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1
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Hu C, Liu H, Hong B, Wang L, Wu Z, Xie W, Luo B, Cao D, Zhong Y, Liu Y, Gong W. Helicobacter pylori reversing the landscape of neoadjuvant immunotherapy for microsatellite stable gastric cancer: a multicenter cohort study. BMC Med 2025; 23:230. [PMID: 40264112 PMCID: PMC12016324 DOI: 10.1186/s12916-025-04047-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 04/01/2025] [Indexed: 04/24/2025] Open
Abstract
BACKGROUND Microsatellite stable (MSS) gastric cancer (GC) is largely unresponsive to immunotherapy, presenting a persistent and formidable challenge in the field. Patients with advanced GC and Helicobacter pylori (H. pylori) infection have shown benefits from immunotherapy. However, it remains unreported whether neoadjuvant immunotherapy is beneficial for H. pylori-positive MSS GC patients. METHODS This retrospective cohort study analyzed data from GC patients treated at three medical centers in China between January 1, 2014, and July 1, 2024. Patients with gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction underwent testing for H. pylori infection prior to receiving neoadjuvant therapy. RESULTS In this retrospective analysis, those positive for H. pylori had a higher objective response rate of 63.77% (95% CI, 51.98-74.11%) compared to 47.73% (95% CI, 39.39-56.19%) in H. pylori-negative patients. Pathological complete remission was higher in H. pylori-positive patients at 17.39% (95% CI, 10.24-27.98%) versus 15.91% (95% CI, 10.65-23.10%). Logistic regression analysis revealed a strong correlation between H. pylori positivity and increased objective remission rate (P = 0.031, OR = 1.928, 95% CI 1.06-3.51). In H. pylori-positive MSS GC patients receiving neoadjuvant immunotherapy pCR rates can reach 27.27% (95% CI, 15.07-44.21%), much higher than the 8.33% (95% CI, 2.87-21.82%) in neoadjuvant chemotherapy patients. Survival analysis showed a 3-year OS rate of 74.2% (95% CI, 56.75-86.30%) in the H. pylori-positive group and 64.3% (95% CI, 51.20-75.55%) in the H. pylori-negative group, and the hazard ratio (HR) of these two groups was 0.50 (95% CI, 0.28-0.87; P <.001). Multivariable analysis for OS further showed the survival benefit of H. pylori, with HRs of 0.51 (95% CI, 0.29-0.91; P = 0.02). CONCLUSIONS H. pylori infection has emerged as a favorable factor for neoadjuvant immunotherapy in MSS GC, underscoring the importance of considering H. pylori status in preoperative treatment strategies.
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Affiliation(s)
- Chengyu Hu
- Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
| | - Hongming Liu
- Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
| | - Bo Hong
- Department of Pathology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Li Wang
- Department of Emergency Medicine, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China
| | - Zelai Wu
- Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
| | - Weixun Xie
- Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
| | - Bixian Luo
- Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
| | - Dong Cao
- Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
- Department of Gastrointestinal Surgery, Affiliated Hospital of Shaoxing University, Shaoxing City, China
| | - Yuxin Zhong
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Yong Liu
- Department of Gastric Surgery, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin, China.
| | - Weihua Gong
- Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
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2
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Boukhris SA, Khadir ME, Karim S, Souho T, Benajah DA, Ibrahimi SA, Chbani L, Abkari ME, Bennani B. Gastric Cancer and Associated Pathogens: Is There Any Association in the Moroccan Region? Jpn J Infect Dis 2025; 78:99-105. [PMID: 39477522 DOI: 10.7883/yoken.jjid.2024.147] [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: 03/26/2025]
Abstract
Helicobacter pylori, Epstein-Barr virus (EBV), and human papillomavirus (HPV) are three pathogens associated with various human cancers. This study aimed to investigate the role of these pathogens in gastric cancer in a Moroccan population. A retrospective study was conducted with participants attending the Gastroenterology Department of Hassan II University Hospital in Fez. In total, 279 participants were enrolled in this study. Helicobacter pylori, EBV, and HPV were detected and genotyped using polymerase chain reaction. Significant associations have been established between H. pylori and EBV and gastric cancer. A total of 93.4% and 43.3% of gastric cancer cases were related to H. pylori and EBV, respectively (P ≤ 0.01). Helicobacter pylori-EBV co-infection was responsible for 31.6% of gastric cancer cases (P < 0.01). Correlation between pathogen genotypes and gastric cancer showed that 54.6% of gastric cancer EBV positive cases had a 30 bp deletion in the LMP1 gene, whereas 16% of gastric cancer cases had high-risk HPV genotypes (P = 0.21). These results highlight the possible role of co-infection in gastric cancer development.
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Affiliation(s)
- Samia Alaoui Boukhris
- URL-CNRST No. 15, Laboratory of Human Pathology Biomedicine and Environment, Faculty of Medicine, Pharmacy and Dentistry of Fez (FMPDF), Sidi Mohammed Ben Abdellah University (USMBA), Morocco
| | - Mounia El Khadir
- URL-CNRST No. 15, Laboratory of Human Pathology Biomedicine and Environment, Faculty of Medicine, Pharmacy and Dentistry of Fez (FMPDF), Sidi Mohammed Ben Abdellah University (USMBA), Morocco
- The Higher Institute of Nursing Professions and Health Techniques (ISPITS), Morocco
| | - Safae Karim
- URL-CNRST No. 15, Laboratory of Human Pathology Biomedicine and Environment, Faculty of Medicine, Pharmacy and Dentistry of Fez (FMPDF), Sidi Mohammed Ben Abdellah University (USMBA), Morocco
| | - Tiatou Souho
- URL-CNRST No. 15, Laboratory of Human Pathology Biomedicine and Environment, Faculty of Medicine, Pharmacy and Dentistry of Fez (FMPDF), Sidi Mohammed Ben Abdellah University (USMBA), Morocco
| | - Dafr-Allah Benajah
- Department of Hepato-Gastroenterology, Hassan II University Hospital Center, Morocco
| | - Sidi Adil Ibrahimi
- Department of Hepato-Gastroenterology, Hassan II University Hospital Center, Morocco
| | - Laila Chbani
- Department of Pathological Anatomy, Hassan II University Hospital Center, Morocco
| | - Mohamed El Abkari
- Department of Hepato-Gastroenterology, Hassan II University Hospital Center, Morocco
| | - Bahia Bennani
- URL-CNRST No. 15, Laboratory of Human Pathology Biomedicine and Environment, Faculty of Medicine, Pharmacy and Dentistry of Fez (FMPDF), Sidi Mohammed Ben Abdellah University (USMBA), Morocco
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3
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Wang H, You W, Zhu Z, Zhang Y, Hu C, Lu J, Huang Y, Peng R, Shan R, Li R, Chen Y, Qi F, Yan F, Zhan Q. Streptococcus lutetiensis inhibits CD8 + IL17A + TRM cells and leads to gastric cancer progression and poor prognosis. NPJ Precis Oncol 2025; 9:43. [PMID: 39924593 PMCID: PMC11808082 DOI: 10.1038/s41698-025-00810-2] [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: 06/26/2024] [Accepted: 01/13/2025] [Indexed: 02/11/2025] Open
Abstract
In many solid tumours, including gastric cancer (GC), the beginning and progression of the tumour are closely correlated with the tumour microbiome. Here, we show the changes in the gastric microbiota and their influence on immune regulation and the promotion of GC progression through 16s rRNA sequencing and single cell RNA sequencing. Streptococcus lutetiensis (S. lutetiensis) was found to be enriched in the tumour tissues of GC patients. Further analysis using single-cell sequencing and flow cytometry showed that S. lutetiensis notably affects the antitumour immunity by suppressing IL17 signalling and reducing the population of CD8+IL17A+ tissue-resident memory T (TRM) cells by activating Nrf2-mediated oxidative stress response. Mouse models confirm S. lutetiensis promotes GC progression by impairing immune responses in CD8+IL17A+TRM cells, suggesting it as a potential GC prognosis indicator and immunotherapy target, highlighting the microbiome's role in cancer progression.
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Affiliation(s)
- Huiyu Wang
- The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Centre, Nanjing Medical University, Wuxi, China
| | - Wenhua You
- Research Center of Surgery，Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Department of Immunology, Nanjing Medical University, Nanjing, China
| | - Zining Zhu
- Department of Clinical Laboratory, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, 42 Baiziting Road, Nanjing, 210009, Jiangsu, China
| | - Yuhan Zhang
- Research Center of Surgery，Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Department of Immunology, Nanjing Medical University, Nanjing, China
| | - Chupeng Hu
- Research Center of Surgery，Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Department of Immunology, Nanjing Medical University, Nanjing, China
| | - Jinying Lu
- Research Center of Surgery，Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Department of Immunology, Nanjing Medical University, Nanjing, China
| | - Yeding Huang
- Research Center of Surgery，Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Department of Immunology, Nanjing Medical University, Nanjing, China
| | - Rui Peng
- Department of General Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, China
| | - Ruimin Shan
- Research Center of Surgery，Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Department of Immunology, Nanjing Medical University, Nanjing, China
| | - Ran Li
- Research Center of Surgery，Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Department of Immunology, Nanjing Medical University, Nanjing, China
| | - Yun Chen
- Research Center of Surgery，Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Department of Immunology, Nanjing Medical University, Nanjing, China.
