{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:49:34Z","timestamp":1790819374724,"version":"4.1.0"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"19","license":[{"start":{"date-parts":[[2017,10,24]],"date-time":"2017-10-24T00:00:00Z","timestamp":1508803200000},"content-version":"vor","delay-in-days":183,"URL":"http:\/\/www.pnas.org\/site\/misc\/userlicense.xhtml"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15K09039"],"award-info":[{"award-number":["15K09039"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2017,5,9]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Death-driven compensatory proliferation to repair tissue defects is an important promoter of inflammation-associated carcinogenesis. Our work using a mouse model demonstrates that a biliary epithelial injury-induced regenerative response mediated by IL-33 accelerates development of extrahepatic cholangiocarcinoma (ECC) from peribiliary glands, an effect that was suppressed by anti\u2013IL-33 treatment. Thus, IL-33 is a potential therapeutic target for ECC, and the mouse model reported in this study will enable identification of the mechanisms of biliary injury-based carcinogenesis.<\/jats:p>","DOI":"10.1073\/pnas.1619416114","type":"journal-article","created":{"date-parts":[[2017,4,24]],"date-time":"2017-04-24T20:55:25Z","timestamp":1493067325000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":73,"title":["Biliary epithelial injury-induced regenerative response by IL-33 promotes cholangiocarcinogenesis from peribiliary glands"],"prefix":"10.1073","volume":"114","author":[{"given":"Hayato","family":"Nakagawa","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobumi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan;"},{"name":"Division of Gastroenterology, Institute for Adult Diseases, Asahi Life Foundation, Chuo-ku, Tokyo 103-0002, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Hirata","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohko","family":"Hikiba","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Institute for Adult Diseases, Asahi Life Foundation, Chuo-ku, Tokyo 103-0002, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoku","family":"Hayakawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroto","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sozaburo","family":"Ihara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Uchino","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, Higashi Asahikawa, Hokkaido 078-8510, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Ijichi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2869-2881","authenticated-orcid":false,"given":"Motoyuki","family":"Otsuka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Arita","sequence":"additional","affiliation":[{"name":"Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihiro","family":"Kokudo","sequence":"additional","affiliation":[{"name":"Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Tateishi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Koike","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2017,4,24]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1053\/j.gastro.2013.10.013","article-title":"Pathogenesis, diagnosis, and management of cholangiocarcinoma","volume":"145","author":"Rizvi S","year":"2013","unstructured":"S Rizvi, GJ Gores, Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology 145, 1215\u20131229 (2013).","journal-title":"Gastroenterology"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.jhep.2006.09.001","article-title":"Cholangiocarcinoma: Modern advances in understanding a deadly old disease","volume":"45","author":"Malhi H","year":"2006","unstructured":"H Malhi, GJ Gores, Cholangiocarcinoma: Modern advances in understanding a deadly old disease. J Hepatol 45, 856\u2013867 (2006).","journal-title":"J Hepatol"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1038\/ng.2806","article-title":"Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers","volume":"45","author":"Chan-On W","year":"2013","unstructured":"W Chan-On, , Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers. Nat Genet 45, 1474\u20131478 (2013).","journal-title":"Nat Genet"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1038\/ng.3375","article-title":"Genomic spectra of biliary tract cancer","volume":"47","author":"Nakamura H","year":"2015","unstructured":"H Nakamura, , Genomic spectra of biliary tract cancer. Nat Genet 47, 1003\u20131010 (2015).","journal-title":"Nat Genet"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1002\/ar.20710","article-title":"Embryology of extra- and intrahepatic bile ducts, the ductal plate","volume":"291","author":"Roskams T","year":"2008","unstructured":"T Roskams, V Desmet, Embryology of extra- and intrahepatic bile ducts, the ductal plate. Anat Rec (Hoboken) 291, 628\u2013635 (2008).","journal-title":"Anat Rec (Hoboken)"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"3914","DOI":"10.1172\/JCI63065","article-title":"Intrahepatic cholangiocarcinoma can arise from Notch-mediated conversion of hepatocytes","volume":"122","author":"Sekiya S","year":"2012","unstructured":"S Sekiya, A Suzuki, Intrahepatic cholangiocarcinoma can arise from Notch-mediated conversion of hepatocytes. J Clin Invest 122, 3914\u20133918 (2012).","journal-title":"J Clin Invest"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1172\/JCI63212","article-title":"Cholangiocarcinomas can originate from hepatocytes in mice","volume":"122","author":"Fan B","year":"2012","unstructured":"B Fan, , Cholangiocarcinomas can originate from hepatocytes in mice. J Clin Invest 122, 2911\u20132915 (2012).","journal-title":"J Clin Invest"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1158\/0008-5472.CAN-13-1911","article-title":"Cell lineage tracing reveals a biliary origin of intrahepatic cholangiocarcinoma","volume":"74","author":"Guest RV","year":"2014","unstructured":"RV Guest, , Cell lineage tracing reveals a biliary origin of intrahepatic cholangiocarcinoma. Cancer Res 74, 1005\u20131010 (2014).","journal-title":"Cancer Res"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1002\/hep.26485","article-title":"Identification of intramural epithelial networks linked to peribiliary glands that express progenitor cell markers and proliferate after injury in mice","volume":"58","author":"Dipaola F","year":"2013","unstructured":"F Dipaola, , Identification of intramural epithelial networks linked to peribiliary glands that express progenitor cell markers and proliferate after injury in mice. Hepatology 58, 1486\u20131496 (2013).","journal-title":"Hepatology"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1002\/hep.28326","article-title":"The hepatic, biliary, and pancreatic network of stem\/progenitor cell niches in humans: A new reference frame for disease and regeneration","volume":"64","author":"Lanzoni G","year":"2016","unstructured":"G Lanzoni, V Cardinale, G Carpino, The hepatic, biliary, and pancreatic network of stem\/progenitor cell niches in humans: A new reference frame for disease and regeneration. Hepatology 64, 277\u2013286 (2016).","journal-title":"Hepatology"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"23899","DOI":"10.1038\/srep23899","article-title":"A novel mouse model of intrahepatic cholangiocarcinoma induced by liver-specific Kras activation and Pten deletion","volume":"6","author":"Ikenoue T","year":"2016","unstructured":"T Ikenoue, , A novel mouse model of intrahepatic cholangiocarcinoma induced by liver-specific Kras activation and Pten deletion. Sci Rep 6, 23899 (2016).","journal-title":"Sci Rep"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1172\/JCI27282","article-title":"Induction of intrahepatic cholangiocellular carcinoma by liver-specific disruption of Smad4 and Pten in mice","volume":"116","author":"Xu X","year":"2006","unstructured":"X Xu, , Induction of intrahepatic cholangiocellular carcinoma by liver-specific disruption of Smad4 and Pten in mice. J Clin Invest 116, 1843\u20131852 (2006).","journal-title":"J Clin Invest"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1002\/dvg.20397","article-title":"A CK19(CreERT) knockin mouse line allows for conditional DNA recombination in epithelial cells in multiple endodermal organs","volume":"46","author":"Means AL","year":"2008","unstructured":"AL Means, Y Xu, A Zhao, KC Ray, G Gu, A CK19(CreERT) knockin mouse line allows for conditional DNA recombination in epithelial cells in multiple endodermal organs. Genesis 46, 318\u2013323 (2008).","journal-title":"Genesis"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1101\/gad.1475506","article-title":"Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-beta signaling in cooperation with active Kras expression","volume":"20","author":"Ijichi H","year":"2006","unstructured":"H Ijichi, , Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-beta signaling in cooperation with active Kras