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Copyright: © 2015 Huynh et al. Glucocorticoids are commonly used as palliative or chemotherapeutic clinical agents for treatment of a variety of cancers. Although steroid treatment is beneficial, the mechanisms by which steroids improve outcome in cancer patients are not well understood. Na, K-ATPase beta-subunit isoform 1 (NaK-β1) is a cell-cell adhesion molecule, and its expression is down-regulated in cancer cells undergoing epithelial- to mesenchymal-transition (EMT), a key event associated with cancer progression to metastatic disease. In this study, we performed high-throughput screening to identify small molecules that could up-regulate NaK-β1 expression in cancer cells. Compounds related to the glucocorticoids were identified as drug candidates enhancing NaK-β1 expression. Of these compounds, triamcinolone, dexamethasone, and fluorometholone were validated to increase NaK-β1 expression at the cell surface, enhance cell-cell adhesion, attenuate motility and invasiveness and induce mesenchymal to epithelial like transition of renal cell carcinoma (RCC) cells in vitro. Treatment of NaK-β1 knockdown cells with these drug candidates confirmed that these compounds mediate their effects through up-regulating NaK-β1. Furthermore, we demonstrated that these compounds attenuate tumor growth in subcutaneous RCC xenografts and reduce local invasiveness in orthotopically-implanted tumors. Our results strongly indicate that the addition of glucocorticoids in the treatment of RCC may improve outcome for RCC patients by augmenting NaK-β1 cell-cell adhesion function.

Antireflux surgery usually gives long lasting control of gastroesophageal reflux disease, but late failures can occur from fundoplication wrap disruption. Disruption presumably occurs when physiological mechanical stresses cause the sutures to pull out of the fundoplication wrap. We hypothesized that complete fundoplications (fundus sutured to fundus) would withstand disruptive forces better than partial fundoplications (fundus sutured to esophagus). Forty-eight rats underwent fundoplication (24 partial and 24 complete). Fundoplication wraps were disrupted by distending the stomach (bursting pressure technique) and by distracting the wrap in a tensiometer (breaking strength technique). Bursting pressures were similar in the partial (103.7 +/- 13.5 mmHg) and complete (100.5 +/- 13.1 mmHg) fundoplication wraps (P = 0.93, not significant). In both groups, all disruptions occurred by sutures tearing through the stomach wall. Breaking strength was also equivalent for the two types of wrap. Partial wraps disrupted at 6.69 +/- 1.49 N and complete wraps disrupted at 6.52 +/- 1.28 N (P = 0.77, not significant). Sutures tore out of the stomach side of the partial wrap in five rats and out of the esophagus in the other seven rats with partial wraps. Disruption occurred by sutures tearing through the stomach in all rats with complete fundoplications. This experimental study in the rat did not show any difference in the ability of partial and complete fundoplication wraps to withstand disruptive forces.