{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:27:43Z","timestamp":1792189663291,"version":"4.4.0"},"reference-count":169,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018154","name":"Fund for Innovation in Cancer Informatics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018154","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003625","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["RS-2023-00269801"],"award-info":[{"award-number":["RS-2023-00269801"]}],"id":[{"id":"10.13039\/501100003625","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK126656"],"award-info":[{"award-number":["R01DK126656"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1P30DK120531-01"],"award-info":[{"award-number":["1P30DK120531-01"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA258449"],"award-info":[{"award-number":["R01CA258449"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ajp.amjpathol.org","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Pathology"],"published-print":{"date-parts":[[2025,3]]},"DOI":"10.1016\/j.ajpath.2024.07.023","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T11:58:31Z","timestamp":1727179111000},"page":"409-421","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hepatic Nuclear Receptors in Cholestasis-to-Cholangiocarcinoma Pathology"],"prefix":"10.1016","volume":"195","author":[{"given":"Inyoung","family":"Cheon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minwook","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang Ho","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungjin","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ajpath.2024.07.023_bib2","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nrgastro.2016.51","article-title":"Expert consensus document: cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)","volume":"13","author":"Banales","year":"2016","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib3","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41575-020-0310-z","article-title":"Cholangiocarcinoma 2020: the next horizon in mechanisms and management","volume":"17","author":"Banales","year":"2020","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib4","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/s41571-023-00770-1","article-title":"Cholangiocarcinoma - novel biological insights and therapeutic strategies","volume":"20","author":"Ilyas","year":"2023","journal-title":"Nat Rev Clin Oncol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib5","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1634\/theoncologist.2015-0446","article-title":"Forty-year trends in cholangiocarcinoma incidence in the U.S.: intrahepatic disease on the rise","volume":"21","author":"Saha","year":"2016","journal-title":"Oncologist"},{"key":"10.1016\/j.ajpath.2024.07.023_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.aohep.2022.100737","article-title":"Clinical treatment of cholangiocarcinoma: an updated comprehensive review","volume":"27","author":"Elvevi","year":"2022","journal-title":"Ann Hepatol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib7","doi-asserted-by":"crossref","first-page":"92","DOI":"10.5582\/bst.2016.01048","article-title":"The current management of cholangiocarcinoma: a comparison of current guidelines","volume":"10","author":"Cai","year":"2016","journal-title":"Biosci Trends"},{"key":"10.1016\/j.ajpath.2024.07.023_bib8","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1093\/annonc\/mdu162","article-title":"Second-line chemotherapy in advanced biliary cancer: a systematic review","volume":"25","author":"Lamarca","year":"2014","journal-title":"Ann Oncol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib9","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1136\/gutjnl-2011-301748","article-title":"Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update","volume":"61","author":"Khan","year":"2012","journal-title":"Gut"},{"key":"10.1016\/j.ajpath.2024.07.023_bib10","first-page":"630","article-title":"Molecular pathways and targeted therapy in cholangiocarcinoma","volume":"17","author":"Dabney","year":"2019","journal-title":"Clin Adv Hematol Oncol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib11","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1158\/2159-8290.CD-21-1168","article-title":"EGFR inhibition potentiates FGFR inhibitor therapy and overcomes resistance in FGFR2 fusion-positive cholangiocarcinoma","volume":"12","author":"Wu","year":"2022","journal-title":"Cancer Discov"},{"key":"10.1016\/j.ajpath.2024.07.023_bib12","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1158\/2159-8290.CD-21-1077","article-title":"Mutant IDH inhibits IFNgamma-TET2 signaling to promote immunoevasion and tumor maintenance in cholangiocarcinoma","volume":"12","author":"Wu","year":"2022","journal-title":"Cancer Discov"},{"key":"10.1016\/j.ajpath.2024.07.023_bib13","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1002\/hep.32424","article-title":"Biology of IDH mutant cholangiocarcinoma","volume":"75","author":"Wu","year":"2022","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2024.07.023_bib14","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.jhep.2020.03.007","article-title":"Molecular targeted therapies: ready for \"prime time\" in biliary tract cancer","volume":"73","author":"Lamarca","year":"2020","journal-title":"J Hepatol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib15","first-page":"42","article-title":"New insights into cholangiocarcinoma: multiple stems and related cell lineages of origin","volume":"31","author":"Bragazzi","year":"2018","journal-title":"Ann Gastroenterol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib16","doi-asserted-by":"crossref","first-page":"14744","DOI":"10.18632\/oncotarget.4539","article-title":"Genetic heterogeneity in cholangiocarcinoma: a major challenge for targeted therapies","volume":"6","author":"Brandi","year":"2015","journal-title":"Oncotarget"},{"key":"10.1016\/j.ajpath.2024.07.023_bib17","doi-asserted-by":"crossref","first-page":"94","DOI":"10.4251\/wjgo.v4.i5.94","article-title":"Multiple cells of origin in cholangiocarcinoma underlie biological, epidemiological and clinical heterogeneity","volume":"4","author":"Cardinale","year":"2012","journal-title":"World J Gastrointest Oncol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib18","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41575-022-00741-4","article-title":"Immunology and immunotherapy of cholangiocarcinoma","volume":"20","author":"Greten","year":"2023","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib19","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1007\/s11912-022-01328-7","article-title":"Immunotherapy in biliary tract cancers: where are we?","volume":"24","author":"Kalyan","year":"2022","journal-title":"Curr Oncol Rep"},{"key":"10.1016\/j.ajpath.2024.07.023_bib20","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/s41467-020-20171-7","article-title":"Intratumoural immune heterogeneity as a hallmark of tumour