Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA290359 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Comparative analysis of gene expression profiles in lymphoma cells after treatment by Dexamethasone or CpdA
| PRJNA290356 | ENA
Project description:The project is directed to the development of selective glucocorticoid receptor agonists for anticancer therapy. Glucocorticoids (GC) are widely used in treatment of many types of cancer due to its ability to induce apoptosis in malignant cells (in blood cancer therapy) and to prevent nausea and emesis (in the chemotherapy of solid tumors). However, severe dose-limiting side effects occur, including osteoporosis, muscle wasting, diabetes and other metabolic complications. Both beneficial and harmful effects of glucocorticoids are due to selective activation or repression of particular genes by glucocorticoid receptor (GR). GR regulates gene expression via transactivation that requires GR homodimer binding to gene promoters and transrepression mediated via negative interaction between GR and other transcription factors as well as binding with negative glucocorticoid response elements (nGRE) in genes. GR transactivation is linked to metabolic side effects, while GR transrepression underlies glucocorticoid therapeutic action. Novel selective GR agonist Compound A (CpdA) prevents GR dimerization and transactivation, specifically activates GR transrepression, and has fewer side effects compared to glucocorticoids. Here we compare the gene expression profiles in prostate cancer cells treated with glucocorticoid Dexamethasone (Dex) or CpdA
2015-07-21 | GSE71099 | GEO
Project description:Comparative analysis of gene expression of radioresistant prostate cancer cells and prostate cancer progenitors
| PRJNA233664 | ENA
Project description:Transcriptional profiling of Homo sapiens inflammatory skin diseases (whole skin biospies): Psoriasis (Pso), vs Atopic Dermatitis (AD) vs Lichen planus (Li), vs Contact Eczema (KE), vs Healthy control (KO) In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation. In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.
2014-12-02 | GSE63741 | GEO
Project description:Glucocorticoids (GC) have been widely used as coadjuvants in the treatment of solid tumors, but GC treatment may be associated with poor pharmacotherapeutic response and/or prognosis. The genomic action of GC in these tumors is largely unknown. Here we find that dexamethasone (Dex, a synthetic GC) regulated genes in triple-negative breast cancer (TNBC) cells are associated with drug resistance. Importantly, these GC-regulated genes are aberrantly expressed in TNBC patients and associated with unfavorable clinical outcomes. Interestingly, in TNBC cells, Compound A (CpdA, a selective GR modulator) only regulates a small number of genes not involved in carcinogenesis and therapy resistance. Mechanistic studies using a ChIP-exo approach reveal that Dex- but not CpdA-liganded glucocorticoid receptor (GR) binds to a single glucocorticoid response element (GRE), which drives the expression of pro-tumorigenic genes. Our data suggest that development of safe coadjuvant therapy should consider the distinct genomic function between Dex- and CpdA-liganded GR. To study GR-regulated genes and define GRE in human genome, RNA-seq and GR ChIP-exo are performed in MDA-MB-231 cells before/after dex and CpdA stimulation. Each experiment includes two replicates.
2015-09-18 | E-GEOD-56022 | biostudies-arrayexpress
Project description:Glucocorticoids (GC) have been widely used as coadjuvants in the treatment of solid tumors, but GC treatment may be associated with poor pharmacotherapeutic response and/or prognosis. The genomic action of GC in these tumors is largely unknown. Here we find that dexamethasone (Dex, a synthetic GC) regulated genes in triple-negative breast cancer (TNBC) cells are associated with drug resistance. Importantly, these GC-regulated genes are aberrantly expressed in TNBC patients and associated with unfavorable clinical outcomes. Interestingly, in TNBC cells, Compound A (CpdA, a selective GR modulator) only regulates a small number of genes not involved in carcinogenesis and therapy resistance. Mechanistic studies using a ChIP-exo approach reveal that Dex- but not CpdA-liganded glucocorticoid receptor (GR) binds to a single glucocorticoid response element (GRE), which drives the expression of pro-tumorigenic genes. Our data suggest that development of safe coadjuvant therapy should consider the distinct genomic function between Dex- and CpdA-liganded GR.
2015-09-18 | GSE56022 | GEO
Project description:41 lung adenocarcinoma from never-smokers hybridized on Illumina SNP arrays on 13 HumanCNV370-Quadv3 chips. High-resolution array comparative genomic hybridization analysis of lung adenocarcinoma in 41 never smokers for identification of new minimal common regions (MCR) of gain or loss. The SNP array analysis validated copy-number aberrations and revealed that RB1 and WRN were altered by recurrent copy-neutral loss of heterozygosity.The present study has uncovered new aberrations containing cancer genes. The oncogene FUS is a candidate gene in the 16p region that is frequently gained in never smokers. Multiple genetic pathways defined by gains of MYC, deletions of RB1 and WRN or gains on 7p and 7q are involved in lung adenocarcinoma in never smokers. A 'Cartes d'Identite des Tumeurs' (CIT) project from the French National League Against Cancer (http://cit.ligue-cancer.net) 41 samples hybridized on Illumina SNP arrays. Submitter : Fabien PETEL petelf@ligue-cancer.net . Project leader : Pr Pierre FOURET pierre.fouret@psl.aphp.fr
2011-07-28 | E-TABM-1169 | biostudies-arrayexpress
Project description:Glucocorticoids are widely used to treat inflammatory disorders. Prolonged use results in side effects including osteoporosis, diabetes and obesity. The selective glucocorticoid receptor (GR) modulator Compound A (CpdA) exhibits an inflammation-suppressive effect, largely in absence of detrimental side effects. To understand the mechanistic differences between the classic glucocorticoid dexamethasone (DEX) and CpdA, we looked for proteins oppositely regulated using an unbiased proteomics approach. We found that the autophagy receptor p62 but not GR mediates the anti-inflammatory action of CpdA in macrophages. CpdA drives the upregulation of p62 by recruiting the NRF2 transcription factor to its promoter. Contrarily, the classic GR ligand dexamethasone recruits GR to p62 and other NRF2 controlled gene promoters, resulting in gene downregulation. Both DEX and CpdA are able to induce autophagy, albeit in a cell-type and time-dependent manner. Suppression of LPS-induced IL-6 and MCP1 genes in bone marrow-derived macrophages by CpdA is hampered upon p62 silencing, confirming that p62 is essential for the anti-inflammatory capacity of CpdA. Together, these results demonstrate how off-target mechanisms of selective GR ligands may establish a more efficient anti-inflammatory therapy
2022-06-03 | PXD007793 | Pride
Project description:gene profiles in prostate cancer and normal prostate tissues
| PRJNA97419 | ENA