Project description:We performed total RNA-seq in the A549 cell line. Cells were treated with either 100 nM dexamethasone or 0.1% ethanol. After 4 hours, cells were washed 2x with PBS and cultured in hormone-free medium for 24 hours, after which cells were treated again for 4 hours with either 100 nM dexamethasone or 0.1% ethanol.
Project description:We performed 4C-seq in the A549 cell line to investigate changes in chromatin interactions at the ZBTB16 locus. Cells were treated with either 100 nM dexamethasone or 0.1% ethanol. After 4 hours, cells were washed 2x with PBS and cultured in hormone-free medium for 24 hours, after which cells were treated again for 4 hours with either 100 nM dexamethasone or 0.1% ethanol. Experiments were performed in two biological replicates. For each treatment, 4C-seq data were generated for the following two viewpoints: ZBTB16 promoter-proximal viewpoint coordinates: chr11:113929670-113930464 (hg19) ZBTB16 intronic viewpoint coordinates: chr11:114051224-114051804 (hg19)
Project description:We performed ATAC-seq in the A549 cell line. Cells were treated with either 100 nM dexamethasone or 0.1% ethanol. After 4 hours, cells were washed 2x with PBS and cultured in hormone-free medium for 24 hours, after which cells were treated again for 4 hours with either 100 nM dexamethasone or 0.1% ethanol.
Project description:To identify the sequences responsible for recruitment of Glucocorticoid receptor (GR) to individual loci, we performed ChIP-seq in four cell lines : A549 (ATTC:CCL-185), Nalm-6 (ATCC:CRL-1567), immortalized mouse embryonic fibroblasts (MEFs)(PMID 21131905), and immortalized PCAF-/-; GCN5flox/ MEFs (PMID 21131905) upon glucocorticoid treatment (1.5 hrs, 1M dexamethasone).
Project description:This is a phase II, randomized, multi-center, open-label, parallel-group study to evaluate the progression-free survival during maintenance therapy.
Eligible patients will be treated within a 12-week induction therapy. Those patients achieving CR/PR or SD at 12 weeks and qualifying for maintenance treatment and re-induction treatment with all potential drug components, will be randomized in a ratio of 1:1 to receive chemotherapy plus panitumumab or chemotherapy alone during maintenance. In case of progression, re-induction treatment will be started.
Project description:Glucocorticoid resistance is a major driver of therapeutic failure in T-cell acute lymphoblastic leukemia (T-ALL). Here we used a systems biology approach, based on the reverse engineering of signaling regulatory networks, which identified the AKT1 kinase as a signaling factor driving glucocorticoid resistance in T-ALL. Indeed, activation of AKT1 in T-ALL lymphoblasts impairs glucocorticoid-induced apoptosis. Mechanistically, AKT1 directly phosphorylates the glucocorticoid receptor NR3C1 protein at position S134 and blocks glucocorticoid-induced NR3C1 translocation to the nucleus. Consistently, inhibition of AKT1 with MK-2206 increases the response of T-ALL cells to glucocorticoid therapy both in T-ALL cell lines and in primary patient samples thus effectively reversing glucocorticoid resistance in vitro and in vivo. These results warrant the clinical testing of ATK1 inhibitors and glucocorticoids, in combination, for the treatment of T-ALL. This study includes 228 T-ALL samples of which 117 samples are re-analysis of GSE26713.