Metastasis is the primary cause of death from many tumors, and novel anti-metastatic therapies are necessary. Recently, we showed that metastatic tumors down-regulate key oxidative phosphorylation (OXPHOS) genes in favor of glycolysis, a further enhancement of the Warburg effect. Therefore, we sought to determine if restriction of glycolysis using 2-deoxy-D-glucose (2DG) would lead to increased utilization of OXPHOS and inhibition of the metastatic phenotype. Noncytotoxic concentrations of 2DG dose-dependently inhibited in vitro migration and invasion in the highly metastatic DLM8-luc-M1 osteosarcoma (OS) cell line, as well as other metastatic human, canine, and murine cancer cells of different histotypes. This was associated with cytoskeletal rearrangement and inhibition of cathepsin L expression. A dose-dependent shift toward OXPHOS was confirmed by demonstrating increased oxygen utilization and decreased lactate production in 2DG treated cells. Finally, 2DG treatment significantly delayed metastasis and prolonged survival in an orthotopic postsurgical OS model. In conclusion, this work suggests that forcing cells away from glycolysis may inhibit key components of the metastatic phenotype, providing a novel avenue for metastasis prevention.
The desymmetrization of p-peroxyquinols using a Brønsted acid catalyzed acetalization/oxa-Michael cascade was achieved in high yields and selectivities for a variety of aliphatic and aryl aldehydes. Mechanistic studies suggest that the reaction proceeds through a dynamic kinetic resolution of the peroxy hemiacetal intermediate. The resulting 1,2,4-trioxane products were derivatized and show potent cancer cytotoxicity.
Interest groups are increasingly turning to new media such as YouTube as vehicles for indirect lobbying. Such a visual medium provides unprecedented ability for interest groups to enter into and have influence on public policy debates through dissemination of policy preferences to wide audiences. While policy narratives are increasingly becoming the subject of policy research, no empirical research has examined whether interest groups' YouTube visual clips constitute policy narratives, with embedded narrative elements and strategies. To explore the intersection of policy narratives with new media, we use the Narrative Policy Framework (NPF) to analyze YouTube videos posted by the interest group Buffalo Field Campaign. Our results indicate that the group's videos were moderately strong in narrativity and that gory images were the most powerful predictor for public attention (measured by a rank order of views per month). The implications of our methodology and results for the empirical study of YouTube and its role in public policy are discussed.
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