{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T22:56:00Z","timestamp":1782946560091,"version":"3.54.5"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,4,22]],"date-time":"2015-04-22T00:00:00Z","timestamp":1429660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2015,5]]},"abstract":"The BRCA<\/jats:styled-content>\/Fanconi anemia (FA<\/jats:styled-content>) pathway plays a key role in the repair of DNA<\/jats:styled-content> double strand breaks. We focused on this pathway to clarify chemoresistance mechanisms in biliary tract cancer (BTC<\/jats:styled-content>). We also investigated changes in the CD<\/jats:styled-content>24+<\/jats:sup>\/44+<\/jats:sup> population that may be involved in chemoresistance, as this population likely includes cancer stem cells. We used three BTC<\/jats:styled-content> cell lines to establish gemcitabine (GEM<\/jats:styled-content>)\u2010resistant (GR<\/jats:styled-content>) cells and evaluated the expression of BRCA<\/jats:styled-content>\/FA<\/jats:styled-content> pathway components, chemoresistance, and the effect of BRCA<\/jats:styled-content>\/FA<\/jats:styled-content> pathway inhibition on the CD<\/jats:styled-content>24+<\/jats:sup>\/44+<\/jats:sup> population. FANCD<\/jats:styled-content>2 and CD<\/jats:styled-content>24 expression were evaluated in 108 resected BTC<\/jats:styled-content> specimens. GR<\/jats:styled-content> cells highly expressed the BRCA<\/jats:styled-content>\/FA<\/jats:styled-content> components. The BRCA<\/jats:styled-content>\/FA<\/jats:styled-content> pathway was upregulated by GEM<\/jats:styled-content> and cisplatin (CDDP<\/jats:styled-content>) exposure. Inhibition using siRNA<\/jats:styled-content> and RAD<\/jats:styled-content>51 inhibitor sensitized GR<\/jats:styled-content> cells to GEM<\/jats:styled-content> or CDDP<\/jats:styled-content>. The CD<\/jats:styled-content>24+<\/jats:sup>\/44+<\/jats:sup> population was increased in GR<\/jats:styled-content> and parent BTC<\/jats:styled-content> cells treated with GEM<\/jats:styled-content> or CDDP<\/jats:styled-content> and highly expressed BRCA<\/jats:styled-content>\/FA<\/jats:styled-content> genes. FANCD<\/jats:styled-content>2 was related to CD<\/jats:styled-content>24 expression in resected BTC<\/jats:styled-content> specimens. Inhibition of the BRCA<\/jats:styled-content>\/FA<\/jats:styled-content> pathway under GEM<\/jats:styled-content> reduced the CD<\/jats:styled-content>24+<\/jats:sup>\/44+<\/jats:sup> population in MzChA1\u2010GR<\/jats:styled-content> cells. Thus, high expression of the BRCA<\/jats:styled-content>\/FA<\/jats:styled-content> pathway is one mechanism of chemoresistance against GEM<\/jats:styled-content> and\/or CDDP<\/jats:styled-content> and is related to the CD<\/jats:styled-content>24+<\/jats:sup>\/44+<\/jats:sup> population in BTC<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/cas.12652","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T14:28:47Z","timestamp":1425392927000},"page":"584-591","source":"Crossref","is-referenced-by-count":22,"title":["BRCA<\/scp>\/Fanconi anemia pathway implicates chemoresistance to gemcitabine in biliary tract cancer"],"prefix":"10.1111","volume":"106","author":[{"given":"Shinsuke","family":"Nakashima","sequence":"first","affiliation":[{"name":"Department of Surgery Graduate School of Medicine Osaka University Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shogo","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Surgery Graduate School of Medicine Osaka University Osaka Japan"},{"name":"Department of Surgery Osaka Medical Center for Cancer and Cardio\u2010Vascular Diseases Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Nagano","sequence":"additional","affiliation":[{"name":"Department of Surgery Graduate School of Medicine Osaka University Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Tomokuni","sequence":"additional","affiliation":[{"name":"Department of Surgery Graduate School of Medicine Osaka University Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshito","family":"Tomimaru","sequence":"additional","affiliation":[{"name":"Department of Surgery Graduate School of Medicine Osaka University Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadafumi","family":"Asaoka","sequence":"additional","affiliation":[{"name":"Department of Surgery Graduate School of Medicine Osaka University Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Hama","sequence":"additional","affiliation":[{"name":"Department of Surgery Graduate School of Medicine Osaka University Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Wada","sequence":"additional","affiliation":[{"name":"Department of Surgery Graduate School of Medicine Osaka University Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Kawamoto","sequence":"additional","affiliation":[{"name":"Department of Surgery Graduate School of Medicine Osaka University Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Marubashi","sequence":"additional","affiliation":[{"name":"Department of Surgery Graduate School of Medicine Osaka University Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Eguchi","sequence":"additional","affiliation":[{"name":"Department of Surgery Graduate School of Medicine Osaka University Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Doki","sequence":"additional","affiliation":[{"name":"Department of Surgery Graduate School of Medicine Osaka University Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Surgery Graduate School of Medicine Osaka University Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,4,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24145"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jso.21971"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijsu.2012.12.006"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00595-011-0057-9"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0908721"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-010-9417-3"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605779"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-010-9553-9"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1159\/000354209"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2014.31"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2013.05.021"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.5114\/fn.2013.39716"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080023"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2013-0163"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000351260"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-013-2181-2"},{"key":"e_1_2_7_18_1","first-page":"6110","article-title":"Action of 2\u2032,2\u2032\u2010difluorodeoxycytidine on DNA synthesis","volume":"51","author":"Huang P","year":"1991","journal-title":"Cancer Res"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-06-0633"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-08-0662"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3399"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc970"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0696-241"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdq628"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2014.04.003"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25317"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2499"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2012.09.001"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-11-1040"},{"key":"e_1_2_7_31_1","first-page":"4469","article-title":"Low production of reactive oxygen species and high DNA repair: mechanism of radioresistance of prostate cancer stem cells","volume":"33","author":"Kim YS","year":"2013","journal-title":"Anticancer Res"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.03.010"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910520217"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840070322"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(85)80002-7"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2012.12.002"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.121616198"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v17.i24.2965"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.10.11.13664"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00534-012-0542-6"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00595-012-0437-9"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.3816\/CLC.2005.n.005"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i9.1438"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/35077232"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb100428c"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.10.5858"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.9.4.10764"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2210-11-7"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203578"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22738"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh260"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0044254"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602935"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcas.12652","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.12652","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.12652","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.12652","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T01:18:11Z","timestamp":1696295891000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.12652"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4,22]]},"references-count":52,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["10.1111\/cas.12652"],"URL":"https:\/\/doi.org\/10.1111\/cas.12652","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,22]]}}}