Homo sapiens
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PROVIDER: PRJNA279535 | ENA |
REPOSITORIES: ENA
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Project description:Expression data of human neuroblastoma IMR32 cells treated with the DHODH inhibitor Teriflunomide [118 ￂﾵM]
2015-06-18 | E-GEOD-67338 | ExpressionAtlas
Project description:Neuroblastoma is an embryonal tumor which originates from neural crest progenitor cells that fail to differentiate along their predefined route to sympathetic neurons or sympatho-adrenergic adrenal cells. It is the most common extracranial tumor of childhood and accounts for 15% of all childhood cancer deaths. Especially patients suffering from high grade or relapsed neuroblastoma have poor outcome in spite of aggressive treatment regimens including autologous stem cell transplantation. Those patients are in urgent need of additional effective therapies which demands the development of targeted approaches. Dihydroorotatedehydrogenase (DHODH) is the fourth enzyme of the pyrimidine synthesis pathway which oxidizes dihydroorotate to orotate. In recent past it became a potential drug target for cancer treatment because of its keyrole in processing essential pyrimidine nucleotides. On the basis of the existing data, functional inhibition of DHODH is considered to be promising therapeutic option for several tumor entities like advanced colorectal, breast or lung-cancers. Leflunomide is an established drug in treatment of the autoimmune diseases rheumatoid arthritis and multiple sclerosis. In the liver Leflunomide becomes converted to its active metabolite called Teriflunomide, which inhibits the activity of DHODH directly. In recent times Leflunomide is also used for therapy against the Cytomegalovirus and the BK virus. Also for Melanoma was shown recently a decreased growth rate due to Leflunomide treatment in a zebrafish and a mouse model. As Melanoma is a malignant tumor of the skin, which derives also from neural crest progenitor cells, a coherent investigation of effictivity of Leflunomide in neuroblastoma celllines showed first promising results. The aim of our study was to reanalyse the effectivity of Leflunomide in Neuroblastoma and to shed further light in its biological mode of action. Three+B52 biological samples of the human neuroblastoma cell line IMR32 were treated with DMSO or Teriflunomide [118 ￂﾵM]
2015-03-27 | E-GEOD-67338 | biostudies-arrayexpress
Project description:IMR32 neuroblastoma cells were treated with ISX, a novel GLI1 inducing HDAC-inhibitor
2021-04-28 | E-MTAB-10249 | biostudies-arrayexpress
Project description:Despite intensive therapy, children with high-risk neuroblastoma are at risk of treatment failure. We applied a multi-omic system approach to evaluate metabolic vulnerabilities in human neuroblastoma. We combined metabolomics, CRISPR screening and transcriptomic data across >700 solid tumor cell lines and identified dihydroorotate dehydrogenase (DHODH), a critical enzyme in pyrimidine synthesis, as a potential treatment target. Of note, DHODH inhibition is currently under clinical investigation in patients with hematologic malignancies. In neuroblastoma, DHODH expression was identified as an independent risk factor for aggressive disease, and high DHODH levels correlated to worse overall and event-free survival. A subset of tumors with the highest DHODH expression was associated with a dismal prognosis, with a 5-year survival of <10%. In xenograft and transgenic neuroblastoma mouse models treated with the DHODH inhibitor brequinar, tumor growth was dramatically reduced, and survival was extended. Furthermore, brequinar treatment was shown to reduce the expression of MYC targets in three different neuroblastoma models in vivo. A combination of brequinar and temozolomide was curative in the majority of transgenic TH-MYCN neuroblastoma mice, indicating a highly active clinical combination therapy. Overall, DHODH inhibition combined with temozolomide has therapeutic potential in neuroblastoma and we propose this combination for clinical testing.
2022-07-27 | GSE209811 | GEO
Project description:Despite intensive therapy, children with high-risk neuroblastoma are at risk of treatment failure. We applied a multi-omic system approach to evaluate metabolic vulnerabilities in human neuroblastoma. We combined metabolomics, CRISPR screening and transcriptomic data across >700 solid tumor cell lines and identified dihydroorotate dehydrogenase (DHODH), a critical enzyme in pyrimidine synthesis, as a potential treatment target. Of note, DHODH inhibition is currently under clinical investigation in patients with hematologic malignancies. In neuroblastoma, DHODH expression was identified as an independent risk factor for aggressive disease, and high DHODH levels correlated to worse overall and event-free survival. A subset of tumors with the highest DHODH expression was associated with a dismal prognosis, with a 5-year survival of <10%. In xenograft and transgenic neuroblastoma mouse models treated with the DHODH inhibitor brequinar, tumor growth was dramatically reduced, and survival was extended. Furthermore, brequinar treatment was shown to reduce the expression of MYC targets in three different neuroblastoma models in vivo. A combination of brequinar and temozolomide was curative in the majority of transgenic TH-MYCN neuroblastoma mice, indicating a highly active clinical combination therapy. Overall, DHODH inhibition combined with temozolomide has therapeutic potential in neuroblastoma and we propose this combination for clinical testing.