evolution and progression in hepatocellular carcinoma","volume":"12","author":"Nguyen","year":"2021","journal-title":"Nat Commun"},{"key":"10.1016\/j.ajpath.2024.07.023_bib21","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/s41586-019-1730-1","article-title":"A view on drug resistance in cancer","volume":"575","author":"Vasan","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.ajpath.2024.07.023_bib22","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1158\/1078-0432.CCR-23-1317","article-title":"Landscape of clinical resistance mechanisms to FGFR inhibitors in FGFR2-altered cholangiocarcinoma","volume":"30","author":"Wu","year":"2024","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.ajpath.2024.07.023_bib23","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1002\/cncr.29936","article-title":"Annual report to the nation on the status of cancer, 1975-2012, featuring the increasing incidence of liver cancer","volume":"122","author":"Ryerson","year":"2016","journal-title":"Cancer"},{"key":"10.1016\/j.ajpath.2024.07.023_bib24","first-page":"1","article-title":"Deaths: final data for 2013","volume":"64","author":"Xu","year":"2016","journal-title":"Natl Vital Stat Rep"},{"key":"10.1016\/j.ajpath.2024.07.023_bib25","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1186\/s12885-019-5391-0","article-title":"Molecular pathogenesis of cholangiocarcinoma","volume":"19","author":"Labib","year":"2019","journal-title":"BMC Cancer"},{"key":"10.1016\/j.ajpath.2024.07.023_bib26","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0186643","article-title":"Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United States: a population-based study in SEER-Medicare","volume":"12","author":"Petrick","year":"2017","journal-title":"PLoS One"},{"key":"10.1016\/j.ajpath.2024.07.023_bib27","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1002\/hep.26565","article-title":"Population-based epidemiology, malignancy risk, and outcome of primary sclerosing cholangitis","volume":"58","author":"Boonstra","year":"2013","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2024.07.023_bib28","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1097\/MOG.0000000000000335","article-title":"Risk of cholangiocarcinoma in patients with primary sclerosing cholangitis: diagnosis and surveillance","volume":"33","author":"Ehlken","year":"2017","journal-title":"Curr Opin Gastroenterol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib29","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1038\/s12276-023-01042-9","article-title":"Primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD): a condition exemplifying the crosstalk of the gut-liver axis","volume":"55","author":"Kim","year":"2023","journal-title":"Exp Mol Med"},{"key":"10.1016\/j.ajpath.2024.07.023_bib30","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jhep.2012.02.022","article-title":"Are common factors involved in the pathogenesis of primary liver cancers? a meta-analysis of risk factors for intrahepatic cholangiocarcinoma","volume":"57","author":"Palmer","year":"2012","journal-title":"J Hepatol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib31","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1146\/annurev-pharmtox-010715-103209","article-title":"Nuclear receptors as therapeutic targets in liver disease: are we there yet?","volume":"56","author":"Rudraiah","year":"2016","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib32","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1080\/17425255.2020.1746268","article-title":"Nuclear receptor CAR-mediated liver cancer and its species differences","volume":"16","author":"Shizu","year":"2020","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib33","doi-asserted-by":"crossref","first-page":"2668","DOI":"10.3390\/ijms23052668","article-title":"Nuclear receptors linking metabolism, inflammation, and fibrosis in nonalcoholic fatty liver disease","volume":"23","author":"Puengel","year":"2022","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.ajpath.2024.07.023_bib34","doi-asserted-by":"crossref","first-page":"4074","DOI":"10.3748\/wjg.v25.i30.4074","article-title":"Role of hepatocyte nuclear factor 4-alpha in gastrointestinal and liver diseases","volume":"25","author":"Yeh","year":"2019","journal-title":"World J Gastroenterol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib35","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.jhep.2022.10.023","article-title":"Hepatic and renal improvements with FXR agonist vonafexor in individuals with suspected fibrotic NASH","volume":"78","author":"Ratziu","year":"2023","journal-title":"J Hepatol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib36","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/s41591-022-02200-8","article-title":"Tropifexor for nonalcoholic steatohepatitis: an adaptive, randomized, placebo-controlled phase 2a\/b trial","volume":"29","author":"Sanyal","year":"2023","journal-title":"Nat Med"},{"key":"10.1016\/j.ajpath.2024.07.023_bib37","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.jhep.2020.02.033","article-title":"A randomized, placebo-controlled, phase II study of obeticholic acid for primary sclerosing cholangitis","volume":"73","author":"Kowdley","year":"2020","journal-title":"J Hepatol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib38","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1016\/j.cgh.2022.07.024","article-title":"Safety and sustained efficacy of the farnesoid X receptor (FXR) agonist cilofexor over a 96-week open-label extension in patients with PSC","volume":"21","author":"Trauner","year":"2023","journal-title":"Clin Gastroenterol Hepatol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib39","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1111\/cts.13469","article-title":"Pharmacokinetics, pharmacodynamics, safety and tolerability of cilofexor, a novel nonsteroidal farnesoid X receptor agonist, in healthy volunteers","volume":"16","author":"Younis","year":"2023","journal-title":"Clin Transl Sci"},{"key":"10.1016\/j.ajpath.2024.07.023_bib40","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1158\/0008-5472.CAN-06-1078","article-title":"Spontaneous development of liver tumors in the absence of the bile acid receptor farnesoid X receptor","volume":"67","author":"Yang","year":"2007","journal-title":"Cancer Res"},{"key":"10.1016\/j.ajpath.2024.07.023_bib41","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1248\/bpb.b19-00267","article-title":"Role of nuclear receptors PXR and CAR in xenobiotic-induced hepatocyte proliferation and chemical carcinogenesis","volume":"42","author":"Yoshinari","year":"2019","journal-title":"Biol Pharm Bull"},{"key":"10.1016\/j.ajpath.2024.07.023_bib42","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3390\/cells11010061","article-title":"The nuclear receptor PXR in chronic liver disease","volume":"11","author":"Sayaf","year":"2021","journal-title":"Cells"},{"key":"10.1016\/j.ajpath.2024.07.023_bib43","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1124\/dmd.121.000481","article-title":"Distinct