DOI: 10.3748/wjg.v19.i47.8986] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2013] [Revised: 10/30/2013] [Accepted: 11/18/2013] [Indexed: 02/06/2023] Open
Abstract
Although the International Agency for Research on Cancer declared Helicobacter pylori (H. pylori) as a definite human carcinogen in 1994, the Japanese Society for Helicobacter Research only recently (February 2013) adopted the position that H. pylori infection should be considered as an indication for either amelioration of chronic gastritis or for decreasing gastric cancer mortality. Japanese researchers have found that H. pylori eradication halts progressive mucosal damage and that successful eradication in patients with non-atrophic gastritis most likely prevents subsequent development of gastric cancer. However, those who have already developed atrophic gastritis/gastric atrophy retain potential risk factors for gastric cancer. Because chronic perpetuated progression of H. pylori-associated gastric inflammation is associated with increased morbidity culminating in gastric carcinogenesis, a non-microbial approach to treatment that provides long-term control of gastric inflammation through nutrients and other interventions may be an effective way to decrease this morbidity. This non-microbial approach might represent a new form of prerequisite "rescue" therapy that provides a quicker path to the prevention of gastric cancer as compared to simple eradication.
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27
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Stein M, Ruggiero P, Rappuoli R, Bagnoli F. Helicobacter pylori CagA: From Pathogenic Mechanisms to Its Use as an Anti-Cancer Vaccine. Front Immunol 2013; 4:328. [PMID: 24133496 PMCID: PMC3796731 DOI: 10.3389/fimmu.2013.00328] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2013] [Accepted: 09/25/2013] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori colonizes the gastric mucosa of more than 50% of the human population, causing chronic inflammation, which however is largely asymptomatic. Nevertheless, H. pylori-infected subjects can develop chronic gastritis, peptic ulcer, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Chronic exposure to the pathogen and its ability to induce epithelial to mesenchymal transition (EMT) through the injection of cytotoxin-associated gene A into gastric epithelial cells may be key triggers of carcinogenesis. By deregulating cell-cell and cell-matrix interactions as well as DNA methylation, histone modifications, expression of micro RNAs, and resistance to apoptosis, EMT can actively contribute to early stages of the cancer formation. Host response to the infection significantly contributes to disease development and the concomitance of particular genotypes of both pathogen and host may turn into the most severe outcomes. T regulatory cells (Treg) have been recently demonstrated to play an important role in H. pylori-related disease development and at the same time the Treg-induced tolerance has been proposed as a possible mechanism that leads to less severe disease. Efficacy of antibiotic therapies of H. pylori infection has significantly dropped. Unfortunately, no vaccine against H. pylori is currently licensed, and protective immunity mechanisms against H. pylori are only partially understood. In spite of promising results obtained in animal models of infection with a number of vaccine candidates, few clinical trials have been conducted so far and with no satisfactory outcomes. However, prophylactic vaccination may be the only means to efficiently prevent H. pylori-associated cancers.
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Affiliation(s)
- Markus Stein
- Albany College of Pharmacy and Health Sciences, Albany, NY, USA
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Emadi-Baygi M, Nikpour P, Mohammad-Hashem F, Maracy MR, Haghjooy-Javanmard S. MSI2 expression is decreased in grade II of gastric carcinoma. Pathol Res Pract 2013; 209:689-91. [PMID: 24002004 DOI: 10.1016/j.prp.2013.07.008] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2013] [Revised: 07/15/2013] [Accepted: 07/29/2013] [Indexed: 12/12/2022]
Abstract
Gastric cancer is the second most frequent cause of cancer death worldwide. In Iran, gastric cancer is the first cause of national cancer-related mortality in men and the second one in women. In mammals, the Musashi family of RNA binding proteins comprises the Musashi1 and Musashi2 proteins, encoded by the MSI1 and MSI2 genes. Mammalian Musashi contributes to the self-renewal of various types of stem cells. Furthermore, there is mounting evidence that stem cells exist in many tissues. Due to this, Msi appears to be associated with tumorigenesis. In the present study, 30 paired gastric tissue samples were examined for MSI2 gene expression by quantitative real-time RT-PCR. Our results demonstrated that the relative expression of the gene did not significantly alter between tumoral and non-tumoral tissues and different tumor types; but there was a statistical difference between the MSI2 gene expression in different tumor grades, of note between grade I and grade II.
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Affiliation(s)
- Modjtaba Emadi-Baygi
- Department of Genetics, Faculty of Basic Sciences, Shahrekord University, Shahrekord, Iran; Research Institute of Biotechnology, Shahrekord University, Shahrekord, Iran
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Singh SR. Gastric cancer stem cells: a novel therapeutic target. Cancer Lett 2013; 338:110-9. [PMID: 23583679 DOI: 10.1016/j.canlet.2013.03.035] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2013] [Revised: 03/25/2013] [Accepted: 03/30/2013] [Indexed: 12/14/2022]
Abstract
Gastric cancer remains one of the leading causes of global cancer mortality. Multipotent gastric stem cells have been identified in both mouse and human stomachs, and they play an essential role in the self-renewal and homeostasis of gastric mucosa. There are several environmental and genetic factors known to promote gastric cancer. In recent years, numerous in vitro and in vivo studies suggest that gastric cancer may originate from normal stem cells or bone marrow-derived mesenchymal cells, and that gastric tumors contain cancer stem cells. Cancer stem cells are believed to share a common microenvironment with normal niche, which play an important role in gastric cancer and tumor growth. This mini-review presents a brief overview of the recent developments in gastric cancer stem cell research. The knowledge gained by studying cancer stem cells in gastric mucosa will support the development of novel therapeutic strategies for gastric cancer.
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Affiliation(s)
- Shree Ram Singh
- Mouse Cancer Genetics Program, National Cancer Institute, Frederick, MD 21702, USA.
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