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Clyne M, Ó Cróinín T. Pathogenicity and virulence of Helicobacter pylori: A paradigm of chronic infection. Virulence 2025; 16:2438735. [PMID: 39725863 DOI: 10.1080/21505594.2024.2438735] [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: 05/13/2024] [Revised: 11/18/2024] [Accepted: 12/02/2024] [Indexed: 12/28/2024] Open
Abstract
Infection with Helicobacter pylori is one of the most common infections of mankind. Infection typically occurs in childhood and persists for the lifetime of the host unless eradicated with antimicrobials. The organism colonizes the stomach and causes gastritis. Most infected individuals are asymptomatic, but infection also causes gastric and duodenal ulceration, and gastric cancer. H. pylori possesses an arsenal of virulence factors, including a potent urease enzyme for protection from acid, flagella that mediate motility, an abundance of outer membrane proteins that can mediate attachment, several immunomodulatory proteins, and an ability to adapt to specific conditions in individual human stomachs. The presence of a type 4 secretion system that injects effector molecules into gastric cells and subverts host cell signalling is associated with virulence. In this review we discuss the interplay of H. pylori colonization and virulence factors with host and environmental factors to determine disease outcome in infected individuals.
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Affiliation(s)
- Marguerite Clyne
- School of Medicine, University College Dublin, Dublin, Ireland
- The Conway Institute of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
| | - Tadhg Ó Cróinín
- The Conway Institute of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
- School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
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2
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Sugimoto M, Matsuhisa T, Aftab H, Limpakan S, Sharma Dhakal SK, Sang K, Htet K, Yee TT, Yamaoka Y. Associations Between Antiparietal Cell Antibody Values and Atrophy in a South and Southeast Asian General Population. J Clin Gastroenterol 2025:00004836-990000000-00444. [PMID: 40339131 DOI: 10.1097/mcg.0000000000002195] [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: 01/17/2025] [Accepted: 03/14/2025] [Indexed: 05/10/2025]
Abstract
GOALS To investigate the association between atrophy severity and antiparietal cell antibody (APCA) levels in South and Southeast Asia. BACKGROUND APCA is an autoantibody that damages gastric parietal cells; autoimmune gastritis (AIG) is a chronic gastric inflammatory disease related to APCA and severe predominant corpus atrophy. Although a positive APCA result is a key clinical diagnostic tool for AIG, its rates vary widely among ethnic groups, and its exact relationship with AIG and predominant corpus atrophy remains unclear. STUDY Associations between histopathology-assessed and endoscopy-assessed atrophy, APCA positivity rates, Helicobacter pylori status, and pepsinogen levels were investigated in 1982 symptomatic patients from Vietnam, Thailand, Myanmar, Bangladesh, and Nepal. RESULTS Overall, 38.5% of participants were negative for Helicobacter pylori infection, while 57.6% had a current infection. A positive APCA result, defined as a titer >10, was present in 44.0% of participants (95% confidence interval: 41.8%-46.3%, 873/1982). Pathologic atrophy, corpus atrophy, and predominant corpus atrophy were found in 8.7% (169/1982), 5.1% (101/1982), and 4.1% (81/1982) of participants, respectively. Positive APCA rates significantly differed among countries (10.6% to 63.8%, P<0.001). No significant correlation was found between APCA results and the presence or severity of atrophy. CONCLUSIONS Although APCA positivity was high among symptomatic patients from South and Southeast Asian countries, few had severe predominant corpus atrophy or positive pepsinogen tests, which suggests a low rate of AIG in this population. Long-term surveillance of APCA-positive individuals is necessary to determine the clinical significance of a positive APCA result without AIG.
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Affiliation(s)
- Mitsushige Sugimoto
- Division of Genome-Wide Infectious Microbiology, Research Center for Global and Local Infectious Disease
| | - Takeshi Matsuhisa
- Division of Genome-Wide Infectious Microbiology, Research Center for Global and Local Infectious Disease
- Department of Gastroenterology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Hafeza Aftab
- Department of Gastroenterology, Dhaka Medical College, Dhaka, Bangladesh
| | - Sirikan Limpakan
- Department of Gastrointestinal Surgery and Endoscopy, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | | | - Kim Sang
- Department of Endoscopy and Gastroenterology, City International Hospital, Ho Chi Minh, Vietnam
| | - Kyaw Htet
- Department of Surgery, Defense Services General Hospital, Yangon
| | - Than Than Yee
- Department of Gastrointestinal and Hepatobiliary Surgery, Defense Services General Hospital, Nay Pyi Taw, Myanmar
| | - Yoshio Yamaoka
- Division of Genome-Wide Infectious Microbiology, Research Center for Global and Local Infectious Disease
- Department of Environmental and Preventive Medicine, Oita University, Yufu
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, TX, USA
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Song S, Wang J, Ouyang X, Huang R, Wang F, Xie J, Chen Q, Hu D. Therapeutic connections between pyroptosis and paclitaxel in anti-tumor effects: an updated review. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-04036-8. [PMID: 40257490 DOI: 10.1007/s00210-025-04036-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Accepted: 03/06/2025] [Indexed: 04/22/2025]
Abstract
As a form of inflammation-associated cell death, pyroptosis has gained widespread attention in recent years. Accumulating evidence indicates that pyroptosis regulates tumor growth and is associated with autoimmune disorders and inflammatory response. Paclitaxel, a traditional Chinese medicine, usually induces death of cancer cells as a chemotherapeutic agent. Previous studies have revealed that paclitaxel can exert an anti-tumor effect through a variety of cell death mechanisms, of which pyroptosis plays a pivotal role in inhibiting tumor growth and enhancing anti-tumor immunity. In this review, we summarize the current advances in therapeutic connections between pyroptosis and paclitaxel in anti-tumor effects.
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Affiliation(s)
- Shuxin Song
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jingbo Wang
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xiaohu Ouyang
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Renyin Huang
- Jingshan Union Hospital, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Fang Wang
- Jingshan Union Hospital, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Junke Xie
- Jingshan Union Hospital, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Qianyun Chen
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Desheng Hu
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- China-Russia Medical Research Center for Stress Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Wu S, Luo Y, Wei F, Li Y, Fan J, Chen Y, Zhang W, Li X, Xu Y, Chen Z, Xia C, Hu M, Li P, Gu Q. Lactic acid bacteria target NF-κB signaling to alleviate gastric inflammation. Food Funct 2025; 16:3101-3119. [PMID: 40152095 DOI: 10.1039/d4fo06308b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/29/2025]
Abstract
Helicobacter pylori (H. pylori) infection and the resulting gastric inflammation are major contributors to gastric cancer development. Probiotics, particularly Lactobacillus, are promising for their anti-inflammatory potential, yet their exact mechanisms in inhibiting H. pylori-induced inflammation are unclear. In our previous study, Lactiplantibacillus plantarum ZJ316 (L. plantarum ZJ316) demonstrated strong anti-inflammatory effects against H. pylori infection in vivo, but its precise mechanisms were not fully understood. Here, we aimed to investigate how L. plantarum ZJ316 inhibits the inflammatory response to H. pylori infection. Our results demonstrated that L. plantarum ZJ316 effectively reduced the expression of pro-inflammatory cytokines in H. pylori-infected AGS cells. Mechanistically, L. plantarum ZJ316 inhibited the NF-κB signaling pathway by preventing the degradation of IκBα, suppressing p65 phosphorylation, and blocking the nuclear translocation of phosphorylated p65. Treatment with the NF-κB inhibitor BAY 11-7082 further decreased tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and interleukin-1β (IL-1β) levels, confirming the inhibitory effect of L. plantarum ZJ316 on the NF-κB pathway. In H. pylori-infected mice, oral administration of L. plantarum ZJ316 significantly alleviated inflammatory cell infiltration, reduced TNF-α and pepsinogen II (PGII) levels, and increased interleukin-10 (IL-10) levels in serum. A comparative metagenomic analysis of the gastric microbiota revealed a decrease in Prevotella and Desulfovibrio, alongside an increase in Ligilactobacillus and Akkermansia, supporting the protective effects of L. plantarum ZJ316 and correlating with their decreased inflammatory response. In summary, administration of L. plantarum ZJ316 demonstrated robust anti-inflammatory effects against H. pylori infection by suppressing NF-κB signaling and promoting favorable changes in the gastric microbiota composition. Therefore, L. plantarum ZJ316 holds promise as a novel functional food for protecting the body against H. pylori infection.
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Affiliation(s)
- Shiying Wu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Yuenuo Luo
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Fangtong Wei
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Yanan Li
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, Jiangsu 210023, China
| | - Jiayi Fan
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Yongqiang Chen
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Wenjie Zhang
- Hangzhou Helixinjian Industry Co., Ltd, No. 48 Zijinghua Road, Gudang Street, Xihu District, Hangzhou, Zhejiang 310050, China
| | - Xuelong Li
- Hangzhou Helixinjian Industry Co., Ltd, No. 48 Zijinghua Road, Gudang Street, Xihu District, Hangzhou, Zhejiang 310050, China
| | - Yang Xu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Ziqi Chen
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Chenlan Xia
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Mingyang Hu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Ping Li
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Qing Gu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
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Keikha M. Comments on 'Genotypic diversity of the Helicobacter pylori vacA c region and its correlation with gastric disease outcomes'. J Med Microbiol 2025; 74:002002. [PMID: 40193187 PMCID: PMC11975057 DOI: 10.1099/jmm.0.002002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2025] [Accepted: 03/17/2025] [Indexed: 04/10/2025] Open
Affiliation(s)
- Masoud Keikha
- Tropical and Communicable Diseases Research Center, Iranshahr University of Medical Sciences, Iranshahr, Iran
- Department of Medical Microbiology, School of Medicine, Iranshahr University of Medical Sciences, Iranshahr, Iran
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Lim SH, Kim N, Choi Y, Choi JM, Han YM, Kwak MS, Chung GE, Seo JY, Baek SM, Yoon H, Park YS, Lee DH. Assessing Serum Pepsinogen and Helicobacter pylori Tests for Detecting Diffuse-Type Gastric Cancer: Insights from a Large-Scale and Propensity-Score-Matched Study in Republic of Korea. Cancers (Basel) 2025; 17:955. [PMID: 40149291 PMCID: PMC11940262 DOI: 10.3390/cancers17060955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 02/25/2025] [Accepted: 03/05/2025] [Indexed: 03/29/2025] Open
Abstract
The incidence of cancer and its associated mortality have increased over the past several decades [...].
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Affiliation(s)
- Seon Hee Lim
- Departments of Internal Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Healthcare Research Institute, Seoul 06236, Republic of Korea; (S.H.L.); (J.M.C.); (Y.M.H.); (M.-S.K.); (G.E.C.); (J.Y.S.)
| | - Nayoung Kim
- Department of Internal Medicine, Research Center for Sex- and Gender-Specific Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Gyeonggi-do, Republic of Korea; (Y.C.); (S.M.B.); (H.Y.); (Y.S.P.); (D.H.L.)
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Yonghoon Choi
- Department of Internal Medicine, Research Center for Sex- and Gender-Specific Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Gyeonggi-do, Republic of Korea; (Y.C.); (S.M.B.); (H.Y.); (Y.S.P.); (D.H.L.)
| | - Ji Min Choi
- Departments of Internal Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Healthcare Research Institute, Seoul 06236, Republic of Korea; (S.H.L.); (J.M.C.); (Y.M.H.); (M.-S.K.); (G.E.C.); (J.Y.S.)
| | - Yoo Min Han
- Departments of Internal Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Healthcare Research Institute, Seoul 06236, Republic of Korea; (S.H.L.); (J.M.C.); (Y.M.H.); (M.-S.K.); (G.E.C.); (J.Y.S.)
| | - Min-Sun Kwak
- Departments of Internal Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Healthcare Research Institute, Seoul 06236, Republic of Korea; (S.H.L.); (J.M.C.); (Y.M.H.); (M.-S.K.); (G.E.C.); (J.Y.S.)
| | - Goh Eun Chung
- Departments of Internal Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Healthcare Research Institute, Seoul 06236, Republic of Korea; (S.H.L.); (J.M.C.); (Y.M.H.); (M.-S.K.); (G.E.C.); (J.Y.S.)
| | - Ji Yeon Seo
- Departments of Internal Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Healthcare Research Institute, Seoul 06236, Republic of Korea; (S.H.L.); (J.M.C.); (Y.M.H.); (M.-S.K.); (G.E.C.); (J.Y.S.)
| | - Sung Min Baek
- Department of Internal Medicine, Research Center for Sex- and Gender-Specific Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Gyeonggi-do, Republic of Korea; (Y.C.); (S.M.B.); (H.Y.); (Y.S.P.); (D.H.L.)
| | - Hyuk Yoon
- Department of Internal Medicine, Research Center for Sex- and Gender-Specific Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Gyeonggi-do, Republic of Korea; (Y.C.); (S.M.B.); (H.Y.); (Y.S.P.); (D.H.L.)
| | - Young Soo Park
- Department of Internal Medicine, Research Center for Sex- and Gender-Specific Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Gyeonggi-do, Republic of Korea; (Y.C.); (S.M.B.); (H.Y.); (Y.S.P.); (D.H.L.)
| | - Dong Ho Lee
- Department of Internal Medicine, Research Center for Sex- and Gender-Specific Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Gyeonggi-do, Republic of Korea; (Y.C.); (S.M.B.); (H.Y.); (Y.S.P.); (D.H.L.)
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
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Lospinoso Severini F, Falco G, Notarangelo T. Role of Soluble Cytokine Receptors in Gastric Cancer Development and Chemoresistance. Int J Mol Sci 2025; 26:2534. [PMID: 40141175 PMCID: PMC11942508 DOI: 10.3390/ijms26062534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 02/28/2025] [Accepted: 03/08/2025] [Indexed: 03/28/2025] Open
Abstract
Gastric cancer is among the top five most important malignancies in the world due to the high burden of the disease and its lethality. Indeed, it is the fourth most common cause of death worldwide, characterized by a poor prognosis and low responsiveness to chemotherapy. Multidrug resistance limits the clinical management of the patient. Among these, the role of chronic activation of inflammatory pathways underlying gastric tumorigenesis should be highlighted. Furthermore, the gastric immunosuppressive TME influences the response to therapy. This review discusses the role of soluble cytokine receptors in the development and chemoresistance of gastric cancer, considered as a molecular marker and target of strategies to overcome resistance.
