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Kusano C, Ishibashi F, Ichita C, Gotoda T. Current Status of Gastric Cancer Screening and Future Perspectives. DEN OPEN 2026; 6:e70148. [PMID: 40433232 PMCID: PMC12106035 DOI: 10.1002/deo2.70148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/31/2025] [Revised: 05/11/2025] [Accepted: 05/13/2025] [Indexed: 05/29/2025]
Abstract
Gastric cancer (GC) remains a major global health concern, particularly in East Asia, Central Asia, and Eastern Europe, where its incidence and mortality rates are high. Helicobacter pylori infection is the primary cause of GC and leads to carcinogenic progression from nonatrophic gastritis to cancer. Although screening programs have been implemented in high-risk countries, such as Japan and South Korea, comprehensive strategies remain limited globally. This study reviewed the status of GC screening worldwide and prevention strategies in regions with different risks. Various GC screening methods have been developed, including H. pylori serology, serum pepsinogen testing, upper gastrointestinal contrast radiography, and endoscopy. Endoscopic screening has shown superior sensitivity and specificity, reducing GC mortality by up to 47% in South Korea and demonstrating higher detection rates than upper gastrointestinal contrast radiography and pepsinogen testing. However, cost-effectiveness remains a challenge, particularly in Western countries where the overall GC prevalence is lower. Risk stratification using a combination of H. pylori serology and pepsinogen testing has been adopted in Japan to optimize screening efficiency. Additionally, H. pylori eradication has been recognized as a cost-effective strategy to reduce the incidence of GC with economic benefits demonstrated in Japan and other high-risk regions. In the United States, targeted screening of high-risk immigrant populations has been suggested to enhance cost-effectiveness. GC screening strategies should consider developing epidemiological trends, cost-effectiveness, and risk-based approaches. Future efforts should focus on expanding targeted screening initiatives to high-risk groups to improve early detection and survival rates.
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Affiliation(s)
- Chika Kusano
- Department of MedicineDivision of Gastroenterology and HepatologyKitasato University School of MedicineSagamiharaJapan
| | - Fumiaki Ishibashi
- Department of GastroenterologyInternational University of Health and Welfare Ichikawa HospitalIchikawaJapan
| | - Chikamasa Ichita
- Gastroenterology Medicine CenterShonan Kamakura General HospitalKamakuraJapan
| | - Takuji Gotoda
- Department of GastroenterologyCancer Institute HospitalTokyoJapan
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Giuliano AR, Palefsky JM, Goldstone SE, Bornstein J, De Coster I, Guevara AM, Mogensen O, Schilling A, Van Damme P, Vandermeulen C, Ellison MC, Kaplan S, Lin J, Bonawitz R, Luxembourg A. Immunogenicity of the 9-valent human papillomavirus vaccine: Post hoc analysis from five phase 3 studies. Hum Vaccin Immunother 2025; 21:2425146. [PMID: 39840832 DOI: 10.1080/21645515.2024.2425146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 10/18/2024] [Accepted: 10/30/2024] [Indexed: 01/23/2025] Open
Abstract
Post hoc analyses of 9-valent human papillomavirus (9vHPV) vaccine immunogenicity were conducted in five Phase 3 studies that enrolled males. Month 7 antibody geometric mean titers (GMTs) after three 9vHPV vaccine doses were analyzed in 10,024 males/females aged 16-26 years from studies 001 (NCT00543543), 002 (NCT00943722), 003 (NCT01651949), and 020 (NCT02114385). Covariates considered were age, gender, sexual orientation, region of residence, and race. GMTs among 2599 males/females aged 9-15 years (studies 002 and 010 [NCT01984697]) were assessed 6 months after one, two, and three 9vHPV vaccine doses. 9vHPV vaccine immunogenicity was robust across populations. Month 7 GMTs were generally higher in participants aged 16-21 versus 22-26 years. Region and race minimally impacted immunogenicity. Adjusted integrated analysis showed lower immunogenicity in men who have sex with men (MSM) versus heterosexual men (HM) for nine HPV types, and higher immunogenicity in HM versus females for seven HPV types. Among 9-15-year-olds, trends toward higher GMTs in males versus females post-Dose 3, similar GMTs post-Dose 2, and lower post-Dose 1 were observed. In conclusion, 9vHPV vaccine immunogenicity was robust in males aged 16-26 years across a range of baseline characteristics. GMT ratios for males versus females aged 9-15 years tended to increase with more doses.
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Affiliation(s)
- Anna R Giuliano
- Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Joel M Palefsky
- Department of Medicine, University of California at San Francisco, San Francisco, CA, USA
| | - Stephen E Goldstone
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jacob Bornstein
- Department of Obstetrics and Gynecology, Galilee Medical Center and Azrieli Faculty of Medicine, Bar-Ilan University, Nahariya, Israel
| | - Ilse De Coster
- Centre for the Evaluation of Vaccination, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
| | - Ana María Guevara
- Research Unit, Pablo Tobon Uribe Hospital, Medellin, Antioquia, Colombia
| | - Ole Mogensen
- Department of Gynecology and Obstetrics, Aarhus University Hospital, Aarhus, Denmark
- Institute of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark
| | - Andrea Schilling
- Clinical Research Center, Institute of Sciences and Innovation in Medicine, Facultad de Medicina Clinica Alemana Universidad del Desarrollo, Santiago, Chile
| | - Pierre Van Damme
- Centre for the Evaluation of Vaccination, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
| | - Corinne Vandermeulen
- Department of Public Health and Primary Care, Leuven University Vaccinology Center, KU Leuven, Leuven, Belgium
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Racovitan V, Goodman E, Cheung WY, Nichols AC, Caulley L, Wurzba S. Human papillomavirus (HPV) related oropharyngeal cancers in Canada: A multicenter retrospective cohort study. Hum Vaccin Immunother 2025; 21:2486768. [PMID: 40264440 PMCID: PMC12026042 DOI: 10.1080/21645515.2025.2486768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 03/13/2025] [Accepted: 03/27/2025] [Indexed: 04/24/2025] Open
Abstract
Oral human papillomavirus (HPV) infection is a risk for oropharyngeal cancer (OPC), now the leading HPV-related cancer in males in Canada. P16 positivity is a marker of HPV positivity. Since 2015, all major Canadian cancer centers perform routine p16 tumor marker testing of OPCs to define their HPV status but recent data on the HPV-attributable fraction for OPC in Canada do not exist. A retrospective chart review was conducted of all squamous cell OPC cases in patients 18 years and older diagnosed from 2016 to 2020 in 4 major Canadian hospital-based regional oncology centers to determine the HPV attributable fraction for OPC in Canada using p16 as a surrogate marker for HPV. 1154 OPC cases were identified. Most patients (85.4%) were male; about one-third 26 (31.4%) had never smoked. Most OPC (80.6%) were P16 positive. p16 positivity was 27 associated with younger age (mean age p16+ 61.6 vs. p16- 66.5 years, p < 0.0001), male sex 28 (p16+ males 84.0% vs p16+ females 60.9%, p < 0.0001), lower tumor stage (Stage 1 p16+ 29 88.1% vs Stage 4 p16+ 69.4%, p < 0.001), and non-smoking (never smoked 92.3% vs past 30 smoker 82.8% vs current smoker 65.0%, p < 0.001). Logistic regression confirmed these 31 associations. This study, the largest cohort of Canadian patients with OPC yet reported, demonstrates the high attributable fraction for HPV-related OPC. HPV-related OPC was more likely in men, younger individuals, and never smokers. These findings highlight the burden of HPV-related OPC in Canada and support gender-neutral HPV vaccination as an important public health strategy to prevent head and neck cancer.
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Affiliation(s)
- Voica Racovitan
- Global Marketing HPV Strategy, Merck & Co. Inc ., North Wales, PA, USA
| | - Elizabeth Goodman
- Vaccine Outcomes Research, Value and Implementation, Merck and Co., Inc ., North Wales, PA, USA
| | - Winson Y. Cheung
- Departments of Medicine and Oncology, University of Calgary and the Charbonneau Cancer Institute, Calgary, AB, Canada
| | - Anthony C. Nichols
- Department of Otolaryngology – Head and Neck Surgery, University of Western Ontario, London, ON, Canada
| | - Lisa Caulley
- Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Sabrina Wurzba
- Department of Otolaryngology – Head and Neck Surgery, McGill University and the Jewish General Hospital, Montreal, QC, Canada
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Xu X, Fei X, Wang H, Wu X, Zhan Y, Li X, Zhou Y, Shu C, He C, Hu Y, Liu J, Lv N, Li N, Zhu Y. Helicobacter pylori infection induces DNA double-strand breaks through the ACVR1/IRF3/POLD1 signaling axis to drive gastric tumorigenesis. Gut Microbes 2025; 17:2463581. [PMID: 39924917 PMCID: PMC11812335 DOI: 10.1080/19490976.2025.2463581] [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: 08/15/2024] [Revised: 01/06/2025] [Accepted: 02/02/2025] [Indexed: 02/11/2025] Open
Abstract
Helicobacter pylori (H. pylori) infection plays a pivotal role in gastric carcinogenesis through inflammation-related mechanisms. Activin A receptor type I (ACVR1), known for encoding the type I receptor for bone morphogenetic proteins (BMPs), has been identified as a cancer diver gene across various tumors. However, the specific role of AVCR1 in H. pylori-induced gastric tumorigenesis remains incompletely understood. We conducted a comprehensive analysis of the clinical relevance of ACVR1 by integrating data from public databases and our local collection of human gastric tissues. In vitro cell cultures, patient-derived gastric organoids, and transgenic INS-GAS mouse models were used for Western blot, qRT-PCR, immunofluorescence, immunohistochemistry, luciferase assays, ChIP, and comet assays. Furthermore, to investigate the therapeutic potential, we utilized the ACVR1 inhibitor DM3189 in our in vivo studies. H. pylori infection led to increased expression of ACVR1 in gastric epithelial cells, gastric organoid and gastric mucosa of INS-GAS mice. ACVR1 activation led to DNA double-strand break (DSB) accumulation by inhibiting POLD1, a crucial DNA repair enzyme. The activation of POLD1 was facilitated by the transcription factor IRF3, with identified binding sites. Additionally, treatment with the ACVR1 inhibitor DM3189 significantly ameliorated H. pylori-induced gastric pathology and reduced DNA damage in INS-GAS mice. Immunohistochemistry analysis showed elevated levels of ACVR1 in H. pylori-positive gastritis tissues, showing a negative correlation with POLD1 expression. This study uncovers a novel signaling axis of AVCR1/IRF3/POLD1 in the pathogenesis of H. pylori infection. The upregulation of ACVR1 and the suppression of POLD1 upon H. pylori infection establish a connection between the infection, genomic instability, and the development of gastric carcinogenesis.
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Affiliation(s)
- Xinbo Xu
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Xiao Fei
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Huan Wang
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Xidong Wu
- Department of Drug Safety Evaluation, Jiangxi Testing Center of Medical Instruments, Nanchang, China
| | - Yuan Zhan
- Department of Pathology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Xin Li
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Yan’an Zhou
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Chunxi Shu
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Cong He
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Yi Hu
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Jianping Liu
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Nonghua Lv
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Nianshuang Li
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Yin Zhu
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
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Xie J, Peng J, Wu S, Yang K, Liu D, Shen L, Gong X, Liu D, Xie Y. Efficacy and safety of tetracycline vs. amoxicillin in furazolidone-based rescue therapy for Helicobacter pylori: a real-world analysis. Ann Med 2025; 57:2464938. [PMID: 39950212 PMCID: PMC11834778 DOI: 10.1080/07853890.2025.2464938] [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: 09/07/2024] [Revised: 01/23/2025] [Accepted: 01/25/2025] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND AND AIM Despite the increasing rates of antibiotic resistance, furazolidone-based regimens have demonstrated promise in Helicobacter pylori eradication. Therefore, this study aims to evaluate the comparative efficacy and safety of tetracycline versus amoxicillin in furazolidone-based quadruple therapy [bismuth quadruple therapy with furazolidone and tetracycline (BQFT) vs. bismuth quadruple therapy with furazolidone and amoxicillin (BQFA)] in rescue treatments. METHODS Patients who received BQFT or BQFA as rescue treatment were enrolled in this study. H. pylori status was determined using the 13C/14C urea breath test or histological examination. Eradication rates, adherence and side effects were carefully recorded. RESULTS A total of 342 participants were included. BQFT showed significantly higher eradication rates (modified intention-to-treat: 96.2% vs. 76%; per-protocol: 97.1% vs. 77.8%, P < 0.001), suggesting superior efficacy for patients with prior treatment failures. However, BQFA demonstrated fewer overall adverse effects (11.6% vs. 20.7%, P = 0.046), highlighting a tolerability advantage. Both groups showed similar symptom improvements and compliance rates. CONCLUSION BQFT exhibits superior efficacy with acceptable tolerability, making it a promising option for patients with refractory H. pylori infections. Clinicians should consider its benefits in cases of multiple prior eradication failures.
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Affiliation(s)
- Jinliang Xie
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Nanchang, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Jianxiang Peng
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Nanchang, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Shuang Wu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Department of Gastroenterology, The Second People’s Hospital of Jingdezhen, Jingdezhen, China
| | - Kaijie Yang
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Department of Gastroenterology, People’s Hospital of Ganzhou, Ganzhou, China
| | - Dingwei Liu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Nanchang, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Liting Shen
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Nanchang, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Xiaomin Gong
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Nanchang, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Dongsheng Liu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Nanchang, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Yong Xie
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Nanchang, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, China
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Karamousouli E, Sabale U, Valente S, Morosan F, Heuser M, Dodd O, Riley D, Heron L, Calabrò GE, Agorastos T, Sevelda P, Krasznai ZT, Nahum S, Horby R. Readiness assessment for cervical cancer elimination and prevention of human papillomavirus (HPV)-related cancers in Europe - are we winning the RACE? Expert Rev Vaccines 2025; 24:11-26. [PMID: 39670677 DOI: 10.1080/14760584.2024.2438759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 11/29/2024] [Accepted: 12/03/2024] [Indexed: 12/14/2024]
Abstract
INTRODUCTION To address the cervical cancer burden globally, the World Health Organization and European Union released strategies to facilitate HPV-related cancers prevention, including cervical cancer elimination. This research assessed European country level readiness to achieve cervical cancer elimination by adhering to such strategies. AREAS COVERED Readiness for cervical cancer elimination was assessed across a range of guiding questions relevant to three defined key domains: vaccination, screening, and treatment, each with two sub-domains focusing on decision making and implementation efforts. Publicly available data sources were used to inform the scoring across domains, to tier countries into either high, moderate-high, moderate-low, and low readiness archetypes.Key parameters identified associated with the high readiness archetype were high vaccination coverage rates (>70%), availability of gender neutral and catch-up vaccination, school-based vaccination availability, organized screening programs, use of HPV DNA primary screening tests, and data surveillance. EXPERT OPINION Our analysis highlights significant variability in decision making and implementation of vaccination, screening, and treatment programmes across Europe. Country scores expose the need for a multifaceted approach to achieve cervical cancer elimination in Europe, encompassing solid decision making commitments, implementation of these commitments, and the ability to collect, surveil, and apply the data use accurately.
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Affiliation(s)
| | - Ugne Sabale
- Value & Implementation Outcomes Research, MSD, Vilnius, Lithuania
| | - Stefano Valente
- Value & Implementation Global Medical and Scientific Affairs, MSD, Rome, Italy
| | - Fanut Morosan
- Regional Market Access, Regional Market Access, MSD, Bucharest, Romania
| | - Maria Heuser
- Adelphi Values PROVE, Macclesfield, Cheshire, UK
| | - Olivia Dodd
- Adelphi Values PROVE, Macclesfield, Cheshire, UK
| | | | - Louise Heron
- Adelphi Values PROVE, Macclesfield, Cheshire, UK
| | - Giovanna Elisa Calabrò
- Department of Human, Social and Health Sciences, University of Cassino and Southern Lazio, Cassino, Italy
| | - Theodoros Agorastos
- School of Health Sciences, Department of Medicine, Third Clinic of Obstetrics and Gyneacology, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Paul Sevelda
- Karl Landsteiner Institute for gynecologic Oncology and Senology, Austrian Cancer Aid, Vienna, Austria
| | - Zoárd Tibor Krasznai
- Department of Obstetrics and Gynecology, University of Debrecen Faculty of Medicine, Debrecen, Hungary
| | - Shay Nahum
- Regional Market Access, MSD, Aviel, Israel
| | - Rune Horby
- Public Policy Mid-European Region, MSD, Copenhagen, Denmark
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Shang LQ, Guo HX, Wang P, Sun XH, You JQ, Ma JT, Wang LK, Liu JX, Wang ZQ, Shao HB. Global scientific trends on hepatocellular carcinoma research from 2004 to 2023: A bibliometric and visualized analysis. World J Gastrointest Oncol 2025; 17:105781. [DOI: 10.4251/wjgo.v17.i6.105781] [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: 02/06/2025] [Revised: 03/22/2025] [Accepted: 04/17/2025] [Indexed: 06/13/2025] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide, and the research landscape has rapidly evolved over the past two decades. Despite significant progress, an in-depth analysis of global research trends, collaborative networks, and emerging themes in HCC remains limited. This study aimed to fill this gap by conducting a bibliometric analysis to map the research output, identify key contributors, and highlight future directions in HCC research. We hypothesized that the analysis would reveal a growing focus on molecular mechanisms and immunotherapy, with increasing contributions from specific countries and institutions.