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, Huai'an, 223300, China.
- Key Laboratory of Emergency and Trauma (Hainan Medical University), Ministry of Education, College of Emergency and Trauma, Hainan Medical University, Haikou, 571199, China.
| | - Fuzhen Qi
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, Huai'an, 223300, China.
| | - Feng Yan
- Department of Clinical Laboratory, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, 42 Baiziting Road, Nanjing, 210009, Jiangsu, China.
| | - Qiang Zhan
- The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Centre, Nanjing Medical University, Wuxi, China.
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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: 11] [Impact Index Per Article: 11.0] [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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Girnyi S, Marano L, Skokowski J, Mocarski P, Kycler W, Gallo G, Dyzmann-Sroka A, Kazmierczak-Siedlecka K, Kalinowski L, Banasiewicz T, Polom K. Prehabilitation approaches for gastrointestinal cancer surgery: a narrative review. Rep Pract Oncol Radiother 2024; 29:614-626. [PMID: 39759553 PMCID: PMC11698552 DOI: 10.5603/rpor.103136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Accepted: 10/17/2024] [Indexed: 01/07/2025] Open
Abstract
Gastrointestinal (GI) cancer patients undergoing surgery are particularly vulnerable to malnutrition, which can significantly impact surgical outcomes. Prehabilitation interventions encompassing nutritional, physical, and psychosocial support have gained attention for their potential to mitigate these risks. However, the efficacy of multidisciplinary prehabilitation programs in this context remains underexplored. This narrative review synthesizes existing literature to evaluate the effectiveness of prehabilitation interventions in improving outcomes for GI cancer patients undergoing surgery. Drawing on a comprehensive analysis of available evidence, the review examines the integration of nutritional, physical, and psychosocial interventions and explores the implications for clinical practice and future research. The review highlights the importance of standardized protocols and interdisciplinary collaboration in optimizing prehabilitation programs for GI cancer patients. It identifies gaps in current research, particularly regarding the synergistic effects of integrating various intervention modalities and the role of innovative strategies such as immunonutrition. Moreover, the review underscores the need for larger studies to assess the effectiveness of multimodal prehabilitation approaches and establish standardized outcome measures. In conclusion, despite advancements in understanding the importance of prehabilitation, significant gaps persist in the literature, warranting further research to refine prehabilitation protocols and improve perioperative outcomes for GI cancer patients. By addressing these research gaps and fostering interdisciplinary partnerships, future studies have the potential to enhance the effectiveness of prehabilitation interventions and optimize perioperative care in this population.
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Affiliation(s)
- Sergii Girnyi
- Department of General Surgery and Surgical Oncology, “Saint Wojciech” Hospital, “Nicolaus Copernicus” Health Center, Gdansk, Poland
| | - Luigi Marano
- Department of General Surgery and Surgical Oncology, “Saint Wojciech” Hospital, “Nicolaus Copernicus” Health Center, Gdansk, Poland
- Department of Medicine, Academy of Applied Medical and Social Sciences (AMiSNS), Elblag, Poland
| | - Jaroslaw Skokowski
- Department of General Surgery and Surgical Oncology, “Saint Wojciech” Hospital, “Nicolaus Copernicus” Health Center, Gdansk, Poland
- Department of Medicine, Academy of Applied Medical and Social Sciences (AMiSNS), Elblag, Poland
| | - Piotr Mocarski
- Department of General Surgery and Surgical Oncology, “Saint Wojciech” Hospital, “Nicolaus Copernicus” Health Center, Gdansk, Poland
| | - Witold Kycler
- Department of Gastrointestinal Surgical Oncology, Greater Poland Cancer Centre, Poznan, Poland
| | - Gaetano Gallo
- Department of Surgery, Sapienza University of Rome, Rome, Italy
| | | | - Karolina Kazmierczak-Siedlecka
- Department of Medical Laboratory Diagnostics — Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Gdansk, Poland
| | - Leszek Kalinowski
- Department of Medical Laboratory Diagnostics — Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Gdansk, Poland
- BioTechMed Centre/Department of Mechanics of Materials and Structures, Gdansk University of Technology, Gdansk, Poland
| | - Tomasz Banasiewicz
- Department of General, Endocrinological Surgery and Gastroenterological Oncology, Poznan University of Medical Sciences, Poznan, Poland
| | - Karol Polom
- Department of Medicine, Academy of Applied Medical and Social Sciences (AMiSNS), Elblag, Poland
- Department of Gastrointestinal Surgical Oncology, Greater Poland Cancer Centre, Poznan, Poland
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6
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Skokowski J, Vashist Y, Girnyi S, Cwalinski T, Mocarski P, Antropoli C, Brillantino A, Boccardi V, Goyal A, Ciarleglio FA, Almohaimeed MA, De Luca R, Abou-Mrad A, Marano L, Oviedo RJ, Januszko-Giergielewicz B. The Aging Stomach: Clinical Implications of H. pylori Infection in Older Adults-Challenges and Strategies for Improved Management. Int J Mol Sci 2024; 25:12826. [PMID: 39684537 PMCID: PMC11641014 DOI: 10.3390/ijms252312826] [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: 10/09/2024] [Revised: 10/25/2024] [Accepted: 11/26/2024] [Indexed: 12/18/2024] Open
Abstract
Aging is a multifactorial biological process characterized by a decline in physiological function and increasing susceptibility to various diseases, including malignancies and gastrointestinal disorders. Helicobacter pylori (H. pylori) infection is highly prevalent among older adults, particularly those in institutionalized settings, contributing to conditions such as atrophic gastritis, peptic ulcer disease, and gastric carcinoma. This review examines the intricate interplay between aging, gastrointestinal changes, and H. pylori pathogenesis. The age-associated decline in immune function, known as immunosenescence, exacerbates the challenges of managing H. pylori infection. Comorbidities and polypharmacy further increase the risk of adverse outcomes in older adults. Current clinical guidelines inadequately address the specific needs of the geriatric population, who are disproportionately affected by antibiotic resistance, heightened side effects, and diagnostic complexities. This review focuses on recent advancements in understanding H. pylori infection among older adults, including epidemiology, diagnostics, therapeutic strategies, and age-related gastric changes. Diagnostic approaches must consider the physiological changes that accompany aging, and treatment regimens need to be carefully tailored to balance efficacy and tolerability. Emerging strategies, such as novel eradication regimens and adjunctive probiotic therapies, show promise for improving treatment outcomes. However, significant knowledge gaps persist regarding the impact of aging on H. pylori pathogenesis and treatment efficacy. A multidisciplinary approach involving gastroenterologists, geriatricians, and other specialists is crucial to providing comprehensive care for this vulnerable population. Future research should focus on refining diagnostic and therapeutic protocols to bridge these gaps, ultimately enhancing clinical outcomes and reducing the burden of H. pylori-associated diseases in the aging population.
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Affiliation(s)
- Jaroslaw Skokowski
- Department of Medicine, Academy of Applied Medical and Social Sciences-AMiSNS: Akademia Medycznych I Spolecznych Nauk Stosowanych, 82-330 Elbląg, Poland;
- Department of General Surgery and Surgical Oncology, “Saint Wojciech” Hospital, “Nicolaus Copernicus” Health Center, 80-000 Gdańsk, Poland; (S.G.); (T.C.); (P.M.)
| | - Yogesh Vashist
- Organ Transplant Center for Excellence, Center for Liver Diseases and Oncology, King Faisal Specialist Hospital and Research Center, 12211 Riyadh, Saudi Arabia; (Y.V.); (M.A.A.)
| | - Sergii Girnyi
- Department of General Surgery and Surgical Oncology, “Saint Wojciech” Hospital, “Nicolaus Copernicus” Health Center, 80-000 Gdańsk, Poland; (S.G.); (T.C.); (P.M.)
| | - Tomasz Cwalinski
- Department of General Surgery and Surgical Oncology, “Saint Wojciech” Hospital, “Nicolaus Copernicus” Health Center, 80-000 Gdańsk, Poland; (S.G.); (T.C.); (P.M.)
| | - Piotr Mocarski
- Department of General Surgery and Surgical Oncology, “Saint Wojciech” Hospital, “Nicolaus Copernicus” Health Center, 80-000 Gdańsk, Poland; (S.G.); (T.C.); (P.M.)
| | - Carmine Antropoli
- Department of Surgery, Antonio Cardarelli Hospital, 80100 Naples, Italy; (C.A.); (A.B.)
| | - Antonio Brillantino
- Department of Surgery, Antonio Cardarelli Hospital, 80100 Naples, Italy; (C.A.); (A.B.)
| | - Virginia Boccardi
- Division of Gerontology and Geriatrics, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy;
| | - Aman Goyal
- Adesh Institute of Medical Sciences and Research, 151001 Bathinda, Punjab, India;
| | - Francesco A. Ciarleglio
- Department of General Surgery and Hepato-Pancreato-Biliary (HPB) Unit-APSS, 38121Trento, Italy;
| | - Muhannad Abdullah Almohaimeed
- Organ Transplant Center for Excellence, Center for Liver Diseases and Oncology, King Faisal Specialist Hospital and Research Center, 12211 Riyadh, Saudi Arabia; (Y.V.); (M.A.A.)
| | - Raffaele De Luca
- Department of Surgical Oncology, IRCCS Istituto Tumori “Giovanni Paolo II”, 70100 Bari, Italy;
| | - Adel Abou-Mrad
- Department of Surgery, Centre Hospitalier Universitaire d’Orléans, 45100 Orléans, France;
| | - Luigi Marano
- Department of Medicine, Academy of Applied Medical and Social Sciences-AMiSNS: Akademia Medycznych I Spolecznych Nauk Stosowanych, 82-330 Elbląg, Poland;
- Department of General Surgery and Surgical Oncology, “Saint Wojciech” Hospital, “Nicolaus Copernicus” Health Center, 80-000 Gdańsk, Poland; (S.G.); (T.C.); (P.M.)
