Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA215713 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Though p53 mutations are rare in Ewing sarcoma, there is a strong indication that p53-mutant tumors form a particularly bad prognosis group. As such, novel treatment strategies are warranted that would specifically target and eradicate tumor cells containing mutant-p53 in this subset of ES patients. PRIMA-1Met/APR-246 is a small organic molecule which has been shown to restore tumor suppressor function primarily to mutant p53 and to also induce cell death in various cancer cell types. We analyzed the apoptosis inducibility on Ewing sarcoma cells harbouring different p53 mutations upon exposure to APR-246. Gene expression profiles of three STA-ET-7 cell lines established from the same patient at different stages of the disease was assessed by microarray analysis as these cell lines responded variably to APR-246.
2013-11-12 | E-GEOD-49967 | biostudies-arrayexpress
Project description:Though p53 mutations are rare in Ewing sarcoma, there is a strong indication that p53-mutant tumors form a particularly bad prognosis group. As such, novel treatment strategies are warranted that would specifically target and eradicate tumor cells containing mutant-p53 in this subset of ES patients. PRIMA-1Met/APR-246 is a small organic molecule which has been shown to restore tumor suppressor function primarily to mutant p53 and to also induce cell death in various cancer cell types.
2013-11-12 | GSE49967 | GEO
Project description:Targeting p53 by the small molecule PRIMA-1Met/APR-246 has shown promising preclinical activity in various cancer types. However, the mechanism of PRIMA-1Met-induced apoptosis is not completely understood and its effect on multiple myeloma (MM) cells is unknown. In this study we evaluated anti-tumor effect of PRIMA-1Met alone or combined with current anti-myeloma agents in MM cell lines, patient samples, and a mouse xenograft model. Results of our study showed that PRIMA-1Met decreased the viability of MM cells irrespective of p53 status with limited cytotoxicity toward normal hematopoietic cells. PRIMA-1Met restored wild type conformation of mutant p53 and induced activation of p73 up-regulating Noxa and down-regulating Mcl-1 without significant modulation of p53 level. Importantly, PRIMA-1Met delayed tumor growth and prolonged survival of mice bearing MM tumor. To identify the potential targets of PRIMA-1Met, we performed gene expression profiling (GEP) by microarray in three different cell lines harboring wild type, mutant or null p53 and analysed differential expression of target genes between PRIMA-1Met treated and non-treated samples. Based on our we conclude that treatment of MM cells with PRIMA-1Met lead to induction of p73-mediated apoptosis by up-regulating Noxa and down-regulating Mcl-1 irrespective of p53 status.
2013-05-04 | GSE46609 | GEO
Project description:Targeting p53 by the small molecule PRIMA-1Met/APR-246 has shown promising preclinical activity in various cancer types. However, the mechanism of PRIMA-1Met-induced apoptosis is not completely understood and its effect on multiple myeloma (MM) cells is unknown. In this study we evaluated anti-tumor effect of PRIMA-1Met alone or combined with current anti-myeloma agents in MM cell lines, patient samples, and a mouse xenograft model. Results of our study showed that PRIMA-1Met decreased the viability of MM cells irrespective of p53 status with limited cytotoxicity toward normal hematopoietic cells. PRIMA-1Met restored wild type conformation of mutant p53 and induced activation of p73 up-regulating Noxa and down-regulating Mcl-1 without significant modulation of p53 level. Importantly, PRIMA-1Met delayed tumor growth and prolonged survival of mice bearing MM tumor. To identify the potential targets of PRIMA-1Met, we performed gene expression profiling (GEP) by microarray in three different cell lines harboring wild type, mutant or null p53 and analysed differential expression of target genes between PRIMA-1Met treated and non-treated samples. Based on our we conclude that treatment of MM cells with PRIMA-1Met lead to induction of p73-mediated apoptosis by up-regulating Noxa and down-regulating Mcl-1 irrespective of p53 status. MM.1S, U266, and 8266R5 cells were treated with 20, 40, and 40 µM PRIMA-1Met, respectively for 8 hrs and total RNA was isolated. Gene expression was analyzed with Illumina RNA analysis Beadchips (Illumina Inc. San Diego, CA) representing 48,000 human genes (Human HT12). Array data analysis was carried out with Bead Studio software. Genes showing at least a 2.0-fold difference in expression levels between control and PRIMA-1Met-treated cells were considered to be modulated by PRIMA-1Met.
