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GSE12581
Mus musculus
16 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used the microarrays to obtain the cancerous signatures of T-cell, B-cell, erythroid and megakaryoblastic leukemias in mice.
Publication Title
Gene profiling of the erythro- and megakaryoblastic leukaemias induced by the Graffi murine retrovirus.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 21 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mutations in Hedgehog (Hh) pathway genes, leading to constitutive activation of Smoothened (Smo), occur in sporadic medulloblastoma, the most common brain cancer in children. Antagonists of Smo induce tumor regression in mouse models of medulloblastoma and hold great promise for targeted therapy for this tumor. However, acquired resistance has emerged as one of the major challenges of targeted cancer therapy. Here, we describe novel mechanisms of acquired resistance to Smo antagonists in medulloblastoma. NVP-LDE225, a potent and selective Smo antagonist, inhibits Hh signaling and induces tumor regressions in allograft models of medulloblastoma that are driven by mutations of Patched (Ptch), a tumor suppressor in the Hh pathway. However, after long-term treatment, evidence of acquired resistance was observed. Genome-wide profiling of resistant tumors revealed distinct mechanisms to evade the inhibitory effects of Smo antagonists. Chromosomal amplification of Gli2, a downstream effector of Hh signaling, reactivated Hh signaling and restored tumor growth. Analysis of pathway gene-expression signatures selectively deregulated in resistant tumors identified increased phosphoinosite-3-kinase (PI3K) signaling as another potential resistance mechanism. Probing the functional relevance of increased PI3K signaling, we showed that the combination of NVP-LDE225 with the dual PI3K/mTOR inhibitor NVP-BEZ235 markedly delayed the development of resistance. Our findings have important clinical implications for future treatment strategies in medulloblastoma.
Publication Title
Interfering with resistance to smoothened antagonists by inhibition of the PI3K pathway in medulloblastoma.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina Genome Analyzer II
Description
OBJECTIVE: MicroRNAs (miRNAs, miRs), a class of small non-coding RNA molecules, are posttranscriptional regulators involved in a plethora of cellular functions and have been proposed as potential therapeutic targets in various diseases, including rheumatoid arthritis (RA). In this study, we sought to discover novel miR associations in synovial fibroblasts (SFs), a key cell type mediating RA pathogenesis, by performing miR expression profiling on cells isolated from the human TNF transgenic mouse model (TghuTNF or Tg197). METHODS: miR expression in SFs isolated from 8-week-old, fully diseased TghuTNF and WT littermate control mice were determined by deep sequencing of small RNAs and the arthritic profile was established by pairwise comparisons of the two groups. qRT-PCR analysis was utilised for profile validation purposes and miR quantitation in patient SFs. Dysregulated miR target genes and pathways were predicted via bioinformatic algorithms. Overall design: Synovial Fibroblasts isolated from TghuTNF mice (2 x biological replicates) and control WT littermate mice (2 x biological replicates)
Publication Title
Identification of microRNA-221/222 and microRNA-323-3p association with rheumatoid arthritis via predictions using the human tumour necrosis factor transgenic mouse model.
Sample Metadata Fields
Specimen part, Cell line, Subject
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