- Department of Medicine, Surgery, and Neurosciences, University of Siena, 53100 Siena, Italy
| | - Rodolfo J. Oviedo
- Department of Surgery, Nacogdoches Medical Center, Nacogdoches, TX 75965, USA;
- Department of Surgery, University of Houston Tilman J. Fertitta Family College of Medicine, Houston, TX 75961, USA
- Department of Surgery, Sam Houston State University College of Osteopathic Medicine, Conroe, TX 77301, USA
| | - Beata Januszko-Giergielewicz
- Department of Medicine, Academy of Applied Medical and Social Sciences-AMiSNS: Akademia Medycznych I Spolecznych Nauk Stosowanych, 82-330 Elbląg, Poland;
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7
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Nardone V, Marmorino F, Germani MM, Cichowska-Cwalińska N, Menditti VS, Gallo P, Studiale V, Taravella A, Landi M, Reginelli A, Cappabianca S, Girnyi S, Cwalinski T, Boccardi V, Goyal A, Skokowski J, Oviedo RJ, Abou-Mrad A, Marano L. The Role of Artificial Intelligence on Tumor Boards: Perspectives from Surgeons, Medical Oncologists and Radiation Oncologists. Curr Oncol 2024; 31:4984-5007. [PMID: 39329997 PMCID: PMC11431448 DOI: 10.3390/curroncol31090369] [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: 07/29/2024] [Revised: 08/24/2024] [Accepted: 08/26/2024] [Indexed: 09/28/2024] Open
Abstract
The integration of multidisciplinary tumor boards (MTBs) is fundamental in delivering state-of-the-art cancer treatment, facilitating collaborative diagnosis and management by a diverse team of specialists. Despite the clear benefits in personalized patient care and improved outcomes, the increasing burden on MTBs due to rising cancer incidence and financial constraints necessitates innovative solutions. The advent of artificial intelligence (AI) in the medical field offers a promising avenue to support clinical decision-making. This review explores the perspectives of clinicians dedicated to the care of cancer patients-surgeons, medical oncologists, and radiation oncologists-on the application of AI within MTBs. Additionally, it examines the role of AI across various clinical specialties involved in cancer diagnosis and treatment. By analyzing both the potential and the challenges, this study underscores how AI can enhance multidisciplinary discussions and optimize treatment plans. The findings highlight the transformative role that AI may play in refining oncology care and sustaining the efficacy of MTBs amidst growing clinical demands.
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Affiliation(s)
- Valerio Nardone
- Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80131 Naples, Italy; (V.N.); (V.S.M.); (P.G.); (A.R.); (S.C.)
| | - Federica Marmorino
- Unit of Medical Oncology 2, Azienda Ospedaliera Universitaria Pisana, 56126 Pisa, Italy; (F.M.); (M.M.G.); (V.S.); (A.T.); (M.L.)
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
| | - Marco Maria Germani
- Unit of Medical Oncology 2, Azienda Ospedaliera Universitaria Pisana, 56126 Pisa, Italy; (F.M.); (M.M.G.); (V.S.); (A.T.); (M.L.)
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
| | | | - Vittorio Salvatore Menditti
- Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80131 Naples, Italy; (V.N.); (V.S.M.); (P.G.); (A.R.); (S.C.)
| | - Paolo Gallo
- Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80131 Naples, Italy; (V.N.); (V.S.M.); (P.G.); (A.R.); (S.C.)
| | - Vittorio Studiale
- Unit of Medical Oncology 2, Azienda Ospedaliera Universitaria Pisana, 56126 Pisa, Italy; (F.M.); (M.M.G.); (V.S.); (A.T.); (M.L.)
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
| | - Ada Taravella
- Unit of Medical Oncology 2, Azienda Ospedaliera Universitaria Pisana, 56126 Pisa, Italy; (F.M.); (M.M.G.); (V.S.); (A.T.); (M.L.)
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
| | - Matteo Landi
- Unit of Medical Oncology 2, Azienda Ospedaliera Universitaria Pisana, 56126 Pisa, Italy; (F.M.); (M.M.G.); (V.S.); (A.T.); (M.L.)
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
| | - Alfonso Reginelli
- Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80131 Naples, Italy; (V.N.); (V.S.M.); (P.G.); (A.R.); (S.C.)
| | - Salvatore Cappabianca
- Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80131 Naples, Italy; (V.N.); (V.S.M.); (P.G.); (A.R.); (S.C.)
| | - Sergii Girnyi
- Department of General Surgery and Surgical Oncology, “Saint Wojciech” Hospital, “Nicolaus Copernicus” Health Center, 80-462 Gdańsk, Poland; (S.G.); (T.C.); (J.S.); (L.M.)
| | - Tomasz Cwalinski
- Department of General Surgery and Surgical Oncology, “Saint Wojciech” Hospital, “Nicolaus Copernicus” Health Center, 80-462 Gdańsk, Poland; (S.G.); (T.C.); (J.S.); (L.M.)
| | - Virginia Boccardi
- Division of Gerontology and Geriatrics, Department of Medicine and Surgery, University of Perugia, 06123 Perugia, Italy;
| | - Aman Goyal
- Adesh Institute of Medical Sciences and Research, Bathinda 151109, Punjab, India;
| | - Jaroslaw Skokowski
- Department of General Surgery and Surgical Oncology, “Saint Wojciech” Hospital, “Nicolaus Copernicus” Health Center, 80-462 Gdańsk, Poland; (S.G.); (T.C.); (J.S.); (L.M.)
- Department of Medicine, Academy of Applied Medical and Social Sciences-AMiSNS: Akademia Medycznych I Spolecznych Nauk Stosowanych, 82-300 Elbląg, Poland
| | - Rodolfo J. Oviedo
- Nacogdoches Medical Center, Nacogdoches, TX 75965, USA
- Tilman J. Fertitta Family College of Medicine, University of Houston, Houston, TX 77021, USA
- College of Osteopathic Medicine, Sam Houston State University, Conroe, TX 77304, USA
| | - Adel Abou-Mrad
- Centre Hospitalier Universitaire d’Orléans, 45100 Orléans, France;
| | - Luigi Marano
- Department of General Surgery and Surgical Oncology, “Saint Wojciech” Hospital, “Nicolaus Copernicus” Health Center, 80-462 Gdańsk, Poland; (S.G.); (T.C.); (J.S.); (L.M.)
- Department of Medicine, Academy of Applied Medical and Social Sciences-AMiSNS: Akademia Medycznych I Spolecznych Nauk Stosowanych, 82-300 Elbląg, Poland
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8
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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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9
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Ergenç M, Uprak TK, Akın Mİ, Hekimoğlu EE, Çelikel ÇA, Yeğen C. Prognostic significance of metastatic lymph node ratio in gastric cancer: a Western-center analysis. BMC Surg 2023; 23:220. [PMID: 37550669 PMCID: PMC10408136 DOI: 10.1186/s12893-023-02127-y] [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: 05/31/2023] [Accepted: 07/27/2023] [Indexed: 08/09/2023] Open
Abstract
BACKGROUND Tumor-node-metastasis (TNM) staging is the central gastric cancer (GC) staging system, but it has some disadvantages. However, the lymph node ratio (LNR) can be used regardless of the type of lymphadenectomy and is considered an important prognostic factor. This study aimed to evaluate the relationship between LNR and survival in patients who underwent curative GC surgery. METHODS All patients who underwent radical gastric surgery between January 2014 and June 2022 were retrospectively evaluated. Clinicopathological features of tumors, TNM stage, and survival rates were analyzed. LNR was defined as the ratio between metastatic lymph nodes and total lymph nodes removed. The LNR groups were classified as follows: LNR0 = 0, 0.01 < LNR1 ≤ 0.1, 0.1 < LNR2 ≤ 0.25 and LNR3 > 0.25. Tumor characteristics and overall survival (OS) of the patients were compared between LNR groups. RESULTS After exclusion, 333 patients were analyzed. The mean age was 62 ± 14 years. According to the LNR classification, no difference was found between groups regarding age and sex. However, TNM stage III disease was significantly more common in LNR3 patients. Most patients (43.2%, n = 144) were in the LNR3 group. In terms of tumor characteristics (lymphatic, vascular, and perineural invasion), the LNR3 group had significantly poorer prognostic factors. The Cox regression model defined LNR3, TNM stage II-III disease, and advanced age as independent risk factors for survival. Patients with LNR3 demonstrated the lowest 5-year OS rate (35.7%) (estimated mean survival was 30 ± 1.9 months) compared to LNR 0-1-2. CONCLUSION Our study showed that a high LNR was significantly associated with poor OS in patients who underwent curative gastrectomy. LNR can be used as an independent prognostic predictor in GC patients.
