000			03445nam a22003737a 4500
008			230411s2022022 xxu||||| |||| 00| 0 eng d
022			_a2767-9764
024			_a10.1158/2767-9764.CRC-22-0203 [doi]
024			_aCRC-22-0203 [pii]
024			_aPMC10035501 [pmc]
040			_aOvid MEDLINE(R)
099			_a36970725
245			_aNovel Paired Normal Prostate and Prostate Cancer Model Cell Systems Derived from African American Patients.
251			_aCancer Research Communications. 2(12):1617-1625, 2022 Dec.
252			_aCancer Res Commun. 2(12):1617-1625, 2022 Dec.
253			_aCancer research communications
260			_c2022
260			_fFY2023
260			_p2022 Dec
265			_sepublish
265			_tPubMed-not-MEDLINE
266			_d2023-04-11
520			_aProstate cancer is the most frequently diagnosed solid malignancy in men. African American (AA) men are at greater risk for developing prostate cancer, and experience higher mortality rates, as compared with Caucasian American men. However, mechanistic studies to understand this health disparity have been limited by the lack of relevant in vitro and in vivo models. There is an urgent need for preclinical cellular models to investigate molecular mechanisms underlying prostate cancer in AA men. We collected clinical specimens from radical prostatectomies of AA patients and established 10 paired tumor-derived and normal epithelial cell cultures from the same donors, which were further cultivated to extend the growth under "conditional reprogramming." Clinical and cellular annotations characterized these model cells as intermediate risk and predominantly diploid. Immunocytochemical analyses demonstrated variable expression levels of luminal (CK8) and basal (CK5, p63) markers in both normal and tumor cells. However, expression levels of TOPK, c-MYC, and N-MYC were markedly increased only in tumor cells. To determine cell utility for drug testing, we examined viability of cells following exposure to the antiandrogen (bicalutamide) and two PARP inhibitors (olaparib and niraparib) and observed decreased viability of tumor-derived cells as compared with viability of normal prostate-derived cells.
520			_aSignificance: Cells derived from prostatectomies of AA patients conferred a bimodal cellular phenotype, recapitulating clinical prostate cellular complexity in this model cell system. Comparisons of viability responses of tumor derived to normal epithelial cells offer the potential for screening therapeutic drugs. Therefore, these paired prostate epithelial cell cultures provide an in vitro model system suitable for studies of molecular mechanisms in health disparities. Copyright © 2022 The Authors; Published by the American Association for Cancer Research.
546			_aEnglish
656			_aMedStar Georgetown University Hospital/MedStar Washington Hospital Center
656			_aRadiation Oncology Residency
657			_aJournal Article
700			_aCarrasquilla, Michael _bMGUH _cRadiation Oncology Residency _dMD _eResident PGY 5
790			_aJung M, Kowalczyk K, Hankins R, Bandi G, Kallakury B, Carrasquilla MA, Banerjee PP, Grindrod S, Dritschilo A
856			_uhttps://dx.doi.org/10.1158/2767-9764.CRC-22-0203 _zhttps://dx.doi.org/10.1158/2767-9764.CRC-22-0203
858			_uCarrasquilla, Michael A _yhttps://orcid.org/0000-0003-0957-0248 _zCarrasquilla, Michael A
942			_cART _dArticle
999			_c11528 _d11528