Dataset Information

Tissue Effects in a Randomized Controlled Trial of Short-term Finasteride in Early Prostate Cancer.

ABSTRACT: 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 (ER?, 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.

SUBMITTER: Kim J

PROVIDER: S-EPMC4909608 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Tissue Effects in a Randomized Controlled Trial of Short-term Finasteride in Early Prostate Cancer.

Kim Jeri J Davis John W JW Klein Eric A EA Magi-Galluzzi Cristina C Lotan Yair Y Ward John F JF Pisters Louis L LL Basler Joseph W JW Pettaway Curtis A CA Stephenson Andrew A Li Ning Tapia Elsa M EM Efstathiou Eleni E Wang Xuemei X Do Kim-Anh KA Lee J Jack JJ Gorlov Ivan P IP Vornik Lana A LA Hoque Ashraful M AM Prokhorova Ina N IN Parnes Howard L HL Lippman Scott M SM Thompson Ian M IM Brown Powel H PH Logothetis Christopher J CJ Troncoso Patricia P

EBioMedicine 20160407

<h4>Background</h4>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.<h4>Methods</h4>From 2007 to 2012, we randomized dynamicall ...[more]

PMID: 27322462

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Project description:Vitamin D deficiency is common and associated with dyslipidemia. However, it is unclear whether oral vitamin D supplementation improves the lipid profile. Therefore, we conducted a randomized, placebo-controlled trial to determine the short-term effects of vitamin D repletion on the lipid profile.One hundred fifty-one vitamin D-deficient (25-hydroxyvitamin D <20 ng/mL) adults with elevated risk for cardiovascular disease were randomized to receive either 50 000 IU of vitamin D3 weekly for 8 weeks or placebo. The primary outcome was the change in small low-density lipoprotein (LDL) particle number. Secondary outcomes included changes in other nuclear magnetic resonance-based and chemical lipid fractions. Vitamin D failed to improve the lipid profile. Compared with the placebo, vitamin D repletion did not change small LDL particle number (mean change, +18 nmol/L; 95% CI [-80 to +116 nmol/L]; P=0.63). There were also no changes in the chemical lipid profile: total cholesterol (+5.8 mg/dL, 95% CI [-1.4 to +13.0 mg/dL], P=0.14); LDL cholesterol (+3.8 mg/dL, 95% CI [-2.5 to +10.2 mg/dL], P=0.13); high-density lipoprotein cholesterol (+0.4 mg/dL 95% CI [-1.6 to +2.6 mg/dL], P=0.71); and triglycerides (+7.9 mg/dL 95% CI [-6.5 to +22.3 mg/dL]). In the vitamin D repletion group, exploratory multivariate regression analysis demonstrates that changes in LDL cholesterol were positively correlated with the changes in serum calcium (P<0.001) and inversely with the changes in serum parathyroid hormone (P=0.02).In contrast to the association between low 25-hydroxyvitamin D levels and dyslipidemia, correcting vitamin D deficiency in the short-term does not improve the lipid profile. Repletion of 25-hydroxyvitamin D levels raised serum calcium levels and decreased serum parathyroid hormone levels. These expected physiological responses to vitamin D therapy were correlated with a significant increase in LDL cholesterol. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01008384.

Project description:BackgroundBalance Body Tape (BBT) is a recently developed taping-method with the aim to reduce pain and improve posture through change in movement behavior. However, the potential effects of a treatment with BBT are scarcely documented. Therefore, the aim with this study was to investigate the effect of a three-week Balance body tape-treatment on the intensity of perceived neck, shoulder and back pain and forward head posture.MethodsIn this RCT study, subjects (n = 26), who reported being university students or having a sedentary work and experiencing pain in neck, back or shoulders, were randomized to either an intervention (n = 12) or control group (n = 14). The intervention group received a three-week treatment with BBT, the control group received no treatment. A questionnaire regarding pain, including a Numeric Rating Scale (NRS) measuring pain intensity, and a Photographic posture analysis measurement (PPAM) regarding the craniovertebral (CV) angle were assessed before and after the intervention for both groups. Wilcoxon's signed rank test and Mann-Whitney U test was used to assess intra- and between group differences respectively. The relationship between pain intensity and CV angle was assessed using Spearman's correlation.ResultsNo difference in demographic and physical characteristics between the groups were noted at baseline (p > 0.05). Pain intensity at baseline was 5 for the intervention group and 4 for the control group (p = 0.330). At follow up, the intervention group reported a lower score (NRS = 2.5, p = 0.003) whereas the control group had no significant difference in pain intensity (NRS = 3, p = 0.086). No significant change was found in the CV angle (p = 0.058) and no correlation was found between NRS and the CV angle (r = 0.102, p = 0.619).ConclusionA short treatment period with BBT may, compared to no treatment, have a small reducing effect on pain intensity in neck, back and/or shoulders. However, no effect was found on forward head posture in this study.Trial registrationRegistered retrospectively on 08/11/2021. NCT05111704 . Trial registration page link.

Dataset Information

Tissue Effects in a Randomized Controlled Trial of Short-term Finasteride in Early Prostate Cancer.

Publications

Tissue Effects in a Randomized Controlled Trial of Short-term Finasteride in Early Prostate Cancer.

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