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Affiliation(s)
- Francesca Lospinoso Severini
- Laboratory of Preclinical and Translational Research, IRCCS CROB Centro di Riferimento Oncologico della Basilicata, 85028 Rionero in Vulture, PZ, Italy
| | - Geppino Falco
- Department of Biology, University of Naples Federico II, 80138 Napoli, NA, Italy
- Biogem, Istituto di Biologia e Genetica Molecolare, 83031 Ariano Irpino, AV, Italy
| | - Tiziana Notarangelo
- Laboratory of Preclinical and Translational Research, IRCCS CROB Centro di Riferimento Oncologico della Basilicata, 85028 Rionero in Vulture, PZ, Italy
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Maciel-Fiuza MF, Sbruzzi RC, Feira MF, Costa PDSS, Bonamigo RR, Vettorato R, Eidt LM, de Moraes PC, Oliveira Fam BSD, Castro SMDJ, Silveira MIDS, Vianna FSL. Influence of Cytokine-Related genetic variants in TNF, IL6, IL1β, and IFNγ genes in the thalidomide treatment for Erythema nodosum leprosum in a Brazilian population sample. Hum Immunol 2025; 86:111260. [PMID: 39956090 DOI: 10.1016/j.humimm.2025.111260] [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: 04/11/2024] [Revised: 01/20/2025] [Accepted: 02/03/2025] [Indexed: 02/18/2025]
Abstract
Erythema nodosum leprosum (ENL), an inflammatory reaction in leprosy, causes painful nodules, fever, and malaise due to immune system activation. Thalidomide is an effective treatment, although associated with important adverse effects. We aimed to evaluate the association of genetic variants in genes encoding tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) with the response to treatment of ENL with thalidomide. 148 patients from the South and Northeast regions of Brazil were included. Genomic DNA was isolated from blood and/or saliva samples using commercial kits, and genetic variants in TNF, IL6, IL1β, and IFNγ genes were genotyped by TaqMan system. We identified an association between polymorphisms in TNF (rs1799964C, rs1800630A, rs1799724T and rs1800629A) IL1β (rs4848306G, rs1143623G, rs16944A, and rs1143627A), IL6 (rs2069840C and rs2069845G) and IFNγ (rs2430561T) with thalidomide dose variation in a time-dependent manner. Associations of IL6 and TNF haplotypes with thalidomide dosage variation over the time of treatment were also observed. Polymorphisms in TNF, IL6, IL1β, and IFNγ genes may modulate their expression levels, potentially impacting the required dosage of thalidomide in the treatment of ENL. Our findings should be confirmed in further studies to estimate the size effect of these polymorphisms on ENL treatment with thalidomide.
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Affiliation(s)
- Miriãn Ferrão Maciel-Fiuza
- Postgraduate Program in Genetics and Molecular Biology, Federal University of Rio Grande do Sul Porto Alegre Rio Grande do Sul Brazil; National Institute of Population Medical Genetics Porto Alegre Rio Grande do Sul Brazil; Genomic Medicine Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre Porto Alegre Rio Grande do Sul Brazil; Immunobiology and Immunogenetics Laboratory, Postgraduate Program in Genetics and Molecular Biology, Department of Genetics, Federal University of Rio Grande do Sul Porto Alegre Rio Grande do Sul Brazil
| | - Renan Cesar Sbruzzi
- Postgraduate Program in Genetics and Molecular Biology, Federal University of Rio Grande do Sul Porto Alegre Rio Grande do Sul Brazil; Genomic Medicine Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre Porto Alegre Rio Grande do Sul Brazil; Immunobiology and Immunogenetics Laboratory, Postgraduate Program in Genetics and Molecular Biology, Department of Genetics, Federal University of Rio Grande do Sul Porto Alegre Rio Grande do Sul Brazil
| | - Mariléa Furtado Feira
- Postgraduate Program in Genetics and Molecular Biology, Federal University of Rio Grande do Sul Porto Alegre Rio Grande do Sul Brazil; National Institute of Population Medical Genetics Porto Alegre Rio Grande do Sul Brazil; Genomic Medicine Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre Porto Alegre Rio Grande do Sul Brazil; Immunobiology and Immunogenetics Laboratory, Postgraduate Program in Genetics and Molecular Biology, Department of Genetics, Federal University of Rio Grande do Sul Porto Alegre Rio Grande do Sul Brazil
| | | | - Renan Rangel Bonamigo
- Postgraduate Program in Pathology, Federal University of Health Sciences of Porto Alegre Porto Alegre Rio Grande do Sul Brazil; Dermatology Service of Hospital Santa Casa de Porto Alegre Porto Alegre Rio Grande do Sul Brazil; Postgraduate Program in Medicine, Medical Sciences, Federal University of Rio Grande do Sul Porto Alegre Rio Grande do Sul Brazil; Dermatology Service of Hospital de Clínicas de Porto Alegre Rio Grande do Sul Brazil
| | - Rodrigo Vettorato
- Dermatology Service of Hospital Santa Casa de Porto Alegre Porto Alegre Rio Grande do Sul Brazil
| | - Letícia Maria Eidt
- Sanitary Dermatology Outpatient Clinic, State Health Department of Rio Grande do Sul Porto Alegre Rio Grande do Sul Brazil
| | - Paulo Cezar de Moraes
- Postgraduate Program in Medicine, Medical Sciences, Federal University of Rio Grande do Sul Porto Alegre Rio Grande do Sul Brazil; Sanitary Dermatology Outpatient Clinic, State Health Department of Rio Grande do Sul Porto Alegre Rio Grande do Sul Brazil
| | - Bibiana Sampaio de Oliveira Fam
- Postgraduate Program in Genetics and Molecular Biology, Federal University of Rio Grande do Sul Porto Alegre Rio Grande do Sul Brazil; National Institute of Population Medical Genetics Porto Alegre Rio Grande do Sul Brazil; Genomic Medicine Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre Porto Alegre Rio Grande do Sul Brazil
| | - Stela Maris de Jezus Castro
- Department of Statistics, Universidade Federal Do Rio Grande Do Sul Porto Alegre Brazil; Postgraduate Program in Epidemiology, Universidade Federal Do Rio Grande Do Sul Porto Alegre Brazil
| | | | - Fernanda Sales Luiz Vianna
- Postgraduate Program in Genetics and Molecular Biology, Federal University of Rio Grande do Sul Porto Alegre Rio Grande do Sul Brazil; National Institute of Population Medical Genetics Porto Alegre Rio Grande do Sul Brazil; Genomic Medicine Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre Porto Alegre Rio Grande do Sul Brazil; Immunobiology and Immunogenetics Laboratory, Postgraduate Program in Genetics and Molecular Biology, Department of Genetics, Federal University of Rio Grande do Sul Porto Alegre Rio Grande do Sul Brazil; Postgraduate Program in Medicine, Medical Sciences, Federal University of Rio Grande do Sul Porto Alegre Rio Grande do Sul Brazil.
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de Melo Viana TC, Nakamura ET, Park A, Filardi KFXC, de Almeida Leite RM, Baltazar LFSR, Usón Junior PLS, Tustumi F. Molecular Abnormalities and Carcinogenesis in Barrett's Esophagus: Implications for Cancer Treatment and Prevention. Genes (Basel) 2025; 16:270. [PMID: 40149421 PMCID: PMC11942460 DOI: 10.3390/genes16030270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2025] [Revised: 02/16/2025] [Accepted: 02/23/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Barrett's esophagus (BE) is described by the transformation of the normal squamous epithelium into metaplastic columnar epithelium, driven by chronic gastroesophageal reflux disease (GERD). BE is a recognized premalignant condition and the main precursor to esophageal adenocarcinoma (EAC). Understanding the molecular mechanisms underlying BE carcinogenesis is crucial for improving prevention, surveillance, and treatment strategies. METHODS This narrative review examines the molecular abnormalities associated with the progression of BE to EAC. RESULTS This study highlights inflammatory, genetic, epigenetic, and chromosomal alterations, emphasizing key pathways and biomarkers. BE progression follows a multistep process involving dysplasia and genetic alterations such as TP53 and CDKN2A (p16) mutations, chromosomal instability, and dysregulation of pathways like PI3K/AKT/mTOR. Epigenetic alterations, including aberrant microRNA expression or DNA methylation, further contribute to this progression. These molecular changes are stage-specific, with some alterations occurring early in BE during the transition to high-grade dysplasia or EAC. Innovations in chemoprevention, such as combining proton pump inhibitors and aspirin, and the potential of antireflux surgery to halt disease progression are promising. Incorporating molecular biomarkers into surveillance strategies and advancing precision medicine may enable earlier detection and personalized treatments. CONCLUSIONS BE is the primary preneoplastic condition for EAC. A deeper understanding of its molecular transformation can enhance surveillance protocols, optimize the management of gastroesophageal reflux inflammation, and refine prevention and therapeutic strategies, ultimately contributing to a reduction in the global burden of EAC.
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Affiliation(s)
| | | | - Amanda Park
- Department of Evidenced-Based Medicine, Centro Universitário Lusíada, Santos 11050-071, Brazil
| | | | | | | | | | - Francisco Tustumi
- Department of Gastroenterology, Universidade de Sao Paulo, Sao Paulo 05508-220, Brazil
- Department of Health Sciences, Hospital Israelita Albert Einstein, Sao Paulo 05652-900, Brazil
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Sirit IS, Peek RM. Decoding the Ability of Helicobacter pylori to Evade Immune Recognition and Cause Disease. Cell Mol Gastroenterol Hepatol 2025; 19:101470. [PMID: 39889829 PMCID: PMC11946503 DOI: 10.1016/j.jcmgh.2025.101470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 01/23/2025] [Accepted: 01/23/2025] [Indexed: 02/03/2025]
Abstract
Helicobacter pylori (H pylori) successfully and chronically colonizes the gastric mucosa of approximately 43% of the world's population. Infection with this organism is the strongest known risk factor for the development of gastric cancer, and disease development is dependent on several interactive components. One H pylori determinant that augments cancer risk is the strain-specific cag type IV secretion system, which not only translocates a pro-inflammatory and oncogenic protein, CagA, into host cells but also DNA, peptidoglycan, and a lipopolysaccharide intermediate, heptose-1,7-bisphosphate. However, cognate interactions between certain microbial and host constituents can also attenuate pro-inflammatory responses, and H pylori harbors multiple effectors that function differently than the respective counterparts in other mucosal pathogens. In this review, we discuss current data related to mechanisms utilized by H pylori to evade the immune response, sustain its longevity in the host, and further disease progression, as well as implications for developing targeted, immune-based eradication strategies.
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Affiliation(s)
- Isabella S Sirit
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee; Molecular Pathology and Immunology Training Program, Vanderbilt University, Nashville, Tennessee
| | - Richard M Peek
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
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Toma FM, Kalam KT, Haque MA, Reza S, Akter R, Islam MS, Islam MR, Nahar Z. Interleukin-1β rs16944 and rs1143627 polymorphisms and risk of developing major depressive disorder: A case-control study among Bangladeshi population. PLoS One 2025; 20:e0317665. [PMID: 39841732 PMCID: PMC11753680 DOI: 10.1371/journal.pone.0317665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 01/02/2025] [Indexed: 01/24/2025] Open
Abstract
BACKGROUND Epidemiological research suggests that altered levels of cytokine are associated with pathophysiology and the development of major depressive disorder (MDD). Based on earlier study, IL-1β rs16944 and rs1143627 polymorphisms may increase the risk of depression. Here, we aimed to evaluate the correlation between these polymorphisms and MDD susceptibility among the population in Bangladesh. METHODS Blood samples were collected from 100 MDD patients and 70 matched controls. Study participants were evaluated by DSM-5 criteria and PCR-RFLP method were applied for genotyping. RESULTS The IL1β rs1143627 and rs16944 polymorphisms were found to have a significant association with the risk of MDD. In case of rs1143627 CT heterozygous genotype (OR = 2.22, 95% CI = 1.08-4.55, p-value = 0.029) and combined CT+TT (OR = 2.35, 95% CI = 1.15-4.79, p-value = 0.019) genotype was strongly associated with the increased risk of MDD in comparison to CC common genotype. Moreover, the over-dominant model indicated a 2.15-fold higher risk for MDD development (OR = 2.15, 95% CI = 1.05-4.40, p-value = 0.036). On the other hand, the IL1β rs16944 polymorphisms revealed that the TC+CC combined genotype in the dominant model showed a 2.06-fold increased risk for MDD development compared to the TT common homozygote (OR = 2.06, 95% CI = 1.06-3.99, p-value = 0.032). CONCLUSION Studies suggests that IL1β rs16944 and rs1143627 polymorphisms are associated with an increased risk of MDD. These findings will provide us with valuable insights into the pathophysiology of MDD.
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Affiliation(s)
| | | | | | - Sejuti Reza
- Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh
| | | | - Mohammad Safiqul Islam
- Department of Pharmacy, Noakhali Science and Technology University, Noakhali, Bangladesh
| | | | - Zabun Nahar
- Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh
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Zolotareva K, Dotsenko PA, Podkolodnyy N, Ivanov R, Makarova AL, Chadaeva I, Bogomolov A, Demenkov PS, Ivanisenko V, Oshchepkov D, Ponomarenko M. Candidate SNP Markers Significantly Altering the Affinity of the TATA-Binding Protein for the Promoters of Human Genes Associated with Primary Open-Angle Glaucoma. Int J Mol Sci 2024; 25:12802. [PMID: 39684516 DOI: 10.3390/ijms252312802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 11/20/2024] [Accepted: 11/25/2024] [Indexed: 12/18/2024] Open
Abstract
Primary open-angle glaucoma (POAG) is the most common form of glaucoma. This condition leads to optic nerve degeneration and eventually to blindness. Tobacco smoking, alcohol consumption, fast-food diets, obesity, heavy weight lifting, high-intensity physical exercises, and many other bad habits are lifestyle-related risk factors for POAG. By contrast, moderate-intensity aerobic exercise and the Mediterranean diet can alleviate POAG. In this work, we for the first time estimated the phylostratigraphic age indices (PAIs) of all 153 POAG-related human genes in the NCBI Gene Database. This allowed us to separate them into two groups: POAG-related genes that appeared before and after the phylum Chordata, that is, ophthalmologically speaking, before and after the camera-type eye evolved. Next, in the POAG-related genes' promoters, we in silico predicted all 3835 candidate SNP markers that significantly change the TATA-binding protein (TBP) affinity for these promoters and, through this molecular mechanism, the expression levels of these genes. Finally, we verified our results against five independent web services-PANTHER, DAVID, STRING, MetaScape, and GeneMANIA-as well as the ClinVar database. It was concluded that POAG is likely to be a symptom of the human self-domestication syndrome, a downside of being civilized.
