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- Jagarlamudi, Kiran Kumar, et al.
(författare)
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The combination of AroCell TK 210 ELISA with Prostate Health Index or prostate-specific antigen density can improve the ability to differentiate prostate cancer from noncancerous conditions
- 2019
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Ingår i: Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 79, s. 856-863
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Tidskriftsartikel (refereegranskat)abstract
- Background Prostate-specific antigen (PSA) is an established tumour marker for prostate cancer (PCa). Serum thymidine kinase 1 is a possible new marker for the detection of PCa. The aim of the study was to investigate the diagnostic value of the AroCell TK 210 enzyme-linked immunosorbent assay (ELISA) together with free PSA, [-2]proPSA, and Prostate Health Index (PHI) in differentiating PCa from benign urological conditions. Methods Serum samples from 140 patients with PSA values in the range between 2 and 10 mu g/L were collected at the Ljubljana University Medical Centre and the Maribor University Medical Centre. Thymidine kinase (TK1) protein levels were determined using the AroCell TK 210 ELISA and PSA-related parameters analysed with commercial assays. Results Serum TK1 protein, total and free PSA, proPSA, PSA density (PSAD), and PHI levels in patients with confirmed PCa were significantly higher than in patients with benign urological conditions (P < 0.05). Overall, the AroCell TK 210 ELISA results showed a significant correlation with PHI (r = 0.25, P = 0.0031). Receiver-operating characteristic curve analyses were used to compare the area under the curve (AUC) of TK 210 ELISA, PHI, and PSA density. For PHI, the AUC was 0.73, comparable to those of TK 210 ELISA (0.67) and PSAD (0.66), with no significant differences in pairwise comparisons (PHI vs TK 210 ELISA P = 0.32, PHI vs PSAD P = 0.24, and TK 210 ELISA vs PSAD P = 0.95). The AUC for the combination of TK1 plus PSAD was significantly higher than those for the individual PSA-related biomarkers and marginally PHI, while the AUC for the combination of TK1 plus PHI was significantly higher than those for the individual PSA-related biomarkers except for PHI and marginally for PSAD. Total PSA concentration was the only marker, that was significantly higher in patients with an increasing Gleason grade. Conclusions These results suggest that TK1 protein determinations together with PHI or PSAD could be a valuable additional tool in PCa management.
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| 2. |
- Oskarsson, Agneta, et al.
(författare)
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Inhibition of CYP17A1 activity by resveratrol, piceatannol and synthetic resveratrol analogs
- 2014
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Ingår i: Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 74, s. 839-851
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDResveratrol (RSV) and resveratrol analogs have a potential use in prostate cancer chemoprevention due to effects on for example, cell growth, apoptosis, angiogenesis, and metastasis. However, inhibition of CYP17A1, a key enzyme in the androgen biosynthesis and a target for prostate cancer therapy, has not been explored as a possible mechanism behind the effects on prostate cancer.METHODSHuman adrenocortical carcinoma cells, H295R, were treated with RSV, piceatannol (PIC), 3,5,4 '-triacetylresveratrol (RSVTA), 3,5-diacetylresveratrol (RSVDA), and 3,5,4 '-trimethylresveratrol (RSVTM) for 24 hr at concentrations of 1, 5, 10, 25, and 50 mu M. Steroid secretion, enzyme activities, and gene expression of key steps in steroidogenesis were investigated.RESULTSSecretion of dihydroepiandrosterone (DHEA), testosterone, and cortisol were drastically decreased by all test compounds at concentrations that did not affect cell viability. Progesterone and aldosterone secretion were increased. This steroid secretion pattern can be explained by the demonstrated inhibition of CYP17A1 enzyme activity. The most efficient CYP17A1 inhibitors were the synthetic analogs RSVTA, RSVDA, and RSVTM. Inhibition by RSVTM was more selective on the 17,20-lyase activity than hydroxylase activity of CYP17A1. Treatment of cells with all compounds, except RSVTM, caused increased estradiol levels, which could be explained by the demonstrated inhibition of estrogen sulfate conjugation, catalyzed by SULT1E1.CONCLUSIONSOur results on CYP17A1 inhibition of RSV and RSV analogs suggest a novel mechanism for chemoprevention of prostate cancer by resveratrol and the analogs. Especially RSVTM, which has a preferential inhibition on the 17,20-lyase activity of CYP17A1, may be a promising candidate for prostate cancer chemoprevention. Prostate 74:839-851, 2014. (c) 2014 Wiley Periodicals, Inc.
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