Alterations of Global Histone H3K9 and H3K27 Methylation Levels in Bladder Cancer

Background: Epigenetic alterations, including histone modifications, play an important role during carcinogenesis. This study was designed to systematically investigate histone H3K9 and H3K27 methylation levels in bladder cancer (BCa) tissue. Methods:A tissue microarray with urothelial BCa (150 non-muscle-invasive BCa, NMIBC; 121 muscle-invasive BCa, MIBC; 31 metastatic BCa, MET) and normal urothelium (29, CTRL) specimen was used to determine the global levels of H3K9 and H3K27 mono-, di- and tri-methylation. Results: Global levels of H3K9 and H3K27 methylation were significantly higher in CTRL than in BCa, and levels in NMIBC were higher compared to MIBC. Histone nnethylation levels of MET resembled MIBC. We observed furthermore a correlation of histone nnethylation levels with pT stage (H3K9me1, H3K9me2, H3K9me3, H3K27me1, H3K27me3) and grade (H3K9nne2, H3K9me3, H3K27nne1) in NMIBC. H3K9me1, H3K9me3, H3K27me1 and H3K27me3 levels were also correlated with pT stage in MIBC. Histone modifications were not associated with recurrence-free or cancer-specific survival. Conclusions: Global histone H3K9 and H3K27 nnethylation levels are altered in BCa. (C) 2014 S. Karger AG, Base

The effects of sodium bicarbonate supplementation at individual time-to-peak blood bicarbonate on 4-km cycling time trial performance in the heat

The purpose of this study was to explore the effect of individualised sodium bicarbonate (NaHCO3) supplementation according to a pre-established individual time-to-peak (TTP) blood bicarbonate (HCO3−) on 4-km cycling time trial (TT) performance in the heat. Eleven recreationally trained male cyclists (age: 28 ± 6 years, height: 180 ± 6 cm, body mass: 80.5 ± 8.4 kg) volunteered for this study in a randomised, crossover, triple-blind, placebo-controlled design. An initial visit was conducted to determine TTP HCO3− following 0.2 g.kg−1 body mass (BM) NaHCO3 ingestion. Subsequently, on three separate occasions, participants completed a 4-km cycling TT in the heat (30 degrees centigrade; °C) (relative humidity ∼40%) following ingestion of either NaHCO3 (0.2 g.kg−1 body mass), a sodium chloride placebo (0.2 g.kg−1 BM; PLA) at the predetermined individual TTP HCO3−, or no supplementation (control; CON) . Absolute peak [HCO3−] prior to the 4-km cycling TT's was elevated for NaHCO3 compared to PLA (+2.8 mmol.l−1; p = 0.002; g = 2.2) and CON (+2.5 mmol.l−1; p < 0.001; g = 2.1). Completion time following NaHCO3 was 5.6 ± 3.2 s faster than PLA (1.6%; CI: 2.8, 8.3; p = 0.001; g = 0.2) and 4.7 ± 2.8 s faster than CON (1.3%; CI: 2.3, 7.1; p = 0.001; g = 0.2). These results demonstrate that NaHCO3 ingestion at a pre-established individual TTP HCO3− improves 4-km cycling TT performance in the heat, likely through enhancing buffering capacity