roles of the sister nuclear receptors PXR and CAR in liver cancer development","volume":"50","author":"Yoshinari","year":"2022","journal-title":"Drug Metab Dispos"},{"key":"10.1016\/j.ajpath.2024.07.023_bib44","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.2174\/138920012803762738","article-title":"PPARalpha\/HNF4alpha interplay on diversified responsive elements: relevance in the regulation of liver peroxisomal fatty acid catabolism","volume":"13","author":"Chamouton","year":"2012","journal-title":"Curr Drug Metab"},{"key":"10.1016\/j.ajpath.2024.07.023_bib45","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.3390\/cells9112395","article-title":"Regulation of CAR and PXR expression in health and disease","volume":"9","author":"Daujat-Chavanieu","year":"2020","journal-title":"Cells"},{"key":"10.1016\/j.ajpath.2024.07.023_bib46","doi-asserted-by":"crossref","first-page":"5944","DOI":"10.1038\/ncomms6944","article-title":"Activating CAR and beta-catenin induces uncontrolled liver growth and tumorigenesis","volume":"6","author":"Dong","year":"2015","journal-title":"Nat Commun"},{"key":"10.1016\/j.ajpath.2024.07.023_bib47","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1002\/hep.22475","article-title":"C-Myc and its target FoxM1 are critical downstream effectors of constitutive androstane receptor (CAR) mediated direct liver hyperplasia","volume":"48","author":"Blanco-Bose","year":"2008","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2024.07.023_bib48","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1210\/me.2004-0520","article-title":"Xenobiotic stress induces hepatomegaly and liver tumors via the nuclear receptor constitutive androstane receptor","volume":"19","author":"Huang","year":"2005","journal-title":"Mol Endocrinol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib49","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/bs.acr.2022.02.003","article-title":"YAP1 activation and hippo pathway signaling in the pathogenesis and treatment of intrahepatic cholangiocarcinoma","volume":"156","author":"Ko","year":"2022","journal-title":"Adv Cancer Res"},{"key":"10.1016\/j.ajpath.2024.07.023_bib50","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1053\/j.gastro.2022.05.007","article-title":"NOTCH-YAP1\/TEAD-DNMT1 axis drives hepatocyte reprogramming into intrahepatic cholangiocarcinoma","volume":"163","author":"Hu","year":"2022","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ajpath.2024.07.023_bib51","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1016\/j.jhep.2022.07.029","article-title":"Combined hepatocellular-cholangiocarcinoma derives from liver progenitor cells and depends on senescence and IL-6 trans-signaling","volume":"77","author":"Rosenberg","year":"2022","journal-title":"J Hepatol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib52","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1053\/j.gastro.2011.03.044","article-title":"A mouse model of cholestasis-associated cholangiocarcinoma and transcription factors involved in progression","volume":"141","author":"Yang","year":"2011","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ajpath.2024.07.023_bib53","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3109\/07357907.2012.762781","article-title":"Bile acids affect the growth of human cholangiocarcinoma via NF-[kappa]B pathway","volume":"31","author":"Dai","year":"2013","journal-title":"Cancer Invest"},{"key":"10.1016\/j.ajpath.2024.07.023_bib54","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1002\/hep.29076","article-title":"The role of sphingosine 1-phosphate receptor 2 in bile-acid-induced cholangiocyte proliferation and cholestasis-induced liver injury in mice","volume":"65","author":"Wang","year":"2017","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2024.07.023_bib55","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1053\/gast.2002.32410","article-title":"Bile acids induce cyclooxygenase-2 expression via the epidermal growth factor receptor in a human cholangiocarcinoma cell line","volume":"122","author":"Yoon","year":"2002","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ajpath.2024.07.023_bib56","doi-asserted-by":"crossref","first-page":"G31","DOI":"10.1152\/ajpgi.00536.2002","article-title":"Bile acids activate EGF receptor via a TGF-alpha-dependent mechanism in human cholangiocyte cell lines","volume":"285","author":"Werneburg","year":"2003","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib57","doi-asserted-by":"crossref","first-page":"819","DOI":"10.21037\/jgo.2016.11.11","article-title":"Advances in cholangiocarcinoma research: report from the third cholangiocarcinoma foundation annual conference","volume":"7","author":"Abou-Alfa","year":"2016","journal-title":"J Gastrointest Oncol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib58","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1172\/JCI63212","article-title":"Cholangiocarcinomas can originate from hepatocytes in mice","volume":"122","author":"Fan","year":"2012","journal-title":"J Clin Invest"},{"key":"10.1016\/j.ajpath.2024.07.023_bib59","doi-asserted-by":"crossref","first-page":"4445","DOI":"10.1158\/0008-5472.CAN-17-1123","article-title":"Kras and Tp53 mutations cause cholangiocyte- and hepatocyte-derived cholangiocarcinoma","volume":"78","author":"Hill","year":"2018","journal-title":"Cancer Res"},{"key":"10.1016\/j.ajpath.2024.07.023_bib60","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1016\/S0140-6736(13)61903-0","article-title":"Cholangiocarcinoma","volume":"383","author":"Razumilava","year":"2014","journal-title":"Lancet"},{"key":"10.1016\/j.ajpath.2024.07.023_bib61","doi-asserted-by":"crossref","first-page":"3229","DOI":"10.1038\/s41388-018-0188-1","article-title":"Notch2 controls hepatocyte-derived cholangiocarcinoma formation in mice","volume":"37","author":"Wang","year":"2018","journal-title":"Oncogene"},{"key":"10.1016\/j.ajpath.2024.07.023_bib62","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1136\/gutjnl-2021-326514","article-title":"Novel microenvironment-based classification of intrahepatic cholangiocarcinoma with therapeutic implications","volume":"72","author":"Martin-Serrano","year":"2023","journal-title":"Gut"},{"key":"10.1016\/j.ajpath.2024.07.023_bib63","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.jhep.2019.05.027","article-title":"Loss of Fbxw7 synergizes with activated Akt signaling to promote c-Myc dependent cholangiocarcinogenesis","volume":"71","author":"Wang","year":"2019","journal-title":"J Hepatol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib64","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/hep.31679","article-title":"Farnesoid X receptor activation impairs liver progenitor cell-mediated liver regeneration via the PTEN-PI3K-AKT-mTOR axis in zebrafish","volume":"74","author":"Jung","year":"2021","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2024.07.023_bib65","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2021.103003","article-title":"Metabolic