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Affiliation(s)
- Muhammer Ergenç
- Department of General Surgery, Marmara University School of Medicine, Başıbüyük Campus Başıbüyük Mah. Maltepe Başıbüyük Yolu Sok. No: 9/1 Maltepe 34854, Istanbul, Turkey.
| | - Tevfik Kıvılcım Uprak
- Department of General Surgery, Marmara University School of Medicine, Başıbüyük Campus Başıbüyük Mah. Maltepe Başıbüyük Yolu Sok. No: 9/1 Maltepe 34854, Istanbul, Turkey
| | - Muhammed İkbal Akın
- Department of General Surgery, Marmara University School of Medicine, Başıbüyük Campus Başıbüyük Mah. Maltepe Başıbüyük Yolu Sok. No: 9/1 Maltepe 34854, Istanbul, Turkey
| | - Ece Elif Hekimoğlu
- Marmara University School of Medicine, Başıbüyük Campus Başıbüyük Mah. Maltepe Başıbüyük Yolu Sok. No: 9/1 Maltepe 34854, Istanbul, Turkey
| | - Çiğdem Ataizi Çelikel
- Department of Pathology, Marmara University School of Medicine, Başıbüyük Campus Başıbüyük Mah. Maltepe Başıbüyük Yolu Sok. No: 9/1 Maltepe 34854, Istanbul, Turkey
| | - Cumhur Yeğen
- Department of General Surgery, Marmara University School of Medicine, Başıbüyük Campus Başıbüyük Mah. Maltepe Başıbüyük Yolu Sok. No: 9/1 Maltepe 34854, Istanbul, Turkey
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10
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Parra-Lara LG, Falla-Martínez JC, Isaza-Pierotti DF, Mendoza-Urbano DM, Tangua-Arias AR, Bravo JC, Bravo LE, Zambrano ÁR. Gastric adenocarcinoma burden, trends and survival in Cali, Colombia: A retrospective cohort study. Front Oncol 2023; 13:1069369. [PMID: 36959805 PMCID: PMC10028196 DOI: 10.3389/fonc.2023.1069369] [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: 10/13/2022] [Accepted: 02/17/2023] [Indexed: 03/09/2023] Open
Abstract
Background Gastric adenocarcinoma (GA) has changed in recent decades. Cancer estimates are often calculated from population-based cancer registries, which lack valuable information to guide decision-making (clinical outcomes). We describe the trends in clinical practice for GA using a hospital-based cancer registry over a timespan of 15 years. Methods A retrospective cohort study was conducted. Data were gathered from adults diagnosed and treated for GA at Fundación Valle del Lili (FVL), between 2000 and 2014, from the hospital's own cancer registry and crossed with Cali's Cancer Registry. Additional data were obtained directly from clinical records, pathology reports and the clinical laboratory. Patients younger than 18 years and those for whom limited information was available in the medical history were excluded. A survival analysis was conducted using Kaplan-Meier method. Results A total of 500 patients met eligibility criteria. Median age was 64 years (IQR: 54-74 years), 39.8% were female, 22.2% were at an early stage, 32.2% had a locally advanced disease, and 29% a metastatic disease, 69% had intestinal subtype, 48.6% had a positive H. pylori test, 85.2% had a distal lesion, 62% underwent gastrectomy, 60.6% lymphadenectomy, and 40.6% received chemotherapy. Survival at 5 years for all cases was 39.9% (CI 95% 35.3-44.5). Survival decreased over time in all groups and was lower in age-groups <39 and 60-79 with either locally advanced or metastatic disease. Prognostic factors that were significant in the Cox proportional-hazards model were late stages of the tumor (locally advanced: HR=2.52; metastatic: HR=4.17), diffuse subtype (HR=1.40), gastrectomy (subtotal: HR=0.42; total: 0.44) and palliative chemotherapy (HR=0.61). Conclusions The treatment of GA has changed in recent decades. GA survival was associated with clinical staging, diffuse subtype, gastrectomy and palliative chemotherapy. These findings must be interpreted in the context of a hospital-based study.
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Affiliation(s)
- Luis Gabriel Parra-Lara
- Facultad de Ciencias de la Salud, Universidad Icesi, Cali, Colombia
- Centro de Investigaciones Clínicas, Fundación Valle del Lili, Cali, Colombia
| | | | | | | | | | | | - Luis Eduardo Bravo
- Registro Poblacional de Cáncer de Cali, Departamento de Patología, Facultad de Salud, Universidad del Valle, Cali, Colombia
| | - Ángela R. Zambrano
- Servicio de Hemato-Oncología, Departamento de Medicina Interna, Fundación Valle del Lili, Cali, Colombia
- *Correspondence: Ángela R. Zambrano,
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11
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Qiang R, Li Y, Dai X, Lv W. NLRP3 inflammasome in digestive diseases: From mechanism to therapy. Front Immunol 2022; 13:978190. [PMID: 36389791 PMCID: PMC9644028 DOI: 10.3389/fimmu.2022.978190] [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: 06/25/2022] [Accepted: 10/12/2022] [Indexed: 09/05/2023] Open
Abstract
Digestive system diseases remain a formidable challenge to human health. NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most characteristic multimeric protein complex and is involved in a wide range of digestive diseases as intracellular innate immune sensors. It has emerged as a research hotspot in recent years. In this context, we provide a comprehensive review of NLRP3 inflammasome priming and activation in the pathogenesis of digestive diseases, including clinical and preclinical studies. Moreover, the scientific evidence of small-molecule chemical drugs, biologics, and phytochemicals, which acts on different steps of the NLRP3 inflammasome, is reviewed. Above all, deep interrogation of the NLRP3 inflammasome is a better insight of the pathomechanism of digestive diseases. We believe that the NLRP3 inflammasome will hold promise as a novel valuable target and research direction for treating digestive disorders.
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Affiliation(s)
- Rui Qiang
- *Correspondence: Rui Qiang, ; Yanbo Li, ; Wenliang Lv,
| | - Yanbo Li
- *Correspondence: Rui Qiang, ; Yanbo Li, ; Wenliang Lv,
| | | | - Wenliang Lv
- *Correspondence: Rui Qiang, ; Yanbo Li, ; Wenliang Lv,
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12
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The role of infections in the causation of cancer in Kenya. Cancer Causes Control 2022; 33:1391-1400. [PMID: 36087193 DOI: 10.1007/s10552-022-01625-3] [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: 03/01/2022] [Accepted: 08/31/2022] [Indexed: 12/09/2022]
Abstract
Cancer constitutes a major health care burden in the world today with the situation worsening in resource poor settings as seen in most Sub-Saharan African (SSA) countries. Infections constitute by far the most common risk factors for cancer in SSA and being a typical country in this region, Kenya has experienced an upsurge in the incidence of various types of cancers in the last few decades. Although there is limited population-based data in Kenya of infections-associated cancers, this review provides an up-to-date literature-based discussion on infections-associated cancers, their pathogenesis, and preventive approaches in the country. The primary infectious agents identified are largely viral (human immunodeficiency virus, human papillomavirus (HPV), Kaposi's sarcoma-associated herpes virus, Epstein-Barr virus, hepatitis B virus (HBV), hepatitis C virus), and also bacterial: Helicobacter pylori and parasitic: Schistosomiasis haematobium. Cancers associated with infections in Kenya are varied but the predominant ones are Non-Hodgkin lymphoma, Kaposi's sarcoma, Hodgkin lymphoma, Burkitt's lymphoma, cervical, liver, and gastric cancers. The mechanisms of infections-induced carcinogenesis are varied but they mainly seem to stem from disruption of signaling, chronic inflammation, and immunosuppression. Based on our findings, actionable cancer-preventive measures that are economically feasible and aligned with existing infrastructure in Kenya include screening and treatment of infections, implementation of cancer awareness and screening, and vaccination against infections primarily HBV and HPV. The development of vaccines against other infectious agents associated with causation of cancer remains also as an important goal in cancer prevention.
