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E-GEOD-71224 - Inhibition of 13-cis retinoic acid-induced gene expression of reactive-resistance genes by thalidomide in glioblastoma tumours in vivo

Status
Released on 23 July 2015, last updated on 20 August 2015
Organism
Homo sapiens
Samples (12)
Array (1)
Protocols (7)
Description
The cell differentiation potential of 13-cis retinoic acid (RA) has not succeeded in the clinical treatment of glioblastoma (GBM) so far. However, RA may also induce the expression of disistance genes such as HOXB7 which can be suppressed by Thalidomide (THAL). Therefore, we tested if combined treatment with RA+THAL may inhibit growth of glioblastoma in vivo. Treatment with RA+THAL but not RA or THAL alone significantly inhibited tumour growth. The synergistic effect of RA and THAL was corroborated by the effect on proliferation of glioblastoma cell lines in vitro. HOXB7 was not upregulated but microarray analysis validated by real-time PCR identified four potential resistance genes (IL-8, HILDPA, IGFBPA, and ANGPTL4) whose upregulation by RA was suppressed by THAL. Furthermore, genes coding for small nucleolar RNAs (snoRNA) were identified as a target for RA for the first time, and their upregulation was maintained after combined treatment. Pathway analysis showed upregulation of the Ribosome pathway and downregulation of pathways associated with proliferation and inflammation. Combined treatment with RA + THAL delayed growth of GBM xenografts and suppressed putative resistance genes associated with hypoxia and angiogenesis. This encourages further pre-clinical and clinical studies of this drug combination in GBM. The purpose was to study differential gene expression in glioblastoma xenografts after treatment with 13-cis retinoic acid (RA), thalidomide (Thal) or a combination of both drugs.
Experiment type
transcription profiling by array 
Contacts
Carsten Sticht <geo@ncbi.nlm.nih.gov>, Carsten Herskind, Dusan Milanovic
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-71224.idf.txt
Sample and data relationshipE-GEOD-71224.sdrf.txt
Raw data (1)E-GEOD-71224.raw.1.zip
Processed data (1)E-GEOD-71224.processed.1.zip
Array designA-GEOD-17556.adf.txt
Links