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Affiliation(s)
- Karina Zolotareva
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
| | - Polina A Dotsenko
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
- Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia
| | - Nikolay Podkolodnyy
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
- Institute of Computational Mathematics and Mathematical Geophysics, SB RAS, Novosibirsk 630090, Russia
| | - Roman Ivanov
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
| | - Aelita-Luiza Makarova
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
| | - Irina Chadaeva
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
| | - Anton Bogomolov
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia
| | - Pavel S Demenkov
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
| | - Vladimir Ivanisenko
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
- Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia
| | - Dmitry Oshchepkov
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
- Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia
| | - Mikhail Ponomarenko
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
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Kővári B, Carneiro F, Lauwers GY. Epithelial tumours of the stomach. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:227-286. [DOI: 10.1002/9781119423195.ch13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Linz B, Sticht H, Tegtmeyer N, Backert S. Cancer-associated SNPs in bacteria: lessons from Helicobacter pylori. Trends Microbiol 2024; 32:847-857. [PMID: 38485609 DOI: 10.1016/j.tim.2024.02.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 02/01/2024] [Accepted: 02/02/2024] [Indexed: 09/06/2024]
Abstract
Several single-nucleotide polymorphisms (SNPs) in human chromosomes are known to predispose to cancer. However, cancer-associated SNPs in bacterial pathogens were unknown until discovered in the stomach pathogen Helicobacter pylori. Those include an alanine-threonine polymorphism in the EPIYA-B phosphorylation motif of the injected effector protein CagA that affects cancer risk by modifying inflammatory responses and loss of host cell polarity. A serine-to-leucine change in serine protease HtrA is associated with boosted proteolytic cleavage of epithelial junction proteins and introduction of DNA double-strand breaks (DSBs) in host chromosomes, which co-operatively elicit malignant alterations. In addition, H. pylori genome-wide association studies (GWAS) identified several other SNPs potentially associated with increased gastric cancer (GC) risk. Here we discuss the clinical importance, evolutionary origin, and functional advantage of the H. pylori SNPs. These exciting new data highlight cancer-associated SNPs in bacteria, which should be explored in more detail in future studies.
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Affiliation(s)
- Bodo Linz
- Department of Biology, Division of Microbiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Staudtstr. 5, 91058 Erlangen, Germany
| | - Heinrich Sticht
- Division of Bioinformatics, Institute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg; 91054 Erlangen, Germany
| | - Nicole Tegtmeyer
- Department of Biology, Division of Microbiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Staudtstr. 5, 91058 Erlangen, Germany
| | - Steffen Backert
- Department of Biology, Division of Microbiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Staudtstr. 5, 91058 Erlangen, Germany.
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15
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Forgerini M, Zanelli CF, Valentini SR, Mastroianni PDC. Influence of IL-β, IL-1RN, and TNF-α variants on the risk of acetylsalicylic acid-induced upper gastrointestinal bleeding: a case-control study. EINSTEIN-SAO PAULO 2024; 22:eAO0746. [PMID: 39194098 DOI: 10.31744/einstein_journal/2024ao0746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 02/05/2024] [Indexed: 08/29/2024] Open
Abstract
OBJECTIVE Forgerini et al. investigated the role of seven genetic variants in the risk of upper gastrointestinal bleeding as an adverse drug reaction. In 289 participants (50 cases and 189 controls), the presence of seven variants in the IL-1β, IL-1RN, and TNF-α genes was not associated with susceptibility to acetylsalicylic acid-induced upper gastrointestinal bleeding. The use of acetylsalicylic acid, even in low doses, may be associated with the onset of upper gastrointestinal bleeding as an idiosyncratic response. Considering the role of the genetic background in inter-individual responses to pharmacotherapy, we aimed to investigate the role of seven variants in the TNF-α, IL-β, and IL-1RN genes in association with the risk of upper gastrointestinal bleeding in users of low-dose acetylsalicylic acid for the prevention of cardiovascular events. METHODS A case-control study was conducted in a Brazilian hospital complex. The Case Group comprised patients diagnosed with upper gastrointestinal bleeding who were administered a low dose of acetylsalicylic acid (n=50). Two Control Groups were recruited: 1) low-dose acetylsalicylic acid users without gastrointestinal complaints and under the supervision of a cardiologist (n=50) and 2) healthy controls (n=189). Sociodemographic, clinical, pharmacotherapeutic, and lifestyle data were recorded through face-to-face interviews. Genomic DNA from all participants was genotyped for rs16944 and rs1143634 (IL-β gene), rs4251961 (IL-1RN gene), and rs1799964, rs1799724, rs361525, and rs1800629 (TNF-α gene). RESULTS No significant difference was noted in the genotypic frequencies of TNF-α, IL-β, and IL-1RN variants between the Case and Control Groups of low-dose acetylsalicylic acid users (p>0.05). The frequency of rs1800629 genotypes (TNF-α gene) differed significantly between the Case Group and healthy controls (p=0.003). None of the evaluated variants were associated with a risk of upper gastrointestinal bleeding. CONCLUSION This study aimed to explore pharmacogenomics biomarkers in low-dose acetylsalicylic acid users. Our data suggest that the presence of IL-1β, IL-1RN, and TNF-α variants was not associated with an increased risk of upper gastrointestinal bleeding.
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Affiliation(s)
- Marcela Forgerini
- Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista "Júlio de Mesquita Filho", Araraquara, SP, Brazil
| | - Cleslei Fernando Zanelli
- Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista "Júlio de Mesquita Filho", Araraquara, SP, Brazil
| | - Sandro Roberto Valentini
- Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista "Júlio de Mesquita Filho", Araraquara, SP, Brazil
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16
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Pădureanu V, Dop D, Caragea DC, Rădulescu D, Pădureanu R, Forțofoiu MC. Cardiovascular and Neurological Diseases and Association with Helicobacter Pylori Infection-An Overview. Diagnostics (Basel) 2024; 14:1781. [PMID: 39202269 PMCID: PMC11353373 DOI: 10.3390/diagnostics14161781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 08/05/2024] [Accepted: 08/14/2024] [Indexed: 09/03/2024] Open
Abstract
This article investigates the link between Helicobacter pylori (H. pylori) infection and cardiovascular and neurological disorders. Recent research suggests that H. pylori may play a role in cardiovascular diseases like atherosclerosis, myocardial infarction, and stroke, as well as neurological diseases including Alzheimer's disease, multiple sclerosis, and Parkinson's disease. Cardiovascular Diseases: H. pylori induces endothelial dysfunction and chronic inflammation, promoting atherosclerotic plaque formation and other cardiac complications. High infection prevalence in cardiovascular patients implies that systemic inflammation from H. pylori accelerates disease progression. Eradication therapies combined with anti-inflammatory and lipid-lowering treatments may reduce cardiovascular risk. Neurological Diseases: H. pylori may contribute to Alzheimer's, multiple sclerosis, and Parkinson's through systemic inflammation, neuroinflammation, and autoimmune responses. Increased infection prevalence in these patients suggests bacterial involvement in disease pathogenesis. The eradication of H. pylori could reduce neuroinflammation and improve outcomes. Discussions and Future Research: Managing H. pylori infection in clinical practice could impact public health and treatment approaches. Further research is needed to clarify these relationships. Longitudinal and mechanistic studies are essential to fully understand H. pylori's role in these conditions. Conclusions: H. pylori infection is a potential risk factor for various cardiovascular and neurological conditions. Additional research is critical for developing effective prevention and treatment strategies. Targeted therapies, including H. pylori eradication combined with anti-inflammatory treatments, could improve clinical outcomes. These findings highlight the need for an integrated clinical approach to include H. pylori evaluation and treatment.
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Affiliation(s)
- Vlad Pădureanu
- Department of Internal Medicine, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania; (V.P.); (M.-C.F.)
| | - Dalia Dop
- Department of Pediatrics, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania;
| | - Daniel Cosmin Caragea
- Department of Nephrology, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania;
| | - Dumitru Rădulescu
- Department of Surgery, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania
| | - Rodica Pădureanu
- Department of Internal Medicine, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania; (V.P.); (M.-C.F.)
| | - Mircea-Cătălin Forțofoiu
- Department of Internal Medicine, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania; (V.P.); (M.-C.F.)
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17
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Sugimoto M, Murata M, Murakami K, Yamaoka Y, Kawai T. Characteristic endoscopic findings in Helicobacter pylori diagnosis in clinical practice. Expert Rev Gastroenterol Hepatol 2024; 18:457-472. [PMID: 39162811 DOI: 10.1080/17474124.2024.2395317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 08/19/2024] [Indexed: 08/21/2024]
Abstract
INTRODUCTION Helicobacter pylori is a major risk factor for gastric cancer. In addition to eradication therapy, early-phase detection of gastric cancer through screening programs using high-vision endoscopy is also widely known to reduce mortality. Although European and US guidelines recommend evaluation of atrophy and intestinal metaplasia by high-vision endoscopy and pathological findings, the guideline used in Japan - the Kyoto classification of gastritis - is based on endoscopic evaluation, and recommends the grading of risk factors. This system requires classification into three endoscopic groups: H. pylori-negative, previous H. pylori infection (inactive gastritis), and current H. pylori infection (active gastritis). Major endoscopic findings in active gastritis are diffuse redness, enlarged folds, nodularity, mucosal swelling, and sticky mucus, while those in H pylori-related gastritis - irrespective of active or inactive status - are atrophy, intestinal metaplasia, and xanthoma. AREAS COVERED This review describes the endoscopic characteristics of current H. pylori infection, and how characteristic endoscopic findings should be evaluated. EXPERT OPINION Although the correct evaluation of endoscopic findings related to H. pylori remains necessary, if findings of possible infection are observed, it is important to diagnose infection by detection methods with high sensitivity and specificity, including the stool antigen test and urea breath test.
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Affiliation(s)
- Mitsushige Sugimoto
- Division of Genome-Wide Infectious Diseases, Research Center for GLOBAL and LOCAL Infectious Disease, Oita University, Yufu, Japan
| | - Masaki Murata
- Department of Gastroenterology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | | | - Yoshio Yamaoka
- Division of Genome-Wide Infectious Diseases, Research Center for GLOBAL and LOCAL Infectious Disease, Oita University, Yufu, Japan
- Department of Environmental and Preventive Medicine, Oita University, Yufu, Japan
| | - Takashi Kawai
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Shinjuku, Japan
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18
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Namba Y, Kobayashi T, Tadokoro T, Fukuhara S, Oshita K, Matsubara K, Honmyo N, Kuroda S, Ohira M, Ohdan H. Effect of genetic polymorphisms of interleukin-1 beta on the microscopic portal vein invasion and prognosis of hepatocellular carcinoma. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2024; 31:528-536. [PMID: 38798075 PMCID: PMC11503458 DOI: 10.1002/jhbp.12009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/29/2024]
Abstract
BACKGROUND Several studies have demonstrated a relationship between genetic polymorphisms of interleukin-1 beta (IL-1β) and cancer development; however, their influence on cancer prognosis is unknown. In the present study, we aimed to evaluate the impact of IL-1β single nucleotide polymorphisms on the hematogenous dissemination and prognosis of hepatocellular carcinoma. METHODS We conducted a retrospective cohort study including patients with hepatocellular carcinoma who underwent primary liver resection at our hospital between April 2015 and December 2018. The primary endpoints were overall and recurrence-free survival. Secondary endpoints were microscopic portal vein invasion and number of circulating tumor cells. RESULTS A total of 148 patients were included, 32 with rs16944 A/A genotype. A/A genotype was associated with microscopic portal vein invasion and number of circulating tumor cells (p = .03 and .04). In multivariate analysis, A/A genotype, alpha-fetoprotein level, and number of circulating tumor cells were associated with microscopic portal vein invasion (p = .01, .01, and <.01). A/A genotype, Child-Pugh B, and intraoperative blood loss were independent predictive factors for overall survival (p = .02, <.01, and <.01). CONCLUSIONS Our results indicate that the IL-1β rs16944 A/A genotype is involved in number of circulating tumor cells, microscopic portal vein invasion, and prognosis in HCC.
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Affiliation(s)
- Yosuke Namba
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
| | - Takeshi Tadokoro
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
| | - Sotaro Fukuhara
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
| | - Ko Oshita
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
| | - Keiso Matsubara
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
| | - Naruhiko Honmyo
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
| | - Shintaro Kuroda
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
| | - Masahiro Ohira
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
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Ozeki K, Hada K, Wakiya Y. Factors Influencing the Degree of Gastric Atrophy in Helicobacter pylori Eradication Patients with Drinking Habits. Microorganisms 2024; 12:1398. [PMID: 39065166 PMCID: PMC11278706 DOI: 10.3390/microorganisms12071398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 07/08/2024] [Accepted: 07/08/2024] [Indexed: 07/28/2024] Open
Abstract
Chronic gastritis caused by Helicobacter pylori (H. pylori) infection can lead to gastric atrophy. This study aimed to identify the factors associated with gastric atrophy in H. pylori eradication patients with drinking habits. Of the 250 patients who visited Hamamatsu University Hospital for H. pylori eradication and underwent eradication treatment between April 2017 and December 2020, 127 patients with drinking habits were included in this study. The degree of gastric atrophy of the patients was classified based on endoscopy. The relationship between patient attributes (sex, age, alcohol consumption, frequency of drinking, smoking status, and medication use) and a highly atrophic stomach was statistically analyzed. The results showed that gastric atrophy was significantly higher in males and in those aged 60 years or older and that gastric atrophy tended to be higher in those who drank 20 g or more per day and 5 days or more a week. There was also a trend toward higher atrophy in sake drinkers and lower atrophy in wine drinkers. This study provides useful knowledge for patient management and guidance after H. pylori eradication treatment and indicates the importance of comprehensive measures, including alcohol consumption control and lifestyle modification, especially for men and older people.
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Affiliation(s)
- Kayoko Ozeki
- Laboratory of Pharmacy Practice and Sciences, Aichi Gakuin University, Nagoya 4648650, Aichi, Japan; (K.H.); (Y.W.)
- Department of Community Health and Preventive Medicine, Hamamatsu University School of Medicine, Hamamatsu 4313192, Shizuoka, Japan
| | - Kazuhiro Hada
- Laboratory of Pharmacy Practice and Sciences, Aichi Gakuin University, Nagoya 4648650, Aichi, Japan; (K.H.); (Y.W.)
| | - Yoshifumi Wakiya
- Laboratory of Pharmacy Practice and Sciences, Aichi Gakuin University, Nagoya 4648650, Aichi, Japan; (K.H.); (Y.W.)
