We used microarray analyses of patient myeloma cells (n=52) to correlate individual miRNA expression profiles with GEP-based risk defined by mRNA expression profilesx as well as clinical features of the disease. Unlike for mRNAs, genome-wide elevation of miRNA expression patterns were significantly positively associated with a mRNA-based GEP-risk score (P <.01) and proliferation index (P <.05). Consistent with our observation of global deregulation of miRNA expression profiles, silencing EIF2C2/AGO2, a gene component of the mRNA-based high-risk signature and a master regulator of the genesis and functionality of all miRNAs, dramatically decreased viability in myeloma cell lines.
High-risk myeloma is associated with global elevation of miRNAs and overexpression of EIF2C2/AGO2.
Specimen part, Disease, Disease stage, Subject
View SamplesPurpose: Because dexamethasone remains a key component of myeloma therapy, we wished to examine the correlation of baseline and relapse expression levels of the glucocorticoid receptor gene NR3C1 with other clinical features. Experimental Design: We investigated the clinical impact of gene expression profiling (GEP)derived expression levels of NR3C1 in 351 patients with GEP data available at baseline and in 130 with data available at relapse, among 668 subjects accrued to Total Therapy 2 (TT2).
Thalidomide in total therapy 2 overcomes inferior prognosis of myeloma with low expression of the glucocorticoid receptor gene NR3C1.
Disease, Treatment
View SamplesThe excessive perchlorate utilization as an oxidizer in rocket propellants and blasting agents had led to the contamination of surface and ground waters. This chemical is known to compete with iodine for binding to the thyroid membrane receptors potentially causing hypothyroidism and fetal retardation in pregnant women. Nevertheless, to date, its biological effects are not completely understood. We have investigated the molecular mechanisms responsive to perchlorate in the nematode C. elegans to nominate a candidate gene for further peruse in the development of a C.elegans perchlorate biosensor. Perchlorate (1 mg/mL) affected the transcriptional response of Regulation of developmental process, growth, defense mechanisms and stress response, among other biological processes.
Perchlorate detection <i>via</i> an invertebrate biosensor.
Treatment
View SamplesLTB4, 50 nmol/L for 30 minutes, induced expression of 27 genes in cultured human elutriated monocytes comparred to vehicle (ethanol) treated control cells.
Cooperative and redundant signaling of leukotriene B4 and leukotriene D4 in human monocytes.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Changes in microRNA and mRNA expression with differentiation of human bronchial epithelial cells.
Specimen part
View SamplesNormal human bronchial epithelial (NHBE) cells cultured in an air-liquid interface (ALI) system form a polarized, pseudostratified epithelium composed of basal, ciliated and goblet cells that closely resemble the in vivo airway epithelium structure. ALI cultures of NHBE cells provide a unique in vitro system to investigate airway epithelial biology, including developmental, structural and physiologic aspects. In this study, we wanted to investigate mRNA expression patterns during airway epithelium differentiation.
Changes in microRNA and mRNA expression with differentiation of human bronchial epithelial cells.
Specimen part
View SamplesThe expression levels of many genes show wide natural variation among strains or populations. This study investigated the potential for animal strain-related genotypic differences to confound gene expression profiles in acute cellular rejection (ACR). Additional analysis allowed for selection of 49 candidate genes uniquely associated with ACR, but only after accounting for the unexpectedly large effect of animal strain. Studies of ACR that examine gene expression in peripheral blood may be confounded by strain differences. These results indicate the need for study designs that eliminate or control for the large effect of genetic background on the transcriptome of immune cells.
Impact of animal strain on gene expression in a rat model of acute cardiac rejection.
