Obesity and prostate cancer-specific mortality after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.

BackgroundAt the population level, obesity is associated with prostate cancer (PC) mortality. However, few studies analyzed the associations between obesity and long-term PC-specific outcomes after initial treatment.MethodsWe conducted a retrospective analysis of 4268 radical prostatectomy patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Cox models accounting for known risk factors were used to examine the associations between body mass index (BMI) and PC-specific mortality (PCSM; primary outcome). Secondary outcomes included biochemical recurrence (BCR) and castration-resistant PC (CRPC). BMI was used as a continuous and categorical variable (normal <25 kg/m2, overweight 25-29.9 kg/m2 and obese ⩾30 kg/m2). Median follow-up among all men who were alive at last follow-up was 6.8 years (interquartile range=3.5-11.0). During this time, 1384 men developed BCR, 117 developed CRPC and 84 died from PC. Hazard ratios were analyzed using competing-risks regression analysis accounting for non-PC death as a competing risk.ResultsOn crude analysis, higher BMI was not associated with risk of PCSM (P=0.112), BCR (0.259) and CRPC (P=0.277). However, when BMI was categorized, overweight (hazard ratio (HR) 1.99, P=0.034) and obesity (HR 1.97, P=0.048) were significantly associated with PCSM. Obesity and overweight were not associated with BCR or CRPC (all P⩾0.189). On multivariable analysis adjusting for both clinical and pathological features, results were little changed in that obesity (HR=2.05, P=0.039) and overweight (HR=1.88, P=0.061) were associated with higher risk of PCSM, but not with BCR or CRPC (all P⩾0.114) with the exception that the association for overweight was no longer statistical significant.ConclusionsOverweight and obesity were associated with increased risk of PCSM after radical prostatectomy. If validated in larger studies with longer follow-up, obesity may be established as a potentially modifiable risk factor for PCSM

Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer

Herein, we describe a novel approach in the search for prostate cancer biomarkers, which relies on the transcriptome within tumour exosomes. As a proof-of-concept, we show the presence of two known prostate cancer biomarkers, PCA-3 and TMPRSS2:ERG the in exosomes isolated from urine of patients, showing the potential for diagnosis and monitoring cancer patients status

Pre-surgical depression and anxiety and recovery following coronary artery bypass graft surgery

We aimed to explore the combined contribution of pre-surgical depression and anxiety symptoms for recovery following coronary artery bypass graft (CABG) using data from 251 participants. Participants were assessed prior to surgery for depression and anxiety symptoms and followed up at 12 months to assess pain and physical symptoms, while hospital emergency admissions and death/major adverse cardiac events (MACE) were monitored on average 2.68 years after CABG. After controlling for covariates, baseline anxiety symptoms, but not depression, were associated with greater pain (β = 0.231, p = 0.014) and greater physical symptoms (β = 0.194, p = 0.034) 12 months after surgery. On the other hand, after controlling for covariates, baseline depression symptoms, but not anxiety, were associated with greater odds of having an emergency admission (OR 1.088, CI 1.010–1.171, p = 0.027) and greater hazard of death/MACE (HR 1.137, CI 1.042–1.240, p = 0.004). These findings point to different pathways linking mood symptoms with recovery after CABG surgery

Augmented acquisition of cocaine self-administration and altered brain glucose metabolism in adult female but not male rats exposed to a cannabinoid agonist during adolescence

Marijuana consumption during adolescence has been proposed to be a stepping stone for adult cocaine addiction. However, experimental evidence for this hypothesis is missing. In this work we chronically injected male and female Wistar rats with either the cannabinoid agonist CP 55,940 (CP; 0.4 mg/kg) or its corresponding vehicle. Adult acquisition (seven 30 min daily sessions) and maintenance (fourteen 2 h daily sessions) of cocaine self administration (1 mg/kg), food reinforced operant learning under conditions of normal (ad libitum access to food), and high motivation (food restriction schedule) were measured. Additionally, brain metabolic activity was analyzed by means of [18F] fluorodeoxyglucose positron emission tomography. During the acquisition phase, female CP treated rats showed a higher rate of cocaine self administration as compared to vehicle treated females and males; no differences were found between both male groups. This effect disappeared in the maintenance phase. Moreover, no differences among groups were evident in the food reinforced operant task, pointing to the cocaine specific nature of the effect seen in self administration rather than a general change in reward processing. Basal brain metabolic activity also changed in CP treated females when compared to their vehicle treated counterparts with no differences being found in the males; more specifically we observed a hyper activation of the frontal cortex and a hypo activation of the amygdalo entorhinal cortex. Our results suggest that a chronic exposure to cannabinoids during adolescence alters the susceptibility to acquire cocaine self administration, in a sex specific fashion. This increased susceptibility could be related to thechanges in brain metabolic activity induced by cannabinoids during adolescenceThis work was supported by Grants FIS G03/05 (Red de Trastornos Adictivos), BSO2001-1099, FIS 01-05-01, Plan Nacional sobre Drogas (PNSD) 2001–2003, PNSD 2004–2007, GR-SAL/0260/2004 to EA and Grants INT/2012/ 2002, CB06/01/0079, and CENIT (2006–2009) to MDPublicad