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20
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Hnatyszyn A, Szalata M, Zielińska A, Wielgus K, Danielewski M, Hnatyszyn PT, Pławski A, Walkowiak J, Słomski R. Mutations in Helicobacter pylori infected patients with chronic gastritis, intestinal type of gastric cancer and familial gastric cancer. Hered Cancer Clin Pract 2024; 22:9. [PMID: 38867324 PMCID: PMC11167877 DOI: 10.1186/s13053-024-00282-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 06/04/2024] [Indexed: 06/14/2024] Open
Abstract
BACKGROUND Development of sequential changes of mucous leading to gastric cancer and familial cases of gastric cancer of intestinal type is widely connected with Helicobacter pylori infections. In this study we analysed variants of genes involved in cancerogenesis and inflammatory processes of intestines in patients infected with H.pylori. Our goal was to test whether mutations in these genes predestinate to development of gastric cancer, and whether there is a genetic factor that makes it more likely for infections with H.pylori to cause gastric cancer. As infections with H. pylori are relatively common, discovering such genetic predispositions could be used for establishing risk-groups and for planning treatments. METHODS Our studies cover analysis of variants in genes involved in cancerogenesis: TP53 (rs11540652, rs587782329, COSM10771), MSH2 (rs193922376), MLH1 (rs63750217), and inflammatory processes of intestine: NOD2 (rs2066847, rs2066842), IL1A (rs1800587) and IL1B (rs1143634) from H.pylori-infected patients. RESULTS Mutations were more common in the group of patients with gastric cancer of intestinal type and familial cases of gastric cancer in comparison with patients with chronic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia or gastric cancer (p-value = 0.00824), with the prevalence of p53 mutations in patients with familial gastric cancer vs. patients with other changes of mucosa (p-value = 0.000049). Additionally, gastric cancer patients have mainly genotype TT or CT of the rs2066842 variant of the NOD2 gene. CONCLUSIONS The lack of statistically significant changes of other interleukin genes involved in inflammatory processes may suggest the presence of H.pylori infection as a potential trigger for the development of the inflammatory process of the mucosa, leading through microbiota dysbiosis to the development of enteric gastric cancer. Mutations in analysed genes correlated with more severe mucosal changes, with a much more frequent presence of TP53 gene mutations, with a limited presence of other mutations in the familial history of gastric cancer.
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Affiliation(s)
- Andrzej Hnatyszyn
- Independent Public Health Care Centre in Nowa Sol, Multispecialty Hospital, Chalubinskiego 7, Nowa Sol, 67-100, Poland
| | - Marlena Szalata
- Department of Biochemistry and Biotechnology, Poznań University of Life Sciences, Dojazd 11, Poznań, 60-632, Poland
| | - Aleksandra Zielińska
- Department of Biotechnology, Institute of Natural Fibres and Medicinal Plants National Research Institute, Wojska Polskiego 71B, Poznań, 60-630, Poland
| | - Karolina Wielgus
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Szpitalna 27/33, Poznań, 60-572, Poland
| | - Mikołaj Danielewski
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Szpitalna 27/33, Poznań, 60-572, Poland
| | | | - Andrzej Pławski
- Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, Poznań, 60-479, Poland
- Department of General, Endocrinological Surgery and Gastrointestinal Oncology, Institute of Surgery, Poznan University of Medical Sciences, Przybyszewskiego 49, Poznań, 60-355, Poland
| | - Jarosław Walkowiak
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Szpitalna 27/33, Poznań, 60-572, Poland
| | - Ryszard Słomski
- Department of Biotechnology, Institute of Natural Fibres and Medicinal Plants National Research Institute, Wojska Polskiego 71B, Poznań, 60-630, Poland.
- Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, Poznań, 60-479, Poland.
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21
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Sgamato C, Rocco A, Compare D, Priadko K, Romano M, Nardone G. Exploring the Link between Helicobacter pylori, Gastric Microbiota and Gastric Cancer. Antibiotics (Basel) 2024; 13:484. [PMID: 38927151 PMCID: PMC11201017 DOI: 10.3390/antibiotics13060484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 05/20/2024] [Accepted: 05/21/2024] [Indexed: 06/28/2024] Open
Abstract
Gastric cancer (GC) still represents one of the leading causes of cancer-related mortality and is a major public health issue worldwide. Understanding the etiopathogenetic mechanisms behind GC development holds immense potential to revolutionize patients' treatment and prognosis. Within the complex web of genetic predispositions and environmental factors, the connection between Helicobacter pylori (H. pylori) and gastric microbiota emerges as a focus of intense research investigation. According to the most recent hypotheses, H. pylori triggers inflammatory responses and molecular alterations in gastric mucosa, while non-Helicobacter microbiota modulates disease progression. In this review, we analyze the current state of the literature on the relationship between H. pylori and non-Helicobacter gastric microbiota in gastric carcinogenesis, highlighting the mechanisms by which microecological dysbiosis can contribute to the malignant transformation of the mucosa.
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Affiliation(s)
- Costantino Sgamato
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, University Federico II of Naples, 80131 Naples, Italy; (C.S.); (D.C.); (G.N.)
| | - Alba Rocco
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, University Federico II of Naples, 80131 Naples, Italy; (C.S.); (D.C.); (G.N.)
| | - Debora Compare
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, University Federico II of Naples, 80131 Naples, Italy; (C.S.); (D.C.); (G.N.)
| | - Kateryna Priadko
- Hepatogastroenterology Unit, Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy; (K.P.); (M.R.)
| | - Marco Romano
- Hepatogastroenterology Unit, Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy; (K.P.); (M.R.)
| | - Gerardo Nardone
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, University Federico II of Naples, 80131 Naples, Italy; (C.S.); (D.C.); (G.N.)
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22
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Rai S, Zhang Y, Grockowiak E, Kimmerlin Q, Hansen N, Stoll CB, Usart M, Luque Paz D, Hao-Shen H, Zhu Y, Roux J, Bader MS, Dirnhofer S, Farady CJ, Schroeder T, Méndez-Ferrer S, Skoda RC. IL-1β promotes MPN disease initiation by favoring early clonal expansion of JAK2-mutant hematopoietic stem cells. Blood Adv 2024; 8:1234-1249. [PMID: 38207211 PMCID: PMC10912850 DOI: 10.1182/bloodadvances.2023011338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 12/26/2023] [Accepted: 01/02/2024] [Indexed: 01/13/2024] Open
Abstract
ABSTRACT JAK 2-V617F is the most frequent somatic mutation causing myeloproliferative neoplasm (MPN). JAK2-V617F can be found in healthy individuals with clonal hematopoiesis of indeterminate potential (CHIP) with a frequency much higher than the prevalence of MPNs. The factors controlling the conversion of JAK2-V617F CHIP to MPN are largely unknown. We hypothesized that interleukin-1β (IL-1β)-mediated inflammation can favor this progression. We established an experimental system using bone marrow (BM) transplantations from JAK2-V617F and GFP transgenic (VF;GFP) mice that were further crossed with IL-1β-/- or IL-1R1-/- mice. To study the role of IL-1β and its receptor on monoclonal evolution of MPN, we performed competitive BM transplantations at high dilutions with only 1 to 3 hematopoietic stem cells (HSCs) per recipient. Loss of IL-1β in JAK2-mutant HSCs reduced engraftment, restricted clonal expansion, lowered the total numbers of functional HSCs, and decreased the rate of conversion to MPN. Loss of IL-1R1 in the recipients also lowered the conversion to MPN but did not reduce the frequency of engraftment of JAK2-mutant HSCs. Wild-type (WT) recipients transplanted with VF;GFP BM that developed MPNs had elevated IL-1β levels and reduced frequencies of mesenchymal stromal cells (MSCs). Interestingly, frequencies of MSCs were also reduced in recipients that did not develop MPNs, had only marginally elevated IL-1β levels, and displayed low GFP-chimerism resembling CHIP. Anti-IL-1β antibody preserved high frequencies of MSCs in VF;GFP recipients and reduced the rate of engraftment and the conversion to MPN. Our results identify IL-1β as a potential therapeutic target for preventing the transition from JAK2-V617F CHIP to MPNs.
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Affiliation(s)
- Shivam Rai
- Department of Biomedicine, Experimental Hematology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Yang Zhang
- Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zurich, Basel, Switzerland
| | - Elodie Grockowiak
- Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, United Kingdom
- Department of Hematology, University of Cambridge, Cambridge, United Kingdom
- National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom
| | - Quentin Kimmerlin
- Department of Biomedicine, Experimental Hematology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Nils Hansen
- Department of Biomedicine, Experimental Hematology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Cedric B. Stoll
- Department of Biomedicine, Experimental Hematology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Marc Usart
- Department of Biomedicine, Experimental Hematology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Damien Luque Paz
- University of Angers, Nantes Université, CHU Angers, INSERM, CNRS, CRCI2NA, Angers, France
| | - Hui Hao-Shen
- Department of Biomedicine, Experimental Hematology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Yexuan Zhu
- Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, United Kingdom
- Department of Hematology, University of Cambridge, Cambridge, United Kingdom
- National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom
| | - Julien Roux
- Department of Biomedicine, Bioinformatics core facility, University of Basel, Basel, Switzerland
- Swiss Institute of Bioinformatics, Basel, Switzerland
| | - Michael S. Bader
- Division of Hematology, University Hospital Basel, Basel, Switzerland
| | - Stefan Dirnhofer
- Department of Pathology, University Hospital Basel, Basel, Switzerland
| | | | - Timm Schroeder
- Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zurich, Basel, Switzerland
| | - Simón Méndez-Ferrer
- Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, United Kingdom
- Department of Hematology, University of Cambridge, Cambridge, United Kingdom
- National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom
| | - Radek C. Skoda
- Department of Biomedicine, Experimental Hematology, University Hospital Basel, University of Basel, Basel, Switzerland
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23
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Rugge M, Genta RM, Malfertheiner P, Dinis-Ribeiro M, El-Serag H, Graham DY, Kuipers EJ, Leung WK, Park JY, Rokkas T, Schulz C, El-Omar EM. RE.GA.IN.: the Real-world Gastritis Initiative-updating the updates. Gut 2024; 73:407-441. [PMID: 38383142 DOI: 10.1136/gutjnl-2023-331164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Accepted: 12/18/2023] [Indexed: 02/23/2024]
Abstract
At the end of the last century, a far-sighted 'working party' held in Sydney, Australia addressed the clinicopathological issues related to gastric inflammatory diseases. A few years later, an international conference held in Houston, Texas, USA critically updated the seminal Sydney classification. In line with these initiatives, Kyoto Global Consensus Report, flanked by the Maastricht-Florence conferences, added new clinical evidence to the gastritis clinicopathological puzzle.The most relevant topics related to the gastric inflammatory diseases have been addressed by the Real-world Gastritis Initiative (RE.GA.IN.), from disease definitions to the clinical diagnosis and prognosis. This paper reports the conclusions of the RE.GA.IN. consensus process, which culminated in Venice in November 2022 after more than 8 months of intense global scientific deliberations. A forum of gastritis scholars from five continents participated in the multidisciplinary RE.GA.IN. consensus. After lively debates on the most controversial aspects of the gastritis spectrum, the RE.GA.IN. Faculty amalgamated complementary knowledge to distil patient-centred, evidence-based statements to assist health professionals in their real-world clinical practice. The sections of this report focus on: the epidemiology of gastritis; Helicobacter pylori as dominant aetiology of environmental gastritis and as the most important determinant of the gastric oncogenetic field; the evolving knowledge on gastric autoimmunity; the clinicopathological relevance of gastric microbiota; the new diagnostic horizons of endoscopy; and the clinical priority of histologically reporting gastritis in terms of staging. The ultimate goal of RE.GA.IN. was and remains the promotion of further improvement in the clinical management of patients with gastritis.
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Affiliation(s)
- Massimo Rugge
- Department of Medicine-DIMED, University of Padova, Padua, Italy
- Azienda Zero, Veneto Tumour Registry, Padua, Italy
| | - Robert M Genta
- Gastrointestinal Pathology, Inform Diagnostics Research Institute, Dallas, Texas, USA
- Pathology, Baylor College of Medicine, Houston, Texas, USA
| | - Peter Malfertheiner
- Medizinische Klinik und Poliklinik II, Ludwig Maximilian Universität Klinikum München, Munich, Germany
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Otto-von-Guericke Universität Magdeburg, Magdeburg, Germany
| | - Mario Dinis-Ribeiro
- Porto Comprehensive Cancer Center & RISE@CI-IPO, University of Porto, Porto, Portugal
- Gastroenterology Department, Portuguese Institute of Oncology of Porto, Porto, Portugal
| | - Hashem El-Serag
- Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA
- Houston VA Health Services Research & Development Center of Excellence, Michael E DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - David Y Graham
- Department of Medicine, Michael E DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - Ernst J Kuipers
- Erasmus University Medical Center, Rotterdam, The Netherlands
| | | | - Jin Young Park
- International Agency for Research on Cancer, Lyon, France
| | - Theodore Rokkas
- Gastroenterology, Henry Dunant Hospital Center, Athens, Greece
| | | | - Emad M El-Omar
- Microbiome Research Centre, University of New South Wales, Sydney, New South Wales, Australia
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24
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Yang S, Hao S, Ye H, Zhang X. Cross-talk between Helicobacter pylori and gastric cancer: a scientometric analysis. Front Cell Infect Microbiol 2024; 14:1353094. [PMID: 38357448 PMCID: PMC10864449 DOI: 10.3389/fcimb.2024.1353094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Accepted: 01/17/2024] [Indexed: 02/16/2024] Open
Abstract
Background Helicobacter pylori (HP) is considered a leading risk factor for gastric cancer (GC). The aim of this article is to conduct bibliometric and visual analysis to assess scientific output, identify highly cited papers, summarize current knowledge, and explore recent hotspots and trends in HP/GC research. Methods A bibliographic search was conducted on October 24, 2023, to retrieve relevant studies on HP/GC research between 2003 and 2022. The search terms were attached to HP and GC. The main data were from the Web of Science Core Collection (WoSCC). Data visualization was performed using Biblioshiny, VOSviewer, and Microsoft Excel. Results In HP/GC research, 1970 papers were retrieved. The total number of papers (Np) in HP/GC was growing from 2003 to 2022. China and Japan were in the leading position and made the most contributions to HP/GC. Vanderbilt University and the US Department of Veterans Affairs had the highest Np. The most productive authors were Peek Jr Richard M. and Piazuelo M Blanca. Helicobacter received the most Np, while Gastroenterology had the most total citations (TC). High-cited publications and keyword clustering were used to identify the current status and trends in HP/GC research, while historical citation analysis provided insight into the evolution of HP/GC research. The hot topics included the effect of HP on gastric tumorigenesis and progression, the pathogenesis of HP-induced GC (HP factors), and the mechanisms by which HP affects GC (host factors). Research in the coming years could focus on topics such as autophagy, gut microbiota, immunotherapy, exosomes, epithelial-mesenchymal transition (EMT), and gamma-glutamyl transpeptidase (GGT). Conclusion This study evaluated the global scientific output in HP/GC research and its quantitative characteristics, identified the essential works, and collected information on the current status, main focuses and emerging trends in HP/GC research to provide academics with guidance for future paths.
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Affiliation(s)
- Shanshan Yang
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Beijing, China
| | - Shaodong Hao
- Spleen-Stomach Department, Fangshan Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Hui Ye
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Beijing, China
| | - Xuezhi Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Beijing, China
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25
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Cheung KS, Chan AOO, Yu Wong BC. Intestinal‐type Gastric Cancer. GASTROINTESTINAL ONCOLOGY ‐ A CRITICAL MULTIDISCIPLINARY TEAM APPROACH 2E 2024:120-138. [DOI: 10.1002/9781119756422.ch7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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26
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Huang HY, Yu RL, Tsai WF, Chuang WL, Huang JF, Dai CY, Tan CH. Impact of interleukin-1β single nucleotide polymorphisms and depressive symptoms in individuals with chronic viral hepatitis. Kaohsiung J Med Sci 2024; 40:94-104. [PMID: 37937732 DOI: 10.1002/kjm2.12776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 09/18/2023] [Accepted: 09/25/2023] [Indexed: 11/09/2023] Open
Abstract
Elevated levels of interleukin 1β (IL-1β) have been identified in patients with chronic viral hepatitis and have been associated with depressive symptoms. Given the high prevalence of depression in this patient population, this study sought to explore the potential influence of IL-1β genetic variations on the severity of depressive symptoms. In a cohort of 181 Taiwanese patients with chronic viral hepatitis, we investigated the impact of five common IL-1β single nucleotide polymorphisms (SNPs), including rs16944, rs1143627, rs1143630, rs1143643, and rs3136558, on depressive symptoms using the Beck's Depression Inventory-II. Additionally, we analyzed the primary domains of IL-1β-related depressive symptoms according to Beck's six symptom categories of depression. Our analysis revealed significant associations between depressive symptoms and three intronic IL-1β SNPs. After controlling for age, sex, marital status, and education level, patients with the rs1143630 GG, rs1143643 CC, and rs3136558 AA genotypes demonstrated higher severity of depressive symptoms in the domains of indecision (p = 0.004), agitation (p = 0.001), and feelings of punishment (p = 0.005), respectively, compared to rs1143630 GA+AA, rs1143643 CT, and rs3136558 AG+GG genotypes. According to Beck's categorization, these symptoms can be classified into three dimensions: disturbances in emotion regulation, energy, and cognition. Our findings demonstrate the association between IL-1β polymorphisms and depressive symptoms and suggest a potential underlying mechanism for specific depressive symptoms within the chronic viral hepatitis population. These insights could improve our understanding and treatment of depressive symptoms in individuals with viral hepatitis.
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Affiliation(s)
- Hsin-Yi Huang
- Department of General Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Rwei-Ling Yu
- Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wei-Fang Tsai
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chun-Hsiang Tan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
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27
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Trembath HE, Yeh JJ, Lopez NE. Gastrointestinal Malignancy: Genetic Implications to Clinical Applications. Cancer Treat Res 2024; 192:305-418. [PMID: 39212927 DOI: 10.1007/978-3-031-61238-1_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Advances in molecular genetics have revolutionized our understanding of the pathogenesis, progression, and therapeutic options for treating gastrointestinal (GI) cancers. This chapter provides a comprehensive overview of the molecular landscape of GI cancers, focusing on key genetic alterations implicated in tumorigenesis across various anatomical sites including GIST, colon and rectum, and pancreas. Emphasis is placed on critical oncogenic pathways, such as mutations in tumor suppressor genes, oncogenes, chromosomal instability, microsatellite instability, and epigenetic modifications. The role of molecular biomarkers in predicting prognosis, guiding treatment decisions, and monitoring therapeutic response is discussed, highlighting the integration of genomic profiling into clinical practice. Finally, we address the evolving landscape of precision oncology in GI cancers, considering targeted therapies and immunotherapies.
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Affiliation(s)
- Hannah E Trembath
- Division of Colon and Rectal Surgery, Department of Surgery, University of California San Diego, 4303 La Jolla Village Drive Suite 2110, San Diego, CA, 92122, USA
- Division of Surgical Oncology, Department of Surgery, University of North Carolina, 170 Manning Drive, CB#7213, 1150 Physician's Office Building, Chapel Hill, NC, 27599-7213, USA
| | - Jen Jen Yeh
- Division of Colon and Rectal Surgery, Department of Surgery, University of California San Diego, 4303 La Jolla Village Drive Suite 2110, San Diego, CA, 92122, USA
- Division of Surgical Oncology, Department of Surgery, University of North Carolina, 170 Manning Drive, CB#7213, 1150 Physician's Office Building, Chapel Hill, NC, 27599-7213, USA
| | - Nicole E Lopez
- Division of Colon and Rectal Surgery, Department of Surgery, University of California San Diego, 4303 La Jolla Village Drive Suite 2110, San Diego, CA, 92122, USA.
- Division of Surgical Oncology, Department of Surgery, University of North Carolina, 170 Manning Drive, CB#7213, 1150 Physician's Office Building, Chapel Hill, NC, 27599-7213, USA.
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28
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Llach J, Salces I, Guerra A, Peñas B, Rodriguez-Alcalde D, Redondo PD, Cubiella J, Murcia Ó, Escalante M, Gratacós-Ginès J, Pocurull A, Daca-Alvarez M, Luzko I, Sánchez A, Herrera-Pariente C, Ocaña T, Carballal S, Elizalde I, Castellví-Bel S, Fernández-Esparrach G, Castells A, Balaguer F, Moreira L. Endoscopic surveillance for familial intestinal gastric cancer in low-incidence areas: An effective strategy. Int J Cancer 2024; 154:124-132. [PMID: 37676082 DOI: 10.1002/ijc.34714] [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: 06/25/2023] [Revised: 08/16/2023] [Accepted: 08/17/2023] [Indexed: 09/08/2023]
Abstract
While clinical practice guidelines for hereditary diffuse gastric cancer are well established, there is no consensus on the approach for familial intestinal gastric cancer (FIGC). In low-incidence gastric cancer (GC) areas such as the United States or most European countries, there are no evidence-based recommendations on endoscopic assessment in FIGC families. We aim to describe the yield of GC surveillance in these families, and to identify epidemiological risk factors for the development of GC and its precursor lesions. This is a multicenter observational study involving nine tertiary Spanish hospitals, in which all individuals fulfilling FIGC criteria who underwent endoscopic surveillance were included between 1991 and 2020. Forty-one healthy individuals of 31 families were recruited. The median number of upper gastrointestinal endoscopies per individual was 3 (interquartile range, IQR, 1-4). The median interval time between tests was 2 years (IQR 1.5-2.5), and the median follow-up was 9 years (IQR 3-14.5). In 18 (43.9%) subjects, a precursor lesion of GC was found during follow-up, and in 2 (4.9%), an early GC was identified, in which curative treatment was offered. Helicobacter pylori (Hp) infection proved to be independently associated with an increased risk of developing precursor lesions or GC, adjusted by age, gender and follow-up, with an Odds Ratio of 6.443 (1.36-30.6, P value .019). We present the first outcomes that support endoscopic surveillance with biopsies and detection of Hp in FIGC families, although the periodicity has yet to be defined.
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Affiliation(s)
- Joan Llach
- Department of Gastroenterology, Hospital Clínic Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain
| | | | - Ana Guerra
- Complejo Hospitalario de Navarra, Navarra, Spain
| | - Beatriz Peñas
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Hospital Universitario Ramón y Cajal, Madrid, Spain
| | | | | | - Joaquin Cubiella
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Grupo de Investigación en Oncología Digestiva-Ourense, Hospital Universitario de Ourense, Ourense, Spain
| | - Óscar Murcia
- Hospital General Universitario de Alicante, Valencia, Spain
| | | | - Jordi Gratacós-Ginès
- Department of Gastroenterology, Hospital Clínic Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain
| | - Anna Pocurull
- Department of Gastroenterology, Hospital Clínic Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain
| | - Maria Daca-Alvarez
- Department of Gastroenterology, Hospital Clínic Barcelona, Barcelona, Spain
- IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain
| | - Irina Luzko
- Department of Gastroenterology, Hospital Clínic Barcelona, Barcelona, Spain
| | - Ariadna Sánchez
- Department of Gastroenterology, Hospital Clínic Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain
| | - Cristina Herrera-Pariente
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain
| | - Teresa Ocaña
- Department of Gastroenterology, Hospital Clínic Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain
| | - Sabela Carballal
- Department of Gastroenterology, Hospital Clínic Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain
| | - Ignasi Elizalde
- Department of Gastroenterology, Hospital Clínic Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain
| | - Sergi Castellví-Bel
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain
| | - Glòria Fernández-Esparrach
- Department of Gastroenterology, Hospital Clínic Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain
- Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
| | - Antoni Castells
- Department of Gastroenterology, Hospital Clínic Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain
- Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
| | - Francesc Balaguer
- Department of Gastroenterology, Hospital Clínic Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain
- Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
| | - Leticia Moreira
- Department of Gastroenterology, Hospital Clínic Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain
- Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
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Zarezadeh Mehrabadi A, Shahba F, Khorramdelazad H, Aghamohammadi N, Karimi M, Bagherzadeh K, Khoshmirsafa M, Massoumi R, Falak R. Interleukin-1 receptor accessory protein (IL-1RAP): A magic bullet candidate for immunotherapy of human malignancies. Crit Rev Oncol Hematol 2024; 193:104200. [PMID: 37981104 DOI: 10.1016/j.critrevonc.2023.104200] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 11/02/2023] [Accepted: 11/13/2023] [Indexed: 11/21/2023] Open
Abstract
IL-1, plays a role in some pathological inflammatory conditions. This pro-inflammatory cytokine also has a crucial role in tumorigenesis and immune responses in the tumor microenvironment (TME). IL-1 receptor accessory protein (IL-1RAP), combined with IL-1 receptor-1, provides a functional complex for binding and signaling. In addition to the direct role of IL-1, some studies demonstrated that IL1-RAP has essential roles in the progression, angiogenesis, and metastasis of solid tumors such as gastrointestinal tumors, lung carcinoma, glioma, breast and cervical cancers. This molecule also interacts with FLT-3 and c-Kit tyrosine kinases and is involved in the pathogenesis of hematological malignancies such as acute myeloid lymphoma. Additionally, IL-1RAP interacts with solute carrier family 3 member 2 (SLC3A2) and thereby increasing the resistance to anoikis and metastasis in Ewing sarcoma. This review summarizes the role of IL-1RAP in different types of cancers and discusses its targeting as a novel therapeutic approach for malignancies.
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Affiliation(s)
- Ali Zarezadeh Mehrabadi
- Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Faezeh Shahba
- Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Hossein Khorramdelazad
- Department of Immunology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Nazanin Aghamohammadi
- Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Milad Karimi
- Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Kowsar Bagherzadeh
- Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Majid Khoshmirsafa
- Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Ramin Massoumi
- Department of Laboratory Medicine, Translational Cancer Research, Faculty of Medicine, Lund University, 22381, Lund, Sweden.
| | - Reza Falak
- Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
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Krzysiek-Maczka G, Brzozowski T, Ptak-Belowska A. Helicobacter pylori-activated fibroblasts as a silent partner in gastric cancer development. Cancer Metastasis Rev 2023; 42:1219-1256. [PMID: 37460910 PMCID: PMC10713772 DOI: 10.1007/s10555-023-10122-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 06/20/2023] [Indexed: 12/18/2023]
Abstract
The discovery of Helicobacter pylori (Hp) infection of gastric mucosa leading to active chronic gastritis, gastroduodenal ulcers, and MALT lymphoma laid the groundwork for understanding of the general relationship between chronic infection, inflammation, and cancer. Nevertheless, this sequence of events is still far from full understanding with new players and mediators being constantly identified. Originally, the Hp virulence factors affecting mainly gastric epithelium were proposed to contribute considerably to gastric inflammation, ulceration, and cancer. Furthermore, it has been shown that Hp possesses the ability to penetrate the mucus layer and directly interact with stroma components including fibroblasts and myofibroblasts. These cells, which are the source of biophysical and biochemical signals providing the proper balance between cell proliferation and differentiation within gastric epithelial stem cell compartment, when exposed to Hp, can convert into cancer-associated fibroblast (CAF) phenotype. The crosstalk between fibroblasts and myofibroblasts with gastric epithelial cells including stem/progenitor cell niche involves several pathways mediated by non-coding RNAs, Wnt, BMP, TGF-β, and Notch signaling ligands. The current review concentrates on the consequences of Hp-induced increase in gastric fibroblast and myofibroblast number, and their activation towards CAFs with the emphasis to the altered communication between mesenchymal and epithelial cell compartment, which may lead to inflammation, epithelial stem cell overproliferation, disturbed differentiation, and gradual gastric cancer development. Thus, Hp-activated fibroblasts may constitute the target for anti-cancer treatment and, importantly, for the pharmacotherapies diminishing their activation particularly at the early stages of Hp infection.
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Affiliation(s)
- Gracjana Krzysiek-Maczka
- Department of Physiology, the Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Kraków, Poland.
| | - Tomasz Brzozowski
- Department of Physiology, the Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Kraków, Poland.
| | - Agata Ptak-Belowska
- Department of Physiology, the Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Kraków, Poland
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Arrè V, Scialpi R, Centonze M, Giannelli G, Scavo MP, Negro R. The 'speck'-tacular oversight of the NLRP3-pyroptosis pathway on gastrointestinal inflammatory diseases and tumorigenesis. J Biomed Sci 2023; 30:90. [PMID: 37891577 PMCID: PMC10612184 DOI: 10.1186/s12929-023-00983-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 10/23/2023] [Indexed: 10/29/2023] Open
Abstract
The NLRP3 inflammasome is an intracellular sensor and an essential component of the innate immune system involved in danger recognition. An important hallmark of inflammasome activation is the formation of a single supramolecular punctum, known as a speck, per cell, which is the site where the pro-inflammatory cytokines IL-1β and IL-18 are converted into their bioactive form. Speck also provides the platform for gasdermin D protein activation, whose N-terminus domain perforates the plasma membrane, allowing the release of mature cytokines alongside with a highly inflammatory form of cell death, namely pyroptosis. Although controlled NLRP3 inflammasome-pyroptosis pathway activation preserves mucosal immunity homeostasis and contributes to host defense, a prolonged trigger is deleterious and could lead, in genetically predisposed subjects, to the onset of inflammatory bowel disease, including Crohn's disease and ulcerative colitis, as well as to gastrointestinal cancer. Experimental evidence shows that the NLRP3 inflammasome has both protective and pathogenic abilities. In this review we highlight the impact of the NLRP3-pyroptosis axis on the pathophysiology of the gastrointestinal tract at molecular level, focusing on newly discovered features bearing pro- and anti-inflammatory and neoplastic activity, and on targeted therapies tested in preclinical and clinical trials.
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Affiliation(s)
- Valentina Arrè
- Personalized Medicine Laboratory, National Institute of Gastroenterology "S. de Bellis", IRCCS Research Hospital, Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Rosanna Scialpi
- Personalized Medicine Laboratory, National Institute of Gastroenterology "S. de Bellis", IRCCS Research Hospital, Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Matteo Centonze
- Personalized Medicine Laboratory, National Institute of Gastroenterology "S. de Bellis", IRCCS Research Hospital, Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Gianluigi Giannelli
- Scientific Direction, National Institute of Gastroenterology "S. de Bellis", IRCCS Research Hospital, Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Maria Principia Scavo
- Personalized Medicine Laboratory, National Institute of Gastroenterology "S. de Bellis", IRCCS Research Hospital, Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Roberto Negro
- Personalized Medicine Laboratory, National Institute of Gastroenterology "S. de Bellis", IRCCS Research Hospital, Via Turi 27, 70013, Castellana Grotte, BA, Italy.
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Jin Y, Cai Q, Wang L, Ji J, Sun Y, Jiang J, Wang C, Wu J, Zhang B, Zhao L, Qi F, Yu B, Zhang J. Paracrine activin B-NF-κB signaling shapes an inflammatory tumor microenvironment in gastric cancer via fibroblast reprogramming. J Exp Clin Cancer Res 2023; 42:269. [PMID: 37858201 PMCID: PMC10585924 DOI: 10.1186/s13046-023-02861-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 10/11/2023] [Indexed: 10/21/2023] Open
Abstract
BACKGROUND Important roles of INHBB in various malignancies are increasingly identified. The underlying mechanisms in gastric cancer (GC) microenvironment are still greatly unexplored. METHODS The clinical significance of INHBB and the correlation between INHBB and p-p65 in GC were assessed through analyzing publicly available databases and human paraffin embedded GC tissues. The biological crosstalk of INHBB between GC cells and fibroblasts was explored both in vitro and in vivo. RNA-seq analyses were performed to determine the mechanisms which regulating fibroblasts reprogramming. Luciferase reporter assay and chromatin immunoprecipitation (CHIP) assay were used to verify the binding relationship of p65 and INHBB in GC cells. RESULTS Our study showed that INHBB level was significantly higher in GC, and that increased INHBB was associated with poor survival. INHBB positively regulates the proliferation, migration, and invasion of GC cells in vitro. Also, activin B promotes the occurrence of GC by reprogramming fibroblasts into cancer-associated fibroblasts (CAFs). The high expression of INHBB in GC cells activates the NF-κB pathway of normal gastric fibroblasts by secreting activin B, and promotes fibroblasts proliferation, migration, and invasion. In addition, activin B activates NF-κB pathway by controlling TRAF6 autoubiquitination to induce TAK1 phosphorylation in fibroblasts. Fibroblasts activated by activin B can induce the activation of p65 phosphorylation of GC cells by releasing pro-inflammatory factors IL-1β. p65 can directly bind to the INHBB promoter and increase the INHBB transcription of GC cells, thus establishing a positive regulatory feedback loop to promote the progression of GC. CONCLUSIONS GC cells p65/INHBB/activin B and fibroblasts p65/IL-1β signal loop led to the formation of a whole tumor-promoting inflammatory microenvironment, which might be a promising therapeutic target for GC.
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Affiliation(s)
- Yangbing Jin
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, 200025, Shanghai, China
| | - Qu Cai
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, 200025, Shanghai, China
| | - Lingquan Wang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, 200025, Shanghai, China
- Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, 200025, Shanghai, China
| | - Jun Ji
- Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, 200025, Shanghai, China
| | - Ying Sun
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, 200025, Shanghai, China
| | - Jinling Jiang
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, 200025, Shanghai, China
| | - Chao Wang
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, 200025, Shanghai, China
| | - Junwei Wu
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, 200025, Shanghai, China
| | - Benyan Zhang
- Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, 200025, Shanghai, China
| | - Liqin Zhao
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, 200025, Shanghai, China
| | - Feng Qi
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, 200025, Shanghai, China
| | - Beiqin Yu
- Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, 200025, Shanghai, China.
| | - Jun Zhang
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, 200025, Shanghai, China.
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Klashami ZN, Mostafavi A, Roudbordeh MG, Abbasi A, Ebrahimi P, Asadi M, Amoli MM. Investigating the relationship between the VNTR variant of the interleukin-1 receptor antagonist gene and coronary in-stent restenosis. Mol Biol Rep 2023; 50:8575-8587. [PMID: 37644369 DOI: 10.1007/s11033-023-08759-w] [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: 06/13/2023] [Accepted: 08/16/2023] [Indexed: 08/31/2023]
Abstract
OBJECTIVE This study aimed to examine the association between the interleukin-1 receptor antagonist gene (IL-1RN) and coronary in-stent restenosis (ISR) through the analysis of the VNTR variant based on the previously reported results. MATERIALS AND METHODS The samples were classified into two clearly defined groups: the case group, which comprised 45 patients diagnosed with in-stent restenosis (ISR+), and the control group, which included 60 patients without ISR (ISR-). Polymerase chain reaction (PCR) was performed to examine the 86-bp VNTR variant of the IL-1RN gene. RESULTS In the analysis of six identified groups consisting of variant alleles of 86 base pairs of VNTR of the IL-1RN gene statistically significant difference was observed for the presence of IL1RN*2 allele between cases and controls (p = 0.04, OR; 0.045). CONCLUSION Individuals with allele 2 of the IL-1Ra gene may be more predisposed to ISR. This could be due to an imbalance between IL-1Ra and IL-1β which is crucial in preventing the initiation or advancement of inflammatory diseases in specific organs. The observed phenomenon can be characterized by increased production of IL-1β and potential reduction of IL-1Ra as a result of functional VNTR variation in IL-RN gene.
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Affiliation(s)
- Zeynab Nickhah Klashami
- Metabolic Disorders Research Centre, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Atoosa Mostafavi
- Department of Cardiology, Faculty of Medicine, Tehran university of medical sciences, Tehran, Iran
| | | | - Ali Abbasi
- Department of Cardiology, Faculty of Medicine, Tehran university of medical sciences, Tehran, Iran
| | - Pirooz Ebrahimi
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata, Italy
| | - Mojgan Asadi
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahsa M Amoli
- Metabolic Disorders Research Centre, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
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Zhou Y, Yu S, Zhang W. NOD-like Receptor Signaling Pathway in Gastrointestinal Inflammatory Diseases and Cancers. Int J Mol Sci 2023; 24:14511. [PMID: 37833958 PMCID: PMC10572711 DOI: 10.3390/ijms241914511] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 09/15/2023] [Accepted: 09/23/2023] [Indexed: 10/15/2023] Open
Abstract
Nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) are intracellular proteins with a central role in innate and adaptive immunity. As a member of pattern recognition receptors (PRRs), NLRs sense specific pathogen-associated molecular patterns, trigger numerous signaling pathways and lead to the secretion of various cytokines. In recent years, cumulative studies have revealed the significant impacts of NLRs in gastrointestinal (GI) inflammatory diseases and cancers. Deciphering the role and molecular mechanism of the NLR signaling pathways may provide new opportunities for the development of therapeutic strategies related to GI inflammatory diseases and GI cancers. This review presents the structures and signaling pathways of NLRs, summarizes the recent advances regarding NLR signaling in GI inflammatory diseases and GI cancers and describes comprehensive therapeutic strategies based on this signaling pathway.
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Affiliation(s)
- Yujie Zhou
- School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China; (Y.Z.); (S.Y.)
| | - Songyan Yu
- School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China; (Y.Z.); (S.Y.)
| | - Wenyong Zhang
- School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China; (Y.Z.); (S.Y.)
- Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen 518055, China
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Waldum H, Fossmark R. Inflammation and Digestive Cancer. Int J Mol Sci 2023; 24:13503. [PMID: 37686307 PMCID: PMC10487643 DOI: 10.3390/ijms241713503] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 08/25/2023] [Accepted: 08/29/2023] [Indexed: 09/10/2023] Open
Abstract
Chronic inflammation is linked to carcinogenesis, particularly in the digestive organs, i.e., the stomach, colon, and liver. The mechanism of this effect has, however, only partly been focused on. In this review, we focus on different forms of chronic hepatitis, chronic inflammatory bowel disease, and chronic gastritis, conditions predisposing individuals to the development of malignancy. Chronic inflammation may cause malignancy because (1) the cause of the chronic inflammation is itself genotoxic, (2) substances released from the inflammatory cells may be genotoxic, (3) the cell death induced by the inflammation induces a compensatory increase in proliferation with an inherent risk of mutation, (4) changes in cell composition due to inflammation may modify function, resulting in hormonal disturbances affecting cellular proliferation. The present review focuses on chronic gastritis (Helicobacter pylori or autoimmune type) since all four mechanisms may be relevant to this condition. Genotoxicity due to the hepatitis B virus is an important factor in hepatocellular cancer and viral infection can similarly be central in the etiology and malignancy of inflammatory bowel diseases. Helicobacter pylori (H. pylori) is the dominating cause of chronic gastritis and has not been shown to be genotoxic, so its carcinogenic effect is most probably due to the induction of atrophic oxyntic gastritis leading to hypergastrinemia.
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Affiliation(s)
- Helge Waldum
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7030 Trondheim, Norway;
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Feilstrecker Balani G, dos Santos Cortez M, Picasky da Silveira Freitas JE, Freire de Melo F, Zarpelon-Schutz AC, Teixeira KN. Immune response modulation in inflammatory bowel diseases by Helicobacter pylori infection. World J Gastroenterol 2023; 29:4604-4615. [PMID: 37662864 PMCID: PMC10472898 DOI: 10.3748/wjg.v29.i30.4604] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 07/01/2023] [Accepted: 07/24/2023] [Indexed: 08/10/2023] Open
Abstract
Many studies point to an association between Helicobacter pylori (H. pylori) infection and inflammatory bowel diseases (IBD). Although controversial, this association indicates that the presence of the bacterium somehow affects the course of IBD. It appears that H. pylori infection influences IBD through changes in the diversity of the gut microbiota, and hence in local chemical characteristics, and alteration in the pattern of gut immune response. The gut immune response appears to be modulated by H. pylori infection towards a less aggressive inflammatory response and the establishment of a targeted response to tissue repair. Therefore, a T helper 2 (Th2)/macrophage M2 response is stimulated, while the Th1/macrophage M1 response is suppressed. The immunomodulation appears to be associated with intrinsic factors of the bacteria, such as virulence factors - such oncogenic protein cytotoxin-associated antigen A, proteins such H. pylori neutrophil-activating protein, but also with microenvironmental changes that favor permanence of H. pylori in the stomach. These changes include the increase of gastric mucosal pH by urease activity, and suppression of the stomach immune response promoted by evasion mechanisms of the bacterium. Furthermore, there is a causal relationship between H. pylori infection and components of the innate immunity such as the NLR family pyrin domain containing 3 inflammasome that directs IBD toward a better prognosis.
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Affiliation(s)
| | | | | | - Fabrício Freire de Melo
- Campus Anísio Teixeira, Universidade Federal da Bahia, Instituto Multidisciplinar em Saúde, Vitória da Conquista 45.029-094, Bahia, Brazil
| | - Ana Carla Zarpelon-Schutz
- Campus Toledo, Universidade Federal do Paraná, Toledo 85.919-899, Paraná, Brazil
- Programa de Pós-graduação em Biotecnologia - Setor Palotina, Universidade Federal do Paraná, Palotina 85.950-000, Paraná, Brazil
| | - Kádima Nayara Teixeira
- Campus Toledo, Universidade Federal do Paraná, Toledo 85.919-899, Paraná, Brazil
- Programa Multicêntrico de Pós-graduação em Bioquímica e Biologia Molecular - Setor Palotina, Universidade Federal do Paraná, Palotina 85.950-000, Paraná, Brazil
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Villarroel-Espindola F, Ejsmentewicz T, Gonzalez-Stegmaier R, Jorquera RA, Salinas E. Intersections between innate immune response and gastric cancer development. World J Gastroenterol 2023; 29:2222-2240. [PMID: 37124883 PMCID: PMC10134417 DOI: 10.3748/wjg.v29.i15.2222] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 11/07/2022] [Accepted: 03/13/2023] [Indexed: 04/14/2023] Open
Abstract
Worldwide, gastric cancer (GC) is the fifth most commonly diagnosed malignancy. It has a reduced prevalence but has maintained its poor prognosis being the fourth leading cause of deaths related to cancer. The highest mortality rates occur in Asian and Latin American countries, where cases are usually diagnosed at advanced stages. Overall, GC is viewed as the consequence of a multifactorial process, involving the virulence of the Helicobacter pylori (H. pylori) strains, as well as some environmental factors, dietary habits, and host intrinsic factors. The tumor microenvironment in GC appears to be chronically inflamed which promotes tumor progression and reduces the therapeutic opportunities. It has been suggested that inflammation assessment needs to be measured qualitatively and quantitatively, considering cell-infiltration types, availability of receptors to detect damage and pathogens, and presence or absence of aggressive H. pylori strains. Gastrointestinal epithelial cells express several Toll-like receptors and determine the first defensive line against pathogens, and have been also described as mediators of tumorigenesis. However, other molecules, such as cytokines related to inflammation and innate immunity, including immune checkpoint molecules, interferon-gamma pathway and NETosis have been associated with an increased risk of GC. Therefore, this review will explore innate immune activation in the context of premalignant lesions of the gastric epithelium and established gastric tumors.
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Affiliation(s)
- Franz Villarroel-Espindola
- Translational Medicine Unit, Instituto Oncologico Fundacion Arturo Lopez Perez, Santiago 7500000, Metropolitan region, Chile
| | - Troy Ejsmentewicz
- Translational Medicine Unit, Instituto Oncologico Fundacion Arturo Lopez Perez, Santiago 7500000, Metropolitan region, Chile
| | - Roxana Gonzalez-Stegmaier
- Translational Medicine Unit, Instituto Oncologico Fundacion Arturo Lopez Perez, Santiago 7500000, Metropolitan region, Chile
| | - Roddy A Jorquera
- Translational Medicine Unit, Instituto Oncologico Fundacion Arturo Lopez Perez, Santiago 7500000, Metropolitan region, Chile
| | - Esteban Salinas
- Translational Medicine Unit, Instituto Oncologico Fundacion Arturo Lopez Perez, Santiago 7500000, Metropolitan region, Chile
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Kamarehei F, Saidijam M, Taherkhani A. Prognostic biomarkers and molecular pathways mediating Helicobacter pylori–induced gastric cancer: a network-biology approach. Genomics Inform 2023; 21:e8. [PMID: 37037466 PMCID: PMC10085735 DOI: 10.5808/gi.22072] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 01/02/2023] [Indexed: 04/03/2023] Open
Abstract
Cancer of the stomach is the second most frequent cancer-related death worldwide. The survival rate of patients with gastric cancer (GC) remains fragile. There is a requirement to discover biomarkers for prognosis approaches. Helicobacter pylori in the stomach is closely associated with the progression of GC. We identified the genes associated with poor/favorable prognosis in H. pylori–induced GC. Multivariate statistical analysis was applied on the Gene Expression Omnibus (GEO) dataset GSE54397 to identify differentially expressed miRNAs (DEMs) in gastric tissues with H. pylori–induced cancer compared with the H. pylori–positive with non-cancerous tissue. A protein interaction map (PIM) was built and subjected to DEMs targets. The enriched pathways and biological processes within the PIM were identified based on substantial clusters. Thereafter, the most critical genes in the PIM were illustrated, and their prognostic impact in GC was investigated. Considering p-value less than 0.01 and |Log2 fold change| as >1, five microRNAs demonstrated significant changes among the two groups. Gene functional analysis revealed that the ubiquitination system, neddylation pathway, and ciliary process are primarily involved in H. pylori–induced GC. Survival analysis illustrated that the overexpression of DOCK4, GNAS, CTGF, TGF-b1, ESR1, SELE, TIMP3, SMARCE1, and TXNIP was associated with poor prognosis, while increased MRPS5 expression was related to a favorable prognosis in GC patients. DOCK4, GNAS, CTGF, TGF-b1, ESR1, SELE, TIMP3, SMARCE1, TXNIP, and MRPS5 may be considered prognostic biomarkers for H. pylori–induced GC. However, experimental validation is necessary in the future.
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Affiliation(s)
- Farideh Kamarehei
- Department of Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan 6517838678, Iran
| | - Massoud Saidijam
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan 6517838678, Iran
| | - Amir Taherkhani
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan 6517838678, Iran
- Corresponding author E-mail:
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Increased IL-17A Serum Levels and Gastric Th17 Cells in Helicobacter pylori-Infected Patients with Gastric Premalignant Lesions. Cancers (Basel) 2023; 15:cancers15061662. [PMID: 36980548 PMCID: PMC10046233 DOI: 10.3390/cancers15061662] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 02/28/2023] [Accepted: 03/06/2023] [Indexed: 03/11/2023] Open
Abstract
Background: Helicobacter pylori infection is characterized by an inflammatory infiltrate that might be an important antecedent of gastric cancer. The purpose of this study was to evaluate whether interleukin (IL)-17 inflammation is elicited by gastric T cells in Helicobacter pylori patients with gastric intestinal metaplasia and dysplasia (IM/DYS). We also investigated the serum IL-17A levels in Helicobacter pylori patients with gastric intestinal metaplasia and dysplasia, and patients with Helicobacter pylori non-atrophic gastritis (NAG). Methods: the IL-17 cytokine profile of gastric T cells was investigated in six patients with IM/DYS and Helicobacter pylori infection. Serum IL-17A levels were measured in 45 Helicobacter pylori-infected IM/DYS patients, 45 Helicobacter pylori-infected patients without IM/DYS and in 45 healthy controls (HC). Results: gastric T cells from all IM/DYS patients with Helicobacter pylori were able to proliferate in response to Helicobacter pylori and to produce IL-17A. The Luminex analysis revealed that IL-17A levels were significantly increased in Helicobacter pylori IM/DYS patients compared to healthy controls and to Helicobacter pylori gastritis patients without IM/DYS (452.34 ± 369.13 pg/mL, 246.82 ± 156.06 pg/mL, 169.26 ± 73.82 pg/mL, respectively; p < 0.01, p < 0.05). Conclusions: the results obtained indicate that Helicobacter pylori is able to drive gastric IL-17 inflammation in IM/DYS Helicobacter pylori-infected patients, and that IL-17A serum levels are significantly increased in Helicobacter pylori-infected patients with IM/DYS.
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Wagner J, Štibi S, Selak N, Alvir I, Mamić I, Marcelić L, Šušnjar L, Puljiz M, Heffer M, Danolić D. Interleukin 10 rs1800896 and interleukin 1B rs16944 polymorphisms and the risk of cervical cancer. Wien Med Wochenschr 2023; 173:57-61. [PMID: 35041104 DOI: 10.1007/s10354-021-00907-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 12/09/2021] [Indexed: 12/18/2022]
Abstract
BACKGROUND The purpose of this study was to evaluate the relationships between interleukin 10 (IL10) (rs1800896) and interleukin 1B (IL1B) (rs16944) genetic polymorphisms and the risk for cervical cancer in a cohort of women from Croatia. METHODS A case-control study of 81 patients with cervical cancer and 80 age-matched healthy controls was performed. We collected peripheral blood samples, extracted deoxiribonucleic acid (DNA), and analyzed two single-nucleotide polymorphisms (SNPs) rs1800896 and rs16944 using TaqMan assays (Fa. Thermo Fisher Scientific, Waltham, MA, USA) and real-time polymerase chain reaction (PCR). We investigated a possible association between two cytokine genetic polymorphisms and the occurrence of cervical cancer. RESULTS Our results showed no significant difference in the frequency of IL10 (rs1800896) and IL1B (rs16944) genotypes between the patients and the controls (χ2 test, P < 0.05). CONCLUSION In this study, no association was found between IL10 rs1800896 and IL1B rs16944 polymorphisms and cervical cancer development.
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Affiliation(s)
- Jasenka Wagner
- Department of Medical Biology and Genetics, Faculty of Medicine, University of Osijek, Osijek, Croatia
| | - Sanela Štibi
- Department of Medical Biology and Genetics, Faculty of Medicine, University of Osijek, Osijek, Croatia
| | - Nikica Selak
- Department of Medical Biology and Genetics, Faculty of Medicine, University of Osijek, Osijek, Croatia
| | - Ilija Alvir
- Department of Gynecologic Oncology, University Hospital for Tumors, Sestre milosrdnice University Hospital Center, Ilica 197, 10000, Zagreb, Croatia
| | - Ivica Mamić
- Department of Gynecologic Oncology, University Hospital for Tumors, Sestre milosrdnice University Hospital Center, Ilica 197, 10000, Zagreb, Croatia
| | - Luka Marcelić
- Department of Gynecologic Oncology, University Hospital for Tumors, Sestre milosrdnice University Hospital Center, Ilica 197, 10000, Zagreb, Croatia
| | - Lucija Šušnjar
- Department of Gynecologic Oncology, University Hospital for Tumors, Sestre milosrdnice University Hospital Center, Ilica 197, 10000, Zagreb, Croatia.
| | - Mario Puljiz
- Department of Gynecologic Oncology, University Hospital for Tumors, Sestre milosrdnice University Hospital Center, Ilica 197, 10000, Zagreb, Croatia
| | - Marija Heffer
- Department of Medical Biology and Genetics, Faculty of Medicine, University of Osijek, Osijek, Croatia
| | - Damir Danolić
- Department of Gynecologic Oncology, University Hospital for Tumors, Sestre milosrdnice University Hospital Center, Ilica 197, 10000, Zagreb, Croatia
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Galán-Huerta KA, Zamora-Márquez MA, Flores-Pérez RO, Bocanegra-Ibarias P, Salas-Treviño D, Rivas-Estilla AMG, Flores-Treviño S, Lozano-Sepúlveda SA, Martínez-Acuña N, Camacho-Ortiz A, Pérez Alba E, Arellanos-Soto D, Nuzzolo-Shihadeh L, Garza-González E. Association of the Interleukin 1B-31*C Proinflammatory Allele with the Severity of COVID-19 Patients: A Preliminary Report. Viral Immunol 2023; 36:241-249. [PMID: 36800236 DOI: 10.1089/vim.2022.0143] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/18/2023] Open
Abstract
Individuals with no known comorbidities or risk factors may develop severe coronavirus disease 2019 (COVID-19). The present study assessed the effect of certain host polymorphisms and viral lineage on the severity of COVID-19 among hospitalized patients with no known comorbidities in Mexico. The analysis included 117 unrelated hospitalized patients with COVID-19. Patients were stratified by whether they required intensive care unit (ICU) admission: the ICU group (n = 40) and non-ICU group (n = 77). COVID-19 was diagnosed on the basis of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription-polymerase chain reaction (RT-PCR) assay and clinical and radiographic criteria. The presence of the IL1B-31 (T/C) polymorphism was determined for all patients using PCR and nucleotide sequencing. Genotyping of the IL-4 (-590, T/C) and IL-8 (-251, T/A) polymorphisms was performed by the amplification refractory mutation system-PCR method. Genotyping of IL1-RN was performed using PCR. Viral genome sequencing was performed using the ARTIC Network amplicon sequencing protocol using a MinION. Logistic regression analysis identified the carriage of IL-1 B*-31 *C as an independent potential risk factor (odds ratio [OR] = 3.1736, 95% confidence interval [CI] = 1.0748-9.3705, p = 0.0366) for ICU admission and the presence of IL-RN*2 as a protective factor (OR = 0.4371, 95% CI = 0.1935-0.9871, p = 0.0465) against ICU admission. Under the codominant model, the CC genotype of IL1B-31 significantly increased the risk of ICU admission (OR: 6.38, 95% CI: 11.57-25.86, p < 0.024). The IL1B-31 *C-IL-4-590 *T haplotype increased the risk of ICU admission (OR = 2.53, 95% CI = 1.02-6.25, p = 0.047). The 42 SARS-CoV-2 genomes sequenced belonged to four clades, 20A-20D. No association was detected between SARS-CoV-2 clades and ICU admission or death. Thus, in patients with no known comorbidities or risk factors, the IL1B-31*C proinflammatory allele was observed to be associated with the risk of ICU admission owing to COVID-19.
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Affiliation(s)
- Kame Alberto Galán-Huerta
- Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, México
| | - Myriam Aseret Zamora-Márquez
- Servicio de Infectología, Hospital Universitario "Dr. José Eleuterio González," Universidad Autónoma de Nuevo León, Monterrey, Mexico
| | - Rómulo Omar Flores-Pérez
- Servicio de Infectología, Hospital Universitario "Dr. José Eleuterio González," Universidad Autónoma de Nuevo León, Monterrey, Mexico
| | - Paola Bocanegra-Ibarias
- Servicio de Infectología, Hospital Universitario "Dr. José Eleuterio González," Universidad Autónoma de Nuevo León, Monterrey, Mexico
| | - Daniel Salas-Treviño
- Servicio de Infectología, Hospital Universitario "Dr. José Eleuterio González," Universidad Autónoma de Nuevo León, Monterrey, Mexico
| | | | - Samantha Flores-Treviño
- Servicio de Infectología, Hospital Universitario "Dr. José Eleuterio González," Universidad Autónoma de Nuevo León, Monterrey, Mexico
| | - Sonia Amelia Lozano-Sepúlveda
- Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, México
| | - Natalia Martínez-Acuña
- Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, México
| | - Adrián Camacho-Ortiz
- Servicio de Infectología, Hospital Universitario "Dr. José Eleuterio González," Universidad Autónoma de Nuevo León, Monterrey, Mexico
| | - Eduardo Pérez Alba
- Servicio de Infectología, Hospital Universitario "Dr. José Eleuterio González," Universidad Autónoma de Nuevo León, Monterrey, Mexico
| | - Daniel Arellanos-Soto
- Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, México
| | - Laura Nuzzolo-Shihadeh
- Servicio de Infectología, Hospital Universitario "Dr. José Eleuterio González," Universidad Autónoma de Nuevo León, Monterrey, Mexico
| | - Elvira Garza-González
- Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, México
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Abed AS, Mokdad-Gargouri R, Raoof WM. Association between interleuleukin-1β polymorphism (rs16944) and biomarkers levels in Iraqi patients with prostate cancer. Mol Biol Rep 2023; 50:1157-1165. [PMID: 36417078 DOI: 10.1007/s11033-022-08077-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 11/01/2022] [Indexed: 11/24/2022]
Abstract
OBJECTIVE Prostate cancer (PCa) is the second-leading cause of mortality in men and the most commonly diagnosed non-cutaneous male malignancy. Host genetic factors, and inflammation-induced cytokines, play a key role in prostate oncogenesis. Single Nucleotide Polymorphisms (SNP) in cytokine genes were suggested to increase the susceptibility for PCa development and progression. This study aimed to investigate the association between the SNP (rs16944) in the interleukin-1 β (IL-1β) gene and the serum levels of Prostate Specific Antigen (PSA) Prolactine (PRL), testosterone, and IL-1β in Iraqi PCa patients versus healthy controls. METHODS Taqman Real Time-PCR, was performed to investigate the IL-1β (rs16944) polymorphism in 100 Iraqi PCa patients and 50 age-matched healthy controls in a case-control study. Serum levels of PSA, PRL, and testosterone were determined by ELISA and FIA, and associated with the IL-1β serum level as well as with the SNP (rs 16944). The association between the clinico-pathological parameters and the genotype distribution of PCa patients was also studied. RESULTS There level of IL-1β was significant increased in the serum of PCa patients compared to controls (P = 8.19 10-7). Serum levels for other biomarkers such as PSA, PRL and testosterone were also significantly elevated in patients compared to controls (P < 0.0001). No differences were seen for genotype and allele distribution between PCa patients and controls. Nevertheless, in the group of controls, we found that 36% carried the GG genotype against only 26% in the patients group.This suggests that this could be a protective genotype (OR 0.62, P = 0.254). In addition, we found that the GA genotype is slightly more frequent in patients as compared to controls (OR 1.22, P = 0.605). Interestingly, serum levels of IL-1β, PSA, PRL and testosterone were significantly higher in PCa patients carrying the GA genotype, and the GA and AA genotypes are strongly associated with the aggressive behavior of the disease such as advanced TNM, and high Gleason score. CONCLUSION Our data suggest that both serum IL-1β level and IL-1β SNP (rs16944) may be considered as candidate biomarkers for PCa. Moreover, the GA, and AA genotypes carriers along with high sera levels of IL-1β, PSA and PRL, have an increased risk for PCa with aggressive behavior in Iraqi men.
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Affiliation(s)
- Arwa Shtaiwi Abed
- Department of Biology, Faculty of Science, University of Sfax, Sfax, Tunisia.,Laboratory of Molecular Biotechnology of Eukaryotes, Center of Biotechnology of Sfax, University of Sfax, Sidi Mansour Street Km 6, BP 1177, 3038, Sfax, Tunisia
| | - Raja Mokdad-Gargouri
- Laboratory of Molecular Biotechnology of Eukaryotes, Center of Biotechnology of Sfax, University of Sfax, Sidi Mansour Street Km 6, BP 1177, 3038, Sfax, Tunisia.
| | - Waad Mahmood Raoof
- Department of Biology, College of Science, University of Tikrit, Tikrit, Iraq
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Malkova AM, Gubal AR, Petrova AL, Voronov E, Apte RN, Semenov KN, Sharoyko VV. Pathogenetic role and clinical significance of interleukin-1β in cancer. Immunology 2023; 168:203-216. [PMID: 35462425 DOI: 10.1111/imm.13486] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 03/28/2022] [Indexed: 01/21/2023] Open
Abstract
In recent years, pro-oncogenic mechanisms of the tumour microenvironment (ТМЕ) have been actively discussed. One of the main cytokines of the TМЕ is interleukin-1 beta (IL-1β), which exhibits proinflammatory properties. Some studies have shown an association between an increase in IL-1β levels and tumour progression. The purpose of this review is to analyse the pathogenic mechanisms induced by IL-1β in the TМЕ, as well as the diagnostic significance of the presence of IL-1β in patients with cancer and the efficacy of treatment with IL-1β inhibitors. According to the literature, IL-1β can induce an increase in tumour angiogenesis due to its effects on the differentiation of epithelial cells, pro-angiogenic molecule secretion and expression of adhesion molecules, thus increasing tumour growth and metastasis. IL-1β is also involved in the suppression of anti-tumour immune responses. The expression and secretion of IL-1β has been noted in various types of tumours. In some clinical studies, an elevated level of IL-1β was found to be associated with low efficacy of anti-cancer therapy and a poor prognosis. In most experimental and clinical studies, the use of IL-1β inhibitors contributed to a decrease in tumour mass and an increase in the response to anti-tumour drugs.
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Affiliation(s)
- Anna M Malkova
- Saint Petersburg State University, Saint Petersburg, Russia.,Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia
| | - Anna R Gubal
- Saint Petersburg State University, Saint Petersburg, Russia
| | | | - Elena Voronov
- The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Ron N Apte
- The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Konstantin N Semenov
- Saint Petersburg State University, Saint Petersburg, Russia.,Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia.,A. M. Granov Russian Research Centre for Radiology and Surgical Technologies, Saint Petersburg, Russia
| | - Vladimir V Sharoyko
- Saint Petersburg State University, Saint Petersburg, Russia.,Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia.,A. M. Granov Russian Research Centre for Radiology and Surgical Technologies, Saint Petersburg, Russia.,Medicinal Chemistry Center, Togliatti State University, Togliatti, Russia
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Singh RD, Dholariya S, Shekher A, Avadhesh, Parchwani D, Gupta SC. Role of IL-1 gene polymorphisms in common solid cancers. MULTIFACETED ROLE OF IL-1 IN CANCER AND INFLAMMATION 2023:1-69. [DOI: 10.1016/b978-0-12-824273-5.00002-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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45
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Castagnini LA, Gilger MA. Helicobacter pylori. PRINCIPLES AND PRACTICE OF PEDIATRIC INFECTIOUS DISEASES 2023:954-959.e5. [DOI: 10.1016/b978-0-323-75608-2.00174-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Wroblewski LE, Peek RM. Clinical Pathogenesis, Molecular Mechanisms of Gastric Cancer Development. Curr Top Microbiol Immunol 2023; 444:25-52. [PMID: 38231214 PMCID: PMC10924282 DOI: 10.1007/978-3-031-47331-9_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
The human pathogen Helicobacter pylori is the strongest known risk factor for gastric disease and cancer, and gastric cancer remains a leading cause of cancer-related death across the globe. Carcinogenic mechanisms associated with H. pylori are multifactorial and are driven by bacterial virulence constituents, host immune responses, environmental factors such as iron and salt, and the microbiota. Infection with strains that harbor the cytotoxin-associated genes (cag) pathogenicity island, which encodes a type IV secretion system (T4SS) confer increased risk for developing more severe gastric diseases. Other important H. pylori virulence factors that augment disease progression include vacuolating cytotoxin A (VacA), specifically type s1m1 vacA alleles, serine protease HtrA, and the outer-membrane adhesins HopQ, BabA, SabA and OipA. Additional risk factors for gastric cancer include dietary factors such as diets that are high in salt or low in iron, H. pylori-induced perturbations of the gastric microbiome, host genetic polymorphisms, and infection with Epstein-Barr virus. This chapter discusses in detail host factors and how H. pylori virulence factors augment the risk of developing gastric cancer in human patients as well as how the Mongolian gerbil model has been used to define mechanisms of H. pylori-induced inflammation and cancer.
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Affiliation(s)
- Lydia E Wroblewski
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Richard M Peek
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
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Kong Q, Zhang Z. Cancer-associated pyroptosis: A new license to kill tumor. Front Immunol 2023; 14:1082165. [PMID: 36742298 PMCID: PMC9889862 DOI: 10.3389/fimmu.2023.1082165] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 01/03/2023] [Indexed: 01/19/2023] Open
Abstract
Pyroptosis is a programmed necrotic cell death mediated by pore-forming Gasdermin (GSDM) proteins. After being unleashed from the C-terminal auto-inhibitory domains by proteolytic cleavage, the N-terminal domains of GSDMs oligomerize and perforate on the plasma membrane to induce cytolytic pyroptosis, releasing immune mediators and alarming the immune system. Upon infection or danger signal perception, GSDMD that functions downstream of the inflammasome, a supramolecular complex for inflammatory caspase activation, is cleaved and activated by inflammasome-activated caspase-1/4/5/11 in immune cells and epithelial cells to trigger pyroptosis and exert anti-infection protection. Unlike this inflammasome-activated pyroptosis (IAP), recent studies also suggest an emerging role of cancer-associated pyroptosis (CAP), mediated by other GSDMs in cancer cells, in provoking anti-tumor immunity. IAP and CAP share common features like cell membrane rupture but also differ in occurrence sites, activating mechanisms, secreting cytokines and biological outcomes. Here we review the most recent knowledge of cancer-associated pyroptosis and present a promising avenue for developing therapeutic interventions to enhance anti-tumor immunity for cancer treatment.
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Affiliation(s)
- Qing Kong
- Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Zhibin Zhang
- Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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Backert S, Linz B, Tegtmeyer N. Helicobacter pylori-Induced Host Cell DNA Damage and Genetics of Gastric Cancer Development. Curr Top Microbiol Immunol 2023; 444:185-206. [PMID: 38231219 DOI: 10.1007/978-3-031-47331-9_7] [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] [Indexed: 01/18/2024]
Abstract
Gastric cancer is a very serious and deadly disease worldwide with about one million new cases every year. Most gastric cancer subtypes are associated with genetic and epigenetic aberrations caused by chromosome instability, microsatellite instability or Epstein-Barr virus infection. Another risk factor is an infection with Helicobacter pylori, which also triggers severe alterations in the host genome. This pathogen expresses an extraordinary repertoire of virulence determinants that take over control of important host cell signaling functions. In fact, H. pylori is a paradigm of persistent infection, chronic inflammation and cellular destruction. In particular, H. pylori profoundly induces chromosomal DNA damage by introducing double-strand breaks (DSBs) followed by genomic instability. DSBs appear in response to oxidative stress and pro-inflammatory transcription during the S-phase of the epithelial cell cycle, which mainly depends on the presence of the bacterial cag pathogenicity island (cagPAI)-encoded type IV secretion system (T4SS). This scenario is closely connected with the T4SS-mediated injection of ADP-glycero-β-D-manno-heptose (ADP-heptose) and oncoprotein CagA. While ADP-heptose links transcription factor NF-κB-induced innate immune signaling with RNA-loop-mediated DNA replication stress and introduction of DSBs, intracellular CagA targets the tumor suppressor BRCA1. The latter scenario promotes BRCAness, a disease characterized by the deficiency of effective DSB repair. In addition, genetic studies of patients demonstrated the presence of gastric cancer-associated single nucleotide polymorphisms (SNPs) in immune-regulatory and other genes as well as specific pathogenic germline variants in several crucial genes involved in homologous recombination and DNA repair, all of which are connected to H. pylori infection. Here we review the molecular mechanisms leading to chromosomal DNA damage and specific genetic aberrations in the presence or absence of H. pylori infection, and discuss their importance in gastric carcinogenesis.
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Affiliation(s)
- Steffen Backert
- Division of Microbiology, Department of Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Staudtstr. 5, 91058, Erlangen, Germany.
| | - Bodo Linz
- Division of Microbiology, Department of Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Staudtstr. 5, 91058, Erlangen, Germany
| | - Nicole Tegtmeyer
- Division of Microbiology, Department of Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Staudtstr. 5, 91058, Erlangen, Germany.
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Ivashkin VT, Lapina TL, Maev IV, Drapkina OM, Kozlov RS, Sheptulin AA, Trukhmanov AS, Abdulkhakov SR, Alekseeva OP, Alekseenko SA, Andreev DN, Bordin DS, Dekhnich NN, Klyaritskaya IL, Korochanskaya NV, Osipenko MF, Poluektova EA, Sarsenbaeva AS, Simanenkov VI, Tkachev AV, Ulyanin AI, Khlynov IB, Tsukanov VV. Clinical Practice Guidelines of Russian Gastroenterological Association, Scientific Society for the Clinical Study of Human Microbiome, Russian Society for the Prevention of Non-Communicable Diseases, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy for <i>H. pylori</i> Diagnostics and Treatment in Adults. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2022; 32:72-93. [DOI: 10.22416/1382-4376-2022-32-6-72-93] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/20/2023]
Abstract
Aim: bring to the attention of practitioners indications for anti-Helicobacter therapy, methods and procedure for diagnostics and eradication therapy ofН. pyloriinfection.Key points. Chronic gastritis caused byН. pyloriinfection, including asymptomatic persons, may be considered as an indication for eradication therapy of Н. pylori as etiological therapy and opportunistic screening for gastric cancer prevention. Indications, for obligatory anti-Helicobacter therapy include peptic ulcer, gastric MALT lymphoma, early gastric cancer (EGC) with endoscopic resection. H. pylori primary diagnostics methods include13C-urea breath test,H. pyloristool antigen lab test, rapid urease test and serological method. The serological method cannot be used after anti-Helicobacter therapy.In RussiaH. pyloristrains' resistance to clarithromycin does not exceed 15 % in most regional studies. The first line therapy forН. pyloriinfection eradication is the standard triple therapy including a proton pump inhibitor (PPI), clarithromycin and amoxicillin, enhanced with bismuthate tripotassium dicitrate. A classic four-component therapy based on bismuthate tripotassium dicitrate or quadrotherapy without bismuth drug products which includes PPI, amoxicillin, clarithromycin and metronidazole, may be used as alternative to the first line eradication therapy. The standard triple therapy may be prescribed for 14 days only in those regions, where it has been proven to be effective. Quadrotherapy with bismuthate tripotassium dicitrate is also used as main second line therapy in case of standard triple therapy, bismuth enhanced standard triple therapy or combined therapy failure. Another second line therapy includes PPI, levofloxacin and amoxicillin, to which a bismuth-containing drug product may be added. The third line therapy is selected individually based on previously used treatment settings.Conclusion. In each case ofH. pyloriinfection the decision for eradication therapy should be made, which is especially relevant as eradication ofH. pylorihas been recognized as an effective measure for the prevention of gastric cancer.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - D. S. Bordin
- Endocrinology Research Centre; Loginov Moscow Clinical Scientific Center; Tver State Medical University
| | | | | | | | | | | | | | | | | | | | | | - V. V. Tsukanov
- Research Institute for Medical Problems in the North - Division of Krasnoyarsk Scientific Centre of Siberian Branch of the RAS
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50
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Ivashkin VT, Lapina TL, Maev IV, Drapkina OM, Kozlov RS, Sheptulin AA, Trukhmanov AS, Abdulkhakov SR, Alekseeva OP, Alekseenko SA, Andreev DN, Bordin DS, Dekhnich NN, Klyaritskaya IL, Korochanskaya NV, Osipenko MF, Poluektova EA, Sarsenbaeva AS, Simanenkov VI, Tkachev AV, Ulyanin AI, Khlynov IB, Tsukanov VV. Clinical Practice Guidelines of Russian Gastroenterological Association, Scientific Society for the Clinical Study of Human Microbiome, Russian Society for the Prevention of Non-Communicable Diseases, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy for <i>H. pylori</i> Diagnostics and Treatment in Adults. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2022; 32:72-93. [DOI: https:/doi.org/10.22416/1382-4376-2022-32-6-72-93] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
Abstract
Aim: bring to the attention of practitioners indications for anti-Helicobacter therapy, methods and procedure for diagnostics and eradication therapy ofН. pyloriinfection.Key points. Chronic gastritis caused byН. pyloriinfection, including asymptomatic persons, may be considered as an indication for eradication therapy of Н. pylori as etiological therapy and opportunistic screening for gastric cancer prevention. Indications, for obligatory anti-Helicobacter therapy include peptic ulcer, gastric MALT lymphoma, early gastric cancer (EGC) with endoscopic resection. H. pylori primary diagnostics methods include13C-urea breath test,H. pyloristool antigen lab test, rapid urease test and serological method. The serological method cannot be used after anti-Helicobacter therapy.In RussiaH. pyloristrains' resistance to clarithromycin does not exceed 15 % in most regional studies. The first line therapy forН. pyloriinfection eradication is the standard triple therapy including a proton pump inhibitor (PPI), clarithromycin and amoxicillin, enhanced with bismuthate tripotassium dicitrate. A classic four-component therapy based on bismuthate tripotassium dicitrate or quadrotherapy without bismuth drug products which includes PPI, amoxicillin, clarithromycin and metronidazole, may be used as alternative to the first line eradication therapy. The standard triple therapy may be prescribed for 14 days only in those regions, where it has been proven to be effective. Quadrotherapy with bismuthate tripotassium dicitrate is also used as main second line therapy in case of standard triple therapy, bismuth enhanced standard triple therapy or combined therapy failure. Another second line therapy includes PPI, levofloxacin and amoxicillin, to which a bismuth-containing drug product may be added. The third line therapy is selected individually based on previously used treatment settings.Conclusion. In each case ofH. pyloriinfection the decision for eradication therapy should be made, which is especially relevant as eradication ofH. pylorihas been recognized as an effective measure for the prevention of gastric cancer.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - D. S. Bordin
- Endocrinology Research Centre; Loginov Moscow Clinical Scientific Center; Tver State Medical University
| | | | | | | | | | | | | | | | | | | | | | - V. V. Tsukanov
- Research Institute for Medical Problems in the North - Division of Krasnoyarsk Scientific Centre of Siberian Branch of the RAS
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