2022-07-27 | GSE209812 | GEO
Project description:The aim of this study is to compare human transcriptomes based on NGS (RNA-seq). The transcriptome of neuroblastoma IMR32 was compared with the transcriptome of neuroblastoma IMR32, which was differentiated for 16 days in the presence of 2.5 mkM BrdU. Methods. Human mRNA profiles of 16-day differentiation of IMR32 neuroblastoma and non-differentiated IMR32 neuroblastoma were obtained by deep three-fold sequencing using Illumina NovaSeq. The mapping is read into the human genome (hg38) using the hisat program. On average, about 89-90% of all data received was unambiguously aligned in each library. The htseq-count utility has counted the number of reads that have been matched against known genes (ncbi - entrezID). The obtained values (cpm - countpermillion) for each gene for each library were combined into one matrix for further analysis. Results: Using an optimized data analysis workflow, we matched about 30 million sequence reads per sample to the human genome (hg38). Filtration, normalization by the method (TMM), variance estimation and differentially expressed genes estimation were performed in the edgeR module. Genes in which the cpm did not exceed 1 in any three libraries were considered low expressing.
2020-12-18 | GSE161759 | GEO
Project description:GSK-inhibitor treatment in IMR32 neuroblastoma cell line
| PRJEB4227 | ENA
Project description:Gene expression after treatment with Nutlin 3a (Nut) and Selinexor (Sel) in Neuroblastoma Cells RNA from NBAT1 knockdown and its respective control (Csh) SH-SY5Y cells after nutlin-3a (10 uM) or DMSO treatement were isolated and sequenced using BGI DNBseq. IMR32 cells were treated with either DMSO, Nut, Sel and with both Nul and Sel and RNA was isolated following treatemnet We observed that knowndown of the NBAT1 lncRNA in NB cells leads to perturbation of the P53 mediated gene expression. Combination treatment with with Nul and Sel in IMR32 cells leads to higher P53 mediated gene expression.
2020-12-23 | GSE137366 | GEO
Project description:The aim of this study is to compare the NGS-derived profiling of human transcriptome (RNA-seq) in wild-type neuroblastoma cells with neuroblastoma transcript with a high level of expression of Oct-1 transcription factor and evaluate the effect of Oct-1 transcription factor on the regulation of nerve cell differentiation. Methods: Human mRNA profiles of 16-day differentiating wild-type neuroblastoma IMR32 and neuroblastoma IMR32 with overexpression primate-specific isoform of transcription factor Oct-1 were generated by deep sequencing, in triplicate, using Illumina NovaSeq. Mapping reads to the human genome (hg38) using hisat program. On average, about 89-90% of all received data was uniquely aligned in each library. The htseq-count utility calculated the number of reads that were mapped to known genes (ncbi - entrezID). The obtained values (cpm - countpermillion) for each gene for each library were combined into one matrix for further analysis. Results: Using an optimized data analysis workflow, we mapped about 30 million sequence reads per sample to the human genome (hg38). Filtration, normalization by the method (TMM), variance estimation and evaluation of differentially expressed genes were performed in the edgeR module. Genes in which cpm did not exceed 1 in any three libraries were considered low-expressing. After filtering the low-expressing genes, 15,108 entries remained. RNA-Seq data confirmed that approximately 8% of the transcripts showed differential expression between the WT and Oct-1 overexpressed differentiating neuroblastoma cells, with FDR<0.01 (p-value adjusted for multiple testing).
2021-03-30 | GSE153980 | GEO
Project description:Transcriptional profiling of neuroblastoma cell line expressing the PML1 isoform. Two-condition experiment: PML1 IMR32 vs empty vector IMR32. Two biological replicates, dye-swapped.
2016-08-09 | E-GEOD-78086 | biostudies-arrayexpress