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INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of colorectal cancer in cyclooxygenase-2 (COX-2) overexpressing colorectal cancers. The present study was designed to evaluate the inhibitory effects of the COX-2 inhibitor celecoxib on the growth of colorectal cancer liver metastases in a syngeneic rat model, CC531. MATERIALS AND METHODS: The effects of celecoxib on cell viability in vitro were evaluated by treatment of CC531 tumor cell cultures with celecoxib. In vivo, Wag/Rij rats were inoculated with CC531 tumor cells at two sites in the liver and treated with celecoxib starting one week before, or directly after tumor inoculation. Control rats were inoculated without treatment. Three weeks after tumor inoculation rats were sacrificed. Tumor size, immune cell infiltration, caspase-3 activity, PGE(2) and celecoxib levels were determined. RESULTS: CC531 tumors did not show COX-2 expression. Tumor growth was significantly inhibited by celecoxib treatment in a dose dependent manner. Immune cell infiltration was decreased after celecoxib treatment, indicating that the immune system was not involved in preventing tumor growth. Tumor caspase-3 levels were only significantly increased if treatment was started before tumor inoculation. Celecoxib serum concentration starting at 0.84 mug/ml significantly inhibited the outgrowth of CC531 liver tumors. In contrast, in vitro concentrations of celecoxib of at least 12 mug/ml were needed to affect tumor cell viability. CONCLUSION: These results suggest that the inhibitory effects of celecoxib on tumor growth are not by direct cytotoxicity, but by creating an unfavorable environment for tumor growth.  相似文献   
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Deoxynivalenol (DON), a highly prevalent mycotoxin food contaminant, is known to have immunotoxic effects. In the current study, the potential of dietary interventions with specific mixtures of trans-galactosyl-oligosaccharides (TOS) to alleviate these effects were assessed in a murine influenza vaccination model. Vaccine-specific immune responses were measured in C57Bl/6JOlaHsd mice fed diets containing DON, TOS or a combination, starting 2 weeks before the first vaccination. The direct effects of TOS and its main oligosaccharide, 3′-galactosyl-lactose (3′-GL), on DON-induced damage were studied in Caco-2 cells, as an in vitro model of the intestinal epithelial barrier. Exposure to DON significantly reduced vaccine-specific immune responses and the percentages of Tbet+ Th1 cells and B cells in the spleen. DON significantly altered epithelial structure and integrity in the ileum and reduced the SCFA levels in the cecum. Adding TOS into DON-containing diets significantly improved vaccine-specific immune responses, restored the immune cell balance in the spleen and increased SCFA concentrations in the cecum. Incubating Caco-2 cells with TOS and 3′-GL in vitro further confirmed their protective effects against DON-induced barrier disruption, supporting immune modulation. Overall, dietary intervention with TOS can attenuate the adverse effects of DON on Th1-mediated immune responses and gut homeostasis. These beneficial properties might be linked to the high levels of 3′-GL in TOS.  相似文献   
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Health promotion (HP) amongst older people is an increasingly prominent policy concern for governments. The development of an evidence-base and the advocacy of effective interventions in the light of this act as legitimation tools for the overall HP phenomenon – assisting the growth of state and non-state funding for public health initiatives for older people. In structuring decision-making as to which individual projects/initiatives receive funding, frameworks for acknowledging efficacy impact on formats of HP work both positively and negatively. Drawing on recent research across the EU and focusing on the specific national contexts of Austria and England, this comparative policy analysis triangulates best-practice modelling, evaluation data and interviews with project coordinators to explore how policy contexts impact on the nature and format of HP interventions. Amidst a developing awareness of what effective practice looks like, successful HP initiatives must advocate their legitimacy within narrow rules of quality, where measurable outcomes have become the keys which unlock financial resources. Findings across both countries suggest that this instrumentalisation of legitimation, driven by economic pressures and bureaucratic generalisability, threatens the rationality of HP. From a Habermasian perspective, tensions emerge between projects’ remaining reflexive towards processes and their need to articulate the ‘success’ of the interventions in a language of outcomes. Over time, in an era where resources are increasingly scarce and competition over these intensifies, a danger exists whereby the instrumentality of HP begins to separate from, and impinge upon, the capacity for projects to think and act holistically.  相似文献   
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