AIM To investigate global research trends, collaborative networks, and emerging themes in HCC from 2004 to 2023.
METHODS A bibliometric analysis was performed using 93987 publications from the Science Citation Index Expanded Database of the Web of Science Core Collection. Data were analyzed using the VOSviewer software to identify publication trends, leading contributors, and research themes. Key metrics included annual publication output, country and institutional contributions, journal impact, and thematic clusters. Statistical analysis was carried out to quantify trends and collaborations.
RESULTS The number of annual publications increased from 2341 in 2004 to 8756 in 2023, with 65583 papers (69.78%) published between 2014 and 2023. China, the United States, and Japan were the top contributors, constituting 58.3% of total publications. PLOS One published the most studies (n = 2145), while Gastroenterology had the highest average number of citations (78.4 citations per paper). Fudan University was the most prolific institution (n = 1872). Thematic analysis identified five main clusters, namely molecular mechanisms, therapeutic strategies, prognosis and immunology, risk factors, and diagnostic approaches.
CONCLUSION This study highlights the growing focus on HCC research, particularly in immunotherapy and molecular mechanisms, underscoring the significance of international collaboration to advance diagnosis and treatment strategies.
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Affiliation(s)
- Li-Qi Shang
- Department of Interventional Radiology, The First Hospital of China Medical University, Shenyang 110000, Liaoning Province, China
| | - Hao-Xin Guo
- Department of Information Center, The First Hospital of China Medical University, Shenyang 110000, Liaoning Province, China
| | - Peng Wang
- Department of Interventional Radiology, The First Hospital of China Medical University, Shenyang 110000, Liaoning Province, China
| | - Xiao-Han Sun
- Department of Interventional Radiology, The First Hospital of China Medical University, Shenyang 110000, Liaoning Province, China
| | - Jia-Qi You
- Department of Interventional Radiology, The First Hospital of China Medical University, Shenyang 110000, Liaoning Province, China
| | - Jun-Ting Ma
- Department of Interventional Radiology, The First Hospital of China Medical University, Shenyang 110000, Liaoning Province, China
| | - Lu-Ke Wang
- Department of Interventional Radiology, The First Hospital of China Medical University, Shenyang 110000, Liaoning Province, China
| | - Jia-Xi Liu
- Department of Interventional Radiology, The First Hospital of China Medical University, Shenyang 110000, Liaoning Province, China
| | - Zhong-Qing Wang
- Department of Information Center, The First Hospital of China Medical University, Shenyang 110000, Liaoning Province, China
| | - Hai-Bo Shao
- Department of Interventional Radiology, The First Hospital of China Medical University, Shenyang 110000, Liaoning Province, China
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Wu X, Zhang Z, Zhang L, Daniels DJ. Role of cytomegalovirus in glioblastoma development: promoter or culprit? Virol J 2025; 22:194. [PMID: 40514716 PMCID: PMC12164097 DOI: 10.1186/s12985-025-02826-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2025] [Accepted: 06/07/2025] [Indexed: 06/16/2025] Open
Abstract
Glioblastoma is the most common primary malignant tumor of the central nervous system, with a median survival of less than two years. While the etiology of glioblastoma is unclear, viral infection has emerged as a potential contributing factor. Cytomegalovirus (CMV) was first reported to be associated with glioblastoma in 2002. Since then, many studies have detected CMV in glioblastoma tissues suggesting it may plays a role in the glioblastoma progression. While there is no direct evidence confirmings CMV as an oncogenic virus, studies have demonstrated that CMV promotes glioblastoma development in cell and animal models, with several CMV-related genes implicated in tumorigenesis. Importantly, adjuvant CMV antiviral therapy has been proven to improve glioblastoma patient survival. This review focuses on clinical studies regarding the relationship between CMV and glioblastoma, the mechanism of CMV in tumorigenesis, advances in animal models of CMV-induced glioblastoma, and key directions for future investigations.
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Affiliation(s)
- Xiaoxin Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China.
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, 55905, USA.
| | - Zhengyu Zhang
- Medical Records Department, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China
| | - Liang Zhang
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, 55905, USA
| | - David J Daniels
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, 55905, USA.
- Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA.
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Saadh MJ, Allela OQB, Kareem RA, Sanghvi G, Ballal S, Naidu KS, Bareja L, Chahar M, Gupta S, Sameer HN, Yaseen A, Athab ZH, Adil M. Exploring preventive and treatment strategies for oral cancer: Modulation of signaling pathways and microbiota by probiotics. Gene 2025; 952:149380. [PMID: 40089085 DOI: 10.1016/j.gene.2025.149380] [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: 10/24/2024] [Revised: 01/11/2025] [Accepted: 02/28/2025] [Indexed: 03/17/2025]
Abstract
The evidence suggests that the microbiome plays a crucial role in cancer development. The oral cavity has many microorganisms that can influence oral cancer progression. Understanding the mechanisms and signaling pathways of the oral, gum, and teeth microbiome in tumor progression can lead to new treatment strategies. Probiotics, which are friendly microorganisms, have shown potential as anti-cancer agents. These positive characteristics of probiotic strains make them suitable for cancer prevention or treatment. The oral-gut microbiome axis supports health and homeostasis, and imbalances in the oral microbiome can disrupt immune signaling pathways, epithelial barriers, cell cycles, apoptosis, genomic stability, angiogenesis, and metabolic processes. Changes in the oral microbiome in oral cancer may suggest using probiotics-based treatments for their direct or indirect positive roles in cancer development, progression, and metastasis, specifically oral squamous cell carcinoma (OSCC). Here, reported relationships between probiotics, oral microbiota, and oral cancer are summarized.
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Affiliation(s)
- Mohamed J Saadh
- Faculty of Pharmacy, Middle East University, Amman 11831, Jordan
| | | | | | - Gaurav Sanghvi
- Marwadi University Research Center, Department of Microbiology, Faculty of Science, Marwadi University, Rajkot 360003 Gujarat, India
| | - Suhas Ballal
- Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
| | - K Satyam Naidu
- Department of Chemistry, Raghu Engineering College, Visakhapatnam, Andhra Pradesh 531162, India
| | - Lakshay Bareja
- Centre for Research Impact & Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura 140401 Punjab, India
| | - Mamata Chahar
- Department of Chemistry, NIMS Institute of Engineering & Technology, NIMS University Rajasthan, Jaipur, India
| | - Sofia Gupta
- Department of Applied Sciences, Chandigarh Engineering College, Chandigarh Group of Colleges-Jhanjeri, Mohali 140307 Punjab, India
| | - Hayder Naji Sameer
- Collage of Pharmacy, National University of Science and Technology, Dhi Qar 64001, Iraq
| | | | - Zainab H Athab
- Department of Pharmacy, Al-Zahrawi University College, Karbala, Iraq
| | - Mohaned Adil
- Pharmacy college, Al-Farahidi University, Baghdad, Iraq
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10
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Li Y, Liu G, Zhou L, Wang Y, Sun Y, Chen Y, Chen L, Xiao J. Helicobacter Pylori-Induced Apoptosis in Gastric Diseases: Mechanisms, Implications, and Diagnostic Applications. Int J Gen Med 2025; 18:2995-3009. [PMID: 40524752 PMCID: PMC12168956 DOI: 10.2147/ijgm.s520982] [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: 02/13/2025] [Accepted: 05/31/2025] [Indexed: 06/19/2025] Open
Abstract
Helicobacter pylori (H. pylori) is a spiral-shaped gram-negative bacterium that causes one of the most common infections worldwide, affecting a significant portion of the human population. It plays a crucial role in regulating cellular activities, such as apoptosis, through various virulence factors, thereby contributing to the development and progression of gastrointestinal diseases including gastritis, ulcers, and gastric cancer. Here, we explored the complex relationship between H. pylori infection and apoptosis, emphasizing how H. pylori induces apoptosis via virulence factors (such as cytotoxin-associated gene A and vacuolating cytotoxin A), death receptor pathways, and host cell responses. Additionally, we critically examine current diagnostic strategies used to detect H. pylori infection and apoptosis, including non-invasive tests, invasive histopathological methods, and emerging molecular techniques. We assess their diagnostic value, limitations, and applicability in clinical settings, with the aim of identifying more effective approaches for early detection and disease monitoring.
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Affiliation(s)
- Yan Li
- Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People’s Republic of China
| | - Guozheng Liu
- The Fourth Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People’s Republic of China
| | - Lijie Zhou
- Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People’s Republic of China
| | - Yinghou Wang
- The Fourth Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People’s Republic of China
| | - Yangyang Sun
- Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People’s Republic of China
| | - Yanyan Chen
- The Fourth Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People’s Republic of China
| | - Liming Chen
- Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People’s Republic of China
| | - Jingdong Xiao
- Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, People’s Republic of China
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11
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Khormi MA, Al-maaqar SM, Al Johni AR, Al-Tayyar NA, Alhamad JA, Ghyathuddin AA, Alblawi Z, Behairy SM, Alghamdi MA, Alsubhi WA, Teklemariam MD. Oncolytic bacteria: A revolutionary approach to cancer therapy. Open Life Sci 2025; 20:20251076. [PMID: 40519767 PMCID: PMC12163578 DOI: 10.1515/biol-2025-1076] [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: 09/14/2024] [Revised: 01/18/2025] [Accepted: 02/11/2025] [Indexed: 06/18/2025] Open
Abstract
Cancer is one of the most devastating diseases all over the globe, and it is the second worldwide cause of death, exceeded only by cardiovascular diseases. The therapeutic approach to human cancer has evolved significantly and has varied depending on the type and stage of cancer, as well as the general health status of the patient. Despite the advancements in cancer treatment, various challenges persist in the treatment of cancer, including side effects, drug resistance, and incomplete eradication of tumors. The use of oncolytic bacteria (cancer targeting and destroying bacteria) has been identified to have several advantages over the traditional methods of cancer treatment. Several bacterial species have been identified to be used in the treatment of different types of cancers. Oncolytic therapy can be achieved through the use of a naturally occurring and/or genetically modified bacterial species, including Clostridium, Salmonella, Escherichia coli, and Listeria spp. with their toxins, enzymes, biofilms, and secondary metabolites as well as their spores that leads to direct or indirect killing of cancer cells. This review provides some highlights about the biology and therapeutic potential of oncolytic bacteria individually or in combination with other therapeutic approaches against different types of cancers. Besides, the current challenges and future perspectives will be explored.
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Affiliation(s)
- Mohsen A. Khormi
- Department of Biology, College of Science, Jazan University, P.O. Box 114, Jazan, 45142, Saudi Arabia
| | - Saleh M. Al-maaqar
- Department of Biology, Faculty of Education, Albaydha University, Al-Baydha, Yemen
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah, 21589, Saudi Arabia
| | | | | | - Jafar Abdullah Alhamad
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah, 21589, Saudi Arabia
| | - Abdullah A. Ghyathuddin
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah, 21589, Saudi Arabia
| | - Zakia Alblawi
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah, 21589, Saudi Arabia
| | - Sabreen M. Behairy
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah, 21589, Saudi Arabia
| | - Mohammed A. Alghamdi
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah, 21589, Saudi Arabia
| | - Wael A. Alsubhi
- Department of Pharmacy Practice, University of Hafr Al Batin, Hafr Al Batin, Saudi Arabia
| | - Mikiyas D. Teklemariam
- School of Nursing, Department of Midwifery, Addis Ababa University, College of Health Sciences, Addis Ababa, Ethiopia
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12
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Zheng Y, Han J, Qu Y, Wang J, Joyce BT, Kim K, Nannini DR, Musa J, Imade GE, Anorlu R, Maiga M, Morhason-Bello I, Simon MA, Silas O, Abdulkareem FB, Badmos K, Nyam CJ, Gursel DB, Wei JJ, Novo J, Sulaimon AA, Kayat LS, Kocherginsky M, Kim KYA, Burdett K, Katam N, Achenbach CJ, Sagay AS, Ogunsola FT, Murphy RL, Hou L. DNA methylation biomarkers for cervical cancer risk prediction in HIV-positive Nigerian women. Int J Cancer 2025. [PMID: 40490892 DOI: 10.1002/ijc.35502] [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: 08/16/2024] [Revised: 03/12/2025] [Accepted: 05/19/2025] [Indexed: 06/11/2025]
Abstract
Cervical cancer (CC) remains a significant public health issue in low- and middle-income countries (LMICs), especially in Western sub-Saharan Africa and Nigeria. While global CC incidence and mortality have declined, these regions continue to face high rates due to inadequate screening and the high prevalence of HIV, which increases CC risk by promoting persistent HPV infections. This study aimed to identify DNA methylation (DNAm) biomarkers for cervical intraepithelial neoplasia (CIN) and CC in HIV-positive Nigerian women and to assess their potential for clinical risk prediction. From 2018 to 2020, 538 participants were recruited from Nigerian tertiary hospitals. Cervical tissue samples were analyzed for DNAm using the Infinium MethylationEPIC BeadChip array, and HPV genotyping was conducted via next-generation sequencing. An epigenome-wide association study revealed 24 significant DNAm biomarkers associated with CIN and CC. These biomarkers showed hypermethylation in tumor suppressor genes (e.g., PRMD8), hypomethylation in oncogenes (e.g., MIR520H), and aberrant methylation in genes related to HIV/HPV infection and oncogenesis (e.g., GNB5, LMO4, FOXK2, NMT1). A machine learning-based DNAm classifier achieved 92.9% sensitivity and 88.6% specificity in predicting CC risk, with higher risk observed in adjacent normal cervical samples from CIN/CC patients and HIV/HPV co-infected women. DNAm biomarkers offer a promising approach to enhancing CC screening and early detection, particularly for HIV-positive women in LMICs. The DNAm-based model developed in this study shows potential for more accurate CC risk stratification, highlighting the need for further optimization, validation, and implementation in low-resource settings.
