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Purpose Adjuvant therapy for intermediate-risk and high-risk localized prostate cancer decreases the number of deaths from this disease. Surrogates for overall survival (OS) could expedite the evaluation of new adjuvant therapies. Methods By June 2013, 102 completed or ongoing randomized trials were identified and individual patient data were collected from 28 trials with 28,905 patients. Disease-free survival (DFS) and metastasis-free survival (MFS) were determined for 21,140 patients from 24 trials and 12,712 patients from 19 trials, respectively. We evaluated the surrogacy of DFS and MFS for OS by using a two-stage meta-analytic validation model by determining the correlation of an intermediate clinical end point with OS and the correlation of treatment effects on both the intermediate clinical end point and OS. Results Trials enrolled patients from 1987 to 2011. After a median follow-up of 10 years, 45% of 21,140 men and 45% of 12,712 men experienced a DFS and MFS event, respectively. For DFS and MFS, 61% and 90% of the patients, respectively, were from radiation trials, and 63% and 66%, respectively, had high-risk disease. At the patient level, Kendall’s τ correlation with OS was 0.85 and 0.91 for DFS and MFS, respectively. At the trial level, R2 was 0.86 (95% CI, 0.78 to 0.90) and 0.83 (95% CI, 0.71 to 0.88) from weighted linear regression of 8-year OS rates versus 5-year DFS and MFS rates, respectively. Treatment effects—measured by log hazard ratios—for the surrogates and OS were well correlated ( R2, 0.73 [95% CI, 0.53 to 0.82] for DFS and 0.92 [95% CI, 0.81 to 0.95] for MFS). Conclusion MFS is a strong surrogate for OS for localized prostate cancer that is associated with a significant risk of death from prostate cancer.

BACKGROUND AND OBJECTIVE: Hypertension is associated with alteration in endothelial function mediated through reduced nitric oxide bioavailability and renal injury. Exercise training has been shown to improve endothelial function in animal models of hypertension and in the patients with essential hypertension. The purpose of this study was to investigate the protective effect of aerobic exercise against some of proinflammatory cytokines in the renal tissue of rats treated with chronic nitric oxide synthase inhibition. METHODS: In this experimental research, 40 male Wistar rats were randomly divided into four groups: (1) control (2) sham (3) nitric oxide synthase inhibition (infusion of N?-Nitro-L-Arginine Methyl Ester, intraperitoneally) and (4) aerobic exercise (exercise + nitric oxide synthase inhibition) (n=10 for any group). The exercise consisted of progressive running training on the treadmill for 15 to 22 m/min, 25 to 64 min /day, and 5 days/week for 8 weeks. Tumor necrosis factor-alpha (TNF-?) and interlukin-6 (IL-6) levels was measured by ELISA method and the groups were compared.FINDINGS: Chronic nitric oxide synthase inhibition significantly enhanced renal TNF-? (2.53 ± 0.52 pg/mg) and IL-6 (4.15 ± 0.88 pg/mg) levels (p=0.000). Conversely, aerobic exercise significantly decreased (p=0.045) this proinflammatory cytokines levels (1.97 ± 0.37, 3.46 ± 0.80 pg/mg, respectively) in rat kidney.CONCLUSION: Regular aerobic exercise with moderate intense may exert protective role against systemic nitric oxide deficiency-induced inflammatory renal injury by down-regulating the proinflammatory cytokines.

Lifestyle modifications, such as physical exercise and dietary supplements, were recommended as protective measures against some neurological disorders. We examined the effects of regular exercise combined with curcumin supplementation against lead-induced oxidative damage of the cerebellum in male rats. Experimental animals (n = 50) were randomly divided into five groups. Lead acetate (20 mg/kg) was i.p. administered to three groups (except sham and control ones), while the sham group received ethyloleate (30 mg/kg) three times per week. The curcumin and curcumin + exercise groups received curcumin (30 mg/kg) i.p. five times per week for eight weeks. The exercise program consisted of progressive running on a treadmill, speed from 15 to 22 m/min, 25 to 64 min per day, five times per week for eight weeks. Two days after the last application, the rats were euthanized, and their cerebellum was removed and homogenized to measure the levels of brain-derived neurotrophic factor (BDNF) and thiobarbituric acid-reactive substances (TBARSs). Chronic administration of lead significantly increased the cerebellar TBARS levels but did not alter considerably the BDNF levels. Curcumin and curcumin + exercise treatments significantly lowered the cerebellar TBARS levels; a significant increase in the BDNF level was observed in the cerebellum of rats treated with combined intervention. Thus, regular exercise combined with curcumin supplementation may exert a significant neuroprotective effect against lead-induced cerebellar injury by attenuating oxidative stress and improving the brain state through an increase in the BDNF amount. Модифікації стилю життя, такі як фізичні тренування та вживання добавок до дієти, рекомендуються як протективні заходи щодо низки неврологічних розладів. Ми дослідили впливи регулярних тренувань, поєднаних з уведенням куркуміну, на індуковане свинцевою інтоксикацією оксидативне ушкодження мозочка у самців щурів. Експериментальні тварини (n = 50) були рандомізовано поділені на п’ять груп. Ацетат свинцю (20 мг/кг) уводився тваринам трьох груп (дві слугували контролем). Одна з контрольних груп отримувала етилолеат (30 мг/кг) тричі на тиждень. У двох інтоксикованих групах тварини отримували 30 мг/кг куркуміну п’ять разів на тиждень протягом восьми тижнів. Програма тренувань включала в себе прогресивно збільшувані епізоди бігу на тредбані (від 15 до 25 м/хв, від 25 до 64 хв/добу, п’ять разів на тиждень протягом восьми тижнів). Через дві доби після закінчення курсів щурів піддавали евтаназії, мозочок видаляли та гомогенізували для вимірювання рівнів мозкового нейротрофічного фактора (BDNF) та речовин, реактивних щодо тіобарбітурової кислоти (TBARSs). Хронічне введення свинцю викликало вірогідне збільшення рівнів TBARS, але не змінювало істотно рівнів BDNF. У групах «куркумін» та «куркумін+тренування» спостерігалися значно нижчі рівні TBARS; вірогідно більший рівень BDNF у мозочку відмічався в групі з комбінацією заходів. Отже, регулярні фізичні тренування, поєднані з уведенням куркуміну, можуть забезпечити істотний протекторний ефект щодо індукованого свинцем ушкодження мозочка, опосередкований зменшенням оксидативного стресу та поліпшенням стану мозку завдяки певному збільшенню кількості BDNF.