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BACKGROUND: Ewing sarcoma (ES) is an aggressive childhood solid tumor in which 30% of cases are metastatic at presentation, and subsequently carry a poor prognosis. We have previously shown that treatment with celecoxib significantly reduces invasion and metastasis of ES cells in a cyclooxygenase-2-independent fashion. Celecoxib is known to downregulate beta-catenin independently of cyclooxygenase-2. Additionally, the actin cytoskeleton is known to play an important role in tumor micrometastasis. We hypothesized that celecoxib's antimetastatic effect in ES acts via modulation of one of these two targets. METHODS: ES cells were treated with celecoxib, and the levels of beta-catenin and total actin were examined by Western blot and quantitative polymerase chain reaction. Cells were transfected with small interfering RNA targeting beta-catenin, and invasion assays were performed. Immunofluorescence staining for beta-catenin and F-actin was performed on treated and untreated cells. Additionally, cells were subjected to a wound healing assay to assess migration. RESULTS: Celecoxib had no effect on the messenger RNA or protein levels of beta-catenin but did significantly decrease the amount of total actin within ES cells. Reduction of beta-catenin by small interfering RNA had no effect on invasion, and celecoxib treatment of the beta-catenin depleted cells continued to inhibit invasion. Immunofluorescence staining demonstrated no change in beta-catenin with treatment but did show a significant reduction in the amount of F-actin, as well as morphologic changes of the cells. Wound healing assays demonstrated that celecoxib significantly inhibited migration. CONCLUSIONS: Celecoxib does not exert its antimetastatic effects in ES through alteration of beta-catenin but does significantly modulate the actin cytoskeleton.

INTRODUCTION: Previously, increasing age has been a part of the exclusion criteria used when determining eligibility for a pancreas transplant. However, the analysis of pancreas transplantation outcomes based on age groupings has largely been based on single-center reports. METHODS: A UNOS database review of all adult pancreas and kidney-pancreas transplants between 1996 and 2012 was performed. Patients were divided into groups based on age categories: 18-29 (n = 1823), 30-39 (n = 7624), 40-49 (n = 7967), 50-59 (n = 3160), and >/=60 (n = 280). We compared survival outcomes and demographic variables between each age grouping. RESULTS: Of the 20 854 pancreas transplants, 3440 of the recipients were 50 yr of age or above. Graft survival was consistently the greatest in adults 40-49 yr of age. Graft survival was least in adults age 18-29 at one-, three-, and five-yr intervals. At 10- and 15-yr intervals, graft survival was the poorest in adults >60 yr old. Patient survival and age were found to be inversely proportional; as the patient population's age increased, survival decreased. CONCLUSION: Pancreas transplants performed in patients of increasing age demonstrate decreased patient and graft survival when compared to pancreas transplants in patients <50 yr of age.

BACKGROUND/INTRODUCTION: Previously, we reported that celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, prevented lung metastases but did not affect tumor growth in a model of Ewing sarcoma. Cyclooxygenase-2 inhibition has been proposed as an antimetastatic strategy. The mechanism of action remains unclear. METHODS: Ewing sarcoma cells were suspended in a soluble basement membrane extract (Cultrex; Trevigen, Inc, Gaithersburg, MD) and supplemented with celecoxib or with rofecoxib, a second COX-2 inhibitor, above a filter. Controls received solvent. After 48 hours, the cells that invaded through the basement membrane and filter were stained and counted. The assay was repeated with the addition of 500-nM prostaglandin E2 (PGE(2)). RESULTS: Invasion was significantly decreased in the celecoxib groups compared with the control. The addition of PGE(2) did not overcome celecoxib inhibition. Rofecoxib did not significantly affect invasion compared with control either with or without PGE(2). CONCLUSIONS: Celecoxib significantly inhibits invasion of Ewing sarcoma cells in vitro. Prostaglandin E2, a downstream product of COX-2, did not reverse in vitro inhibition, suggesting that celecoxib acts through a COX-2-independent mechanism. This is further supported by the failure of rofecoxib to inhibit invasion despite more selectively inhibiting COX-2.