{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:03:45Z","timestamp":1790751825326,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T00:00:00Z","timestamp":1537315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["A21139"],"award-info":[{"award-number":["A21139"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["A12481"],"award-info":[{"award-number":["A12481"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["A17196"],"award-info":[{"award-number":["A17196"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000672","name":"Pathological Society of Great Britain and Ireland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000672","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent studies of muscle\u2010invasive bladder cancer show that <jats:italic>FGFR3<\/jats:italic> mutations are generally found in a luminal papillary tumour subtype that is characterised by better survival than other molecular subtypes. To better understand the role of FGFR3 in invasive bladder cancer, we examined the process of tumour development induced by the tobacco carcinogen OH\u2010BBN in genetically engineered models that express mutationally activated FGFR3 S249C or FGFR3 K644E in the urothelium. Both occurrence and progression of OH\u2010BBN\u2010driven tumours were increased in the presence of an S249C mutation compared to wild\u2010type control mice. Interestingly, at an early tumour initiation stage, the acute inflammatory response in OH\u2010BBN\u2010treated bladders was suppressed in the presence of an S249C mutation. However, at later stages of tumour progression, increased inflammation was observed in S249C tumours, long after the carcinogen administration had ceased. Early\u2010phase neutrophil depletion using an anti\u2010Ly6G monoclonal antibody resulted in an increased neutrophil\u2010to\u2010lymphocyte ratio at later stages of pathogenesis, indicative of enhanced tumour pathogenesis, which supports the hypothesis that suppression of acute inflammation could play a causative role. Statistical analyses of correlation showed that while initial bladder phenotypes in morphology and inflammation were FGFR3\u2010dependent, increased levels of inflammation were associated with tumour progression at the later stage. This study provides a novel insight into the tumour\u2010promoting effect of <jats:italic>FGFR3<\/jats:italic> mutations via regulation of inflammation at the pre\u2010tumour stage in the bladder. Copyright \u00a9 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.5143","type":"journal-article","created":{"date-parts":[[2018,7,25]],"date-time":"2018-07-25T04:04:02Z","timestamp":1532491442000},"page":"331-343","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["<i>FGFR3<\/i> mutation increases bladder tumourigenesis by suppressing acute inflammation"],"prefix":"10.1002","volume":"246","author":[{"given":"Mona","family":"Foth","sequence":"first","affiliation":[{"name":"School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences University of Glasgow  Glasgow UK"},{"name":"Cancer Research UK Beatson Institute  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur Faezah Binti","family":"Ismail","sequence":"additional","affiliation":[{"name":"School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeng Sum Charmaine","family":"Kung","sequence":"additional","affiliation":[{"name":"School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"Leeds Institute of Cancer and Pathology St James's University Hospital  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret A","family":"Knowles","sequence":"additional","affiliation":[{"name":"Leeds Institute of Cancer and Pathology St James's University Hospital  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pontus","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Division of Oncology and Pathology, Department of Clinical Sciences Lund University  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gottfrid","family":"Sj\u00f6dahl","sequence":"additional","affiliation":[{"name":"Division of Urological Research, Department of Translational Medicine Lund University, Sk\u00e5ne University Hospital  Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M","family":"Salmond","sequence":"additional","affiliation":[{"name":"Department of Pathology Queen Elizabeth University Hospital  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9540-3010","authenticated-orcid":false,"given":"Owen J","family":"Sansom","sequence":"additional","affiliation":[{"name":"Cancer Research UK Beatson Institute  Glasgow UK"},{"name":"Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences University of Glasgow  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9634-9738","authenticated-orcid":false,"given":"Tomoko","family":"Iwata","sequence":"additional","affiliation":[{"name":"School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2016.06.020"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2015.02.009"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-0077-T"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2798"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1318376111"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2014.01.009"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.007"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1203486"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2015.02.032"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.262"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw170"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2017.11"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-22126-x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2207"},{"key":"e_1_2_7_16_1","first-page":"850","article-title":"Mechanisms of FGFR\u2010mediated carcinogenesis","volume":"2012","author":"Ahmad I","year":"1823","journal-title":"Biochim Biophys Acta"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0696-233"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds486"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12965"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.8"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI38017"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6606016"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm2006222"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-3034"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-12-1150"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2014.10.013"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2267"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.67.2048"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.60.7341"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-015-0221-6"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.006874"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4334"},{"key":"e_1_2_7_33_1","first-page":"727","article-title":"Review: BBN as an urothelial carcinogen","volume":"26","author":"Vasconcelos\u2010Nobrega C","year":"2012","journal-title":"In Vivo"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2956"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3038"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2005.07.017"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep24039"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djk113"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2015.232"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI61067"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-15-0274"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw373.14"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3612"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700772"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2017.05.013"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00215.2011"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgh275"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.20075"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.52"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dju124"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3909"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2014.07.033"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2016.10.006"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.008888"},{"key":"e_1_2_7_55_1","first-page":"S13","article-title":"Establishment of tumour progression scale for invasive bladder cancer models. Winter Meeting. Abstracts of the 205th Meeting of the Pathological Society of Great Britain & Ireland, 7\u20138 January 2016, London","volume":"238","author":"Kung CJS","year":"2016","journal-title":"J Pathol"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.280"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-14-0022"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00368.2004"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/gene.10036"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.5143","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.5143","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T13:47:27Z","timestamp":1760968047000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.5143"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,19]]},"references-count":58,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1002\/path.5143"],"URL":"https:\/\/doi.org\/10.1002\/path.5143","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,19]]},"assertion":[{"value":"2018-02-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}