{"entity": "journal", "iuid": "761acf9458aa412c8f18e8d8254b63c7", "timestamp": "2026-08-20T21:30:37.691Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/journal/Prostate.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/journal/Prostate"}}, "title": "Prostate", "issn": "1097-0045", "issn-l": null, "publications_count": 2, "publications": [{"entity": "publication", "iuid": "c772d0857e5e4f559522e733765e6155", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/c772d0857e5e4f559522e733765e6155.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/c772d0857e5e4f559522e733765e6155"}}, "title": "Fibroblast as a critical stromal cell type determining prognosis in prostate cancer.", "authors": [{"family": "Blom", "given": "Sami", "initials": "S"}, {"family": "Erickson", "given": "Andrew", "initials": "A"}, {"family": "\u00d6stman", "given": "Arne", "initials": "A"}, {"family": "Rannikko", "given": "Antti", "initials": "A"}, {"family": "Mirtti", "given": "Tuomas", "initials": "T"}, {"family": "Kallioniemi", "given": "Olli", "initials": "O"}, {"family": "Pellinen", "given": "Teijo", "initials": "T", "orcid": "0000-0001-9652-7373", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8e73595c0cc64a68a59cd95772784859.json"}}], "type": "journal article", "published": "2019-09-00", "journal": {"title": "Prostate", "issn": "1097-0045", "volume": "79", "issue": "13", "pages": "1505-1513", "issn-l": null}, "abstract": "Tumor stroma associates with prostate cancer (PCa) progression, but its specific cellular composition and association to patient survival outcome have not been characterized.\n\nWe analyzed stromal composition in human PCa using multiplex immunohistochemistry and quantitative, high-resolution image analysis in two retrospective, formalin-fixed paraffin embedded observational clinical cohorts (Cohort I, n = 117; Cohort II, n = 340) using PCa-specific mortality as outcome measurement.\n\nA high proportion of fibroblasts associated with aggressive disease and castration-resistant prostate cancer (CRPC). In a multivariate analysis, increase in fibroblast proportion predicted poor cancer-specific outcome independently in the two clinical cohorts studied.\n\nFibroblasts were the most important cell type in determining prognosis in PCa and associated with CRPC. Thus, the stromal composition could be critically important in developing diagnostic and therapeutic approaches to aggressive prostate cancer.", "doi": "10.1002/pros.23867", "pmid": "31269283", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6813917"}], "notes": [], "created": "2026-08-20T06:35:14.499Z", "modified": "2026-08-20T06:35:14.575Z"}, {"entity": "publication", "iuid": "d137a4dadf634fa0992583e6368ce25c", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/d137a4dadf634fa0992583e6368ce25c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/d137a4dadf634fa0992583e6368ce25c"}}, "title": "Targeting genotoxic and proteotoxic stress-response pathways in human prostate cancer by clinically available PARP inhibitors, vorinostat and disulfiram.", "authors": [{"family": "Majera", "given": "Dusana", "initials": "D", "orcid": "0000-0002-9238-3437", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6402cf7a866a49a88d4ad6f88a0782a3.json"}}, {"family": "Skrott", "given": "Zdenek", "initials": "Z"}, {"family": "Bouchal", "given": "Jan", "initials": "J", "orcid": "0000-0003-4842-1720", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1672398006694de6827848a1b8303e4f.json"}}, {"family": "Bartkova", "given": "Jirina", "initials": "J"}, {"family": "Simkova", "given": "Dana", "initials": "D"}, {"family": "Gachechiladze", "given": "Mariam", "initials": "M"}, {"family": "Steigerova", "given": "Jana", "initials": "J"}, {"family": "Kurfurstova", "given": "Daniela", "initials": "D"}, {"family": "Gursky", "given": "Jan", "initials": "J"}, {"family": "Korinkova", "given": "Gabriela", "initials": "G"}, {"family": "Cwiertka", "given": "Karel", "initials": "K"}, {"family": "Hodny", "given": "Zdenek", "initials": "Z"}, {"family": "Mistrik", "given": "Martin", "initials": "M"}, {"family": "Bartek", "given": "Jiri", "initials": "J"}], "type": "journal article", "published": "2019-03-00", "journal": {"title": "Prostate", "issn": "1097-0045", "volume": "79", "issue": "4", "pages": "352-362", "issn-l": null}, "abstract": "Castration-resistant prostate cancer (PCa) represents a serious health challenge. Based on mechanistically-supported rationale we explored new therapeutic options based on clinically available drugs with anticancer effects, including inhibitors of PARP1 enzyme (PARPi), and histone deacetylases (vorinostat), respectively, and disulfiram (DSF, known as alcohol-abuse drug Antabuse) and its copper-chelating metabolite CuET that inhibit protein turnover.\n\nDrugs and their combination with ionizing radiation (IR) were tested in various cytotoxicity assays in three human PCa cell lines including radio-resistant stem-cell like derived cells. Mechanistically, DNA damage repair, heat shock and unfolded protein response (UPR) pathways were assessed by immunofluorescence and immunoblotting.\n\nWe observed enhanced sensitivity to PARPi/IR in PC3 cells consistent with lower homologous recombination (HR) repair. Vorinostat sensitized DU145 cells to PARPi/IR and decreased mutant p53. Vorinostat also impaired HR-mediated DNA repair, as determined by Rad51 foci formation and downregulation of TOPBP1 protein, and overcame radio-resistance of stem-cell like DU145-derived cells. All PCa models responded well to CuET or DSF combined with copper. We demonstrated that DSF interacts with copper in the culture media and forms adequate levels of CuET indicating that DSF/copper and CuET may be considered as comparable treatments. Both DSF/copper and CuET evoked hallmarks of UPR in PCa cells, documented by upregulation of ATF4, CHOP and phospho-eIF2\u03b1, with ensuing heat shock response encompassing activation of HSF1 and HSP70. Further enhancing the cytotoxicity of CuET, combination with an inhibitor of the anti-apoptotic protein survivin (YM155, currently undergoing clinical trials) promoted the UPR-induced toxicity, yielding synergistic effects of CuET and YM155.\n\nWe propose that targeting genotoxic and proteotoxic stress responses by combinations of available drugs could inspire innovative strategies to treat castration-resistant PCa.", "doi": "10.1002/pros.23741", "pmid": "30499118", "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T06:35:12.313Z", "modified": "2026-08-20T06:35:12.463Z"}], "created": "2026-08-20T06:35:12.422Z", "modified": "2026-08-20T06:35:12.422Z"}