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Affiliation(s)
- Yinan Zheng
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Robert J. Havey MD Institute for Global Health, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Jingzhe Han
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Yishu Qu
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Jun Wang
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Robert J. Havey MD Institute for Global Health, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Brian T Joyce
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Robert J. Havey MD Institute for Global Health, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Kyeezu Kim
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Sungkyunkwan University School of Medicine, Suwon, South Korea
| | - Drew R Nannini
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Jonah Musa
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Robert J. Havey MD Institute for Global Health, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Department of Obstetrics and Gynecology, College of Health Sciences, University of Jos, Jos, Nigeria
| | - Godwin E Imade
- Department of Obstetrics and Gynecology, College of Health Sciences, University of Jos, Jos, Nigeria
- Genomics and Postgraduate Core Facility, College of Health Sciences, University of Jos, Jos, Nigeria
| | - Rose Anorlu
- Department of Obstetrics and Gynecology, College of Medicine, University of Lagos, Lagos, Nigeria
| | - Mamoudou Maiga
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Robert J. Havey MD Institute for Global Health, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Imran Morhason-Bello
- Department of Obstetrics and Gynecology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Melissa A Simon
- Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Olugbenga Silas
- Department of Anatomic and Forensic Pathology, College of Health Sciences, University of Jos, Jos, Nigeria
| | - Fatimah B Abdulkareem
- Department of Anatomic and Molecular Pathology, College of Medicine, University of Lagos, Lagos, Nigeria
| | - Kabir Badmos
- Department of Anatomic and Molecular Pathology, College of Medicine, University of Lagos, Lagos, Nigeria
| | - Chuwang J Nyam
- Genomics and Postgraduate Core Facility, College of Health Sciences, University of Jos, Jos, Nigeria
| | - Demirkan B Gursel
- Robert J. Havey MD Institute for Global Health, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Jian-Jun Wei
- Robert J. Havey MD Institute for Global Health, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Jorge Novo
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Akanmu A Sulaimon
- Department of Hematology and Blood Transfusion, College of Medicine, University of Lagos, Lagos, Nigeria
| | - Laith S Kayat
- Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Masha Kocherginsky
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Robert J. Havey MD Institute for Global Health, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Kwang-Youn A Kim
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Robert J. Havey MD Institute for Global Health, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Kirsten Burdett
- Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Neelima Katam
- Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Chad J Achenbach
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Robert J. Havey MD Institute for Global Health, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Atiene S Sagay
- Department of Obstetrics and Gynecology, College of Health Sciences, University of Jos, Jos, Nigeria
| | - Folasade T Ogunsola
- Department of Medical Microbiology, College of Medicine, University of Lagos, Lagos, Nigeria
| | - Robert L Murphy
- Robert J. Havey MD Institute for Global Health, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Lifang Hou
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Robert J. Havey MD Institute for Global Health, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
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13
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Feng HH, Zhang WH, Liu K, Chen XL, Zhao LY, Chen XZ, Yang K, Hu JK. Prognostic Value of a Serological-Based Clinical Model for Gastric Cancer Patients. J Clin Med 2025; 14:4043. [PMID: 40565788 DOI: 10.3390/jcm14124043] [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: 04/25/2025] [Revised: 06/03/2025] [Accepted: 06/05/2025] [Indexed: 06/28/2025] Open
Abstract
Background: Surgery remains the cornerstone of diagnosis and treatment for gastric cancer. This study aims to develop and validate a serology-based clinical scoring system to predict and evaluate the prognosis of gastric cancer patients. Methods: Clinicopathological data of primary gastric cancer patients who underwent surgical treatment from 2009 to 2018 were collected and divided into training and validation cohorts. Preoperative serological indicators were screened, and a serum risk score (SerScore) was developed using LASSO-Cox analysis. Prognosis prediction models incorporating the SerScore were established and validated. Results: A total of 5493 patients were screened, and 43 serological indicators were assessed. Twelve serological indicators were selected to construct the SerScore. Patients with a SerScore below the cut-off value of -1.73 had significantly better survival rates compared to those with higher scores. Multivariate Cox analysis identified SerScore, age, tumor location, T stage, and N stage as independent prognostic factors for overall survival in the training cohort. A multivariate nomogram was developed, achieving a C-index of 0.745 in the training cohort and 0.750 in the validation cohort. The nomogram demonstrated superior predictive accuracy compared to the SerScore alone, with AUC values of 0.783 versus 0.639 in the training cohort and 0.805 versus 0.657 in the validation cohort. Calibration curves closely aligned with ideal predictions in both cohorts. Conclusions: The SerScore model provides an effective tool for prognostic assessment in primary gastric cancer patients. This model not only enhances prognostic evaluation but also establishes a foundation for developing advanced prediction tools for gastric cancer.
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Affiliation(s)
- Hai-Huan Feng
- Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China
- Gastric Cancer Center, Laboratory of Gastric Cancer, Department of General Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
- Medical Insurance Office, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Wei-Han Zhang
- Gastric Cancer Center, Laboratory of Gastric Cancer, Department of General Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Kai Liu
- Gastric Cancer Center, Laboratory of Gastric Cancer, Department of General Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Xiao-Long Chen
- Gastric Cancer Center, Laboratory of Gastric Cancer, Department of General Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Lin-Yong Zhao
- Gastric Cancer Center, Laboratory of Gastric Cancer, Department of General Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Xin-Zu Chen
- Gastric Cancer Center, Laboratory of Gastric Cancer, Department of General Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Kun Yang
- Gastric Cancer Center, Laboratory of Gastric Cancer, Department of General Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Jian-Kun Hu
- Gastric Cancer Center, Laboratory of Gastric Cancer, Department of General Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
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14
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Chen Y, Zou S, Xu L, Chen J, Wang L, Shen Y, Xu Y, Wei Y, Xu X. NSMCE2 promotes the occurrence and development of HCC by regulating the SUMOylation of PPARα. Int Immunopharmacol 2025; 157:114762. [PMID: 40318278 DOI: 10.1016/j.intimp.2025.114762] [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: 02/15/2025] [Revised: 04/17/2025] [Accepted: 04/27/2025] [Indexed: 05/07/2025]
Abstract
BACKGROUND Primary liver cancer is a malignant tumor of the digestive system and ranks as the sixth most commonly diagnosed cancer globally. It has also risen to become the third leading cause of cancer-related deaths globally, following lung and colorectal cancers. Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancer, approximately 75 to 85 %. Several studies suggest that NSMCE2 contributes to cancer through its SUMO E3 ligase activity, yet its specific role in HCC remains poorly understood. METHODS We gathered data from various databases and obtained 10 pairs of tissue samples from HCC patients to detect the NSMCE2 expression levels. Additionally, we conducted both in vivo and in vitro experiments to confirm the impact of NSMCE2 on the development and progression of HCC. We further analyzed the potential mechanism of NSMCE2 regulation on HCC by bioinformatics, and detected the specific mechanism of NSMCE2 regulating PPARα by co-immunoprecipitation. RESULTS Our study shows that NSMCE2 is an important tumor promoter in HCC and acts through the PPARα-CYP7A1 axis. Specifically, NSMCE2 affects the occurrence and progression of HCC by SUMOylating PPARα, reducing its ubiquitination degradation, and activating the PPARα-CYP7A1 axis. CONCLUSIONS Our study uncovered the role of NSMCE2 in the development and progression of HCC, providing new insights into the pathogenesis and potential therapeutic strategies of HCC.
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Affiliation(s)
- Yukai Chen
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China
| | - Shishi Zou
- Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China
| | - Le Xu
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China
| | - Jiayu Chen
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China
| | - Ling Wang
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China
| | - Yang Shen
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China
| | - Yangtao Xu
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China
| | - Yuxin Wei
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China
| | - Ximing Xu
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China.
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15
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Wang Z, Zhao X, Du W, Zhang X, Li X, Wang L. Prevention and management strategies of anal squamous cell carcinoma among men who have sex with men living with HIV. Int J STD AIDS 2025; 36:533-541. [PMID: 40221878 DOI: 10.1177/09564624251333035] [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: 04/15/2025]
Abstract
The incidence of anal squamous cell carcinoma (SCCA) has been rapidly increasing in recent years. The burden of the disease is expected to increase in the forthcoming years. Men who have sex with men living with HIV (MSMLWH) have a higher incidence of SCCA than the general population. The progression of SCCA usually develops from high risk human papillomavirus (HR-HPV) infection to high grade squamous intra-epithelial lesions (HSIL). HPV infection is highly prevalent in MSMLWH and is considered the most important risk factor for SCCA in MSMLWH. Although the prevalence worldwide is largely similar, the distribution of high-risk HPV genotypes varies. Education on sexuality and lifestyle, use of condoms, fixed sexual partner, effective antiretroviral therapy (ART), smoking cessation, and preventive male circumcision could reduce HPV infection in MSMLWH. Screening and treatment of HSIL have been widely applied to prevent SCCA, but divergence still exists in many studies. When treating HSIL, patients of different ages and risk factors need more consideration to develop standardized management strategies, especially for MSMLWH. Very few studies have examined the treatment of SCCA with MSMLWH. ART has dramatically changed the treatment of SCCA in MSMLWH. The safety and outcome of treatment are still primary concerns for MSMLWH. More studies in this field are necessary to develop treatment strategies for MSMLWH.
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Affiliation(s)
- Zhi Wang
- Department of Proctology, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, China
| | - Xudong Zhao
- Department of Proctology, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, China
| | - Wenchao Du
- Department of Proctology, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, China
| | - Xiaoliang Zhang
- Department of Proctology, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, China
| | - Xingxing Li
- Department of Proctology, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, China
| | - Linquan Wang
- Department of Proctology, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, China
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16
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Monisha S, Ajithkumar S, Myithili T, Sudharsan K, Keerthana T, Sarikalakshmi B, Soundharya V, Pandi M, Kalimuthu P. Investigation of singlet oxygen quantum yield of protonated water-soluble glycosylated porphyrin photosensitizer for photodynamic therapy. Photochem Photobiol Sci 2025; 24:1003-1016. [PMID: 40425949 DOI: 10.1007/s43630-025-00741-8] [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: 12/17/2024] [Accepted: 05/12/2025] [Indexed: 05/29/2025]
Abstract
In this study, we explored the photophysical properties of three forms of glycosylated porphyrin photosensitizers, mainly focusing on their ability to generate singlet oxygen for photodynamic therapy. Porphyrin derivatives are known for their efficacy in photodynamic therapy due to their ability to generate singlet oxygen, a reactive oxygen species crucial for cellular damage in cancer therapy. The three porphyrin molecules are designated as free-base (GPPOH), protonated (PGPPOH), and metalated (ZnGPPOH) glycosylated porphyrins. The singlet oxygen quantum yield (ΦΔ) values were determined through the UV-visible spectroscopic technique using a singlet oxygen quenchers, 1,3-diphenylisobenzofuran, and anthracene1,3-dimethyl malonate. Our findings reveal that PGPPOH porphyrin photosensitizer exhibits the highest ΦΔ value, followed by ZnGPPOH and GPPOH, indicating a correlation between molecular structure and photodynamic efficiency. Photo-cytotoxicity studies also demonstrate that PGPPOH exhibits greater cell apoptosis in HeLa cells, while showing minimal cytotoxic effects in HEK cells than GPPOH and ZnGPPOH. PGPPOH has two positive charges in its core, which may preferentially localize it to cancer cells with negative mitochondrial membrane potential. This study provides valuable insights for optimizing porphyrin-based photosensitizers in therapeutic applications.
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Affiliation(s)
- Sekar Monisha
- Department of Chemistry, The Gandhigram Rural Institute-Deemetd to be University, Gandhigram, Dindigul, Tamilnadu, 624302, India
| | - Samuthirakani Ajithkumar
- Department of Chemistry, The Gandhigram Rural Institute-Deemetd to be University, Gandhigram, Dindigul, Tamilnadu, 624302, India
| | - Thangavel Myithili
- School of Biotechnology, Madurai Kamaraj University, Madurai, Tamilnadu, India
| | - Kumaresan Sudharsan
- Department of Chemistry, The Gandhigram Rural Institute-Deemetd to be University, Gandhigram, Dindigul, Tamilnadu, 624302, India
| | - Thangaraj Keerthana
- Department of Chemistry, The Gandhigram Rural Institute-Deemetd to be University, Gandhigram, Dindigul, Tamilnadu, 624302, India
| | - Baskaran Sarikalakshmi
- Department of Chemistry, The Gandhigram Rural Institute-Deemetd to be University, Gandhigram, Dindigul, Tamilnadu, 624302, India
| | - Venkatesh Soundharya
- Department of Chemistry, The Gandhigram Rural Institute-Deemetd to be University, Gandhigram, Dindigul, Tamilnadu, 624302, India
| | - Mohan Pandi
- School of Biotechnology, Madurai Kamaraj University, Madurai, Tamilnadu, India
| | - Palanisamy Kalimuthu
- Department of Chemistry, The Gandhigram Rural Institute-Deemetd to be University, Gandhigram, Dindigul, Tamilnadu, 624302, India.
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Noorani R, Botting-Provost S, Barsoum GK, Laurie C, El-Zein M, Franco EL. Comprehensive appraisal of the association between sexually transmitted infections and prostate cancer: A scoping review of empirical studies, reviews, and meta-analyses. Cancer Epidemiol 2025; 96:102781. [PMID: 40031094 DOI: 10.1016/j.canep.2025.102781] [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: 08/28/2024] [Revised: 02/09/2025] [Accepted: 02/23/2025] [Indexed: 03/05/2025]
Abstract
We performed a scoping review on the association of sexually transmitted infections (STIs) with prostate cancer and identified knowledge gaps. Searching four databases (Medline, Embase, Scopus, and Cochrane) identified 286 eligible records. Most empirical studies (n = 191) were cross-sectional (n = 66) and case-control (n = 52). The most studied STIs were human papillomavirus (HPV) (n = 82), human immunodeficiency virus (HIV) (n = 52), and herpes simplex virus (HSV) (n = 30). We included 68 narrative reviews, 10 systematic reviews, and 17 meta-analyses. Most effect estimates (odds ratios, hazard ratios, risk ratios and standardised incidence ratios) did not support an association between STIs and prostate cancer: 373 and 218 of 591 effect estimates were above and below the null, respectively, except for HIV where 74 of 108 estimates were below the null. Knowledge gaps included case-control studies, insights into HIV-related mechanisms for a lower risk for prostate cancer, studies on Mycoplasma and Ureaplasma, studies adjusting for co-infection with other STIs, and studies assessing whether STIs predispose men to a more aggressive form of prostate cancer. A key research priority identified is the need for more evidence on the biological mechanisms driving infection-mediated prostate carcinogenesis.
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Affiliation(s)
- Rodrigo Noorani
- Division of Cancer Epidemiology, McGill University, Montréal, QC, Canada.
| | | | - George Kas Barsoum
- Division of Cancer Epidemiology, McGill University, Montréal, QC, Canada
| | - Cassandra Laurie
- Division of Cancer Epidemiology, McGill University, Montréal, QC, Canada
| | - Mariam El-Zein
- Division of Cancer Epidemiology, McGill University, Montréal, QC, Canada
| | - Eduardo L Franco
- Division of Cancer Epidemiology, McGill University, Montréal, QC, Canada
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18
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de Oliveira THA, Anderson LA, Craig SG, Coleman HG, Gheit T, McKay-Chopin S, Jamison J, McManus DT, Cardwell CR, Bingham V, Johnston BT, James JA, Kunzmann AT. Infectious agents and progression from Barrett's oesophagus to oesophageal adenocarcinoma: a nested case-control study. Br J Cancer 2025; 132:1050-1055. [PMID: 40200065 PMCID: PMC12119926 DOI: 10.1038/s41416-025-03003-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 03/10/2025] [Accepted: 03/26/2025] [Indexed: 04/10/2025] Open
Abstract
BACKGROUND A causal role of high-risk HPV in oesophageal adenocarcinoma development has been hypothesised, but longitudinal evidence is limited. This study aims to investigate a potential causal role of infectious agents in the malignant progression of Barrett's oesophagus. METHODS Using a retrospective nested case-control study design, index Barrett's biopsies were retrieved for individuals within the Northern Ireland Barrett's oesophagus register who subsequently progressed to oesophageal adenocarcinoma (n = 150) and matched non-progressors (n = 298). Index Barrett's biopsies were assessed for the presence of 142 infectious agents by multiplex polymerase chain reaction using the Luminex platform. RNA in-situ hybridisation assessed persistent transcriptional activity in subsequent tissue samples, for infectious agents detected more frequently in progressors. RESULTS High-risk HPV genotypes (HPV16 and HPV18) were only identified in the index biopsies of progressors but not non-progressors (4% [5/150] versus 0% [0/298], P = 0.004), though no signs of persistence or transcriptional activity were observed in subsequent tissue. Prevalence of infections did not differ between progressors and non-progressors for any other infectious agents, including Helicobacter Pylori and Herpes. CONCLUSION Despite a higher prevalence of high-risk HPV in progressors than non-progressors, no evidence of transcriptionally active high-risk HPV was observed in subsequent samples, indicating presence in Barrett's is likely non-causal.
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Affiliation(s)
- Talita H A de Oliveira
- Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, Antrim, United Kingdom.
| | - Lesley A Anderson
- Aberdeen Centre for Health Data Science, University of Aberdeen, Aberdeen, United Kingdom
| | - Stephanie G Craig
- Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, Antrim, United Kingdom
| | - Helen G Coleman
- Centre for Public Health, Queen's University Belfast, Belfast, Antrim, United Kingdom
| | - Tarik Gheit
- International Agency for Research on Cancer-World Health Organization, Lyon, France
| | | | | | - Damian T McManus
- Institute of Pathology, Queen's University Belfast, Belfast, Antrim, United Kingdom
| | | | - Victoria Bingham
- Precision Medicine Centre, Queen's University Belfast, Belfast, Antrim, United Kingdom
| | - Brian T Johnston
- Belfast Health and Social Care Trust, Belfast, Antrim, United Kingdom
| | - Jacqueline A James
- Northern Ireland Biobank, Queen's University Belfast, Belfast, Antrim, United Kingdom
| | - Andrew T Kunzmann
- Centre for Public Health, Queen's University Belfast, Belfast, Antrim, United Kingdom
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19
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Solak B, Arslan M. Evaluation of HPV and Related Cancer Awareness and Vaccination Attitudes Among Patients with Anogenital Warts: a Survey-Based Study. J Community Health 2025; 50:560-567. [PMID: 39894901 PMCID: PMC12069137 DOI: 10.1007/s10900-025-01444-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/13/2025] [Indexed: 02/04/2025]
Abstract
We aimed to evaluate awareness of HPV and its associated cancers, attitudes toward HPV vaccination, and vaccination rates in individuals with anogenital warts. This cross-sectional study was conducted at Sakarya University Training and Research Hospital using a questionnaire completed by individuals diagnosed with anogenital warts. A total of 105 respondents were included in the study, comprising 80 males (76.2%) and 25 females (23.8%). The mean age of participants was 34.7 ± 11.2 years. HPV awareness was 70.5%, while cervical cancer awareness was 38.1%. Women demonstrated significantly higher levels of HPV and cervical cancer awareness, as well as knowledge of Pap smear testing, compared to men. Women were also significantly more likely than men to express willingness to vaccinate their children against HPV (84.0% vs. 58.8%, p = 0.039). Higher education levels were associated with increased awareness of HPV, HPV vaccination, and willingness to vaccinate children. Physicians were the primary source of HPV-related information across the cohort. HPV vaccine awareness was 73.3%, but the overall vaccination rate was only 10.5%, with women showing significantly higher vaccination rates than men (24% vs. 6.2%, p = 0.021). The most commonly reported barriers to vaccination were cost (60%) and lack of information (45.7%). None of the participants had vaccinated their children. This study highlights that awareness of HPV and its vaccination is associated with gender and education level but does not translate into higher vaccination rates. Efforts should focus on targeting men and individuals with lower educational attainment by strengthening physicians' roles in public education. Incorporating HPV vaccination into national programs and implementing culturally tailored campaigns may effectively improve vaccination rates.