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

iTRAQ Identification of Candidate Serum Biomarkers Associated with Metastatic Progression of Human Prostate Cancer

A major challenge in the management of patients with prostate cancer is identifying those individuals at risk of developing metastatic disease, as in most cases the disease will remain indolent. We analyzed pooled serum samples from 4 groups of patients (n = 5 samples/group), collected prospectively and actively monitored for a minimum of 5 yrs. Patients groups were (i) histological diagnosis of benign prostatic hyperplasia with no evidence of cancer ‘BPH’, (ii) localised cancer with no evidence of progression, ‘non-progressing’ (iii) localised cancer with evidence of biochemical progression, ‘progressing’, and (iv) bone metastasis at presentation ‘metastatic’. Pooled samples were immuno-depleted of the 14 most highly abundant proteins and analysed using a 4-plex iTRAQ approach. Overall 122 proteins were identified and relatively quantified. Comparisons of progressing versus non-progressing groups identified the significant differential expression of 25 proteins (p<0.001). Comparisons of metastatic versus progressing groups identified the significant differential expression of 23 proteins. Mapping the differentially expressed proteins onto the prostate cancer progression pathway revealed the dysregulated expression of individual proteins, pairs of proteins and ‘panels’ of proteins to be associated with particular stages of disease development and progression. The median immunostaining intensity of eukaryotic translation elongation factor 1 alpha 1 (eEF1A1), one of the candidates identified, was significantly higher in osteoblasts in close proximity to metastatic tumour cells compared with osteoblasts in control bone (p = 0.0353, Mann Whitney U). Our proteomic approach has identified leads for potentially useful serum biomarkers associated with the metastatic progression of prostate cancer. The panels identified, including eEF1A1 warrant further investigation and validation

Determinants of male reproductive health disorders: the Men in Australia Telephone Survey (MATeS)

Background: The relationship between reproductive health disorders and lifestyle factors in middle-aged and older men is not clear. The aim of this study is to describe lifestyle and biomedical associations as possible causes of erectile dysfunction (ED), prostate disease (PD), lower urinary tract symptoms (LUTS) and perceived symptoms of androgen deficiency (pAD) in a representative population of middle-aged and older men, using the Men in Australia Telephone Survey (MATeS). Methods: A representative sample (n = 5990) of men aged 40+ years, stratified by age and State, was contacted by random selection of households, with an individual response rate of 78%. All men participated in a 20-minute computer-assisted telephone interview exploring general and reproductive health. Associations between male reproductive health disorders and lifestyle and biomedical factors were analysed using multivariate logistic regression (odds ratio [95% confidence interval]). Variables studied included age, body mass index, waist circumference, smoking, alcohol consumption, physical activity, co-morbid disease and medication use for hypertension, high cholesterol and symptoms of depression. Results: Controlling for age and a range of lifestyle and co-morbid exposures, sedentary lifestyle and being underweight was associated with an increased likelihood of ED (1.4 [1.1-1.8]; 2.9 [1.5-5.8], respectively) and pAD (1.3 [1.1-1.7]; 2.7 [1.4-5.0], respectively. Diabetes and cardiovascular disease were both associated with ED, with hypertension strongly associated with LUTS and pAD. Current smoking (inverse association) and depressive symptomatology were the only variables independently associated with PD. All reproductive disorders showed consistent associations with depression (measured either by depressive symptomatology or medication use) in both age-adjusted and multivariate analyses. Conclusion: A range of lifestyle factors, more often associated with chronic disease, were significantly associated with male reproductive health disorders. Education strategies directed to improving general health may also confer benefits to male reproductive health.Carol A. Holden, Robert I. McLachlan, Marian Pitts, Robert Cumming, Gary Wittert, Johnathon P. Ehsani, David M. de Kretser, David J. Handelsma