Identification of differential gene expression uging endoscopic biliary brushings
Whole genome RNA expression profiling of endoscopic biliary brushings provides data suitable for biomarker discovery in cholangiocarcinoma.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Attenuated adenosine-to-inosine editing of microRNA-376a* promotes invasiveness of glioblastoma cells.
Cell line
View SamplesGliomas are the most devastating of primary adult malignant brain tumors. These tumors are highly infiltrative and can arise from cells with extensive self-renewal capability and chemoresistance, frequently termed glioma-propagating cells (GPCs). GPCs are thus the plausible culprits of tumor recurrence. Treatment strategies that eradicate GPCs will greatly improve disease outcome. Such findings support the use of GPCs as in vitro cellular systems for small molecule screening. However, the nuances in utilizing GPCs as a cellular screening platform are not trivial. These slow-growing cells are typically cultured as suspension, spheroid structures in serum-free condition supplemented with growth factors. Consequently, replenishment of growth factors throughout the screening period must occur to maintain cells in their undifferentiated state, as the more lineage-committed, differentiated cells are less tumorigenic. We will present a case study of a small molecule screen conducted with GPCs and explain how unique sphere activity assays were implemented to distinguish drug efficacies against the long-term, self-renewing fraction, as opposed to transient-amplifying progenitors, latter of which are detected in conventional viability assays. We identified Pololike kinase 1 as a regulator of GPC survival. Finally, we leveraged on public glioma databases to illustrate GPC contribution to disease progression and patient survival outcome.
Glioma-propagating cells as an in vitro screening platform: PLK1 as a case study.
Specimen part, Disease stage
View SamplesGenes specific to Sox9+ pancreatic progenitors were identified by comparing the gene expression in embryonic and adult Sox9+ cells.
A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation.
Specimen part
View SamplesSeveral biological pathways can be under the regulation of miRNAs. These pathways can be indentified by the enforced expression of a miRNA and analysing the expression data for enrichment of specific pathways represented among the genes differentially expressed upon miRNA overexpression.
Attenuated adenosine-to-inosine editing of microRNA-376a* promotes invasiveness of glioblastoma cells.
Cell line
View SamplesEnforced expression of miRNAs in cells leads to down-regulation of several mRNAs which harbour binding sites in their 3'UTRs for the overexpressed miRNA and represent potential target genes of the miRNA
Attenuated adenosine-to-inosine editing of microRNA-376a* promotes invasiveness of glioblastoma cells.
Cell line
View SamplesEnforced expression of miRNAs in cells leads to down-regulation of several mRNAs, which harbour binding sites in their 3'UTRs for the overexpressed miRNA and represent potential target genes of the miRNA
Attenuated adenosine-to-inosine editing of microRNA-376a* promotes invasiveness of glioblastoma cells.
Cell line
View SamplesBrain tumors are among the most malignant cancers and can arise from neural stem cells or oligodendrocyte progenitor cells (OPCs). Glioma-propagating cells (GPCs) that have stem-like properties have been derived from tumor variants such as glioblastoma multiforme (GBM) and oligodendroglial tumors, the latter being more chemosensitive with better prognosis. It has been suggested that such differences in chemosensitivity arise from the different profiles of OPCs versus neural stem cells. We thus explored if GPCs derived from these glioma variants can serve as reliable in vitro culture systems for studies. We utilized gene expression analyses, since GBM and oligodendrogliomas can be molecularly classified. Accordingly, we derived a gene signature distinguishing oligodendroglial GPCs from GBM GPCs collated from different studies, which was enriched for the Wnt, Notch and TGF-beta pathways. Using a novel method in glioma biology, the Connectivity Map, we mapped the strength of gene signature association with patient gene expression profiles in 2 independent glioma databases [GSE16011, http://caintegrator-info.nci.nih.gov/rembrandt]. Our gene signature consistently stratified survival in glioma patients. This data would suggest that in vitro low passage GPCs are similarly driven by transcriptomic changes that characterize the favorable outcome of oligodendrogliomas over GBM. Additionally, the gene signature was associated with the 1p/19q co-deletion status, the current clinical indicator of chemosensitivity. Our gene signature detects molecular heterogeneity in oligodendroglioma patients that cannot be accounted for by histology or the 1p/19q status alone, and highlights the limitation of morphology-based histological analyses in tumor classification, consequently impacting on treatment decisions.
Progenitor-like traits contribute to patient survival and prognosis in oligodendroglial tumors.
Sex, Age, Disease stage, Subject
View SamplesSpinal cord injury leads to impaired motor and sensory functions. After spinal cord injury there is a an initial phase of hypo-reflexia followed by a developing hyper-reflexia, often termed spasticity. Previous studies have suggested a relationship between the reappearence of plateau potentials in motor neurons and the development of spasticity after spinalizaion. To understand the moleclar mechanism behind this pheneomona we examined the transcriptional response of the motor neurons after spinal cord injury as it progress over time.
Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury.
Sex, Specimen part
View SamplesMutations in the parkin gene, which encodes a ubiquitin ligase, are a major genetic cause of parkinsonism. Interestingly, parkin also plays a role in cancer as a putative tumor suppressor, and the gene is frequently targeted by deletion and inactivation in human malignant tumors. Here, we investigated a potential tumor suppressor role for parkin in gliomas. We found that parkin expression was dramatically reduced in glioma cells. Restoration of parkin expression promoted G1 phase cell cycle arrest and mitigated the proliferation rate of glioma cells in vitro and in vivo. Notably, parkin-expressing glioma cells showed a reduction in levels of cyclin D1, but not cyclin E, and a selective downregulation of Akt serine-473 phosphorylation and VEGF receptor levels. In accordance, cells derived from a parkin null mouse model exhibited increased levels of cyclin D1, VEGF receptor and Akt phosphorylation and divided significantly faster when compared with wild type cells, with suppressionof these changes following parkin re-introduction. Clinically, analysis of parkin pathway activation was predictive for the survival outcome of glioma patients. Taken together, our study provides mechanistic insight into the tumor suppressor function of parkin in brain tumors, and suggests that measurement of parkin pathway activation may be used clinically as a prognostic tool in brain tumor patients.
Parkin pathway activation mitigates glioma cell proliferation and predicts patient survival.
Cell line, Treatment
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