Ubiquitin C-terminal hydrolase-L1 (UCH-L1) catalyses the hydrolysis of ubiquitin ester and amide mainly in neuronal cells. Recently it was proposed as a marker with a potential role in carcinogenesis. However, the molecular mechanism underlying the biological function of UCH-L1 in tumor cells is poorly understood. We found that UCH-L1 is highly expressed in non-small lung cancer cell line H157, having high invasive potential, and that the expression of UCH-L1 in tumor cells enhances their invasive potential in vitro and in vivo. UCH-L1 changes cell morphology by regulating cell adhesion through Akt-mediated pathway. Suppressing UCH-L1 expression by RNAi significantly suppressed the invasion in vitro and in vivo, and the activation of Akt and downstream mitogen activated protein kinases c-Jun N-terminal kinases and p38, but not ERK. In Akt-negative mutants, overexpression of UCH-L1 does not affect the invasion and migration capability of H157 cells. These results suggest that UCH-L1 is a key molecule to regulate tumor-cell invasion by upstream activation of Akt.
Early intervention before ICU admission was independently associated with decreased in-hospital mortality in critically ill cancer patients admitted to the ICU.
IntroductionThe aim of this study is to evaluate the effects of emergency department (ED) crowding on the implementation of tasks in the early resuscitation bundle during acute care of patients with severe sepsis and septic shock, as recommended by the Surviving Sepsis Campaign guidelines.MethodsWe analyzed the sepsis registry from August 2008 to March 2012 for patients presenting to an ED of a tertiary urban hospital and meeting the criteria for severe sepsis or septic shock. The ED occupancy rate, which was defined as the total number of patients in the ED divided by the total number of ED beds, was used for measuring the degree of ED crowding. It was categorized into three groups (low; intermediate; high crowding). The primary endpoint was the overall compliance with the entire resuscitation bundle.ResultsA total of 770 patients were enrolled. Of the eligible patients, 276 patients were assigned to the low crowding group, 250 patients to the intermediate crowding group, and 244 patients to the high crowding group (ED occupancy rate: ≤ 115; 116–149; ≥ 150%). There was significant difference in compliance rates among the three groups (31.9% in the low crowding group, 24.4% in the intermediate crowding group, and 16.4% in the high crowding group, P < 0.001). In a multivariate model, the high crowding group had a significant association with lower compliance (adjusted odds ratio (OR), 0.44; 95% confidence interval (CI), 0.26 to 0.76; P = 0.003). When the ED occupancy rate was included as a continuous variable in the model, it had also a negative correlation with the overall compliance (OR of 10% increase of the ED occupancy rate, 0.90; 95% CI, 0.84 to 0.96, P = 0.002).ConclusionsED crowding was significantly associated with lower compliance with the entire resuscitation bundle and decreased likelihood of the timely implementation of the bundle elements.
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