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Articles by Y Xiao
Total Records ( 5 ) for Y Xiao
  H Zhou , Y Xiao , R Li , S Hong , S Li , L Wang , R Zeng and K. Liao

Adipocyte is not only a central player involved in storage and release of energy, but also in regulation of energy metabolism in other organs via secretion of peptides and proteins. During the pathogenesis of insulin resistance and type 2 diabetes, adipocytes are subjected to the increased levels of insulin, which may have a major impact on the secretion of adipokines. We have undertaken cleavable isotope-coded affinity tag (cICAT) and label-free quantitation approaches to identify and quantify secretory factors that are differentially secreted by 3T3-L1 adipocytes with or without insulin treatment. Combination of cICAT and label-free results, there are 317 proteins predicted or annotated as secretory proteins. Among these secretory proteins, 179 proteins and 53 proteins were significantly up-regulated and down-regulated, respectively. A total of 77 reported adipokines were quantified in our study, such as adiponectin, cathepsin D, cystatin C, resistin, and transferrin. Western blot analysis of these adipokines confirmed the quantitative results from mass spectrometry, and revealed individualized secreting patterns of these proteins by increasing insulin dose. In addition, 240 proteins were newly identified and quantified as secreted proteins from 3T3-L1 adipocytes in our study, most of which were up-regulated upon insulin treatment. Further comprehensive bioinformatics analysis revealed that the secretory proteins in extracellular matrix-receptor interaction pathway and glycan structure degradation pathway were significantly up-regulated by insulin stimulation.

  C Syme , M Abrahamowicz , G. T Leonard , M Perron , L Richer , S Veillette , Y Xiao , D Gaudet , T Paus and Z. Pausova

Objectives  To investigate during adolescence (1) sex differences in blood pressure (BP) and hemodynamic factors at rest and during physical and mental challenges and (2) whether these differences are mediated by body composition and glucose and lipid metabolism.

Design  Cross-sectional study of a population-based cohort.

Setting  Saguenay Youth Study, Quebec, Canada, from November 2003 to June 2007.

Participants  A total of 425 adolescents (225 girls aged 12-18 years).

Outcome Measures  Systolic and diastolic BP measured using a Finometer. Secondary outcome measures were (1) hemodynamic parameters also measured with a Finometer, (2) body composition assessed with magnetic resonance imaging, bioimpedance, and anthropometry, and (3) metabolic indices determined from a fasting blood sample.

Results  Girls vs boys demonstrated lower systolic and diastolic BP at rest and during challenges, with the differences being greatest during a math-stress test (adjusted difference, 7 mm Hg; 95% confidence interval [CI], 4-10 mm Hg and adjusted difference, 6 mm Hg; 95% CI, 4-8 mm Hg, respectively). The differences were mainly due to girls vs boys having lower stroke volume while lying down, standing (adjusted difference, 4 mL; 95% CI, 1-7 mL), and sitting, and lower total peripheral resistance during the math-stress test (adjusted difference, 0.14 mm Hg · s/mL; 95% CI, 0.09-0.21 mm Hg · s/mL). Intra-abdominal fat was positively associated with BP, but less in girls than in boys, and fat-free mass, fat mass, and insulin resistance were also positively associated with BP, similarly in boys and girls.

Conclusions  In adolescence, BP is lower in girls than boys, with the difference being determined mainly by lower stroke volume during physical challenges and by lower total peripheral resistance during mental challenges. Body composition and insulin resistance contribute to these differences.

  J. A Schwartzbaum , Y Xiao , Y Liu , S Tsavachidis , M. S Berger , M. L Bondy , J. S Chang , S. M Chang , P. A Decker , B Ding , S. J Hepworth , R. S Houlston , F. J Hosking , R. B Jenkins , M. L Kosel , L. S McCoy , P. A McKinney , K Muir , J. S Patoka , M Prados , T Rice , L. B Robertson , M. J Schoemaker , S Shete , A. J Swerdlow , J. L Wiemels , J. K Wiencke , P Yang and M. R. Wrensch