expression. Genes Dev 20, 3147\u20133160 (2006).","journal-title":"Genes Dev"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"a003129","DOI":"10.1101\/cshperspect.a003129","article-title":"Involvement of members of the cadherin superfamily in cancer","volume":"1","author":"Berx G","year":"2009","unstructured":"G Berx, F van Roy, Involvement of members of the cadherin superfamily in cancer. Cold Spring Harb Perspect Biol 1, a003129 (2009).","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1038\/bjc.2014.415","article-title":"Prognostic significance of epithelial-mesenchymal transition-related markers in extrahepatic cholangiocarcinoma: Comprehensive immunohistochemical study using a tissue microarray","volume":"111","author":"Nitta T","year":"2014","unstructured":"T Nitta, , Prognostic significance of epithelial-mesenchymal transition-related markers in extrahepatic cholangiocarcinoma: Comprehensive immunohistochemical study using a tissue microarray. Br J Cancer 111, 1363\u20131372 (2014).","journal-title":"Br J Cancer"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1073\/pnas.1322731111","article-title":"Loss of liver E-cadherin induces sclerosing cholangitis and promotes carcinogenesis","volume":"111","author":"Nakagawa H","year":"2014","unstructured":"H Nakagawa, , Loss of liver E-cadherin induces sclerosing cholangitis and promotes carcinogenesis. Proc Natl Acad Sci USA 111, 1090\u20131095 (2014).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"4985","DOI":"10.3748\/wjg.v18.i36.4985","article-title":"Novel insight into mechanisms of cholestatic liver injury","volume":"18","author":"Woolbright BL","year":"2012","unstructured":"BL Woolbright, H Jaeschke, Novel insight into mechanisms of cholestatic liver injury. World J Gastroenterol 18, 4985\u20134993 (2012).","journal-title":"World J Gastroenterol"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nature11826","article-title":"In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration","volume":"494","author":"Huch M","year":"2013","unstructured":"M Huch, , In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature 494, 247\u2013250 (2013).","journal-title":"Nature"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.immuni.2015.06.006","article-title":"Interleukin-33 in tissue homeostasis, injury, and inflammation","volume":"42","author":"Molofsky AB","year":"2015","unstructured":"AB Molofsky, AK Savage, RM Locksley, Interleukin-33 in tissue homeostasis, injury, and inflammation. Immunity 42, 1005\u20131019 (2015).","journal-title":"Immunity"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"3241","DOI":"10.1172\/JCI73742","article-title":"Biliary repair and carcinogenesis are mediated by IL-33-dependent cholangiocyte proliferation","volume":"124","author":"Li J","year":"2014","unstructured":"J Li, , Biliary repair and carcinogenesis are mediated by IL-33-dependent cholangiocyte proliferation. J Clin Invest 124, 3241\u20133251 (2014).","journal-title":"J Clin Invest"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.immuni.2009.05.007","article-title":"Suppression of interleukin-33 bioactivity through proteolysis by apoptotic caspases","volume":"31","author":"L\u00fcthi AU","year":"2009","unstructured":"AU L\u00fcthi, , Suppression of interleukin-33 bioactivity through proteolysis by apoptotic caspases. Immunity 31, 84\u201398 (2009).","journal-title":"Immunity"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"10762","DOI":"10.1073\/pnas.1509070112","article-title":"IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions","volume":"112","author":"Monticelli LA","year":"2015","unstructured":"LA Monticelli, , IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions. Proc Natl Acad Sci USA 112, 10762\u201310767 (2015).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1038\/ni.2131","article-title":"Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus","volume":"12","author":"Monticelli LA","year":"2011","unstructured":"LA Monticelli, , Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus. Nat Immunol 12, 1045\u20131054 (2011).","journal-title":"Nat Immunol"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1007\/s10753-013-9802-0","article-title":"IL-33 neutralization suppresses lupus disease in lupus-prone mice","volume":"37","author":"Li P","year":"2014","unstructured":"P Li, W Lin, X Zheng, IL-33 neutralization suppresses lupus disease in lupus-prone mice. Inflammation 37, 824\u2013832 (2014).","journal-title":"Inflammation"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1242\/jcs.112.8.1237","article-title":"E-cadherin binding prevents beta-catenin nuclear localization and beta-catenin\/LEF-1-mediated transactivation","volume":"112","author":"Orsulic S","year":"1999","unstructured":"S Orsulic, O Huber, H Aberle, S Arnold, R Kemler, E-cadherin binding prevents beta-catenin nuclear localization and beta-catenin\/LEF-1-mediated transactivation. J Cell Sci 112, 1237\u20131245 (1999).","journal-title":"J Cell Sci"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"17206","DOI":"10.18632\/oncotarget.4043","article-title":"YAP is a critical oncogene in human cholangiocarcinoma","volume":"6","author":"Pei T","year":"2015","unstructured":"T Pei, , YAP is a critical oncogene in human cholangiocarcinoma. Oncotarget 6, 17206\u201317220 (2015).","journal-title":"Oncotarget"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"11930","DOI":"10.1073\/pnas.1103345108","article-title":"E-cadherin mediates contact inhibition of proliferation through Hippo signaling-pathway components","volume":"108","author":"Kim NG","year":"2011","unstructured":"NG Kim, E Koh, X Chen, BM Gumbiner, E-cadherin mediates contact inhibition of proliferation through Hippo signaling-pathway components. Proc Natl Acad Sci USA 108, 11930\u201311935 (2011).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_29_2","first-page":"6971","article-title":"Constitutive expression of ErbB-2 in gallbladder epithelium results in development of adenocarcinoma","volume":"61","author":"Kiguchi K","year":"2001","unstructured":"K Kiguchi, , Constitutive expression of ErbB-2 in gallbladder epithelium results in development of adenocarcinoma. Cancer Res 61, 6971\u20136976 (2001).","journal-title":"Cancer Res"},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.cell.2010.01.025","article-title":"Immunity, inflammation, and cancer","volume":"140","author":"Grivennikov SI","year":"2010","unstructured":"SI Grivennikov, FR Greten, M Karin, Immunity, inflammation, and cancer. Cell 140, 883\u2013899 (2010).","journal-title":"Cell"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.cell.2005.04.014","article-title":"IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis","volume":"121","author":"Maeda S","year":"2005","unstructured":"S Maeda, H Kamata, JL Luo, H Leffert, M Karin, IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell 121, 977\u2013990 (2005).","journal-title":"Cell"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ccr.2014.07.001","article-title":"ER stress cooperates with hypernutrition to trigger TNF-dependent spontaneous HCC development","volume":"26","author":"Nakagawa H","year":"2014","unstructured":"H Nakagawa, , ER stress cooperates with hypernutrition to trigger TNF-dependent spontaneous HCC development. Cancer Cell 26, 331\u2013343 (2014).","journal-title":"Cancer Cell"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1016\/j.jhep.2015.06.018","article-title":"Activation of biliary tree stem cells within peribiliary glands in primary sclerosing cholangitis","volume":"63","author":"Carpino G","year":"2015","unstructured":"G Carpino, , Activation of biliary tree stem cells within peribiliary glands in primary sclerosing cholangitis. J Hepatol 63, 1220\u20131228 (2015).","journal-title":"J Hepatol"},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1136\/jcp.2005.033712","article-title":"Liver fluke-associated and sporadic cholangiocarcinoma: An immunohistochemical study of bile duct, peribiliary gland and tumour cell phenotypes","volume":"59","author":"Hughes NR","year":"2006","unstructured":"NR Hughes, C Pairojkul, SG Royce, A Clouston, PS Bhathal, Liver fluke-associated and sporadic cholangiocarcinoma: An immunohistochemical study of bile duct, peribiliary gland and tumour cell phenotypes. J Clin Pathol 59, 1073\u20131078 (2006).","journal-title":"J Clin Pathol"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1002\/cncr.27955","article-title":"KRAS and GNAS mutations and p53 overexpression in biliary intraepithelial neoplasia and intrahepatic cholangiocarcinomas","volume":"119","author":"Hsu M","year":"2013","unstructured":"M Hsu, M Sasaki, S Igarashi, Y Sato, Y Nakanuma, KRAS and GNAS mutations and p53 overexpression in biliary intraepithelial neoplasia and intrahepatic cholangiocarcinomas. Cancer 119, 1669\u20131674 (2013).","journal-title":"Cancer"},{"key":"e_1_3_4_36_2","first-page":"161","article-title":"Profiling