nuclear receptors coordinate energy metabolism to regulate Sox9(+) hepatocyte fate","volume":"24","author":"Liu","year":"2021","journal-title":"iScience"},{"key":"10.1016\/j.ajpath.2024.07.023_bib66","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1007362","article-title":"Cancer epigenetics: moving forward","volume":"14","author":"Nebbioso","year":"2018","journal-title":"PLoS Genet"},{"key":"10.1016\/j.ajpath.2024.07.023_bib67","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/j.1478-3231.2007.01624.x","article-title":"Epigenetic DNA hypermethylation in cholangiocarcinoma: potential roles in pathogenesis, diagnosis and identification of treatment targets","volume":"28","author":"Sandhu","year":"2008","journal-title":"Liver Int"},{"key":"10.1016\/j.ajpath.2024.07.023_bib68","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1055\/s-2006-960172","article-title":"MDR3 (ABCB4) defects: a paradigm for the genetics of adult cholestatic syndromes","volume":"27","author":"Trauner","year":"2007","journal-title":"Semin Liver Dis"},{"key":"10.1016\/j.ajpath.2024.07.023_bib69","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.3390\/biomedicines10061238","article-title":"Gene therapy for acquired and genetic cholestasis","volume":"10","author":"Martinez-Garcia","year":"2022","journal-title":"Biomedicines"},{"key":"10.1016\/j.ajpath.2024.07.023_bib70","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/0092-8674(93)90380-9","article-title":"Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease","volume":"75","author":"Smit","year":"1993","journal-title":"Cell"},{"key":"10.1016\/j.ajpath.2024.07.023_bib71","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.ajpath.2014.10.013","article-title":"A new Mdr2(-\/-) mouse model of sclerosing cholangitis with rapid fibrosis progression, early-onset portal hypertension, and liver cancer","volume":"185","author":"Ikenaga","year":"2015","journal-title":"Am J Pathol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib72","doi-asserted-by":"crossref","first-page":"3421","DOI":"10.3390\/cancers14143421","article-title":"Genetics in familial intrahepatic cholestasis: clinical patterns and development of liver and biliary cancers: a review of the literature","volume":"14","author":"Vitale","year":"2022","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.ajpath.2024.07.023_bib73","doi-asserted-by":"crossref","DOI":"10.1038\/srep21782","article-title":"Activated FXR inhibits leptin signaling and counteracts tumor-promoting activities of cancer-associated fibroblasts in breast malignancy","volume":"6","author":"Giordano","year":"2016","journal-title":"Sci Rep"},{"key":"10.1016\/j.ajpath.2024.07.023_bib74","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2023.114233","article-title":"Polygoni multiflori radix exacerbates idiosyncratic inflammatory liver injury through the FXR-SHP pathway and altered pharmacokinetic behavior","volume":"160","author":"Zhang","year":"2023","journal-title":"Biomed Pharmacother"},{"key":"10.1016\/j.ajpath.2024.07.023_bib75","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1023\/A:1007082515548","article-title":"Cholangiocarcinoma and liver cirrhosis in relation to changes due to thioacetamide","volume":"208","author":"Al-Bader","year":"2000","journal-title":"Mol Cell Biochem"},{"key":"10.1016\/j.ajpath.2024.07.023_bib76","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/0163-7258(96)00062-9","article-title":"N-nitrosodiethylamine mechanistic data and risk assessment: bioactivation, DNA-adduct formation, mutagenicity, and tumor initiation","volume":"71","author":"Verna","year":"1996","journal-title":"Pharmacol Ther"},{"key":"10.1016\/j.ajpath.2024.07.023_bib77","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1126\/science.108.2814.626","article-title":"Liver tumors in rats fed thiourea or thioacetamide","volume":"108","author":"Fitzhugh","year":"1948","journal-title":"Science"},{"key":"10.1016\/j.ajpath.2024.07.023_bib78","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1007\/s00204-015-1561-2","article-title":"Toxicogenomic assessment of liver responses following subchronic exposure to furan in fischer F344 rats","volume":"90","author":"Dong","year":"2016","journal-title":"Arch Toxicol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib79","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s12016-008-8085-y","article-title":"Medical treatment of primary sclerosing cholangitis: a role for novel bile acids and other (post-)transcriptional modulators?","volume":"36","author":"Beuers","year":"2009","journal-title":"Clin Rev Allergy Immunol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib80","doi-asserted-by":"crossref","first-page":"420","DOI":"10.5217\/ir.2023.00039","article-title":"Treatment of primary sclerosing cholangitis combined with inflammatory bowel disease","volume":"21","author":"Kim","year":"2023","journal-title":"Intest Res"},{"key":"10.1016\/j.ajpath.2024.07.023_bib81","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1053\/j.gastro.2024.01.049","article-title":"Immunopathogenesis of primary biliary cholangitis, primary sclerosing cholangitis and autoimmune hepatitis: themes and concepts","volume":"166","author":"Trivedi","year":"2024","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ajpath.2024.07.023_bib82","doi-asserted-by":"crossref","DOI":"10.1016\/j.mce.2022.111618","article-title":"Discovery of farnesoid X receptor and its role in bile acid metabolism","volume":"548","author":"Chiang","year":"2022","journal-title":"Mol Cell Endocrinol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib83","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/164_2019_231","article-title":"Targeting FXR in cholestasis","volume":"256","author":"Keitel","year":"2019","journal-title":"Handb Exp Pharmacol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib84","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3390\/diseases8020020","article-title":"Primary biliary cholangitis and bile acid farnesoid X receptor agonists","volume":"8","author":"Abenavoli","year":"2020","journal-title":"Diseases"},{"key":"10.1016\/j.ajpath.2024.07.023_bib85","doi-asserted-by":"crossref","first-page":"11323","DOI":"10.1073\/pnas.0604772103","article-title":"Benefit of farnesoid X receptor inhibition in obstructive cholestasis","volume":"103","author":"Stedman","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ajpath.2024.07.023_bib86","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1002\/jat.4298","article-title":"Farnesoid X receptor contributes to oleanolic acid-induced cholestatic liver injury in mice","volume":"42","author":"Feng","year":"2022","journal-title":"J Appl Toxicol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib87","doi-asserted-by":"crossref","first-page":"G295","DOI":"10.1152\/ajpgi.00134.2015","article-title":"Mice with hepatocyte-specific FXR deficiency are resistant to spontaneous but susceptible to cholic acid-induced