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Affiliation(s)
- Berna Solak
- Department of Dermatology, School of Medicine, Sakarya University, Sakarya, Turkey.
| | - Mustafa Arslan
- Department of Dermatology, School of Medicine, Sakarya University, Sakarya, Turkey
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20
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Lang R, Coburn SB, Gill MJ, Grossman J, Mayor A, Horberg MA, Silverberg MJ, Rabkin CS, Moore RD, Kirk GD, Karris MY, Justice AC, Althoff KN. The Association of Anemia on Non-AIDS-Defining Cancer and Subsequent Survival Among People With HIV After Antiretroviral Initiation. J Acquir Immune Defic Syndr 2025; 99:175-184. [PMID: 39972549 DOI: 10.1097/qai.0000000000003647] [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: 08/02/2024] [Accepted: 12/27/2024] [Indexed: 02/21/2025]
Abstract
BACKGROUND The association of anemia as a predictive and prognostic indicator of non-AIDS-defining cancer (NADC) among people with HIV (PWH) remains unknown. We evaluated the presence of anemia and its severity as a predictor of NADC and 5-year all-cause survival after an NADC diagnosis among PWH who had initiated antiretroviral therapy. SETTING North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). METHODS We included PWH (≥18 years) on ART between January 01, 2007, and December 31, 2016, with no prior cancer diagnosis. Annual median hemoglobin was categorized into mild (11.0-12.9 g/dL men, 11.0-11.9 g/dL women) and moderate/severe (<10.9 g/dL regardless of sex) anemia. Discrete time-to-event models using a complementary log-log link estimated crude and adjusted hazards ratios (aHR) and 95% confidence intervals for NADC by anemia severity. Five-year mortality after NADC diagnosis by anemia was evaluated. RESULTS Among 67,228 PWH contributing 301,421 annual median hemoglobin observations, 244,658 (81%) were not anemic, 40,134 (13%) had mild, and 16,629 (6%) had moderate/severe anemia. The risk of NADC was higher among PWH with anemia (aHR 2.40 [2.19 to 2.63]) (vs. no anemia) and greater among men (aHR 2.42 [2.20 to 2.66]) than women (aHR 2.02 [1.42 to 2.89]). NADC risk increased with worsening anemia (mild: aHR 2.01 [1.81 to 2.23], moderate/severe: aHR 3.59 [3.13 to 4.11]). The 5-year all-cause mortality after NADC diagnosis was higher (aHR 1.37 [1.21 to 1.55]) among PWH with anemia. CONCLUSIONS Among PWH who initiated ART, anemia may serve as a predictive indicator of NADC risk. Identification of anemia should warrant investigations into the underlying etiology, including evaluation for NADC. Anemia is also a prognostic indicator among PWH diagnosed with NADC.
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Affiliation(s)
- Raynell Lang
- Department of Medicine, University of Calgary School of Medicine, Calgary, Alberta, Canada
| | - Sally B Coburn
- Department of Epidemiology, Johns Hopkins University, Baltimore, MD
| | - M John Gill
- Department of Medicine, University of Calgary School of Medicine, Calgary, Alberta, Canada
| | - Jennifer Grossman
- Department of Medicine, University of Calgary School of Medicine, Calgary, Alberta, Canada
| | - Angel Mayor
- Department of Medicine, Universidad Central Del Caribe, Bayamon Puerto Rico
| | | | | | - Charles S Rabkin
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD
| | - Richard D Moore
- Department of Medicine, Johns Hopkins University, Baltimore, MD
| | - Greg D Kirk
- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | | | - Amy C Justice
- Yale University Schools of Medicine and Public Health, New Haven, CT; and
- Veterans Affairs Connecticut Healthcare System, West Haven, CT
| | - Keri N Althoff
- Department of Epidemiology, Johns Hopkins University, Baltimore, MD
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21
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Feng Z, Burgermeister E, Philips A, Zuo T, Wen W. The gut virome in association with the bacteriome in gastrointestinal diseases and beyond: roles, mechanisms, and clinical applications. PRECISION CLINICAL MEDICINE 2025; 8:pbaf010. [PMID: 40520768 PMCID: PMC12163992 DOI: 10.1093/pcmedi/pbaf010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2025] [Revised: 05/11/2025] [Accepted: 05/25/2025] [Indexed: 06/18/2025] Open
Abstract
The gut virome, an essential component of the intestinal microbiome, constitutes ∼0.1% of the total microbial biomass but contains a far greater number of particles than bacteria, with phages making up 90%-95% of this virome. This review systematically examines the developmental patterns of the gut virome, focusing on factors influencing its composition, including diet, environment, host genetics, and immunity. Additionally, it explores the gut virome's associations with various diseases, its interactions with gut bacteria and the immune system, and its emerging clinical applications.
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Affiliation(s)
- Zhiyang Feng
- Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou 510655, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
| | - Elke Burgermeister
- Department of Medicine II, Medical Faculty Mannheim, University of Heidelberg, Mannheim 69120, Germany
| | - Anna Philips
- Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan 61704, Poland
| | - Tao Zuo
- Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou 510655, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
| | - Weijie Wen
- Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou 510655, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
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22
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Brumbaugh B, Sugden B. A Critical Role for Epstein-Barr Virus in Primary Effusion Lymphoma. Curr Top Microbiol Immunol 2025. [PMID: 40423780 DOI: 10.1007/82_2025_310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/28/2025]
Abstract
Some human cancers are caused by coinfections with two viruses. Here we focus on primary effusion lymphomas (PEL), which arise from coinfection of B cells with Kaposi's Sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) and often are accompanied by systemic infections with human immunodeficiency virus (HIV). Both KSHV and EBV contribute to this oncogenesis of a rare B cell subset and HIV, by limiting the host immune response to coinfected cells, can too. Some of the mechanisms underlying the lymphomagenesis mediated by two tumor viruses are clear; some remain to be elucidated.
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Affiliation(s)
- Beniah Brumbaugh
- McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI, USA
| | - Bill Sugden
- McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI, USA.
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23
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Li M, Cai W, Chandrasekhar A, Hu H, Chow EPF, Wu D. Factors associated with primary care providers' recommendation of HPV vaccination for adolescent males in China: A mixed-methods study. Vaccine 2025; 59:127299. [PMID: 40413900 DOI: 10.1016/j.vaccine.2025.127299] [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: 03/06/2025] [Revised: 05/19/2025] [Accepted: 05/19/2025] [Indexed: 05/27/2025]
Abstract
BACKGROUND The Chinese government has not yet included male population for HPV vaccination but there are increasingly more discussions about including them. Primary care providers' (PCPs) recommendation is an important driver for increasing vaccine uptake but understanding of PCPs' recommendation of HPV vaccine for adolescent males in China is limited. This study examined multidimensional factors associated with PCPs' recommendation of HPV vaccine for male adolescents, aiming to inform future HPV vaccination programs targeting adolescent males in China. METHODS A sequential explanatory mixed-methods was used. In the quantitative phase, we conducted an online survey with PCPs in Eastern China. Multivariable logistic regression analysis identified individual, interpersonal, community, organizational, and policy factors associated with their recommendation of HPV vaccines for adolescent males. Specialty, job title, and income were adjusted as potential confounding factors. The qualitative phase involved thematic analysis to explore these findings further. RESULTS Among the 605 PCPs recruited, only 16.4 % recommended HPV vaccines to adolescent males in the past 12 months. Multivariable logistic regression analysis showed that institutional support for HPV vaccination policies for adolescent males (AOR = 3.05, 95 % CI: 1.65-5.64), frequent institutional vaccine promotion activities (AOR = 1.82, 95 % CI: 1.12-2.96), and institutional incentives for vaccine promotion (AOR = 2.12, 95 % CI: 1.18-3.83) were associated with their recommendation behaviors. Additionally, those who perceived a community norm that HPV vaccines are only for females were less likely to recommend HPV vaccines to adolescent males (AOR = 0.54, 95 % CI: 0.33-0.87). Qualitative research further explained these findings, highlighting the role of organizational factors in PCPs' recommendation of HPV vaccination for adolescent males. CONCLUSIONS A low proportion of PCPs recently recommended HPV vaccines to adolescent males. Organizational-level factors were found to be significantly associated with their recommendation behaviors, and these may help inform future vaccination programs targeting adolescent males.
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Affiliation(s)
- Meiling Li
- Department of Social Medicine and Health Education, School of Public Health & National Vaccine Innovation Platform, Nanjing Medical University, Nanjing 211166, China
| | - Weiping Cai
- MiShi Alley Community Health Service Center, Gongshu District, Hangzhou 310005, China
| | - Anjali Chandrasekhar
- University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514, USA
| | - Hongyan Hu
- Gulou Clinical Medical College, Nanjing Medical University, Nanjing 210000, China
| | - Eric P F Chow
- Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC 3053, Australia; School of Translational Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, VIC 3004, Australia
| | - Dan Wu
- Department of Social Medicine and Health Education, School of Public Health & National Vaccine Innovation Platform, Nanjing Medical University, Nanjing 211166, China.
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24
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Cheng J, Hu X, Dai Z, Zeng Y, Jin J, Mu W, Wei Q, Jia X, Liu J, Xie M, Luo Q, Hu G, Wang G, Zhu X, Zhou J, Xiao M, Wang J, Tan T, Huang L. Targeting intracellular LMP2 with costimulatory signal-armed antibody-like TCR T cells. JCI Insight 2025; 10:e178572. [PMID: 40401520 DOI: 10.1172/jci.insight.178572] [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: 12/20/2023] [Accepted: 04/04/2025] [Indexed: 05/23/2025] Open
Abstract
Expanding the repertoire of CAR therapies to include intracellular antigens holds promise for treating a broad spectrum of malignancies. TCR-like T cells, capable of recognizing intracellular antigen-derived peptides in complex with HLA molecules (pHLA), represent a promising strategy in the field of engineered cellular therapy. This study introduced antibody-like TCR (abTCR) T cells that specifically targeted HLA-A*02:01-restricted LMP2426 peptides, a typical Epstein-Barr virus (EBV) latency II protein, for the treatment of EBV-associated lymphoproliferative diseases (EBV-LPDs). Compared with classic CAR T cells targeting the same epitope, abTCR T cells demonstrated superior efficiency, including increased CD107A expression, enhanced cytotoxicity, and elevated IFN-γ secretion, even when engaging with target cells that naturally present antigens. Moreover, a costimulatory signal-armed abTCR (Co-abTCR), which integrated a costimulatory structure with the abTCR, further enhanced the proliferation and in vivo tumoricidal efficacy of transfected T cells. Collectively, our study developed a potentially novel TCR-like T cell therapy that targets HLA-A*02/LMP2426 for the treatment of EBV-LPDs, providing a potential therapeutic solution for targeting of intracellular antigens in cancer immunotherapy.
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Affiliation(s)
- Jiali Cheng
- Department of Hematology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China
| | - Xuelian Hu
- Department of Hematology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China
- Department of Hematology, The First Affiliated Hospital of Zhejiang University, Zhejiang University, Hangzhou, China
| | - Zhenyu Dai
- Department of Hematology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China
| | - Yuhao Zeng
- Department of Internal Medicine, Cleveland Clinic, Akron General, Cleveland, Ohio, USA
- Division of General Internal Medicine, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Jin Jin
- Department of Hematology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China
| | - Wei Mu
- Department of Hematology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China
| | - Qiaoe Wei
- IASO Biotherapeutics, Nanjing, China
| | | | | | - Meng Xie
- IASO Biotherapeutics, Nanjing, China
| | - Qian Luo
- IASO Biotherapeutics, Nanjing, China
| | - Guang Hu
- IASO Biotherapeutics, Nanjing, China
| | - Gaoxiang Wang
- Department of Hematology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China
| | - Xiaojian Zhu
- Department of Hematology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China
| | - Jianfeng Zhou
- Department of Hematology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China
| | - Min Xiao
- Department of Hematology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China
| | - Jue Wang
- Department of Hematology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China
| | | | - Liang Huang
- Department of Hematology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
- Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
- Tianjin Institutes of Health Science, Tianjin, China
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25
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Plewa P, Kiełbowski K, Mentel O, Figiel K, Bakinowska E, Becht R, Banach B, Pawlik A. Bacteria and Carcinogenesis and the Management of Cancer: A Narrative Review. Pathogens 2025; 14:509. [PMID: 40430828 PMCID: PMC12114594 DOI: 10.3390/pathogens14050509] [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: 04/17/2025] [Revised: 05/17/2025] [Accepted: 05/19/2025] [Indexed: 05/29/2025] Open
Abstract
There is a widely known relationship between certain microbes and cancer progression. For instance, Helicobacter pylori is associated with the occurrence of gastric cancer, while HPV is associated with cervical and head and neck cancers. Recent studies have uncovered novel and important associations between bacterial presence and tumor formation and treatment response. Apart from the influence of the intestinal microbiome on cancer, the local activity of bacteria affects disease properties as well. Bacteria can localize within tumors in less vascularized niches. Their presence mediates the activity of signaling pathways, which contribute to tumorigenesis. Furthermore, they affect the composition of the tumor microenvironment, a highly complex structure composed of immunoregulatory cells and secreted inflammatory mediators. Recently, researchers have analyzed the properties of bacteria to develop novel anticancer strategies. The aim of this review is to discuss the latest findings regarding the relationships between bacteria and cancer and the properties of bacteria that could be used to kill cancer cells.
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Affiliation(s)
- Paulina Plewa
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (P.P.)
| | - Kajetan Kiełbowski
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (P.P.)
- Department of Clinical Oncology, Chemotherapy and Cancer Immunotherapy, Pomeranian Medical University, 71-252 Szczecin, Poland
| | - Oliwia Mentel
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (P.P.)
| | - Karolina Figiel
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (P.P.)
| | - Estera Bakinowska
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (P.P.)
| | - Rafał Becht
- Department of Clinical Oncology, Chemotherapy and Cancer Immunotherapy, Pomeranian Medical University, 71-252 Szczecin, Poland
| | - Bolesław Banach
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (P.P.)
| | - Andrzej Pawlik
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (P.P.)
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Sun F, Colevas AD. Update: Immunotherapeutic Strategies in HPV-Associated Head and Neck Squamous Cell Carcinoma. Viruses 2025; 17:712. [PMID: 40431723 PMCID: PMC12115775 DOI: 10.3390/v17050712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2025] [Revised: 05/14/2025] [Accepted: 05/15/2025] [Indexed: 05/29/2025] Open
Abstract
The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has increased substantially over the past three decades, and since 2017, it has been recognized in the AJCC staging system as distinct from its HPV-negative counterpart. The underlying mechanisms of HPV-associated carcinogenesis, tumor microenvironment, and host immune response represent opportunities for therapeutic development. While anti-PD-1 immunotherapy is now part of standard treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) in general, there are no established immunotherapeutic strategies specifically for HPV-related HNSCC. In this context, multiple emerging approaches are being actively studied-among these are therapeutic vaccines with or without anti-PD-(L)1 adjuvants, peptide-HLA-based immunotherapeutic platforms, and adoptive cell therapies including tumor-infiltrating lymphocytes (TILs), T-cell receptor (TCR) therapy, and chimeric antigen receptor (CAR) T-cell therapy. Beyond further maturation of these novel immunotherapeutic strategies, additional work is needed to delineate the optimal disease state of application (localized versus recurrent/metastatic), as well as in the development of small molecule inhibitors targeting HPV-specific mechanisms of viral oncogenesis.
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Affiliation(s)
| | - A. Dimitrios Colevas
- Division of Oncology, Department of Medicine, Stanford University, Stanford, CA 94305, USA;
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27
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Munday JS, French AF, Broughton L, Lin X, Bond SD, Kraberger S, Knox MA. First Detection and Genetic Characterization of Felis catus Papillomavirus Type 11, the First Treisetapapillomavirus Type to Infect Domestic Cats. Animals (Basel) 2025; 15:1416. [PMID: 40427293 PMCID: PMC12108386 DOI: 10.3390/ani15101416] [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: 04/11/2025] [Revised: 04/30/2025] [Accepted: 05/13/2025] [Indexed: 05/29/2025] Open
Abstract
Domestic cats are currently recognized to be infected by 10 different Felis catus papillomavirus (FcaPV) types that are classified into three genera. Examination of a skin sample from a cat with presumptive allergic dermatitis revealed clusters of large amphophilic intracytoplasmic bodies within epidermal cells. A 312 bp section of DNA from a novel PV type was amplified from the sample, while the entire 7569 bp genome was amplified and sequenced from a skin swab. The novel PV, which was designated FcaPV11, was predicted to contain coding regions for five early proteins and two late ones. Phylogenetic analysis of the L1 gene sequence showed FcaPV11 clusters with members of the Treisetapapillomavirus genus and shares less than 64% similarity with any of the previously fully sequenced FcaPV types. FcaPV11 DNA was not detected in a series of neoplastic and non-neoplastic skin samples from an additional 30 cats. These results show, for the first time, that cats can be infected by members of the Treisetapapillomavirus genus and suggest PVs in this genus may have co-evolved with a common Carnivora ancestor. While FcaPV11 was considered unlikely to have caused skin lesions in this cat, the prominent PV-induced cell changes indicate the PV can influence cell regulation. This suggests FcaPV11 may have the potential to cause skin disease in cats.
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Affiliation(s)
- John S. Munday
- Pathobiology, School of Veterinary Science, Massey University, Palmerston North 4410, New Zealand;
| | | | | | - Xiaoxiao Lin
- Massey Genome Service, Massey University, Palmerston North 4410, New Zealand;
| | - Sarah D. Bond
- Pathobiology, School of Veterinary Science, Massey University, Palmerston North 4410, New Zealand;
| | - Simona Kraberger
- The Biodesign Center for Fundamental and Applied Microbiomics, Arizona State University, Tempe, AZ 85287, USA;
| | - Matthew A. Knox
- Molecular Epidemiology Laboratory, School of Veterinary Science, Massey University, Palmerston North 4410, New Zealand;
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Yao S, Chen S, Wang A, Liang Z, Liu X, Gao Y, Cai H. BAG2 Inhibits Cervical Cancer Progression by Modulating Type I Interferon Signaling through Stabilizing STING. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025:e70005. [PMID: 40364789 DOI: 10.1002/advs.202414637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 04/30/2025] [Indexed: 05/15/2025]
Abstract
Cervical cancer possesses high morbidity and mortality rates, and a comprehensive understanding of its molecular underpinnings is essential for advancing clinical management strategies. The innate immune sensor STING, which activates type I interferon signaling, plays a pivotal role in enhancing anti-tumor activity. Despite increased attention to STING's involvement in cervical cancer, the regulatory mechanisms governing its protein homeostasis remain poorly understood. In this study, it is found that the BAG2-STUB1 complex regulates ubiquitin proteasomal degradation of STING, which affects the development of cervical cancer. Mechanistically, BAG2 inhibits ubiquitination of STING and stabilizes it by interacting with STING. Specifically, BAG2 inhibits STUB1 from attaching the K48-linked ubiquitin chains at K338 and K370 of STING by forming a complex with STUB1. Functionally, enhanced BAG2 expression suppresses cervical cancer progression by activating the type I interferon pathway in a STING-dependent manner. Notably, clinical cervical cancer samples revealed a positive correlation between BAG2 and STING levels, with low BAG2 expression is strongly linked to advanced disease and poor prognosis in cervical cancer. Collectively, these findings elucidate the molecular mechanism by which the BAG2-STUB1 complex regulates STING homeostasis, underscoring BAG2's potential as a diagnostic biomarker and therapeutic target in cervical cancer.
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Affiliation(s)
- Shijie Yao
- Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China
- Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, 430071, China
- Hubei Cancer Clinical Study Center, Wuhan, 430071, China
| | - Siming Chen
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Anjin Wang
- Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China
- Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, 430071, China
- Hubei Cancer Clinical Study Center, Wuhan, 430071, China
| | - Ziyan Liang
- Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China
- Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, 430071, China
- Hubei Cancer Clinical Study Center, Wuhan, 430071, China
| | - Xuelian Liu
- Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China
- Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, 430071, China
- Hubei Cancer Clinical Study Center, Wuhan, 430071, China
| | - Yang Gao
- Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China
- Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, 430071, China
- Hubei Cancer Clinical Study Center, Wuhan, 430071, China
| | - Hongbing Cai
- Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China
- Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, 430071, China
- Hubei Cancer Clinical Study Center, Wuhan, 430071, China
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Bryant KN, Frick-Cheng AE, Solecki LE, Kroh HK, McDonald WH, Lacy DB, McClain MS, Ohi MD, Cover TL. Species-specific components of the Helicobacter pylori Cag type IV secretion system. Infect Immun 2025; 93:e0049324. [PMID: 40208031 PMCID: PMC12070742 DOI: 10.1128/iai.00493-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Accepted: 03/08/2025] [Indexed: 04/11/2025] Open
Abstract
Helicobacter pylori strains containing the cag pathogenicity island (PAI) deliver an effector protein (CagA) and non-protein substrates into gastric cells through a process that requires the Cag type IV secretion system (T4SS). The Cag T4SS outer membrane core complex (OMCC) contains multiple copies of five proteins, two of which are species-specific proteins. By using modifications of a previously described OMCC immunopurification method and optimized mass spectrometric methods, we have now isolated additional cag PAI-encoded proteins that are present in lower relative abundance. Four of these proteins (CagW, CagL, CagI, and CagH) do not exhibit sequence relatedness to T4SS components in other bacterial species. Size exclusion chromatography analysis of immunopurified samples revealed that CagW, CagL, CagI, and CagH co-elute with OMCC components. These four Cag proteins are copurified with the OMCC in immunopurifications from a Δcag3 mutant strain (lacking peripheral OMCC components), but not from a ΔcagX mutant strain (defective in OMCC assembly). Negative stain electron microscopy analysis indicated that OMCC preparations isolated from ΔcagW, cagL::kan, ΔcagI, and ΔcagH mutant strains are indistinguishable from wild-type OMCCs. In summary, by using several complementary methods, we have identified multiple species-specific Cag proteins that are associated with the Cag T4SS OMCC and are required for T4SS activity.
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Affiliation(s)
- Kaeli N. Bryant
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | | | - Lauren E. Solecki
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Heather K. Kroh
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - W. Hayes McDonald
- Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
- Department of Biochemistry, Vanderbilt University, Nashville, Tennessee, USA
| | - D. Borden Lacy
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA
- Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Mark S. McClain
- Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Melanie D. Ohi
- Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA
- Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA
| | - Timothy L. Cover
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA
- Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
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Fernandez E, Wargo JA, Helmink BA. The Microbiome and Cancer: A Translational Science Review. JAMA 2025:2833859. [PMID: 40354071 DOI: 10.1001/jama.2025.2191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
Abstract
Importance Growing evidence suggests that microbes located within the gastrointestinal tract and other anatomical locations influence the development and progression of diseases such as cancer. Observations Clinical and preclinical evidence suggests that microbes in the gastrointestinal tract and other anatomical locations, such as the respiratory tract, may affect carcinogenesis, development of metastases, cancer treatment response, and cancer treatment-related adverse effects. Within tumors of patients with cancer, microbes may affect response to treatment, and therapies that reduce or eliminate these microbes may improve outcomes in patients with cancer. Modulating gastrointestinal tract (gut) microbes through fecal microbiota transplant and other strategies such as dietary intervention (eg, high-fiber diet intervention) has improved outcomes in small studies of patients treated with cancer immunotherapy. In contrast, disruption of the gut microbiota by receipt of broad-spectrum antibiotics prior to treatment with cancer immunotherapy has been associated with poorer overall survival and higher rates of adverse effects in patients treated with immune checkpoint blockade for solid tumors and also with chimeric antigen receptor T-cell therapy for hematologic malignancies. Conclusions and Relevance Microbes in the gut and other locations in the body may influence the development and progression of cancer and may affect the response to adverse effects from cancer therapy. Future therapies targeting microbes in the gut and other locations in the body could potentially improve outcomes in patients with cancer.
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Affiliation(s)
- Estefania Fernandez
- Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston
| | - Jennifer A Wargo
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston
| | - Beth A Helmink
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston
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Xiao Q, Liu Y, Li T, Wang C, He S, Zhai L, Yang Z, Zhang X, Wu Y, Liu Y. Viral oncogenesis in cancer: from mechanisms to therapeutics. Signal Transduct Target Ther 2025; 10:151. [PMID: 40350456 PMCID: PMC12066790 DOI: 10.1038/s41392-025-02197-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 01/22/2025] [Accepted: 03/03/2025] [Indexed: 05/14/2025] Open
Abstract
The year 2024 marks the 60th anniversary of the discovery of the Epstein-Barr virus (EBV), the first virus confirmed to cause human cancer. Viral infections significantly contribute to the global cancer burden, with seven known Group 1 oncogenic viruses, including hepatitis B virus (HBV), human papillomavirus (HPV), EBV, Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis C virus (HCV), human T-cell leukemia virus type 1 (HTLV-1), and human immunodeficiency virus (HIV). These oncogenic viruses induce cellular transformation and cancer development by altering various biological processes within host cells, particularly under immunosuppression or co-carcinogenic exposures. These viruses are primarily associated with hepatocellular carcinoma, gastric cancer, cervical cancer, nasopharyngeal carcinoma, Kaposi sarcoma, lymphoma, and adult T-cell leukemia/lymphoma. Understanding the mechanisms of viral oncogenesis is crucial for identifying and characterizing the early biological processes of virus-related cancers, providing new targets and strategies for treatment or prevention. This review first outlines the global epidemiology of virus-related tumors, milestone events in research, and the process by which oncogenic viruses infect target cells. It then focuses on the molecular mechanisms by which these viruses induce tumors directly or indirectly, including the regulation of oncogenes or tumor suppressor genes, induction of genomic instability, disruption of regular life cycle of cells, immune suppression, chronic inflammation, and inducing angiogenesis. Finally, current therapeutic strategies for virus-related tumors and recent advances in preclinical and clinical research are discussed.
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Affiliation(s)
- Qing Xiao
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Department of Hematology-Oncology, Chongqing University Cancer Hospital, Chongqing, China
| | - Yi Liu
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Department of Hematology-Oncology, Chongqing University Cancer Hospital, Chongqing, China
| | - Tingting Li
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Department of Hematology-Oncology, Chongqing University Cancer Hospital, Chongqing, China
| | - Chaoyu Wang
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Department of Hematology-Oncology, Chongqing University Cancer Hospital, Chongqing, China
| | - Sanxiu He
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Department of Hematology-Oncology, Chongqing University Cancer Hospital, Chongqing, China
| | - Liuyue Zhai
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Department of Hematology-Oncology, Chongqing University Cancer Hospital, Chongqing, China
| | - Zailin Yang
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Department of Hematology-Oncology, Chongqing University Cancer Hospital, Chongqing, China
| | - Xiaomei Zhang
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Department of Hematology-Oncology, Chongqing University Cancer Hospital, Chongqing, China.
| | - Yongzhong Wu
- Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing, China.
| | - Yao Liu
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Department of Hematology-Oncology, Chongqing University Cancer Hospital, Chongqing, China.
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Passerini S, Messina S, Moens U, Pietropaolo V. Merkel Cell Polyomavirus (MCPyV) and Its Possible Role in Head and Neck Cancers. Biomedicines 2025; 13:1180. [PMID: 40427007 PMCID: PMC12109148 DOI: 10.3390/biomedicines13051180] [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: 03/31/2025] [Revised: 05/08/2025] [Accepted: 05/12/2025] [Indexed: 05/29/2025] Open
Abstract
Despite significant progress in its prevention, diagnosis, and treatment, head and neck cancer (HNC) remains a major global health issue due to its multifactorial pathogenesis. Indeed, HNCs have been found to be associated with different environmental and lifestyle factors, as well as with infection with oncogenic viruses. To date, seven viruses are recognized for their tumorigenic properties and have been proposed as implicated in HNC development, including Merkel Cell Polyomavirus (MCPyV). MCPyV is well recognized as the major etiological agent of Merkel cell carcinoma (MCC), a rare but rapidly metastasizing skin neoplasm. Specifically, in almost 80% of MCC cases, viral genome integration occurs, and a truncated form of Large T Antigen (tLT) is expressed. Although MCC is a rare cancer, MCPyV is a ubiquitous virus, widely distributed among the human population. Therefore, a plausible role of the virus has been proposed, even for other tumors. The current review provides an overview of the available data describing the presence of MCPyV in non-MCC tumors, such as HNCs, with the aim of elucidating the potential contribution of MCPyV to oral cancer. Understanding the role of viral infections in the etiology of cancer opens up the opportunity for developing preventive measures and targeted therapies that effectively address HNC progression while reducing treatment-related side effects.
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Affiliation(s)
- Sara Passerini
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00185 Rome, Italy;
| | - Sara Messina
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00185 Rome, Italy;
| | - Ugo Moens
- Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, UiT-The Arctic University of Norway, 9037 Tromsø, Norway;
| | - Valeria Pietropaolo
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00185 Rome, Italy;
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Wan X, Jiang H, Peng K. Comparison of Efficacy on First-Line Helicobacter Pylori Eradication Between Potassium-Competitive Acid Blocker (P-CAB)-Based Therapies Versus Proton-Pump Inhibitor (PPI)-Based Therapies: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. J Clin Gastroenterol 2025:00004836-990000000-00445. [PMID: 40339055 DOI: 10.1097/mcg.0000000000002190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2025] [Accepted: 03/24/2025] [Indexed: 05/10/2025]
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is a gram-negative bacterium that infects over half of the world population, accountable for 89% of all gastric cancer cases. The efficacy of the proton-pump inhibitor (PPI) based-triple therapy is declining, while the novel potassium-competitive acid blocker (P-CAB) based therapy gets new attention. However, it remains unclear regarding the optimal duration and number of comedication(s) for P-CAB-based regimens, which P-CAB is the best-in-class, and whether P-CABs perform better than all PPIs. OBJECTIVE To compare the efficacy on first-line H. pylori eradication between P-CAB-based therapies versus PPI-based therapies. METHODS A systematic review on randomized controlled trials, with network meta-analysis conducted under the Frequentist approach. The P-score method was used to rank the probability of being the best intervention. RESULTS For the first-line treatment eradicating H. pylori infection, the 7-day vonoprazan-based triple therapy (VAC7) has the highest P-score for the probability of being the best intervention (0.96). VAC7 has a significantly higher eradication rate of H. pylori than most PPI-based therapies, including esomeprazole-based, lansoprazole-based, pantoprazole-based, and omeprazole-based regimens, as well as the other P-CAB based regimens, such as tegroprazan-based triple regimen (OR: 2.41, 95% CI: 1.13-5.15). CONCLUSION Vonoprazan-based triple therapy has a higher eradication rate than PPI-based triple therapies, as well as other P-CABs based regimens. It remains unclear whether VAC7 is superior over vonoprazan-based dual therapy (VA7). Overall, VAC7 should be recommended for clinical and public health interventions, with VA7 as a possible alternative considering the local antimicrobial resistance profiles.
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Affiliation(s)
- Xiaoyu Wan
- Department of Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong
| | - Heng Jiang
- Department of Medicine, Westchester Medical Center, Valhalla, NY
| | - Kangning Peng
- Department of Medicine, Cambridge Health Alliance, Cambridge
- Department of Medicine, Harvard Medical School, Boston, MA
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Njoh AA, Waheed DEN, Kedakse TSNJ, Ebongue LJ, Kongnyuy EJ, Amani A, Tambasho AC, Saidu Y, Kaba MI, Sangwe CN, Kenfack H, Seungue J, Nebongo D, Nnang NE, Vorsters A, Cleenewerck de Kiev L. Overcoming challenges and achieving high HPV vaccination uptake in Cameroon: lessons learned from a gender-neutral and single-dose program and community engagement. BMC Public Health 2025; 25:1696. [PMID: 40340822 PMCID: PMC12060551 DOI: 10.1186/s12889-025-22776-3] [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: 11/27/2024] [Accepted: 04/11/2025] [Indexed: 05/10/2025] Open
Abstract
INTRODUCTION Human papillomavirus (HPV) is sexually transmissible and affects almost all sexually active people. The virus infects females and males, causing genital warts, cervical cancer, and oropharyngeal cancers in some. The disease burden is highest in resource-constrained countries, and it is a leading cause of cancer-related mortality in Cameroon. HPV infection is preventable by vaccination. Despite the merits of HPV vaccination, improving coverage has remained difficult in Cameroon. This paper highlights the challenges, lessons learned, and progress in HPV vaccination as part of Cameroon's gender-neutral-single-dose approach and the periodic intensification of routine immunization (PIRI). METHODS This ecological cross-sectional study, conducted from July to December 2023, examines the introduction of the HPV vaccine in Cameroon, along with associated challenges, strategies, and progress. Vaccination data from 2020 to 2023 were retrieved from Cameroon's District Health Information Software (DHIS2), while information on the vaccine introduction process and challenges was sourced from Expanded Programme on Immunisation (EPI) reports. Data analysis was performed using Python. The Shapiro-Wilk test assessed normality, and segmented regression analysis within an interrupted time series framework was applied to evaluate the contribution of each intervention to HPV vaccination uptake among girls. Statistical significance was set at a 95% confidence interval (CI) with a p-value < 0.05. Microsoft Excel 365 was used for calculating vaccination coverage proportions and visualizing results through figures and tables. RESULTS Cameroon introduced the HPV vaccine to nine-year-old girls in October 2020 amidst negative rumours. The first dose coverage stayed around 20% for three years. Following the National Immunization Technical Advisory Group recommendation, the Ministry of Health intensified communication and community engagement, switched to a single-dose vaccination for nine-year-old boys and girls in January 2023, and PIRI in households and schools in March 2023. All regions improved, with four (Adamawa, East, Far North, and North) having coverages for girls over 90% and around 40% for boys. National-level vaccination coverage for girls improved three-fold, and boys recorded 26%. Interrupted time series highlighted an immediate improvement in girls' vaccination following PIRI in 70% of regions and nationally. In contrast gender-neutral-single-dose vaccination led to immediate improvement in coverage in 30% of regions (Far North, South, South West) and at the national level, while intensified communication lacked significant contribution. CONCLUSION HPV vaccination in Cameroon has faced significant challenges. However, interventions such as adopting a gender-neutral, single-dose policy and implementing PIRI have greatly improved coverage across various levels of the health system since 2023.
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Affiliation(s)
- Andreas Ateke Njoh
- Expanded Program on Immunization, Ministry of Public Health, Yaoundé, Cameroon
- School of Global Health and Bioethics, Euclid University, Bangui, Central African Republic
| | - Dur-E-Nayab Waheed
- Centre for Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
| | | | | | | | - Adidja Amani
- Faculty of Medicine and Biomedical Sciences, University of Yaoundé 1, Yaoundé, Cameroon
| | | | - Yauba Saidu
- Clinton Health Access Initiative Inc, Yaoundé, Cameroon
| | - Mohamed Ii Kaba
- World Health Organization, Cameroon Country Office, Yaoundé, Cameroon
| | - Clovis Nchinjoh Sangwe
- Division of Public Health, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa
| | - Herman Kenfack
- Expanded Program on Immunization, Ministry of Public Health, Yaoundé, Cameroon
| | - Judith Seungue
- Expanded Program on Immunization, Ministry of Public Health, Yaoundé, Cameroon
| | - Daniel Nebongo
- Expanded Program on Immunization, Ministry of Public Health, Yaoundé, Cameroon
| | | | - Alex Vorsters
- Centre for Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
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Osaki M, Terakura S, Hirano S, Iwasa T, Hatanaka KC, Hatanaka Y, Sunagawa M, Kokuryo T, Adachi Y, Takeuchi Y, Hanajiri R, Sakanaka C, Murata M, Ebata T, Kiyoi H. Development and optimization of Eva1 ( MPZL2) targeting chimeric antigen receptor T cells. J Immunother Cancer 2025; 13:e009825. [PMID: 40341026 DOI: 10.1136/jitc-2024-009825] [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] [Accepted: 04/16/2025] [Indexed: 05/10/2025] Open
Abstract
BACKGROUND Whereas chimeric antigen receptor gene modified T (CAR-T) cell therapy has been clinically applied to malignant lymphomas and multiple myeloma, CAR-T cell therapy for solid tumors has so far not reached clinical application. Epithelial V-like antigen 1 (Eva1), transcribed from myelin protein zero-like 2 (MPZL2), is a small surface protein highly expressed on various tumor cells. We selected Eva1 as a novel solid tumor-target antigen because of its broad expression across various tumor types. The purpose of the present study is to develop and optimize CAR-T cells targeting Eva1. METHOD We prepared various humanized single chain variable fragment sequences based on a mouse anti-human Eva1 monoclonal antibody. We constructed six humanized Eva1CAR-Ts and selected one that maintained specificity and good cellular proliferation after antigen stimulation. We further optimized the length of the extracellular spacer domain and the choice of the intracellular domain in vitro and in two different xenograft mouse models. RESULTS We confirmed Eva1 expression on various tumor cell lines by flow cytometry and analysis of public database, but we also observed that normal monocytes weakly expressed Eva1. A combination of short spacer domain and 4-1BB or CD79A/CD40 intracellular domain provided higher treatment efficacy both in vitro and in vivo. The cytokine release on autologous monocyte stimulation to Eva1CAR-T cells was comparable to that on autologous B cell stimulation to CD19CAR-T cells. Humanized Eva1CAR-T cells demonstrated excellent therapeutic efficacy by infusing a single dose of Eva1CAR-T cells (1×106) in both NCI-H1975 lung cancer and CFPAC-1 pancreatic cancer cell line grafted model. CONCLUSIONS In summary, these data suggest that humanized Eva1CAR-T has promising therapeutic potential for the treatment of various Eva1-positive solid tumors. Regarding on-target/off-tumor recognition, further detailed analyses of the Eva1CAR-T cell responses to normal tissues are needed.
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Affiliation(s)
- Masahide Osaki
- Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Seitaro Terakura
- Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shiho Hirano
- Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | | | - Kanako C Hatanaka
- Center for Development of Advanced Diagnostics, Hokkaido University Hospital, Sapporo, Japan
| | - Yutaka Hatanaka
- Center for Development of Advanced Diagnostics, Hokkaido University Hospital, Sapporo, Japan
| | - Masaki Sunagawa
- Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Toshio Kokuryo
- Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshitaka Adachi
- Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yuki Takeuchi
- Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Ryo Hanajiri
- Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | | | - Makoto Murata
- Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tomoki Ebata
- Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hitoshi Kiyoi
- Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Sun L, Yang Q, Lyu B, Shen Y, He Y, Zhang Y, Han L. Differential Rates of Early Gastric Cancer in the Urban and Rural Medical Centers of Hangzhou, China. Clin Transl Gastroenterol 2025:01720094-990000000-00393. [PMID: 40327383 DOI: 10.14309/ctg.0000000000000851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Accepted: 04/28/2025] [Indexed: 05/07/2025] Open
Abstract
INTRODUCTION The aim of this study was to compare gastric cancer (GC) and early GC (EGC) diagnosis rates between urban and rural and to investigate potential reasons for the increased GC morbidity in rural areas. METHODS Patients who underwent endoscopy at rural and urban medical centers from 2019 to 2024 were included. We analyzed differences in patients' pre-endoscopic chief complaints and endoscopic diagnoses across the 2 areas. RESULTS Thirty-two thousand six hundred thirteen patients from rural medical centers and 70,195 patients from urban centers were included. Significant differences in endoscopic diagnoses were found between the groups, with the EGC diagnosis rate being significantly lower in rural areas than in urban (10.19% vs. 27.19%). Rural patients were more likely to undergo endoscopy for abdominal pain, reflux, abdominal fullness, and melena (relative risk [RR] = 1.340, 1.431, 1.106, and 1.231, respectively). Fewer rural patients underwent endoscopy because of laboratory abnormality, including Helicobacter pylori infection, elevated tumor markers, positive fecal occult blood tests, and anemia (RR = 0.591, 0.295, 0.251, and 0.400, respectively). In addition, rural patients were significantly less likely to undergo endoscopy owing to health screening or surveillance for chronic atrophic gastritis (RR = 0.362 and 0.527, respectively). DISCUSSION The diagnosis rate of EGC is significantly lower in rural than in urban. Rural patients are more likely to seek endoscopy because they are symptomatic and are less likely to undergo endoscopy for health screening, surveillance for chronic atrophic gastritis, or laboratory abnormality. Enhanced health education and awareness programs in rural areas are needed to encourage proactive endoscopic screening and surveillance.
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Affiliation(s)
- Lu Sun
- Department of Gastroenterology, Hangzhou Ninth People's Hospital (Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine Qiantang Campus), Hangzhou, China
| | - Qingfeng Yang
- Department of Gastroenterology, Hangzhou Ninth People's Hospital (Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine Qiantang Campus), Hangzhou, China
| | - Bin Lyu
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
- Key Laboratory of Digestive Pathophysiology of Zhejiang Province, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Yanjie Shen
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Yeqi He
- Department of Pathology, Hangzhou Ninth People's Hospital (Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine Qiantang Campus), Hangzhou, China
| | - Yi Zhang
- Department of Pathology, Hangzhou Ninth People's Hospital (Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine Qiantang Campus), Hangzhou, China
| | - Liang Han
- Department of Gastroenterology, Hangzhou Ninth People's Hospital (Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine Qiantang Campus), Hangzhou, China
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Kazlauskaitė J, Žukienė G, Rudaitis V, Bartkevičienė D. The Vaginal Microbiota, Human Papillomavirus, and Cervical Dysplasia-A Review. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:847. [PMID: 40428805 PMCID: PMC12112763 DOI: 10.3390/medicina61050847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/30/2025] [Revised: 04/24/2025] [Accepted: 05/03/2025] [Indexed: 05/29/2025]
Abstract
Background and Objectives: The relationship between the vaginal microbiota, human papillomavirus infection (HPV), and cervical precancerous lesions is a critical area of research, as it influences both the progression of HPV-related diseases and potential treatment strategies. New evidence suggests that Lactobacillus crispatus dominance in the microbiota may protect against HPV persistence and speed the elimination of HPV. This study aims to explore the relationship between the vaginal microbiota composition and HPV infection, focusing on the impact of these factors on the development of cervical precancerous lesions. Materials and Methods: A comprehensive literature review was conducted using the PubMed database, focusing on studies that analyzed the association between the vaginal microbiota and HPV infection in the context of cervical dysplasia. This study was primarily based on clinical data on HPV integration in women with low-grade squamous intraepithelial lesions (LSILs), high-grade squamous intraepithelial lesions (HSILs), and cervical cancer. Results: Different types of vaginal microbiota communities (CSTs) have different pathogenic or protective potential. Healthy women predominantly exhibited CST I, with Lactobacillus crispatus as the dominant microorganism. CST IV, associated with increased anaerobic bacteria, was most common in HSIL and cervical cancer patients. Statistical analysis revealed that bacterial vaginosis (BV) was significantly associated with HPV persistence, with studies reporting a 1.8-3.4-fold increased risk (p < 0.05) of persistent HR-HPV infection in BV-positive women. Conclusions: Our literature review suggests that the composition of the vaginal microbiota can modulate the local immune response, the expression of viral oncogenes, and the integrity of the epithelial barrier. Furthermore, certain bacterial genes or metabolic pathways can be associated with a favorable or unfavorable outcome of the disease. Analysis of the vaginal microbiota could serve as an additional risk assessment tool, helping to distinguish between regressing and progressive precancerous conditions.
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Affiliation(s)
| | - Guoda Žukienė
- Clinic of Obstetrics and Gynaecology, Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, LT-03101 Vilnius, Lithuania; (V.R.); (D.B.)
| | - Vilius Rudaitis
- Clinic of Obstetrics and Gynaecology, Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, LT-03101 Vilnius, Lithuania; (V.R.); (D.B.)
| | - Daiva Bartkevičienė
- Clinic of Obstetrics and Gynaecology, Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, LT-03101 Vilnius, Lithuania; (V.R.); (D.B.)
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Romanishin A, Efimenko B, Katserov D, Agapov M, Kakotkin V, Rubina K, Zadorkina T, Semina E. Comprehensive cross-sectional study of CIN prevalence, HPV genotyping, genetic alterations, and microbiota as molecular biomarkers for early cervical cancer detection: A pilot clinical study among women in Russia. Int J Gynaecol Obstet 2025. [PMID: 40323698 DOI: 10.1002/ijgo.70090] [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: 12/18/2024] [Revised: 03/01/2025] [Accepted: 03/10/2025] [Indexed: 05/07/2025]
Abstract
OBJECTIVE To explore the relationships between HPV genotypes, vaginal microbiota, oncogenic mutations, and cervical intraepithelial neoplasia (CIN) to develop a risk assessment model for predicting CIN. METHODS A cross-sectional analysis was conducted on 264 women living in the Kaliningrad region, assessing CIN presence, HPV genotypes, vaginal microbiota composition, and mutations in key oncogenes. RESULTS HPV genotypes 16, 31, 33, 35, 58, and 66 were identified as the most prevalent among patients with HPV infections. However, in a multifactorial model, only HPV genotypes 16 and 58 demonstrated a significant association with high-grade squamous intraepithelial lesions and above. Genetic analysis revealed mutations in TP53 and ERBB2 genes in 20 and 17 patients, respectively, with TP53 mutations showing a notable correlation with CIN progression. Two patients with diagnoses of "Negative for Intraepithelial Lesion or Malignancy" carried the TP53 R248W mutation, a well-established neoplasia-related variant, highlighting its potential as a predictor of precancerous conditions. Increased copy numbers of human DNA and Enterobacteriaceae DNA correlated with low-grade squamous intraepithelial lesions, though many DNA-derived features displayed instability in logistic regression models, suggesting the need for further validation. CONCLUSION These findings suggest that although HPV genotypes, genetic mutations, and microbiota profiles may serve as markers for CIN, their predictive reliability requires further investigation. The present study represents the first large-scale exploration of these factors conducted within the Russian female population.
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Affiliation(s)
- Alexander Romanishin
- Institute of Medicine and Life Sciences, Immanuel Kant Baltic Federal University, Kaliningrad, Russia
| | - Bogdan Efimenko
- Institute of Medicine and Life Sciences, Immanuel Kant Baltic Federal University, Kaliningrad, Russia
| | - Dmitriy Katserov
- Institute of Medicine and Life Sciences, Immanuel Kant Baltic Federal University, Kaliningrad, Russia
| | - Mikhail Agapov
- Institute of Medicine and Life Sciences, Immanuel Kant Baltic Federal University, Kaliningrad, Russia
- Moscow State University, Moscow, Russia
| | - Viktor Kakotkin
- Institute of Medicine and Life Sciences, Immanuel Kant Baltic Federal University, Kaliningrad, Russia
| | | | - Tatiana Zadorkina
- Kaliningrad Regional Centre for Specialized Medical Care, Kaliningrad, Russia
| | - Ekaterina Semina
- Institute of Medicine and Life Sciences, Immanuel Kant Baltic Federal University, Kaliningrad, Russia
- Moscow State University, Moscow, Russia
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39
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Yang F, Shaibu Z, Liu Q, Zhu W. Cytokine profiles as predictive biomarkers for treatment outcomes in advanced gastric cancer patients undergoing PD-1 blockade immunochemotherapy: a meta-analysis. Clin Exp Med 2025; 25:136. [PMID: 40317367 PMCID: PMC12049293 DOI: 10.1007/s10238-025-01676-1] [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: 02/03/2025] [Accepted: 04/07/2025] [Indexed: 05/07/2025]
Abstract
Immunotherapy, specifically PD-1 blockade, is a promising treatment for advanced gastric cancer (AGC). However, predicting patient response is challenging. Cytokines, key immune response regulators, could be important biomarkers for forecasting patient outcomes and susceptibility to PD-1 blockade immunochemotherapy in AGC. This meta-analysis aims to evaluate the potential of cytokine profiles as predictive biomarkers for treatment outcomes in patients with AGC undergoing immunochemotherapy. Meta-analysis. Original studies on the evaluation of various serum samples of cytokines in AGC patients after immunochemotherapy were searched in PubMed, Google Scholar, Embase, Cochrane Library, and Web of Science, with a focus on literature published up to October 31, 2023. Data from multiple studies were pooled to analyze the impact of IL-2, IL-4, IL-6, IL-8, IL-10, and IFN-γ expression on treatment outcomes using RevMan 5.4.1. Prospero ID: CRD42024557837. Five studies were included. In AGC patients receiving immunochemotherapy, high levels of IL-4 were correlated with enhanced PFS following therapy. In contrast, there were no significant differences observed in the expression of IL-2, IL-6, IL-10, and IFN-γ for PFS in AGC after treatment. Notably, elevated IL-6 expression was significantly associated with poorer OS in AGC patients undergoing immunochemotherapy. The findings suggest that expression levels of cytokines, particularly IL-4 and IL-6, play a significant role in predicting treatment outcomes in AGC patients undergoing immunochemotherapy. Further research is warranted to validate these results and elucidate the underlying mechanisms driving these associations.
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Affiliation(s)
- Fumeng Yang
- School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China
- Department of Laboratory Medicine, Lianyungang Clinical College, Jiangsu University & The Second People's Hospital of Lianyungang, Lianyungang, 222006, Jiangsu, China
| | - Zakari Shaibu
- School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China
| | - Qian Liu
- Department of Laboratory Medicine, Lianyungang Clinical College, Jiangsu University & The Second People's Hospital of Lianyungang, Lianyungang, 222006, Jiangsu, China.
| | - Wei Zhu
- School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China.
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Aguayo F, Tapia JC, Calaf GM, Muñoz JP, Osorio JC, Guzmán-Venegas M, Moreno-León C, Levican J, Andrade-Madrigal C. The Role of Xenobiotics and Anelloviruses in Colorectal Cancer: Mechanisms and Perspectives. Int J Mol Sci 2025; 26:4354. [PMID: 40362591 PMCID: PMC12072659 DOI: 10.3390/ijms26094354] [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: 02/24/2025] [Revised: 04/29/2025] [Accepted: 05/01/2025] [Indexed: 05/15/2025] Open
Abstract
Xenobiotics are non-natural chemical compounds to which the human population is exposed. Chronic exposure to certain xenobiotics is associated with various diseases, including cancer development. Anelloviruses (AVs), including Torque Teno Virus (TTV), Torque Teno Mini Virus (TTMV), and Torque Teno Midi Virus (TTMDV), are ubiquitous viruses found in the general population. As no disease has been definitively associated with AVs, they are sometimes referred to as "viruses awaiting a disease". This review explores the potential roles of xenobiotics and AVs in colorectal cancer (CRC) development and suggests a potential interplay between them. Evidence suggests an association between certain xenobiotics (like pesticides, cigarette smoke components, and dietary factors) and CRC, while such an association is less clear for AVs. The high prevalence of AVs suggests these infections alone may be insufficient to disrupt homeostasis; thus, additional factors might be required to promote disease, potentially including cancer.
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Affiliation(s)
- Francisco Aguayo
- Laboratorio de Oncovirología, Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad de Tarapacá, Arica 1000000, Chile; (J.C.O.); (M.G.-V.); (C.M.-L.); (C.A.-M.)
| | - Julio C. Tapia
- Laboratorio de Transformación Celular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Av. Independencia 1027, Santiago 8380453, Chile
| | - Gloria M. Calaf
- Instituto de Alta Investigación, Universidad de Tarapacá, Arica 1000000, Chile;
| | - Juan P. Muñoz
- Laboratorio de Bioquímica, Departamento de Química, Facultad de Ciencias, Universidad de Tarapacá, Arica 1000007, Chile;
| | - Julio C. Osorio
- Laboratorio de Oncovirología, Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad de Tarapacá, Arica 1000000, Chile; (J.C.O.); (M.G.-V.); (C.M.-L.); (C.A.-M.)
| | - Matías Guzmán-Venegas
- Laboratorio de Oncovirología, Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad de Tarapacá, Arica 1000000, Chile; (J.C.O.); (M.G.-V.); (C.M.-L.); (C.A.-M.)
| | - Carolina Moreno-León
- Laboratorio de Oncovirología, Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad de Tarapacá, Arica 1000000, Chile; (J.C.O.); (M.G.-V.); (C.M.-L.); (C.A.-M.)
| | - Jorge Levican
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;
| | - Cristian Andrade-Madrigal
- Laboratorio de Oncovirología, Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad de Tarapacá, Arica 1000000, Chile; (J.C.O.); (M.G.-V.); (C.M.-L.); (C.A.-M.)
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Aftab S, Zarlish QM. Trends in mortality related to malignant neoplasms of female genital organs in young females in the United States, 1999-2023. Int J Gynaecol Obstet 2025. [PMID: 40318212 DOI: 10.1002/ijgo.70162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 03/31/2025] [Accepted: 04/02/2025] [Indexed: 05/07/2025]
Abstract
OBJECTIVE To evaluate the site-specific mortality and demographic, racial, and regional trends of mortality related to malignant neoplasms of female genital organs in young females in the USA, 1999-2023 and to highlight the importance of targeted health policies. METHODS This was an analysis of a database that was collected by the CDC prospectively between 1999 and 2023. RESULTS An overall decrease in age-adjusted gynecologic cancer-related mortality rates in young females through the years 1999-2023, although the age-adjusted mortality rate increased slightly from 2010 to 2023. CONCLUSION There is an urgent need to devise targeted health policies to reduce the burden of malignant neoplasms of genital organs in young females, keeping in view the site and demographic, regional, and racial disparities.
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Affiliation(s)
- Sameen Aftab
- Department of Obstetrics and Gynecology, Nishtar Hospital, Multan, Punjab, Pakistan
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Hosseini MS, Sadeqi A, Heidari Z, Boozari M. A Comprehensive Review of Biologically Active Natural Products on Human Papillomavirus (HPV) at a Glance. Phytother Res 2025; 39:2262-2290. [PMID: 40127892 DOI: 10.1002/ptr.8444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Revised: 08/25/2024] [Accepted: 08/26/2024] [Indexed: 03/26/2025]
Abstract
Human papillomavirus (HPV) is widespread known as the sexually transmitted infection, which is responsible, for genital warts and certain types of cancer. Low-risks HPV types are responsible for genital warts. Genital warts can be treated through various medical and surgical methods. High-risks HPV types may cause dangerous cancers such as cervical cancer. The clinical approach in treatment of HPV-related cancers were different depending on the diseases stage ranging from surveillance and minor procedures for dysplasia to chemotherapy for more advanced cases. It is crucial to vaccinate adolescents against HPV to prevent infections from high risk strains. Researchers have explored natural products as potential solutions against viral infections with eight biologically active compounds. Including EGCG, curcumin, podophyllotoxin, resveratrol, pterostilbene, tanshinone IIA, indole-3-carbinol, and carrageenan. They are showing promising therapeutic effects in treating different stages of HPV-related diseases. Clinical trials have demonstrated the effectiveness of EGCG and podophyllotoxin in treating warts while other compounds, like curcumin, resveratrol, pterostilbene, indole-3-carbinol, and tanshinone IIA offer benefits in combating cervical cancer. In addition, carrageenan shows promising effects in HPV transmission prevention. It appears that compounds from nature may have an impact, on different phases of the HPV infection like genital warts treatment, disease transmission prevention, and healing-related cancers. These findings highlight the potential of natural products as valuable sources to combat HPV infection and related cancers. Further more extensive studies are necessary to discover the effective mechanism of these natural compounds as anti-HPV agents.
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Affiliation(s)
- Mahsa Sadat Hosseini
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirreza Sadeqi
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zinat Heidari
- Department of Clinical Pharmacy, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Motahareh Boozari
- Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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Booth ME, Wood HM, Travis MA, Quirke P, Grabsch HI. The relationship between the gastric cancer microbiome and clinicopathological factors: a metagenomic investigation from the 100,000 genomes project and The Cancer Genome Atlas. Gastric Cancer 2025; 28:358-371. [PMID: 39961991 PMCID: PMC11993446 DOI: 10.1007/s10120-025-01588-9] [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: 11/27/2024] [Accepted: 01/15/2025] [Indexed: 04/13/2025]
Abstract
BACKGROUND Findings from previous gastric cancer microbiome studies have been conflicting, potentially due to patient and/or tumor heterogeneity. The intratumoral gastric cancer microbiome and its relationship with clinicopathological variables have not yet been characterized in detail. We hypothesized that variation in gastric cancer microbial abundance, alpha diversity, and composition is related to clinicopathological characteristics. METHODS Metagenomic analysis of 529 GC samples was performed, including whole exome sequencing data from The Cancer Genome Atlas (TCGA) and whole genome sequencing data from the 100,000 Genomes Project. Microbial abundance, alpha diversity, and composition were compared across patient age, sex, tumor location, geographic origin, pathological depth of invasion, pathological lymph node status, histological phenotype, microsatellite instability status, and TCGA molecular subtype. RESULTS Gastric cancer microbiomes resembled previous results, with Prevotella, Selenomonas, Stomatobaculum, Streptococcus, Lactobacillus, and Lachnospiraceae commonly seen across both cohorts. Within the TCGA cohort, microbial abundance and alpha diversity were greater in gastric cancers with microsatellite instability, lower pathological depth of invasion, intestinal-type histology, and those originating from Asia. Microsatellite instability status was associated with microbiome composition in both cohorts. Sex and pathological depth of invasion were associated with microbiome composition in the TCGA cohort. CONCLUSION The intratumoral gastric cancer microbiome appears to differ according to clinicopathological factors. Certain clinicopathological factors associated with favourable outcomes in gastric cancer were observed to be associated with greater microbial abundance and diversity. This highlights the need for further work to understand the underlying biological mechanisms behind the observed microbiome differences and their potential clinical and therapeutic impact.
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Affiliation(s)
- Mary E Booth
- Division of Pathology & Data Analytics, Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Henry M Wood
- Division of Pathology & Data Analytics, Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Mark A Travis
- Lydia Becker Institute for Immunology and Inflammation, Wellcome Trust Centre for Cell-Matrix Research, Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK
| | - Phil Quirke
- Division of Pathology & Data Analytics, Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Heike I Grabsch
- Division of Pathology & Data Analytics, Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.
- Department of Pathology, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, The Netherlands.
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Groen-van Schooten TS, Cabeza-Segura M, Ferreira RM, Martínez-Ciarpaglini C, Barros R, Santos-Antunes J, Costa A, Fernández-Figueroa EA, Lino-Silva L, Hernandez-Guerrero AI, Ruiz-García E, Caballero C, Boggino H, Gauna C, Cantero D, Freile B, Esteso F, O Connor J, Riquelme A, Owen G, Riquelme E, Roa JC, Latorre G, Garrido M, Ruiz-Pace F, Diez García M, Alsina M, Lordick F, Farrés J, Carbonell-Asins JA, Villagrasa R, Pereira R, Pouw RE, Jimenez-Martí E, Miralles A, Dientsmann R, Figueiredo C, Carneiro F, Cervantes A, Derks S, Fleitas T. Immune profiling of gastric adenocarcinomas in EU and LATAM countries identifies global differences in immune subgroups and microbiome influence. Br J Cancer 2025; 132:783-792. [PMID: 40113862 PMCID: PMC12041472 DOI: 10.1038/s41416-025-02979-6] [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: 10/01/2024] [Revised: 02/04/2025] [Accepted: 03/10/2025] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND Gastric cancer (GC) patients from European (EU) and especially Latin American (LATAM) countries are underrepresented in previous large-scale multi-omic studies that have identified clinically relevant subgroups. The LEGACY study aimed to profile the molecular and immunological features of GCs from EU and LATAM countries. METHODS Tumor biopsies from 95 EU and 56 LATAM GCs were profiled with immunohistochemistry (CD3, CD8, FOXP3, PD-L1, MSI and HER2), Nanostring mRNA expression analyses, and microbiome sequencing. RESULTS Immune profiling identified four distinct immune clusters: a T cell dominant cluster with enriched activation pathways, a macrophage dominant cluster and an immune excluded microenvironment which were equally distributed among the countries. A fourth cluster of mostly Mexican patients consisted of excessive T cell numbers accompanied by enhanced cytokine signaling in absence of enhanced antigen presentation and cytotoxicity signatures and a strong association with H. pylori infection. DISCUSSION Both EU and LATAM countries have GCs with a T cell inflamed microenvironment that might benefit from checkpoint inhibition. We identified a highly inflamed GC subgroup that lacked antigen presentation and cytotoxicity associated with H. pylori CagA-positive strains, suggesting their contribution to tumor immune tolerance. Future studies are needed to unravel whether these cancers benefit from immunotherapy as well.
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Affiliation(s)
- Tessa S Groen-van Schooten
- Department of Medical Oncology, Amsterdam University Medical Center (UMC) location Vrije Universiteit Amsterdam, Amsterdam, Netherlands
- Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, Netherlands
- Oncode Institute, Amsterdam, Netherlands
| | - Manuel Cabeza-Segura
- Department of Medical Oncology, Hospital Clinico Universitario, INCLIVA, Biomedical Research Institute, University of Valencia, Valencia, Spain
| | - Rui M Ferreira
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
| | | | - Rita Barros
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
- Faculty of Medicine of the University of Porto, Porto, Portugal
- Department of Pathology, Unidade Local de Saúde São João, Porto, Portugal
| | - João Santos-Antunes
- Department of Gastroenterology, Unidade Local de Saúde São João, Porto, Portugal
| | - Andreia Costa
- Department of Oncology, Unidade Local de Saúde São João, Porto, Portugal
| | - Edith A Fernández-Figueroa
- Núcleo B de Innovación en Medicina de Precisión, Instituto Nacional de Medicina Genómica, Ciudad de, México, México
| | - Leonardo Lino-Silva
- Head of Division. Surgical Pathology, National Cancer Institute (INCan), Mexico City, Mexico
| | | | - Erika Ruiz-García
- Departamento de Tumores de Tubo Digestivo, Instituto Nacional de Cancerología, Ciudad de, México, México
- Laboratorio de Medicina Traslacional, Instituto Nacional de Cancerología, Ciudad de México, México
| | | | - Hugo Boggino
- Department of Pathology, GENPAT, Asunción, Paraguay
| | - Cinthia Gauna
- Medical Oncology Department, Instituto de Previsión Social, Asunción, Paraguay
| | - Daniel Cantero
- Department of Gastroenterology, Instituto de Previsión Social, Asunción, Paraguay
| | - Berenice Freile
- Medical Oncology Department, Instituto Alexander Fleming, Buenos Aires, Argentina
| | - Federico Esteso
- Medical Oncology Department, Instituto Alexander Fleming, Buenos Aires, Argentina
| | - Juan O Connor
- Medical Oncology Department, Instituto Alexander Fleming, Buenos Aires, Argentina
| | - Arnoldo Riquelme
- Department of Gastroenterology, Faculty of Medicine. Pontificia Universidad Catolica de Chile. Center for Prevention and Control of Cancer (CECAN), Santiago, Chile
| | - Gareth Owen
- Faculty of Biological Sciences & Faculty of Medicine. Pontificia Universidad Católica de Chile, Millennium Institute for Immunology and Immunotherapy, Center for Prevention and Control of Cancer (CECAN), Advance Center for Chronic Disease (ACCDIS), Santiago, Chile
| | - Erick Riquelme
- Department of Respiratory Diseases, Faculty of Medicine. Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Juan Carlos Roa
- Department of Pathology, Faculty of Medicine. Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Gonzalo Latorre
- Department of Gastroenterology, Faculty of Medicine. Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Marcelo Garrido
- Facultad de Ciencia de la Salud, Centro de Oncología de Precision, Universidad Mayor, Huechuraba, Chile
| | - Fiorella Ruiz-Pace
- Oncology Data Science, Vall d'Hebron Institute of Oncology, Barcelona, Spain
| | - Marc Diez García
- Medical Oncology Department, Vall d'Hebron Institute of Oncology, Barcelona, Spain
| | - Maria Alsina
- Medical Oncology Department, Vall d'Hebron Institute of Oncology, Barcelona, Spain
- Hospital Universitario de Navarra, Navarrabiomed-IdiSNA, Pamplona, Spain
| | - Florian Lordick
- Department of Medicine (Oncology, Gastroenterology, Hepatology, and Pulmonology), University of Leipzig Medical Center, Comprehensive Cancer Center Central Germany (CCCG), Leipzig, Germany
| | | | | | - Rossana Villagrasa
- Department of Gastroenterology, Hospital Clínico Universitario de Valencia, Valencia, Spain
| | - Rita Pereira
- Department of Gastroenterology, Instituto de Previsión Social, Asunción, Paraguay
| | - Roos E Pouw
- Gastroenterology Department. Amsterdam UMC, Amsterdam, The Netherlands
| | - Elena Jimenez-Martí
- Department of Medical Oncology, Hospital Clinico Universitario, INCLIVA, Biomedical Research Institute, University of Valencia, Valencia, Spain
| | - Ana Miralles
- Department of Medical Oncology, Hospital Clinico Universitario, INCLIVA, Biomedical Research Institute, University of Valencia, Valencia, Spain
| | - Rodrigo Dientsmann
- Oncology Data Science, Vall d'Hebron Institute of Oncology, Barcelona, Spain
| | - Ceu Figueiredo
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
- Department of Pathology, Unidade Local de Saúde São João, Porto, Portugal
| | - Fatima Carneiro
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
- Faculty of Medicine of the University of Porto, Porto, Portugal
- Department of Pathology, Unidade Local de Saúde São João, Porto, Portugal
| | - Andrés Cervantes
- Department of Medical Oncology, Hospital Clinico Universitario, INCLIVA, Biomedical Research Institute, University of Valencia, Valencia, Spain
- CiberOnc. Carlos III Institute, Madrid, Spain
| | - Sarah Derks
- Department of Medical Oncology, Amsterdam University Medical Center (UMC) location Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
- Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, Netherlands.
