Recent reports on the role of the membrane-cytoskeleton linker protein ezrin in sarcomas showed an effect on the formation of metastases, dependent on the level of ezrin expression. In this study, we explore the role of ezrin in Ewing's sarcoma, a frequently fatal mesenchymal neoplasm of children and young adults. Through both immunohistochemistry and Western immunoblot studies we find ubiquitous, high-level expression of ezrin in Ewing's sarcoma. In contrast to the observations in osteosarcoma and rhabdomyosarcoma, we demonstrate that inhibition of ezrin-mediated signal transduction, through the expression of a non-phosphorylatable T567A mutant, slows primary growth of Ewing's sarcoma cells in vitro. This reduction in growth is a result of increased apoptosis in the mutant expressing cells. We further show that expression of this mutant reduces the ability of Ewing's sarcoma cells to form experimental metastases in vivo. Molecular examination reveals that the action of ezrin in Ewing's sarcoma is dependent on the AKT/mTOR signal transduction cascade, but not MAP Kinase. These results, therefore, demonstrate that, in Ewing's sarcoma, the biology of ezrin is distinct from that described in other sarcomas. This study further validates ezrin as a potential therapeutic target.

Despite adequate reduction and casting of type-2 supracondylar fractures, some fractures will lose reduction and require delayed pinning. The degree of extension of the distal fragment at the time of injury may help to predict the likelihood of failure of nonoperative treatment.

Purpose:The purpose of this study was to measure and compare the subjective, objective, and radiographic healing outcomes of single-row (SR), double-row (DR), and transosseous equivalent (TOE) suture techniques for arthroscopic rotator cuff repair.Materials and Methods:A retrospective comparative analysis of arthroscopic rotator cuff repairs by one surgeon from 2004 to 2010 at minimum 2-year followup was performed. Cohorts were matched for age, sex, and tear size. Subjective outcome variables included ASES, Constant, SST, UCLA, and SF-12 scores. Objective outcome variables included strength, active range of motion (ROM). Radiographic healing was assessed by magnetic resonance imaging (MRI). Statistical analysis was performed using analysis of variance (ANOVA), Mann — Whitney and Kruskal — Wallis tests with significance, and the Fisher exact probability test <0.05.Results:Sixty-three patients completed the study requirements (20 SR, 21 DR, 22 TOE). There was a clinically and statistically significant improvement in outcomes with all repair techniques (ASES mean improvement P = <0.0001). The mean final ASES scores were: SR 83; (SD 21.4); DR 87 (SD 18.2); TOE 87 (SD 13.2); (P = 0.73). There was a statistically significant improvement in strength for each repair technique (P < 0.001). There was no significant difference between techniques across all secondary outcome assessments: ASES improvement, Constant, SST, UCLA, SF-12, ROM, Strength, and MRI re-tear rates. There was a decrease in re-tear rates from single row (22%) to double-row (18%) to transosseous equivalent (11%); however, this difference was not statistically significant (P = 0.6).Conclusions:Compared to preoperatively, arthroscopic rotator cuff repair, using SR, DR, or TOE techniques, yielded a clinically and statistically significant improvement in subjective and objective outcomes at a minimum 2-year follow-up.Level of Evidence:Therapeutic level 3.

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