Assessing Transcriptome Changes in PDX Glioblastoma cells following treatment with a Super-Enhancer Inhibitor
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA556030 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Assessing eRNAs associated with a cytokine-sensing mammary super-enhancer
| PRJNA412035 | ENA
Project description:Patient-derived xenograft (PDX) models represent an essential tool for the preclinical evaluation of novel targeted therapies and their combinations. In this project, we molecularly characterized a comprehensive panel of glioma PDX models with well conserved molecular and pathological features over multiple passages. PDX samples were subjected to next generation sequencing (NGS). Characterization of cancer-relevant features including driver mutations or cellular processes was performed using mutational and gene expression data in order to identify potential biomarker or treatment targets in glioblastoma. In summary, we reported a newly established and molecularly characterized panel of glioma PDX models with high relevance for translational preclinical research.
| EGAS00001007119 | EGA
Project description:Analysis of primary PDAC cells established from Pdx-1CreAPCL/+p53L/L and Pdx-1Crep53L/L mice. APC haploinsufficiency combined with P53 loss in the pancreas drives MCN progression in mice. Results provide insight into molecular mechanisms invloved in the MCN formation of Pdx-1Cre APCL/+P53L/L mice. Pdx-1CreAPC+/LP53L/L PDAC cell lines and 2 Pdx-1CreP53L/L ductal cell lines were analyzed.
2014-10-01 | E-GEOD-61894 | biostudies-arrayexpress
Project description:The aim of this study was to characterize phosphoproteome in response to AZD1775 in patient derived xenografts (PDX) lines and clinical specimens in glioblastoma. Tyrosine and motif specific serine and threonine phosphorylation were measured using quantitative LC-MS/MS based on TMT labeling.
2022-10-13 | PXD018782 | Pride
Project description:Enhancers are transcription factor platforms that also bind RNA polymerase II and generate enhancer RNAs (eRNA). Although eRNAs have been suggested as predictors of enhancer activities and possibly key components facilitating transcription, there is little genetic evidence to support this. We address the biology of eRNAs in vivo and investigate eRNA patterns, expression levels and possible functions within a mammary-specific super-enhancer that is composed of three units with distinct transcriptional capacities. We show that eRNA levels do not correspond with the activities of their respective enhancer units. However, changes in eRNA expression upon deletion of individual enhancer units reflect the change in overall super-enhancer activity. These data provide genetic evidence that eRNA levels are not a reliable readout of individual enhancers, but they predict superenhancer activity in the absence of constituent elements.
2018-06-01 | GSE104206 | GEO
Project description:Data interpreting of PDX proteome is still a problem because with the growth of human cancerous tissue in an immunodeficient mouse, the endothelial cells and fibroblasts from the host mouse replaced human stromal components, making PDX sample a mixture of human and mouse cells. In this study, we created four human and mouse protein mixtures with different human protein percentages as the standard testing sets. We established an easy algorithm to fit the known proportions and used this strategy on a pair of PDX samples. Our data suggested that our new algorithm is feasible and may help to offer more information on PDX proteome data analysis.
2022-05-19 | PXD008611 | Pride
Project description:We investigated the gene expression changes in a library of meso PDX models.
2022-06-17 | E-MTAB-11783 | biostudies-arrayexpress
Project description:Chromatin regulators have become highly attractive targets for cancer therapy, yet many of these regulators are expressed in a broad range of healthy cells and contribute generally to gene expression. An important conundrum has thus emerged: how can inhibition of a general regulator of gene expression produce selective effects at specific oncogenes? Here we investigate how inhibition of the transcriptional coactivator BRD4 (Bromodomain containing 4) leads to selective inhibition of disease-critical oncogenes in a highly malignant blood cancer, multiple myeloma (MM). We found that BRD4 generally occupies the promoter elements of active genes together with the Mediator coactivator, but remarkably high levels of these two coactivator proteins were associated with a small set of exceptionally large enhancers. These super-enhancers are associated with genes that feature prominently in MM biology, including the MYC oncogene. Treatment of MM tumor cells with the BET-bromodomain inhibitor JQ1 led to preferential loss of BRD4 at super-enhancers and consequent transcription elongation defects that preferentially impact genes with super-enhancers, including the c-MYC oncogene. Super-enhancers were found at key oncogenic drivers in many other tumor cells. Thus, super-enhancers can regulate oncogenic drivers in tumor cells, which in some cells can be preferentially disrupted by BRD4 inhibition, which in turn contributes to the selective transcriptional effects observed at these oncogenes. These observations have implications for the discovery of novel cancer therapeutics directed at components of super-enhancers in diverse tumor types. ChIP-Seq for chromatin regulators and RNA Polymerase II in multiple myeloma, glioblastoma multiforme, and small cell lung cancer
2013-01-02 | E-GEOD-42355 | biostudies-arrayexpress
Project description:The patient-derived xenograft (PDX) model retains the heterogeneity of patient tumors, allowing a means to not only examine efficacy of a therapy across a population, but also study crucial aspects of cancer biology in response to treatment. Herein we describe the development and characterization of an ovarian-PDX model in order to study the development of chemoresistance. We demonstrate that PDX tumors are not simply composed of tumor-initiating cells, but recapitulate the original tumor’s heterogeneity, oncogene expression profiles, and clinical response to chemotherapy. Combined carboplatin/paclitaxel treatment of PDX tumors enriches the cancer stem cell populations, but persistent tumors are not entirely composed of these populations. RNA-Seq analysis of treated PDX tumors compared to untreated tumors demonstrates a consistently contrasting genetic profile after therapy, suggesting similar, but few, pathways are mediating chemoresistance. The pathways most significantly altered included Protein Kinase A signaling, GNRH signaling, and sphingosine-1-phosphate signaling. Pathways and genes identified by this methodology represent novel approaches to targeting the chemoresistant population in ovarian cancer 6 pairs of Patient-Derived Xenografts (PDX) were ananlyzed using RNA-seq for a total of 12 samples. Each pair consists of a treated and untreated PDX of ovarian cancer. Treated Ovarian cancer PDXs were treated with 4 weeks of a combination of carboplatin and taxol. RNA was isolated and converted to cDNA. RNA-seq was conductred on the Illumina HiSeq 2000 with 50 bp paired end sequencing
2015-06-17 | E-GEOD-58586 | biostudies-arrayexpress
Project description:We investigated the gene expression changes in a library of small cell lung carcinoma (SCLC) patient-derived xenograft (PDX) models.
2022-02-07 | E-MTAB-11230 | biostudies-arrayexpress