Hepatitis C virus (HCV) infection is a global health problem. A number of studies have implicated a direct role of cellular lipid metabolism in the HCV life cycle and inhibitors of the mevalonate pathway have been demonstrated to result in an antiviral state within the host cell. Transcriptome profiling was also conducted on Huh-7 human hepatoma cells bearing subgenomic HCV replicons with and without treatment with 25-hydroxycholesterol (25-HC), an inhibitor of the mevalonate pathway that alters lipid metabolism, to assess metabolic determinants of pro- and antiviral states within the host cell.
Transcriptional profiling of the effects of 25-hydroxycholesterol on human hepatocyte metabolism and the antiviral state it conveys against the hepatitis C virus.
No sample metadata fields
View SamplesAnalysis of MCF-7 cells treated for 4h with Ethanol, Estradiol (E2), Dexamethasone (Dex), or Estradiol + Dexamethasone (E2 + Dex)
GR and ER Coactivation Alters the Expression of Differentiation Genes and Associates with Improved ER+ Breast Cancer Outcome.
Cell line
View SamplesUnderstanding the mechanisms by which cells respond to chemotherapeutics is key to identifying means to improve therapy effiicacy while reducing systemic toxicity of these widely used classes of drugs. While determining the role of NRF2-GSH and ER stress in cells exposed to alkylating compounds such as methyl-methanesulfonate (MMS), we asked if these pathways could also be a general cell damage response relevant to other clinically used chemotherapeutics or if it is an alkylation specific response. With this intent, we performed RNA sequencing of MDA-MB231 breast cancer and U2OS osteosarcoma cells lines treated for 8 hours with a topoisomerase II inhibitor etoposide (20 µM), the antimitotic beta-tubulin-interacting drug paclitaxel (0.2 µM), doxorubicin (1 µM) and compared to MMS (40 µg/mL) treated cells. Doses represent IC50 level after 72 hours exposure. We observed that even though non-alkylating drugs, especially etoposide, caused an increase in the mRNA expression of some NRF2 and ER stress signaling markers, the number and magnitude of upregulation of genes markers in either pathway was more pronounced in alkylation treatments compared to other drugs. This indicates that alterations in NRF2 and ER stress pathways could be more likely associated with differential sensitivity to alkylating chemotherapies. Overall design: MDA-MB231 breast cancer and U2OS osteosarcoma cells lines were treated with the 72 h IC50 dose of etoposide (20 µM), paclitaxel (0.2 µM), doxorubicin (1 µM) or MMS (40 µg/mL) for 8 h, and RNA was extracted and analyzed.
Alkylating Agent-Induced NRF2 Blocks Endoplasmic Reticulum Stress-Mediated Apoptosis via Control of Glutathione Pools and Protein Thiol Homeostasis.
Specimen part, Cell line, Treatment, Subject
View SamplesThis study was performed to test the hypothesis that cigarette smoke extract would alter the responses of primary cultures of human bronchial epithelial cells to infection with purified human rhinovirus 16.
Cigarette smoke modulates expression of human rhinovirus-induced airway epithelial host defense genes.
Specimen part, Subject
View SamplesTo identify candidate genes involved in enhanced tumorigenicity and metastasis of CD90+ esophageal tumor-initiating cells.
A CD90(+) tumor-initiating cell population with an aggressive signature and metastatic capacity in esophageal cancer.
Specimen part, Cell line
View SamplesMolecular targeted compounds are emerging as important component to improve the efficacy of classical chemotherapeutics. In this study, we tested whether using low dose sorafenib to reduce off target inhibitions of kinases impacts the antitumor effect of alkylating agents in breast cancer models. Overall design: MDA-MB231 cells were treated with 1 µM sorafenib, 40 µg/mL MMS, or pre-incubated with 1 µM sorafenib for 12 h followed by 40 µg/mL MMS, each in two independent experiments. RNA was harvested 8 and 24 h, or post MMS treatment for combination treatment.
Sorafenib improves alkylating therapy by blocking induced inflammation, invasion and angiogenesis in breast cancer cells.
Specimen part, Cell line, Subject
View SamplesAlbeit increased serum CK level and abnormal muscle histology are always present, boys with DMD are phenotipically indistinguishable from the normal ones at birth and, in their first years of life, acquire early motor milestones at normal times. A clear defect in muscle function becomes generally apparent by the end of the second year. As the disease is typically diagnosed between the ages of 3 and 7, the first two years are often considered and referred to as clinically presymptomatic.
Gene expression profiling in the early phases of DMD: a constant molecular signature characterizes DMD muscle from early postnatal life throughout disease progression.
Sex, Age
View SamplesThe tumor suppressor p53 is a transcription factor that coordinates the cellular response to DNA damage. Here we provide an integrated analysis of p53 genomic occupancy and p53-dependent gene regulation in the splenic B and non-B cell compartments of mice exposed to whole-body ionizing radiation, providing insight into general principles of p53 activity in vivo. In unstressed conditions, p53 bound few genomic targets; induction of p53 by ionizing radiation increased the number of p53 bound sites, leading to highly overlapping profiles in the different cell types. Comparison of these profiles with chromatin features in unstressed B cells revealed that, upon activation, p53 localized at active promoters, distal enhancers, and a smaller set of unmarked distal regions. At promoters, recognition of the canonical p53 motif as well as binding strength were associated with p53-dependent transcriptional activation, but not repression, indicating that the latter was most likely indirect. p53-activated targets constituted the core of a cell type-independent response, superimposed onto a cell type-specific program. Core response genes included most of the known p53-regulated genes, as well as many new ones. Our data represent a unique characterization of the p53-regulated response to ionizing radiation in vivo. Overall design: Total RNA profiling of gene expression in the splenic B and non-B cell compartments of wild-type and Trp53-/-mice exposed to whole-body ionizing radiation by Illumina sequencing
p53 transcriptional programs in B cells upon exposure to genotoxic stress in vivo: Computational analysis of next-generation sequencing data.
No sample metadata fields
View SamplesTranscriptomic studies revealed that hundreds of mRNAs show differential expression in the brains of sleeping versus awake rats, mice, flies, and sparrows. Although these results have offered clues regarding the molecular consequences of sleep and sleep loss, their functional significance thus far has been limited. This is because the previous studies pooled transcripts from all brain cells, including neurons and glia.
Transcriptome profiling of sleeping, waking, and sleep deprived adult heterozygous Aldh1L1 - eGFP-L10a mice.
Disease
View SamplesActivity-dependent transcriptional profiling was performed in the basolateral amygdala in order to identify unique genetic markers for functionally distinct neuronal populations
Antagonistic negative and positive neurons of the basolateral amygdala.
No sample metadata fields
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