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13
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Parreira P, Martins MCL. The biophysics of bacterial infections: Adhesion events in the light of force spectroscopy. Cell Surf 2021; 7:100048. [PMID: 33665520 PMCID: PMC7898176 DOI: 10.1016/j.tcsw.2021.100048] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2018] [Revised: 08/10/2020] [Accepted: 12/03/2020] [Indexed: 02/08/2023] Open
Abstract
Bacterial infections are the most eminent public health challenge of the 21st century. The primary step leading to infection is bacterial adhesion to the surface of host cells or medical devices, which is mediated by a multitude of molecular interactions. At the interface of life sciences and physics, last years advances in atomic force microscopy (AFM)-based force spectroscopy techniques have made possible to measure the forces driving bacteria-cell and bacteria-materials interactions on a single molecule/cell basis (single molecule/cell force spectroscopy). Among the bacteria-(bio)materials surface interactions, the life-threatening infections associated to medical devices involving Staphylococcus aureus and Escherichia coli are the most eminent. On the other hand, Pseudomonas aeruginosa binding to the pulmonary and urinary tract or the Helicobacter pylori binding to the gastric mucosa, are classical examples of bacteria-host cell interactions that end in serious infections. As we approach the end of the antibiotic era, acquisition of a deeper knowledge of the fundamental forces involved in bacteria - host cells/(bio)materials surface adhesion is crucial for the identification of new ligand-binding events and its assessment as novel targets for alternative anti-infective therapies. This article aims to highlight the potential of AFM-based force spectroscopy for new targeted therapies development against bacterial infections in which adhesion plays a pivotal role and does not aim to be an extensive overview on the AFM technical capabilities and theory of single molecule force spectroscopy.
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Affiliation(s)
- Paula Parreira
- INEB – Instituto de Engenharia Biomédica, Universidade do Porto, Portugal
- i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
| | - M. Cristina L. Martins
- INEB – Instituto de Engenharia Biomédica, Universidade do Porto, Portugal
- i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
- ICBAS – Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Portugal
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14
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Ailloud F, Estibariz I, Suerbaum S. Evolved to vary: genome and epigenome variation in the human pathogen Helicobacter pylori. FEMS Microbiol Rev 2021; 45:5900976. [PMID: 32880636 DOI: 10.1093/femsre/fuaa042] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 08/31/2020] [Indexed: 12/24/2022] Open
Abstract
Helicobacter pylori is a Gram-negative, spiral shaped bacterium that selectively and chronically infects the gastric mucosa of humans. The clinical course of this infection can range from lifelong asymptomatic infection to severe disease, including peptic ulcers or gastric cancer. The high mutation rate and natural competence typical of this species are responsible for massive inter-strain genetic variation exceeding that observed in all other bacterial human pathogens. The adaptive value of such a plastic genome is thought to derive from a rapid exploration of the fitness landscape resulting in fast adaptation to the changing conditions of the gastric environment. Nevertheless, diversity is also lost through recurrent bottlenecks and H. pylori's lifestyle is thus a perpetual race to maintain an appropriate pool of standing genetic variation able to withstand selection events. Another aspect of H. pylori's diversity is a large and variable repertoire of restriction-modification systems. While not yet completely understood, methylome evolution could generate enough transcriptomic variation to provide another intricate layer of adaptive potential. This review provides an up to date synopsis of this rapidly emerging area of H. pylori research that has been enabled by the ever-increasing throughput of Omics technologies and a multitude of other technological advances.
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Affiliation(s)
- Florent Ailloud
- Max von Pettenkofer Institute, Faculty of Medicine, LMU München, Pettenkoferstr. 9a, 80336 München, Germany
| | - Iratxe Estibariz
- Max von Pettenkofer Institute, Faculty of Medicine, LMU München, Pettenkoferstr. 9a, 80336 München, Germany
| | - Sebastian Suerbaum
- Max von Pettenkofer Institute, Faculty of Medicine, LMU München, Pettenkoferstr. 9a, 80336 München, Germany.,DZIF Deutsches Zentrum für Infektionsforschung, Partner Site Munich, Pettenkoferstr. 9a, 80336 München, Germany.,National Reference Center for Helicobacter pylori, Pettenkoferstr. 9a, 80336 München, Germany
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15
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Hajeebu S, Ngembus NJ, Bandi PS, Panigrahy PK, Heindl S. Machine Learning as a Tool in Investigating the Possible Role of Microbiome in Development and Treatment of Cancer. Cureus 2021; 13:e17415. [PMID: 34589326 PMCID: PMC8459918 DOI: 10.7759/cureus.17415] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 08/24/2021] [Indexed: 11/18/2022] Open
Abstract
In recent times, cancer has become a leading cause of death worldwide, and a need for new therapeutic methods to save lives has become an inevitable necessity. Microbiome and its composition have been a key area of interest among the scientific community. Microbiota appears to hold the key to the therapeutic outcome of cancer by modulating the anti-tumor activity of drugs. Furthermore, the genetic composition of the microbiota and its matching gene sequences in the oncogene has added a new dimension to cancer research. However, it requires adaptive learning techniques and high computational power to bring this research to light empirically. This paper explores the role of machine learning (ML), a subset of artificial intelligence (AI), as a tool to investigate the possible role of the microbiome in the detection and treatment of cancer.
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Affiliation(s)
- Sreehita Hajeebu
- Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Ngonack J Ngembus
- Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Pushyami Satya Bandi
- Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | | | - Stacey Heindl
- Neurology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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16
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Shakhatreh MAK, Khabour OF, Alzoubi KH, BaniHani MN, Abu-Siniyeh A, Bashir NA, Sabi SH, Mahafdah M. The Influence of IL-1B Gene Polymorphisms on H. pylori Infection and Triple Treatment Response Among Jordanian Population. APPLICATION OF CLINICAL GENETICS 2020; 13:139-145. [PMID: 32669867 PMCID: PMC7337447 DOI: 10.2147/tacg.s253778] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 06/10/2020] [Indexed: 12/29/2022]
Abstract
Background Helicobacter pylori (H. pylori) is considered the main cause of gastritis, peptic ulcer and gastric carcinoma in the human populations. H. pylori infection influences the secretion level of several proinflammatory cytokines including IL-1β, which encoded by the IL-1B gene. Objective The current study aimed to investigate whether IL-1B gene polymorphisms are associated with H. pylori infection among the Jordanian population and responses to triple therapy. Subjects and Methods The gastroscopic examination was performed on 412 subjects for H. pylori infection diagnosis, 257 subjects were found to be infected by H. Pylori (positive cases), whereas 155 subjects were uninfected (negative controls). The IL-1B gene T-31C and C3954T polymorphisms were genotyped by PCR-RFLP. Results It was found that the T-31C polymorphism has a significant association with H. pylori infection (P<0.05), and the TT genotype frequency was significantly higher in infected subjects (50.2%) compared to controls (38.7%). On the other hand, no significant association was detected between C3954T SNPs and H. pylori infection among the Jordanian population. In addition, none of the examined polymorphisms were found to influence the responses to triple therapy. Conclusion The IL-1B gene T-31C SNP might be associated with an enhanced risk of H. pylori infection among the Jordanian population.
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Affiliation(s)
- Muhamad Ali K Shakhatreh
- Department of Medical Laboratory Sciences, Jordan University of Science and Technology, Irbid, Jordan
| | - Omar F Khabour
- Department of Medical Laboratory Sciences, Jordan University of Science and Technology, Irbid, Jordan
| | - Karem H Alzoubi
- Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid, Jordan
| | - Mohammed N BaniHani
- Department of General Surgery and Urology, Jordan University of Science and Technology, Irbid, Jordan
| | - Ahmed Abu-Siniyeh
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Kingdom of Saudi Arabia
| | - Nabil A Bashir
- Department of Physiology and Biochemistry, Jordan University of Science and Technology, Irbid, Jordan
| | - Salsabeel H Sabi
- Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid, Jordan
| | - Mahmoud Mahafdah
- Department of General Surgery and Urology, Jordan University of Science and Technology, Irbid, Jordan
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17
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Negovan A, Iancu M, Fülöp E, Bănescu C. Helicobacter pylori and cytokine gene variants as predictors of premalignant gastric lesions. World J Gastroenterol 2019; 25:4105-4124. [PMID: 31435167 PMCID: PMC6700706 DOI: 10.3748/wjg.v25.i30.4105] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2019] [Revised: 07/12/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer remains the third leading cause of mortality from cancer worldwide and carries a poor prognosis, due largely to late diagnosis. The importance of the interaction between Helicobacter pylori (H. pylori) infection, the main risk factor, and host-related genetic factors has been studied intensively in recent years. The genetic predisposition for non-hereditary gastric cancer is difficult to assess, as neither the real prevalence of premalignant gastric lesions in various populations nor the environmental risk factors for cancer progression are clearly defined. For non-cardiac intestinal-type cancer, identifying the factors that modulate the progression from inflammation toward cancer is crucial in order to develop preventive strategies. The role of cytokines and their gene variants has been questioned in regard to non-self-limiting H. pylori gastritis and its evolution to gastric atrophy and intestinal metaplasia; the literature now includes various and non-conclusive results on this topic. The influence of the majority of cytokine single nucleotide polymorphisms has been investigated for gastric cancer but not for preneoplastic gastric lesions. Among the investigated gene variants onlyIL10T-819C, IL-8-251, IL-18RAP917997, IL-22 rs1179251, IL1-B-511, IL1-B-3954, IL4R-398 and IL1RN were identified as predictors for premalignant gastric lesions risk. One of the most important limiting factors is the inhomogeneity of the studies (e.g., the lack of data on concomitant H. pylori infection, methods used to assess preneoplastic lesions, and source population). Testing the modifying effect of H. pylori infection upon the relationship between cytokine gene variants and premalignant gastric lesions, or even testing the interaction between H. pylori and cytokine gene variants in multivariable models adjusted for potential covariates, could increase generalizability of results.
