Oxidative stress as a result of cigarette smoking is an important etiological factor in the pathogenesis of chronic obstructive pulmonary disease (COPD), a chronic steroid-insensitive inflammatory disease of the airways. The activity of the transcriptional co-repressor Histone deacetylase-2 (HDAC2) is dramatically reduced in COPD and cells exposed to oxidative stress or cigarette smoke. Moreover, curcumin (diferuloylmethane), a dietary polyphenol, at concentrations upto 1uM specifically restores cigarette smoke extract (CSE)- or oxidative stress- impaired HDAC2 activity. The aim of this study was to therefore identify any links through those gene sets that are affected by oxidative stress and subsequent treatment with curcumin in order to determine whether or not this could explain the impact of curcumin on restoration of oxidant impaired HDAC2 transcriptional co-repressor activity.
Curcumin restores corticosteroid function in monocytes exposed to oxidants by maintaining HDAC2.
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View SamplesHuman CD4+ T cells and CD14+ monocytes from healthy donors were co-cultured with anti-CD3 for three days in the presence or absence of TNF-alpha mAb (Adalimumab). Classical Th17 cells (Th17) or those generated in the presence of the inhibitor (iTh17) were then sorted and analyzed by full transcriptome microarray analysis.
TNF-α blockade induces IL-10 expression in human CD4+ T cells.
Specimen part, Treatment, Subject
View SamplesChronic obstructive pulmonary disease is a smoking-related disease that lacks effective therapies due partly to the poor understanding of disease pathogenesis. The aim of this study was to identify molecular pathways which could be responsible for the damaging consequences of smoking. To do this, we employed recently described bioinformatic methods to analyze differences in global gene expression, which we then related to the pathological changes induced by cigarette smoke (CS). Sprague-Dawley rats were exposed to whole-body CS for 1 day and for various periods up to 8 months.
Comprehensive gene expression profiling of rat lung reveals distinct acute and chronic responses to cigarette smoke inhalation.
Sex, Specimen part
View SamplesNC1153 was shown to inhibit JAK3 tyrosine kinase. Lymphocytes survival depends on the integrity of STAT5, the primary downstream target of JAK3.
Uncoupling JAK3 activation induces apoptosis in human lymphoid cancer cells via regulating critical survival pathways.
Cell line
View SamplesPurpose: Resistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer remains a major clinical problem. Recently, the CDK4/6 inhibitor palbociclib combined with letrozole was approved for treatment of ER+ advanced breast cancer, and other CDK4/6 inhibitors are being investigated in combination with different endocrine treatments. However, the role of CDK4/6 in endocrine resistance and their potential as predictive biomarkers of endocrine treatment response remains undefined.
High CDK6 Protects Cells from Fulvestrant-Mediated Apoptosis and is a Predictor of Resistance to Fulvestrant in Estrogen Receptor-Positive Metastatic Breast Cancer.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome wide mapping reveals PDE4B as an IL-2 induced STAT5 target gene in activated human PBMCs and lymphoid cancer cells.
Specimen part, Cell line
View SamplesIdentify IL-2 mediated genes in Kit225 cells.
Genome wide mapping reveals PDE4B as an IL-2 induced STAT5 target gene in activated human PBMCs and lymphoid cancer cells.
Specimen part, Cell line
View SamplesPurpose: A 128-gene signature has been proposed to predict poor outcomes in patients with stage II and III colorectal cancer. In the present study we aimed to validate this previously published 128-gene signature on external and independent data from patients with stage II and III colon cancer.
Gene expression profiles in stages II and III colon cancers: application of a 128-gene signature.
Sex, Age, Disease stage, Race
View SamplesUremic media calcification is not only driven by systemic factors such as hyperphosphatemia, but also crticially dependent on vascular smooth muscle cells per se. We hypothesized that the different developmental origins of vscular smooth muscle cells might lead to a heterogeneous susceptibility to develop media calcification.
Heterogeneous susceptibility for uraemic media calcification and concomitant inflammation within the arterial tree.
Specimen part
View SamplesAlthough a large set of data is available concerning organogenesis in animal models, information remains scarce on human organogenesis. In this work, we performed temporal mapping of human fetal pancreatic organogenesis using cell surface markers. We demonstrate that in the human fetal pancreas at 7 weeks of development, the glycoprotein 2 (GP2) marks a multipotent cell population that will differentiate either into the acinar, ductal and endocrine lineages. Development towards the acinar lineage is paralleled by a substantial increase in GP2 expression. Conversely, a subset of the multipotent GP2+ population undergoes endocrine differentiation by down-regulating GP2 and CD142 and turning on NEUROG3, an early marker of endocrine differentiation. Endocrine maturation will progress by up-regulating SUSD2 and lowering ECAD levels. Finally, we show that in vitro differentiation of pancreatic endocrine cells derived from human pluripotent stem cells mimics key in vivo events. Our work constitutes a powerful approach to more precisely define intermediate cell population during conversion of multipotent progenitors into the 3 main human pancreatic cell types (acinar, ductal and endocrine) in vivo. As such, the data pave the way to extend our understanding of the origin of mature human pancreatic cell types and how such lineage decisions are regulated.
Reconstructing human pancreatic differentiation by mapping specific cell populations during development.
Specimen part
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