hepatocarcinogenesis","volume":"310","author":"Kong","year":"2016","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib88","doi-asserted-by":"crossref","first-page":"34606","DOI":"10.18632\/oncotarget.5314","article-title":"FXR induces SOCS3 and suppresses hepatocellular carcinoma","volume":"6","author":"Guo","year":"2015","journal-title":"Oncotarget"},{"key":"10.1016\/j.ajpath.2024.07.023_bib89","doi-asserted-by":"crossref","first-page":"4226","DOI":"10.18632\/oncotarget.2899","article-title":"Farnesoid X receptor associates with beta-catenin and inhibits its activity in hepatocellular carcinoma","volume":"6","author":"Liu","year":"2015","journal-title":"Oncotarget"},{"key":"10.1016\/j.ajpath.2024.07.023_bib90","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.bbrc.2016.04.106","article-title":"FXR blocks the growth of liver cancer cells through inhibiting mTOR-s6K pathway","volume":"474","author":"Huang","year":"2016","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.ajpath.2024.07.023_bib91","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1002\/hep.26971","article-title":"SIRT1 controls liver regeneration by regulating bile acid metabolism through farnesoid X receptor and mammalian target of rapamycin signaling","volume":"59","author":"Garcia-Rodriguez","year":"2014","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2024.07.023_bib92","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0043044","article-title":"FXR controls the tumor suppressor NDRG2 and FXR agonists reduce liver tumor growth and metastasis in an orthotopic mouse xenograft model","volume":"7","author":"Deuschle","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.ajpath.2024.07.023_bib93","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0048461","article-title":"Src-mediated cross-talk between farnesoid X and epidermal growth factor receptors inhibits human intestinal cell proliferation and tumorigenesis","volume":"7","author":"Peng","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.ajpath.2024.07.023_bib94","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1093\/carcin\/bgl249","article-title":"Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice","volume":"28","author":"Kim","year":"2007","journal-title":"Carcinogenesis"},{"key":"10.1016\/j.ajpath.2024.07.023_bib95","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0210077","article-title":"The FXR agonist obeticholic acid inhibits the cancerogenic potential of human cholangiocarcinoma","volume":"14","author":"Di Matteo","year":"2019","journal-title":"PLoS One"},{"key":"10.1016\/j.ajpath.2024.07.023_bib96","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1159\/000491715","article-title":"FXR acts as a metastasis suppressor in intrahepatic cholangiocarcinoma by inhibiting IL-6-induced epithelial-mesenchymal transition","volume":"48","author":"Lv","year":"2018","journal-title":"Cell Physiol Biochem"},{"key":"10.1016\/j.ajpath.2024.07.023_bib97","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1053\/j.gastro.2018.04.032","article-title":"Mechanisms of MAFG dysregulation in cholestatic liver injury and development of liver cancer","volume":"155","author":"Liu","year":"2018","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ajpath.2024.07.023_bib98","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1016\/j.bbadis.2017.08.016","article-title":"Differential effects of FXR or TGR5 activation in cholangiocarcinoma progression","volume":"1864","author":"Erice","year":"2018","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"10.1016\/j.ajpath.2024.07.023_bib99","doi-asserted-by":"crossref","first-page":"34617","DOI":"10.18632\/oncotarget.8964","article-title":"FXR agonists enhance the sensitivity of biliary tract cancer cells to cisplatin via SHP dependent inhibition of Bcl-xL expression","volume":"7","author":"Wang","year":"2016","journal-title":"Oncotarget"},{"key":"10.1016\/j.ajpath.2024.07.023_bib100","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1756-8722-4-41","article-title":"Impact of bile acids on the growth of human cholangiocarcinoma via FXR","volume":"4","author":"Dai","year":"2011","journal-title":"J Hematol Oncol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib101","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1002\/path.5780","article-title":"Disordered farnesoid X receptor signaling is associated with liver carcinogenesis in Abcb11-deficient mice","volume":"255","author":"Wang","year":"2021","journal-title":"J Pathol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib102","article-title":"Effect of FXR agonist GW4064 in the treatment of hilar cholangiocarcinoma in rats","volume":"12","author":"Wang","year":"2022","journal-title":"Sci Rep"},{"key":"10.1016\/j.ajpath.2024.07.023_bib103","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.gene.2011.11.028","article-title":"MicroRNA-421 functions as an oncogenic miRNA in biliary tract cancer through down-regulating farnesoid X receptor expression","volume":"493","author":"Zhong","year":"2012","journal-title":"Gene"},{"key":"10.1016\/j.ajpath.2024.07.023_bib104","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/j.jhep.2014.12.034","article-title":"Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity","volume":"62","author":"Mueller","year":"2015","journal-title":"J Hepatol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib105","doi-asserted-by":"crossref","first-page":"4021","DOI":"10.1210\/endo.141.11.7771","volume":"141","author":"Memon","year":"2000","journal-title":"Endocrinology"},{"key":"10.1016\/j.ajpath.2024.07.023_bib106","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1159\/000450912","article-title":"Regulation of liver energy balance by the nuclear receptors farnesoid X receptor and peroxisome proliferator activated receptor alpha","volume":"35","author":"Kim","year":"2017","journal-title":"Dig Dis"},{"key":"10.1016\/j.ajpath.2024.07.023_bib107","doi-asserted-by":"crossref","first-page":"389","DOI":"10.5551\/jat.48918","article-title":"Clinical applications of a novel selective PPARalpha modulator, pemafibrate, in dyslipidemia and metabolic diseases","volume":"26","author":"Yamashita","year":"2019","journal-title":"J Atheroscler Thromb"},{"key":"10.1016\/j.ajpath.2024.07.023_bib108","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/ncpcardio1278","article-title":"Fibrates and future PPARalpha agonists in the treatment of cardiovascular disease","volume":"5","author":"Staels","year":"2008","journal-title":"Nat Clin Pract Cardiovasc Med"},{"key":"10.1016\/j.ajpath.2024.07.023_bib109","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1002\/cpt.1930","article-title":"Fenofibrate improves liver function and reduces the toxicity of the bile acid pool in patients with primary biliary cholangitis and primary sclerosing cholangitis who are partial responders to ursodiol","volume":"108","author":"Ghonem","year":"2020","journal-title":"Clin Pharmacol Ther"},{"key":"10.1016\/j.ajpath.2024.07.023_bib110","doi-asserted-by":"crossref","DOI":"10.1016\/j.jtauto.2023.100188","article-title":"PPAR