Abstract | BACKGROUND: METHODS: From 2009 to 2014, we conducted a dbRCT including 60 patients with primary mHGPIN and/or ASAP receiving daily lycopene 35 mg, selenium 55 µg, and GTCs 600 mg, or placebo for 6 months. Pharmacokinetic analysis were performed with UV-Visible spectrophotometric assay under standard (SC) and accelerated (AC) conditions. Upon plasma lycopene concentrations falling within the expected range (1.2-90 mcg/l) and no side-effects of grade >1, study proceeded to phase II (n = 50). After unblinding of results, eight men (4 per arm, 2 without and 2 with PCa, respectively) were randomly selected and totRNA extracted from "non-pathological" tissues. MicroRNA profiling was performed with the Agilent platform. Raw data processing used R-statistical language and linear models for microarray analysis. RESULTS: Samples were stable except for lycopene, showing significant degradation (SC = 56%, AC = 59%) and consequently stabilized under vacuum in a dark packaging. Mean plasmatic lycopene concentration was 1,45 ± 0,4 μM. At 6 months, 53 men underwent re-biopsy and 13 (24.5%) were diagnosed with PCa (supplementation n = 10, placebo n = 3 [P = 0.053]). At a mean 37 months follow-up, 3 additional PCa were found in the placebo group. No significant variations in PSA, IPSS, and PR25 questionnaires were observed. Stronger modulation of miRNAs was present on re-biopsy in the supplementation group compared to the placebo, including: (i) overexpression of miRNAs present in PCa versus non- cancer tissue; (ii) underexpression of miRNAs suppressing PCa proliferation; (iii) detection of 35 miRNAs in PCa patients versus disease-free men, including androgen-regulated miR-125b-5p and PTEN-targeting miR-92a-3p (both upregulated). CONCLUSION: Administration of high doses of lycopene, GTCs, and selenium in men harboring HGPIN and/or ASAP was associated with a higher incidence of PCa at re-biopsy and expression of microRNAs implicated in PCa progression at molecular analysis. The use of these supplements should be avoided.
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Authors | Paolo Gontero, Giancarlo Marra, Francesco Soria, Marco Oderda, Andrea Zitella, Francesca Baratta, Giovanna Chiorino, Ilaria Gregnanin, Lorenzo Daniele, Luigi Cattel, Bruno Frea, Paola Brusa |
Journal | The Prostate
(Prostate)
Vol. 75
Issue 11
Pg. 1177-86
(Aug 01 2015)
ISSN: 1097-0045 [Electronic] United States |
PMID | 25893930
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | © 2015 Wiley Periodicals, Inc. |
Chemical References |
- Anticarcinogenic Agents
- Antioxidants
- Carotenoids
- Prostate-Specific Antigen
- Selenium
- Lycopene
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Topics |
- Anticarcinogenic Agents
(pharmacology)
- Antioxidants
(pharmacology)
- Biological Availability
- Biopsy
- Carotenoids
(pharmacology)
- Chemoprevention
(methods)
- Dietary Supplements
- Disease Progression
- Double-Blind Method
- Drug Monitoring
- Humans
- Lycopene
- Male
- Prostate
(metabolism, pathology)
- Prostate-Specific Antigen
(blood)
- Prostatic Intraepithelial Neoplasia
(blood, drug therapy, pathology)
- Prostatic Neoplasms
(metabolism, pathology, prevention & control)
- Selenium
(pharmacology)
- Treatment Outcome
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