GEO DataSets

(Submitter supplied) 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. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

16 Samples

Download data: CEL

(Submitter supplied) 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. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

12 Samples

Download data: CSV

(Submitter supplied) As part of a clinical trial of the MDM2 inhibitor DS-3032b, 41 primary tumor samples were obtained before treatment from 38 patients newly diagnosed with AML, or relapsed or refractory to standard induction chemotherapy Gene expression features of pretreatment samples, along with TP53 mutation status, were found to correlate with clinical response to DS-3032b (manuscript under review).

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

41 Samples

Download data: CEL

(Submitter supplied) Microarray-based gene expression analysis showed that combination treatment with RG7388 and GSK2830371 increases the subset of early RG7388 induced p53-transcriptional target genes. These findings demonstrate that potent and selective WIP1 inhibition potentiates the response to MDM2 inhibitors in TP53 wild-type cells.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

12 Samples

Download data: IDAT, TXT

(Submitter supplied) Analysis of H292 cells infected with Mycoplasma hyorhinis. Mycoplasma infection reduces the cytotoxic effect of Nutlin3 on H292 cells. The results provide insight into molecular mechanisms underlying the response of H292 cells to Nutlin3.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

4 Samples

Download data: IDAT, TXT

(Submitter supplied) Analysis of steady-state mRNA levels in liposarcoma cells treated for 28 hr with 0.05% DMSO or 10 uM Nutlin3R and/or 12.5 nM Carfilzomib

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

16 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platforms:

GPL24676 GPL16791

30 Samples

Download data

(Submitter supplied) SLN screen highlights the 26s proteasome as a putitive theraputic target.

Organism:

Homo sapiens

Type:

Other

Platform:

GPL16791

6 Samples

Download data: TXT

(Submitter supplied) Analysis of steady-state mRNA levels in liposarcoma cells treated for 16 hr with 0.05% DMSO or 10 uM Nutlin3R

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

8 Samples

Download data: TXT

(Submitter supplied) Epigenetic modifications have been shown to be important in developmental tumors as Ewing sarcoma. We profiled the DNA methylation status of 15 primary tumors and 7 cell lines using the Infinium Human Methylation 450k. Differential methylation analysis between Ewing sarcoma and reference samples revealed 1,166 hypermethylated and 864 hypomethylated CpG sites (Bonferroni p<0.05, δ-β-value with absolute difference of >0.20) corresponding to 392 and 470 genes respectively. more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL13534

22 Samples

Download data

(Submitter supplied) Several genome-wide transcriptome analyses that focused on p53-induced cellular responses in many cellular contexts have continued to expand the already vast p53-regulated transcriptional networks. To investigate post-transcriptional controls as an additional dimension of p53-directed gene expression responses we performed translatome analysis by polysomal profiling on MCF7 cells treated with Doxorubicin and Nutlin-3a. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6480

27 Samples

Download data: TXT

(Submitter supplied) CDK4 inhibitors have reached clinical approval for cancer therapy. In parallel, the p53 antagonist Mdm2 remains an attractive target for anti-cancer therapy, including numerous clinical studies. The genes encoding Mdm2 and CDK4 are frequently co-amplified in human malignancies, most notably in liposarcomas, suggesting their combined targeting for therapy. Here we show, however, that small compounds that inhibit Mdm2 and CDK4 antagonize each other rather than synergize in their cytotoxicity towards sarcoma cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

18 Samples

Download data: CSV, XLSX

(Submitter supplied) p53 is critically important in preventing oncogenesis but its role in non-cancer biology remains unclear. Macrophages exist as two subtypes (M1 and M2). Nutlin-3a (p53 activator) inhibits M2 gene expression and phenotype. p53 acts by suppressing transcription of c-Myc and thence regulates expression of a subset of M2 markers. This work has implications for our understanding of the mechanisms that regulate plasticity of macrophages in health and disease. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

15 Samples

Download data: CEL

(Submitter supplied) The wild-type p53-inducible protein phosphatase WIP1, encoded by the PPM1D gene, is a negative regulator of p53 and is involved in cell cycle control and DNA damage stress-response. In acute myeloid leukemia (AML), the restoration of p53 activity through MDM2 inhibition proved efficacy in a number of combination strategies. We investigated the therapeutic potential of its inhibition through the selective WIP1 inhibitor (WIP1i) GSK2830371, in association with the MDM2 inhibitor Nutlin-3a (Nut-3a) in a panel of AML cell lines and performed gene expression analysis of single agent and combined treatments. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL23159

24 Samples

Download data: CEL

(Submitter supplied) Loss of Pten in the KrasG12D;Amhr2-Cre mutant mice leads to the transformation of ovarian surface epithelial (OSE) cells and rapid development of low-grade, invasive serous adenocarcinomas. Tumors occur with 100% penetrance and express elevated expression of wild type tumor repressor protein 53 (TRP53). To test the functions of TRP53 in the Pten;Kras (Trp53+) mice, we disrupted the Trp53 gene yielding Pten;Kras(Trp53-) mice. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

3 Samples

Download data: CEL

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by array

Platforms:

GPL570 GPL10999

20 Samples

Download data: BED, CEL, CHP, WIG

(Submitter supplied) The effects of diverse stresses on promoter selectivity and transcription regulation by the tumor suppressor p53 are poorly understood. We have taken a comprehensive approach to characterizing the human p53 network that includes p53 levels, binding, expression and chromatin changes under diverse stresses. Human osteosarcoma U2OS cells treated with anti-cancer drugs Doxorubicin or Nutlin-3 led to strikingly different p53 gene binding patterns based on ChIP-seq experiments. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL10999

8 Samples

Download data: BED, WIG

(Submitter supplied) The effects of diverse stresses on promoter selectivity and transcription regulation by the tumor suppressor p53 are poorly understood. We have taken a comprehensive approach to characterizing the human p53 network that includes p53 levels, binding, expression and chromatin changes under diverse stresses. Human osteosarcoma U2OS cells treated with anti-cancer drugs Doxorubicin or Nutlin-3 led to strikingly different p53 gene binding patterns based on ChIP-seq experiments. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

12 Samples

Download data: CEL, CHP

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by array; Methylation profiling by array

Platforms:

GPL8490 GPL6947

190 Samples

Download data: TXT

(Submitter supplied) We used the Infinium HumanMethylation27 platform to profile DNA methylation in 80 primary, untreated high-grade soft tissue sarcomas, representing eight relevant subtypes, two non-neoplastic fat samples and 14 representative sarcoma cell lines.

Organism:

Homo sapiens

Type:

Methylation profiling by array

Platform:

GPL8490

96 Samples

Download data: TXT