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Expression data from human sarcoma patient samples treated with either vehicle control or Nutlin-3a

ABSTRACT: This study has examined the molecular mechanisms underlying sensitivity of sarcomas to Nutlin-3a, a non-genotoxic activator of the p53 pathway. Human patient material was collected immediately following surgical resection, dissected into small pieces and ex planted onto gelatin sponges immersed in media containing either vehicle control or Nutlin-3a (10uM and/or 50uM) for 48 hours. Nutlin-3a represents a novel targeted therapy for the treatment of sarcomas. We have examined expression profiles of genes upregulated in sarcoma patient derived tissues following nutlin-3a treatment ex vivo

ORGANISM(S): Homo sapiens

PROVIDER: GSE48296 | GEO | 2014/03/10

SECONDARY ACCESSION(S): PRJNA209564

REPOSITORIES: GEO

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Expression data from human sarcoma patient samples treated with either vehicle control or Nutlin-3a

Project description:This study has examined the molecular mechanisms underlying sensitivity of sarcomas to Nutlin-3a, a non-genotoxic activator of the p53 pathway. Human patient material was collected immediately following surgical resection, dissected into small pieces and ex planted onto gelatin sponges immersed in media containing either vehicle control or Nutlin-3a (10uM and/or 50uM) for 48 hours. Nutlin-3a represents a novel targeted therapy for the treatment of sarcomas. We have examined expression profiles of genes upregulated in sarcoma patient derived tissues following nutlin-3a treatment ex vivo 16 samples ((Vehicle control and Nutlin-3a (10uM and 50uM) treated samples)) from 6 sarcoma patients

2014-03-10 | E-GEOD-48296 | biostudies-arrayexpress

Transcriptome-profiling (RNA-seq) and Ribosome-profiling (Ribo-seq) of BJ cells treated with Nutlin-3a, an MDM2 inhibitor, which induces p53.

Project description:We applied in parallel RNA-Seq and Ribosome-profiling analyses to immortalized human primary BJ fibroblast cells in which p53 was induced by Nutlin-3a RNA-seq, using Illumina HiSeq 2000, was applied to BJ cells treated with Nutlin-3a, at 5 timepoints: 0, 2, 4, 6, 19 hrs Ribosome profiling was applied to BJ cells treated with Nutlin-3a, at 5 timepoints: 0, 2, 4, 6, 19 hrs

2013-06-01 | E-GEOD-45785 | biostudies-arrayexpress

Interruption of p53-MDM2 Interaction by Nutlin-3a in Human Lymphoma Cell Models Initiates a Cell-Dependent Global Effect on Transcriptome and Proteome Level

Project description:In most lymphomas, p53 signaling pathway is inactivated by various mechanisms independent to p53 gene mutations or deletions. In many cases, p53 function is largely regulated by alterations in the protein abundance levels by the action of E3 ubiquitin-protein ligase MDM2, targeting p53 to proteasome-mediated degradation. In the present study, an integrating transcriptomics and pro-teomics analysis was employed to investigate the effect of p53 activation by a small-molecule MDM2-antagonist, nutlin 3a, on three lymphoma cell models following p53 activation. Our analy-sis revealed a system-wide nutlin 3a-associated effect in all examined lymphoma types, identifying in total of 4037 differentially affected proteins involved in a plethora of pathways, with significant heterogeneity among lymphomas. Our findings include known p53-targets and novel p53 activa-tion effects, involving transcription, translation, or degradation of protein components of path-ways, such as a decrease in key members of PI3K/mTOR pathway, heat-shock response, and gly-colysis, and an increase in key members of oxidative phoshosphorylation, autophagy and mito-chondrial translation. Combined inhibition of HSP90 or PI3K/mTOR pathway with nutlin 3a-mediated p53-activation enhanced the apoptotic effects suggesting a promising strategy against human lymphomas. Integrated omic profiling after p53 activation offered novel insights on the regulatory role specific proteins and pathways may have in lymphomagenesis.

2023-07-30 | PXD009290 | Pride

Transcriptomics analysis in 3T3L1 preadipocytes with activation of p53 via Nutlin-3a treatment

Project description:3T3L1 preadipocytes were treated with DMSO control and Nutlin-3a (prepared in DMSO) and total RNA extracted from the treated cells were subjected to illumina based RNA-seq to analyze and compare transcriptome to understand gene expression regulation influenced by p53 activation via Nutlin-3a treatment.

2018-07-05 | GSE100811 | GEO

Nutlin-3a-induced changes in the proteome of parental and RFX7 knock-out U2OS cells

Project description:Mass spectrometry-based whole proteome analysis of parental and RFX7 knock-out U2OS cells treated with 10 µM Nutlin-3a or DMSO solvent control. Ten biological replicates were used.

2023-03-11 | PXD024869 | Pride

MicroRNA profiling by array of human multiple myloma p53 wild type cells treated with nutlin 3A

Project description:The miRNA profiles were analyzed for nutlin 3A treated and untreated multiple myloma p53 wild type cells

2010-07-22 | E-TABM-1038 | biostudies-arrayexpress

mRNA-seq from Nutlin-3a, doxorubicin, and DMSO treated HCT116 p21-/- cells

Project description:We sequenced mRNA from HCT116 p21-/- cells treated with Nutlin-3a, doxorubicin, or DMSO for 24 h.

2016-06-09 | GSE77841 | GEO

Nutlin-3a induced changes in the transcriptome of parental and RFX7-/- U2OS cells

Project description:RNA-seq from parental and RFX7-/- U2OS cells treated with Nutlin-3a or DMSO control

2023-02-28 | GSE173483 | GEO

Cooperation of Nutlin-3a and a Wip1 inhibitor to induce p53 activity

Project description:Targeting the Mdm2 oncoprotein by drugs has the potential of re-establishing p53 function and tumor suppression. However, Mdm2-antagonizing drug candidates, e. g. Nutlin-3a, often fail to abolish cancer cell growth sustainably. To overcome these limitations, we inhibited Mdm2 and simultaneously a second negative regulator of p53, the phosphatase Wip1/PPM1D. When combining Nutlin-3a with the Wip1 inhibitor GSK2830371 in the treatment of p53-proficient but not p53-deficient cells, we observed enhanced phosphorylation (Ser 15) and acetylation (Lys 382) of p53, increased expression of p53 target gene products, and synergistic inhibition of cell proliferation. Surprisingly, when testing the two compounds individually, largely distinct sets of genes were induced, as revealed by deep sequencing analysis of RNA. In contrast, the combination of both drugs led to an expression signature that largely comprised that of Nutlin-3a alone. Moreover, the combination of drugs, or the combination of Nutlin-3a with Wip1-depletion by siRNA, activated p53-responsive genes to a greater extent than either of the compounds alone. Simultaneous inhibition of Mdm2 and Wip1 enhanced cell senescence and G2/M accumulation. Taken together, the inhibition of Wip1 might fortify p53-mediated tumor suppression by Mdm2 antagonists.

2016-05-02 | GSE80716 | GEO

PolyA RNA-seq from CHP212 WT and FAM193AKO cells treated with Nutlin-3

Project description:Analysis of steady-state mRNA levels in CHP212 WT and FAM193AKO cells following DMSO or Nutlin-3a treatment.

2022-12-19 | GSE189133 | GEO