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G. Harvey Agnew 《CMAJ》1932,26(2):182-186
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Seidler DG Goldoni S Agnew C Cardi C Thakur ML Owens RT McQuillan DJ Iozzo RV 《The Journal of biological chemistry》2006,281(36):26408-26418
Decorin is not only a regulator of matrix assembly but also a key signaling molecule that modulates the activity of tyrosine kinase receptors such as the epidermal growth factor receptor (EGFR). Decorin evokes protracted internalization of the EGFR via a caveolar-mediated endocytosis, which leads to EGFR degradation and attenuation of its signaling pathway. In this study, we tested if systemic delivery of decorin protein core would affect the biology of an orthotopic squamous carcinoma xenograft. After tumor engraftment, the animals were given intraperitoneal injections of either vehicle or decorin protein core (2.5-10 mg kg(-1)) every 2 days for 18-38 days. This regimen caused a significant and dose-dependent inhibition of the tumor xenograft growth, with a concurrent decrease in mitotic index and a significant increase in apoptosis. Positron emission tomography showed that the metabolic activity of the tumor xenografts was significantly reduced by decorin treatment. Decorin protein core specifically targeted the tumor cells enriched in EGFR and caused a significant down-regulation of EGFR and attenuation of its activity. In vitro studies showed that the uptake of decorin by the A431 cells was rapid and caused a protracted down-regulation of the EGFR to levels similar to those observed in the tumor xenografts. Furthermore, decorin induced apoptosis via activation of caspase-3. This could represent an additional mechanism whereby decorin might influence cell growth and survival. 相似文献
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Christy A. Lotz Michael J. Agnew Alison A. Godwin Joan M. Stevenson 《Journal of electromyography and kinesiology》2009,19(2):331-340
Occupations demanding frequent and heavy lifting are associated with an increased risk of injury. A personal lift assist device (PLAD) was designed to assist human muscles through the use of elastic elements. This study was designed to determine if the PLAD could reduce the level of general and local back muscle fatigue during a cyclical lifting task. Electromyography of two erector spinae sites (T9 and L3) was recorded during a 45-min lifting session at six lifts/lowers per minute in which male participants (n = 10) lifted a box scaled to represent 20% of their maximum back extensor strength. The PLAD device reduced the severity of muscular fatigue at both muscle sites. RMS amplitude increased minimally (22% and 26%) compared to the no-PLAD condition (104% and 88%). Minimal median frequency decreases (0.33% and 0.41%) were observed in the PLAD condition compared to drops of 12% and 20% in the no-PLAD condition. The PLAD had an additional benefit of minimizing pre–post changes in muscular strength and endurance. The PLAD also resulted in a significantly lower rate of perceived exertion across the lifting session. It was concluded that the PLAD was effective at decreasing the level of back muscular fatigue. 相似文献