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Affiliation(s)
- Anca Negovan
- Department of Clinical Science-Internal Medicine, University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Mureș 540139, Romania
| | - Mihaela Iancu
- Department of Medical Informatics and Biostatistics, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Cluj 400349, Romania
| | - Emőke Fülöp
- Department of Morphological Sciences, Histology, University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Mureș 540139, Romania
| | - Claudia Bănescu
- Genetics Laboratory, Center for Advanced Medical and Pharmaceutical Research, University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Mureș 540139, Romania
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18
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Differential Helicobacter pylori Plasticity in the Gastric Niche of Subjects at Increased Gastric Cancer Risk. Pathogens 2019; 8:pathogens8020065. [PMID: 31109082 PMCID: PMC6630233 DOI: 10.3390/pathogens8020065] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 05/09/2019] [Accepted: 05/15/2019] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori (H. pylori) represents an independent risk factor for Gastric Cancer (GC). First Degree Relatives (FDR) of GC subjects and Autoimmune Gastritis (AG) patients are both at increased risk for GC. H. pylori genetic heterogeneity within the gastric niche of FDR and AG individuals has been little explored. To understand whether they exploit an increased H. pylori stability and virulence, 14 AG, 25 FDR, 39 GC and 13 dyspeptic patients (D) were investigated by a cultural PCR-based approach characterizing single colonies-forming-units. We chose three loci within the Cytotoxin-associated gene-A Pathogenicity Island (CagPAI) (cagA,cagE,virB11), vacA, homA and homB as markers of virulence with reported association to GC. Inflammatory/precancerous lesions were staged according to Sydney System. When compared to D, FDR, similarly to GC patients, were associated to higher atrophy (OR = 6.29; 95% CI:1.23-31.96 in FDR; OR = 7.50; 95% CI:1.67-33.72 in GC) and a lower frequency of mixed infections (OR = 0.16; 95% CI:0.03-0.81 in FDR; OR = 0.10; 95% CI:0.02-0.48 in GC). FDR presented also an increased neutrophil infiltration (OR = 7.19; 95% CI:1.16-44.65). Both FDR and GC carried a higher proportion of CagPAI+vacAs1i1mx+homB+ profiles (OR = 2.71; 95% CI: 1.66-4.41 and OR = 3.43; 95% CI: 2.16-5.44, respectively). Conversely, AG patients presented a lower frequency of subtypes carrying a stable CagPAI and vacAs1i1mx. These results underline different H. pylori plasticity in FDR and AG individuals, and thus, a different host-bacterium interaction capacity that should be considered in the context of eradication therapies.
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Genetic polymorphisms in TLR1, TLR2, TLR4, and TLR10 of Helicobacter pylori-associated gastritis: a prospective cross-sectional study in Thailand. Eur J Cancer Prev 2019; 27:118-123. [PMID: 28368946 PMCID: PMC5802262 DOI: 10.1097/cej.0000000000000347] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The toll-like receptors (TLRs) mediate the recognition of Helicobacter pylori and initiate the innate immune response to infection. We hypothesized those genetic polymorphisms in the TLR1, TLR2, TLR4, and TLR10 influence bacterial infection, affecting susceptibility H. pylori to disease outcomes. Genomic DNA was extracted and genotypes of TLR1 (rs4833095), TLR2 (rs3804099 and rs3804100), TLR4(rs10759932), and TLR10 (rs10004195) polymorphism were detected by the TagMan single-nucleotide epolymorphisms genotyping assay using the real-time PCR hybridization probe method. The TLR1 (rs4833095), C allele and the TLR10 (rs10004195), A allele frequency was significantly increased risk in the H. pylori infection group (odds ratio=1.76, 95% confidence interval=1.84–2.15, P=0.01 and odds ratio=1.81, 95% confidence interval=1.18–3.26, P=0.04, respectively). The TLR1 (rs4833095), C allele and TLR10 (rs10004195), A allele are susceptible TLRs polymorphisms in the Thai population. These findings suggest that TLR1 rs4833095 and TLR10 rs10004195 may play crucial roles in H. pylori susceptibility and gastric pathogenesis.
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Yin L, Liu F, Guo C, Wang Q, Pan K, Xu L, Xiong Y, Chen Y, Chen Z. Analysis of virulence diversity of 73 Helicobacter pylori strains isolated in Guizhou province, China. Mol Med Rep 2018; 18:4611-4620. [PMID: 30221659 DOI: 10.3892/mmr.2018.9462] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Accepted: 08/07/2018] [Indexed: 11/05/2022] Open
Abstract
The present study aimed to investigate the virulence diversity of Helicobacter pylori (H. pylori) in major ethnic groups residing in Guizhou province, China, and its association with clinical outcomes. Gastric mucosal biopsies were collected from the pylorus of patients with gastrointestinal disorders. H. pylori was identified by colonial morphology, Gram staining, a urease test and H. pylori‑specific 16S rRNA gene fragment PCR amplification. DNA was extracted from pure culture and used for virulence gene analysis. The cytotoxin associated gene A (cagA), vacuolating cytotoxin A (vacA) and induced by contact with epithelium gene A (iceA) genes were analyzed by polymerase chain reaction analysis. The cagA gene was further analyzed through sequencing of the C‑terminal region containing EPIYA motifs, and phylogenetic analysis of the cagA C‑terminal variable region was performed using MEGA 6.0 software. In the present study, 73 H. pylori strains were isolated from clinical samples. cagA genotypes were detected in all strains, namely cagA‑AB, ‑ABC, ‑ABD and ‑BD genotypes were found in five (6.85%), three (4.11%), 63 (86.30%) and two (2.74%) isolates, respectively. Phylogenetic analysis showed that there was a clustering association between the cagA‑AB and cagA‑ABC genotypes, and between the cagA‑ABD and cagA‑BD genotypes. In terms of the frequency of the four EPIYA or EPIYA‑like motifs, the most predominant was EPIYA (92.92%), followed by EPIYT (3.77%), ESIYA (2.83%) and ESIYT (0.47%). The predominant vacA genotype was s1c/m2 (65.75%), and the predominant iceA genotype was iceA1 (79.45%). There were no associations between the H. pylori cagA, vacA or iceA genotypes and clinical outcomes. No significant difference was found in the distribution of these genotypes according to the age, ethnicity or location of residence of patients. In conclusion, H. pylori isolated from patients in Guizhou region, China, showed a unique genotype, which was mainly East Asia‑type cagA (ABD), vacA s1c/m2 genotype or iceA1‑postiive. These results provide important information on the distribution of H. pylori virulence genotypes in Guizhou province, China.