2013-05-04 | E-GEOD-46609 | biostudies-arrayexpress
Project description:p53 mutation is common and highly related to radiotherapy resistance in rectal cancer. APR-246, as a small molecule, can restore the tumor-suppressor function to mutant p53. There is no study on combining APR-246 with radiation in rectal cancer; therefore, we examined whether APR-246 sensitized colorectal cancer cells with different p53 status to radiation. The combination treatment had synergistic effects on HCT116p53-R248W/-(p53Mut) cells, followed by HCT116p53+/+(p53WT) cells, and exhibited an additive effect on HCT116p53-/-(p53Null) cells through inhibiting proliferation, enhancing reactive oxygen species, and apoptosis. The results were confirmed in zebrafish xenografts. Comparison of the transcriptome in colorectal cancer cells with different p53 status 72hrs post-treatment with APR-246, irradiation, or the combination of APR-246 with irradiation was carried out. p53Mut and p53WT cells shared more activated pathways and differentially expressed genes following the combination treatment, compared to p53Null cells, although the combination treatment regulated individual pathways in the different cell lines. APR-246 mediated radio-sensitization effects through p53-dependent and -independent ways.
2023-05-12 | GSE232305 | GEO
Project description:Expression of genes in sorted CD4, CD8 and non-T CD45 cells isolated from TME of B16 tumors in wildtype B6, APR-246 treated wildtype B6 and Super p53 mice.
2022-02-11 | GSE166637 | GEO
Project description:Identification of ovarian cancer (OvCa) patient subpopulations with increased sensitivity to targeted therapies could offer significant clinical benefit. We report that 22 % of the high grade OvCa tumors at diagnosis express CIP2A oncoprotein at low levels. Further, regardless of their significantly lower likelihood of disease relapse after standard chemotherapy, a portion of relapsed tumors retain their CIP2A-deficient phenotype. Through a screen for therapeutics that would preferentially kill CIP2A-deficient OvCa cells, we identified reactive oxygen species inducer APR-246, tested previously in OvCa clinical trials. Consistent with CIP2A-deficient OvCa subtype in humans, CIP2A is dispensable for development of MISIIR-Tag-driven mouse OvCa tumors. Nevertheless, CIP2A null OvCa tumor cells from MISIIR-Tag mice displayed APR-246 hypersensitivity both in vitro and in vivo. Mechanistically, the lack of CIP2A expression hypersensitizes the OvCa cells to APR-246 by inhibition of NF-kB activity. Accordingly, combination of APR-246 and NF-kB inhibitor compounds strongly synergized in killing of CIP2A positive OvCa cells. Collectively, the results warrant consideration of clinical testing of APR-246 for CIP2A-deficient OvCa tumor subtype patients. Results also reveal CIP2A as a candidate APR-246 combination therapy target for ovarian cancer.
2022-02-02 | GSE195984 | GEO
Project description:We performed reduced representation bisulfite seqeuncing (RRBS) and ChIP-seq of histone modification marks on three Ewing sarcoma tumor samples, and we quantified epigenetic heterogeneity on three levels. First, we identified a Ewing sarcoma specific hypomethylation signature at EWS-FLI1 regulated enhancers, showing that epigenetic enhancer reprogramming is a defining feature of Ewing sarcoma. Second, inter-individual DNA methylation differences in Ewing sarcoma samples identified a continuous disease spectrum with two dimensions: the strength of the EWS-FLI1 regulatory signature and the balance of mesenchymal versus stem cell regulatory signatures. Third, we observed substantial epigenetic heterogeneity within individual tumors. In summary, our study provides a comprehensive assessment of epigenetic heterogeneity in Ewing sarcoma, highlighting its importance as a source of variability for genetically homogeneous tumors.
2017-01-30 | GSE89026 | GEO
Project description: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. Gene Ontology analysis of genes differentially methylated in Ewing sarcoma samples showed a significant enrichment of developmental genes. Membrane and cell signal genes were also enriched, among those, 11 were related to caveola formation. We identified differential hypermethylation of CpGs located in the body and S-Shore of the PTRF gene in Ewing sarcoma that correlated with its repressed transcriptional state. Reintroduction of PTRF/Cavin-1 in Ewing sarcoma cells revealed a role of this protein as a tumor suppressor. Restoration of caveolae in the membrane of Ewing sarcoma cells, by exogenously reintroducing PTRF, disrupts the MDM2/p53 complex, which consequently results in the activation of p53 and the induction of apoptosis.
2016-11-28 | GSE89041 | GEO
Project description:To explore the sensitivity of ARID1A-KO cells to APR-246
2019-01-28 | GSE122925 | GEO