|
1
|
Rimassa L, Khan S, Groot Koerkamp B, Roessler S, Andersen JB, Raggi C, Lleo A, Nault JC, Calderaro J, Gabbi C, Kather JN, Banales JM, Bargellini I, Morement H, Krawczyk M, Farazi PA, Carpino G, Avila MA, Saborowski A, Cardinale V, Braconi C, Macias RI. Mapping the landscape of biliary tract cancer in Europe: challenges and controversies. THE LANCET REGIONAL HEALTH. EUROPE 2025; 50:101171. [PMID: 40093398 PMCID: PMC11910794 DOI: 10.1016/j.lanepe.2024.101171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 11/22/2024] [Accepted: 11/25/2024] [Indexed: 03/19/2025]
Abstract
Biliary tract cancer (BTC) is becoming more common worldwide, with geographic differences in incidence and risk factors. In Europe, BTC may be associated with primary sclerosing cholangitis, lithiasis, and liver cirrhosis, but is more frequently observed as a sporadic disease. BTC increasingly affects patients under 60 years, resulting in a significant social and economic burden. Early diagnosis remains challenging due to vague symptoms in 50% of patients with BTC, and lack of specific biomarkers, resulting in late presentation and poor prognosis. The identification of patients at increased risk and reliable biomarkers require collaborative efforts to make faster progress. This Series paper highlights the disparities in access to diagnostic tools and multidisciplinary care in Europe, particularly in economically disadvantaged regions, while identifying priority areas for improvement. Addressing these inequities requires harmonised guidelines, accelerated pathways to curative treatments, and improved awareness among healthcare professionals and the public. Multidisciplinary teams (MDTs) are crucial for the diagnosis of BTC and for improving patient outcomes, yet inconsistencies exist in their implementation not only between different countries, but also between different centres within a country. Collaboration and standardisation of diagnostic and treatment protocols across Europe are essential to effectively address the management of patients with BTC.
Collapse
Affiliation(s)
- Lorenza Rimassa
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072, Pieve Emanuele, Milan, Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via A. Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Shahid Khan
- Department of Metabolism, Digestion and Reproduction, Imperial College London, Liver Unit, St Mary's Hospital Campus, South Wharf Road, W2 1NY, London, UK
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Doctor Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands
| | - Stephanie Roessler
- Heidelberg University, Medical Faculty, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany
| | - Jesper B. Andersen
- Biotech Research & Innovation Centre (BRIC), Department of Health and Medical Sciences, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen N, DK-2200, Denmark
| | - Chiara Raggi
- Department of Experimental and Clinical Medicine, University of Florence, Cubo Centro Polivalente 2, Viale Pieraccini 6, 50139, Florence, Italy
| | - Ana Lleo
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072, Pieve Emanuele, Milan, Italy
- Internal Medicine and Hepatology Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Jean-Charles Nault
- Cordeliers Research Center, Sorbonne University, Inserm, Paris Cité University, “Functional Genomics of Solid Tumors” Team, Ligue Nationale Contre le Cancer Accredited Team, Labex OncoImmunology, 16 rue de l'École de Médecine, 75006, Paris, France
- Liver Unit, Avicenne Hospital, APHP, University Sorbonne Paris Nord, 125 Avenue de Stalingrad, 93000, Bobigny, France
| | - Julien Calderaro
- Université Paris Est Créteil, INSERM, IMRB, 61 Av. du Général de Gaulle, 94000, Créteil, France
- Department of Pathology, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, 1 Rue Gustave Eiffel, 94010, Créteil, France
- MINT-Hep, Mondor Integrative Hepatology, 1 Rue Gustave Eiffel, 94010, Créteil, France
| | - Chiara Gabbi
- Humanitas Medical Care, Via Domodossola 9/a, 20145, Milan, Italy
| | - Jakob N. Kather
- Else Kroener Fresenius Center for Digital Health, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, 01307, Dresden, Germany
- Department of Medicine I, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, 01307, Dresden, Germany
- Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany
| | - Jesus M. Banales
- Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute – Donostia University Hospital, CIBERehd, Paseo Dr. Begiristain, s/n, 20014, San Sebastian, Spain
- IKERBASQUE, Basque Foundation for Science, Euskadi Pl., 5, Abando, 48009, Bilbao, Spain
- Department of Medicine, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Barrio Sarriena, s/n, 48940, Leioa, Spain
- Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Calle Irunlarrea 1, 31008, Pamplona, Spain
| | - Irene Bargellini
- Department of Surgical Sciences, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy
- Division of Diagnostic and Interventional Radiology, Candiolo Cancer Institute FPO-IRCCS, Strada Provinciale 142, 10060, Candiolo (TO), Italy
| | - Helen Morement
- AMMF – The Cholangiocarcinoma Charity, Enterprise House, Bassingbourn Road, Stansted, CM24 1QW, Essex, UK
| | - Marcin Krawczyk
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany
- Laboratory of Metabolic Liver Diseases, Medical University of Warsaw, Banacha Street 1B, 02-097, Warsaw, Poland
| | - Paraskevi A. Farazi
- School of Medicine, European University Cyprus, 6 Diogenes Street, 2404, Engomi, Nicosia, Cyprus
| | - Guido Carpino
- Department of Anatomical, Histological, Legal Medicine and Orthopedic Sciences, Sapienza University of Rome, Via Alfonso Borelli 50, 00161, Rome, Italy
| | - Matias A. Avila
- Hepatology Laboratory, Solid Tumors Program, CIMA, IdiSNA, CIBERehd, University of Navarra, Calle Irunlarrea 1, 31008, Pamplona, Spain
| | - Anna Saborowski
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Carl Neuberg Str. 1, 30625, Hannover, Germany
| | - Vincenzo Cardinale
- Department of Translational and Precision Medicine, Sapienza University of Rome, Via Alfonso Borelli 50, 00161, Rome, Italy
| | - Chiara Braconi
- School of Cancer Sciences, University of Glasgow, Switchback rd, G61 1QH, Glasgow, UK
- Beatson West of Scotland Cancer Centre, 1053 Great Western rd, G12 0YN, Glasgow, UK
- CRUK Scotland Cancer Centre, G61 1BD, Glasgow, UK
| | - Rocio I.R. Macias
- Experimental Hepatology and Drug Targeting (HEVEPHARM) Group, University of Salamanca, IBSAL, CIBERehd, Campus M. Unamuno s/n, 37007, Salamanca, Spain
| |
Collapse
|
|
2
|
Tang Z, Wei C, Deng X, Lin Q, Hu Q, Li S, Wang J, Wu Y, Liu D, Fang M, Zhan T. Serum proteomic and metabolomic profiling of hepatocellular carcinoma patients co-infected with Clonorchis sinensis. Front Immunol 2025; 15:1489077. [PMID: 39840062 PMCID: PMC11746118 DOI: 10.3389/fimmu.2024.1489077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Accepted: 12/10/2024] [Indexed: 01/23/2025] Open
Abstract
Background Clonorchis sinensis (C. sinensis) infection is a significant risk factor for hepatocellular carcinoma (HCC), yet its underlying mechanisms remain poorly understood. This study aimed to investigate the impact of C. sinensis infection on the serum proteomic and metabolomic profiling of HCC patients, focusing on the potential mechanisms. Method A retrospective clinical analysis was conducted on 1121 HCC patients, comparing those with and without C. sinensis infection. The influence of C. sinensis on serum proteome and metabolome in HCC was further assessed. Result C. sinensis infection correlated with a younger age at cancer onset, male predominance, advanced cancer stage, liver cirrhosis, and microvascular invasion in HCC patients. It also associated with shorter overall survival (OS) and recurrence-free survival (RFS). The levels of blood lipids (e.g., APO-A, HDL-C, and TG) were significantly altered after C. sinensis infection. Proteomic and metabolomic analyses revealed metabolic reprogramming caused by C. sinensis, with excessive depletion of argininosuccinate synthase (ASS) and D-glucose as potential factors in C. sinensis-associated HCC malignancy. Key molecules ILF2, CNN2, OLFM4, NOTCH3, and LysoPA were implicated in HCC progression. Furthermore, C. sinensis triggered inflammation, insulin resistance, and pro-tumor immune escape, and exacerbated the complication of degenerative diseases. Conclusion This study not only provides compelling evidence for elucidating the mechanisms underlying C. sinensis-mediated HCC development but also identifies potential therapeutic targets for HCC patients co-infected with C. sinensis.
Collapse
Affiliation(s)
- Zeli Tang
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Guangxi Medical University, Nanning, China
- Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Guangxi Medical University, Nanning, China
- Key Laboratory of Basic Research on Regional Diseases, Education Department of Guangxi Zhuang Autonomous Region, Guangxi Medical University, Nanning, China
| | - Caibiao Wei
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Xueling Deng
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Guangxi Medical University, Nanning, China
| | - Qiumei Lin
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Qiping Hu
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Guangxi Medical University, Nanning, China
- Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Guangxi Medical University, Nanning, China
- Key Laboratory of Basic Research on Regional Diseases, Education Department of Guangxi Zhuang Autonomous Region, Guangxi Medical University, Nanning, China
| | - Shitao Li
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Guangxi Medical University, Nanning, China
| | - Jilong Wang
- Department of Parasitology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, China
| | - Yuhong Wu
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Guangxi Medical University, Nanning, China
| | - Dengyu Liu
- Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Guangxi Medical University, Nanning, China
- Key Laboratory of Basic Research on Regional Diseases, Education Department of Guangxi Zhuang Autonomous Region, Guangxi Medical University, Nanning, China
- Department of Parasitology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, China
| | - Min Fang
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
- Engineering Research Center for Tissue & Organ Injury and Repair Medicine, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Tingzheng Zhan
- Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Guangxi Medical University, Nanning, China
- Key Laboratory of Basic Research on Regional Diseases, Education Department of Guangxi Zhuang Autonomous Region, Guangxi Medical University, Nanning, China
- Department of Parasitology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, China
| |
Collapse
|
|
3
|
Lee SO, Dai F, Park EJ, Hong YP, Quan FS, Song JH, Hong SJ. Risk factors for Clonorchis sinensis infections and control measures reinforced with focused interviews. Parasitol Res 2024; 123:414. [PMID: 39699664 DOI: 10.1007/s00436-024-08437-1] [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: 08/08/2024] [Accepted: 12/11/2024] [Indexed: 12/20/2024]
Abstract
Clonorchiosis, a disease that develops following the consumption of raw freshwater fish that harbors Clonorchis sinensis metacercariae, seriously threatens the health of residents in endemic areas. We aimed to assess the level of awareness of liver fluke infections among infected residents and restaurant workers in liver fluke infection-endemic areas. To identify and provide a more realistic description of C. sinensis infections, we conducted a focused interview and questionnaire survey of local residents in endemic areas in Korea. Most residents knew that freshwater fish are a source of C. sinensis infection. Nevertheless, the consumption of raw freshwater fish was the main risk factor for their infection with C. sinensis. The residents had little knowledge regarding their residential area being endemic to C. sinensis or about the symptoms and complications of C. sinensis infection. Although the participants had no experience with C. sinensis prevention or health education, they preferred on-site education during visits to village halls. The in-depth interviewees had a high level of knowledge about C. sinensis infection but were unaware that eating raw freshwater fish was its cause. Family and social gatherings encourage the habit of eating raw freshwater fish, which is a risk factor for repetitive infections. Based on these findings, to eliminate clonorchiosis, we propose strengthening the capacity of public health care personnel, giving C. sinensis prevention education, and screening educational videos during visits to village halls. Furthermore, intensive education is recommended for reinfected people and community opinion leaders, as well as reservoir host control.
Collapse
Affiliation(s)
- Soon-Ok Lee
- Department of Medical Sciences, Chung-Ang University College of Medicine, Seoul, Republic of Korea
- Department of Medical Zoology and Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea
| | - Fuhong Dai
- Department of Medical Sciences, Chung-Ang University College of Medicine, Seoul, Republic of Korea
- Department of Parasitology, School of Biology and Basic Medical Sciences, Medical College, Soochow University, Suzhou, China
| | - Eun Joo Park
- Seoul National University Dental Research Institute, Seoul, Republic of Korea
| | - Yun Pyo Hong
- Department of Preventive Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Fu-Shi Quan
- Department of Medical Zoology and Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea
| | - Jin-Ho Song
- Department of Pharmacology, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
| | - Sung-Jong Hong
- Department of Medical Sciences, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
| |
Collapse
|
|
4
|
Lee SO, Chu KB, Yoon KW, Heo SI, Song JH, Li J, Hong SJ, Quan FS. Combinatorial Treatment with Praziquantel and Curcumin Reduces Clonorchis sinensis Parasite Burden and Clonorchiasis-Associated Pathologies in Rats. Pharmaceutics 2024; 16:1550. [PMID: 39771529 PMCID: PMC11678916 DOI: 10.3390/pharmaceutics16121550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 11/20/2024] [Accepted: 11/26/2024] [Indexed: 01/11/2025] Open
Abstract
Background/Objectives: Clonorchiasis is a foodborne parasitic disease that can lead to severe biliary fibrosis and cholangiocarcinoma. While praziquantel (PZQ) is available for clonorchiasis treatment, it cannot revert the histopathological damage incurred through parasite-induced fibrosis. Curcumin (CUR) is an emerging experimental drug possessing anti-inflammatory and fibrosis-alleviating effects, thus signifying its potential as an anthelmintic drug. Here, we evaluated the effect of CUR+PZQ combinatorial drug treatment on C. sinensis infection as well as its effect on ameliorating fibrotic tissue damage in rats. Methods: Worm viabilities following CUR and PZQ treatments were confirmed through microscopy and tetrazolium salt absorption. Anthelminthic effect and hepatobiliary damage mitigation in rats were determined by quantifying worm recovery, histopathological staining, and enzyme-linked immunosorbent assay. Results: CUR+PZQ at LD50 doses demonstrated a time- and dose-dependent antiparasitic effect in vitro, which was markedly greater than either drug alone. Rats were infected with C. sinensis, and drugs were administered at 1 and 4 weeks post-infection (wpi) to assess drug-induced changes in worm burden. Significant reductions in worm burden recoveries were observed following CUR+PZQ treatment at both time points, accompanied by markedly reduced serum and mucosal IgG responses. ALT and AST levels were also substantially lower in combinatorial drug treatment groups than controls. Histopathological examinations confirmed that parasite-induced bile duct lumen widening and liver fibrosis were suppressed at 1 wpi, implying that CUR+PZQ co-treatment can alleviate clonorchiasis-associated pathologies. Conclusions: Our findings indicate that CUR+PZQ co-treatment improved parasite clearance and promoted the resolution of hepatobiliary tissue damage resulting from chronic clonorchiasis.
