MicroRNA signatures and treatment response in patients with advanced classical Hodgkin lymphoma.

Although specific microRNA (miRNA) signatures in classical Hodgkin lymphoma (cHL) have been proposed, their relationship with clinical outcome remains unclear. Despite treatment advances, a substantial subset of patients with advanced cHL are refractory to standard therapies based on adriamycin and its variants. Global miRNA expression data of 29 advanced cHL patients and five cHL-derived cell lines were used to identify profiles from Hodgkin-Reed-Sternberg (HRS) cells and their non-tumoural microenvironment. A cHL-miRNA signature was identified with 234 miRNAs differentially expressed. A subset of these miRNAs was associated with outcome and selected for study in an independent set of 168 cHL samples using quantitative reverse transcription polymerase chain reaction. Multivariate Cox regression analyses including cross-validation with failure-free survival (FFS) as clinical endpoint revealed a miRNA signature with MIR21, MIR30E, MIR30D and MIR92B* that identified two risk-groups with significant differences in 5-year FFS (81% vs. 35.7%; P < 0.001). Additionally, functional silencing of MIR21 and MIR30D in L428 cells showed increased sensitivity to doxorubicin-induced apoptosis, pointing towards abnormalities of mitochondrial intrinsic and TP53-CDKN1A pathways as related to miRNA deregulation in cHL. These results suggest that clinical outcome in cHL is associated with a specific miRNA signature. Moreover, functional analyses suggest a role for MIR21 and MIR30D in cHL pathogenesis and therapeutic resistance.

Are Young Swimmers Short and Middle Distances Energy Cost Sex-Specific?

This study assessed the energy cost in swimming (C) during short and middle distances to analyze the sex-specific responses of C during supramaximal velocity and whether body composition account to the expected differences. Twenty-six swimmers (13 men and 13 women: 16.7 ± 1.9 vs. 15.5 ± 2.8 years old and 70.8 ± 10.6 vs. 55.9 ± 7.0 kg of weight) performed maximal front crawl swimming trials in 50, 100, and 200 m. The oxygen uptake ( V ˙ O2) was analyzed along with the tests (and post-exercise) through a portable gas analyser connected to a respiratory snorkel. Blood samples were collected before and after exercise (at the 1st, 3rd, 5th, and 7th min) to determine blood lactate concentration [La-]. The lean mass of the trunk (LM Trunk ), upper limb (LM UL ), and lower limb (LM LL ) was assessed using dual X-ray energy absorptiometry. Anaerobic energy demand was calculated from the phosphagen and glycolytic components, with the first corresponding to the fast component of the V ˙ O2 bi-exponential recovery phase and the second from the 2.72 ml × kg-1 equivalent for each 1.0 mmol × L-1 [La-] variation above the baseline value. The aerobic demand was obtained from the integral value of the V ˙ O2 vs. swimming time curve. The C was estimated by the rate between total energy releasing (in Joules) and swimming velocity. The sex effect on C for each swimming trial was verified by the two-way ANOVA (Bonferroni post hoc test) and the relationships between LM Trunk , LM UL , and LM LL to C were tested by Pearson coefficient. The C was higher for men than women in 50 (1.8 ± 0.3 vs. 1.3 ± 0.3 kJ × m-1), 100 (1.4 ± 0.1 vs. 1.0 ± 0.2 kJ × m-1), and 200 m (1.0 ± 0.2 vs. 0.8 ± 0.1 kJ × m-1) with p < 0.01 for all comparisons. In addition, C differed between distances for each sex (p < 0.01). The regional LM Trunk (26.5 ± 3.6 vs. 20.1 ± 2.6 kg), LM UL (6.8 ± 1.0 vs. 4.3 ± 0.8 kg), and LM LL (20.4 ± 2.6 vs. 13.6 ± 2.5 kg) for men vs. women were significantly correlated to C in 50 (R 2 adj = 0.73), 100 (R 2 adj = 0.61), and 200 m (R 2 adj = 0.60, p < 0.01). Therefore, the increase in C with distance is higher for men than women and is determined by the lean mass in trunk and upper and lower limbs independent of the differences in body composition between sexes.