To determine whether inherited variations in immune function single-nucleotide polymorphisms (SNPs), genes or pathways affect glioblastoma risk, we analyzed data from recent genome-wide association studies in conjunction with predefined immune function genes and pathways. Gene and pathway analyses were conducted on two independent data sets using 6629 SNPs in 911 genes on 17 immune pathways from 525 glioblastoma cases and 602 controls from the University of California, San Francisco (UCSF) and a subset of 6029 SNPs in 893 genes from 531 cases and 1782 controls from MD Anderson (MDA). To further assess consistency of SNP-level associations, we also compared data from the UK (266 cases and 2482 controls) and the Mayo Clinic (114 cases and 111 controls). Although three correlated epidermal growth factor receptor (EGFR) SNPs were consistently associated with glioblastoma in all four data sets (Mantel–Haenzel P values = 1 x 10–5 to 4 x 10–3), independent replication is required as genome-wide significance was not attained. In gene-level analyses, eight immune function genes were significantly (minP < 0.05) associated with glioblastoma; the IL-2RA (CD25) cytokine gene had the smallest minP values in both UCSF (minP = 0.01) and MDA (minP = 0.001) data sets. The IL-2RA receptor is found on the surface of regulatory T cells potentially contributing to immunosuppression characteristic of the glioblastoma microenvironment. In pathway correlation analyses, cytokine signaling and adhesion–extravasation–migration pathways showed similar associations with glioblastoma risk in both MDA and UCSF data sets. Our findings represent the first systematic description of immune genes and pathways that characterize glioblastoma risk.

  Z Pausova , C Syme , M Abrahamowicz , Y Xiao , G. T Leonard , M Perron , L Richer , S Veillette , G. D Smith , O Seda , J Tremblay , P Hamet , D Gaudet and T. Paus

Background— FTO is the first gene established as contributing to common forms of obesity. The gene is highly expressed in the hypothalamus and is thought to mediate this effect through its influence on energy homeostasis. The hypothalamus, however, also regulates blood pressure (BP). Therefore, we investigated whether the FTO-risk variant is associated not only with increased adiposity but also with elevated BP and whether the latter may be mediated, in part, by increased sympathetic modulation of vasomotor tone.

Methods and Results— The primary study was carried out in 485 adolescents recruited from a French Canadian founder population who underwent detailed body-composition and cardiovascular phenotyping. Body fat was examined with MRI, bioimpedance, and anthropometry. BP was recorded beat to beat at rest and during physical and mental challenges. Sympathetic modulation of vasomotor tone was assessed with power spectral analysis of BP. We found that individuals with the FTO-risk genotype compared with those without it demonstrate greater adiposity, including the amount of intra-abdominal fat (by 38%). They also showed higher systolic BP throughout the entire protocol, with a maximum difference during a mental stress (6.4 [1.5 to 11.3] mm Hg). The difference in BP was accompanied by elevated index of sympathetic modulation of vasomotor tone. A replication in an independent sample of adults from the same founder population confirmed the association between FTO and BP.

Conclusions— These results suggest that, in a French Canadian founder population, FTO may increase not only risk for obesity, as demonstrated in other populations, but also for hypertension. The latter may be related, at least in part, to the regulation of sympathetic vasomotor tone.

  Y Xiao , X Gao , S Maragh , W. G Telford and A. Tona

Background: Human epidermal growth factor receptor 2 (HER2) is an important biomarker whose status plays a pivotal role in therapeutic decision-making for breast cancer patients and in determining their clinical outcomes. Ensuring the accuracy and reproducibility of HER2 assays by immunohistochemistry (IHC) and by fluorescence in situ hybridization (FISH) requires a reliable standard for monitoring assay sensitivity and specificity, and for assessing methodologic variation. A prior NIST workshop addressed this need by reaching a consensus to create cell lines as reference materials for HER2 testing.

Methods: Breast carcinoma cell lines SK-BR-3 and MCF-7 were characterized quantitatively by IHC with chicken anti-HER2 IgY antibody and by FISH with biotinylated bacterial artificial chromosome DNA probes; both assays used quantum dots as detectors. Formalin-fixed and paraffin-embedded (FFPE) cell blocks were prepared and tested for suitability as candidate reference materials by IHC and FISH with commercially available reagents. IHC and FISH results were also compared with those obtained by laser-scanning cytometry and real-time PCR, respectively.

Results: MCF-7 cells had typical numbers of gene copies and very low production of HER2 protein, whereas SK-BR-3 cells contained approximately 10-fold more copies of the gene and exhibited approximately 15-fold higher amounts of HER2 protein than MCF-7 cells. FFPE SK-BR-3 cells showed results similar to those for fresh SK-BR-3 cells.

Conclusions: SK-BR-3 and MCF-7 are suitable as candidate reference materials in QC of HER2 testing. Coupled with the associated assay platforms, they provide valuable controls for quantitative measurement of HER2 amplification and production in breast cancer samples, irrespective of the antibody/probe or detector used.

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