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Affiliation(s)
- Lin Yin
- Department of Microbiology, School of Basic Medical Science, Guizhou Medical University, Key Laboratory of Medical Microbiology and Parasitology of Guizhou Province, Guiyang, Guizhou 550025, P.R. China
| | - Fang Liu
- Department of Microbiology, School of Basic Medical Science, Guizhou Medical University, Key Laboratory of Medical Microbiology and Parasitology of Guizhou Province, Guiyang, Guizhou 550025, P.R. China
| | - Changcheng Guo
- Department of Microbiology, School of Basic Medical Science, Guizhou Medical University, Key Laboratory of Medical Microbiology and Parasitology of Guizhou Province, Guiyang, Guizhou 550025, P.R. China
| | - Qiong Wang
- Department of Microbiology, School of Basic Medical Science, Guizhou Medical University, Key Laboratory of Medical Microbiology and Parasitology of Guizhou Province, Guiyang, Guizhou 550025, P.R. China
| | - Ke Pan
- Department of Gastrointestinal Medicine, The People's Hospital of Qiannan Autonomous Prefecture, Duyun, Guizhou 558000, P.R. China
| | - Liangbi Xu
- Department of Gastrointestinal Medicine, The First Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
| | - Yan Xiong
- Department of Gastrointestinal Medicine, Guiyang Children's Hospital, Guiyang, Guizhou 550000, P.R. China
| | - Yingting Chen
- Department of Gastrointestinal Medicine, The First Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
| | - Zhenghong Chen
- Department of Microbiology, School of Basic Medical Science, Guizhou Medical University, Key Laboratory of Medical Microbiology and Parasitology of Guizhou Province, Guiyang, Guizhou 550025, P.R. China
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Zhang X, Shi D, Liu YP, Chen WJ, Wu D. Effects of the Helicobacter pylori Virulence Factor CagA and Ammonium Ion on Mucins in AGS Cells. Yonsei Med J 2018; 59:633-642. [PMID: 29869461 PMCID: PMC5990679 DOI: 10.3349/ymj.2018.59.5.633] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Revised: 04/17/2018] [Accepted: 04/25/2018] [Indexed: 12/22/2022] Open
Abstract
PURPOSE To investigate the effects of Helicobacter pylori (H. pylori)-CagA and the urease metabolite NH₄⁺ on mucin expression in AGS cells. MATERIALS AND METHODS AGS cells were transfected with CagA and/or treated with different concentrations of NH₄CL. Mucin gene and protein expression was assessed by qPCR and immunofluorescence assays, respectively. RESULTS CagA significantly upregulated MUC5AC, MUC2, and MUC5B expression in AGS cells, but did not affect E-cadherin and MUC6 expression. MUC5AC, MUC6, and MUC2 expression in AGS cells increased with increasing NH₄⁺ concentrations until reaching a peak level at 15 mM. MUC5B mRNA expression in AGS cells (NH₄⁺ concentration of 15 mM) was significantly higher than that at 0, 5, and 10 mM NH₄⁺. No changes in E-cadherin expression in AGS cells treated with NH₄⁺ were noted, except at 20 mM. The expression of MUC5AC, MUC2, and MUC6 mRNA in CagA-transfected AGS cells at an NH₄⁺ concentration of 15 mM was significantly higher than that at 0 mM, and decreased at higher concentrations. The expression of MUC5B mRNA increased with increases in NH₄⁺ concentration, and was significantly higher compared to that in untreated cells. No significant change in the expression of E-cadherin mRNA in CagA-transfected AGS cells was observed. Immunofluorescence assays confirmed the observed changes. CONCLUSION H. pylori may affect the expression of MUC5AC, MUC2, MUC5B, and MUC6 in AGS cells via CagA and/or NH₄⁺, but not E-cadherin.
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Affiliation(s)
- Xiaoyu Zhang
- Department of Gastroenterology, Henan University of Chinese Medicine, Zhengzhou, China
| | - Ding Shi
- Department of Gastroenterology, Ningbo No. 2 Hospital, Ningbo, China.
| | - Yong Pan Liu
- Department of Gastroenterology, the First People's Hospital of Yuhang District, Hangzhou, China
| | - Wu Jie Chen
- Department of Gastroenterology, Ningbo No. 2 Hospital, Ningbo, China
| | - Dong Wu
- Department of Gastroenterology, Ningbo No. 2 Hospital, Ningbo, China
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Shi D, Liu Y, Wu D, Hu X. Transfection of the Helicobacter pylori CagA gene alters MUC5AC expression in human gastric cancer cells. Oncol Lett 2018; 15:5208-5212. [PMID: 29552159 DOI: 10.3892/ol.2018.7960] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Accepted: 08/24/2017] [Indexed: 12/22/2022] Open
Abstract
Helicobacter pylori, the primary causative agent of stomach cancer, is known to affect gastric mucin expression. However, the underlying molecular mechanisms mediating this H. pylori-dependent effect remain unknown. In the present study, the effect of exogenous expression of the H. pylori virulence factor, CagA, on mucin 5AC oligomeric muscus/gel-forming (MUC5AC) expression was investigated using an in vitro model of the gastric mucosa. AGS cells were either untreated or transfected by a vector control (pCDNA3.1) or heterologous DNA, which induced CagA overexpression (pCDNA3.1-CagA). The expression and functionality of MUC5AC was analyzed using the reverse transcription-quantitative polymerase chain reaction and immunofluorescence assays. The expression of H. pylori-CagA in AGS cells was able to significantly upregulate MUC5AC expression compared to the vector control. In addition, immunofluorescence assays were able to validate increased MUC5AC expression following exogenous expression of H. pylori-CagA. The results of the present study revealed that the H. pylori-derived virulence factor CagA was able to increase the expression of MUC5AC. As this mucin constitutes an important ecological niche for H. pylori, this response may be involved in H. pylori colonization of the stomach.
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Affiliation(s)
- Ding Shi
- Department of Gastroenterology, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315000, P.R. China
| | - Yongpan Liu
- Department of Gastroenterology, First People's Hospital of Yuhang District, Hangzhou, Zhejiang 31100, P.R. China
| | - Dong Wu
- Department of Gastroenterology, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315000, P.R. China
| | - Xujun Hu
- Department of Gastroenterology, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315000, P.R. China
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Chang CH, Wu JB, Yang JS, Lai YJ, Su CH, Lu CC, Hsu YM. The Suppressive Effects of Geniposide and Genipin on Helicobacter pylori
Infections In Vitro
and In Vivo. J Food Sci 2017; 82:3021-3028. [PMID: 29135040 DOI: 10.1111/1750-3841.13955] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Revised: 08/29/2017] [Accepted: 09/19/2017] [Indexed: 12/14/2022]
Affiliation(s)
- Chiung-Hung Chang
- Dept. of Traditional Chinese Medicine; Tainan Municipal Hospital; Tainan Taiwan
- Dept. of Traditional Chinese Medicine; Taichung Veterans General Hospital; Taichung Taiwan
| | - Jin-Bin Wu
- School of Pharmacy; China Medical Univ.; Taichung Taiwan
| | - Jai-Sing Yang
- Dept. of Medical Research, China Medical Univ. Hospital; China Medical Univ.; Taichung Taiwan
| | - Yen-Ju Lai
- Dept. of Biological Science and Technology; China Medical Univ.; Taichung Taiwan
| | - Chiu-Hsian Su
- Dept. of Biological Science and Technology; China Medical Univ.; Taichung Taiwan
| | - Chi-Cheng Lu
- Dept. of Pharmacy; Buddhist Tzu Chi General Hospital; Hualien Taiwan
| | - Yuan-Man Hsu
- Dept. of Biological Science and Technology; China Medical Univ.; Taichung Taiwan
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Ponzetto A, Figura N. Letter: the risk of cancer in patients with gastric intestinal metaplasia. Aliment Pharmacol Ther 2017; 46:1020-1021. [PMID: 29052860 DOI: 10.1111/apt.14329] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Affiliation(s)
- A Ponzetto
- Department of Medical Sciences, University of Turin, Torino, Italy
| | - N Figura
- Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy
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Kim JY, Bae BN, Kang G, Kim HJ, Park K. Cytokine expression associated with Helicobacter pylori and Epstein-Barr virus infection in gastric carcinogenesis. APMIS 2017; 125:808-815. [PMID: 28736845 DOI: 10.1111/apm.12725] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2016] [Accepted: 04/28/2017] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori and Epstein-Barr virus (EBV) infection, and associated cytokines are involved in gastric carcinogenesis. We investigated the expression of these cytokines and their relationship with clinicopathological characteristics. The study included specimens from 207 patients with gastric adenocarcinoma, 56 with chronic gastritis, 32 with metaplasia, and 30 with low-grade epithelial dysplasia. Tissue microarrays were constructed and immunohistochemical staining for IL-1β, IL-6, IL-10, IL-17, p16, p21, TNF-α, and TNFR1 was performed. EBV and H. pylori infection status was determined. IL-1β, IL-6, IL-17, p16, and p21 protein expression was significantly higher in adenocarcinoma cases than in the other cases (p < 0.05). EBV was only noted in adenocarcinoma (13 cases, 6.3%). The H. pylori infection rate in adenocarcinoma was significantly higher than that in the other cases (p < 0.005). IL-6 expression was associated with improved survival (p < 0.05), whereas IL-17 expression was associated with decreased survival (p < 0.05). IL-6 expression was inversely associated with angioinvasion, and disease stage (p < 0.05), whereas IL-17 expression was associated with disease stage (p < 0.05). IL-10 expression was correlated with IL-1β and TNF-α expression, and p16 expression was correlated with IL-17 and EBV status. Our results indicate that IL-6 and IL-17 are associated with gastric carcinogenesis and may be considered prognostic factors.