Collapse
Affiliation(s)
- Soon-Ok Lee
- Department of Medical Zoology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea;
- Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Ki Back Chu
- Department of Parasitology, College of Medicine, Inje University, Busan 47392, Republic of Korea;
- Department of Infectious Disease and Malaria, Paik Institute of Clinical Research, Inje University, Busan 47392, Republic of Korea
| | - Keon-Woong Yoon
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; (K.-W.Y.); (S.I.H.)
| | - Su In Heo
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; (K.-W.Y.); (S.I.H.)
| | - Jin-Ho Song
- Department Pharmacology, College of Medicine, Chung-Ang University, Seoul 06974, Republic of Korea;
| | - Jianhua Li
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Sung-Jong Hong
- Chung-Ang University College of Medicine, Seoul 06974, Republic of Korea;
| | - Fu-Shi Quan
- Department of Medical Zoology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea;
- Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
| |
Collapse
|
|
5
|
Lishai EA, Zaparina OG, Kapushchak YK, Sripa B, Hong SJ, Cheng G, Pakharukova MY. Comparative liver transcriptome analysis in hamsters infected with food-borne trematodes Opisthorchis felineus, Opisthorchis viverrini, or Clonorchis sinensis. PLoS Negl Trop Dis 2024; 18:e0012685. [PMID: 39652576 PMCID: PMC11627427 DOI: 10.1371/journal.pntd.0012685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Accepted: 11/07/2024] [Indexed: 12/12/2024] Open
Abstract
BACKGROUND Epidemiologically important food-borne trematodes Opisthorchis viverrini and Clonorchis sinensis are recognized as biological carcinogens of Group 1A, while Opisthorchis felineus is in Group 3 as noncarcinogenic to humans. Mechanisms of the biological carcinogenesis are still elusive. Some studies highlight chronic inflammation as a key factor and common pathway for cancer initiation and progression. Nonetheless, the chronic inflammation alone does not explain why these three species differ in carcinogenicity. We focused this study on genome-wide landscapes of liver gene expression and activation of cellular pathways in Mesocricetus auratus golden hamsters infected with C. sinensis (South Korea), O. viverrini (Thailand), or O. felineus (Russia) at 1 and 3 months after infection initiation. METHODOLOGY/PRINCIPAL FINDINGS Liver transcriptomes of golden hamsters (HiSeq Illumina, 2X150 bp) were sequenced at 1 and 3 months postinfection. Data processing was carried out using the following bioinformatic and experimental approaches: analysis of differential gene expression, estimates of proportions of affected liver cell types, liver histopathology, and examination of weighted gene coexpression networks. All infections caused enrichment with inflammatory response signaling pathways, fibrogenesis and cell proliferation, and IL2-STAT5, TNF-NF-κB, TGF-β, Hippo, MAPK, and PI3K-Akt signaling pathways. Nevertheless, species-specific responses to each infection were noted too. We also identified species-specific responses of liver cell types, differentially expressed gene clusters, and cellular pathways associated with structural liver damage (such as periductal fibrosis, epithelial neoplasia, and inflammation). CONCLUSIONS/SIGNIFICANCE This is the first comparative analysis of gene expression landscapes in the liver of experimental animals infected with O. viverrini, O. felineus, or C. sinensis. The trematodes have species-specific effects on the hepatobiliary system by triggering signaling pathways, thereby leading to differences in the severity of hepatobiliary structural lesions and contributing to the pathogenicity of closely related foodborne trematodes.
Collapse
Affiliation(s)
- Ekaterina A. Lishai
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (ICG SB RAS), Novosibirsk, Russia
- Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia
| | - Oxana G. Zaparina
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (ICG SB RAS), Novosibirsk, Russia
| | - Yaroslav K. Kapushchak
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (ICG SB RAS), Novosibirsk, Russia
| | - Banchob Sripa
- Chung-Ang University College of Medicine, Seoul, Korea
| | - Sun-Jong Hong
- WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian Liver Fluke Disease), Tropical Disease Research Center, Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Guofeng Cheng
- Shanghai Tenth People’s Hospital, Institute for Infectious Diseases and Vaccine Development, Tongji University School of Medicine, Shanghai, China
| | - Maria Y. Pakharukova
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (ICG SB RAS), Novosibirsk, Russia
- Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia
| |
Collapse
|
|
6
|
Huang YL, Zhang KY, Sun YL, Qian MB, Wang Z. The risk of hepatobiliary complications in Clonorchis and Opisthorchis infection: A systematic review and meta-analysis. Acta Trop 2024; 260:107457. [PMID: 39521195 DOI: 10.1016/j.actatropica.2024.107457] [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: 08/12/2024] [Revised: 10/16/2024] [Accepted: 11/06/2024] [Indexed: 11/16/2024]
Abstract
Clonorchis sinensis, Opisthorchis viverrini, and Opisthorchis felineus are the three important liver flukes, infecting approximately 25 million people worldwide. Despite the reporting of the carcinogenesis of these liver flukes, the comprehensive and systematic analysis of the pathogenicity of these parasites in hepatobiliary system is still not sufficient. We conducted a thorough systematic review and search for published articles in MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure databases until early 2024. Cohort studies, case-control studies, and cross-sectional studies associated with C. sinensis, O. viverrini, or O. felineus infection were selected. Pooled risk ratio (RR), odds ratio (OR) and their 95 % confidence intervals (95 % CIs) were calculated to assess the risk of hepatobiliary complications due to these liver fluke infections. From a total of 6488 articles, 22 eligible studies and 34,367 participants were included for review. Our results showed C. sinensis, O. viverrini, and O. felineus infections were significantly associated with cholangiocarcinoma, with an overall OR of 4.24 (95 % CI: 3.33-5.39, P < 0.00001) and an overall RR of 10.43 (95 % CI: 2.90-37.47, P = 0.0003). The ORs for the association between cholangiocarcinoma and C. sinensis and O. viverrini infection were 4.49 (95 % CI:3.43-5.87, P < 0.00001) and 3.69 (95 % CI: 2.07-6.55, P < 0.00001) respectively. For the association between cholelithiasis and C. sinensis infection, the OR was 6.46 (95 % CI: 5.15-8.11, P < 0.00001). C. sinensis infection increased the risk of cholecystitis and cirrhosis, with the RR of 21.02 (95 % CI: 17.27-25.58) and an overall RR of 8.77 (95 % CI: 6.79-11.33, P < 0.00001) respectively. C. sinensis infection was also significantly associated with fatty liver, with an overall OR of 2.46 (95 % CI: 1.79-3.37, P < 0.00001). This comprehensive study, reviewing the largest dataset to date, provided an overall risk of hepatobiliary complications due to Clonorchis and Opisthorchis infections, and aids more systematic understanding for the pathogenicity of Opisthorchiidae family parasites.
Collapse
Affiliation(s)
- Yi-Lin Huang
- Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Kai-Yan Zhang
- Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Yan-Lin Sun
- Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Men-Bao Qian
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, WHO Collaborating Centre for Tropical Diseases, NHC Key Laboratory of Parasite and Vector Biology, National Center for International Research on Tropical Diseases, Shanghai 200025, China.
| | - Zhaojun Wang
- Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
| |
Collapse
|
|
7
|
Wei C, Chen J, Yu Q, Qin Y, Huang T, Liu F, Pan X, Lin Q, Tang Z, Fang M. Clonorchis sinensis infection contributes to hepatocellular carcinoma progression via enhancing angiogenesis. PLoS Negl Trop Dis 2024; 18:e0012638. [PMID: 39527585 PMCID: PMC11554034 DOI: 10.1371/journal.pntd.0012638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Accepted: 10/20/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Clonorchis sinensis (C. sinensis) infection plays an important role in the progression of hepatocarcinogenesis. However, its specific role in HCC progression remains unclear. This study aimed to investigate whether C. sinensis contributes to angiogenesis in HCC. METHODS A comprehensive clinical analysis was conducted on 947 HCC patients, divided into two groups: C. sinensis (-) HCC and C. sinensis (+) HCC. Kaplan-Meier survival curves and log-rank tests were utilized to assess survival outcomes. Microvessel density (MVD) was evaluated through CD34 immunohistochemistry on hepatectomy specimens. A chemistry analyzer and blood analyzer were employed to measure the concentration of circulating angiogenesis-related biomarkers. Quantitative reverse transcription-PCR (qRT-PCR) was used to analyze the expression of angiogenesis-related genes (CD34, Ang1, Ang2, VEGF, PDGF) in HCC tissues. RESULTS C. sinensis infection was associated with poorer outcomes in HCC patients, with significantly shorter overall survival (OS) (p = 0.014) and recurrence-free survival (RFS) (p<0.001). Notably, C. sinensis infection led to an upregulation of MVD in HCC tissues (p = 0.041). C. sinensis (+) HCC patients exhibited significantly higher levels of circulating angiogenesis-related biomarkers, including MONO (p = 0.004), EOSO (p < 0.001), C3 (p = 0.001), FIB (p = 0.010), PLT (p = 0.003), LDH (p = 0.004), GLDH (p = 0.003), compared to C. sinensis (-) HCC patients. Moreover, qRT-PCR analysis revealed that most angiogenesis-related genes were overexpressed in patients with C. sinensis infection. CONCLUSION C. sinensis infection is closely associated with inflammatory responses and may promote metabolic reprogramming in HCC, thereby enhancing its malignant characteristics.
Collapse
Affiliation(s)
- Caibiao Wei
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Junxian Chen
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Qiuhai Yu
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Yuling Qin
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Taijun Huang
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Fengfei Liu
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Xiaolan Pan
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Qiumei Lin
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Zeli Tang
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Guangxi Medical University, Nanning, China
| | - Min Fang
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
- Engineering Research Center for Tissue & Organ Injury and Repair Medicine, Guangxi Medical University Cancer Hospital, Nanning, China
| |
Collapse
|
|
8
|
Wen L, Li M, Yin J. PTEN Deficiency Induced by Extracellular Vesicle miRNAs from Clonorchis sinensis Potentiates Cholangiocarcinoma Development by Inhibiting Ferroptosis. Int J Mol Sci 2024; 25:10350. [PMID: 39408679 PMCID: PMC11477024 DOI: 10.3390/ijms251910350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 09/21/2024] [Accepted: 09/24/2024] [Indexed: 10/20/2024] Open
Abstract
The human phosphatase and tensin homolog (PTEN) is a tumor suppressor. A slight deficiency in PTEN might cause cancer susceptibility and progression. Infection by the liver fluke Clonorchis sinensis could lead to persistent loss of PTEN in cholangiocarcinoma. However, the mechanism of PTEN loss and its malignant effect on cholangiocarcinoma have not yet been elucidated. Extracellular vesicles secreted by Clonorchis sinensis (CS-EVs) are rich in microRNAs (miRNAs) and can mediate communication between hosts and parasites. Herein, we delved into the miRNAs present in CS-EVs, specifically those that potentially target PTEN and modulate the progression of cholangiocarcinoma via ferroptosis mechanisms. CS-EVs were extracted by differential ultra-centrifugation for high-throughput sequencing of miRNA. Lentiviral vectors were used to construct stably transfected cell lines. Erastin was used to construct ferroptosis induction models. Finally, 36 miRNAs were identified from CS-EVs. Among them, csi-miR-96-5p inhibited PTEN expression according to the predictions and dual luciferase assay. The CCK-8 assay, xenograft tumor assays and transwell assay showed that csi-miR-96-5p overexpression and PTEN knockout significantly increased the proliferation and migration of cholangiocarcinoma cells and co-transfection of PTEN significantly reversed the effect. In the presence of erastin, the cell proliferation and migration ability of the negative transfection control group were significantly impaired, although they did not significantly change with transfection of csi-miR-96-5p and PTEN knockout, indicating that they obtained ferroptosis resistance. Mechanistically, csi-miR-96-5p and PTEN knockout significantly inhibited ferroptosis through a decrease in ferrous ion (Fe2+) and malondialdehyde (MDA), and an increase in glutathione reductase (GSH), Solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). In conclusion, loss of PTEN promoted the progression of cholangiocarcinoma via the ferroptosis pathway and csi-miR-96-5p delivered by CS-EVs may mediate this process.
Collapse
Affiliation(s)
| | | | - Jigang Yin
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China; (L.W.); (M.L.)
| |
Collapse
|
|
9
|
Qian MB, Keiser J, Utzinger J, Zhou XN. Clonorchiasis and opisthorchiasis: epidemiology, transmission, clinical features, morbidity, diagnosis, treatment, and control. Clin Microbiol Rev 2024; 37:e0000923. [PMID: 38169283 PMCID: PMC10938900 DOI: 10.1128/cmr.00009-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 07/18/2023] [Indexed: 01/05/2024] Open
Abstract
Clonorchis sinensis, Opisthorchis viverrini, and Opisthorchis felineus are important liver flukes that cause a considerable public health burden in eastern Asia, southeastern Asia, and eastern Europe, respectively. The life cycles are complex, involving humans, animal reservoirs, and two kinds of intermediate hosts. An interplay of biological, cultural, ecological, economic, and social factors drives transmission. Chronic infections are associated with liver and biliary complications, most importantly cholangiocarcinoma. With regard to diagnosis, stool microscopy is widely used in epidemiologic surveys and for individual diagnosis. Immunologic techniques are employed for screening purposes, and molecular techniques facilitate species differentiation in reference laboratories. The mainstay of control is preventive chemotherapy with praziquantel, usually combined with behavioral change through information, education and communication, and environmental control. Tribendimidine, a drug registered in the People's Republic of China for soil-transmitted helminth infections, shows potential against both C. sinensis and O. viverrini and, hence, warrants further clinical development. Novel control approaches include fish vaccine and biological control. Considerable advances have been made using multi-omics which may trigger the development of new interventions. Pressing research needs include mapping the current distribution, disentangling the transmission, accurately estimating the disease burden, and developing new diagnostic and treatment tools, which would aid to optimize control and elimination measures.
Collapse
Affiliation(s)
- Men-Bao Qian
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), Shanghai, People’s Republic of China
- NHC Key Laboratory of Parasite and Vector Biology, Shanghai, People’s Republic of China
- WHO Collaborating Centre for Tropical Diseases, Shanghai, People’s Republic of China
- School of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Jennifer Keiser
- Swiss Tropical and Public Health Institute, Allschwil, Switzerland
- University of Basel, Basel, Switzerland
| | - Jürg Utzinger
- Swiss Tropical and Public Health Institute, Allschwil, Switzerland
- University of Basel, Basel, Switzerland
| | - Xiao-Nong Zhou
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), Shanghai, People’s Republic of China
- NHC Key Laboratory of Parasite and Vector Biology, Shanghai, People’s Republic of China
- WHO Collaborating Centre for Tropical Diseases, Shanghai, People’s Republic of China
- School of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| |
Collapse
|
|
10
|
Alshewered AS. The Parasitism and Tumors Carcinogenesis: A Review Subject. Acta Parasitol 2024; 69:183-189. [PMID: 38489011 DOI: 10.1007/s11686-024-00832-z] [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: 11/30/2022] [Accepted: 02/26/2024] [Indexed: 03/17/2024]
Abstract
BACKGROUND Multi-factorial reasons are an induction to cause cancer. Different infections and infestations with viruses, bacteria, and parasites have been detected for many years to be related to human carcinogenesis. PURPOSE The study aimed to review all ideas of tumor carcinogenesis and its associations with parasitic infections and infestations. METHODS We reviewed several articles (published and imprinted) by selecting, extracting, and synthesizing data about the relationship between cancers and parasites. RESULTS Several helminths infections as schistosomiasis, are highly carcinogenic agents for bladder cancer, whereas trypanosomiasis has a bi-model role in cancer development. Leishmaniasis may be a cause of hepatocarcinoma, skin cancer, and lymphomas. In addition, malaria appears to be causative in the carcinogenesis of some cancers; as Burkitt lymphoma. Also, data from previous studies suggested that Strongyloides stercoralis may be a relevant co-factor in lymphomas. CONCLUSION There are different mechanisms of parasitic infection to be enhancing in carcinogenesis of cancer in human.
