Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

PML1: IMR32 vs empty vector IMR32

ABSTRACT: Transcriptional profiling of neuroblastoma cell line expressing the PML1 isoform. Two-condition experiment: PML1 IMR32 vs empty vector IMR32. Two biological replicates, dye-swapped.

ORGANISM(S): Homo sapiens

SUBMITTER: Paolo Salomoni

PROVIDER: E-GEOD-78086 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A Promyelocytic Leukemia Protein-Thrombospondin-2 Axis and the Risk of Relapse in Neuroblastoma.

Dvorkina Maria M Nieddu Valentina V Chakelam Shalini S Pezzolo Annalisa A Cantilena Sandra S Leite Ana Paula AP Chayka Olesya O Regad Tarik T Pistorio Angela A Sementa Angela Rita AR Virasami Alex A Barton Jack J Montano Ximena X Lechertier Tanguy T Brindle Nicola N Morgenstern Daniel D Lebras Morgane M Burns Alan J AJ Saunders Nigel J NJ Hodivala-Dilke Kairbaan K Bagella Luigi L De The Hugues H Anderson John J Sebire Neil N Pistoia Vito V Sala Arturo A Salomoni Paolo P

Clinical cancer research : an official journal of the American Association for Cancer Research 20160413 13

<h4>Purpose</h4>Neuroblastoma is a childhood malignancy originating from the sympathetic nervous system with a complex biology, prone to metastasize and relapse. High-risk, metastatic cases are explained in part by amplification or mutation of oncogenes, such as MYCN and ALK, and loss of tumor suppressor genes in chromosome band 1p. However, it is fundamental to identify other pathways responsible for the large portion of neuroblastomas with no obvious molecular alterations.<h4>Experimental desi ...[more]

PMID: 27076624

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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]

Dataset Information

PML1: IMR32 vs empty vector IMR32

Publications

A Promyelocytic Leukemia Protein-Thrombospondin-2 Axis and the Risk of Relapse in Neuroblastoma.

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