agonists for the treatment of primary biliary cholangitis: old and new tales","volume":"6","author":"Colapietro","year":"2023","journal-title":"J Transl Autoimmun"},{"key":"10.1016\/j.ajpath.2024.07.023_bib111","doi-asserted-by":"crossref","first-page":"16492","DOI":"10.1073\/pnas.2002672117","article-title":"JNK-mediated disruption of bile acid homeostasis promotes intrahepatic cholangiocarcinoma","volume":"117","author":"Manieri","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ajpath.2024.07.023_bib112","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.dld.2014.09.002","article-title":"Recruited metastasis suppressor NM23-H2 attenuates expression and activity of peroxisome proliferator-activated receptor delta (PPARdelta) in human cholangiocarcinoma","volume":"47","author":"He","year":"2015","journal-title":"Dig Liver Dis"},{"key":"10.1016\/j.ajpath.2024.07.023_bib113","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1053\/jhep.2003.50296","article-title":"PPARgamma ligands inhibit cholangiocarcinoma cell growth through p53-dependent GADD45 and p21 pathway","volume":"38","author":"Han","year":"2003","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2024.07.023_bib114","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1007\/s10620-005-9064-2","article-title":"A ligand for peroxisome proliferator-activated receptor gamma inhibits human cholangiocarcinoma cell growth: potential molecular targeting strategy for cholangioma","volume":"51","author":"Kobuke","year":"2006","journal-title":"Dig Dis Sci"},{"key":"10.1016\/j.ajpath.2024.07.023_bib115","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1245\/s10434-017-5871-x","article-title":"Micro-RNA-130a-3p regulates gemcitabine resistance via PPARG in cholangiocarcinoma","volume":"24","author":"Asukai","year":"2017","journal-title":"Ann Surg Oncol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib116","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s13402-022-00668-7","article-title":"Soluble TGFBI aggravates the malignancy of cholangiocarcinoma through activation of the ITGB1 dependent PPARgamma signalling pathway","volume":"45","author":"Lee","year":"2022","journal-title":"Cell Oncol (Dordr)"},{"key":"10.1016\/j.ajpath.2024.07.023_bib117","doi-asserted-by":"crossref","first-page":"236","DOI":"10.4103\/2231-4040.90879","article-title":"The peroxisome proliferator-activated receptor: a family of nuclear receptors role in various diseases","volume":"2","author":"Tyagi","year":"2011","journal-title":"J Adv Pharm Technol Res"},{"key":"10.1016\/j.ajpath.2024.07.023_bib118","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.bbalip.2007.02.013","article-title":"PPARs and molecular mechanisms of transrepression","volume":"1771","author":"Ricote","year":"2007","journal-title":"Biochim Biophys Acta"},{"key":"10.1016\/j.ajpath.2024.07.023_bib119","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1111\/bph.14886","article-title":"Rosiglitazone alleviates intrahepatic cholestasis induced by alpha-naphthylisothiocyanate in mice: the role of circulating 15-deoxy-delta(12,14) -PGJ(2) and Nogo","volume":"177","author":"Zhang","year":"2020","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib120","article-title":"Roles of PPARgamma\/NF-kappaB signaling pathway in the pathogenesis of intrahepatic cholestasis of pregnancy","volume":"9","author":"Zhang","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.ajpath.2024.07.023_bib121","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/j.bbrc.2018.09.035","article-title":"PPARgamma provides anti-inflammatory and protective effects in intrahepatic cholestasis of pregnancy through NF-kappaB pathway","volume":"504","author":"Zhang","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.ajpath.2024.07.023_bib122","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1097\/HEP.0000000000000784","article-title":"Oleic acid-PPARgamma-FABP4 loop fuels cholangiocarcinoma colonization in lymph node metastases microenvironment","volume":"80","author":"Zhang","year":"2024","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2024.07.023_bib123","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.bbrc.2008.04.086","article-title":"Quantitative expression patterns of peroxisome proliferator-activated receptor-beta\/delta (PPARbeta\/delta) protein in mice","volume":"371","author":"Girroir","year":"2008","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.ajpath.2024.07.023_bib124","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1210\/er.2005-0012","article-title":"Roles of skeletal muscle and peroxisome proliferator-activated receptors in the development and treatment of obesity","volume":"27","author":"Lopez-Soriano","year":"2006","journal-title":"Endocr Rev"},{"key":"10.1016\/j.ajpath.2024.07.023_bib125","doi-asserted-by":"crossref","first-page":"E1369","DOI":"10.1073\/pnas.1202464109","article-title":"Protection from liver fibrosis by a peroxisome proliferator-activated receptor delta agonist","volume":"109","author":"Iwaisako","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ajpath.2024.07.023_bib126","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2022.102056","article-title":"Selective PPARdelta agonist seladelpar suppresses bile acid synthesis by reducing hepatocyte CYP7A1 via the fibroblast growth factor 21 signaling pathway","volume":"298","author":"Kouno","year":"2022","journal-title":"J Biol Chem"},{"key":"10.1016\/j.ajpath.2024.07.023_bib127","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1056\/NEJMoa2312100","article-title":"A phase 3 trial of seladelpar in primary biliary cholangitis","volume":"390","author":"Hirschfield","year":"2024","journal-title":"N Engl J Med"},{"key":"10.1016\/j.ajpath.2024.07.023_bib128","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1056\/NEJMoa2306185","article-title":"Efficacy and safety of elafibranor in primary biliary cholangitis","volume":"390","author":"Kowdley","year":"2024","journal-title":"N Engl J Med"},{"key":"10.1016\/j.ajpath.2024.07.023_bib129","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.1002\/tox.23906","article-title":"Estrogen receptor alpha-mediated mitochondrial damage in intrahepatic bile duct epithelial cells leading to the pathogenesis of primary biliary cholangitis","volume":"38","author":"Liang","year":"2023","journal-title":"Environ Toxicol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib130","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1053\/j.gastro.2004.03.059","article-title":"Estrogen receptor alpha, but not beta, plays a major role in 17beta-estradiol-induced murine cholesterol gallstones","volume":"127","author":"Wang","year":"2004","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ajpath.2024.07.023_bib131","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1016\/j.ajpath.2023.06.010","article-title":"Sex-dependent differences in cholestasis: why estrogen signaling may be a key pathophysiological