{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T10:27:46Z","timestamp":1718188066739},"reference-count":47,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2015,3,26]],"date-time":"2015-03-26T00:00:00Z","timestamp":1427328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A significant proportion of men diagnosed with prostate cancer (<jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content>a) eventually develop metastatic disease, which progresses to castration resistance, despite initial response to androgen deprivation. As anticancer therapy has become increasingly effective, acquired drug resistance has emerged, limiting efficacy. Combination treatment, utilizing different drug classes, exemplifies a possible strategy to foil resistance development. The effects of the triple application of the histone deacetylase (<jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>) inhibitor valproic acid (<jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>), the mammalian target of rapamycin inhibitor everolimus and low dosed interferon alpha (<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u03b1) on <jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content>a cell growth and dissemination capacity were investigated. For that purpose, the human <jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content>a cell lines, <jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content>\u20103, <jats:styled-content style=\"fixed-case\">DU<\/jats:styled-content>\u2010145 and <jats:styled-content style=\"fixed-case\">LNC<\/jats:styled-content>aP were treated with the combined regimen or separate single agents. Cell growth was investigated by the <jats:styled-content style=\"fixed-case\">MTT<\/jats:styled-content> dye reduction assay. Flow cytometry served to analyse cell cycle progression. Adhesion to vascular endothelium or immobilized collagen, fibronectin and laminin was quantified. Migration and invasion characteristics were determined by the modified Boyden chamber assay. Integrin \u03b1 and \u03b2 subtypes were investigated by flow cytometry, western blotting and <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>. Integrin related signalling, Epidermal Growth Factor Receptor (EGFr), Akt, p70S6kinase and extracellular signal\u2010regulated kinases (ERK)1\/2 activation were also assessed. The triple application of <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>, everolimus and low dosed <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u03b1 blocked tumour cell growth and dissemination significantly better than any agent alone. Antitumour effects were associated with pronounced alteration in the cell cycle machinery, intracellular signalling and integrin expression profile. Combining <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>, everolimus and low dosed <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u03b1 might be a promising option to counteract resistance development and improve outcome in <jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content>a patients.<\/jats:p>","DOI":"10.1111\/jcmm.12583","type":"journal-article","created":{"date-parts":[[2015,3,26]],"date-time":"2015-03-26T18:03:13Z","timestamp":1427392993000},"page":"1795-1804","source":"Crossref","is-referenced-by-count":9,"title":["Intensified antineoplastic effect by combining an <scp>HDAC<\/scp>\u2010inhibitor, an <scp>mTOR<\/scp>\u2010inhibitor and low dosed interferon alpha in prostate cancer cells"],"prefix":"10.1111","volume":"19","author":[{"given":"Igor","family":"Tsaur","sequence":"first","affiliation":[{"name":"Department of Urology Johann Wolfgang Goethe\u2010University Frankfurt am Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukasz","family":"Hudak","sequence":"additional","affiliation":[{"name":"Department of Urology Johann Wolfgang Goethe\u2010University Frankfurt am Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasmina","family":"Makarevi\u0107","sequence":"additional","affiliation":[{"name":"Department of Urology Johann Wolfgang Goethe\u2010University Frankfurt am Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Juengel","sequence":"additional","affiliation":[{"name":"Department of Urology Johann Wolfgang Goethe\u2010University Frankfurt am Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Mani","sequence":"additional","affiliation":[{"name":"Department of Urology Johann Wolfgang Goethe\u2010University Frankfurt am Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hendrik","family":"Borgmann","sequence":"additional","affiliation":[{"name":"Department of Urology Johann Wolfgang Goethe\u2010University Frankfurt am Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kilian M.","family":"Gust","sequence":"additional","affiliation":[{"name":"Department of Urology Johann Wolfgang Goethe\u2010University Frankfurt am Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Schilling","sequence":"additional","affiliation":[{"name":"Department of Urology Johann Wolfgang Goethe\u2010University Frankfurt am Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"Bartsch","sequence":"additional","affiliation":[{"name":"Department of Urology Johann Wolfgang Goethe\u2010University Frankfurt am Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Vascular and Endovascular Surgery Johann Wolfgang Goethe\u2010University Frankfurt am Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel","family":"Haferkamp","sequence":"additional","affiliation":[{"name":"Department of Urology Johann Wolfgang Goethe\u2010University Frankfurt am Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman A.","family":"Blaheta","sequence":"additional","affiliation":[{"name":"Department of Urology Johann Wolfgang Goethe\u2010University Frankfurt am Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,3,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2012.12.027"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCO.0b013e32835ff161"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2013.09.046"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2011.04.038"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2013.08.008"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737140.2013.811154"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.53.082901.103929"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000086183"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22525"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2010.12.017"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-011-9386-8"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2013.11.002"},{"key":"e_1_2_7_14_1","first-page":"620","article-title":"Targeted therapy in the treatment of castration\u2010resistant prostate cancer","volume":"27","author":"Derleth CL","year":"2013","journal-title":"Oncology"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2014.05.008"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2010.136"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.02.017"},{"key":"e_1_2_7_18_1","first-page":"62","article-title":"Increased expression of histone deacetylaces (HDACs) and inhibition of prostate cancer growth and invasion by HDAC inhibitor SAHA","volume":"1","author":"Wang L","year":"2009","journal-title":"Am J Transl Res"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604199"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2007.04.006"},{"key":"e_1_2_7_21_1","first-page":"97","article-title":"Induction of differentiation and suppression of malignant phenotype of human neuroblastoma BE(2)\u2010C cells by valproic acid: enhancement by combination with interferon\u2010alpha","volume":"20","author":"Cinatl J","year":"2002","journal-title":"Int J Oncol"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-6-68"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210586"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.83"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.4103\/1477-3163.90440"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568009043481669"},{"key":"e_1_2_7_27_1","first-page":"3593","article-title":"Use of RNA interference to target cyclin E\u2010overexpressing hepatocellular carcinoma","volume":"63","author":"Li K","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2011.08.026"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.1.2.115"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-0283"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.02872"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.02171-06"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.446"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-1313"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-1898"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201719"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-11-375"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0000000000000145"},{"key":"e_1_2_7_39_1","first-page":"863","article-title":"Decreased expression of integrin adhesive protein receptors in adenocarcinoma of the breast","volume":"137","author":"Zutter MM","year":"1990","journal-title":"Am J Pathol"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42328"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2588"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/aja.2010.20"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22574"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-12-147"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-0917"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-12-85"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22862"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.342"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjcmm.12583","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjcmm.12583","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.12583","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T21:12:36Z","timestamp":1696281156000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.12583"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,26]]},"references-count":47,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2015,8]]}},"alternative-id":["10.1111\/jcmm.12583"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.12583","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,26]]}}}