Background: In the Prostate Cancer Prevention Trial, finasteride selectively suppressed low-grade prostate cancer and significantly reduced the incidence of prostate cancer in men treated with finasteride compared with placebo. However, an apparent increase in high-grade disease was also observed among men randomized to finasteride. We aimed to determine why and hypothesized that there is a grade-dependent response to finasteride.
Methods: From 2007 to 2012, we randomized dynamically by intranet-accessible software 183 men with localized prostate cancer to receive 5mg finasteride or placebo daily in a double-blind study during the 4-6weeks preceding prostatectomy. As the primary end point, the expression of a predefined molecular signature (ERβ, UBE2C, SRD5A2, and VEGF) differentiating high- and low-grade tumors in Gleason grade (GG) 3 areas of finasteride-exposed tumors from those in GG3 areas of placebo-exposed tumors, adjusted for Gleason score (GS) at prostatectomy, was compared. We also determined androgen receptor (AR) levels, Ki-67, and cleaved caspase 3 to evaluate the effects of finasteride on the expression of its downstream target, cell proliferation, and apoptosis, respectively. The expression of these markers was also compared across grades between and within treatment groups. Logistic regression was used to assess the expression of markers.
Findings: We found that the predetermined molecular signature did not distinguish GG3 from GG4 areas in the placebo group. However, AR expression was significantly lower in the GG4 areas of the finasteride group than in those of the placebo group. Within the finasteride group, AR expression was also lower in GG4 than in GG3 areas, but not significantly. Expression of cleaved caspase 3 was significantly increased in both GG3 and GG4 areas in the finasteride group compared to the placebo group, although it was lower in GG4 than in GG3 areas in both groups.
Interpretation: We showed that finasteride's effect on apoptosis and AR expression is tumor grade dependent after short-term intervention. This may explain finasteride's selective suppression of low-grade tumors observed in the PCPT.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4909608 | PMC |
http://dx.doi.org/10.1016/j.ebiom.2016.03.047 | DOI Listing |
Arch Ital Urol Androl
January 2025
Department of Urology, School of Medicine, Shiraz University of Medical Sciences, Shiraz.
Objectives: This research aimed to compare the prostate cancer (PCa) features, survival rate, and functional outcomes after open suprapubic Radical Prostatectomy (RP) between younger men (≤ 55 years) and older men (> 55 years).
Methods: In this retrospective cohort study, we studied 134 patients with clinically localized PCa who underwent RP at our centers between 2011 and 2019, with 26 (19.40%) patients aged ≤ 55.
Oncol Lett
March 2025
College of Pharmacy, Korea University, Sejong 30019, Republic of Korea.
Cancer stem cells (CSCs) contribute to the resistance of intractable prostate cancer, and dopamine receptor (DR)D2 antagonists exhibit anticancer activity against prostate cancer and CSCs. Human prostate cancer PC-3 cells were used to generate CSC-like cells, serving as a surrogate system to identify the specific DR subtype the inhibition of which significantly affects prostate-derived CSCs. Additionally, the present study aimed to determine the downstream signaling molecules of this DR subtype that exert more profound effects compared with other DR subtypes.
View Article and Find Full Text PDFFront Pharmacol
January 2025
Wuxi School of Medicine, Jiangnan University, Wuxi, China.
Background: Prostate cancer was the fourth most diagnosed cancer worldwide in 2022. Radical treatments and androgen deprivation therapy benefit newly diagnosed patients but impact quality of life, often leading to castration-resistant prostate cancer. Short-term dietary changes significantly affect the gut microbiota, which differs markedly between prostate cancer patients and healthy individuals, impacting both cancer progression and treatment response.
View Article and Find Full Text PDFFront Pharmacol
January 2025
Institute for Personalized Oncology, Center for Digital Biodesign and Personalized Healthcare, First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University), Moscow, Russia.
Background: The natural killer (NK) activity of peripheral blood mononuclear cells (PBMCs) is a crucial defense against the onset and spread of cancer. Studies have shown that patients with reduced NK activity are more susceptible to cancer, and NK activity tends to decrease due to cancer-induced immune suppression. Enhancing the natural cytotoxicity of PBMCs remains a significant task in cancer research.
View Article and Find Full Text PDFBiochem Res Int
January 2025
Department of Medical Biochemistry, Faculty of Medicine, Ege University, İzmir, Türkiye.
Recently, it has been shown that protein phosphatase 2A (PP2A) dysfunction was common in many cancer types and was mediated by various inactivation mechanisms. Although many research studies observed antitumor effect of propolis extracts in various types of cancer, the mechanism of effect are still obscure. In this study, we investigated the effect of propolis on PPP2R1A expression and its relationship with apoptosis in the SW-620 (colorectal cancer), DU-145 and PC-3 (prostate cancer), and MCF-7 (breast cancer) cell lines, with WI-38 (healthy fibroblast) cells serving as the control.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!