Suppression of colitis-related mouse colon carcinogenesis by a COX-2 inhibitor and PPAR ligands

BACKGROUND: It is generally assumed that inflammatory bowel disease (IBD)-related carcinogenesis occurs as a result of chronic inflammation. We previously developed a novel colitis-related mouse colon carcinogenesis model initiated with azoxymethane (AOM) and followed by dextran sodium sulfate (DSS). In the present study we investigated whether a cyclooxygenase (COX)-2 inhibitor nimesulide and ligands for peroxisome proliferator-activated receptors (PPARs), troglitazone (a PPARγ ligand) and bezafibrate (a PPARα ligand) inhibit colitis-related colon carcinogenesis using our model to evaluate the efficacy of these drugs in prevention of IBD-related colon carcinogenesis. METHODS: Female CD-1 (ICR) mice were given a single intraperitoneal administration of AOM (10 mg/kg body weight) and followed by one-week oral exposure of 2% (w/v) DSS in drinking water, and then maintained on the basal diets mixed with or without nimesulide (0.04%, w/w), troglitazone (0.05%, w/w), and bezafibrate (0.05%, w/w) for 14 weeks. The inhibitory effects of dietary administration of these compounds were determined by histopathological and immunohistochemical analyses. RESULTS: Feeding with nimesulide and troglitazone significantly inhibited both the incidence and multiplicity of colonic adenocarcinoma induced by AOM/DSS in mice. Bezafibrate feeding significantly reduced the incidence of colonic adenocarcinoma, but did not significantly lower the multiplicity. Feeding with nimesulide and troglitazone decreased the proliferating cell nuclear antigen (PCNA)-labeling index and expression of β-catenin, COX-2, inducible nitric oxide synthase (iNOS) and nitrotyrosine. The treatments increased the apoptosis index in the colonic adenocarcinoma. Feeding with bezafibrate also affected these parameters except for β-catenin expression in the colonic malignancy. CONCLUSION: Dietary administration of nimesulide, troglitazone and bezafibrate effectively suppressed the development of colonic epithelial malignancy induced by AOM/DSS in female ICR mice. The results suggest that COX-2 inhibitor and PPAR ligands could serve as an effective agent against colitis-related colon cancer development

Spatial clustering and space–time clusters of leukemia among children in Germany, 1987–2007

International audienceLeukemia is the most frequent malignancy in children under the age of 15 years. The question of whether childhood leukemia has a tendency for clustering or forms clusters has been studied for several decades. The environmental risk factor discussed most often is infection, which might result in spatial clustering and space-time clusters. The German Childhood Cancer Registry provided data on 11,946 children with leukemia diagnosed during 1987-2007, as classified in the International Classification for Childhood Cancer (third edition), aggregated by municipality. We used the Potthoff-Whittinghill model to test for a general trend for clustering and the spatial scan statistic to search for localized clusters. No evidence of global clustering was found, neither for the whole study population nor in sub-groups by age, period or population density, or for different types of leukemia. A similar result was found for localized clusters. The analysis shows no evidence of a tendency to clustering, however, aggregation of data at the municipality level might have diluted small localized clusters. The results of this study do not provide support for the hypothesis of an infectious or a spatial environmental etiology of childhood leukemia

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

UK back pain exercise and manipulation (UK BEAM) trial - national randomised trial of physical treatments for back pain in primary care: objectives, design and interventions

Low back pain has major health and social implications. Although there have been many randomised controlled trials of manipulation and exercise for the management of low back pain, the role of these two treatments in its routine management remains unclear. A previous trial comparing private chiropractic treatment with National Health Service (NHS) outpatient treatment, which found a benefit from chiropractic treatment, has been criticised because it did not take treatment location into account. There are data to suggest that general exercise programmes may have beneficial effects on low back pain. The UK Medical Research Council (MRC) has funded this major trial of physical treatments for back pain, based in primary care. It aims to establish if, when added to best care in general practice, a defined package of spinal manipulation and a defined programme of exercise classes (Back to Fitness) improve participant-assessed outcomes. Additionally the trial compares outcomes between participants receiving the spinal manipulation in NHS premises and in private premises