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Breast Cancer Research and Treatment - Preclinical evidence suggests that natural killer cell (NK-cell) function and myokines facilitate the protective effects of exercise for breast cancer...  相似文献   
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Aurora B kinase phosphorylates and instigates degradation of p53   总被引:1,自引:0,他引:1  
Aurora B is a mitotic checkpoint kinase that plays a pivotal role in the cell cycle, ensuring correct chromosome segregation and normal progression through mitosis. Aurora B is overexpressed in many types of human cancers, which has made it an attractive target for cancer therapies. Tumor suppressor p53 is a genome guardian and important negative regulator of the cell cycle. Whether Aurora B and p53 are coordinately regulated during the cell cycle is not known. We report that Aurora B directly interacts with p53 at different subcellular localizations and during different phases of the cell cycle (for instance, at the nucleus in interphase and the centromeres in prometaphase of mitosis). We show that Aurora B phosphorylates p53 at S183, T211, and S215 to accelerate the degradation of p53 through the polyubiquitination-proteasome pathway, thus functionally suppressing the expression of p53 target genes involved in cell cycle inhibition and apoptosis (e.g., p21 and PUMA). Pharmacologic inhibition of Aurora B in cancer cells with WT p53 increased p53 protein level and expression of p53 target genes to inhibit tumor growth. Together, these results define a mechanism of p53 inactivation during the cell cycle and imply that oncogenic hyperactivation or overexpression of Aurora B may compromise the tumor suppressor function of p53. We have elucidated the antineoplastic mechanism for Aurora B kinase inhibitors in cancer cells with WT p53.  相似文献   
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Fine particles were collected in three indoor environments and an outdoor reference site. Samples were acid and aqueous extracted for metal analyses and cytokine expression study using a BEAS-2B line. Results revealed that the average PM(2.5) concentration indoors was 5.8 μg/m(3) while outside, it was 9.4 μg/m(3). The airborne metal concentrations in indoor air ranged from 0.01 ng/m(3) (Cd) to 620 ng/m(3) (Al). All metals analyzed were higher indoors when compared to outdoor (I/O ratio) indicating a contribution from the workplace. Some metals were more efficiently extracted (e.g., Ni, V, As) in the aqueous phase than others (e.g., Fe and Al). Toxicological assays showed that the aqueous extracts at 20% induced IL-6 and subsequently inhibited it at a higher concentration (50%); both IL-8 and MCP-1 were inhibited at 20 and 50%. As, Ni and V concentrations seem to be the most important metals associated with the cytokine induction/inhibition response probably due to the higher bioavailability.  相似文献   
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This study assessed the association of cardiometabolic risk factors with systemic inflammation, insulin resistance, and adypocytokines in a Hispanic adolescent subgroup. A clinic-based sample of 101 Puerto Rican adolescents, 48 of whom were overweight or obese based on body mass index percentiles for age and sex, was recruited during 2010. Data were collected through interviews, blood pressure and anthropometric measurements, and blood drawing. Overall prevalence of the metabolic syndrome was 16.8 % and increased to 37.5 % among overweight/obese youth. The overweight/obese group exhibited significantly (p < 0.05) higher values for abdominal obesity measures, systolic blood pressure, triglycerides, insulin resistance, C peptide, high-sensitivity C reactive protein, fibrinogen, leptin, and IL-6 and lower levels of high density lipoprotein cholesterol, adiponectin, and IGF-1. Total adiponectin significantly correlated with most cardiovascular risk factors independent of sex, Tanner stage, and adiposity. Altered cardiometabolic and adipocytokine profiles were present in this Hispanic subgroup, reinforcing the need to strengthen strategies addressing childhood obesity.  相似文献   
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