No abstract

No outside funding supported this study. The authors have nothing to disclose. Study concept and design were principally contributed by Bagwell and Newman, along with the other authors. Lee took the lead in data collection, along with Carver, Bagwell, Kelley, and Newman. Data interpretation was performed by Carver, Kelley, Lee, and Bagwell, with assistance from Newman. The manuscript was written by Bagwell, Carver, Kelley, and Lee and revised primarily by Bagwell, along with the other authors.

Antineoplastic platinum agents are used in first-line treatment of ovarian cancer, but treatment failure frequently results from platinum drug resistance. Emerging observations suggest a role of reactive oxygen species (ROS) in the resistance of cancer drugs including platinum drugs. However, the molecular link between ROS and cellular survival pathway is poorly understood. Using quantitative high-throughput combinational screen (qHTCS) and genomic sequencing, we show that in platinum-resistant ovarian cancer elevated ROS levels sustain high level of IL-11 by stimulating FRA1-mediated IL-11 expression and increased IL-11 causes resistance to platinum drugs by constitutively activating JAK2-STAT5 via an autocrine mechanism. Inhibition of JAK2 by LY2784544 or IL-11 by anti-IL-11 antibody overcomes the platinum resistance in vitro or in vivo. Significantly, clinic studies also confirm the activated IL-11-JAK2 pathway in platinum-resistant ovarian cancer patients, which highly correlates with poor prognosis. These findings not only identify a novel ROS-IL-11-JAK2-mediated platinum resistance mechanism but also provide a new strategy for using LY2784544- or IL-11-mediated immunotherapy to treat platinum-resistant ovarian cancer.

The purpose of this study was to examine the relationship of off-ice performance measures with on-ice turning, crossover, and forward skating performance in high school male hockey players. Thirty-eight players aged 15-18 (mean age ± SD: 16.4 ± 1.1 years; height: 177.9 ± 6.8 cm; weight: 72.5 ± 8.9 kg) participated in this study. On-ice tests included a forward sprint, short radius turns, and crossover turns. Off-ice tests included a 40-yd sprint, vertical jumps, horizontal jumps, and a dynamic balance test using a Y balance testing device. Five off-ice variables correlated with all on-ice performance measures. These variables included the 40-yd sprint, lateral bound right to left limb, double limb horizontal hop, balance on right in posterolateral direction, and composite balance performance on the right. Hierachical regression demonstrated that off-ice sprint time was most predictive of on-ice skating performance, accounting for 65.4% of the variability in forward skate time, 45.0% of the variability in left short radius time, 21.8% of the variance in right short radius time, 36.2% of the variance in left crossover time, and 30.8% of the variability in right crossover time. When using off-ice tests to evaluate hockey players, the 40-yd sprint is the best predictor of skating performance. Based on our regression equation, for every 1-second difference in the 40-yd sprint time, there will be approximately a 0.6-second difference in the 34.5-m on-ice sprint. The 40-yd sprint predicts forward skating performance and to a lesser degree; it also predicts crossover and tuning performance.