50 research outputs found

    Alterations in Gene Array Patterns in Dendritic Cells from Aged Humans

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    <div><p>Dendritic cells (DCs) are major antigen-presenting cells that play a key role in initiating and regulating innate and adaptive immune responses. DCs are critical mediators of tolerance and immunity. The functional properties of DCs decline with age. The purpose of this study was to define the age-associated molecular changes in DCs by gene array analysis using Affymatrix GeneChips. The expression levels of a total of 260 genes (1.8%) were significantly different (144 down-regulated and 116 upregulated) in monocyte-derived DCs (MoDCs) from aged compared to young human donors. Of the 260 differentially expressed genes, 24% were down-regulated by more than 3-fold, suggesting that a large reduction in expression occurred for a notable number of genes in the aged. Our results suggest that the genes involved in immune response to pathogens, cell migration and T cell priming display significant age-related changes. Furthermore, downregulated genes involved in cell cycle arrest and DNA replication may play a critical role in aging-associated genetic instability. These changes in gene expression provide molecular based evidence for age-associated functional abnormalities in human DCs that may be responsible for the defects in adaptive immunity observed in the elderly.</p></div

    An Accurate Prostate Cancer Prognosticator Using a Seven-Gene Signature Plus Gleason Score and Taking Cell Type Heterogeneity into Account

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    <div><p>One of the major challenges in the development of prostate cancer prognostic biomarkers is the cellular heterogeneity in tissue samples. We developed an objective Cluster-Correlation (CC) analysis to identify gene expression changes in various cell types that are associated with progression. In the Cluster step, samples were clustered (unsupervised) based on the expression values of each gene through a mixture model combined with a multiple linear regression model in which cell-type percent data were used for decomposition. In the Correlation step, a Chi-square test was used to select potential prognostic genes. With CC analysis, we identified 324 significantly expressed genes (68 tumor and 256 stroma cell expressed genes) which were strongly associated with the observed biochemical relapse status. Significance Analysis of Microarray (SAM) was then utilized to develop a seven-gene classifier. The Classifier has been validated using two independent Data Sets. The overall prediction accuracy and sensitivity is 71% and 76%, respectively. The inclusion of the Gleason sum to the seven-gene classifier raised the prediction accuracy and sensitivity to 83% and 76% respectively based on independent testing. These results indicated that our prognostic model that includes cell type adjustments and using Gleason score and the seven-gene signature has some utility for predicting outcomes for prostate cancer for individual patients at the time of prognosis. The strategy could have applications for improving marker performance in other cancers and other diseases.</p> </div

    Treatment with MWCNT significantly changes protein expression.

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    <p>Protein extracts (200 µg) were separated on a pH 3–10, 24 cm IPG strip, followed by 12% SDS-PAGE. Proteins spots were visualized by silver staining. Shown are representative 2-DE proteomic maps of A549 cells treated with MWCNT at the indicated concentrations (a, 0.3; b, 3; c, 30 µg/ml) for various time periods (A, 2 h; B, 12 h; C, 24 h). Arrows indicate the spots identified by MS (↑up-regulated protein, down-regulated protein), and details of the corresponding spots are listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084974#pone-0084974-t002" target="_blank">Table 2</a>. The location (D) and function classification (E) of identified proteins are shown in the pie charts.</p

    Cell cycle phases are different between MoDCs from aged and young donors.

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    <p>(A) Distribution of aged and young MoDCs existing in the various phases of the cell cycle as determined by FACS. (B) Statistical analysis and percentages of MoDCs from young and aged donors in each phase of the cell cycle (n = 5, each group). Donors' information sees <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106471#pone-0106471-t002" target="_blank">Table 2</a>.</p

    Demographical information of 97 patients used for the analysis of Egr3 in relapse and non-relapse prostate cancer.

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    *<p>84 prostate cancer patients provided 108 arrays and 13 normal prostate donors provided 19 arrays.</p

    19 probe sets that are consistently associated with relapse.

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    <p>The entries in boldface are genes associated with apoptosis while the <i>italicized</i> entries are genes associated with cell death.</p

    Distinct karyotypes of three subpopulation cells in U251.

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    <p><b>A</b>, representative metaphase FISH pictures of PTEN/CEP10 and EGFR/CEP7 dual probes showing all cells carrying one copy of Chr10, an unknown chromosome with a PTEN translocation, and three cell types differing in their composition of normal and derivative Chr7 (dChr7). <i>Arrow</i> points to dChr7; <i>arrowhead</i> to normal Chr7. <b>B</b>, percentage of majority cells in the parental culture, derived or converted SA or NS subcultures, and the parental culture after lentiviral transductions by pTRIPZ-Vec (P-Vec), pTRIPZ-EFEMP1 with (P-E1) or after withdrawal (P-E1wd) of doxycyclin. <b>C–D</b>, comparison of DNA copy number variation in chromosomes 7, 8, 17, and 22 for U251 parental derived or converted NS subcultures of NS1 or SA1-NS, respectively. The Y axis is the log ratio of intensity (the ratio of test sample and normal blood) from comparative genome hybridization. Amplifications or deletions are shown by blue lines above or below the red or green areas, respectively, based on Z-score, and those with marked changes are highlighted in purple.</p

    Effects of MWCNT exposure on the expression of Th1/Th2 cytokines.

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    <p>Following treatment with MWCNT at 0.3, 3 and 30 µg/ml for 2, 12 and 24 h, the supernatants of A549 cells were collected and detected using a Human Th1/Th2 Cytokine Kit II by flow cytometry. Shown are expression levels of IFN-γ, IL-10, IL-4, IL-2 (A) and IL-6 (B).</p

    MWCNT does not cause genotoxic injury to A549 cells.

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    <p>(A) Following treatment with MWCNT at 0.3, 3 and 30 µg/ml for 2, 12 and 24 h, cells were fixed and stained with anti-γH2AX antibody, then subjected to immunofluorescent microscopy. Blue, Hoechst3358 stain for nuclei; Green, γH2AX. (B) Cells were treated with MWCNT for 24 h at 0.3, 3 and 30 µg/ml, and then subjected to the comet assay detection. The nucleus was stained with gel-red. 10 µM cisplatin (Pt) treated cells were used as a positive control.</p
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