- Oncode Institute, Amsterdam, Netherlands.
| | - Tania Fleitas
- Department of Medical Oncology, Hospital Clinico Universitario, INCLIVA, Biomedical Research Institute, University of Valencia, Valencia, Spain.
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Wong SY, Rowan C, Brockmans ED, Law CCY, Giselbrecht E, Ang C, Khaitov S, Sachar D, Polydorides AD, Winata LSH, Verstockt B, Spinelli A, Rubin DT, Deepak P, McGovern DPB, McDonald BD, Lung P, Lundby L, Lightner AL, Holubar SD, Hanna L, Hamarth C, Geldof J, Dige A, Cohen BL, Carvello M, Bonifacio C, Bislenghi G, Behrenbruch C, Ballard DH, Altinmakas E, Sebastian S, Tozer P, Hart A, Colombel JF. Perianal Fistulizing Crohn's Disease-Associated Anorectal and Fistula Cancers: Systematic Review and Expert Consensus. Clin Gastroenterol Hepatol 2025; 23:927-945.e2. [PMID: 38871152 DOI: 10.1016/j.cgh.2024.05.029] [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: 02/18/2024] [Revised: 04/30/2024] [Accepted: 05/24/2024] [Indexed: 06/15/2024]
Abstract
BACKGROUND & AIMS Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and consequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of these cancers. To inform clinical practice, we developed consensus guidelines on PFCD-associated anorectal and fistula cancers by multidisciplinary experts from the international TOpClass consortium. METHODS We conducted a systematic review by standard methodology, using the Newcastle-Ottawa Scale quality assessment tool. We subsequently developed consensus statements using a Delphi consensus approach. RESULTS Of 561 articles identified, 110 were eligible, and 76 articles were included. The overall quality of evidence was low. The TOpClass consortium reached consensus on 6 structured statements addressing screening, risk assessment, and management of PFCD-associated anorectal and fistula cancers. Patients with long-standing (>10 years) PFCD should be considered at small but increased risk of developing perianal cancer, including squamous cell carcinoma of the anus and anorectal carcinoma. Risk factors for squamous cell carcinoma of the anus, notably human papilloma virus, should be considered. New, refractory, or progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Multiple modalities may be required for diagnosis, including an examination under anesthesia with biopsy. Multidisciplinary team efforts were deemed central to the management of fistula cancers. CONCLUSIONS Inflammatory bowel disease clinicians should be aware of the risk of PFCD-associated anorectal and fistula cancers in all patients with PFCD. The TOpClass consortium consensus statements outlined herein offer guidance in managing this challenging scenario.
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Affiliation(s)
- Serre-Yu Wong
- Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.
| | - Cathy Rowan
- Department of Gastroenterology, Beaumont Hospital, Dublin, Ireland
| | - Elvira Diaz Brockmans
- Department of Medicine, Universidad Iberoamericana, Santo Domingo, Dominican Republic
| | - Cindy C Y Law
- Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Elisabeth Giselbrecht
- Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Celina Ang
- Department of Oncology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Sergey Khaitov
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, New York
| | - David Sachar
- Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Alexandros D Polydorides
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | | | - Bram Verstockt
- Department of Gastroenterology, University Hospitals of Leuven, Leuven, Belgium
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; IRCCS Humanitas Research Hospital, Milan, Italy
| | - David T Rubin
- University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, Illinois
| | - Parakkal Deepak
- Department of Gastroenterology, Washington University School of Medicine in St. Louis, St. Louis, Missouri
| | - Dermot P B McGovern
- The F. Widjaja Foundation Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Benjamin D McDonald
- University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, Illinois
| | - Phillip Lung
- Radiology Department, St. Mark's Hospital and Academic Institute, London, United Kingdom
| | - Lilli Lundby
- Department of Surgery, Pelvic Floor Unit, Aarhus University Hospital, Aarhus, Denmark
| | - Amy L Lightner
- Department of Colorectal Surgery, Scripps Clinic, San Diego, California
| | - Stefan D Holubar
- Department of Colorectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
| | - Luke Hanna
- IBD Unit, St. Mark's Hospital and Academic Institute, London, United Kingdom; Imperial College London, London, United Kingdom
| | - Carla Hamarth
- Department of Radiology, University of Chicago Medicine, Chicago, Illinois
| | - Jeroen Geldof
- Department of Gastroenterology and Hepatology, University Hospital Ghent, Ghent, Belgium
| | - Anders Dige
- Department of Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Benjamin L Cohen
- Department of Gastroenterology, Hepatology, and Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
| | - Michele Carvello
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; IRCCS Humanitas Research Hospital, Milan, Italy
| | | | - Gabriele Bislenghi
- Department of Abdominal Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Corina Behrenbruch
- Department of Colorectal Surgery, St. Vincent's Hospital, Melbourne, Australia
| | - David H Ballard
- Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri
| | - Emre Altinmakas
- Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Shaji Sebastian
- IBD Unit, Hull University Teaching Hospitals NHS Trust, Hull, United Kingdom
| | - Phil Tozer
- Imperial College London, London, United Kingdom; Department of Colorectal Surgery, St. Mark's Hospital and Academic Institute, London, United Kingdom; Robin Phillips Fistula Research Unit, St. Mark's Hospital and Academic Institute, London, United Kingdom
| | - Ailsa Hart
- IBD Unit, St. Mark's Hospital and Academic Institute, London, United Kingdom; Imperial College London, London, United Kingdom
| | - Jean-Frederic Colombel
- Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
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Pinto A, Singhi AD, Voltaggio L, Salimian K, Birkness-Gartman J, Montgomery EA. TP53 Wild-Type, Human Papillomavirus-Independent Anal Growth/(Intra)Epithelial Lesion (ANGEL): A Potential Precursor of Anal Squamous Cell Carcinoma. Mod Pathol 2025; 38:100721. [PMID: 39863109 DOI: 10.1016/j.modpat.2025.100721] [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: 07/01/2024] [Revised: 01/08/2025] [Accepted: 01/10/2025] [Indexed: 01/27/2025]
Abstract
Human papillomavirus (HPV) underpins ∼90% of squamous cell carcinomas (SCCs) of the anus and perianal region. These tumors usually arise in association with precursor lesions such as anal intraepithelial neoplasia/high-grade squamous intraepithelial lesion, whereas a small subset of HPV-negative cancers may harbor mutations in TP53. Recently, vulvar lesions termed differentiated exophytic vulvar intraepithelial lesion/vulvar acanthosis with altered differentiated have been recognized as HPV-independent, TP53 wild-type precursors for vulvar carcinoma; however, analogous anal lesions have not been described. Cases of diagnostically challenging, TP53 wild-type HPV-negative anal squamous lesions with unusual histologic features including acanthosis and/or verrucous architecture were retrospectively identified. Lesions with koilocytic changes, lack of surface maturation, or significant cytologic atypia were excluded. HPV status was determined by immunohistochemistry for p16 and/or in situ hybridization for low- and high-risk strains, whereas TP53 status was assessed using immunohistochemistry and molecular studies in a subset of cases, with targeted molecular sequencing performed in 3 of these. All lesions (5/5) arose in men, ages ranging from 55 to 78 years (median: 65 years). Verrucous architecture was seen in 2 of 5 cases, 2 of 5 were predominantly acanthotic, and 1 of 5 had both verrucous and acanthotic growth. The lesions were characterized by hyperkeratosis (5/5), hypergranulosis (5/5), and cytoplasmic pallor of upper epithelial layers (2/5). All cases were negative for HPV and had wild-type p53 expression. Three cases with sufficient material for sequencing lacked alterations within the entire coding sequencing of TP53. Invasive SCC was concurrently present in 3 of 5 cases. In summary, verrucous and acanthotic HPV-independent TP53 wild-type squamous proliferation of the anal and perianal region, referred to herein as anal growth/(intra)epithelial lesion (ANGEL), are premalignant lesions that have the potential to become invasive, as most of our cases demonstrated synchronous SCC.
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Affiliation(s)
- Andre Pinto
- Department of Pathology and Laboratory Medicine, University of Miami, Miami, Florida.
| | - Aatur D Singhi
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Lysandra Voltaggio
- Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Kevan Salimian
- Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland
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Lycke KD, Steben M, Garland SM, Woo YL, Cruickshank ME, Perkins RB, Bhatla N, Ryser MD, Gravitt PE, Hammer A. An updated understanding of the natural history of cervical human papillomavirus infection-clinical implications. Am J Obstet Gynecol 2025; 232:453-460. [PMID: 39983886 DOI: 10.1016/j.ajog.2025.02.029] [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: 12/15/2024] [Revised: 02/03/2025] [Accepted: 02/10/2025] [Indexed: 02/23/2025]
Abstract
Recently, the International Papillomavirus Society convened a working group on cervical human papillomavirus latency, which resulted in an updated understanding of the human papillomavirus natural history. While the previous human papillomavirus natural history model considered human papillomavirus detection to be a result of human papillomavirus acquisition or possibly reinfection, and loss of human papillomavirus detection to be a result of viral clearance, the updated understanding of the human papillomavirus natural history is more nuanced. Thus, human papillomavirus detection may occur as a result of autoinoculation, deposition from a recent sex act, or as a redetection of a previously acquired infection. Similarly, loss of human papillomavirus detection likely reflects immune control rather than complete viral clearance. As it is practically impossible to identify the "true" source of a new human papillomavirus detection or determine why human papillomavirus is no longer detectable, we propose that healthcare providers and researchers use the terminology human papillomavirus detected vs human papillomavirus not detected. Moreover, we describe the updated understanding in a clinical context. Specifically, we discuss the potential implications of the updated understanding regarding clinical counseling in screening, recommendations on cervical screening, and human papillomavirus vaccination. We also suggest key phrases that healthcare providers may use when counseling women attending routine human papillomavirus-based cervical screening.
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Affiliation(s)
- Kathrine D Lycke
- University Clinic for HPV-related gynecological disease, Department of Obstetrics and Gynecology, Gødstrup Hospital, Herning, Denmark; NIDO - Center for research and education, Gødstrup Hospital, Herning, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Marc Steben
- School of Public Health, Université de Montréal, Montreal, QC, Canada
| | - Suzanne M Garland
- Reproductive & Neonatal Infectious Diseases, Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Australia; Centre for Women's Infectious Diseases Research, Royal Women's Hospital, Infection and Immunity, Murdoch Children's Research, Melbourne, Australia
| | - Yin Ling Woo
- Department of Obstetrics and Gynaecology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
| | | | - Rebecca B Perkins
- Boston Medical Center/Boston University Chobanian and Avedesian School of Medicine, Boston, MA
| | - Neerja Bhatla
- Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, New Delhi, India
| | - Marc D Ryser
- Department of Population Health Sciences, Duke University School of Medicine, Durham, NC; Department of Mathematics, Duke University, Durham, NC
| | - Patti E Gravitt
- Division of Global Health, National Cancer Institute, Bethesda, MD
| | - Anne Hammer
- University Clinic for HPV-related gynecological disease, Department of Obstetrics and Gynecology, Gødstrup Hospital, Herning, Denmark; NIDO - Center for research and education, Gødstrup Hospital, Herning, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
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48
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Zhang R, Zhang X, Lau HCH, Yu J. Gut microbiota in cancer initiation, development and therapy. SCIENCE CHINA. LIFE SCIENCES 2025; 68:1283-1308. [PMID: 39821827 DOI: 10.1007/s11427-024-2831-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Accepted: 12/12/2024] [Indexed: 01/19/2025]
Abstract
Cancer has long been associated with genetic and environmental factors, but recent studies reveal the important role of gut microbiota in its initiation and progression. Around 13% of cancers are linked to infectious agents, highlighting the need to identify the specific microorganisms involved. Gut microbiota can either promote or inhibit cancer growth by influencing oncogenic signaling pathways and altering immune responses. Dysbiosis can lead to cancer, while certain probiotics and their metabolites may help reestablish micro-ecological balance and improve anti-tumor immune responses. Research into targeted approaches that enhance therapy with probiotics is promising. However, the effects of probiotics in humans are complex and not yet fully understood. Additionally, methods to counteract harmful bacteria are still in development. Early clinical trials also indicate that modifying gut microbiota may help manage side effects of cancer treatments. Ongoing research is crucial to understand better how gut microbiota can be used to improve cancer prevention and treatment outcomes.
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Affiliation(s)
- Ruyi Zhang
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - Xiang Zhang
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - Harry Cheuk Hay Lau
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - Jun Yu
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
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49
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Tso J, Galeas S, Martinez B, Vallecillo K, Abidalhassan MF, Webster N, Leiva H, Al-Qaraghli M, Gaskill C. Feasibility of a Symptomatic Screening Program for Early Detection of Gastric Cancer in Roatán, Honduras. JCO Glob Oncol 2025; 11:e2400574. [PMID: 40403197 DOI: 10.1200/go-24-00574] [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: 11/08/2024] [Revised: 01/16/2025] [Accepted: 02/26/2025] [Indexed: 05/24/2025] Open
Abstract
PURPOSE Gastric cancer (GC) is a leading cause of cancer-related death in Central America, with late-stage diagnosis common because of nonspecific early symptoms. Symptomatic screening guidelines validated in high-income settings have been used to identify patients requiring urgent referral for upper GI endoscopy. METHODS This tool was piloted to assess feasibility for early detection of GC at a primary care clinic in Roatán, Honduras. If positive, a referral to endoscopy was placed, and patients contacted monthly for up to 4 months to collect information on demographics, GC risk factors, barriers to receiving endoscopy, and if they received an endoscopy. Provider questionnaires assessed endoscopy capacity and perceived patient barriers. RESULTS Five hundred patients were screened over 12 months. Nine screened positive, with seven clinically relevant to GC. Of these, four (57%) were female, average age was 49 years (IQR, 18), average number of years lived in Roatán was 29 (IQR, 34), and hypertension (57%) and hyperlipidemia (29%) were the most reported comorbidities. Two (29%) had a family history of cancer, four (57%) had a previous H. pylori infection, six (71%) took medication for acid reflux, and four (57%) had dietary risk factors for GC. All patients cited cost as a barrier to care, while two (29%) each reported difficulty traveling to a facility, lack of knowledge on which facilities did endoscopy, and uncertainty of whether they needed the procedure as other barriers. CONCLUSION Although symptomatic screening guidelines are feasible for screening GC in Honduras, limitations in endoscopy access and capacity pose barriers to early diagnosis. These findings highlight the need to increase diagnostic capacity and address financial barriers to endoscopy.
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Affiliation(s)
- Jade Tso
- School of Medicine, Academic Research Careers for Medical Doctors (ARC-MD) Program, University of California-Davis, Sacramento, CA
| | | | | | | | | | | | - Heidy Leiva
- Clínica Esperanza, Sandy Bay, Roatán, Honduras
| | | | - Cameron Gaskill
- Department of Surgery, Division of Surgical Oncology, University of California-Davis, Sacramento, CA
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50
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Fei X, Li N, Xu X, Zhu Y. Macrophage biology in the pathogenesis of Helicobacter pylori infection. Crit Rev Microbiol 2025; 51:399-416. [PMID: 39086061 DOI: 10.1080/1040841x.2024.2366944] [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: 08/03/2023] [Revised: 05/31/2024] [Accepted: 06/04/2024] [Indexed: 08/02/2024]
Abstract
Infection with H. pylori induces chronic gastric inflammation, progressing to peptic ulcer and stomach adenocarcinoma. Macrophages function as innate immune cells and play a vital role in host immune defense against bacterial infection. However, the distinctive mechanism by which H. pylori evades phagocytosis allows it to colonize the stomach and further aggravate gastric preneoplastic pathology. H. pylori exacerbates gastric inflammation by promoting oxidative stress, resisting macrophage phagocytosis, and inducing M1 macrophage polarization. M2 macrophages facilitate the proliferation, invasion, and migration of gastric cancer cells. Various molecular mechanisms governing macrophage function in the pathogenesis of H. pylori infection have been identified. In this review, we summarize recent findings of macrophage interactions with H. pylori infection, with an emphasis on the regulatory mechanisms that determine the clinical outcome of bacterial infection.
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Affiliation(s)
- Xiao Fei
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Nianshuang Li
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Xinbo Xu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Yin Zhu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
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