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© 2018 Office of the Federal Register. All rights reserved. A Belousov-Zhabotinsky reaction in a liquid-liquid system was observed under non-stirring conditions to evaluate control of the non-equilibrium reaction by microwave irradiation through color changes of the solution. Irradiation power and time, and droplet size were important factors to control the oscillatory reaction in the droplet. During irradiation, the oscillatory period of any droplet sizes became shorter because the reaction rate became faster. In smaller droplets (2 mm), this behavior can be explained by the non-thermal effect because the temperature was equal to the temperature of the surrounding oil. Moreover, the oscillatory behaviors of the reaction in smaller droplets did not change after the irradiation even under higher power and longer irradiation time. On the other hand, shorter oscillatory period was observed in larger droplets (7 mm) after the irradiation, and the special microwave effect persisted. Overall, microwave irradiation was useful for controlling the non-linear reaction in a liquid-liquid system because of activation of the interface through the oil phase.

Item does not contain fulltext, BACKGROUND: Pazopanib, a multitargeted tyrosine kinase inhibitor, has single-agent activity in patients with advanced non-adipocytic soft-tissue sarcoma. We investigated the effect of pazopanib on progression-free survival in patients with metastatic non-adipocytic soft-tissue sarcoma after failure of standard chemotherapy. METHODS: This phase 3 study was done in 72 institutions, across 13 countries. Patients with angiogenesis inhibitor-naive, metastatic soft-tissue sarcoma, progressing despite previous standard chemotherapy, were randomly assigned by an interactive voice randomisation system in a 2:1 ratio in permuted blocks (with block sizes of six) to receive either pazopanib 800 mg once daily or placebo, with no subsequent cross-over. Patients, investigators who gave the treatment, those assessing outcomes, and those who did the analysis were masked to the allocation. The primary endpoint was progression-free survival. Efficacy analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00753688. FINDINGS: 372 patients were registered and 369 were randomly assigned to receive pazopanib (n=246) or placebo (n=123). Median progression-free survival was 4.6 months (95% CI 3.7-4.8) for pazopanib compared with 1.6 months (0.9-1.8) for placebo (hazard ratio [HR] 0.31, 95% CI 0.24-0.40; p<0.0001). Overall survival was 12.5 months (10.6-14.8) with pazopanib versus 10.7 months (8.7-12.8) with placebo (HR 0.86, 0.67-1.11; p=0.25). The most common adverse events were fatigue (60 in the placebo group [49%] vs 155 in the pazopanib group [65%]), diarrhoea (20 [16%] vs 138 [58%]), nausea (34 [28%] vs 129 [54%]), weight loss (25 [20%] vs 115 [48%]), and hypertension (8 [7%] vs 99 [41%]). The median relative dose intensity was 100% for placebo and 96% for pazopanib. INTERPRETATION: Pazopanib is a new treatment option for patients with metastatic non-adipocytic soft-tissue sarcoma after previous chemotherapy. FUNDING: GlaxoSmithKline.

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CD44 is a widely distributed cell surface adhesion molecule and is implicated in diverse biological processes. However, the nature of intracellular signaling triggered by CD44 remains to be elucidated. Here, we show that CD44 undergoes sequential proteolytic cleavage in the ectodomain and intracellular domain, resulting in the release of a CD44 intracellular domain (ICD) fragment. Consequently, CD44ICD acts as a signal transduction molecule, where it translocates to the nucleus and activates transcription mediated through the 12-O-tetradecanoylphorbol 13-acetate-responsive element, which is found in numerous genes involved in diverse cellular processes. Expression of an uncleavable CD44 mutant as well as metalloprotease inhibitor treatment blocks CD44-mediated transcriptional activation. In search of the underlying mechanism, we have found that CD44ICD potentiates transactivation mediated by the transcriptional coactivator CBP/p300. Furthermore, we show that cells expressing CD44ICD produce high levels of CD44 messenger RNA, suggesting that the CD44 gene is one of the potential targets for transcriptional activation by CD44ICD. These observations establish a novel CD44 signaling pathway and shed new light on the functional link between proteolytic processing of an adhesion molecule at the cell surface and transcriptional activation in the nucleus.