Project description:The introduction in the 1960s of the glucocorticoids-based therapy for the management of the vasogenic edema forming in brain tumour patients is considered as a revolution in the history of neurosurgery. Since then, although it is impossible to deny the ability of glucocorticoids to reduce mortality and morbidity of brain tumour patients worldwide, many scientific papers have highlighted the controversial effects that they can exert on glioma cells, for instance in terms of enhanced proliferation and interference with chemotherapeutics drugs. Among synthetic glucocorticoids, the most widely used is Dexamethasone (Dex). Using 4 different Glioblastoma Patient-Derived Xenograft (PDX) cell lines, we treated them with or without Dex 0.1 µM in order to look at the drug-related changes in the transcriptome of the cells. Each experiment has produced 8 samples (1 CTR sample and 1 DEX-treated sample for each cell line) and the experiment has been repeated 3 times, thus giving a total of 24 samples.
Project description:Bromodomain and extraterminal domain (BET) proteins have emerged as therapeutic targets in multiple cancers, including the most common primary adult brain tumor glioblastoma (GBM). Although several bet inhibitors have entered clinical trials, few are brain penetrant. We have generated UM-002, a novel brain penetrant BET inhibitor that reduces GBM cell proliferation in vitro and in a human cerebral brain organoid model. Since UM-002 is more potent than other BET inhibitors, it could potentially be developed for GBM treatment. Furthermore, UM-002 treatment reduces the expression of cell-cycle related genes in vivo, and reduces the expression of invasion related genes within the non-proliferative cells present in tumors as measured by single cell RNAsequencing. These studies suggest that BET inhibition alters the transcriptional landscape of GBM tumors, which has implications for designing combination therapies. Importantly, they also provide an integrated dataset that combines in vitro and ex vivo studies with in vivo single-cell RNA-sequencing to characterize a novel BET inhibitor in GBM.
Project description:Investigation of whole genome expression pattern of 24 hours post fertilization Danio rerio embryos exposed to bisphenol A, 17beta-estradiol, GSK4716, or 0.1% DMSO vehicle control
Project description:Genome-wide DNA methylation profiling of parental (native) and 3-bromopyruvate-resistant UM-UC-3 bladder cancer cells. The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 450,000 CpGs in treatment-naive and 3-bromopyruvate-resistant UM-UC-3 bladder cancer cells.
Project description:Transcriptional profiling of Murine BaF3 cells infected with MPLW515L grown under either normal conditions (Naive) or in 0.8 uM INCB18424 for 4-6 weeks (Persistent). Naive and Persistent cells were then treated with either DMSO (Control) or 0.8 uM INCB18424 for 4 hours. Goal was to determine transcriptional changes conditioned upon sensitivity/resistance of BaF3 MPLW515L mutants to JAK1/2 specific inhibitor.
Project description:Combination therapy with Smo and PI3K inhibitors results in a synergistic effect in reducing tumor growth in PTEN-deficient Glioblastoma. To identify consequences of combination therapy with an Smo inhibitor and a PI3K inhibitor on a genome-wide scale, we performed Affymetrix microarrays with two different PTEN-deficient GBMs treated with single drugs or combination therapy. A small set of genes was significantly affected by combination therapy in hBT70 and/or hBT112, including several genes implicated in GBM prognosis, or identified as targets of Shh, PI3K or S6 pathways 29-33 . There are two different human GBM tumors (BT70 and BT112). Both are PTEN deficient. Samples were treated with DMSO (Control), LDE225 at 1 uM for 5 days, BKM 120 100 nM for 5 days, or LDE225 1 uM and BKM 120 100 nM for 5 days (Combo). Two biological replicates of each condition were analyzed.
Project description:Transcriptional profiling of Murine BaF3 cells infected with MPLW515L grown under either normal conditions (Naive) or in 0.8 uM INCB18424 for 4-6 weeks (Persistent). Naive and Persistent cells were then treated with either DMSO (Control) or 0.8 uM INCB18424 for 4 hours. Goal was to determine transcriptional changes conditioned upon sensitivity/resistance of BaF3 MPLW515L mutants to JAK1/2 specific inhibitor. 3 condition experiment consiting of: 1) Naive cells treated with DMSO (Control) , 2) Naïve cells treated with 0.8 uM INCB18424 for 4 hours (Acute) and 3) Persistent cells treated with 0.8 uM INCB18424 for 4 hours (Persistent). Biological replicates: 3 DMSO control replicates, 3 Acute replicates, 3 Persistent replicates.
Project description:2-cell embryo RNA was sequenced following IVF of naive untreated oocytes with sperm harvested 2 weeks after 2mg/kg dexamethasone or vehicle intraperitoneal injection in males.