Collapse
Affiliation(s)
- Ahmed Salih Alshewered
- Misan Radiation Oncology Center, Misan Health Directorate, Ministry of Health/Environment, Misan, Iraq.
| |
Collapse
|
|
11
|
Ni HH, Lu Z, Yang CL, Lv YT, Lu CX, Xiang BD. Clonorchis sinensis on the prognosis of patients with spontaneous rupture of Hepatocellular Carcinoma: An inverse probability of treatment weighting analysis. PLoS Negl Trop Dis 2024; 18:e0011987. [PMID: 38381766 PMCID: PMC10911612 DOI: 10.1371/journal.pntd.0011987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 03/04/2024] [Accepted: 02/12/2024] [Indexed: 02/23/2024] Open
Abstract
BACKGROUND We examined the impact of the Clonorchis sinensis (C. sinensis) infection on the survival outcomes of spontaneous rupture Hepatocellular Carcinoma (srHCC) patients undergoing hepatectomy. METHODS Between May 2013 and December 2021, 157 consecutive srHCC patients who underwent hepatectomy were divided into an no C. sinensis group (n = 126) and C. sinensis group (n = 31). To adjust for differences in preoperative characteristics an inverse probability of treatment weighting (IPTW) analysis was done, using propensity scores. Overall survival (OS) and recurrence-free survival (RFS) were compared before and after IPTW. Multivariate Cox regression analysis was performed to determine whether the C. sinensis infection was an independent prognostic factor after IPTW. RESULTS In original cohort, the no C. sinensis group did not show a survival advantage over the C. sinensis group. After IPTW adjustment, the median OS for the C. sinensis group was 9 months, compared to 29 months for the no C. sinensis group. C. sinensis group have worse OS than no C. sinensis group (p = 0.024), while it did not differ in RFS(p = 0.065). The multivariate Cox regression analysis showed that C. sinensis infection and lower age were associated with worse OS. CONCLUSIONS The C. sinensis infection has an adverse impact on os in srHCC patients who underwent hepatectomy.
Collapse
Affiliation(s)
- Hang-Hang Ni
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
- Department of Hepatobiliary Surgery, Zhongshan City People’s Hospital, Zhongshan, People’s Republic of China
| | - Zhan Lu
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
| | - Cheng-Lei Yang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
| | - Yu-Ting Lv
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
| | - Chun-Xiu Lu
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
| | - Bang-De Xiang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
- Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumors, Ministry of Education, Nanning, People’s Republic of China
| |
Collapse
|
|
12
|
Lin Q, Tang Z, Qin Y, Deng X, Wei C, Liu F, Pan X, Liu D, Zhan T, Fang M. Clonorchis sinensis infection amplifies hepatocellular carcinoma stemness, predicting unfavorable prognosis. PLoS Negl Trop Dis 2024; 18:e0011906. [PMID: 38285640 PMCID: PMC10824460 DOI: 10.1371/journal.pntd.0011906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Accepted: 01/08/2024] [Indexed: 01/31/2024] Open
Abstract
BACKGROUND Extensive evidence links Clonorchis sinensis (C. sinensis) to cholangiocarcinoma; however, its association with hepatocellular carcinoma (HCC) is less acknowledged, and the underlying mechanism remains unclear. This study was designed to investigate the association between C. sinensis infection and HCC and reveal the relationship between C. sinensis infection and cancer stemness. METHODS A comprehensive analysis of 839 HCC patients categorized into C. sinensis (-) HCC and C. sinensis (+) HCC groups was conducted. Chi-square and Mann-Whitney U tests were used to assess the association between C. sinensis infection and clinical factors. Kaplan-Meier and Cox regression analyses were used to evaluate survival outcomes. Immunohistochemistry was used to determine CK19 and EpCAM expression in HCC specimens. RESULTS Compared to C. sinensis (-) HCC patients, C. sinensis (+) HCC patients exhibited advanced Barcelona Clinic Liver Cancer (BCLC) stage, higher male prevalence and more liver cirrhosis as well as elevated alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), eosinophil, complement 3 (C3), and complement 4 (C4) values. C. sinensis infection correlated with shorter overall survival (OS) (p < 0.05) and recurrence-free survival (RFS) (p < 0.05). Furthermore, Cox multivariate analysis revealed that C. sinensis infection was an independent prognostic factor for OS in HCC patients. Importantly, C. sinensis infection upregulated the expression of HCC cancer stem cell markers CK19 and EpCAM. CONCLUSION HCC patients with C. sinensis infection exhibit a poor prognosis following hepatectomy. Moreover, C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC. AUTHOR SUMMARY Clonorchis sinensis (C. sinensis) is a prominent food-borne parasite prevalent in regions such as China, particularly in Guangxi. C. sinensis has been associated with various hepatobiliary system injuries, encompassing inflammation, periductal fibrosis, cholangiocarcinoma and even hepatocellular carcinoma (HCC). A substantial body of evidence links C. sinensis to cholangiocarcinoma, However, the connection between C. sinensis and HCC and the intricate mechanisms underlying its contribution to HCC development remain incompletely elucidated. Our study demonstrates clear clinicopathological associations between C. sinensis and HCC, such as gender, BCLC stage, liver cirrhosis, MVI, AFP, CA19-9, circulating eosinophils and complements. Furthermore, we found that the co-occurrence of C. sinensis exhibited a significant association with shorter OS and RFS in patients diagnosed with HCC. A major finding was that C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC. Our results provide a more comprehensive comprehension of the interplay between C. sinensis and HCC, shedding fresh light on the carcinogenic potential of C. sinensis.
Collapse
Affiliation(s)
- Qiumei Lin
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
| | - Zeli Tang
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Guangxi Medical University, Nanning, People’s Republic of China
| | - Yuling Qin
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
| | - Xueling Deng
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Guangxi Medical University, Nanning, People’s Republic of China
| | - Caibiao Wei
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
| | - Fengfei Liu
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
| | - Xiaolan Pan
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
| | - Dengyu Liu
- Department of Parasitology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, People’s Republic of China
| | - Tingzheng Zhan
- Department of Parasitology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, People’s Republic of China
| | - Min Fang
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
- Engineering Research Center for Tissue & Organ Injury and Repair Medicine, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
| |
Collapse
|
|
13
|
Caligiuri A, Becatti M, Porro N, Borghi S, Marra F, Pastore M, Taddei N, Fiorillo C, Gentilini A. Oxidative Stress and Redox-Dependent Pathways in Cholangiocarcinoma. Antioxidants (Basel) 2023; 13:28. [PMID: 38247453 PMCID: PMC10812651 DOI: 10.3390/antiox13010028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 12/19/2023] [Accepted: 12/20/2023] [Indexed: 01/23/2024] Open
Abstract
Cholangiocarcinoma (CCA) is a primary liver tumor that accounts for 2% of all cancer-related deaths worldwide yearly. It can arise from cholangiocytes of biliary tracts, peribiliary glands, and possibly from progenitor cells or even hepatocytes. CCA is characterized by high chemoresistance, aggressiveness, and poor prognosis. Potentially curative surgical therapy is restricted to a small number of patients with early-stage disease (up to 35%). Accumulating evidence indicates that CCA is an oxidative stress-driven carcinoma resulting from chronic inflammation. Oxidative stress, due to enhanced reactive oxygen species (ROS) production and/or decreased antioxidants, has been recently suggested as a key factor in cholangiocyte oncogenesis through gene expression alterations and molecular damage. However, due to different experimental models and conditions, contradictory results regarding oxidative stress in cholangiocarcinoma have been reported. The role of ROS and antioxidants in cancer is controversial due to their context-dependent ability to stimulate tumorigenesis and support cancer cell proliferation or promote cell death. On these bases, the present narrative review is focused on illustrating the role of oxidative stress in cholangiocarcinoma and the main ROS-driven intracellular pathways. Heterogeneous data about antioxidant effects on cancer development are also discussed.
Collapse
Affiliation(s)
- Alessandra Caligiuri
- Department of Experimental and Clinical Medicine, University of Florence, 50139 Florence, Italy; (A.C.); (F.M.); (M.P.)
| | - Matteo Becatti
- Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, Italy; (M.B.); (N.P.); (S.B.); (N.T.)
| | - Nunzia Porro
- Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, Italy; (M.B.); (N.P.); (S.B.); (N.T.)
| | - Serena Borghi
- Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, Italy; (M.B.); (N.P.); (S.B.); (N.T.)
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, University of Florence, 50139 Florence, Italy; (A.C.); (F.M.); (M.P.)
| | - Mirella Pastore
- Department of Experimental and Clinical Medicine, University of Florence, 50139 Florence, Italy; (A.C.); (F.M.); (M.P.)
| | - Niccolò Taddei
- Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, Italy; (M.B.); (N.P.); (S.B.); (N.T.)
| | - Claudia Fiorillo
- Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, Italy; (M.B.); (N.P.); (S.B.); (N.T.)
| | - Alessandra Gentilini
- Department of Experimental and Clinical Medicine, University of Florence, 50139 Florence, Italy; (A.C.); (F.M.); (M.P.)
| |
Collapse
|
|
14
|
Wen LJ, Yin JG, Wang YX, Liu K, Zhao JX. csi-miR-96-5p delivered by Clonorchis sinensis extracellular vesicles promotes intrahepatic cholangiocarcinoma proliferation and migration via the ferroptosis-related PTEN/SLC7A11/GPX4 axis. Parasit Vectors 2023; 16:465. [PMID: 38124152 PMCID: PMC10734124 DOI: 10.1186/s13071-023-06075-7] [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: 11/04/2023] [Accepted: 11/30/2023] [Indexed: 12/23/2023] Open
Abstract
BACKGROUND Clonorchis sinensis (CS) is classified as a group 1 carcinogen and can cause intrahepatic cholangiocarcinoma (ICC). CS extracellular vesicles (CsEVs) play important roles in mediating communication between parasitic helminths and humans. Ferroptosis is a novel cell death mechanism that is mainly induced by lipid peroxidation and iron overload. However, the role of CsEVs in the regulation of ferroptosis in ICC remains unclear. This study aimed to explore the role of CS-secreted miR-96-5p (csi-miR-96-5p) delivered by CsEVs in ICC progression and ferroptosis. METHODS Tissue samples were collected from ICC patients with CS infection (CS-ICC) or without CS infection (NC-ICC). The levels of csi-miR-96-5p and PTEN gene were determined by quantitative polymerase chain reaction (qPCR) and western blotting, and survival analysis was performed. CsEVs were isolated and identified by ultracentrifugation and transmission electron microscopy. Lentiviruses were used to establish stable cell lines with csi-miR-96-5p mimic expression, PTEN overexpression (PTEN-EXO) and PTEN CRISPR/Cas9-based knockout (PTEN-KO) and their respective negative controls. Cell proliferation was assessed by performing Cell Counting Kit-8 assays in vitro and in a tumor xenograft model in vivo, and cell migration was assessed by performing Transwell assays. Erastin is used to induce ferroptosis. Ferroptosis levels were evaluated using biomarkers. RESULTS High csi-miR-96-5p and low PTEN expression was observed in CS-ICC tissues and was associated with poor overall survival. csi-miR-96-5p was highly enriched in CsEVs and was taken up by ICC cells. csi-miR-96-5p mimics or PTEN-KO significantly promoted the growth and migration of ICC cells in vitro and in vivo, whereas PTEN-EXO exerted the opposite effect. Mechanistically, csi-miR-96-5p mimics or PTEN-KO inhibited erastin-induced ferroptosis, including reducing the accumulation of Fe2+, lipid reactive oxygen species, and malondialdehyde, increasing the GSH/GSSG ratio and levels of SLC7A11 and GPX4, whereas PTEN-EXOs exerted the opposite effect. CONCLUSIONS csi-miR-96-5p delivered by CsEVs reduced ferroptosis by regulating the expression of the PTEN/SLC7A11/GPX4 axis, thereby promoting ICC proliferation and migration. For the first time to our knowledge, we found that CS miRNAs could promote tumor development through ferroptosis.
Collapse
Affiliation(s)
- Li-Jia Wen
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, 130062, Jilin, China
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, 130021, Jilin, China
| | - Ji-Gang Yin
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, 130062, Jilin, China
| | - Yong-Xin Wang
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, 130021, Jilin, China
| | - Kai Liu
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, 130021, Jilin, China
| | - Ji-Xue Zhao
- Department of Pediatric Surgery, The First Hospital of Jilin University, Changchun, 130021, Jilin, China.
| |
Collapse
|
|
15
|
Borlase A, Prada JM, Crellen T. Modelling morbidity for neglected tropical diseases: the long and winding road from cumulative exposure to long-term pathology. Philos Trans R Soc Lond B Biol Sci 2023; 378:20220279. [PMID: 37598702 PMCID: PMC10440174 DOI: 10.1098/rstb.2022.0279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Accepted: 07/13/2023] [Indexed: 08/22/2023] Open
Abstract
Reducing the morbidities caused by neglected tropical diseases (NTDs) is a central aim of ongoing disease control programmes. The broad spectrum of pathogens under the umbrella of NTDs lead to a range of negative health outcomes, from malnutrition and anaemia to organ failure, blindness and carcinogenesis. For some NTDs, the most severe clinical manifestations develop over many years of chronic or repeated infection. For these diseases, the association between infection and risk of long-term pathology is generally complex, and the impact of multiple interacting factors, such as age, co-morbidities and host immune response, is often poorly quantified. Mathematical modelling has been used for many years to gain insights into the complex processes underlying the transmission dynamics of infectious diseases; however, long-term morbidities associated with chronic or cumulative exposure are generally not incorporated into dynamic models for NTDs. Here we consider the complexities and challenges for determining the relationship between cumulative pathogen exposure and morbidity at the individual and population levels, drawing on case studies for trachoma, schistosomiasis and foodborne trematodiasis. We explore potential frameworks for explicitly incorporating long-term morbidity into NTD transmission models, and consider the insights such frameworks may bring in terms of policy-relevant projections for the elimination era. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.
Collapse
Affiliation(s)
- Anna Borlase
- Department of Biology, University of Oxford, Oxford OX1 3SZ, UK
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, UK
| | - Joaquin M. Prada
- Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK
| | - Thomas Crellen
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, UK
- School of Biodiversity, One Health & Veterinary Medicine, Graham Kerr Building, University of Glasgow, Glasgow G12 8QQ, UK
- Wellcome Centre for Integrative Parasitology, Sir Graeme Davies Building, University of Glasgow, Glasgow G12 8TA, UK
| |
Collapse
|
|
16
|
Fonti N, Parisi F, Mancianti F, Freer G, Poli A. Cancerogenic parasites in veterinary medicine: a narrative literature review. Infect Agent Cancer 2023; 18:45. [PMID: 37496079 PMCID: PMC10373346 DOI: 10.1186/s13027-023-00522-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Accepted: 07/17/2023] [Indexed: 07/28/2023] Open
Abstract
Parasite infection is one of the many environmental factors that can significantly contribute to carcinogenesis and is already known to be associated with a variety of malignancies in both human and veterinary medicine. However, the actual number of cancerogenic parasites and their relationship to tumor development is far from being fully understood, especially in veterinary medicine. Thus, the aim of this review is to investigate parasite-related cancers in domestic and wild animals and their burden in veterinary oncology. Spontaneous neoplasia with ascertained or putative parasite etiology in domestic and wild animals will be reviewed, and the multifarious mechanisms of protozoan and metazoan cancer induction will be discussed.
