Ontology highlight
ABSTRACT:
PROVIDER: PRJNA116681 | ENA |
REPOSITORIES: ENA
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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:Our compound (PRIMA) selectively kills tumor cells expressing mutant p53. Here in our study we decided to investigate the impact of our compound on the transcriptome of Saos2 cells lacking p53. We plated Saos-2 cells, and treated them with our compound for 6h or 12h. We then harvested the cells, extracted the RNA, and followed the protocol to run affymetrix array to analyse the impact of our drug on the whole transcriptome of cells lacking p53.
2009-04-15 | E-GEOD-15367 | biostudies-arrayexpress
Project description:Our compound (PRIMA) selectively kills tumor cells expressing mutant p53. Here in our study we decided to investigate the impact of our compound on the transcriptome of p53 mutant-expressing cells, Saos2-His273. We plated Saos-2-His273 cells and treated them with our compound for 6h or 12h. We then harvested the cells, extracted the RNA, and followed the protocol to run affymetrix array to analyse the impact of our drug on the whole transcriptome of cells expressing mutant p53.
2009-04-15 | E-GEOD-15368 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE15367: Expression analysis of Saos-2 p53-null cells GSE15368: Expression analysis of Saos-2 cells expressing p53-His273 Refer to individual Series
2009-04-15 | E-GEOD-15658 | biostudies-arrayexpress
Project description:H1299 cells and Saos-2 cells (p53 null cells) were transfected with Flag vector, Flag-p53 WT or Flag-p53 SA.
2010-10-14 | E-MEXP-2556 | biostudies-arrayexpress
Project description:Our compound (PRIMA) selectively kills tumor cells expressing mutant p53. Here in our study we decided to investigate the impact of our compound on the transcriptome of Saos2 cells lacking p53.
2009-04-15 | GSE15367 | GEO
Project description:Our compound (PRIMA) selectively kills tumor cells expressing mutant p53. Here in our study we decided to investigate the impact of our compound on the transcriptome of p53 mutant-expressing cells, Saos2-His273.
2009-04-15 | GSE15368 | GEO
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