{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:03:08Z","timestamp":1790744588397,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T00:00:00Z","timestamp":1695686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science (JSPS)","doi-asserted-by":"publisher","award":["18K07968"],"award-info":[{"award-number":["18K07968"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science (JSPS)","doi-asserted-by":"publisher","award":["21K07892"],"award-info":[{"award-number":["21K07892"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care (2017)","award":["18K07968"],"award-info":[{"award-number":["18K07968"]}]},{"name":"Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care (2017)","award":["21K07892"],"award-info":[{"award-number":["21K07892"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cholangiocarcinoma is the second most common primary cancer of the liver and has a poor prognosis. Various animal models, including carcinogen-induced and genetically engineered rodent models, have been established to clarify the mechanisms underlying cholangiocarcinoma development. In the present study, we developed a novel mouse model of malignant lesions in the biliary ducts induced by the administration of the carcinogen azoxymethane to obese C57BLKS\/J-db\/db mice. A histopathological analysis revealed that the biliary tract lesions in the liver appeared to be an intrahepatic cholangiocarcinoma with higher tumor incidence, shorter experimental duration, and a markedly increased incidence in obese mice. Molecular markers analyzed using a microarray and a qPCR indicated that the cancerous lesions originated from the cholangiocytes and developed in the inflamed livers. These findings indicated that this is a novel mouse model of intrahepatic cholangiocarcinoma in the context of steatohepatitis. This model can be used to provide a better understanding of the pathogenic mechanisms of cholangiocarcinoma and to develop novel therapeutic strategies for this malignancy.<\/jats:p>","DOI":"10.3390\/ijms241914581","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T08:55:01Z","timestamp":1695718501000},"page":"14581","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Novel Mouse Model of Intrahepatic Cholangiocarcinoma Induced by Azoxymethane"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2471-090X","authenticated-orcid":false,"given":"Yohei","family":"Shirakami","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Ohnishi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6626-7320","authenticated-orcid":false,"given":"Daisuke","family":"Taguchi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihide","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayasu","family":"Ideta","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Kubota","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyasu","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3291-0274","authenticated-orcid":false,"given":"Hiroyuki","family":"Tomita","sequence":"additional","affiliation":[{"name":"Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1428-1582","authenticated-orcid":false,"given":"Takuji","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Pathological Diagnosis, Gifu Municipal Hospital, Gifu 500-8513, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1151-2058","authenticated-orcid":false,"given":"Masahito","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1093\/jnci\/djj234","article-title":"Impact of classification of hilar cholangiocarcinomas (Klatskin tumors) on the incidence of intra- and extrahepatic cholangiocarcinoma in the United States","volume":"98","author":"Welzel","year":"2006","journal-title":"J. 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