driver","volume":"193","author":"Ismail","year":"2023","journal-title":"Am J Pathol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib132","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/j.1478-3231.2004.00920.x","article-title":"Tamoxifen: a novel treatment for primary biliary cirrhosis?","volume":"24","author":"Reddy","year":"2004","journal-title":"Liver Int"},{"key":"10.1016\/j.ajpath.2024.07.023_bib133","doi-asserted-by":"crossref","first-page":"3537","DOI":"10.3748\/wjg.v12.i22.3537","article-title":"Estrogens and the pathophysiology of the biliary tree","volume":"12","author":"Alvaro","year":"2006","journal-title":"World J Gastroenterol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib134","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1007\/s00432-012-1207-1","article-title":"Estrogen is increased in male cholangiocarcinoma patients' serum and stimulates invasion in cholangiocarcinoma cell lines in\u00a0vitro","volume":"138","author":"Hunsawong","year":"2012","journal-title":"J Cancer Res Clin Oncol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib135","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/s41416-020-0835-5","article-title":"Exogenous hormone use, reproductive factors and risk of intrahepatic cholangiocarcinoma among women: results from cohort studies in the liver cancer pooling project and the UK Biobank","volume":"123","author":"Petrick","year":"2020","journal-title":"Br J Cancer"},{"key":"10.1016\/j.ajpath.2024.07.023_bib136","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.omto.2021.06.017","article-title":"R-2HG downregulates ERalpha to inhibit cholangiocarcinoma via the FTO\/m6A-methylated ERalpha\/miR16-5p\/YAP1 signal pathway","volume":"23","author":"Gao","year":"2021","journal-title":"Mol Ther Oncolytics"},{"key":"10.1016\/j.ajpath.2024.07.023_bib137","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.fct.2018.06.014","article-title":"Glyphosate induces growth of estrogen receptor alpha positive cholangiocarcinoma cells via non-genomic estrogen receptor\/ERK1\/2 signaling pathway","volume":"118","author":"Sritana","year":"2018","journal-title":"Food Chem Toxicol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib138","first-page":"183","article-title":"[Differences in nutrition manners among short-statured and tall-statured girls and boys from Swietokrzyskie Voivodeship]","volume":"15","author":"Suliga","year":"2009","journal-title":"Pediatr Endocrinol Diabetes Metab"},{"key":"10.1016\/j.ajpath.2024.07.023_bib139","doi-asserted-by":"crossref","first-page":"877","DOI":"10.2353\/ajpath.2006.050464","article-title":"Estrogens and insulin-like growth factor 1 modulate neoplastic cell growth in human cholangiocarcinoma","volume":"169","author":"Alvaro","year":"2006","journal-title":"Am J Pathol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib140","first-page":"1743","article-title":"Tamoxifen-mediated growth inhibition of human cholangiocarcinoma","volume":"57","author":"Sampson","year":"1997","journal-title":"Cancer Res"},{"key":"10.1016\/j.ajpath.2024.07.023_bib141","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0002-9440(10)65113-9","article-title":"Apoptosis and tumorigenesis in human cholangiocarcinoma cells: involvement of Fas\/APO-1 (CD95) and calmodulin","volume":"155","author":"Pan","year":"1999","journal-title":"Am J Pathol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib142","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2133\/dmpk.23.2","article-title":"Regulation of hepatocyte nuclear factor 4 alpha-mediated transcription","volume":"23","author":"Gonzalez","year":"2008","journal-title":"Drug Metab Pharmacokinet"},{"key":"10.1016\/j.ajpath.2024.07.023_bib143","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1517\/17425250802707342","article-title":"Hepatocyte nuclear factor 4alpha regulation of bile acid and drug metabolism","volume":"5","author":"Chiang","year":"2009","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib144","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1002\/hep.20155","article-title":"Progression of HCC in mice is associated with a downregulation in the expression of hepatocyte nuclear factors","volume":"39","author":"Lazarevich","year":"2004","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2024.07.023_bib145","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1124\/mol.115.098822","article-title":"Estrogen-induced cholestasis leads to repressed CYP2D6 expression in CYP2D6-humanized mice","volume":"88","author":"Pan","year":"2015","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib146","doi-asserted-by":"crossref","first-page":"12759","DOI":"10.1074\/jbc.RA118.001789","article-title":"Cholestasis-induced bile acid elevates estrogen level via farnesoid X receptor-mediated suppression of the estrogen sulfotransferase SULT1E1","volume":"293","author":"Liu","year":"2018","journal-title":"J Biol Chem"},{"key":"10.1016\/j.ajpath.2024.07.023_bib147","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1016\/j.jhep.2021.08.011","article-title":"Therapeutic HNF4A mRNA attenuates liver fibrosis in a preclinical model","volume":"75","author":"Yang","year":"2021","journal-title":"J Hepatol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib148","doi-asserted-by":"crossref","first-page":"2480","DOI":"10.1002\/hep.26251","article-title":"Hepatocyte nuclear factor 4 alpha deletion promotes diethylnitrosamine-induced hepatocellular carcinoma in rodents","volume":"57","author":"Walesky","year":"2013","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2024.07.023_bib149","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/nature13441","article-title":"Mutant IDH inhibits HNF-4alpha to block hepatocyte differentiation and promote biliary cancer","volume":"513","author":"Saha","year":"2014","journal-title":"Nature"},{"key":"10.1016\/j.ajpath.2024.07.023_bib150","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.jcmgh.2022.10.011","article-title":"Vitamin D receptor activation targets ROS-mediated crosstalk between autophagy and apoptosis in hepatocytes in cholestasic mice","volume":"15","author":"Zheng","year":"2023","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib151","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1586\/17512433.2013.841078","article-title":"Hepatic actions of vitamin D receptor ligands: a sunshine option for chronic liver disease?","volume":"6","author":"Ding","year":"2013","journal-title":"Expert Rev Clin Pharmacol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib152","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1002\/hep.26453","article-title":"Vitamin D nuclear receptor deficiency promotes cholestatic liver injury by disruption of biliary epithelial cell junctions in mice","volume":"58","author":"Firrincieli","year":"2013","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2024.07.023_bib153","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbadis.2020.166067","article-title":"Cholangiopathy aggravation is caused by VDR ablation and alleviated