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Mechanistic findings from hamsters and in vitro cell models indicate synergistic stimulation by C. sinensis and nitrogen compounds toward neoplastic transformation and disrupted intercellular regulation.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/clonorchis-sinensis-and-cholangiocarcinoma-review-article/374403/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/clonorchis-sinensis-and-cholangiocarcinoma-review-article/374403.png","ImageObject",300,407,{"name":42,"@type":43},"Rhys","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-31","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",11,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What causes clonorchiasis and where does the parasite reside?","Question",{"text":63,"@type":64},"Clonorchiasis is caused by Clonorchis sinensis. The trematode inhabits the intrahepatic bile ducts in humans and mammals.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How is Clonorchis sinensis linked to cholangiocarcinoma?",{"text":68,"@type":64},"International Agency for Research on Cancer reclassified C. sinensis as a Group 1 biological carcinogen for human cholangiocarcinoma. Evidence includes epidemiological associations, CCA development in experimental animals, and molecular findings.",{"name":70,"@type":61,"acceptedAnswer":71},"What do the experimental and in vitro results suggest about the mechanism?",{"text":72,"@type":64},"Hamsters exposed to both C. sinensis and NDMA developed CCA, while exposure to either alone did not. In vitro models showed shifts in cell-cycle phase, increased proliferation, suppressed apoptosis, and altered connexin gap-junction proteins, indicating synergistic stimulation toward neoplastic change.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},374403,1790440729,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146},687207024643,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","J Korean Med Sci. 2025 Apr 28;40(16):e145 [https://doi.org/10.3346/jkms.2025.40.e145](https://doi.org/10.3346/jkms.2025.40.e145)[ ](https://doi.org/10.3346/jkms.2025.40.e145)eISSN 1598-6357·pISSN 1011-8934  \nReview Article  \nInfectious Diseases  \nReceived: Mar 11, 2025  \nAccepted: Mar 24, 2025  \nPublished online: Apr 9, 2025  \nAddress for Correspondence:  \nSung-Tae Hong, MD, PhD  \nDepartment of Tropical Medicine and Parasitology and Institute of Endemic Disease, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Korea.  \nEmail: [hst@snu.ac.kr](hst@snu.ac.kr)  \n© 2025 The Korean Academy of Medical Sciences.  \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ([https://](https://)[ ](https://)[creativecommons.org/licenses/by-nc/4.0/](creativecommons.org/licenses/by-nc/4.0/)) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.  \nORCID iDs  \nEun-Min Kim  [https://orcid.org/0000-0001-5495-2339](https://orcid.org/0000-0001-5495-2339)[ ](https://orcid.org/0000-0001-5495-2339)[Sung-Tae Hong](Sung-Tae Hong)  [https://orcid.org/0000-0002-0300-1944](https://orcid.org/0000-0002-0300-1944)  \nDisclosure  \nThe authors have no potential conflicts of interest to disclose.  \nAuthor Contributions  \nConceptualization: Hong ST. Data curation: Hong ST, Kim EM. Formal analysis: Hong ST, Kim EM. Writing-original draft: Hong ST. Writing-review & editing: Hong ST, Kim EM.  \nClonorchis sinensis and Cholangiocarcinoma  \nEun-Min Kim  1 and Sung-Tae Hong  2  \n1Department of Microbiology, College of Medicine and Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Korea  \n2Department of Tropical Medicine and Parasitology and Institute of Endemic Disease, Seoul National University College of Medicine, Seoul, Korea  \nABSTRACT  \nClonorchiasis is a parasitic disease caused by Clonorchis sinensis, a trematode that inhabits the intrahepatic bile ducts of humans and mammals. C. sinensis is one of common foodborne trematodes, prevalent in East Asia including Korea. The International Agency for Research on Cancer reclassified C. sinensisas the Group 1 biological carcinogen of human cholangiocarcinoma (CCA). Evidence supporting the carcinogenicity ofC. sinensis includes epidemiological studies showing increased prevalence and odds ratio (OR) ofCCA inclonorchiasis patients, the development ofCCA in experimental animals, and molecular studies. Approximately 10% ofCCA in Korea are believed to be solely caused by clonorchiasis, with an OR of 4.7 for CCA risk among clonorchiasis patients. All hamsters exposed to both ofC. sinensis and N-nitrosodimethylamine (NDMA) developed CCA while those exposed to either C. sinensisor NDMA alone did not. In vitro studies using cell models investigated carcinogenetic changes of the intracellular molecules and genes following stimulation with a soluble extract ofC. sinensis. The in vitro stimulated cells showed a significant shift to G2/Mphage, produced oncogenic molecules, changed expression of oncogenes, increased cell proliferation and suppressed apoptosis. Additionally, the gap-junction proteins between cells, such as connexin (Cx) 43, Cx 26, and Cx 32, were changed significantly, disrupting intercellular homeostasis. These findings suggest that C. sinensis and nitrogen compounds synergistically stimulate the cholangiocytes to become neoplastic. C. sinensis is a biological carcinogen of human CCA, and the World Health Organization guidelines enlist food-borne trematodes as one of target neglected tropical diseases to be eliminated by 2030. The present article reviews and updates perspectives on clonorchiasis, focusing on carcinogenesis.  \nKeywords: Clonorchis sinensis; Clonorchiasis; Cholangiocarcinoma; Biocarcinogen, Group 1; N-nitrosodimethylamine; Epidemiology; Syrian Golden Hamster; H69 Cells;  \nFood-borne Trematodes  \nINTRODU","cbCairmAnVqn3DgS","https://ap.wps.com/l/cbCairmAnVqn3DgS","pdf",11920686,23,"English","# Abstract\n# Introduction","[{\"question\":\"What causes clonorchiasis and where does the parasite reside?\",\"answer\":\"Clonorchiasis is caused by Clonorchis sinensis. The trematode inhabits the intrahepatic bile ducts in humans and mammals.\"},{\"question\":\"How is Clonorchis sinensis linked to cholangiocarcinoma?\",\"answer\":\"International Agency for Research on Cancer reclassified C. sinensis as a Group 1 biological carcinogen for human cholangiocarcinoma. Evidence includes epidemiological associations, CCA development in experimental animals, and molecular findings.\"},{\"question\":\"What do the experimental and in vitro results suggest about the mechanism?\",\"answer\":\"Hamsters exposed to both C. sinensis and NDMA developed CCA, while exposure to either alone did not. In vitro models showed shifts in cell-cycle phase, increased proliferation, suppressed apoptosis, and altered connexin gap-junction proteins, indicating synergistic stimulation toward neoplastic change.\"}]","Clonorchis sinensis and Cholangiocarcinoma - Review Article | PDF",1790201596,58]