Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA283437 | ENA |
REPOSITORIES: ENA
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Project description:The bromodomain inhibitor JQ1 and the histone deacetylase inhibitor panobinostat induce synergistic anticancer effects We analyzed whether JQ1 and panobinostat synergistically modulate gene expression Neuroblastoma SK-N-BE(2) cells were treated with vehicle control, 1 microM JQ1, 10 nM panobinostat, or combination of JQ1 and panobinostat for 6 hours, and subjected to differential gene expression studies with Affymetrix microarrays.
2015-12-31 | E-GEOD-68690 | biostudies-arrayexpress
Project description:Differential gene expression in neuroblastoma cells after treatment with JQ1, nanaomycin, or combination of JQ1 and nanaomycin
| PRJNA306144 | ENA
Project description:Neuroblastoma is the most common extra-cranial malignancy in childhood and accounts for approximately 15% of childhood cancer deaths. Amplification of N-Myc in neuroblastoma is associated with aggressive disease and predicts for poor prognosis. Novel therapeutic approaches are therefore essential to improving patient outcomes in this setting. The histone deacetylases are known to interact with N-Myc and regulate numerous cellular processes, including differentiation in neuroblastoma. We therefore investigated the antitumor activity of the histone deacetylase inhibitor, panobinostat in the setting of N-Myc amplified neuroblastoma using the TH-MYCN murine model. Continuous treatment of tumor bearing TH-MYCN transgenic mice with panobinostat for 9 weeks led to a significant improvement in survival as compared to mice treated with vehicle, or continuous treatment with panobinostat for a three week period. Panobinostat induced rapid tumor regression with no regrowth observed during the treatment period. Tumor response was associated with an initial apoptosis phenotype mediated via up-regulation of BMF and BIM. When treated was stopped at three weeks 100% of mice relapsed with aggressive neuroblastoma. Differentiation of neuroblastoma into benign ganglioneuroma, with a characteristic increase in S100 expression and reduction of N-Myc expression, was observed in mice treated for nine weeks, resulting in a sustained remission on 90% of mice treated. RNA-sequencing analysis of tumors from treated animals confirmed significant up-regulation of gene pathways associated with apoptosis and differentiation as early as 24 hours after treatment. Together our data demonstrate the potential of panobinostat as a therapeutic strategy for high-risk neuroblastoma patients. Eight homozygous TH-MYCN mice bearing neuroblastomas were treated with either 5mg/kg panobinostat (4 animals) or vehicle (4 animals) for 24hr (two doses) and tumours harvested 4hr post the second dose.
2015-07-15 | E-GEOD-69869 | biostudies-arrayexpress
Project description:Purpose: We applied RNA sequencing technology for high-throughput analysis of transcriptional changes within human MM cell lines JJN3 and U266 due to individual and combination drug treatment. Methods: JJN3 and U266 cells were treated with pan-HDACi panbobinostat, DNMTi 5-Azacytidine, panobinostat+5-Azacytidine or NMP for 4h or 24h in triplicate and transcriptional changes assessed by RNAseq using Illumina HiSeq platform. Specifically, JJN3 cells were treated with 10nM panobinostat, 2.5µM 5-Azacytidine, panobinostat+5-Azacytidine (at given doses), or 10mM NMP. U266 cells were treated with 10nM panobinostat, 10µM 5-Azacytidine, panobinostat+5-Azacytidine (at given doses), or 10mM NMP. Results: We report unique and overlapping transcriptional signatures that lead to the induction of apoptosis in human MM cell lines in a cell-specific manner due to individual or combination treatments. Conclusions: A detailed analysis of differential transcriptional events in human MM cell lines due to HDACi, DNMTi, HDACi+DNMTi and NMP appear to define the molecular events leading to apoptosis and drug mechanism of action. We tested triplicate experiments at 4h and 24hr time points in JJN3 and U266 cell lines against vehicle control treated cells.
