Project description:Glioblastoma multiforme is the most lethal form of glioma with an overall survival at 5 years nearly null, which mainly results from acquired resistance to therapies. Large scale sequencing studies on human cancer biopsies defined IRE1alpha as the fifth most oncogenic mutated kinase in human cancer. IRE1alpha is a major component of the Unfolded Protein Response signaling and increasing evidence suggests that it is a central player in GBM development.
Project description:GL261-derived glioblastoma stem cells (GSCs) form aggressive tumors when implanted into the brains of C57BL/6 mice. We used spatial transcriptomics to analyze brain sections of tumor-bearing C57BL/6 mice at 28 days post-implantation
Project description:Glioblastoma multiforme is one of the most devastating cancers and presents unique challenges to therapy due to its aggressive behaviour. Cancer stem cells have been described to be the only cell population with tumorogenic capacity in glioblastoma. Therefore, effective therapeutic strategies targeting these cells may be beneficial. We have established different cultures of glioblastoma stem cells (GSCs) derived from surgical specimens and found that, after induction of differentiation, NFκB was activated, which allows intermediate tumor precursor cells to remain cycling. We also showed that blockade of NFκB signaling in differentiating GSCs by different genetic strategies or treatment with small molecule inhibitors, promoted replication arrest, progression to a mature phenotype, mainly neuronal cells, and senescence. This effect was partly mediated by downregulation of the NFκB target gene cyclin D1. Furthermore, intravenous treatment of immunodeficient mice bearing human GSC-derived tumors with a novel small-molecule inhibitor of the NFκB pathway induced senescence of tumor cells but no ultraestructural alterations of the brain parenchymal cells were detected. These findings reveal that activation of NFκB may keep differentiating GSCs from acquiring a mature postmitotic phenotype, thus allowing cell proliferation, and support the rationale for therapeutic strategies aimed at promoting premature senescence in GSCs undergoing differentiation. Gene expression in differentiated cells relative to stem cells in three different glioblastoma cultures
Project description:To investigate the effects of PTEN activity on gene expression in 3D cultured glioblastoma cells and the contributions of PTEN's lipid and protein phosphatase activities to these effects. We expressed wild type PTEN, a catalytically dead mutant (C124S) or mutants selectively lacking protein or lipid phosphatase activity (Y138L and G129E respectively) in U87MG cells at physiological levels by transient unselected polyclonal lentiviral transduction. Cells were then seeded into 3D matrigel and RNA prepared after 15 hours.
Project description:Transcriptional profiles on different yeast strain mutants (DEgd2/1, DEgd2/Btt1)were identified by microarray analysis comparing total mutant RNA vs wild type RNA.
Project description:To further understand the molecular mechanisms in the development of glioblastoma cancer, we employed this microarray to identify lncRNAs associated with glioblastoma cancer.
Project description:Treatment with carborane bearing amino acid on U87 cells showed cytostatic effect followed by cell death. We used microarrays to investigate the effect of the carborane bearing amino acid on U87 cell gene expression profile and explore the mechanism.