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Obeagu EI, Obeagu GU. Exploring the intricate relationship between peptic ulcers and immunohematological responses: A narrative review. Medicine (Baltimore) 2025; 104:e42187. [PMID: 40228282 PMCID: PMC11999392 DOI: 10.1097/md.0000000000042187] [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: 04/11/2024] [Accepted: 03/25/2025] [Indexed: 04/16/2025] Open
Abstract
Peptic ulcers have long been a focus of medical research due to their significant impact on public health worldwide. Traditionally attributed to factors such as Helicobacter pylori infection and excessive gastric acid secretion, recent scientific endeavors have increasingly unveiled the pivotal role of immunohematological responses in the pathogenesis and clinical course of peptic ulcers. This review aims to synthesize and analyze the intricate relationship between peptic ulcers and immunohematological responses, shedding light on the complex interplay between the immune system and ulcer development, progression, and healing. Immunological factors, encompassing inflammatory mediators, immune cells, and the host response to H pylori, play a substantial role in the multifaceted landscape of peptic ulcers. Inflammation orchestrated by cytokines and chemokines derived from immune cells intricately contributes to mucosal damage and repair processes. Moreover, the chronic nature of H pylori infection triggers a cascade of immune responses, involving both innate and adaptive immunity, which significantly influences the course of ulceration. This paper consolidates current knowledge while highlighting the need for further research elucidating the intricate immunological pathways involved in peptic ulcer pathogenesis. The integration of immunology into the broader context of peptic ulcer disease presents opportunities for innovative therapeutic interventions aimed at modulating immune responses for improved clinical outcomes and enhanced patient care. Ultimately, unraveling the intricate relationship between peptic ulcers and immunohematological responses holds significant promise in advancing the understanding and management of this prevalent gastrointestinal disorder.
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Bi J, Wang Y, Wang Y. MiR-3613-5p targets AQP4 to promote the progression of chronic atrophic gastritis to gastric cancer. Front Pharmacol 2025; 16:1523689. [PMID: 40255569 PMCID: PMC12006049 DOI: 10.3389/fphar.2025.1523689] [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: 11/06/2024] [Accepted: 03/07/2025] [Indexed: 04/22/2025] Open
Abstract
Introduction: Gastric cancer (GC) exhibits high invasiveness, delayed diagnosis, and poor prognosis. Chronic atrophic gastritis (CAG), an initial stage within the Correa cascade, induces gastric mucosal inflammation and atrophy, promoting genetic and epigenetic alterations. MicroRNAs (miRNAs) dysregulation has been implicated in gastric tumorigenesis, yet their specific roles in CAG progression to GC remain unclear. Methods: Using clinical data from the GEO database, we identified miRNAs differentially expressed in gastric mucosa and serum samples from GC patients. Murine CAG models were established through administration of N-methyl-N-nitrosourea (MNU) and high-salt diet (HSD). In vitro functional assays evaluated proliferation and migration after miRNA modulation in gastric cancer cell lines. MiRNA target validation involved luciferase reporter assays. Results: MiR-3613-5p expression was significantly elevated in gastric mucosal and serum samples of GC patients, mucosal tissues of CAG patients, tumor tissues, and human gastric cancer cell lines. Murine models demonstrated increased miR-3613-5p expression in gastric mucosa following MNU and HSD-induced CAG. Functionally, miR-3613-5p overexpression promoted gastric cancer cell proliferation and migration in vitro, whereas silencing miR-3613-5p alleviated pathological gastric mucosal alterations (atrophy, hyperplasia, inflammatory infiltration) in vivo. Mechanistically, miR-3613-5p inhibited Aquaporin 4 (AQP4) expression by directly targeting its 3'UTR. Discussion: Our findings provide the first evidence that miR-3613-5p facilitates CAG progression toward GC via negative regulation of AQP4. These results highlight miR-3613-5p as a promising biomarker and therapeutic target, suggesting antagomiR-3613-5p as a potential novel strategy to prevent gastric carcinogenesis.
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Affiliation(s)
- Jian Bi
- Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yufen Wang
- Department of Digestive Endoscopy, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yingde Wang
- Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, China
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Damiano OM, Stevens AJ, Kenwright DN, Seddon AR. Chronic Inflammation to Cancer: The Impact of Oxidative Stress on DNA Methylation. FRONT BIOSCI-LANDMRK 2025; 30:26142. [PMID: 40152377 DOI: 10.31083/fbl26142] [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: 08/15/2024] [Revised: 11/10/2024] [Accepted: 11/21/2024] [Indexed: 03/29/2025]
Abstract
The genomic landscape of cancer cells is complex and heterogeneous, with aberrant DNA methylation being a common observation. Growing evidence indicates that oxidants produced from immune cells may interact with epigenetic processes, and this may represent a mechanism for the initiation of altered epigenetic patterns observed in both precancerous and cancerous cells. Around 20% of cancers are linked to chronic inflammatory conditions, yet the precise mechanisms connecting inflammation with cancer progression remain unclear. During chronic inflammation, immune cells release oxidants in response to stimuli, which, in high concentrations, can cause cytotoxic effects. Oxidants are known to damage DNA and proteins and disrupt normal signalling pathways, potentially initiating a sequence of events that drives carcinogenesis. While research on the impact of immune cell-derived oxidants on DNA methylation remains limited, this mechanism may represent a crucial link between chronic inflammation and cancer development. This review examines current evidence on inflammation-associated DNA methylation changes in cancers related to chronic inflammation.
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Affiliation(s)
- Olivia M Damiano
- Genetics and Epigenetics Research Group, Department of Pathology and Molecular Medicine, University of Otago, 6021 Wellington, New Zealand
| | - Aaron J Stevens
- Genetics and Epigenetics Research Group, Department of Pathology and Molecular Medicine, University of Otago, 6021 Wellington, New Zealand
| | - Diane N Kenwright
- Genetics and Epigenetics Research Group, Department of Pathology and Molecular Medicine, University of Otago, 6021 Wellington, New Zealand
| | - Annika R Seddon
- Genetics and Epigenetics Research Group, Department of Pathology and Molecular Medicine, University of Otago, 6021 Wellington, New Zealand
- Mātai Hāora - Centre for Redox Biology and Medicine, Department of Pathology and Biomedical Science, University of Otago, 8011 Christchurch, New Zealand
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Cayuela L, Peiró Villalba C, Flox-Benítez G, Cayuela A. Divergent trends in gastric cancer incidence by sex and age in Spain (1990-2019). REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2025; 117:68-75. [PMID: 39324626 DOI: 10.17235/reed.2024.10443/2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/27/2024]
Abstract
OBJECTIVE to investigate trends in gastric cancer (GC) incidence in Spain from 1990 to 2019, analyzing variations by sex and age. METHOD GC incidence data from the Global Burden of Disease database and population data from the Spanish National Institute of Statistics were used to calculate age-specific and age-standardized incidence rates (ASIR) with the European population as the reference. Temporal trends by sex and age groups were analyzed using joinpoint regression. RESULTS while the total number of cases increased slightly, ASIR showed a consistent annual decrease of 1.8 % for both men and women. Both sexes experienced this increase in total cases (women: 4,023 to 4,359; men: 6,243 to 6,591). Men consistently had a higher GC burden compared to women (approximately 2.2:1 ratio). Younger adults (< 35 years) of both sexes showed significant decreases in ASIR. However, the joinpoint analysis revealed a recent increase in young men (25-34 years) during the period 2014-2019. Adults aged 35-64 showed a decrease in ASIR for both sexes, with a slightly steeper decline in men. Adults over 65 had a similar decrease in ASIR for both sexes, but the joinpoint analysis suggests different patterns within this age group. CONCLUSION our study revealed a decline in overall age-adjusted GC incidence in Spain. However, the recent rise observed in young men warrants further investigation to understand potential risk factors in this specific population group.
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Affiliation(s)
- Lucía Cayuela
- Internal Medicine, Hospital Universitario Severo Ochoa
| | | | | | - Aurelio Cayuela
- Public Health, Prevention and Health Promotion, Hospital Universitario Virgen de Valme, España
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Duan Y, Xu Y, Dou Y, Xu D. Helicobacter pylori and gastric cancer: mechanisms and new perspectives. J Hematol Oncol 2025; 18:10. [PMID: 39849657 PMCID: PMC11756206 DOI: 10.1186/s13045-024-01654-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 12/23/2024] [Indexed: 01/25/2025] Open
Abstract
Gastric cancer remains a significant global health challenge, with Helicobacter pylori (H. pylori) recognized as a major etiological agent, affecting an estimated 50% of the world's population. There has been a rapidly expanding knowledge of the molecular and pathogenetic mechanisms of H. pylori over the decades. This review summarizes the latest research advances to elucidate the molecular mechanisms underlying the H. pylori infection in gastric carcinogenesis. Our investigation of the molecular mechanisms reveals a complex network involving STAT3, NF-κB, Hippo, and Wnt/β-catenin pathways, which are dysregulated in gastric cancer caused by H. pylori. Furthermore, we highlight the role of H. pylori in inducing oxidative stress, DNA damage, chronic inflammation, and cell apoptosis-key cellular events that pave the way for carcinogenesis. Emerging evidence also suggests the effect of H. pylori on the tumor microenvironment and its possible implications for cancer immunotherapy. This review synthesizes the current knowledge and identifies gaps that warrant further investigation. Despite the progress in our previous knowledge of the development in H. pylori-induced gastric cancer, a comprehensive investigation of H. pylori's role in gastric cancer is crucial for the advancement of prevention and treatment strategies. By elucidating these mechanisms, we aim to provide a more in-depth insights for the study and prevention of H. pylori-related gastric cancer.
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Affiliation(s)
- Yantao Duan
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yonghu Xu
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yi Dou
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Dazhi Xu
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
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Xu J, Xu X, Zhang H, Wu J, Pan R, Zhang B. Tumor-associated inflammation: The role and research progress in tumor therapy. J Drug Deliv Sci Technol 2024; 102:106376. [DOI: 10.1016/j.jddst.2024.106376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Ou L, Hao Y, Liu H, Zhu Z, Li Q, Chen Q, Wei R, Feng Z, Zhang G, Yao M. Chebulinic acid isolated from aqueous extracts of Terminalia chebula Retz inhibits Helicobacter pylori infection by potential binding to Cag A protein and regulating adhesion. Front Microbiol 2024; 15:1416794. [PMID: 39421559 PMCID: PMC11483367 DOI: 10.3389/fmicb.2024.1416794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 09/16/2024] [Indexed: 10/19/2024] Open
Abstract
BACKGROUND Terminalia chebula Retz, known as the King of Tibet, is considered a functional food in China, celebrated for its antioxidant, immune-modulating, antibacterial, and anti-inflammatory properties. Chebulinic acid, derived from aqueous extracts of Terminalia chebula Retz, is known for its anti-inflammatory properties. However, its potential as an anti-Helicobacter pylori (HP) agent has not been fully explored. METHODS Herein, we extracted the main compound from Terminalia chebula Retz using a semi-preparative liquid chromatography (LC) system and identified compound 5 as chebulinic acid through Ultra-high performance liquid chromatography-MS/MS (UPLC-MS/MS) and Nuclear Magnetic Resonance (NMR). To evaluate its role, we conducted minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays, scanning electron microscope (SEM) imaging, inhibiting kinetics curves, urea fast test, cell counting kit-8 (CCK-8) assay, western blot analysis, griess reagent system, and molecular docking. RESULTS Our results showed that chebulinic acid effectively inhibited the growth of the HP strain ATCC 700392, damaged the HP structure, and exhibited selective antimicrobial activity without affecting normal epithelial cells GES-1. Importantly, it suppressed the expression of Cytotoxin-associated gene A (Cag A) protein, a crucial factor in HP infection. Molecular docking analysis predicted a strong affinity (-9.7 kcal/mol) between chebulinic acid and Cag A protein. CONCLUSION Overall, our findings suggest that chebulinic acid acts as an anti-adhesive agent, disrupting the adhesion of HP to host cells, which is a critical step in HP infection. It also suppresses the Cag A protein. These results highlight the potential of chebulinic acid against HP infections.
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Affiliation(s)
- Ling Ou
- School of Pharmaceutical Sciences, Sun Yat-sen University, Shenzhen, China
| | - Yajie Hao
- International Pharmaceutical Engineering Lab of Shandong Province, Feixian, China
| | - Hengrui Liu
- Cancer Institute, Jinan University, Guangzhou, China
- Yinuo Biomedical Company, Tianjin, China
| | - Zhixiang Zhu
- International Pharmaceutical Engineering Lab of Shandong Province, Feixian, China
- School of Medicine and Pharmacy, Ocean University of China, Qingdao, China
| | - Qingwei Li
- International Pharmaceutical Engineering Lab of Shandong Province, Feixian, China
| | - Qingchang Chen
- Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, Singapore
| | - Ruixia Wei
- International Pharmaceutical Engineering Lab of Shandong Province, Feixian, China
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. Ltd., Linyi, China
| | - Zhong Feng
- School of Pharmaceutical Sciences, Sun Yat-sen University, Shenzhen, China
- International Pharmaceutical Engineering Lab of Shandong Province, Feixian, China
- School of Medicine and Pharmacy, Ocean University of China, Qingdao, China
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. Ltd., Linyi, China
| | - Guimin Zhang
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. Ltd., Linyi, China
| | - Meicun Yao
- School of Pharmaceutical Sciences, Sun Yat-sen University, Shenzhen, China
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Wang X, Zhao G, Shao S, Yao Y. Helicobacter pylori triggers inflammation and oncogenic transformation by perturbing the immune microenvironment. Biochim Biophys Acta Rev Cancer 2024; 1879:189139. [PMID: 38897421 DOI: 10.1016/j.bbcan.2024.189139] [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: 04/08/2024] [Revised: 06/09/2024] [Accepted: 06/14/2024] [Indexed: 06/21/2024]
Abstract
The immune microenvironment plays a critical regulatory role in the pathogenesis of Helicobacter pylori (H. pylori). Understanding the mechanisms that drive the transition from chronic inflammation to cancer may provide new insights for early detection of gastric cancer. Although chronic inflammation is frequent in precancerous gastric conditions, the monitoring function of the inflammatory microenvironment in the progression from H. pylori-induced chronic inflammation to gastric cancer remains unclear. This literature review summarizes significant findings on how H. pylori triggers inflammatory responses and facilitates cancer development through the immune microenvironment. Furthermore, the implications for future research and clinical applications are also addressed. The review is divided into four main sections: inflammatory response and immune evasion mechanisms induced by H. pylori, immune dysregulation associated with gastric cancer, therapeutic implications, and future perspectives on H. pylori-induced gastric carcinogenesis with a focus on the immune microenvironment.
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Affiliation(s)
- Xiuping Wang
- Department of Clinical Laboratory, Affiliated Kunshan Hospital of Jiangsu University, Kunshan 215300, Jiangsu, China
| | - Guang Zhao
- Department of Clinical Laboratory, Affiliated Kunshan Hospital of Jiangsu University, Kunshan 215300, Jiangsu, China; Department of Emergency Medicine, Kunshan Hospital Affiliated to Jiangsu University, Kunshan 215300, Jiangsu, China
| | - Shihe Shao
- School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, China.
| | - Yongliang Yao
- Department of Clinical Laboratory, Affiliated Kunshan Hospital of Jiangsu University, Kunshan 215300, Jiangsu, China.
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Lin M, Tu RH, Wu SZ, Zhong Q, Weng K, Wu YK, Lin GT, Wang JB, Zheng CH, Xie JW, Lin JX, Chen QY, Huang CM, Cao LL, Li P. Increased ONECUT2 induced by Helicobacter pylori promotes gastric cancer cell stemness via an AKT-related pathway. Cell Death Dis 2024; 15:497. [PMID: 38997271 PMCID: PMC11245518 DOI: 10.1038/s41419-024-06885-2] [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] [Received: 01/26/2024] [Revised: 06/28/2024] [Accepted: 07/02/2024] [Indexed: 07/14/2024]
Abstract
Helicobacter pylori (HP) infection initiates and promotes gastric carcinogenesis. ONECUT2 shows promise for tumor diagnosis, prognosis, and treatment. This study explored ONECUT2's role and the specific mechanism underlying HP infection-associated gastric carcinogenesis to suggest a basis for targeting ONECUT2 as a therapeutic strategy for gastric cancer (GC). Multidimensional data supported an association between ONECUT2, HP infection, and GC pathogenesis. HP infection upregulated ONECUT2 transcriptional activity via NFκB. In vitro and in vivo experiments demonstrated that ONECUT2 increased the stemness of GC cells. ONECUT2 was also shown to inhibit PPP2R4 transcription, resulting in reduced PP2A activity, which in turn increased AKT/β-catenin phosphorylation. AKT/β-catenin phosphorylation facilitates β-catenin translocation to the nucleus, initiating transcription of downstream stemness-associated genes in GC cells. HP infection upregulated the reduction of AKT and β-catenin phosphorylation triggered by ONECUT2 downregulation via ONECUT2 induction. Clinical survival analysis indicated that high ONECUT2 expression may indicate poor prognosis in GC. This study highlights a critical role played by ONECUT2 in promoting HP infection-associated GC by enhancing cell stemness through the PPP2R4/AKT/β-catenin signaling pathway. These findings suggest promising therapeutic strategies and potential targets for GC treatment.
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Affiliation(s)
- Mi Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Ru-Hong Tu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Sheng-Ze Wu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Qing Zhong
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Kai Weng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Yu-Kai Wu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Guang-Tan Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Jia-Bin Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China.
| | - Long-Long Cao
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China.
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China.
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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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11
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Couvineau A, Haumaitre C. Special Issue: "Digestive Inflammation and New Therapeutical Targets". Int J Mol Sci 2024; 25:4361. [PMID: 38673946 PMCID: PMC11050353 DOI: 10.3390/ijms25084361] [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: 03/11/2024] [Accepted: 04/11/2024] [Indexed: 04/28/2024] Open
Abstract
Inflammatory diseases commonly associated with humans are chronic inflammatory gastrointestinal diseases (CIGDs) [...].
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Affiliation(s)
- Alain Couvineau
- INSERM UMR1149/Inflammation Research Center (CRI), Faculty of Medicine X. Bichat, Université Paris Cité, 75018 Paris, France
| | - Cécile Haumaitre
- INSERM UMR1149/Inflammation Research Center (CRI), Faculty of Medicine X. Bichat, Université Paris Cité, 75018 Paris, France
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12
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Ren JY, Xu M, Niu XD, Ma SX, Jiao YJ, Wang D, Yu M, Cai H. Systemic inflammatory response index is a predictor of prognosis in gastric cancer patients: Retrospective cohort and meta-analysis. World J Gastrointest Surg 2024; 16:382-395. [PMID: 38463377 PMCID: PMC10921201 DOI: 10.4240/wjgs.v16.i2.382] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 12/25/2023] [Accepted: 02/01/2024] [Indexed: 02/25/2024] Open
Abstract
BACKGROUND The systemic inflammatory response index (SIRI) has been demonstrated to make a significant difference in assessing the prognosis of patients with different solid neoplasms. However, research is needed to ascertain the accuracy and reliability of applying the SIRI to patients who undergo robotic radical gastric cancer surgery. AIM To validate the applicability of the SIRI in assessing the survival of gastric cancer patients and evaluate the clinical contribution of preoperative SIRI levels to predicting long-term tumor outcomes in patients, who received robotic radical gastric cancer surgery. METHODS Initially, an exhaustive retrieval was performed in the PubMed, the Cochrane Library, EMBASE, Web of Science, and Scopus databases to identify relevant studies. Subsequently, a meta-analysis was executed on 6 cohort studies identifying the value of the SIRI in assessing the survival of gastric cancer patients. Additionally, the clinical data of 161 patients undergoing robotic radical gastric cancer surgery were retrospectively analyzed to evaluate their clinicopathological characteristics and relevant laboratory indicators. The association between preoperative SIRI levels and 5-year overall survival (OS) and disease-free survival (DFS) was assessed. RESULTS The findings demonstrated an extensive connection between SIRI values and the outcome of patients with gastric cancer. Preoperative SIRI levels were identified as an independent hazard feature for both OS and DFS among those who received robotic surgery for gastric cancer. SIRI levels in gastric cancer patients were observed to be associated with the presence of comorbidities, T-stage, carcinoembryonic antigen levels, the development of early serious postoperative complications, and the rate of lymph node metastasis. CONCLUSION SIRI values are correlated with adverse in the gastric cancer population and have the potential to be utilized in predicting long-term oncological survival in patients who undergo robotic radical gastric cancer surgery.
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Affiliation(s)
- Jing-Yao Ren
- School of Clinical Medicine, Ningxia Medical University, Yinchuan 750000, Ningxia Hui autonomous region, China
| | - Meng Xu
- Gansu Provincial Hospital, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Xiang-Dong Niu
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Shi-Xun Ma
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Ya-Jun Jiao
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Da Wang
- Medical College of Jiangsu University, Jiangsu University, Zhenjiang 212013, Jiangsu Province, China
| | - Miao Yu
- Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Hui Cai
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
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13
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Feng Z, Li H, Hao Y, Peng C, Ou L, Jia J, Xun M, Zou Y, Chen M, Zhang G, Yao M. In vitro anti- Helicobacter pylori activity and the underlining mechanism of an empirical herbal formula - Hezi Qingyou. Front Microbiol 2024; 15:1355460. [PMID: 38440143 PMCID: PMC10910045 DOI: 10.3389/fmicb.2024.1355460] [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: 12/14/2023] [Accepted: 02/05/2024] [Indexed: 03/06/2024] Open
Abstract
Background Helicobacter pylori (H. pylori) is thought to primarily colonize the human stomach and lead to various gastrointestinal disorders, such as gastritis and gastric cancer. Currently, main eradication treatment is triple or quadruple therapy centered on antibiotics. Due to antibiotic resistance, the eradication rate of H. pylori is decreasing gradually. Therefore, searching for anti-H. pylori drugs from herbal sources has become a strategy for the treatment. Our team proposed a Hezi Qingyou Formula (HZQYF), composed of Chebulae Fructus, Ficus hirta Vahl and Cloves, and studied its anti-H. pylori activity and mechanism. Methods Chemical components of HZQYF were studied using UHPLC-MS/MS and HPLC. Broth microdilution method and agar dilution method were used to evaluate HZQYF's antibacterial activity. The effects of HZQYF on expression of adhesion genes (alpA, alpB, babA), urease genes (ureE, ureF), and flagellar genes (flaA, flaB) were explored using Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) technology. Effects on morphology and permeability of the extracellular membrane were studied using scanning electron microscopy (SEM) and N-phenylnaphthalen-1-amine (NPN) uptake. Effect on urease activity was studied using a urease kinetics analysis in vitro. Immunofluorescence staining method was used to examine the effect on adhesion. Western blot was used to examine the effect on cagA protein. Results Minimum inhibitory concentration (MIC) values of the formula against H. pylori clinical strains and standard strains were 80-160 μg/mL, and minimum bactericidal concentration (MBC) values were 160-320 μg/mL. The formula could down-regulate the expression of adhesion genes (alpA, alpB, babA), urease genes (ureE, ureF) and flagellar genes (flaA, flaB), change the morphology of H. pylori, increase its extracellular membrane permeability, and decrease its urease activity. Conclusion Present studies confirmed that HZQYF had promising in vitro anti-H. pylori activities and demonstrated its possible mechanism of action by down-regulating the bacterial adhesion, urease, and flagellar gene expression, which provided scientific bases for further clinical investigations.
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Affiliation(s)
- Zhong Feng
- School of Pharmaceutical Sciences, Sun Yat-sen University, Shenzhen, China
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co., Ltd., Linyi, China
- International Pharmaceutical Engineering Laboratory in Shandong Province, Shandong New Time Pharmaceutical Co., Ltd., Linyi, China
| | - Hui Li
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co., Ltd., Linyi, China
- International Pharmaceutical Engineering Laboratory in Shandong Province, Shandong New Time Pharmaceutical Co., Ltd., Linyi, China
| | - Yajie Hao
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co., Ltd., Linyi, China
- International Pharmaceutical Engineering Laboratory in Shandong Province, Shandong New Time Pharmaceutical Co., Ltd., Linyi, China
| | - Chang Peng
- School of Pharmaceutical Sciences, Sun Yat-sen University, Shenzhen, China
| | - Ling Ou
- School of Pharmaceutical Sciences, Sun Yat-sen University, Shenzhen, China
| | - Junwei Jia
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co., Ltd., Linyi, China
- International Pharmaceutical Engineering Laboratory in Shandong Province, Shandong New Time Pharmaceutical Co., Ltd., Linyi, China
| | - Mingjin Xun
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co., Ltd., Linyi, China
- International Pharmaceutical Engineering Laboratory in Shandong Province, Shandong New Time Pharmaceutical Co., Ltd., Linyi, China
| | - Yuanjing Zou
- School of Pharmaceutical Sciences, Sun Yat-sen University, Shenzhen, China
| | - Meiyun Chen
- School of Pharmaceutical Sciences, Sun Yat-sen University, Shenzhen, China
| | - Guimin Zhang
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co., Ltd., Linyi, China
- International Pharmaceutical Engineering Laboratory in Shandong Province, Shandong New Time Pharmaceutical Co., Ltd., Linyi, China
| | - Meicun Yao
- School of Pharmaceutical Sciences, Sun Yat-sen University, Shenzhen, China
- Nanchang Research Institute, Sun Yat-sen University, Jiangxi, China
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14
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Wang Y, Wang X, Cao XY, Zhu HL, Miao L. Comparative effectiveness of different probiotics supplements for triple helicobacter pylori eradication: a network meta-analysis. Front Cell Infect Microbiol 2023; 13:1120789. [PMID: 37256113 PMCID: PMC10226649 DOI: 10.3389/fcimb.2023.1120789] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Accepted: 04/24/2023] [Indexed: 06/01/2023] Open
Abstract
Background Probiotics has been reported as an effective supplement for Helicobacter pylori eradication. However, knowledge of their comparative efficacy is still lacking. Aim In this study, we used network meta-analysis of current probiotics supplement used in standard triple therapy to assess and rank their comparative effectiveness. Methods All randomized controlled trials from three main databases (PubMed, Embase and Cochrane Library) up to April 2022 were collected and filtered to meet our criterion. We used Bayesian network meta-analysis to evaluate the eligible randomized controlled trials and gave a rank for the efficiency and incidence of side effects of each probiotics supplement. The ranking probability for each therapy was assessed by means of surfaces under cumulative ranking values. Subgroup analysis was conducted to evaluate other possible influencing factors. Results 34 eligible randomized controlled trials entered the following meta-analysis, including 9,004 patients randomized to 10 kinds of therapies. Result showed that most probiotics added therapies had better outcomes than triple therapy, among which Bifidobacterium-Lactobacillus and Bifidobacterium-Lactobacillus-Saccharomyces adjuvant therapy could obtain comprehensive benefit with high eradication rate (78.3% and 88.2% respectively), and cause few side effects. Combination of different probiotics, adding probiotics before or after triple therapy and longer duration of probiotics can improve therapeutic effect in H.pylori infected individuals. Conclusion For triple therapy of H.pylori infection, adding probiotics can increase eradication rate and bring protective effect. Considering the overall influence, Bifidobacterium-Lactobacillus or Bifidobacterium-Lactobacillus-Saccharomyces therapy can be a better choice in improving H.pylori eradication process.
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Affiliation(s)
- Yue Wang
- Medical Centre for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xue Wang
- Medical Centre for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xue-Yan Cao
- Medical Centre for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Han-Long Zhu
- Department of Gastroenterology and Hepatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Lin Miao
- Medical Centre for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
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15
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Baral B, Kashyap D, Varshney N, Verma TP, Jain AK, Chatterji D, Kumar V, Mishra A, Kumar A, Jha HC. Data on differential pathogenic ability of Helicobacter pylori isolated from distinct gastric niches. Data Brief 2023; 47:108981. [PMID: 36875222 PMCID: PMC9975699 DOI: 10.1016/j.dib.2023.108981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 02/06/2023] [Accepted: 02/08/2023] [Indexed: 02/16/2023] Open
Abstract
Helicobacter pylori infection is associated with various gastrointestinal diseases and gastric cancer. Our data shows the H. pylori isolates and their associated pathology, isolated from two different stomach niches: gastric epithelium and gastric juice. Gastric adenocarcinoma (AGS) cells were infected with H. pylori juice (HJ1, HJ10 and HJ14) and biopsy (HB1, HB10 and HB14) isolates for 6, 12 and 24 hrs. To determine the cell migration ability of the infected cells, scratch wound assay was performed. The decrease in the wound area was measured by Image J software. Status of cell proliferation accessed by counting the cell number through trypan blue exclusion method. Further assessment of pathogenic potential and carcinogenic ability of the isolates was done by determining the genomic instability in the cell post infection. Cells were stained with DAPI and number of micro and macro nuclei was counted in the acquired images. The data will be helpful in understanding the difference in the carcinogenic ability of H. pylori with respect to their physiological niche.
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Affiliation(s)
- Budhadev Baral
- Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore, Madhya Pradesh 453552, India
| | - Dharmendra Kashyap
- Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore, Madhya Pradesh 453552, India
| | - Nidhi Varshney
- Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore, Madhya Pradesh 453552, India
| | - Tarun Prakash Verma
- Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore, Madhya Pradesh 453552, India
| | - Ajay Kumar Jain
- Choithram Hospital and research center, Indore, Madhya Pradesh 452014, India
| | - Debi Chatterji
- Choithram Hospital and research center, Indore, Madhya Pradesh 452014, India
| | - Vinod Kumar
- Department of Metallurgy Engineering and Materials Science, Indian Institute of Technology Indore, Simrol, Indore, Madhya Pradesh 453552, India
| | - Amit Mishra
- Department of Bioscience & Bioengineering, Indian Institute of Technology Jodhpur, NH 65 Nagaur Road, Karwar, Jodhpur District, Rajasthan 342037, India
| | - Awanish Kumar
- Department of Biotechnology, National Institute of Technology Raipur, GE Road, Raipur, Chhattisgarh 492010, India
| | - Hem Chandra Jha
- Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore, Madhya Pradesh 453552, India
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16
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Lopes C, Almeida TC, Pimentel-Nunes P, Dinis-Ribeiro M, Pereira C. Linking dysbiosis to precancerous stomach through inflammation: Deeper than and beyond imaging. Front Immunol 2023; 14:1134785. [PMID: 37063848 PMCID: PMC10102473 DOI: 10.3389/fimmu.2023.1134785] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Accepted: 03/17/2023] [Indexed: 04/03/2023] Open
Abstract
Upper gastrointestinal endoscopy is considered the gold standard for gastric lesions detection and surveillance, but it is still associated with a non-negligible rate of missing conditions. In the Era of Personalized Medicine, biomarkers could be the key to overcome missed lesions or to better predict recurrence, pushing the frontier of endoscopy to functional endoscopy. In the last decade, microbiota in gastric cancer has been extensively explored, with gastric carcinogenesis being associated with progressive dysbiosis. Helicobacter pylori infection has been considered the main causative agent of gastritis due to its interference in disrupting the acidic environment of the stomach through inflammatory mediators. Thus, does inflammation bridge the gap between gastric dysbiosis and the gastric carcinogenesis cascade and could the microbiota-inflammation axis-derived biomarkers be the answer to the unmet challenge of functional upper endoscopy? To address this question, in this review, the available evidence on the role of gastric dysbiosis and chronic inflammation in precancerous conditions of the stomach is summarized, particularly targeting the nuclear factor-κB (NF-κB), toll-like receptors (TLRs) and cyclooxygenase-2 (COX-2) pathways. Additionally, the potential of liquid biopsies as a non-invasive source and the clinical utility of studied biomarkers is also explored. Overall, and although most studies offer a mechanistic perspective linking a strong proinflammatory Th1 cell response associated with, but not limited to, chronic infection with Helicobacter pylori, promising data recently published highlights not only the diagnostic value of microbial biomarkers but also the potential of gastric juice as a liquid biopsy pushing forward the concept of functional endoscopy and personalized care in gastric cancer early diagnosis and surveillance.
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Affiliation(s)
- Catarina Lopes
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI‐IPOP)/Rise@CI‐IPOP (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
- CINTESIS – Center for Health Technology and Services Research, University of Porto, Porto, Portugal
- ICBAS-UP – Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal
| | - Tatiana C. Almeida
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI‐IPOP)/Rise@CI‐IPOP (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
| | - Pedro Pimentel-Nunes
- Department of Surgery and Physiology, Faculty of Medicine, University of Porto (FMUP), Porto, Portugal
- Department of Gastroenterology, Unilabs, Porto, Portugal
| | - Mário Dinis-Ribeiro
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI‐IPOP)/Rise@CI‐IPOP (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
- Department of Gastroenterology, Portuguese Institute of Oncology of Porto, Porto, Portugal
| | - Carina Pereira
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI‐IPOP)/Rise@CI‐IPOP (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
- CINTESIS – Center for Health Technology and Services Research, University of Porto, Porto, Portugal
- *Correspondence: Carina Pereira,
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17
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Zhang YH, Chen XL, Wang YR, Hou YW, Zhang YD, Wang KJ. Prevention of malignant digestive system tumors should focus on the control of chronic inflammation. World J Gastrointest Oncol 2023; 15:389-404. [PMID: 37009320 PMCID: PMC10052658 DOI: 10.4251/wjgo.v15.i3.389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 01/17/2023] [Accepted: 02/07/2023] [Indexed: 03/14/2023] Open
Abstract
Chronic inflammation, through a variety of mechanisms, plays a key role in the occurrence and development of digestive system malignant tumors (DSMTs). In this study, we feature and provide a comprehensive understanding of DSMT prevention strategies based on preventing or controlling chronic inflammation. The development and evaluation of cancer prevention strategies is a longstanding process. Cancer prevention, especially in the early stage of life, should be emphasized throughout the whole life course. Issues such as the time interval for colon cancer screening, the development of direct-acting antiviral drugs for liver cancer, and the Helicobacter pylori vaccine all need to be explored in long-term, large-scale experiments in the future.
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Affiliation(s)
- Yue-Hua Zhang
- College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases, Henan Children's Hospital Zhengzhou Children’s Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan Province, China
| | - Xiao-Lin Chen
- Department of Prenatal Diagnosis Center, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Yi-Ran Wang
- Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases, Henan Children's Hospital Zhengzhou Children’s Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan Province, China
| | - Yu-Wei Hou
- Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases, Henan Children's Hospital Zhengzhou Children’s Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan Province, China
| | - Yao-Dong Zhang
- Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases, Henan Children's Hospital Zhengzhou Children’s Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan Province, China
| | - Kai-Juan Wang
- Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases, Henan Children's Hospital Zhengzhou Children’s Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan Province, China
- Henan Children’s Hospital Zhengzhou Children’s Hospital, Children’s Hospital Affiliated to Zhengzhou University, Key Laboratory of Tumor Epidemiology of Henan Province, State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou 450001, Henan Province, China
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18
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Yang H, Mou Y, Hu B. Discussion on the common controversies of Helicobacter pylori infection. Helicobacter 2023; 28:e12938. [PMID: 36436202 DOI: 10.1111/hel.12938] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 11/02/2022] [Accepted: 11/03/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Helicobacter pylori ( H. pylori ) can persistently colonize on the gastric mucosa after infection and cause gastritis, atrophy, metaplasia, and even gastric cancer (GC). METHODS Therefore, the detection and eradication of H. pylori are the prerequisite. RESULTS Clinically, there are some controversial issues, such as why H. pylori infection is persistent, why it translocases along with the lesser curvature of the stomach, why there is oxyntic antralization, what the immunological characteristic of gastric chronic inflammation caused by H. pylori is, whether H. pylori infection is associated with extra-gastric diseases, whether chronic atrophic gastritis (CAG) is reversible, and what the potential problems are after H. pylori eradication. What are the possible answers? CONCLUSION In the review, we will discuss these issues from the attachment to eradication in detail.
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Affiliation(s)
- Hang Yang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Yi Mou
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Bing Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
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19
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Dogan I, Gurbuz M, Aydin E, Karabulut S, Tastekin D, Utkan G. Distributions and prognostic effects of ABO/Rh blood groups in patients with HER2/neu positive gastric and gastroesophageal junction cancer. J Cancer Res Ther 2023; 19:S747-S751. [PMID: 38384050 DOI: 10.4103/jcrt.jcrt_1520_22] [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: 07/22/2022] [Accepted: 08/06/2022] [Indexed: 02/23/2024]
Abstract
BACKGROUND The aim of study was to look at ABO/Rh blood types frequency and prognostic significance in patients with HER2/neu positive gastric cancer. METHODS The study was designed retrospectively. Clinicopathological characteristics, treatment approaches, and the ABO/Rh blood groups features were noted. The ABO/Rh blood types for patients and healthy donors were compared by the Chi-square method. RESULTS The average age was 61 years. The average survival time was 17.9 months (13.2-22.5). ABO blood types frequencies were not similar between patients (25.9% O, 6.3% AB, 57.1% A, and 10.7% B) and control group (34.9% O, 7.9% AB, 41.9% A, and 15.3% B) (P = 0.01). Patients and controls had the same Rh factor distribution (P = 0.07). CONCLUSIONS We showed that A blood group frequency was increased in patients with HER2/neu receptor-positive gastric cancer than in a healthy population. Also, we detected that the frequency of O blood type was decreased. ABO/Rh blood types were not linked with prognosis for overall survival.
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Affiliation(s)
- Izzet Dogan
- Medical Oncology, Istanbul University Institute of Oncology, Istanbul, Turkey
| | - Mustafa Gurbuz
- Medical Oncology, Ankara University Faculty of Medicine, Ankara, Turkey
| | - Esra Aydin
- Medical Oncology, Istanbul University Institute of Oncology, Istanbul, Turkey
| | - Senem Karabulut
- Medical Oncology, Istanbul University Institute of Oncology, Istanbul, Turkey
| | - Didem Tastekin
- Medical Oncology, Istanbul University Institute of Oncology, Istanbul, Turkey
| | - Gungor Utkan
- Medical Oncology, Ankara University Faculty of Medicine, Ankara, Turkey
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20
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Yang H, Guan L, Hu B. Detection and Treatment of Helicobacter pylori: Problems and Advances. Gastroenterol Res Pract 2022; 2022:4710964. [PMID: 36317106 PMCID: PMC9617708 DOI: 10.1155/2022/4710964] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 09/28/2022] [Accepted: 10/12/2022] [Indexed: 12/24/2022] Open
Abstract
Helicobacter pylori (H. pylori) infection is chronic and etiologically linked to gastric cancer (GC) derived from gastric epithelium. The potential mechanism is complex, covering chronic inflammation, epithelial senescence, NF-κB activation, the cytotoxin-associated gene A protein translocation, and related abnormal signaling pathways. In clinical practice, the test-and-treat strategy, endoscopy-based strategy, and (family-based) screen-and-treat strategy are recommended to detect H. pylori and prevent GC. It has been demonstrated that the decreasing annual incidence of GC is largely attributable to the management of H. pylori. This study reviews the current clinical practice of H. pylori on the detection and eradication, alternative treatment strategies, and related problems and advances, and hopes to contribute to the better clinical management of H. pylori.
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Affiliation(s)
- Hang Yang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Liwen Guan
- Department of Gastroenterology, Sanya Central Hospital (Hainan Third People's Hospital), Sanya, China
| | - Bing Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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21
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Wang M, Bi C, Li H, Lu L, Gao T, Huang P, Liu C, Wang B. The emerging double-edged sword role of Sirtuins in the gastric inflammation-carcinoma sequence revealed by bulk and single-cell transcriptomes. Front Oncol 2022; 12:1004726. [PMID: 36324577 PMCID: PMC9619065 DOI: 10.3389/fonc.2022.1004726] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 09/12/2022] [Indexed: 12/03/2022] Open
Abstract
Histone modification and the inflammation-carcinoma sequence (ICS) have been acknowledgedly implicated in gastric carcinogenesis. However, the extremum expression of some histone modification genes (HMGs) in intestinal metaplasia (IM) rather than GC obscures the roles of HMGs in ICS. In this study, we assumed an explanation that the roles of HMGs in ICS were stage specific. Bulk RNA-seq on endoscopy biopsy samples from a total of 50 patients was accompanied by reanalysis of a set of published single-cell transcriptomes, which cross-sectionally profiled the transcriptomic features of chronic superficial gastritis (SG), atrophy gastritis (AG), IM, and early gastric cancer (GC). Differential analysis observed significantly peaked expression of SIRT6 and SIRT7 at IM. Weighted correlation network analysis on bulk transcriptome recognized significant correlations between SIRT1/6 and IM. The single-cell atlas identified one subgroup of B cells expressing high level of TFF1 (TFF1hi naive B cell) that theoretically played important roles in defending microbial infection, while SIRT6 displayed a positive correlation with TFF1low naive B cells. Moreover, gene set enrichment analysis at different lesions (SG-AG, AG-IM, and IM-GC) highlighted that gene sets contributing to IM, e.g., Brush Border, were largely enriched from co-expressing genes of Sirtuins (SIRTs) in AG-IM. Surveys of the genes negatively correlated with SIRT6 in public databases considered SIRT6 as tumor suppressors, which was confirmed by the cell proliferation and migration assays after transient transfection of SIRT6 overexpression vector into AGS cells. All the above observations were then confirmed by serial section-based immunohistochemistry against Ki-67, MUC2, MUC5AC, p53, and SIRT6 on the endoscopic submucosal dissection tissue. By contrast, the expression of the other HMGs varied even opposite within same family. Taken together, this study preliminarily demonstrated the two-edged sword role of SIRTs in ICS and, by extension, showed that the roles of HMGs in ICS were probably stage specific. Our study may provide new insights into and attract attention on gastric prevention and therapy targeting HMGs.
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Affiliation(s)
- Mengyang Wang
- Department of Immunology, Binzhou Medical University, Yantai, China
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China
| | - Chenxiao Bi
- Department of Immunology, Binzhou Medical University, Yantai, China
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China
| | - Hong Li
- Department of Pathology, Binzhou Medical University Hospital, Binzhou, China
| | - Lizhen Lu
- Department of Pathology, Binzhou Medical University Hospital, Binzhou, China
| | - Tao Gao
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China
| | - Panpan Huang
- Department of Immunology, Binzhou Medical University, Yantai, China
| | - Chengxia Liu
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China
- *Correspondence: Chengxia Liu, ; Bin Wang,
| | - Bin Wang
- Department of Immunology, Binzhou Medical University, Yantai, China
- *Correspondence: Chengxia Liu, ; Bin Wang,
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22
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Zou Y, Chen X, Sun Y, Li P, Xu M, Fang P, Zhang S, Yuan G, Deng X, Hu H. Antibiotics-free nanoparticles eradicate Helicobacter pylori biofilms and intracellular bacteria. J Control Release 2022; 348:370-385. [PMID: 35662575 DOI: 10.1016/j.jconrel.2022.05.044] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 05/19/2022] [Accepted: 05/25/2022] [Indexed: 02/07/2023]
Abstract
Biofilms and intracellular survival tremendously help Helicobacter pylori (H. pylori) escape from antibacterial agents attacking, therefore issuing extreme challenges to clinical therapies. Herein, we constructed fucoidan (FU)-coated nanoparticles (FU/ML-LA/EB NPs) via simple self-assembly of biguanide derivative (metformin-linoleic acid, ML) and linoleic acid (LA), encapsulating urease inhibitor ebselen (EB) instead of antibiotics to take antibacterial effect. Negatively charged FU/ML-LA/EB NPs easily penetrated through the gastric mucus layer to arrive at infection sites, then eradicated extracellular polymeric substances (EPS) to destroy H. pylori biofilms structure. After strengthening bacterial membrane permeability, the nanoparticles could enter H. pylori and kill bacteria by inhibiting the activity of urease. FU/ML-LA/EB NPs also entered H. pylori-infected host cells through receptor-mediated internalization, in which they activated AMPK to recover lysosomal acidification for killing intracellular H. pylori. Additionally, FU/ML-LA/EB NPs alleviated oxidative stress, hence reducing gastric mucosal damage and cutting off the pathways of carcinogenesis. Notably, H. pylori burden after FU/ML-LA/EB NPs treatment was reduced to a great extent in vivo, which was significantly lower than that after treatment with clinical therapy. Antibiotics-free FU/ML-LA/EB NPs improving bacterial eradication and alleviating oxidation stress made it a powerful approach against H. pylori.
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Affiliation(s)
- Yiqing Zou
- Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, PR China
| | - Xiaonan Chen
- Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, PR China
| | - Yingying Sun
- Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, PR China
| | - Pengyu Li
- Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, PR China
| | - Mao Xu
- Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, PR China
| | - Pengchao Fang
- Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, PR China
| | - Shuqi Zhang
- Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, PR China
| | - Gang Yuan
- Department of Geriatrics, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, PR China
| | - Xin Deng
- Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong SAR 999077, China
| | - Haiyan Hu
- Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, PR China; Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, Sun Yat-Sen University, Guangzhou 510006, PR China.
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23
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Yang H, Zhou X, Hu B. The 'reversibility' of chronic atrophic gastritis after the eradication of Helicobacter pylori. Postgrad Med 2022; 134:474-479. [PMID: 35382697 DOI: 10.1080/00325481.2022.2063604] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 03/31/2022] [Indexed: 02/07/2023]
Abstract
Gram-negative bacterium Helicobacter pylori (H. pylori) infection is lifelong and usually acquired in childhood, which is etiologically linked to gastric cancer (GC). H. pylori gastritis is defined as an infectious disease with varying severity in virtually all infected subjects. Chronic atrophic gastritis (CAG) is the precancerous condition with the decrease or the loss of gastric glands, which can further be replaced by metaplasia or fibrosis. Patients with advanced stages of CAG are at higher risk of GC and should be followed up with a high-quality endoscopy every 3 years. H. pylori infection is the most common cause and its eradication is recommended, which may contribute to the regression of CAG. However, it is controversial whether CAG is reversible after eradication therapy. In the review, we discuss recent studies which provide important insights into whether CAG is 'reversibility' and when it may progress into GC after eradicating H. pylori.
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Affiliation(s)
- Hang Yang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xinyue Zhou
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Bing Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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24
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Tsuyuki S, Takeshima H, Sekine S, Yamagata Y, Ando T, Yamashita S, Maeda S, Yoshikawa T, Ushijima T. Comparable genetic alteration profiles between gastric cancers with current and past Helicobacter pylori infection. Sci Rep 2021; 11:23443. [PMID: 34873204 PMCID: PMC8648804 DOI: 10.1038/s41598-021-02761-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 11/23/2021] [Indexed: 11/09/2022] Open
Abstract
Gastric cancers can develop even after Helicobacter pylori (H. pylori) eradication in 0.2-2.9% cases per year. Since H. pylori is reported to directly activate or inactivate cancer-related pathways, molecular profiles of gastric cancers with current and past H. pylori infection may be different. Here, we aimed to analyze whether profiles of point mutation and gene amplification are different between the two groups. Current or past infection by H. pylori was determined by positive or negative amplification of H. pylori jhpr3 gene by PCR, and past infection was established by the presence of endoscopic atrophy. Among the 90 gastric cancers analyzed, 55 were with current infection, and 35 were with past infection. Target sequencing of 46 cancer-related genes revealed that 47 gastric cancers had 68 point mutations of 15 different genes, such as TP53 (36%), KRAS (4%), and PIK3CA (4%) and that gene amplification was present for ERBB2, KRAS, PIK3CA, and MET among the 26 genes assessed for copy number alterations. Gastric cancers with current and past infection had similar frequencies of TP53 mutations (38% and 31%, respectively; p = 0.652) and oncogene activation (20% and 29%, respectively; p = 0.444). Gastric cancers with current and past infection had comparable profiles of genetic alterations.
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Affiliation(s)
- Sho Tsuyuki
- Division of Epigenomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.,Department of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
| | - Hideyuki Takeshima
- Division of Epigenomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Shigeki Sekine
- Division of Molecular Pathology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Yukinori Yamagata
- Department of Gastric Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Takayuki Ando
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan
| | - Satoshi Yamashita
- Division of Epigenomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Shin Maeda
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
| | - Takaki Yoshikawa
- Department of Gastric Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Toshikazu Ushijima
- Division of Epigenomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
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