{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:34:15Z","timestamp":1790735655211,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,1,8]],"date-time":"2015-01-08T00:00:00Z","timestamp":1420675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000892","name":"Prostate Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000892","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"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Inflammation is associated with several diseases of the prostate including benign enlargement and cancer, but a causal relationship has not been established. Our objective was to characterize the prostate inflammatory microenvironment after infection with a human prostate\u2010derived bacterial strain and to determine the effect of inflammation on prostate cancer progression. To this end, we mimicked typical human prostate infection with retrograde urethral instillation of <jats:styled-content style=\"fixed-case\">CP1<\/jats:styled-content>, a human prostatic isolate of <jats:italic>Escherichia coli<\/jats:italic>. <jats:styled-content style=\"fixed-case\">CP1<\/jats:styled-content> bacteria were tropic for the accessory sex glands and induced acute inflammation in the prostate and seminal vesicles, with chronic inflammation lasting at least 1 year. Compared to controls, infection induced both acute and chronic inflammation with epithelial hyperplasia, stromal hyperplasia, and inflammatory cell infiltrates. In areas of inflammation, epithelial proliferation and hyperplasia often persist, despite decreased expression of androgen receptor (<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>). Inflammatory cells in the prostates of <jats:styled-content style=\"fixed-case\">CP1<\/jats:styled-content>\u2010infected mice were characterized at 8 weeks post\u2010infection by flow cytometry, which showed an increase in macrophages and lymphocytes, particularly Th17 cells. Inflammation was additionally assessed in the context of carcinogenesis. Multiplex cytokine profiles of inflamed prostates showed that distinct inflammatory cytokines were expressed during prostate inflammation and cancer, with a subset of cytokines synergistically increased during concurrent inflammation and cancer. Furthermore, <jats:styled-content style=\"fixed-case\">CP1<\/jats:styled-content> infection in the Hi\u2010Myc mouse model of prostate cancer accelerated the development of invasive prostate adenocarcinoma, with 70% more mice developing cancer by 4.5\u2009months of age. This study provides direct evidence that prostate inflammation accelerates prostate cancer progression and gives insight into the microenvironment changes induced by inflammation that may accelerate tumour initiation or progression. Copyright \u00a9 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4472","type":"journal-article","created":{"date-parts":[[2014,10,28]],"date-time":"2014-10-28T03:55:10Z","timestamp":1414468510000},"page":"478-489","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["A human prostatic bacterial isolate alters the prostatic microenvironment and accelerates prostate cancer progression"],"prefix":"10.1002","volume":"235","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0644-211X","authenticated-orcid":false,"given":"Brian W","family":"Simons","sequence":"first","affiliation":[{"name":"The Brady Urological Institute, Department of Urology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas M","family":"Durham","sequence":"additional","affiliation":[{"name":"Department of Oncology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tullia C","family":"Bruno","sequence":"additional","affiliation":[{"name":"Department of Oncology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph F","family":"Grosso","sequence":"additional","affiliation":[{"name":"Department of Oncology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J","family":"Schaeffer","sequence":"additional","affiliation":[{"name":"Department of Urology, Feinberg School of Medicine Northwestern University  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley E","family":"Ross","sequence":"additional","affiliation":[{"name":"The Brady Urological Institute, Department of Urology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula J","family":"Hurley","sequence":"additional","affiliation":[{"name":"The Brady Urological Institute, Department of Urology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M","family":"Berman","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine Queen's University  Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles G","family":"Drake","sequence":"additional","affiliation":[{"name":"Department of Oncology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen","family":"Thumbikat","sequence":"additional","affiliation":[{"name":"Department of Urology, Feinberg School of Medicine Northwestern University  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward M","family":"Schaeffer","sequence":"additional","affiliation":[{"name":"The Brady Urological Institute, Department of Urology Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Department of Oncology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,1,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01322"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2090"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgh317"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000108131.43160.77"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008736"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000142058.99614.ff"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2007.11.026"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10156-011-0350-y"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005562"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)67987-6"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)67145-5"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.21071"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3130017"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.191"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-3228"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-5164"},{"key":"e_1_2_8_18_1","first-page":"552","article-title":"IL\u201017 expression by macrophages is associated with proliferative inflammatory atrophy lesions in prostate cancer patients","volume":"4","author":"Vykhovanets EV","year":"2011","journal-title":"Int J Clin Exp Pathol"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2015"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.21327"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22648"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.080747"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)41924-0"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1318157111"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.21433"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20445"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00910-10"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(03)00197-1"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000415"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-4213"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-0946"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20297"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.20753"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.101388"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2008.111"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.071054"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009427"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1200706"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.09.033"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0060987"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090207"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-3795"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)67497-6"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.06280"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.07307"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(01)64369-6"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.21948"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-022038"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.4472","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.4472","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T11:05:48Z","timestamp":1760958348000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.4472"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1,8]]},"references-count":47,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,2]]}},"alternative-id":["10.1002\/path.4472"],"URL":"https:\/\/doi.org\/10.1002\/path.4472","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,1,8]]},"assertion":[{"value":"2014-03-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-10-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-01-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}