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Affiliation(s)
- Jung Yeon Kim
- Department of Pathology, Inje University Sanggye Paik Hospital, Seoul, Korea
| | - Byung-Noe Bae
- Department of Surgery, Inje University Sanggye Paik Hospital, Seoul, Korea
| | - Guhyun Kang
- Department of Pathology, Inje University Sanggye Paik Hospital, Seoul, Korea
| | - Hyun-Jung Kim
- Department of Pathology, Inje University Sanggye Paik Hospital, Seoul, Korea
| | - Kyeongmee Park
- Department of Pathology, Inje University Sanggye Paik Hospital, Seoul, Korea
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26
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Bernardini G, Figura N, Ponzetto A, Marzocchi B, Santucci A. Application of proteomics to the study of Helicobacter pylori and implications for the clinic. Expert Rev Proteomics 2017; 14:477-490. [PMID: 28513226 DOI: 10.1080/14789450.2017.1331739] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Helicobacter pylori (H. pylori) is a gram-negative bacterium that colonizes the gastric epithelium and mucous layer of more than half the world's population. H. pylori is a primary human pathogen, responsible for the development of chronic gastritis, peptic ulceration and gastric cancer. Proteomics is impacting several aspects of medical research: understanding the molecular basis of infection and disease manifestation, identification of therapeutic targets and discovery of clinically relevant biomarkers. Areas covered: The main aim of the present review is to provide a comprehensive overview of the contribution of proteomics to the study of H. pylori infection pathophysiology. In particular, we focused on the role of the bacterium and its most important virulence factor, CagA, in the progression of gastric cells transformation and cancer progression. We also discussed the proteomic approaches aimed at the investigation of the host response to bacterial infection. Expert commentary: In the field of proteomics of H. pylori, comprehensive analysis of clinically relevant proteins (functional proteomics) rather than entire proteomes will result in important medical outcomes. Finally, we provided an outlook on the potential development of proteomics in H. pylori research.
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Affiliation(s)
- Giulia Bernardini
- a Dipartimento di Biotecnologie , Chimica e Farmacia, Università degli Studi di Siena , Siena , Italy
| | - Natale Figura
- a Dipartimento di Biotecnologie , Chimica e Farmacia, Università degli Studi di Siena , Siena , Italy
| | - Antonio Ponzetto
- b Dipartimento di Scienze Mediche , Università degli Studi di Torino , Torino , Italy
| | - Barbara Marzocchi
- a Dipartimento di Biotecnologie , Chimica e Farmacia, Università degli Studi di Siena , Siena , Italy
| | - Annalisa Santucci
- a Dipartimento di Biotecnologie , Chimica e Farmacia, Università degli Studi di Siena , Siena , Italy
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Jia ZF, Wu YH, Cao DH, Cao XY, Jiang J, Zhou BS. Polymorphisms of cancer stem cell marker gene CD133 are associated with susceptibility and prognosis of gastric cancer. Future Oncol 2017; 13:979-989. [PMID: 28326835 DOI: 10.2217/fon-2017-0019] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Accepted: 02/03/2017] [Indexed: 02/07/2023] Open
Abstract
AIM This study was aimed to investigate the associations between single nucleotide polymorphisms of cancer stem cell marker genes, CD44 and CD133, and susceptibility and prognosis of gastric cancer. PATIENTS & METHODS Five single nucleotide polymorphisms in CD44 and CD133 genes were genotyped in 898 gastric cancer cases and 992 controls. RESULTS The A/C or C/C genotypes of CD133 rs2240688 were associated with decreased risk of gastric cancer comparing with the A/A genotype (odds ratio: 0.81; 95% CI: 0.67-0.97; p = 0.023). The T allele of CD133 rs3130 predicted a worse survival for gastric cancer patients receiving tumorectomy (hazard ratio: 1.28; 95% CI: 1.04-1.58; p = 0.020), independent from tumor node metastasis stage, vessel invasion and postoperational chemotherapy. CONCLUSION CD133 polymorphisms are promising biomarkers for genetic susceptibility and prognosis prediction of gastric cancer.
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Affiliation(s)
- Zhi-Fang Jia
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110112, PR China
- Division of Clinical Research, First Hospital of Jilin University, Changchun 130021, PR China
| | - Yan-Hua Wu
- Division of Clinical Research, First Hospital of Jilin University, Changchun 130021, PR China
| | - Dong-Hui Cao
- Division of Clinical Research, First Hospital of Jilin University, Changchun 130021, PR China
| | - Xue-Yuan Cao
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun 130021, PR China
| | - Jing Jiang
- Division of Clinical Research, First Hospital of Jilin University, Changchun 130021, PR China
| | - Bao-Sen Zhou
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110112, PR China
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Xu Q, Chen TJ, He CY, Sun LP, Liu JW, Yuan Y. MiR-27a rs895819 is involved in increased atrophic gastritis risk, improved gastric cancer prognosis and negative interaction with Helicobacter pylori. Sci Rep 2017; 7:41307. [PMID: 28150722 PMCID: PMC5288699 DOI: 10.1038/srep41307] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Accepted: 12/19/2016] [Indexed: 12/15/2022] Open
Abstract
MiR-27a rs895819 is a loop-stem structure single nucleotide polymorphism affecting mature miR-27a function. In this study, we performed a comprehensive analysis about the association of rs895819 with gastric cancer risk and prognosis, atrophic gastritis risk, as well as the interactions with environmental factors. A total of 939 gastric cancer patients, 1,067 atrophic gastritis patients and 1,166 healthy controls were screened by direct sequencing and MALDI-TOF-MS. The association of rs895819 with clinical pathological parameters and prognostic survival in 357 gastric cancer patients was also been analyzed. The rs895819 variant genotype increased the risk for atrophic gastritis (1.58-fold) and gastric cancer (1.24-fold). While in stratified analysis, the risk effect was demonstrated more significantly in the female, age >60y, Helicobacter pylori (H. pylori) negative and non-drinker subgroups. Rs895819 and H. pylori showed an interaction effect for atrophic gastritis risk. In the survival analysis, the rs895819 AG heterozygosis was associated with better survival than the AA wild-type in the TNM stage I–II subgroup. In vitro study by overexpressing miR-27a, cells carrying polymorphic-type G allele expressed lower miR-27a than wild-type A allele. In conclusion, miR-27a rs895819 is implicated as a biomarker for gastric cancer and atrophic gastritis risk, and interacts with H. pylori in gastric carcinogenesis.
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Affiliation(s)
- Qian Xu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China
| | - Tie-Jun Chen
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China
| | - Cai-Yun He
- Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Li-Ping Sun
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China
| | - Jing-Wei Liu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China
| | - Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China
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Drici AEM, Moulessehoul S, Tifrit A, Diaf M, Turki DK, Bachir M, Tou A. Effect of IL-1β and IL-1RN polymorphisms in carcinogenesis of the gastric mucosa in patients infected with Helicobacter pylori in Algeria. Libyan J Med 2016; 11:31576. [PMID: 27340011 PMCID: PMC4919366 DOI: 10.3402/ljm.v11.31576] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2016] [Accepted: 05/27/2016] [Indexed: 12/12/2022] Open
Abstract
Background Infection with Helicobacter pylori is considered a potential risk of developing gastric cancer in association with contributing host genetic factor. IL-1β and IL-1RN polymorphisms appear to maintain and promote Helicobacter pylori infection and to stimulate neoplastic growth of the gastric mucosa. Objective and methods In order to elucidate the effect of these polymorphisms in combination with gastric cancer in a population from northwestern Algeria, a case-control study was carried out on 79 patients infected with H. pylori with chronic atrophic gastritis and/or gastric carcinoma, and 32 subjects were recruited as case-control. IL-1β-31 bi-allelic and IL-1β-511 bi-allelic polymorphisms and IL-1RN penta-allelic were genotyped. Results IL-1β-31C was associated with an increased risk of developing gastric carcinoma (OR=4.614 [1.43−14.81], p=0.01). However, IL-1RN2 heterozygous allele type was significantly associated with chronic atrophic gastritis (OR=4.2 [1.23−3.61], p=0.022). IL-1β-511T was associated with an increased risk of development of chronic atrophic gastritis (OR=4.286 [1.54−11.89], p=0.005). Conclusion IL-1β and IL-1RN polymorphisms associated with H. pylori infection contribute to the development of chronic atrophic gastritis and gastric carcinomas in an Algerian population. The alleles IL-1β-31C and IL-1RN were associated with an increased risk of developing gastric carcinoma, and IL-1β-511T with an increased risk of developing chronic atrophic gastritis with no significant association of developing gastric carcinoma.
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Affiliation(s)
- Amine El-Mokhtar Drici
- Department of Biology, Faculty of Natural and Life Sciences, Djillali LIABES University, Sidi-Bel-Abbes, Algeria;
| | - Soraya Moulessehoul
- Department of Biology, Faculty of Natural and Life Sciences, Djillali LIABES University, Sidi-Bel-Abbes, Algeria
| | - Abdelkarim Tifrit
- Department of Biology, Faculty of Natural and Life Sciences, Djillali LIABES University, Sidi-Bel-Abbes, Algeria
| | - Mustapha Diaf
- Department of Biology, Faculty of Natural and Life Sciences, Djillali LIABES University, Sidi-Bel-Abbes, Algeria
| | - Douidi Kara Turki
- Department of Gastroenterology, University Hospital of Sidi-Bel-Abbes, Sidi-Bel-Abbes, Algeria
| | - Meryem Bachir
- Department of Biology, Faculty of Sciences, Hassiba Ben Bouali University, Chlef, Algeria
| | - Abdenacer Tou
- Anatomopathology Department, University Hospital of Sidi-Bel-Abbes, Sidi-Bel-Abbes, Algeria
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