Specimen part
View SamplesObesity induces macrophages to drive inflammation in adipose tissue, a crucial step towards the development of type 2 diabetes. The tricarboxylic acid (TCA) cycle intermediate succinate is released from cells under metabolic stress and has recently emerged as a metabolic signal induced by proinflammatory stimuli. We therefore investigated whether succinate receptor 1 (SUCNR1) could play a role in the development of adipose tissue inflammation and type 2 diabetes. Succinate levels were determined in human plasma samples from individuals with type 2 diabetes and non-diabetic participants. Succinate release from adipose tissue explants was studied. Sucnr1 -/- and wild-type (WT) littermate mice were fed a high-fat diet (HFD) or low-fat diet (LFD) for 16 weeks. Serum metabolic variables, adipose tissue inflammation, macrophage migration and glucose tolerance were determined. We show that hypoxia and hyperglycaemia independently drive the release of succinate from mouse adipose tissue (17-fold and up to 18-fold, respectively) and that plasma levels of succinate were higher in participants with type 2 diabetes compared with non-diabetic individuals (+53%; p < 0.01). Sucnr1 -/- mice had significantly reduced numbers of macrophages (0.56 0.07 vs 0.92 0.15 F4/80 cells/adipocytes, p < 0.05) and crown-like structures (0.06 0.02 vs 0.14 0.02, CLS/adipocytes p < 0.01) in adipose tissue and significantly improved glucose tolerance (p < 0.001) compared with WT mice fed an HFD, despite similarly increased body weights. Consistently, macrophages from Sucnr1 -/- mice showed reduced chemotaxis towards medium collected from apoptotic and hypoxic adipocytes (-59%; p < 0.05). Our results reveal that activation of SUCNR1 in macrophages is important for both infiltration and inflammation of adipose tissue in obesity, and suggest that SUCNR1 is a promising therapeutic target in obesity-induced type 2 diabetes.
SUCNR1-mediated chemotaxis of macrophages aggravates obesity-induced inflammation and diabetes.
No sample metadata fields
View SamplesBackground: Genes upregulated by low oxygen have been suggested as endogenous markers for tumor hypoxia. Yet, most of the genes investigated have shown inconsistent results, which have led to concerns about their ability to be true hypoxia markers. Previous studies have demonstrated that expression of hypoxia induced genes can be affected by extracellular pH (pH e ). Methods: Five different human cell lines (SiHa, FaDu DD, UTSCC5, UTSCC14 and UTSCC15) were exposed to different oxygen concentrations and pH (7.5 or 6.3), and gene expression analyzed with microarray (Affymetrix - Human Genome U133 Plus 2.0 Array). Results: An analysis of two of the cell lines using SAM identified 461 probesets that were able to separate the four groups Normal oxygen, normal pH , Low oxygen, normal pH , Normal oxygen, low pH and Low oxygen, low pH . From here it was possible to identify a fraction of probesets induced at low oxygen independent of pH in these two cell lines, this fraction included HIG2, NDRG1, PAI1 and RORA. Further verifi cation by qPCR highlighted the necessity of using more cell lines to obtain a robust gene expression profi les. To specifi cally select pH independent hypoxia regulated genes across more cell lines, data for FaDu DD, UTSCC5, UTSCC14 and UTSCC15 were analyzed to identify genes that were induced by hypoxia in each cell line, where the induction was not affected by low pH, and where the gene was not signifi cantly induced by low pH alone. Each cell line had 65 122 probesets meeting these criteria. For genes to be considered as target genes (hypoxia inducible pH independent), genes had to be present in three of four cell lines. Conclusion: The result is a robust hypoxia profile unaffected by pH across cell lines consisting of 27 genes. This study demonstrates a way to identify hypoxia markers by microarray, where other factors in the tumor microenvironment are taken into account.
Identifying pH independent hypoxia induced genes in human squamous cell carcinomas in vitro.
Cell line
View SamplesNeuroendocrine prostate cancer (NEPC) is rare historically but may be increasingin prevalence as patients potentially develop resistance to contemporary anti-androgen treatment through a neuroendocrine phenotype. Diagnosis can be straightforward when classic morphological features are accompanied by a prototypical immunohistochemistry profile, however there is increasing recognition of disease heterogeneity and hybrid phenotypes. In the primary setting, small cell prostatic carcinoma (SCPC) is frequently admixed with adenocarcinomas that may be clonally related, while a small fraction of SCPCs express markers typical of prostatic adenocarcinoma. Gene expression patterns may eventually help elucidate the biology underlying equivocal cases with discordant IHC, however studies to date have focused on prototypical cases and been based on few patients due to disease rarity.
Gene expression signatures of neuroendocrine prostate cancer and primary small cell prostatic carcinoma.
Subject
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