23 research outputs found

    An evaluation of urinary microRNA reveals a high sensitivity for bladder cancer

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    Background: Urinary biomarkers are needed to improve the care and reduce the cost of managing bladder cancer. Current biomarkers struggle to identify both high and low-grade cancers due to differing molecular pathways. Changes in microRNA (miR) expression are seen in urothelial carcinogenesis in a phenotype-specific manner. We hypothesised that urinary miRs reflecting low- and high-grade pathways could detect bladder cancers and overcome differences in genetic events seen within the disease. Methods: We investigated urinary samples (n ¼ 121) from patients with bladder cancer (n ¼ 68) and age-matched controls (n ¼ 53). Fifteen miRs were quantified using real-time PCR. Results: We found that miR is stable within urinary cells despite adverse handling and detected differential expression of 10 miRs from patients with cancer and controls (miRs 15a/15b/24-1/27b/100/135b/203/212/328/1224, ANOVA Po0.05). Individually, miR-1224-3p had the best individual performance with specificity, positive and negative predictive values and concordance of 83%, 83%, 75% and 77%, respectively. The combination of miRs-135b/15b/1224-3p detected bladder cancer with a high sensitivity (94.1%), sufficient specificity (51%) and was correct in 86% of patients (concordance). Conclusion: The use of this panel in patients with haematuria would have found 94% of urothelial cell carcinoma, while reducing cystoscopy rates by 26%. However, two invasive cancers (3%) would have been missed

    Integrated Epigenome Profiling of Repressive Histone Modifications, DNA Methylation and Gene Expression in Normal and Malignant Urothelial Cells

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    Epigenetic regulation of gene expression is commonly altered in human cancer. We have observed alterations of DNA methylation and microRNA expression that reflect the biology of bladder cancer. This common disease arises by distinct pathways with low and high-grade differentiation. We hypothesized that epigenetic gene regulation reflects an interaction between histone and DNA modifications, and differences between normal and malignant urothelial cells represent carcinogenic events within bladder cancer. To test this we profiled two repressive histone modifications (H3K9m3 and H3K27m3) using ChIP-Seq, cytosine methylation using MeDIP and mRNA expression in normal and malignant urothelial cell lines. In genes with low expression we identified H3K27m3 and DNA methylation each in 20–30% of genes and both marks in 5% of genes. H3K9m3 was detected in 5–10% of genes but was not associated with overall expression. DNA methylation was more closely related to gene expression in malignant than normal cells. H3K27m3 was the epigenetic mark most specifically correlated to gene silencing. Our data suggest that urothelial carcinogenesis is accompanied by a loss of control of both DNA methylation and H3k27 methylation. From our observations we identified a panel of genes with cancer specific-epigenetic mediated aberrant expression including those with reported carcinogenic functions and members potentially mediating a positive epigenetic feedback loop. Pathway enrichment analysis revealed genes marked by H3K9m3 were involved with cell homeostasis, those marked by H3K27m3 mediated pro-carcinogenic processes and those marked with cytosine methylation were mixed in function. In 150 normal and malignant urothelial samples, our gene panel correctly estimated expression in 65% of its members. Hierarchical clustering revealed that this gene panel stratified samples according to the presence and phenotype of bladder cancer

    Integrating genetics and epigenetics in breast cancer: biological insights, experimental, computational methods and therapeutic potential

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    Epoxy composites reinforced basalt fiber

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    W pracy przedstawiono wyniki badań właściwości mechanicznych i termomechanicznych kompozytów epoksydowych wzmacnianych włóknem bazaltowym. Wykonano kompozyty warstwowe na osnowie żywicy epoksydowej Epidian 6, utwardzanej trietylenotetraaminą i modyfikowanej metalosilsekwioksanem. Ponadto porównano właściwości mechaniczne i termomechaniczne kompozytów wzmacnianych tkaniną bazaltową z właściwościami kompozytów wzmacnianych tkaniną szklaną.The results of mechanical and thermomechanical properties of epoxy composites with basalt fiber were presented in this paper. The composites were prepared from the epoxy resin Epidian 6 mixed with amine curing agent and metalsilsesqioxane. The properties of the composites with basalt woven fabric were compared to the properties of the composites with glass woven fabric

    A novel functional MgO ∙ SiO2/polyhedral oligomeric silsesquioxane hybrids as an active filler of polypropylene

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    New organic/inorganic hybrid fillers were obtained by mechanical modification of magnesium silicate with selected polyhedral oligomeric silsesquioxane and characterized afterwards. MgO ∙ SiO2 was precipitated in a water system. The effect of chemical modification of magnesium silicate surface on their physicochemical properties was determined. Functionalization was carried out with the use of different amount of (1-(3-hydroxypropyl)dimethylsiloxy- 3,5,7,9,11,13,15-hepta(isobutyl)pentacyclo-[9.5.1.13, 9.15, 15.17, 13]octasiloxane). The polypropylene composites of 0.5, 1.0 and 1.5 wt.% modified by 10 weight parts by the mass of the filler were also produced. For the obtained polypropylene composites measurements of the tensile strength, Young’s modulus and elongation at break were performed
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