{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T19:19:36Z","timestamp":1786389576210,"version":"build-2736575974"},"reference-count":66,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Urology"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>To identify the sequence of inflammation\u2010driven signaling cascades and other molecular events that might cause tumor\u2010like transformation of prostatic cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cytokine array analysis, Reactome and STRING analysis, immunoblotting, and immunocytochemistry were used to investigate the molecular mechanisms governing inflammation\u2010driven adverse changes in human prostatic cells caused by the sexually transmitted infection, <jats:italic>Trichomonas vaginalis<\/jats:italic>, resulting in prostatitis, benign prostatic hyperplasia and prostate cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Array analysis showed upregulation of 23 cytokines within 24\u00a0h of infection of human prostatic epithelial RWPE\u20101 cells with the parasite, <jats:italic>in\u00a0vitro<\/jats:italic>. Reactome and STRING analysis of array data identified interleukin\u20106, interleukin\u20108, nuclear factor kappa B, signal transducer and activator of transcription\u00a03 and cyclooxygenase\u00a02 as chief instigators of prostatic anomaly, which were found to be significantly upregulated by immunofluorescence and western blotting analyses. STRING further connected these instigators with macrophage migration inhibitory factor, PIM\u20101 and prostate\u2010specific antigen; which was confirmed by their marked stimulation in infected prostatic cells by immunoblotting and immunocytochemistry. Upregulated proliferation markers, such as Ki67, proliferating cell nuclear antigen and B\u2010cell lymphoma\u00a02, suggested tumor\u2010like signaling in infected RWPE\u20101 cells, which was further supported by downregulation of E\u2010cadherin, upregulation of vimentin and activation of focal adhesion kinase. Prostate tumor DU145 cells were more sensitive to parasite invasion, and showed rapid upregulation with nuclear translocation of sensitive parameters, such as nuclear factor kappa B, signal transducer and activator of transcription\u00a03, and macrophage migration inhibitory factor. The migration of DU145 cells augmented when incubated in spent media from parasite\u2010infected RWPE\u20101 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The initiation of inflammation driven tumor\u2010like cell signaling in parasite\u2010infected human prostatic epithelial cells is apparent, with the prostate tumor (DU145) cells being more sensitive to <jats:italic>T. vaginalis<\/jats:italic> than normal (RWPE\u20101) prostatic cells.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iju.14431","type":"journal-article","created":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T08:57:31Z","timestamp":1606726651000},"page":"225-240","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Inflammation driven tumor\u2010like signaling in prostatic epithelial cells by sexually transmitted <i>Trichomonas vaginalis<\/i>"],"prefix":"10.1111","volume":"28","author":[{"given":"Bhavana","family":"Kushwaha","sequence":"first","affiliation":[{"name":"Division of Endocrinology CSIR\u2010Central Drug Research Institute Lucknow India"},{"name":"Academy of Scientific and Innovative Research Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana","family":"Devi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology CSIR\u2010Central Drug Research Institute Lucknow India"},{"name":"Academy of Scientific and Innovative Research Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagdamba P","family":"Maikhuri","sequence":"additional","affiliation":[{"name":"Division of Endocrinology CSIR\u2010Central Drug Research Institute Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Singh","family":"Rajender","sequence":"additional","affiliation":[{"name":"Division of Endocrinology CSIR\u2010Central Drug Research Institute Lucknow India"},{"name":"Academy of Scientific and Innovative Research Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gopal","family":"Gupta","sequence":"additional","affiliation":[{"name":"Division of Endocrinology CSIR\u2010Central Drug Research Institute Lucknow India"},{"name":"Academy of Scientific and Innovative Research Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,11,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01244-12"},{"key":"e_1_2_8_3_1","volume-title":"Global Incidence and Prevalence of Selected Curable Sexually Transmitted Infection","author":"World Health Organization","year":"2012"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00952-06"},{"key":"e_1_2_8_5_1","first-page":"430","article-title":"Trichomonas \n                  vaginalis in the prostate gland","volume":"110","author":"Gardner WA","year":"1986","journal-title":"Arch. Pathol. Lab. Med."},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1155\/2007\/196046"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-011-0205-2"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23227"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1321884111"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22766"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.4081\/aiua.2017.4.259"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31565"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1442-2042.2001.00358.x"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-017-1559-2"},{"issue":"1","key":"e_1_2_8_15_1","first-page":"D561","article-title":"The STRING database in 2011: functional interaction networks of proteins globally integrated and scored","volume":"39","author":"Szklarczyk D","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092444"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.386"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002801"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djp306"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-9378-5-11"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01322"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.03.030"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2002.01309.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-7364-5-1-30"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.4110\/in.2018.18.e27"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)67497-6"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.7.3951-3960.2004"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00037-17"},{"key":"e_1_2_8_29_1","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.4049\/jimmunol.148.4.1102","article-title":"Transforming growth factor\u2010beta enhances the M\u2010CSF and GM\u2010CSF\u2010stimulated proliferation of macrophages","volume":"148","author":"Celada AN","year":"1992","journal-title":"J. Immunol."},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2011.286"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2006.07.016"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0801875"},{"key":"e_1_2_8_33_1","first-page":"1","article-title":"The role of inflammatory mediators in the development of prostatic hyperplasia and prostate cancer","volume":"5","author":"Elkahwaji JE","year":"2013","journal-title":"Res. Rep. Urol."},{"key":"e_1_2_8_34_1","first-page":"147","article-title":"Role of inflammation in benign prostatic hyperplasia","volume":"13","author":"Chughtai B","year":"2011","journal-title":"Rev. Urol."},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64535-X"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.3109\/08977190009003239"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20051"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.10020"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099-0496(199711)24:5<331::AID-PPUL5>3.0.CO;2-L"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0130146"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)35267-9"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-016-5098-7"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-1162"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-3-11"},{"key":"e_1_2_8_45_1","first-page":"6659","article-title":"Constitutive activation of Stat3 in human prostate tumors and cell lines: direct inhibition of Stat3 signaling induces apoptosis of prostate cancer cells","volume":"62","author":"Mora LB","year":"2002","journal-title":"Cancer Res."},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0130146"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.02.015"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.3.2011"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-1664"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22815"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(01)01255-9"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01995"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.15-273904"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1835863100"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/35090585"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20064"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12282-019-00966-3"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23886"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2017.6668"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-003-1282-9"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0956-5507.2003.00090.x"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2019.172655"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.7747"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-19-0595"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20306"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00744.x"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1177\/1947601913507951"}],"container-title":["International Journal of Urology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/iju.14431","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/iju.14431","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/iju.14431","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T15:50:49Z","timestamp":1693669849000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/iju.14431"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,30]]},"references-count":66,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,2]]}},"alternative-id":["10.1111\/iju.14431"],"URL":"https:\/\/doi.org\/10.1111\/iju.14431","archive":["Portico"],"relation":{},"ISSN":["0919-8172","1442-2042"],"issn-type":[{"value":"0919-8172","type":"print"},{"value":"1442-2042","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,30]]},"assertion":[{"value":"2020-06-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}