Genome-wide association studies (GWAS) have identified 19 risk variants associated with colorectal cancer. As most of these risk variants reside outside the coding regions of genes, we conducted cis-expression quantitative trait loci (cis-eQTL) analyses to investigate possible regulatory functions on the expression of neighboring genes.
cis-Expression QTL analysis of established colorectal cancer risk variants in colon tumors and adjacent normal tissue.
Disease, Disease stage
View SamplesOne of the hallmarks of Pseudomonas aeruginosa cystic fibrosis (CF) infection is very high-cell-density (HCD) replication in the lung, allowing this bacterium to induce virulence controlled by HCD quorum-sensing systems. However, the nutrient sources sustaining HCD replication in this chronic infection is largely unknown. Hence, understanding the nutrient factors contributing to HCD in the CF lung will yield new insights into the 'metabolic pathogenicity' and potential treatment of CF infections caused by P. aeruginosa. Herein, we performed microarray studies of P. aeruginosa directly isolated from the CF lung to demonstrate its metabolic capability and virulence in vivo. Our in vivo microarray data, confirmed by real-time reverse-transcription-PCR, indicated P. aeruginosa expressed several genes for virulence, drug-resistance, and utilization of multiple nutrient sources (lung surfactant lipids and amino acids) contributing to HCD replication. The data also indicates deregulation of several pathways, suggesting in vivo evolution by deregulation of a large portion of the transcriptome during chronic CF infection. To our knowledge, this is the first in vivo transcriptome of P. aeruginosa in a natural CF infection, and it indicates several important aspects of pathogenesis, drug-resistance, and nutrient-utilization never before observed in vivo.
In vivo evidence of Pseudomonas aeruginosa nutrient acquisition and pathogenesis in the lungs of cystic fibrosis patients.
No sample metadata fields
View Samplesb-Oxidative enzymes for fatty acid degradation (Fad) of long-chain fatty acid (LCFA), a component of lung surfactant phosphatidylcholine, are induced in vivo during lung infection in cystic fibrosis patients, which could contribute to nutrient acquisition and pathogenesis of Pseudomonas aeruginosa. In addition, fatty acid biosynthesis (Fab) is essential for the syntheses of two virulence controlling acylated-homoserine-lactone molecules in this organism. We mapped the promoter regions of the fadBA5-operon (PA3014 and PA3013) and a fadE homologue (PA2815) involved in Fad and the fabAB-operon involved in Fab. Focusing on the transposon mutagenesis of strain PAO1 carrying the PfadBA5-lacZ fusion, we identified a regulator for the fadBA5-operon to be PsrA (PA3006). Transcriptome analysis of the DpsrA mutant indicates its importance in regulating b-oxidative enzymes, which confirms a previous proteomic study. We further showed that induction of the fadBA-operon responds to LCFA signals, and this induction requires the presence of PsrA, suggesting that PsrA binds to LCFA to derepress fadBA5. Electrophoresis mobility shift assay indicate specific binding of PsrA to the fadBA5-promoter region. This binding is disrupted by specific LCFA (C18:1D9, C16:0, and to a lesser extent C14:0), but not by the first intermediate of b-oxidation, acyl-CoA. We proposed that PsrA is a Fad-regulator that binds and responds to LCFA signals in Pseudomonas aeruginosa.
The Pseudomonas aeruginosa PsrA responds to long-chain fatty acid signals to regulate the fadBA5 beta-oxidation operon.
No sample metadata fields
View SamplesRNA-seq study of tumors that develop in mice after injection of gastric carcinoma cell line, AGS, with or without Epstein-Barr virus infection
No associated publication
Sex, Specimen part, Disease, Cell line
View SamplesRNA-Seq study of tumors that develop in mice after injection of nasopharyngeal carcinoma (NPC) cell line C666.1 and the xenograph tumors C15 and C17
No associated publication
Sex, Specimen part, Disease, Cell line
View Samplesthe goal of this study are to reveal potential functions of novel lncRNAs in PDLSCs ,systematicly characterize PDLSC related lncRNAs and protein coding genes in uPDLSCs,dPDLSCs and TNF-a-dPDLSCs with Next Generation Sequencing.
No associated publication
Sex, Specimen part, Treatment
View SamplesMesenchymal stromal cells (MSCs), which have immunosuppressive and trophic abilities that are induced by inflammatory cytokines, have emerged as a promising option for cell-based therapy. The cytokine profiles vary substantially across different diseases and stages of disease progression, which has been shown to influence the curative properties of MSCs. Our knowledge about how MSCs respond systemically to cytokines is still limited. Here, we individually stimulated MSCs in vitro with IFN-?and used RNA-Seq to analyze their expression profiles.
No associated publication
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Time-dependent transcriptional response of GOT1 human small intestine neuroendocrine tumor after <sup>177</sup>Lu[Lu]-octreotate therapy.
Time
View SamplesThe radiolabelled somatostatin analogue 177Lu-octreotate is a promising treatment option for malignant neuroendocrine tumors that overexpress somatostatin receptors. The human small intestine neuroendocrine tumor cell line GOT1 and Medullary thyroid carcinoma model GOT2 have shown promising treatment response to 177Lu-octreotate in xenografted mice. In clinical studies, however, only low cure rates have been achieved to date. In vitro and preclinical in vivo studies have shown that irradiation can up-regulate the expression of somatostatin receptors and thereby give an increased uptake of 177Lu-octreotate. The cellular processes that underlie positive treatment response to 177Lu-octreotate are otherwise largely unknown. Genome-wide analysis of tumor cell responses in this successful mouse model offers a venue to identify critical treatment parameters and to optimize clinical effectiveness of 177Lu-octreotate therapy. Combining 177Lu-octreotate with other anti-tumor agents has also been proposed as a strategy for optimization. Some studies have shown synergistic effects in tumor cell killing and volume reduction The hedgehog signaling pathway is involved in embryonic development and tissue regeneration and can be/is abnormally activated in various cancers. Inhibition of the hedgehog signaling pathway has yielded promising therapeutic effects on NE tumors and may potentially enhance the effects of 177Lu-octreotate treatment in patients.
Priming increases the anti-tumor effect and therapeutic window of <sup>177</sup>Lu-octreotate in nude mice bearing human small intestine neuroendocrine tumor GOT1.
Time
View SamplesRecent studies suggest the potential involvement of common antigenic stimuli on the ontogeny of monoclonal TCRalphabeta+/CD4+/NKa+/CD8-/+dim T-large granular lymphocyte (LGL) lymphocytosis. Since healthy individuals show (oligo)clonal expansions of hCMV-specific TCRVbeta+/CD4+/cytotoxic/memory T-cells, we investigate the potential involvement of hCMV in the origin and/or expansion of monoclonal CD4+ T-LGL. A detailed characterization of those genes that underwent changes in T-LGL cells responding to hCMV was performed by microarray gene expression profile (GEP) analysis.
Expanded cells in monoclonal TCR-alphabeta+/CD4+/NKa+/CD8-/+dim T-LGL lymphocytosis recognize hCMV antigens.
Sex, Subject
View Samples