Study on gene expression in multifunctional protein 2 deficient mice. Liver samples of two days old mice in normal conditions are used. In total 8 arrays were hybridized corresponding to 4 KO mice and 4 WT mice Results: Cholesterol synthesis is induced and ppar alpha targets also differentially expressed between KO and WT.
Coordinate induction of PPAR alpha and SREBP2 in multifunctional protein 2 deficient mice.
No sample metadata fields
View SamplesThese arrays contain data from the livers of 10 week old L-Pex5 -/- male mice
Carbohydrate metabolism is perturbed in peroxisome-deficient hepatocytes due to mitochondrial dysfunction, AMP-activated protein kinase (AMPK) activation, and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) suppression.
Sex, Age, Specimen part
View SamplesMicroRNA-520f regulates EMT, as it activates CDH1 (mRNA) and E-cadherin (protein) expression, and it suppresses tumor cell invasion. We have characterized miR-520f target genes through whole genome transcriptional profiling of miRNA transfected pancreas cancer cells (PANC-1).
miRNA-520f Reverses Epithelial-to-Mesenchymal Transition by Targeting <i>ADAM9</i> and <i>TGFBR2</i>.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Multi-OMIC profiling of survival and metabolic signaling networks in cells subjected to photodynamic therapy.
Cell line, Treatment
View SamplesPhotodynamic therapy (PDT) is a tumor treatment strategy that relies on the production of reactive oxygen species (ROS) in the tumor following local illumination. Although PDT has shown promising results in the treatment of non-resectable perihilar cholangiocarcinoma, it is still employed palliatively. In this study, tumor-comprising cells (i.e., cancer cells, endothelial cells, macrophages) were treated with the photosensitizer zinc phthalocyanine that was encapsulated in cationic liposomes (ZPCLs). Post-PDT survival pathways were studied following sublethal (50% lethal concentration (LC50)) and supralethal (LC90) PDT using a multi-omics approach. ZPCLs did not exhibit toxicity in any of the cells as assessed by toxicogenomics. Sublethal PDT induced survival signaling in perihilar cholangiocarcinoma (SK-ChA-1) cells via mainly hypoxia-inducible factor 1 (HIF-1)-, nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-B)-, activator protein 1 (AP-1)-, and heat shock factor (HSF)-mediated pathways. In contrast, supralethal PDT damage was associated with a dampened survival response. (Phospho)proteomic and metabolomic analysis showed that PDT-subjected SK-ChA-1 cells downregulated proteins associated with epidermal growth factor receptor (EGFR) signaling, particularly at LC50. PDT also affected various components of glycolysis and the tricarboxylic acid cycle as well as metabolites involved in redox signaling. In conclusion, sublethal PDT activates multiple pathways in tumor parenchymal and non-parenchymal cells that, in tumor cells, transcriptionally regulate cell survival, proliferation, energy metabolism, detoxification, inflammation/angiogenesis, and metastasis. Accordingly, sublethally afflicted tumor cells are a major therapeutic culprit. Our multi-omics analysis unveiled multiple druggable targets for pharmacological intervention.
Multi-OMIC profiling of survival and metabolic signaling networks in cells subjected to photodynamic therapy.
Cell line, Treatment
View SamplesHIV-1 nucleoside reverse transcriptase inhibitor (NRTI) use is associated with severe adverse events. However, the exact mechanisms behind their toxicity has not been fully understood. Mitochondrial dysfunction after chronic exposure to NRTIs has predominantly been assigned to mitochondrial polymerase-? inhibition by NRTIs. However, an increasing amount of data suggests that this is not the sole mechanism. Many NRTI induced adverse events have been linked to the incurrence of oxidative stress, although the causality of events leading to reactive oxygen species (ROS) production and their role in toxicity is unclear. In this study we show that short-term effects of these drugs, which are rarely discussed in the literature, include direct inhibition of the mitochondrial respiratory chain (MRC), decreased ATP levels and increased ROS production. Collectively these events affect fitness and longevity of C. elegans through mitohormetic signalling events. Furthermore, we demonstrate that these effects can be normalized by addition of the anti-oxidant N-acetylcysteine (NAC), which suggests that ROS likely influence the onset and severity of adverse events upon drug exposure. Overall design: RNA-seq on Caenorhabditis elegans exposed to DMSO, 3''-azido-3''-deoxythymidine (zidovudine or AZT), 2'',3''-didehydro-2'',3''-deoxythymidine (stavudine or d4T), 3''-deoxy-3''-fluorothymidine (alovudine or FLT) or untreated control after 24 or 72 hours of exposure.
Beyond the polymerase-γ theory: Production of ROS as a mode of NRTI-induced mitochondrial toxicity.
Specimen part, Subject
View SamplesChildhood acute lymphoblastic leukemia (ALL) comprises a large group of genetic subtypes with a favorable prognosis characterized by a TEL-AML1-fusion, hyperdiploidy (>50 chromosomes) or E2A-PBX1 fusion and a smaller group with unfavorable outcome characterized by either a BCR-ABL-fusion, MLL-rearrangement or T-ALL.
A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study.
No sample metadata fields
View SamplesChildhood acute lymphoblastic leukemia (ALL) comprises a large group of genetic subtypes with a favorable prognosis characterized by a TEL-AML1-fusion, hyperdiploidy (>50 chromosomes) or E2A-PBX1 fusion and a smaller group with unfavorable outcome characterized by either a BCR-ABL-fusion, MLL-rearrangement or T-ALL.
A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study.
No sample metadata fields
View SamplesIn parallel with the inconsistency in observational studies and chemoprevention trials, the molecular mechanisms by which selenium may affect prostate cancer risk have not been elucidated. We conducted a randomized, placebo-controlled intervention trial to examine the effects of a short-term intervention with selenized yeast on whole-genome expression profiles in non-malignant prostate tissue. Twenty-three men receiving prostate biopsies were randomly assigned to take 300 g selenized yeast per day (n=12) or placebo (non-selenized yeast, n=11) during a median intervention period of 35 (interquartile range: 31-35) days. Prostate specimens, collected from the transition zone before and after intervention, of 15 participants (n=8 selenium, n=7 placebo) were available for analysis using Affymetrix GeneChip Human 1.0 ST Arrays. Pathway and gene set enrichment analyses revealed that the intervention with selenium resulted in a down-regulated expression of genes involved in signaling pathways related to cellular adhesion, migration, invasion, remodeling and immune responses. Specifically, expression of the well-established epithelial marker E-cadherin was up-regulated, while mesenchymal markers, such as vimentin and fibronectin, were down-regulated after the intervention with selenium. This implies an effect of selenium on the epithelial-to-mesenchymal transition (EMT). Moreover, selenium affected expression of genes involved in wound healing and inflammation, processes which are both related to EMT. In conclusion, our data showed that selenium affected expression of genes implicated in EMT, mainly represented by a change in the direction of the epithelial rather than the mesenchymal phenotype.
A short-term intervention with selenium affects expression of genes implicated in the epithelial-to-mesenchymal transition in the prostate.
Sex, Specimen part, Time
View SamplesThese experiments were done to compare the gene expression profiles in CD4+ T cells responding to antigen presented by dendritic cells transiently or persistently. Some treatments include the activation of the dendritic cells by CD40 engagement.
Sustained antigen presentation can promote an immunogenic T cell response, like dendritic cell activation.
Specimen part
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