by VDR-independent vitamin D signaling in ABCB4 knockout mice","volume":"1867","author":"Gonzalez-Sanchez","year":"2021","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"10.1016\/j.ajpath.2024.07.023_bib154","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1002\/cncr.22716","article-title":"Overexpression of vitamin D receptor indicates a good prognosis for cholangiocarcinoma: implications for therapeutics","volume":"109","author":"Seubwai","year":"2007","journal-title":"Cancer"},{"key":"10.1016\/j.ajpath.2024.07.023_bib155","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.dld.2012.12.012","article-title":"Dysregulation of vitamin D3 synthesis leads to enhanced cholangiocarcinoma growth","volume":"45","author":"Kennedy","year":"2013","journal-title":"Dig Liver Dis"},{"key":"10.1016\/j.ajpath.2024.07.023_bib156","doi-asserted-by":"crossref","DOI":"10.1038\/srep43773","article-title":"MART-10 represses cholangiocarcinoma cell growth and high vitamin D receptor expression indicates better prognosis for cholangiocarcinoma","volume":"7","author":"Chiang","year":"2017","journal-title":"Sci Rep"},{"key":"10.1016\/j.ajpath.2024.07.023_bib157","doi-asserted-by":"crossref","first-page":"3849","DOI":"10.18632\/oncotarget.2000","article-title":"Chemopreventive and chemotherapeutic effect of dietary supplementation of vitamin D on cholangiocarcinoma in a chemical-induced animal model","volume":"5","author":"Chiang","year":"2014","journal-title":"Oncotarget"},{"key":"10.1016\/j.ajpath.2024.07.023_bib158","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbadis.2021.166085","article-title":"The role of the retinoid receptor, RAR\/RXR heterodimer, in liver physiology","volume":"1867","author":"Li","year":"2021","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"10.1016\/j.ajpath.2024.07.023_bib159","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2023.105255","article-title":"Energy status regulates levels of the RAR\/RXR ligand 9-cis-retinoic acid in mammalian tissues: glucose reduces its synthesis in beta-cells","volume":"299","author":"Yoo","year":"2023","journal-title":"J Biol Chem"},{"key":"10.1016\/j.ajpath.2024.07.023_bib160","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1053\/gast.2002.34758","article-title":"Organ-specific alterations in RAR alpha:RXR alpha abundance regulate rat Mrp2 (Abcc2) expression in obstructive cholestasis","volume":"123","author":"Denson","year":"2002","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ajpath.2024.07.023_bib161","doi-asserted-by":"crossref","first-page":"G798","DOI":"10.1152\/ajpgi.00319.2004","article-title":"Role of nuclear receptors and hepatocyte-enriched transcription factors for Ntcp repression in biliary obstruction in mouse liver","volume":"289","author":"Zollner","year":"2005","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib162","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1111\/j.1478-3231.2007.01506.x","article-title":"Expression of bile acid synthesis and detoxification enzymes and the alternative bile acid efflux pump MRP4 in patients with primary biliary cirrhosis","volume":"27","author":"Zollner","year":"2007","journal-title":"Liver Int"},{"key":"10.1016\/j.ajpath.2024.07.023_bib163","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.bbrc.2018.06.001","article-title":"9-Cis-retinoic acid elevates MRP3 expression by inhibiting sumoylation of RXRalpha to alleviate cholestatic liver injury","volume":"503","author":"Yuan","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.ajpath.2024.07.023_bib164","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1111\/liv.13698","article-title":"Cenicriviroc, a cytokine receptor antagonist, potentiates all-trans retinoic acid in reducing liver injury in cholestatic rodents","volume":"38","author":"Yu","year":"2018","journal-title":"Liver Int"},{"key":"10.1016\/j.ajpath.2024.07.023_bib165","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.1097\/MCG.0000000000000591","article-title":"Combination therapy of all-trans retinoic acid with ursodeoxycholic acid in patients with primary sclerosing cholangitis: a human pilot study","volume":"51","author":"Assis","year":"2017","journal-title":"J Clin Gastroenterol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib166","article-title":"Analysis of harmony between color and fragrance in lighting environments by the reaction of the orbitofrontal area","volume":"13","author":"Yamashita","year":"2022","journal-title":"Iperception"},{"key":"10.1016\/j.ajpath.2024.07.023_bib167","doi-asserted-by":"crossref","first-page":"3602","DOI":"10.3892\/mmr.2016.5701","article-title":"Upregulation of retinoic acid receptor-beta reverses drug resistance in cholangiocarcinoma cells by enhancing susceptibility to apoptosis","volume":"14","author":"Ren","year":"2016","journal-title":"Mol Med Rep"},{"key":"10.1016\/j.ajpath.2024.07.023_bib168","doi-asserted-by":"crossref","first-page":"373","DOI":"10.2174\/1568009615666150817120931","article-title":"Epigallocatechin-3-gallate increases RXRgamma-mediated pro-apoptotic and anti-invasive effects in gastrointestinal cancer cell lines","volume":"16","author":"Papi","year":"2016","journal-title":"Curr Cancer Drug Targets"},{"key":"10.1016\/j.ajpath.2024.07.023_bib169","doi-asserted-by":"crossref","first-page":"3416","DOI":"10.1128\/MCB.00384-13","article-title":"Oncogenic activity of retinoic acid receptor gamma is exhibited through activation of the Akt\/NF-kappaB and Wnt\/beta-catenin pathways in cholangiocarcinoma","volume":"33","author":"Huang","year":"2013","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.ajpath.2024.07.023_bib170","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1111\/cas.12802","article-title":"Retinoid X receptor alpha enhances human cholangiocarcinoma growth through simultaneous activation of Wnt\/beta-catenin and nuclear factor-kappaB pathways","volume":"106","author":"Huang","year":"2015","journal-title":"Cancer Sci"}],"container-title":["The American Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002944024003584?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002944024003584?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T11:11:13Z","timestamp":1762081873000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002944024003584"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":169,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["S0002944024003584"],"URL":"https:\/\/doi.org\/10.1016\/j.ajpath.2024.07.023","relation":{},"ISSN":["0002-9440"],"issn-type":[{"value":"0002-9440","type":"print"}],"subject":[],"published":{"date-parts":[[2025,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Hepatic Nuclear Receptors in Cholestasis-to-Cholangiocarcinoma Pathology","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Pathology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ajpath.2024.07.023","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 American Society for Investigative Pathology. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}