of transcripts and proteins modulated by K-ras oncogene in the lung tissues of K-ras transgenic mice by omics approaches","volume":"34","author":"Lee S","year":"2009","unstructured":"S Lee, , Profiling of transcripts and proteins modulated by K-ras oncogene in the lung tissues of K-ras transgenic mice by omics approaches. Int J Oncol 34, 161\u2013172 (2009).","journal-title":"Int J Oncol"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1002\/eji.201041135","article-title":"TGF-\u03b2 limits IL-33 production and promotes the resolution of colitis through regulation of macrophage function","volume":"41","author":"Rani R","year":"2011","unstructured":"R Rani, AG Smulian, DR Greaves, SP Hogan, DR Herbert, TGF-\u03b2 limits IL-33 production and promotes the resolution of colitis through regulation of macrophage function. Eur J Immunol 41, 2000\u20132009 (2011).","journal-title":"Eur J Immunol"},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/nm.2760","article-title":"T cell homing to epithelial barriers in allergic disease","volume":"18","author":"Islam SA","year":"2012","unstructured":"SA Islam, AD Luster, T cell homing to epithelial barriers in allergic disease. Nat Med 18, 705\u2013715 (2012).","journal-title":"Nat Med"},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1007\/s00436-016-4974-9","article-title":"Expression and potential roles of IL-33\/ST2 in the immune regulation during Clonorchis sinensis infection","volume":"115","author":"Yu Q","year":"2016","unstructured":"Q Yu, , Expression and potential roles of IL-33\/ST2 in the immune regulation during Clonorchis sinensis infection. Parasitol Res 115, 2299\u20132305 (2016).","journal-title":"Parasitol Res"},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.immuni.2016.06.017","article-title":"Allergen-experienced group 2 innate lymphoid cells acquire memory-like properties and enhance allergic lung inflammation","volume":"45","author":"Martinez-Gonzalez I","year":"2016","unstructured":"I Martinez-Gonzalez, , Allergen-experienced group 2 innate lymphoid cells acquire memory-like properties and enhance allergic lung inflammation. Immunity 45, 198\u2013208 (2016).","journal-title":"Immunity"},{"key":"e_1_3_4_41_2","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1002\/dvg.22384","article-title":"Non-parallel recombination limits Cre-LoxP-based reporters as precise indicators of conditional genetic manipulation","volume":"51","author":"Liu J","year":"2013","unstructured":"J Liu, , Non-parallel recombination limits Cre-LoxP-based reporters as precise indicators of conditional genetic manipulation. Genesis 51, 436\u2013442 (2013).","journal-title":"Genesis"},{"key":"e_1_3_4_42_2","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/5007","article-title":"Generalized lacZ expression with the ROSA26 Cre reporter strain","volume":"21","author":"Soriano P","year":"1999","unstructured":"P Soriano, Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat Genet 21, 70\u201371 (1999).","journal-title":"Nat Genet"},{"key":"e_1_3_4_43_2","volume-title":"Guide for the Care and Use of Laboratory Animals","author":"National Research Council","year":"2011","unstructured":"; National Research Council Guide for the Care and Use of Laboratory Animals (National Academies Press, 8th Ed, Washington, DC, 2011).","edition":"8"},{"key":"e_1_3_4_44_2","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.cell.2015.07.026","article-title":"Hybrid periportal hepatocytes regenerate the injured liver without giving rise to cancer","volume":"162","author":"Font-Burgada J","year":"2015","unstructured":"J Font-Burgada, , Hybrid periportal hepatocytes regenerate the injured liver without giving rise to cancer. Cell 162, 766\u2013779 (2015).","journal-title":"Cell"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1619416114","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1619416114","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T11:43:17Z","timestamp":1654602197000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1619416114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,24]]},"references-count":44,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2017,5,9]]}},"alternative-id":["10.1073\/pnas.1619416114"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1619416114","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,24]]},"assertion":[{"value":"2017-04-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}