2014-04-09 | E-GEOD-56623 | biostudies-arrayexpress
Project description:Neuroblastoma is the most common extra-cranial malignancy in childhood and accounts for approximately 15% of childhood cancer deaths. Amplification of N-Myc in neuroblastoma is associated with aggressive disease and predicts for poor prognosis. Novel therapeutic approaches are therefore essential to improving patient outcomes in this setting. The histone deacetylases are known to interact with N-Myc and regulate numerous cellular processes, including differentiation in neuroblastoma. We therefore investigated the antitumor activity of the histone deacetylase inhibitor, panobinostat in the setting of N-Myc amplified neuroblastoma using the TH-MYCN murine model. Continuous treatment of tumor bearing TH-MYCN transgenic mice with panobinostat for 9 weeks led to a significant improvement in survival as compared to mice treated with vehicle, or continuous treatment with panobinostat for a three week period. Panobinostat induced rapid tumor regression with no regrowth observed during the treatment period. Tumor response was associated with an initial apoptosis phenotype mediated via up-regulation of BMF and BIM. When treated was stopped at three weeks 100% of mice relapsed with aggressive neuroblastoma. Differentiation of neuroblastoma into benign ganglioneuroma, with a characteristic increase in S100 expression and reduction of N-Myc expression, was observed in mice treated for nine weeks, resulting in a sustained remission on 90% of mice treated. RNA-sequencing analysis of tumors from treated animals confirmed significant up-regulation of gene pathways associated with apoptosis and differentiation as early as 24 hours after treatment. Together our data demonstrate the potential of panobinostat as a therapeutic strategy for high-risk neuroblastoma patients.
2015-07-15 | GSE69869 | GEO
Project description:Global mRNA expression profiles of murine primary PDAC cells following JQ1 or SAHA monotherapy as well as JQ1-SAHA combination therapy were collected using Affymetix mouse whole genome array (Mouse Genome 430A 2.0 Array) . Primary PDAC cells isolated from Ptf1aCre/+;Kras+/LSL-G12D;p53lox/lox (Kras;p53) mice were treated either with JQ1 (100 nM) or SAHA (2000 nM) or vehicle 10% (2-Hydroxypropyl)-β-cyclodextrin (Sigma-Aldrich) or as combination therapy with the indicated dosage for monotherapy. Total RNA isolation was performed after 6 hours of treatment. Primary PDAC cells from Ptf1aCre/+;Kras+/LSL-G12D;p53lox/lox (Kras;p53) mice treated either with JQ1, SAHA, vehicle or JQ1-SAHA combination were analyzed by global gene expression analysis.
2015-09-20 | E-GEOD-64836 | biostudies-arrayexpress
Project description:BET bromodomain inhibitors are emerging as very promising novel anticancer agents. Combination of BET bromodomain inhibitor JQ1 and quinone-containing compound nanaomycin exerts synergistic anticancer effect in neuroblastoma We analysed whether a treatment with BET bromodomain inhibitor JQ1, and quinone-containing compound Nanaomycin synergistically modulate gene expression
2016-12-31 | GSE76066 | GEO
Project description:RNA-seq upon JQ1 (1 uM), THZ1 (35 nM), UT (untreated) or combination treatment in the neuroblastoma cell line IMR-5/75. Analysis was performed 10h upon treament. Four biological replicates per condition.
2018-08-17 | E-MTAB-7025 | biostudies-arrayexpress
Project description:The BET (bromodomain and extra terminal) protein family members including BRD4 bind to acetylated lysines on histones and regulate the expression of important oncogenes, e.g., MYC and BCL2. Here we demonstrate the sensitizing effects of the histone hyperacetylation inducing pan-histone deacetylase inhibitor (HDI) panobinostat (PS) on human AML blast progenitor cells (BPCs) to the BET protein inhibitor JQ1. Treatment with JQ1 but not its inactive enantiomer (R-JQ1) was highly lethal against AML BPCs expressing mutant NPM1c+ with or without co-expression of FLT3-ITD, or AML expressing MLL fusion oncoprotein. JQ1 treatment reduced binding of BRD4 and RNA polymerase II to the DNA of MYC and BCL2, and reduced their levels in the AML cells. Co-treatment with JQ1 and the HDAC inhibitor panobinostat (PS) synergistically induced apoptosis of the AML BPCs, but not of normal CD34+ hematopoietic progenitor cells. This was associated with greater attenuation of MYC and BCL2, while increasing p21, BIM and cleaved PARP levels in the AML BPCs. Co-treatment with JQ1 and PS significantly improved the survival of the NOD/SCID mice engrafted with OCI-AML3 or MOLM13 cells (p < 0.01). These findings highlight co-treatment with a BRD4 antagonist and an HDI as a potentially efficacious therapy of AML. Two samples were analyzed (untreated cells, cells treated with JQ1)
2014-01-01 | E-GEOD-51950 | biostudies-arrayexpress
Project description:The bromodomain inhibitor JQ1 and the histone deacetylase inhibitor panobinostat induce synergistic anticancer effects We analyzed whether JQ1 and panobinostat synergistically modulate gene expression
2015-12-31 | GSE68690 | GEO