Collapse
Affiliation(s)
- Niccolò Fonti
- Dipartimento di Scienze veterinarie, Università di Pisa, Viale delle Piagge, 2, 56124, Pisa, Italy.
| | - Francesca Parisi
- Dipartimento di Scienze veterinarie, Università di Pisa, Viale delle Piagge, 2, 56124, Pisa, Italy
| | - Francesca Mancianti
- Dipartimento di Scienze veterinarie, Università di Pisa, Viale delle Piagge, 2, 56124, Pisa, Italy
| | - Giulia Freer
- Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Università di Pisa, Via Savi, 10, 56126, Pisa, Italy
| | - Alessandro Poli
- Dipartimento di Scienze veterinarie, Università di Pisa, Viale delle Piagge, 2, 56124, Pisa, Italy
| |
Collapse
|
|
17
|
Fedorova OS, Kovshirina AE, Kovshirina YV, Hattendorf J, Onishchenko SV, Katanakhova LL, Taslicki SS, Chizhikov AV, Tataurov IA, Vtorushin SV, Sripa B, Ogorodova LM, Odermatt P. Opisthorchis Felineus Infection is a Risk Factor for Cholangiocarcinoma in Western Siberia: A Hospital-based Case-control Study. Clin Infect Dis 2023; 76:e1392-e1398. [PMID: 35723279 DOI: 10.1093/cid/ciac497] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 06/09/2022] [Accepted: 06/14/2022] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Cholangiocarcinoma (CCA), a fatal bile duct cancer, has a high incidence in Western Siberia, Russian Federation. In addition, Opisthorchis felineus, a bile duct-dwelling trematode liver fluke is highly endemic. Closely related species have been shown to be cancerogenic agents in Asia. We therefore examined the association between O felineus infection and CCA in Western Siberia. METHODS We conducted a hospital-based, individually matched case-control study between January 2017 and August 2020 in Tomsk Oblast and Khanty-Mansiysk Autonomous Okrug, Yugra, Russian Federation. Histologically confirmed CCA patients (cases) were compared with matched age, sex, and place of residence hospital controls. The examination of study participants included the diagnosis of current and past O felineus infection, abdominal ultrasonographical assessment, physical examination, and interview on exposures to potential risk factors. RESULTS We identified 40 patients with CCA and 160 controls. Exposures to O felineus infection was strongly associated with CCA (odds ratio [OR], 3.9; 95% confidence interval [CI], 1.4-10.8; P = .008). Also, cases reported more often that they were currently or in the past were infected by O felineus compared with controls (OR, 4.03; 95% CI, 1.7-9.5; P = .001). Furthermore, cases reported river fish consumption and fishing habits significantly more often than controls (OR, 5.5; 95% CI, 1.5-19.8; P = .009 and OR, 3.3; 95% CI, 1.4-7.7; P = .005). CONCLUSIONS The study results revealed a strong significantly increased risk for CCA development in O felineus-infected individuals. Elaboration of the guidelines on screening programs for early CCA diagnosis, prevention, and treatment is socially important in endemic regions.
Collapse
Affiliation(s)
- Olga S Fedorova
- Federal State Budget Educational Institution of Higher Education, Siberian State Medical University, Ministry of Healthcare of Russian Federation, Tomsk, Russian Federation
| | - Anna E Kovshirina
- Federal State Budget Educational Institution of Higher Education, Siberian State Medical University, Ministry of Healthcare of Russian Federation, Tomsk, Russian Federation
| | - Yulia V Kovshirina
- Federal State Budget Educational Institution of Higher Education, Siberian State Medical University, Ministry of Healthcare of Russian Federation, Tomsk, Russian Federation
| | - Jan Hattendorf
- Swiss Tropical and Public Health Institute, Allschwil, Switzerland.,University of Basel, Basel, Switzerland
| | - Sergey V Onishchenko
- Surgut State University, Surgut, Russian Federation.,Surgut Regional Clinical Hospital 14, Surgut, Russian Federation
| | | | | | | | - Ilya A Tataurov
- Regional Clinical Hospital 40, Khanty-Mansiysk, Russian Federation
| | - Sergey V Vtorushin
- Federal State Budget Educational Institution of Higher Education, Siberian State Medical University, Ministry of Healthcare of Russian Federation, Tomsk, Russian Federation
| | | | - Ludmila M Ogorodova
- Federal State Budget Educational Institution of Higher Education, Siberian State Medical University, Ministry of Healthcare of Russian Federation, Tomsk, Russian Federation
| | - Peter Odermatt
- Swiss Tropical and Public Health Institute, Allschwil, Switzerland.,University of Basel, Basel, Switzerland
| |
Collapse
|
|
18
|
Li YK, Zhao JF, Yang CL, Zhan GH, Zhang J, Qin SD, Zhou M, Li MJ, Huang JT, Kong FY, Huang H, Chen JH, Xiang BD. Effects of Clonorchis sinensis combined with Hepatitis B virus infection on the prognosis of patients with Hepatocellular Carcinoma following Hepatectomy. PLoS Negl Trop Dis 2023; 17:e0011012. [PMID: 36638133 PMCID: PMC9879467 DOI: 10.1371/journal.pntd.0011012] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 01/26/2023] [Accepted: 12/09/2022] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND This study aimed to determine the impact of co-infection of Clonorchis sinensis (CS) and hepatitis B virus (HBV) on the prognosis of patients with hepatocellular carcinoma (HCC) following hepatectomy. METHODS The clinicopathological information of 946 patients with HCC following hepatectomy was retrospectively analyzed. The patients were divided into four groups depending on whether they had CS infection and/or HBV infection: double-negative group (infected with neither CS nor HBV), simple CS group (infected with only CS), simple HBV group (infected with only HBV), and double-positive group (co-infected with CS and HBV). Kaplan-Meier curves were used to evaluate the overall survival (OS) and recurrence-free survival (RFS), while log-rank tests were used to compare survival rates. Further, Cox regression was used to perform both univariate and multivariate survival analyses to identify variables linked to the prognosis of HCC. RESULTS The median overall survival (OS) and recurrence-free survival (RFS) in the double-positive, simple CS, simple HBV, and double-negative groups were 27 months and 9 months, 20 months and 7 months, 44 months and 12 months, and 42 months and 17 months, respectively. The double-positive group's 1-year, 3-year, and 5-year OS and RFS rates were 79.2% and 46.9%, 62.6% and 28.4%, 47.8%, and 12.2%, respectively. The simple CS group's 1-year, 3-year, and 5-year OS and RFS rates were 86.3% and 41.5%, 56.5% and 27.7%, 50.2%, and 18.5%, respectively. The simple HBV group's 1-year, 3-year, and 5-year OS and RFS rates were 89.8% and 56.0%, 72.5% and 30.5%, 63.8%, and 19.9%, respectively. The double-negative group's 1-year, 3-year, and 5-year OS and RFS rates were 91.5% and 62.3%, 76.1% and 32.9%, 64.0%, and 22.4%, respectively. Further, according to a Cox multivariate analysis, tumor size (> 5cm), Edmonson grade (III-IV), BCLC-C stage, and tumor satellite focus were independent risk factors for RFS and OS in patients with HCC. CONCLUSION Patients with HCC and Clonorchis sinensis infection experience a poor prognosis after hepatectomy, regardless of whether they are co-infected with HBV.
Collapse
Affiliation(s)
- Yuan-Kuan Li
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
| | - Jing-Fei Zhao
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
| | - Cheng-Lei Yang
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
| | - Guo-Hua Zhan
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
| | - Jie Zhang
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
| | - Shang-Dong Qin
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
| | - Min Zhou
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
| | - Min-Jun Li
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
| | - Jun-Tao Huang
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
| | - Feng-Yao Kong
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
| | - Hai Huang
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Wuming Hospital, Guangxi, China
| | - Jia-Hao Chen
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Wuming Hospital, Guangxi, China
| | - Bang-De Xiang
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi, China
- * E-mail:
| |
Collapse
|
|
19
|
Ludwig DR, Anderson MA, Itani M, Sharbidre KG, Lalwani N, Paspulati RM. Secondary sclerosing cholangitis: mimics of primary sclerosing cholangitis. Abdom Radiol (NY) 2023; 48:151-165. [PMID: 35585354 PMCID: PMC9116710 DOI: 10.1007/s00261-022-03551-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 05/01/2022] [Accepted: 05/02/2022] [Indexed: 01/21/2023]
Abstract
Sclerosing cholangitis is a chronic cholestatic disease characterized by stricturing, beading, and obliterative fibrosis of the bile ducts. Sclerosing cholangitis is considered primary (PSC) if no underlying etiology is identified or secondary (SSC) if related to another identifiable cause. In this article, we will review the clinical features, pathogenesis, diagnosis, and imaging findings of PSC and SSC, with an emphasis on features that may aid in the distinction of these entities. We will also discuss various etiologies of SSC including recurrent pyogenic cholangitis, other infectious etiologies, ischemic damage, toxic insults, and immunologic, congenital, and miscellaneous causes, highlighting the unique imaging findings and clinical context of each diagnosis.
Collapse
Affiliation(s)
- Daniel R. Ludwig
- grid.4367.60000 0001 2355 7002Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, Campus Box 8131, Saint Louis, MO 63110 USA
| | - Mark A. Anderson
- grid.38142.3c000000041936754XDepartment of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA USA
| | - Malak Itani
- grid.4367.60000 0001 2355 7002Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, Campus Box 8131, Saint Louis, MO 63110 USA
| | - Kedar G. Sharbidre
- grid.265892.20000000106344187Department of Radiology, The University of Alabama at Birmingham, Birmingham, AL USA
| | - Neeraj Lalwani
- grid.224260.00000 0004 0458 8737Department of Radiology, Virginia Commonwealth University, Richmond, VA USA
| | - Raj M. Paspulati
- grid.67105.350000 0001 2164 3847Department of Radiology, Case Western Reserve University, Cleveland, OH USA
| |
Collapse
|
|
20
|
Pakharukova MY, Mordvinov VA. Similarities and differences among the Opisthorchiidae liver flukes: insights from Opisthorchis felineus. Parasitology 2022; 149:1306-1318. [PMID: 35570685 PMCID: PMC11010525 DOI: 10.1017/s0031182022000397] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 03/12/2022] [Accepted: 03/19/2022] [Indexed: 11/08/2022]
Abstract
The foodborne liver trematode Opisthorchis felineus (Rivolta, 1884) is a member of the triad of phylogenetically related epidemiologically important Opisthorchiidae trematodes, which also includes O. viverrini (Poirier, 1886) and Clonorchis sinensis (Loos, 1907). Despite similarity in the life cycle, Opisthorchiidae liver flukes also have marked differences. Two species (O. viverrini and C. sinensis) are recognized as Group 1A biological carcinogens, whereas O. felineus belongs to Group 3A. In this review, we focus on these questions: Are there actual differences in carcinogenicity among these 3 liver fluke species? Is there an explanation for these differences? We provide a recent update of our knowledge on the liver fluke O. felineus and highlight its differences from O. viverrini and C. sinensis. In particular, we concentrate on differences in the climate of endemic areas, characteristics of the life cycle, the range of intermediate hosts, genomic and transcriptomic features of the pathogens, and clinical symptoms and morbidity of the infections in humans. The discussion of these questions can stimulate new developments in comparative studies on the pathogenicity of liver flukes and should help to identify species-specific features of opisthorchiasis and clonorchiasis pathogenesis.
Collapse
Affiliation(s)
- Maria Y. Pakharukova
- Laboratory of Molecular Mechanisms of Pathological Processes, Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), 10 Akad. Lavrentieva Ave., Novosibirsk 630090, Russia
- Department of Natural Sciences, Novosibirsk State University, 2 Pirogova Str., Novosibirsk 630090, Russia
| | - Viatcheslav A. Mordvinov
- Laboratory of Molecular Mechanisms of Pathological Processes, Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), 10 Akad. Lavrentieva Ave., Novosibirsk 630090, Russia
| |
Collapse
|
|
21
|
Zhang H, Yu Y, Li J, Gong P, Wang X, Li X, Cheng Y, Yu X, Zhang N, Zhang X. Changes of gut microbiota in colorectal cancer patients with Pentatrichomonas hominis infection. Front Cell Infect Microbiol 2022; 12:961974. [PMID: 36118043 PMCID: PMC9471007 DOI: 10.3389/fcimb.2022.961974] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Accepted: 07/27/2022] [Indexed: 01/11/2023] Open
Abstract
Pentatrichomonas hominis is a parasitic trichomonads protozoa that parasitizes in the colon and cecum of humans and other animals. Our previous studies have demonstrated that infection with P. hominis is associated with the incidence of colon cancer (37.93%). However, the mechanism by which P. hominis infections increase the incidence of colon cancer remains unclear. Previous studies have suggested that certain parasites promote colon cancer by regulating gut microbiota. This study aimed to elucidate whether the association between P. hominis infections and the increased incidence of colon cancer is related to changes in gut microbiota. Therefore, the gut microbiota patients with colon cancer who were infected with P. hominis and uninfected patients with colon cancer were analyzed by 16S rRNA high-throughput sequencing. The results demonstrated that patients with colon cancer who were not infected with P. hominis showed increased gut bacterial diversity, a higher relative abundance of Alcaligenes sp., Leucobacter sp., Paraprevotella sp., Ruminococcaceae UCG-002, and a significant reduction in the abundance of Veillonella sp., compared to individuals without colon cancer. Additionally, the relative abundance of the Ruminococcaceae UCG-002 and the Eubacterium eligens groups was reduced, while the relative abundance of bacteria associated with colon cancer, including Flavonifractor sp., Lachnoclostridium sp., and the Ruminococcus gnavus group, increased significantly in patients with colon cancer who were infected with P. hominis, compared to those of uninfected patients with colon cancer. In conclusion, these results suggested that P. hominis infections may aggravate the development of colon cancer and the findings provide new insights for subsequent in-depth studies on the pathogenesis, diagnosis, and prevention of colon cancer.
Collapse
Affiliation(s)
- Hongbo Zhang
- Key Laboratory of Zoonosis Research by Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Yanhui Yu
- Second Affiliated Hospital, Jilin University, Changchun, China
| | - Jianhua Li
- Key Laboratory of Zoonosis Research by Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Pengtao Gong
- Key Laboratory of Zoonosis Research by Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Xiaocen Wang
- Key Laboratory of Zoonosis Research by Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Xin Li
- Key Laboratory of Zoonosis Research by Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Yidan Cheng
- Key Laboratory of Zoonosis Research by Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Xiuyan Yu
- Clinical Laboratory, Jilin Cancer Hospital, Changchun, China
| | - Nan Zhang
- Key Laboratory of Zoonosis Research by Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, China
- *Correspondence: Nan Zhang, ; Xichen Zhang,
| | - Xichen Zhang
- Key Laboratory of Zoonosis Research by Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
- *Correspondence: Nan Zhang, ; Xichen Zhang,
| |
Collapse
|
|
22
|
Kim HS, Nam HW, Ahn HJ, Kim D, Kim YH. Relationship between Clonorchis sinensis Infection and Cholangiocarcinoma in Korea. THE KOREAN JOURNAL OF PARASITOLOGY 2022; 60:261-271. [PMID: 36041488 PMCID: PMC9441450 DOI: 10.3347/kjp.2022.60.4.261] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 07/28/2022] [Indexed: 12/02/2022]
Abstract
This study provides an overview of the current status of clonorchiasis and cholangiocarcinoma (CCA), and their relationship in Korea during 2012–2020. Data were obtained from the Health Insurance Review & Assessment Service of Korea. Cluster, trend, and correlation analyses were performed. Gyeongsangnam-do and Seoul had the highest average number of cases (1,026 and 4,208) and adjusted rate (306 and 424) for clonorchiasis and CCA, respectively. The most likely clusters (MLC) for clonorchiasis and CCA were Busan/Gyeongsangnam-do/Ulsan/Daegu/Gyeongsangbuk-do (Relative Risk; RR=4.55, Likelihood Ratio; LLR=9,131.115) joint cluster and Seoul (RR=2.29, LLR=7,602.472), respectively. The MLC for clonorchiasis was in the southeastern part of Korea, while that for CCA was in the southern part. Clonorchiasis showed a decreasing trend in the southeastern districts, while increased in the southwestern districts. Cities in the central region had a decreasing trend, while the western districts had an increasing trend. In most adults (30–59), infection rate of clonorchiasis showed a significant decrease until 2018, while thereafter increased, although not significant. CCA showed a sharply decreasing tendency. The incidence of clonorchiasis and CCA were positively correlated. In general, the correlation was weak (r=0.39, P<0.001), but it was strongly positive around the 4 river basins (r=0.74, P<0.001). This study might provide an analytic basis for developing an effective system against clonorchiasis and CCA.
Collapse
Affiliation(s)
- Hwa Sun Kim
- Department of Family Medicine, Veterans Health Service Medical Center, Seoul 05368, Korea
| | - Ho-Woo Nam
- Department of Parasitology, College of Medicine, Catholic University of Korea, Seoul 06591, Korea
| | - Hye-Jin Ahn
- Department of Parasitology, College of Medicine, Catholic University of Korea, Seoul 06591, Korea
| | - Dongjae Kim
- Department of Biomedicine Health Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
| | - Yeong Hoon Kim
- Department of Ophthalmology, College of Medicine, Catholic University of Korea, Seoul 06591, Korea
- Corresponding author ()
| |
Collapse
|
|
23
|
Current status of Clonorchis sinensis and clonorchiasis in Korea: epidemiological perspectives integrating the data from human and intermediate hosts. Parasitology 2022; 149:1296-1305. [PMID: 35698752 PMCID: PMC10090769 DOI: 10.1017/s0031182022000798] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Clonorchis sinensis is a carcinogenic liver fluke that causes clonorchiasis in humans. Clonorchiasis is prevalent in East Asian countries, and approximately 15–20 million individuals are estimated to be infected with this fluke globally. This review highlights the current status of C. sinensis and clonorchiasis in Korea from the epidemiological perspective involving the analysis of humans and intermediate hosts. Despite the recent decline in C. sinensis infection rate in Korea, C. sinensis infections remain endemic in 5 major river basins (Han-gang, Geum-gang, Seomjin-gang, Yeongsan-gang and Nakdong-gang; gang means river) with a high incidence of cholangiocarcinoma. A noticeable pattern involves increasing mild infections among patients diagnosed positive for C. sinensis eggs. The infection rate of C. sinensis metacercariae in the second intermediate host, freshwater fish, is also maintained at a substantial level. Thus, the One Health approach integrating different sectors and disciplines is recommended to accelerate and sustain control of C. sinensis, thereby leading to successful eradication. Health promotion via information dissemination and health education should be extended to prevent the consumption of raw freshwater fish by residents living in high-risk areas.
Collapse
|
|
24
|
DiMaio D, Emu B, Goodman AL, Mothes W, Justice A. Cancer Microbiology. J Natl Cancer Inst 2022; 114:651-663. [PMID: 34850062 PMCID: PMC9086797 DOI: 10.1093/jnci/djab212] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 08/18/2021] [Accepted: 11/15/2021] [Indexed: 12/12/2022] Open
Abstract
Microbes play important roles in cancer from direct carcinogenic effects to their use in treatment. Cancers caused by microorganisms account for approximately 15% of cancers, primarily in low- and middle-income countries. Unique features of infectious carcinogens include their transmissibility, mutability, and specific immune interactions, which provide challenges and opportunities for cancer prevention and treatment. For these agents, infection control through exposure reduction, antivirals, antibiotics, and vaccines is cancer control. In addition, developing evidence suggests that microorganisms including the human microbiome can indirectly modulate cancer formation and influence the effectiveness and toxicity of cancer treatments. Finally, microorganisms themselves can be used to prevent or treat cancer. The convergence of these factors signals the emergence of a new field, cancer microbiology. Recognition of cancer microbiology will spur research, stimulate cross-disciplinary training, inform drug development, and improve public health.
Collapse
Affiliation(s)
- Daniel DiMaio
- Department of Genetics, Yale School of Medicine, New Haven, CT, USA
- Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT, USA
- Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT, USA
- Yale Cancer Center, New Haven, CT, USA
| | - Brinda Emu
- Yale Cancer Center, New Haven, CT, USA
- Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT, USA
| | - Andrew L Goodman
- Yale Cancer Center, New Haven, CT, USA
- Department of Microbial Pathogenesis, Yale University, New Haven, CT, USA
| | - Walther Mothes
- Yale Cancer Center, New Haven, CT, USA
- Department of Microbial Pathogenesis, Yale University, New Haven, CT, USA
| | - Amy Justice
- Yale Cancer Center, New Haven, CT, USA
- Department of General Medicine, Yale University, VA Medical Center, New Haven, CT, USA
| |
Collapse
|
|
25
|
Fragkou N, Sideras L, Panas P, Emmanouilides C, Sinakos E. Update on the association of hepatitis B with intrahepatic cholangiocarcinoma: Is there new evidence? World J Gastroenterol 2021; 27:4252-4275. [PMID: 34366604 PMCID: PMC8316913 DOI: 10.3748/wjg.v27.i27.4252] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 04/12/2021] [Accepted: 06/18/2021] [Indexed: 02/06/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is a subgroup of cholangiocarcinoma that accounts for about 10%-20% of the total cases. Infection with hepatitis B virus (HBV) is one of the most important predisposing factors leading to the formation of iCCA. It has been recently estimated based on abundant epidemiological data that the association between HBV infection and iCCA is strong with an odds ratio of about 4.5. The HBV-associated mechanisms that lead to iCCA are under intense investigation. The diagnosis of iCCA in the context of chronic liver disease is challenging and often requires histological confirmation to distinguish from hepatocellular carcinoma. It is currently unclear whether antiviral treatment for HBV can decrease the incidence of iCCA. In terms of management, surgical resection remains the mainstay of treatment. There is a need for effective treatment modalities beyond resection in both first- and second-line treatment. In this review, we summarize the epidemiological evidence that links the two entities, discuss the pathogenesis of HBV-associated iCCA, and present the available data on the diagnosis and management of this cancer.
Collapse
Affiliation(s)
- Nikolaos Fragkou
- Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Lazaros Sideras
- Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Panteleimon Panas
- Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | | | - Emmanouil Sinakos
- Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| |
Collapse
|
|
26
|
Li M, Du M, Cong H, Gu Y, Fang Y, Li J, Gan Y, Tu H, Gu J, Xia Q. Characterization of hepatitis B virus DNA integration patterns in intrahepatic cholangiocarcinoma. Hepatol Res 2021; 51:102-115. [PMID: 33037855 DOI: 10.1111/hepr.13580] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 09/19/2020] [Accepted: 09/24/2020] [Indexed: 12/13/2022]
Abstract
AIM Hepatitis B virus (HBV) integration is one of the mechanisms contributing to hepatocellular carcinoma (HCC) development. However, the status of HBV integration in intrahepatic cholangiocarcinoma (ICC) is poorly understood. This study aims to characterize the viral integration in HBV-related ICC. METHODS The presence of HBV S and C gene in ICCs and the paratumor tissue was determined by polymerase chain reaction direct sequencing. Hepatitis B virus integration was detected by a high-throughput capture sequencing method. The expression analysis of the genes targeted by HBV in ICC was undertaken in The Cancer Genome Atlas dataset. RESULTS Hepatitis B virus S and/or C gene fragments were detected in 71.43% (10/14) ICCs and 57.14% (8/14) paratumor tissues. Using the high-throughput capture sequencing approach, 139 and 183 HBV integration breakpoints were identified from seven ICC and seven paired paratumor tissues, respectively. Seven genes (TERT, CEACAM20, SPATA18, TRERF1, ZNF23, LINC01449, and LINC00486) were recurrently targeted by HBV-DNA in different ICC tissues or different cell populations of the same tissue. TERT, which is the most preferential HBV target gene in HCC, was found to be repeatedly interrupted by HBV-DNA in three different ICC tissues. Based on The Cancer Genome Atlas dataset, TERT, as well as three other HBV recurrently targeted genes (SPATA18, TRERF1, and ZNF23), showed differential expression levels between ICC and para-ICC tissues. CONCLUSIONS Taken together, HBV integration is a common event in HBV-related ICC. The HBV recurrent integration genes identified from this study, such as TERT, provide new clues for further research on the causative link between HBV infection and ICC.
Collapse
Affiliation(s)
- Mengge Li
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Min Du
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hui Cong
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuanyuan Gu
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Department of Emergency, Nanjing First Hospital, Nanjing, China
| | - Yuan Fang
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Organ Transplantation Center, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Jin Li
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yu Gan
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hong Tu
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jinyang Gu
- Department of Transplantation, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qiang Xia
- Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| |
Collapse
|
|
27
|
Jacobs BA, Prince S, Smith KA. Gastrointestinal Nematode-Derived Antigens Alter Colorectal Cancer Cell Proliferation and Migration through Regulation of Cell Cycle and Epithelial-Mesenchymal Transition Proteins. Int J Mol Sci 2020; 21:ijms21217845. [PMID: 33105843 PMCID: PMC7660063 DOI: 10.3390/ijms21217845] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 10/15/2020] [Accepted: 10/19/2020] [Indexed: 12/02/2022] Open
Abstract
As the global incidences of colorectal cancer rises, there is a growing importance in understanding the interaction between external factors, such as common infections, on the initiation and progression of this disease. While certain helminth infections have been shown to alter the severity and risk of developing colitis-associated colorectal cancer, whether these parasites can directly affect colorectal cancer progression is unknown. Here, we made use of murine and human colorectal cancer cell lines to demonstrate that exposure to antigens derived from the gastrointestinal nematode Heligmosomoides polygyrus significantly reduced colorectal cancer cell proliferation in vitro. Using a range of approaches, we demonstrate that antigen-dependent reductions in cancer cell proliferation and viability are associated with increased expression of the critical cell cycle regulators p53 and p21. Interestingly, H. polygyrus-derived antigens significantly increased murine colorectal cancer cell migration, which was associated with an increased expression of the adherens junction protein β-catenin, whereas the opposite was true for human colorectal cancer cells. Together, these findings demonstrate that antigens derived from a gastrointestinal nematode can significantly alter colorectal cancer cell behavior. Further in-depth analysis may reveal novel candidates for targeting and treating late-stage cancer.
Collapse
Affiliation(s)
- Brittany-Amber Jacobs
- Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town 7925, South Africa;
| | - Sharon Prince
- Department of Human Biology, University of Cape Town, Cape Town 7925, South Africa;
| | - Katherine Ann Smith
- Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town 7925, South Africa;
- School of Medicine, Cardiff University, Cardiff CF14 3XN, UK
- Correspondence: ; Tel.: +44-2920-874-303
| |
Collapse
|
|
28
|
Shi Y, Yu K, Liang A, Huang Y, Ou F, Wei H, Wan X, Yang Y, Zhang W, Jiang Z. Identification and Analysis of the Tegument Protein and Excretory-Secretory Products of the Carcinogenic Liver Fluke Clonorchis sinensis. Front Microbiol 2020; 11:555730. [PMID: 33072014 PMCID: PMC7538622 DOI: 10.3389/fmicb.2020.555730] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Accepted: 08/26/2020] [Indexed: 12/14/2022] Open
Abstract
Liver fluke proteins, including excretory-secretory products (ESPs) and tegument proteins, are critical for the pathogenesis, nutrient metabolism, etiology and immune response of liver cancer. To understand the functions of various proteins in Clonorchis sinensis physiology and human clonorchiasis, the ESPs and tegument proteins of C. sinensis were identified. Supernatants containing ESPs from adult C. sinensis after culture for 6 h were harvested and concentrated. The tegument was detached using a freeze/thaw method and successively extracted using various extraction buffers. The outer surface proteins of C. sinensis were labeled with biotin, and the biotinylated proteins were purified. The ESP, tegument and labeled outer surface proteins were identified and analyzed by high-resolution LC-MS/MS. The identified proteins were compared with those of other flukes, and the protein functions associated with pathogenesis, carcinogenesis and potential vaccine antigens and drug targets were predicted and analyzed. A total of 175 proteins were identified after the 6-h culture of C. sinensis ESPs. A total of 352 tegument proteins were identified through sequential solubilization of the isolated teguments, and a subset of these proteins were localized to the surface membrane of the tegument by labeling with biotin. Thirty identified proteins, including annexins, actin and tetraspanins, were identified as potential immunomodulators and promising vaccine antigens. Interestingly, among the 352 tegument proteins, as many as 155 were enzymes, and most were oxidoreductases, hydrolases or transferases. A comparison of the outer surface proteins of C. sinensis with those of other flukes indicated that flukes have some common outer surface proteins, such as actin, tetraspanin, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and annexin. Granulin, thioredoxin peroxiredoxin, carbonyl reductase 1 and cystatin were identified in the C. sinensis proteome and predicted to be related to liver disease and cancer. The analysis of the C. sinensis proteome could contribute to a more in-depth understanding of complex parasite-host relationships, improve the diagnosis of clonorchiasis and benefit research on the pathogenesis and development of novel interventions, drugs and vaccines to control C. sinensis infection.
Collapse
Affiliation(s)
- Yunliang Shi
- Institute of Parasitic Disease Control and Prevention, Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning, China.,Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning, China
| | - Kai Yu
- College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Anli Liang
- Xiangsihu College of Guangxi University for Nationalities, Nanning, China
| | - Yan Huang
- Institute of Parasitic Disease Control and Prevention, Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning, China
| | - Fangqi Ou
- Institute of Parasitic Disease Control and Prevention, Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning, China
| | - Haiyan Wei
- Institute of Parasitic Disease Control and Prevention, Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning, China
| | - Xiaoling Wan
- Institute of Parasitic Disease Control and Prevention, Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning, China
| | - Yichao Yang
- Institute of Parasitic Disease Control and Prevention, Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning, China
| | - Weiyu Zhang
- College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Zhihua Jiang
- Institute of Parasitic Disease Control and Prevention, Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning, China
| |
Collapse
|
|
29
|
Florio AA, Ferlay J, Znaor A, Ruggieri D, Alvarez CS, Laversanne M, Bray F, McGlynn KA, Petrick JL. Global trends in intrahepatic and extrahepatic cholangiocarcinoma incidence from 1993 to 2012. Cancer 2020; 126:2666-2678. [PMID: 32129902 PMCID: PMC7323858 DOI: 10.1002/cncr.32803] [Citation(s) in RCA: 186] [Impact Index Per Article: 37.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2019] [Revised: 01/13/2020] [Accepted: 01/31/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Intrahepatic cholangiocarcinomas (ICCs) and extrahepatic cholangiocarcinomas (ECCs) are highly lethal bile duct tumors. Their incidence can be difficult to estimate because of changes in cancer coding over time. No studies to date have examined their global incidence and trends with high-quality topography- and histology-specific cancer registry data. Therefore, this study examined ICC and ECC incidence with the Cancer Incidence in Five Continents Plus database. METHODS Regional and national cancer registry data were used to estimate age-standardized incidence rates (ASRs) per 100,000 person-years, 95% confidence intervals, and average annual percent changes (AAPCs) for ICC in 38 countries and for ECC in 33 countries from 1993 to 2012. ICC and ECC trends were tabulated and plotted by country. Rates versus birth cohort by age were plotted, and an age-period-cohort analysis was performed to assess age and cohort incidence rate ratios. RESULTS The highest rates of ICC and ECC were in Asia, specifically South Korea (ASR for ICC, 2.80; ASR for ECC, 2.24), Thailand (ASR for ICC, 2.19; ASR for ECC, 0.71), and Japan (ASR for ICC, 0.95; ASR for ECC, 0.83). Between 1993 and 2012, incidence rates of both ICC and ECC increased in most countries. The largest ASR increases over the study period occurred in Latvia (AAPC, 20.1%) and China (AAPC, 11.1%) for ICC and in Thailand (AAPC, 8.8%) and Colombia (AAPC, 8.5%) for ECC. CONCLUSIONS In the 20 years examined, ICC and ECC incidence increased in the majority of countries worldwide. ICC and ECC incidence may continue to increase because of metabolic and infectious etiologic factors. Efforts to further elucidate risk factors contributing to these increases in incidence are warranted.
Collapse
Affiliation(s)
- Andrea A. Florio
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Jacques Ferlay
- Cancer Surveillance Section, International Agency for Research on Cancer, Lyon, France
| | - Ariana Znaor
- Cancer Surveillance Section, International Agency for Research on Cancer, Lyon, France
| | - David Ruggieri
- Information Management Services, Inc., Rockville, MD, USA
| | - Christian S. Alvarez
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Mathieu Laversanne
- Cancer Surveillance Section, International Agency for Research on Cancer, Lyon, France
| | - Freddie Bray
- Cancer Surveillance Section, International Agency for Research on Cancer, Lyon, France
| | - Katherine A. McGlynn
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Jessica L. Petrick
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
- Slone Epidemiology Center, Boston University, Boston, MA, USA
| |
Collapse
|
|
30
|
Sadaow L, Sanpool O, Rodpai R, Yamasaki H, Ittiprasert W, Mann VH, Brindley PJ, Maleewong W, Intapan PM. Development of an Immunochromatographic Point-of-Care Test for Serodiagnosis of Opisthorchiasis and Clonorchiasis. Am J Trop Med Hyg 2020; 101:1156-1160. [PMID: 31482789 DOI: 10.4269/ajtmh.19-0446] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
Chronic infections with the food-borne liver flukes, Opisthorchis viverrini or Clonorchis sinensis, associate with cholangiocarcinoma, bile duct cancer, which generally has a poor prognosis. We have produced a rapid and simple immunochromatographic test (ICT) kit for the diagnosis of opisthorchiasis and clonorchiasis by the detection of IgG antibodies in human infection sera. Sera from volunteers with proven opisthorchiasis and several other parasitic diseases and from healthy controls were evaluated for the presence of liver fluke infection-specific antibodies using a preparation of excretory-secretory antigen from adult stage O. viverrini absorbed onto ICT strips. Diagnostic values were compared with an ELISA. The diagnostic sensitivity, specificity, and positive and negative predictive values of the ELISA were 100%, 98.3%, 97.9%, and 100%, whereas those for the ICT were 94.6%, 91.2%, 89.7%, and 95.4%, respectively. There was 91.7% concordance between the ICT with ELISA, and differences in performance between the tests were not statistically significant (P > 0.05). Twenty-seven of 30 (90%) of the clonorchiasis sera also were positive by ICT. This new ICT provides a facile, rapid test for point-of-care testing tool, which can be used at the bedside without the need for sophisticated equipment. Moreover, the ICT can be anticipated to supplement stool examination as a screening tool in the clinic for the diagnosis of opisthorchiasis and clonorchiasis, and in addition, it may be useful in screens of populations at risk of liver fluke infection-associated cholangiocarcinoma.
Collapse
Affiliation(s)
- Lakkhana Sadaow
- Department of Parasitology, Faculty of Medicine and Research and Diagnostic Center for Emerging Infectious Diseases, Mekong Health Science Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Oranuch Sanpool
- Department of Parasitology, Faculty of Medicine and Research and Diagnostic Center for Emerging Infectious Diseases, Mekong Health Science Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Rutchanee Rodpai
- Department of Parasitology, Faculty of Medicine and Research and Diagnostic Center for Emerging Infectious Diseases, Mekong Health Science Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Hiroshi Yamasaki
- Department of Parasitology, National Institute of Infectious Diseases, Ministry of Health, Labour and Welfare, Tokyo, Japan
| | - Wannaporn Ittiprasert
- Department of Microbiology, Immunology and Tropical Medicine, Research Center for Neglected Diseases of Poverty, School of Medicine and Health Science, George Washington University, Washington, District of Columbia
| | - Victoria H Mann
- Department of Microbiology, Immunology and Tropical Medicine, Research Center for Neglected Diseases of Poverty, School of Medicine and Health Science, George Washington University, Washington, District of Columbia
| | - Paul J Brindley
- Department of Microbiology, Immunology and Tropical Medicine, Research Center for Neglected Diseases of Poverty, School of Medicine and Health Science, George Washington University, Washington, District of Columbia
| | - Wanchai Maleewong
- Department of Parasitology, Faculty of Medicine and Research and Diagnostic Center for Emerging Infectious Diseases, Mekong Health Science Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Pewpan M Intapan
- Department of Parasitology, Faculty of Medicine and Research and Diagnostic Center for Emerging Infectious Diseases, Mekong Health Science Research Institute, Khon Kaen University, Khon Kaen, Thailand
| |
Collapse
|
|
31
|
Zhu TJ, Chen YD, Qian MB, Zhu HH, Huang JL, Zhou CH, Zhou XN. Surveillance of clonorchiasis in China in 2016. Acta Trop 2020; 203:105320. [PMID: 31877282 DOI: 10.1016/j.actatropica.2019.105320] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Revised: 12/20/2019] [Accepted: 12/21/2019] [Indexed: 01/31/2023]
Abstract
Clonorchiasis is an important food-borne parasitic disease in China, and infection with C. sinensis can cause hepatobiliary diseases. Comprehensive and systematic prevention and control of clonorchiasis requires the establishment of an effective surveillance. A total of 301 surveillance points were set up in 30 provinces across China in 2016, and 1000 people were selected by cluster sampling at each surveillance point annually for C. sinensis infection screening using Kato-Katz thick smear method. C. sinensis infection was detected in 6226 people following screening of 305081 people at the 301 surveillance points in 2016. Infection rate was 2.04%; with C. sinensis infection detected in 70 counties spread across 15 provinces, 89.37% of the infected people were distributed in Jilin, Heilongjiang, Guangdong and Guangxi provinces. Highest infection rate was observed in Da'an city, Jilin Province (49%). The national infection rate in male and female was 2.70% and 1.40% respectively. Infection rate between male and female was significantly different (P <0.01). Disease prevalence increases with age in both male and female, reaches peak in age group 40-49. Result obtained indicate that major C. sinensis endemic areas are distributed in the north and south of China, and areas with high prevalence are distributed along the river system at county level. Result, also, shows that middle-aged men are at high-risk of infection. These results suggest that surveillance activities should be sustained nationwide and highlight the need for an integrated approach to control C. sinensis transmission in regions with high disease prevalence in China.
Collapse
Affiliation(s)
- Ting-Jun Zhu
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, No.207 Ruijin Road, Huangpu District, Shanghai 200025, China
| | - Ying-Dan Chen
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, No.207 Ruijin Road, Huangpu District, Shanghai 200025, China
| | - Men-Bao Qian
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, No.207 Ruijin Road, Huangpu District, Shanghai 200025, China
| | - Hui-Hui Zhu
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, No.207 Ruijin Road, Huangpu District, Shanghai 200025, China
| | - Ji-Lei Huang
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, No.207 Ruijin Road, Huangpu District, Shanghai 200025, China
| | - Chang-Hai Zhou
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, No.207 Ruijin Road, Huangpu District, Shanghai 200025, China.
| | - Xiao-Nong Zhou
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, No.207 Ruijin Road, Huangpu District, Shanghai 200025, China.
| |
Collapse
|
|
32
|
Betson M, Alonte AJI, Ancog RC, Aquino AMO, Belizario VY, Bordado AMD, Clark J, Corales MCG, Dacuma MG, Divina BP, Dixon MA, Gourley SA, Jimenez JRD, Jones BP, Manalo SMP, Prada JM, van Vliet AHM, Whatley KCL, Paller VGV. Zoonotic transmission of intestinal helminths in southeast Asia: Implications for control and elimination. ADVANCES IN PARASITOLOGY 2020; 108:47-131. [PMID: 32291086 DOI: 10.1016/bs.apar.2020.01.036] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Intestinal helminths are extremely widespread and highly prevalent infections of humans, particularly in rural and poor urban areas of low and middle-income countries. These parasites have chronic and often insidious effects on human health and child development including abdominal problems, anaemia, stunting and wasting. Certain animals play a fundamental role in the transmission of many intestinal helminths to humans. However, the contribution of zoonotic transmission to the overall burden of human intestinal helminth infection and the relative importance of different animal reservoirs remains incomplete. Moreover, control programmes and transmission models for intestinal helminths often do not consider the role of zoonotic reservoirs of infection. Such reservoirs will become increasingly important as control is scaled up and there is a move towards interruption and even elimination of parasite transmission. With a focus on southeast Asia, and the Philippines in particular, this review summarises the major zoonotic intestinal helminths, risk factors for infection and highlights knowledge gaps related to their epidemiology and transmission. Various methodologies are discussed, including parasite genomics, mathematical modelling and socio-economic analysis, that could be employed to improve understanding of intestinal helminth spread, reservoir attribution and the burden associated with infection, as well as assess effectiveness of interventions. For sustainable control and ultimately elimination of intestinal helminths, there is a need to move beyond scheduled mass deworming and to consider animal and environmental reservoirs. A One Health approach to control of intestinal helminths is proposed, integrating interventions targeting humans, animals and the environment, including improved access to water, hygiene and sanitation. This will require coordination and collaboration across different sectors to achieve best health outcomes for all.
Collapse
Affiliation(s)
- Martha Betson
- University of Surrey, Guildford, Surrey, United Kingdom.
| | | | - Rico C Ancog
- University of the Philippines Los Baños, Laguna, Philippines
| | | | | | | | - Jessica Clark
- University of Surrey, Guildford, Surrey, United Kingdom
| | | | | | - Billy P Divina
- University of the Philippines Los Baños, Laguna, Philippines
| | | | | | | | - Ben P Jones
- University of Surrey, Guildford, Surrey, United Kingdom
| | | | | | | | | | | |
Collapse
|
|
33
|
Masarone M, Persico M. Hepatitis C virus infection and non-hepatocellular malignancies in the DAA era: A systematic review and meta-analysis. Liver Int 2019; 39:1292-1306. [PMID: 30983083 DOI: 10.1111/liv.14119] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Revised: 03/12/2019] [Accepted: 04/05/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Direct antiviral agents have greatly improved therapeutic options for chronic hepatitis C. Indeed, former "difficult-to-treat" patients can now be treated and can achieve sustained response. Hepatitis C virus (HCV) is associated with hepatocellular carcinoma and with B-cell non-Hodgkin lymphoma (B-NHL). Other malignancies have been reported to be associated with HCV infection albeit with various grades of evidence. Antineoplastic treatment is often reduced or suspended in HCV-positive cancer patients to avoid "HCV reactivation." In this setting, antiviral therapy combined with antineoplastic protocols may improve the outcome. For this reason, we conducted a systematic review and a meta-analysis to update the association between HCV infection and non-hepatocellular malignancies, and to shed light on the effects exerted by antiviral treatment on the natural history of oncological diseases. METHODS Relevant studies were identified by searching PUBMED, EMBASE and MEDLINE up to 1 August 2018. Pooled risk estimates were calculated with random-effects models according to PRISMA guidelines. RESULTS A total of 58 studies were included in the analysis: 27 studies of the association between HCV and B-NHL(OR 3.36; 95% CI 2.40-4.72;P < 0.00001);13 studies of the association between sustained virological response and progression-free survival (PFS) in B-NHL patients(OR 9.34; 95% CI 4.90-17.79; P < 0.00001); 13 studies of the association between HCV and intrahepatic-cholangio-carcinoma (OR 3.95;95% CI 2.25-6.94; P < 0.00001); and 5 studies of the association between HCV infection and pancreatic adeno-carcinoma(OR 1.60; 95% CI:1.25-2.04; P = 0.0002). CONCLUSIONS This study updates the strong association between B-NHL and HCV infection, confirms the association between HCV and non-hepatocellular tumours, and demonstrates a very strong association between viral eradication and a better outcome of HCV-positive B-NHL.
Collapse
Affiliation(s)
- Mario Masarone
- Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
| | - Marcello Persico
- Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
| |
Collapse
|
|
34
|
Navas MC, Glaser S, Dhruv H, Celinski S, Alpini G, Meng F. Hepatitis C Virus Infection and Cholangiocarcinoma: An Insight into Epidemiologic Evidences and Hypothetical Mechanisms of Oncogenesis. THE AMERICAN JOURNAL OF PATHOLOGY 2019; 189:1122-1132. [PMID: 30953604 DOI: 10.1016/j.ajpath.2019.01.018] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Revised: 12/14/2018] [Accepted: 01/08/2019] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) infection is a global public health problem because it is a main cause of liver cirrhosis and hepatocellular carcinoma. This human oncogenic virus is also associated with the development of non-Hodgkin lymphoma and cholangiocarcinoma (CCA). The association between HCV infection and CCA has been examined in a number of epidemiologic studies. However, in vivo and in vitro results demonstrating the oncogenic mechanisms of HCV in CCA development and progression are insufficient. Here, we review the epidemiologic association of HCV and CCA and recent publications of studies of HCV infection of cholangiocytes and CCA cell lines as well as studies of viral infection performed with liver samples obtained from patients. In addition, we also discuss the preliminary results of in vitro assays of HCV protein expression in CCA cell lines. Finally, we discuss the hypothetical role of HCV infection in CCA development by induction of epithelial-mesenchymal transition and up-regulation of hedgehog signaling, and consequently biliary tree inflammation and liver fibrosis. Further studies are required to demonstrate these hypotheses and therefore to elucidate the mechanisms of HCV as a risk factor for CCA.
Collapse
Affiliation(s)
- Maria-Cristina Navas
- Grupo Gastrohepatologia, School of Medicine, University of Antioquia, Medellin, Colombia; Department of Medical Physiology, Texas A&M University College of Medicine, Temple, Texas.
| | - Shannon Glaser
- Department of Medical Physiology, Texas A&M University College of Medicine, Temple, Texas; Baylor Scott & White Digestive Disease Research Center, Baylor Scott & White Health, Temple, Texas; Division of Research, Central Texas Veterans Health Care System, Temple, Texas
| | - Harshil Dhruv
- Translational Genomics Research Institute, Phoenix, Arizona
| | - Scott Celinski
- Department of Surgery, Baylor University Medical Center, Dallas, Texas
| | - Gianfranco Alpini
- Department of Medical Physiology, Texas A&M University College of Medicine, Temple, Texas; Baylor Scott & White Digestive Disease Research Center, Baylor Scott & White Health, Temple, Texas; Division of Research, Central Texas Veterans Health Care System, Temple, Texas
| | - Fanyin Meng
- Baylor Scott & White Digestive Disease Research Center, Baylor Scott & White Health, Temple, Texas; Division of Research, Central Texas Veterans Health Care System, Temple, Texas.
| |
Collapse
|
|
35
|
Xu M, Jiang Z, Huang W, Yin J, Ou S, Jiang Y, Meng L, Cao S, Yu A, Cao J, Shen Y. Altered Gut Microbiota Composition in Subjects Infected With Clonorchis sinensis. Front Microbiol 2018; 9:2292. [PMID: 30323795 PMCID: PMC6172334 DOI: 10.3389/fmicb.2018.02292] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2018] [Accepted: 09/07/2018] [Indexed: 12/29/2022] Open
Abstract
Clonorchiasis is an infectious disease caused by helminths of Clonorchis sinensis (C. sinensis). The adult parasite mainly inhabits the bile duct and gall bladder, and results in various complications to the hepatobiliary system. The amount of bile secreted into the intestine is reduced in cases of C. sinensis infection, which may alter the pH of the gut and decrease the amount of surfactant protein D released from the gallbladder. However, the impact of parasitic infection on the human gut microbiome remains unclear. To this end, we examined the gut microbiota composition in 47 modified Kato–Katz thick smear-positive (egg-positive) volunteers and 42 healthy controls from five rural communities. Subjects were grouped into four sub-populations based on age and infection status. High-throughput 16S rRNA gene sequencing revealed significant changes in alpha diversity between EP1 and EN1. The beta diversity showed alterations between C. sinensis-infected subjects and healthy controls. In C. sinensis infected patients, we found the significant reduction of certain taxa, such as Bacteroides and anti-inflammatory Bifidobacterium (P < 0.05). Bacteroides, a predominant gut bacteria in healthy populations, was negatively correlated with the number of C. sinensis eggs per gram (EPG, r = −0.37, P adjust < 0.01 in 20–60 years old group; r = −0.64, P adjust = 0.04 in the 60+ years old group). What’s more, the reduction in the abundance of Bifidobacterium, a common probiotic, was decreased particularly in the 60 + years old group (r = −0.50, P = 0.04). The abundance of Dorea, a potentially pro-inflammatory microbe, was higher in infected subjects than in healthy individuals (P < 0.05). Variovorax was a unique bacteria that was only detected in infected subjects. These results clearly demonstrate the significant influence of C. sinensis infection on the human gut microbiota and provided new insights into the control, prevention, diagnosis, and clinical study of clonorchiasis through the human gut microbiota.
Collapse
Affiliation(s)
- Meng Xu
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China.,Chinese Center for Tropical Diseases Research, Shanghai, China.,World Health Organization Collaborating Centre for Tropical Diseases, Shanghai, China.,National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Shanghai, China.,Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, China
| | - Zhihua Jiang
- Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning, China
| | - Wen Huang
- Tengxian Center for Disease Control and Prevention, Tengxian, China
| | - Jianhai Yin
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China.,Chinese Center for Tropical Diseases Research, Shanghai, China.,World Health Organization Collaborating Centre for Tropical Diseases, Shanghai, China.,National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Shanghai, China.,Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, China
| | - Shen Ou
- Tengxian Center for Disease Control and Prevention, Tengxian, China
| | - Yanyan Jiang
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China.,Chinese Center for Tropical Diseases Research, Shanghai, China.,World Health Organization Collaborating Centre for Tropical Diseases, Shanghai, China.,National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Shanghai, China.,Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, China
| | - Liyu Meng
- Tengxian Center for Disease Control and Prevention, Tengxian, China
| | - Shengkui Cao
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China.,Chinese Center for Tropical Diseases Research, Shanghai, China.,World Health Organization Collaborating Centre for Tropical Diseases, Shanghai, China.,National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Shanghai, China.,Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, China
| | - Aiping Yu
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China.,Chinese Center for Tropical Diseases Research, Shanghai, China.,World Health Organization Collaborating Centre for Tropical Diseases, Shanghai, China.,National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Shanghai, China.,Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, China
| | - Jianping Cao
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China.,Chinese Center for Tropical Diseases Research, Shanghai, China.,World Health Organization Collaborating Centre for Tropical Diseases, Shanghai, China.,National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Shanghai, China.,Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, China
| | - Yujuan Shen
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China.,Chinese Center for Tropical Diseases Research, Shanghai, China.,World Health Organization Collaborating Centre for Tropical Diseases, Shanghai, China.,National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Shanghai, China.,Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, China
| |
Collapse
|
|
36
|
Lee MR, Yoo WG, Kim YJ, Chung EJ, Cho SH, Ju JW. Venom allergen-like protein 28 in Clonorchis sinensis: four epitopes on its surface and the potential role of Cys124 for its conformational stability. Parasitol Res 2018; 117:2521-2530. [PMID: 29876859 DOI: 10.1007/s00436-018-5941-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Accepted: 05/23/2018] [Indexed: 11/26/2022]
Abstract
Venom allergen-like (VAL) proteins are important to host-parasite interactions. We previously demonstrated that a Clonorchis sinensis VAL (CsVAL) protein-derived synthetic peptide suppresses allergic and inflammatory responses. However, little is known regarding the physicochemical and antigenic properties of CsVAL proteins. Here, we identified a novel 194 amino acid VAL protein, named C. sinensis VAL 28 (CsVAL28), and characterized its functional motifs and structural details as a new member of the CAP superfamily. Unlike members of the Schistosoma mansoni VAL (SmVAL) family, CsVAL28 has a single CAP1 motif and six highly conserved disulfide bond-forming cysteines. Tertiary models of wild-type CsVAL28 and mutants were built using SmVAL4 as template via homology modeling. Normal mode analysis predicted that disulfide bond breaking by mutation of cysteine 124 to serine would greatly affect protein mobility. Four major immunoreactive linear epitopes were identified in the surface-exposed region or its vicinity via epitope mapping, using sera from clonorchiasis patients and healthy controls. Our findings provide in-depth knowledge on the structure-function properties of VAL proteins and may help determine highly antigenic regions for developing new diagnostic approaches.
Collapse
Affiliation(s)
- Myoung-Ro Lee
- Division of Vectors and Parasitic Diseases, Center for Laboratory control of Infectious Diseases, Korea Centers for Disease Control and Prevention, Chungbuk, 28159, Republic of Korea
| | - Won Gi Yoo
- Division of Vectors and Parasitic Diseases, Center for Laboratory control of Infectious Diseases, Korea Centers for Disease Control and Prevention, Chungbuk, 28159, Republic of Korea
- Department of Medical Environmental Biology, Chung-Ang University College of Medicine, Seoul, 06974, Republic of Korea
| | - Yu Jung Kim
- Division of Vectors and Parasitic Diseases, Center for Laboratory control of Infectious Diseases, Korea Centers for Disease Control and Prevention, Chungbuk, 28159, Republic of Korea
| | - Eun Ju Chung
- Division of Vectors and Parasitic Diseases, Center for Laboratory control of Infectious Diseases, Korea Centers for Disease Control and Prevention, Chungbuk, 28159, Republic of Korea
| | - Shin-Hyeong Cho
- Division of Vectors and Parasitic Diseases, Center for Laboratory control of Infectious Diseases, Korea Centers for Disease Control and Prevention, Chungbuk, 28159, Republic of Korea
| | - Jung-Won Ju
- Division of Vectors and Parasitic Diseases, Center for Laboratory control of Infectious Diseases, Korea Centers for Disease Control and Prevention, Chungbuk, 28159, Republic of Korea.
| |
Collapse
|
|
37
|
Hoyos S, Navas MC, Restrepo JC, Botero RC. Current controversies in cholangiocarcinoma. Biochim Biophys Acta Mol Basis Dis 2018; 1864:1461-1467. [PMID: 28756216 DOI: 10.1016/j.bbadis.2017.07.027] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Revised: 07/20/2017] [Accepted: 07/24/2017] [Indexed: 12/13/2022]
Abstract
Cholangiocarcinoma represents 10% of primary liver malignancies and accounts for less than 3% of all gastrointestinal malignant tumors, with an enormous geographical variation. This neoplasia can arise from the biliary tract epithelium or hepatic progenitor cells. Depending on the anatomic localization, it is classified into three subtypes: intrahepatic, perihilar and distal. This fact is one of the main difficulties, because there are many studies that indistinctly include the results in the management of these different types of cholangiocarcinoma, without differentiating its location and even including gallbladder cancer. There are many controversial points in epidemiology, liver transplantation as a treatment, limitations of different results by group and type of treatment, histological testing and chemotherapy. This is a narrative review about topics in cholangiocarcinoma. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.
Collapse
Affiliation(s)
- Sergio Hoyos
- Hepatobiliary and Liver Transplant Program, Hospital Pablo Tobon Uribe-Universidad de Antioquia, Medellín, Colombia; Grupo Gastrohepatologia, Facultad de Medicina, Universidad of Antioquía UdeA, Calle 70 No. 52-21, Medellin, Colombia; Epidemiology, University CES, Medellin, Colombia.
| | - Maria-Cristina Navas
- Grupo Gastrohepatologia, Facultad de Medicina, Universidad of Antioquía UdeA, Calle 70 No. 52-21, Medellin, Colombia
| | - Juan-Carlos Restrepo
- Hepatobiliary and Liver Transplant Program, Hospital Pablo Tobon Uribe-Universidad de Antioquia, Medellín, Colombia; Grupo Gastrohepatologia, Facultad de Medicina, Universidad of Antioquía UdeA, Calle 70 No. 52-21, Medellin, Colombia
| | | |
Collapse
|
|
38
|
Recombinant adenylate kinase 3 from liver fluke Clonorchis sinensis for histochemical analysis and serodiagnosis of clonorchiasis. Parasitology 2018; 145:1531-1539. [PMID: 29580315 DOI: 10.1017/s0031182018000434] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Due to the lack of an effective prophylactic intervention and diagnosis, human liver fluke Clonorchis sinensis continues to afflict a large human population, causing a chronic inflammatory bile duct disease. With an aim to identify target antigens for sensitive serodiagnosis, adenylate kinase 3 of C. sinensis (CsAK3) was successfully expressed in soluble form in Escherichia coli by fusion to an RNA-interacting domain derived from human Lys-tRNA synthetase and purified by Ni2+-affinity chromatography. Anti-CsAK3 serum was raised by immunization of mice, and Western blotting confirmed that CsAK3 was expressed in adult-stage C. sinensis. Histochemical analysis showed that CsAK3 was localized to the subtegumental tissue of C. sinensis and was excreted into the bile duct of the host. When tested against sera from various parasite-infected patients by enzyme-linked immunosorbent assay, the recombinant CsAK3 elicited a specific response to C. sinensis-infected sera. The results suggest that CsAK3, either alone or in combination with other antigens, could be used for improving the clinical diagnosis of clonorchiasis.
Collapse
|
|
39
|
Nguyen HM, Tatonova YV, Madsen H. Infections by Hepatic Trematodes in Cats from Slaughterhouses in Vietnam. J Parasitol 2018; 104:306-309. [PMID: 29466091 DOI: 10.1645/18-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Domestic cats are a final host for some hepatic trematodes, and cat meat is used for human consumption in several parts of northern Vietnam. Since there is no tradition for commercial cat rearing in the area, cats are purchased alive from other areas as well, i.e., southern Vietnam and neighboring countries, and brought to slaughterhouses. This uncontrolled trade in live cats could pose a risk for spread of various parasites, including hepatic trematodes. Hence, in this study, we investigated the infections by hepatic trematodes in cats from the slaughterhouses. Cat livers were sampled from 12 slaughterhouses. Clonorchis sinensis and Platynosomum fastosum were found in 14 of 78 necropsied cats of local origin, while more than half of the non-local cats (170 of 318) were infected by C. sinensis, P. fastosum, or Opisthorchis viverrini. The non-local cats had higher prevalence (odds ratio = 6.61, P < 0.01, 95% CI: 2.34-19.41) and intensity of infection (count ratio = 6.47, P < 0.01, 95% CI: 1.77-23.59) by C. sinensis than local cats. Prevalence of P. fastosum infection did not differ significantly between the 2 groups of cats. Opisthorchis viverrini was found at low prevalence (2.5%) in non-local cats. The presence of O. viverrini in cats sampled in northern Vietnam and the high prevalence and intensity of infection in cats of non-local origin suggest that cats are transported over great distances, and this poses a risk of spreading these trematodes.
Collapse
Affiliation(s)
- Hung Manh Nguyen
- 1 Institute of Ecology and Biological Resources (IEBR), Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet St., Cau Giay Dist., Hanoi, Vietnam
| | - Yulia V Tatonova
- 2 Federal Scientific Center of the East Asia Terrestrial Biodiversity, Far Eastern Branch, Russian Academy of Sciences, 159 100-letiya St., Vladivostok 690022, Russia
| | - Henry Madsen
- 3 Parasitology and Aquatic Diseases, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Thorvaldsensvej 57, 1871 Frederiksberg C, Copenhagen, Denmark
| |
Collapse
|
|
40
|
Bragazzi MC, Ridola L, Safarikia S, Matteo SD, Costantini D, Nevi L, Cardinale V. New insights into cholangiocarcinoma: multiple stems and related cell lineages of origin. Ann Gastroenterol 2017; 31:42-55. [PMID: 29333066 PMCID: PMC5759612 DOI: 10.20524/aog.2017.0209] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Accepted: 09/14/2017] [Indexed: 12/12/2022] Open
Abstract
Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies that may develop at any level of the biliary tree. CCA is currently classified into intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA) on the basis of its anatomical location. Notably, although these three CCA subtypes have common features, they also have important inter- and intra-tumor differences that can affect their pathogenesis and outcome. A unique feature of CCA is that it manifests in the hepatic parenchyma or large intrahepatic and extrahepatic bile ducts, furnished by two distinct stem cell niches: the canals of Hering and the peribiliary glands, respectively. The complexity of CCA pathogenesis highlights the need for a multidisciplinary, translational, and systemic approach to this malignancy. This review focuses on advances in the knowledge of CCA histomorphology, risk factors, molecular pathogenesis, and subsets of CCA.
