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GSE19657
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- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Negative-pressure wound therapy (NPWT) is widely used to improve skin wound healing and to accelerate wound bed preparation. Although NPWT has been extensively studied as a treatment for deep wounds, its effect on epithelialization of superficial dermal wounds remains unclear. To clarify the effect of NPWT on reepithelialization, we applied NPWT on split- thickness skin graft donor sites from the first postoperative day (POD) to the seventh POD. Six patients took part in the study and two samples were obtained from each. The first biopsy sample was taken at elective surgery before split-thickness skin grafting and the second one during reepithelialization on the seventh POD. In all 12 samples (eight from four NPWT patients, and four from two control patients) were collected for this study. From each sample, we carried out a comprehensive genome-wide microarray analysis. Data from patients receiving NPWT were compared groupwise with data from those not receiving NPWT.
Publication Title
Gene expression profiling of negative-pressure-treated skin graft donor site wounds.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In order to clarify the human response of re-epithelialization, we biopsied split-thickness skin graft donor site wounds immediately before and after harvesting, as well as during the healing process 3 and 7 days thereafter. Altogether 25 biopsies from 8 patients qualified for the study. All samples were analysed by genome-wide microarrays. Here we identified the genes associated with normal skin re-epithelialization on time-scale, and organized them by similarities according to their induction or suppression patterns during wound healing.
Publication Title
Human skin transcriptome during superficial cutaneous wound healing.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 54 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Down syndrome (DS) is the most frequent cause of human congenital mental retardation. Cognitive deficits in DS result from perturbations of normal cellular processes both during development and in adult tissues, but the mechanisms underlying DS etiology remain poorly understood. To assess the ability of iPSCs to model DS phenotypes, as a prototypical complex human disease, we generated bona-fide DS and wild-type (WT) non-viral iPSCs by episomal reprogramming. DS iPSCs selectively overexpressed chromosome 21 genes, consistent with gene dosage, which was associated with deregulation of thousands of genes throughout the genome. DS and WT iPSCs were neurally converted at >95% efficiency, and had remarkably similar lineage potency, differentiation kinetics, proliferation and axon extension at early time points. However, at later time points DS cultures showed a two-fold bias towards glial lineages.
Publication Title
Integration-free induced pluripotent stem cells model genetic and neural developmental features of down syndrome etiology.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Cell line
View Samples- Mus musculus
- 31 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Neuroblastoma is an embryonal neoplasm that remains of dramatic prognosis in its aggressive forms. Activating mutations of the ALK tyrosine kinase receptor have been identified in sporadic and familial cases of this cancer. We generated knock-in mice carrying the two most frequent Alk mutations observed in neuroblastoma patients. We used microarrays to detail the global programme of gene expression underlying the impact of ALK mutations on neuroblastoma formation in a MYCN amplified background.
Publication Title
Activated Alk triggers prolonged neurogenesis and Ret upregulation providing a therapeutic target in ALK-mutated neuroblastoma.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
Primary mammary gland stromal fibroblasts from pubertal SHARPIN-deficient cpdm/cpdm -mice and their littermate controls Overall design: mRNA seq data from 3 wt and 3 Sharpincpdm mouse mammary gland stromal fibroblast cell samples
Publication Title
SHARPIN regulates collagen architecture and ductal outgrowth in the developing mouse mammary gland.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples