Prostate cancer - evidence of exercise and nutrition trial (PrEvENT):Study protocol for a randomised controlled feasibility trial

Background: A growing body of observational evidence suggests that nutritional and physical activity interventions are associated with beneficial outcomes for men with prostate cancer, including brisk walking, lycopene intake, increased fruit and vegetable intake and reduced dairy consumption. However, randomised controlled trial data are limited. The ‘Prostate Cancer: Evidence of Exercise and Nutrition Trial’ investigates the feasibility of recruiting and randomising men diagnosed with localised prostate cancer and eligible for radical prostatectomy to interventions that modify nutrition and physical activity. The primary outcomes are randomisation rates and adherence to the interventions at 6 months following randomisation. The secondary outcomes are intervention tolerability, trial retention, change in prostate specific antigen level, change in diet, change in general physical activity levels, insulin-like growth factor levels, and a range of related outcomes, including quality of life measures. Methods/design: The trial is factorial, randomising men to both a physical activity (brisk walking or control) and nutritional (lycopene supplementation or increased fruit and vegetables with reduced dairy consumption or control) intervention. The trial has two phases: men are enrolled into a cohort study prior to radical prostatectomy, and then consented after radical prostatectomy into a randomised controlled trial. Data are collected at four time points (cohort baseline, true trial baseline and 3 and 6 months post-randomisation). Discussion: The Prostate Cancer: Evidence of Exercise and Nutrition Trial aims to determine whether men with localised prostate cancer who are scheduled for radical prostatectomy can be recruited into a cohort and subsequently randomised to a 6-month nutrition and physical activity intervention trial. If successful, this feasibility trial will inform a larger trial to investigate whether this population will gain clinical benefit from long-term nutritional and physical activity interventions post-surgery. Prostate Cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) is registered on the ISRCTN registry, ref number ISRCTN99048944. Date of registration 17 November 2014.10 page(s

A systematic review of dietary, nutritional, and physical activity interventions for the prevention of prostate cancer progression and mortality

PURPOSE: Given the long-term, although potentially fatal, nature of prostate cancer, there is increasing observational evidence for the reduction in disease progression and mortality through changes in lifestyle factors. METHODS: We systematically reviewed dietary, nutritional, and physical activity randomized interventions aimed at modifying prostate cancer progression and disease-specific mortality, including a detailed assessment of risk of bias and methodological quality. RESULTS: Forty-four randomized controlled trials of lifestyle interventions, with prostate cancer progression or mortality outcomes, were identified. Substantial heterogeneity of the data prevented a meta-analysis. The included trials involved 3,418 prostate cancer patients, median 64 men per trial, from 13 countries. A trial of a nutritional supplement of pomegranate seed, green tea, broccoli, and turmeric; a trial comparing flaxseed, low-fat diet, flaxseed, and low-fat diet versus usual diet; and a trial supplementing soy, lycopene, selenium, and coenzyme Q10, all demonstrated beneficial effects. These trials were also assessed as having low risk of bias and high methodological quality (as were seven other trials with no evidence of benefit). The remaining trials were either underpowered, at high or unclear risk of bias, inadequately reported, of short duration or measured surrogate outcomes of unproven relationship to mortality or disease progression, which precluded any benefits reported being reliable. CONCLUSION: Large, well-designed randomized trials with clinical endpoints are recommended for lifestyle modification interventions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10552-015-0659-4) contains supplementary material, which is available to authorized users

Symmetric (A) and asymmetric (B) forms of citrate synthase as generated by the geometric simulations (red, blue) biased along normal modes 9 (A) and 7 (B), started from the open structure (PDB ID: 3ENJ), compared to the closed structure (PDB ID: 2CTS, light gray).

<p>Symmetric (A) and asymmetric (B) forms of citrate synthase as generated by the geometric simulations (red, blue) biased along normal modes 9 (A) and 7 (B), started from the open structure (PDB ID: 3ENJ), compared to the closed structure (PDB ID: 2CTS, light gray).</p

Pig heart citrate synthase (CS) crystal structures with the angle and dihedral measurements labelled.

<p>Chain A is depicted in dark blue, chain B in dark green, with the small domains transparent. A) open structure, PDB ID: 3ENJ.[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133372#pone.0133372.ref023" target="_blank">23</a>] B) closed structure, PDB ID: 2CTS.[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133372#pone.0133372.ref007" target="_blank">7</a>]</p

Structures obtained from geometric simulations of flexible motion biased along different normal mode directions (mode 7+8 in red–see text, mode 8 in blue) and MD simulations (light green) that are most similar to (A) the asymmetric structure (gray; PDB ID: 1XMM) and (B) the chain-swapped asymmetric structure (gray).

<p>C) Cα RMSDs to the symmetric (1XML) and asymmetric (1XMM) crystal structures for every 100^th frame of the flexible motion simulations along mode 8 (blue) and mode 8+7 (red).</p