Collapse
Affiliation(s)
- Maria Consiglia Bragazzi
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Lorenzo Ridola
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Samira Safarikia
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Sabina Di Matteo
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Daniele Costantini
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Lorenzo Nevi
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| |
Collapse
|
|
41
|
Tatonova YV, Chelomina GN, Nguyen HM. Inter-individual and intragenomic variations in the ITS region of Clonorchis sinensis (Trematoda: Opisthorchiidae) from Russia and Vietnam. INFECTION GENETICS AND EVOLUTION 2017; 55:350-357. [DOI: 10.1016/j.meegid.2017.10.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Revised: 10/06/2017] [Accepted: 10/06/2017] [Indexed: 01/18/2023]
|
|
42
|
Clonorchis sinensis infection and co-infection with the hepatitis B virus are important factors associated with cholangiocarcinoma and hepatocellular carcinoma. Parasitol Res 2017; 116:2645-2649. [PMID: 28801696 PMCID: PMC5599464 DOI: 10.1007/s00436-017-5572-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Accepted: 07/26/2017] [Indexed: 01/08/2023]
Abstract
To evaluate the contributions of Clonorchis sinensis and hepatitis B virus to the development of cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC), C. sinensis and hepatitis B virus infections in 20 clinical liver cancer cases from a C. sinensis- and hepatitis B virus-epidemic region were detected. Eight cases of ICC, 11 cases of HCC and one mixed ICC and HCC case were verified by CT, pathological section and (or) observations during surgery. The C. sinensis infection was detected by stool microscopy and ELISA, and the worms and eggs found during surgery and in pathological sections also allowed for diagnoses. Hepatitis B virus infections were detected by ELISA. In the 20 cases, 18 patients were diagnosed with C. sinensis infections. Eight of the 20 patients were infected with the hepatitis B virus, and seven were co-infected with C. sinensis. In the eight ICC patients, seven were diagnosed with C. sinensis infection, and two had mixed infections with the hepatitis B virus. In the 11 HCC patients, 10 were diagnosed with C. sinensis, four had mixed infections with the hepatitis B virus, and only one HCC patient presented a single infection by the hepatitis B virus. These clinical observations revealed that C. sinensis infection and C. sinensis co-infection with the hepatitis B virus are important factors in ICC and HCC.
Collapse
|
|
43
|
Jeong S, Tong Y, Sha M, Gu J, Xia Q. Hepatitis B virus-associated intrahepatic cholangiocarcinoma: a malignancy of distinctive characteristics between hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Oncotarget 2017; 8:17292-17300. [PMID: 28030846 PMCID: PMC5370041 DOI: 10.18632/oncotarget.14079] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2016] [Accepted: 12/13/2016] [Indexed: 12/15/2022] Open
Abstract
It has been a decade since hepatitis B virus infection was identified as an etiological factor for the development of intrahepatic cholangiocarcinoma (ICC). In recent years, several studies have elucidated the critical impact of hepatitis B virus in ICC that significantly influenced the clinicopathological characteristics of ICC patients with intrahepatic cholangiocarcinoma. Distinctive features of patients with hepatitis B virus-associated ICC included younger age, preponderance of male patients, frequent elevation of alpha-fetoprotein, and infrequent lymph node metastasis. Furthermore, several studies indicated that the presence of hepatitis B virus is a favorable prognostic factor in terms of overall survival and relapse-free survival. However, there are also a few studies demonstrating that hepatitis B virus negatively influenced or showed no significant association with survival outcomes of patients with ICC. At present, there are no consensus on diagnostic procedures and treatments for such population. Therefore, we elucidated current knowledge and recent identifications of HBV-associated ICC to clarify the impact of chronic HBV infection on patients with ICC and to precisely conduct diagnostic procedures and curative treatments for HBV-associated ICC.
Collapse
Affiliation(s)
- Seogsong Jeong
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Ying Tong
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Meng Sha
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Jinyang Gu
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Qiang Xia
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| |
Collapse
|
|
44
|
Oikonomopoulou K, Yu H, Wang Z, Vasiliou SK, Brinc D, Christofi G, Theodorou M, Pavlou P, Hadjisavvas A, Demetriou CA, Kyriacou K, Diamandis EP. Association between Echinococcus granulosus infection and cancer risk - a pilot study in Cyprus. Clin Chem Lab Med 2017; 54:1955-1961. [PMID: 27327131 DOI: 10.1515/cclm-2016-0125] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Accepted: 05/03/2016] [Indexed: 01/06/2023]
Abstract
BACKGROUND Infections from microorganisms and parasites have been connected with either increased or decreased cancer risk. The objective of this study was to investigate whether infection by Echinococcus granulosus is associated with cancer risk. METHODS We assembled a pilot retrospective cohort of patients who were diagnosed as being infected by E. granulosus in Cyprus between 1930 and 2011. Age/gender-matched non-infected family members and neighbors were selected as references. Medical history was ascertained from each study subject through in-person interview. Cox proportional hazards regression analysis was performed to assess the association of being infected by E. granulosus with cancer risk. RESULTS Individuals with prior infection by E. granulosus (n=249) were more likely to have cancer compared to those without infection (n=753), 11.65% vs. 8.37% (p=0.0492). Survival analysis also showed that subjects with prior infection had a higher risk for developing cancer. The hazards ratio (HR) was 1.595, [95% confidence interval (CI) between 1.008 and 2.525]. The risk ratio did not change significantly (HR=1.536; 95% CI: 0.965-2.445) after adjusting for gender, year of birth, smoking status, alcohol consumption, and family history of cancer. CONCLUSIONS Our study suggests that infection by E. granulosus may increase cancer risk. If this observation can be confirmed independently, further investigation of the mechanisms underlying the association is warranted.
Collapse
|
|
45
|
Kim TS, Pak JH, Kim JB, Bahk YY. Clonorchis sinensis, an oriental liver fluke, as a human biological agent of cholangiocarcinoma: a brief review. BMB Rep 2017; 49:590-597. [PMID: 27418285 PMCID: PMC5346318 DOI: 10.5483/bmbrep.2016.49.11.109] [Citation(s) in RCA: 74] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2016] [Indexed: 01/11/2023] Open
Abstract
Parasitic diseases remain an unarguable public health problem worldwide. Liver fluke Clonorchis sinensis is a high risk pathogenic parasitic helminth which is endemic predominantly in Asian countries, including Korea, China, Taiwan, Vietnam, and the far eastern parts of Russia, and is still actively transmitted. According to the earlier 8th National Survey on the Prevalence of Intestinal Parasitic Infections in 2012, C. sinensis was revealed as the parasite with highest prevalence of 1.86% in general population among all parasite species surveyed in Korea. This fluke is now classified under one of the definite Group 1 human biological agents (carcinogens) by International Agency of Research on Cancer (IARC) along with two other parasites, Opisthorchis viverrini and Schistosoma haematobium. C. sinensis infestation is mainly linked to liver and biliary disorders, especially cholangiocarcinoma (CCA). For the purposes of this mini-review, we will only focus on C. sinensis and review pathogenesis and carcinogenesis of clonorchiasis, disease condition by C. sinensis infestation, and association between C. sinensis infestation and CCA. In this presentation, we briefly consider the current scientific status for progression of CCA by heavy C. sinensis infestation from the food-borne trematode and development of CCA.
Collapse
Affiliation(s)
- Tong-Soo Kim
- Department of Parasitology and Tropical Medicine, School of Medicine, Inha University, Incheon 22212, Korea
| | - Jhang Ho Pak
- Department of Convergence Medicine, College of Medicine, University of Ulsan, Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Korea
| | - Jong-Bo Kim
- Department of Biotechnology, Konkuk University, Chungju 27478, Korea
| | - Young Yil Bahk
- Department of Biotechnology, Konkuk University, Chungju 27478, Korea
| |
Collapse
|
|
46
|
van Tong H, Brindley PJ, Meyer CG, Velavan TP. Parasite Infection, Carcinogenesis and Human Malignancy. EBioMedicine 2016; 15:12-23. [PMID: 27956028 PMCID: PMC5233816 DOI: 10.1016/j.ebiom.2016.11.034] [Citation(s) in RCA: 97] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2016] [Revised: 11/24/2016] [Accepted: 11/29/2016] [Indexed: 12/14/2022] Open
Abstract
Cancer may be induced by many environmental and physiological conditions. Infections with viruses, bacteria and parasites have been recognized for years to be associated with human carcinogenicity. Here we review current concepts of carcinogenicity and its associations with parasitic infections. The helminth diseases schistosomiasis, opisthorchiasis, and clonorchiasis are highly carcinogenic while the protozoan Trypanosoma cruzi, the causing agent of Chagas disease, has a dual role in the development of cancer, including both carcinogenic and anticancer properties. Although malaria per se does not appear to be causative in carcinogenesis, it is strongly associated with the occurrence of endemic Burkitt lymphoma in areas holoendemic for malaria. The initiation of Plasmodium falciparum related endemic Burkitt lymphoma requires additional transforming events induced by the Epstein-Barr virus. Observations suggest that Strongyloides stercoralis may be a relevant co-factor in HTLV-1-related T cell lymphomas. This review provides an overview of the mechanisms of parasitic infection-induced carcinogenicity.
The helminth diseases schistosomiasis, opisthorchiasis, and clonorchiasis are highly carcinogenic. Trypanosoma cruzi has a dual role in cancer development including both carcinogenic and anticancer properties. Initiation of Plasmodium falciparum related endemic Burkitt lymphoma requires additional transforming events induced by EBV. Strongyloides stercoralis may be a relevant co-factor in HTLV-1-related T cell lymphomas. We searched MEDLINE database and PubMed for articles from 1970 through June 30, 2016. Search terms used in various combinations were “parasite infection”, “carcinogenesis”, “cancer”, “human malignancy”, “parasite and cancer”, “infection-associated cancer”, “parasite-associated cancer” “schistosomiasis”, “opisthorchiasis”, “malaria”, “Chagas disease”, and “strongyloidiasis”. Articles resulting from these searches and relevant references cited in those articles were selected based on their related topics and were reviewed. Abstracts and reports from meetings were also included. Articles published in English were included.
Collapse
Affiliation(s)
- Hoang van Tong
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; Biomedical and Pharmaceutical Applied Research Center, Vietnam Military Medical University, Hanoi, Vietnam.
| | - Paul J Brindley
- Research Center for Neglected Diseases of Poverty, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine & Health Sciences, George Washington University, Washington, D.C., USA
| | - Christian G Meyer
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; Health Focus GmbH, Potsdam, Germany; Duy Tan University, Da Nang, Viet Nam; Vietnamese - German Centre for Medical Research (VG-CARE), Hanoi, Viet Nam
| | - Thirumalaisamy P Velavan
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; Duy Tan University, Da Nang, Viet Nam; Vietnamese - German Centre for Medical Research (VG-CARE), Hanoi, Viet Nam.
| |
Collapse
|
|
47
|
Kim JG, Ahn CS, Kim SH, Bae YA, Kwon NY, Kang I, Yang HJ, Sohn WM, Kong Y. Clonorchis sinensis omega-class glutathione transferases play major roles in the protection of the reproductive system during maturation and the response to oxidative stress. Parasit Vectors 2016; 9:337. [PMID: 27296469 PMCID: PMC4906895 DOI: 10.1186/s13071-016-1622-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2016] [Accepted: 06/02/2016] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Clonorchis sinensis causes a major food-borne helminthic infection. This species locates in mammalian hepatobiliary ducts, where oxidative stressors and hydrophobic substances are profuse. To adapt to the hostile micromilieu and to ensure its long-term survival, the parasite continuously produces a diverse repertoire of antioxidant enzymes including several species of glutathione transferases (GSTs). Helminth GSTs play pertinent roles during sequestration of harmful xenobiotics since most helminths lack the cytochrome P-450 detoxifying enzyme. METHODS We isolated and analyzed the biochemical properties of two omega-class GSTs of C. sinensis (CsGSTo1 and CsGSTo2). We observed spatiotemporal expression patterns in accordance with the maturation of the worm's reproductive system. Possible biological protective roles of CsGSTos in these organs under oxidative stress were investigated. RESULTS The full-length cDNAs of CsGSTo1 and 2 constituted 965 bp and 1,061 bp with open reading frames of 737 bp (246 amino acids) and 669 bp (223 amino acids). They harbored characteristic N-terminal thioredoxin-like and C-terminal α-helical domains. A cysteine residue, which constituted omega-class specific active site, and the glutathione-binding amino acids, were recognized in appropriate positions. They shared 44 % sequence identity with each other and 14.8-44.8 % with orthologues/homologues from other organisms. Bacterially expressed recombinant proteins (rCsGSTo1 and 2) exhibited dehydroascorbate reductase (DHAR) and thioltransferase activities. DHAR activity was higher than thioltransferase activity. They showed weak canonical GST activity toward 1-chloro-2,4-dinitrobenzene. S-hexylglutathione potently and competitively inhibited the active-site at nanomolar concentrations (0.63 and 0.58 nM for rCsGSTo1 and 2). Interestingly, rCsGSTos exhibited high enzyme activity toward mu- and theta-class GST specific substrate, 4-nitrobenzyl chloride. Expression of CsGSTo transcripts and proteins increased beginning in 2-week-old juveniles and reached their highest levels in 4-week-old adults. The proteins were mainly expressed in the elements of the reproductive system, such as vitelline follicles, testes, seminal receptacle, sperm and eggs. Oxidative stressors induced upregulated expression of CsGSTos in these organs. Regardless of oxidative stresses, CsGSTos continued to be highly expressed in eggs. CsGSTo1 or 2 overexpressing bacteria demonstrated high resistance under oxidative killing. CONCLUSIONS CsGSTos might be critically involved in protection of the reproductive system during maturation of C. sinensis worms and in response to oxidative conditions, thereby contributing to maintenance of parasite fecundity.
Collapse
Affiliation(s)
- Jeong-Geun Kim
- Department of Molecular Parasitology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon, 16419, Korea
| | - Chun-Seob Ahn
- Department of Molecular Parasitology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon, 16419, Korea
| | - Seon-Hee Kim
- Department of Microbiology, Graduate School of Medicine, Gachon University, Incheon, Korea
| | - Young-An Bae
- Department of Microbiology, Graduate School of Medicine, Gachon University, Incheon, Korea
| | - Na-Young Kwon
- Department of Molecular Parasitology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon, 16419, Korea
| | - Insug Kang
- Department of Molecular Biology and Biochemistry, School of Medicine, Kyung Hee University, Seoul, Korea
| | - Hyun-Jong Yang
- Department of Parasitology, Ewha Womans University, School of Medicine, Seoul, Korea
| | - Woon-Mok Sohn
- Department of Parasitology and Tropical Medicine, Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju, Korea
| | - Yoon Kong
- Department of Molecular Parasitology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon, 16419, Korea.
| |
Collapse
|
|
48
|
Pomaznoy MY, Logacheva MD, Young ND, Penin AA, Ershov NI, Katokhin AV, Mordvinov VA. Whole transcriptome profiling of adult and infective stages of the trematode Opisthorchis felineus. Parasitol Int 2016; 65:12-19. [DOI: 10.1016/j.parint.2015.09.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2015] [Revised: 08/11/2015] [Accepted: 09/08/2015] [Indexed: 01/22/2023]
|
|
49
|
Lai DH, Hong XK, Su BX, Liang C, Hide G, Zhang X, Yu X, Lun ZR. Current status ofClonorchis sinensisand clonorchiasis in China. Trans R Soc Trop Med Hyg 2016; 110:21-7. [DOI: 10.1093/trstmh/trv100] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
|
|
50
|
Yeom JS, Kong Y. Medical treatment of tropical parasitic diseases. JOURNAL OF THE KOREAN MEDICAL ASSOCIATION 2016. [DOI: 10.5124/jkma.2016.59.9.721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Affiliation(s)
- Joon Sup Yeom
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yoon Kong
- Department of Molecular Parasitology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| |
Collapse
|