Project description:We performed microarray analysis in order to evaluate the combination effect of the mitochondrial matrix chaperone inhibitor gamitrinib-triphenylphosphonium (G-TPP) and Liver X receptor agonist LXR623 on gene expression in stem cell like glioma cells (NCH644).
Project description:We used microarray global gene expression profiling to investigate the effect caused by neuro-condition media of MSCs on the growth and pluripotency of glioma stem cells. The effect was specifically investigated for cell cycle arrest, cell differentiation, invasion and self renewal ability of glioma stem cells,
Project description:The experiment was carried out in triplicates in untreated, etomoxir treated and etomoxir plus beta-hydroxybutyrate (3HB) treated conditions. MES83 (Glioma-derived Mesenchymal stem cells) were either untreated or treated with 40uM of etomoxir alone or in combination with 0.5mM of beta-hydroxybutyrate for 48 hrs. The cells were collected and total RNA was extracted and the library was prepared according to the manufacturer protocol.
Project description:Spatiotemporal analyses using brain slice culture and brain clearing demonstrated that human induced pluripotent stem cell-derived neural stem cells (iPSC-NSCs) possess higher tumor-trophic migratory capacity than fetal NSCs, adipose tissue and bone marrow derived mesenchymal stem cells (MSCs). NSCs expressing prodrug converting enzyme fusion gene exhibited strong anti-tumor effect for glioma stem cell in vivo models. The present research concepts may become a platform of cell-based gene therapy for glioma.
Project description:Elevated aldehyde dehydrogenase (ALDH) activity correlates with poor outcome for many solid tumors as ALDHs potentially regulate cell proliferation and chemoresistance of cancer stem cells (CSCs). Accordingly, potent and selective inhibitors of key ALDHs may represent a novel CSC-directed treatment paradigm for ALDH+ cancer types. Of the many ALDH isoforms, we and others have implicated the elevated expression of ALDH1A3 in mesenchymal glioma stem cells (MES GSCs) as a target for the development of novel therapeutics. To this end, we used our structure of human ALDH1A3 combined with in silico modeling to identify a selective, active-site inhibitor of ALDH1A3. The lead compound, MCI-INI-3, is a selective competitive inhibitor of human ALDH1A3 and shows poor inhibitory effect on the structurally related isoform ALDH1A1. Mass spectrometry-based cellular thermal shift analysis revealed that ALDH1A3 is the primary binding protein for MCI-INI-3 in MES GSC lysates. The inhibitory effect of MCI-INI-3 on retinoic acid biosynthesis is comparable with that of ALDH1A3 knockout, suggesting that effective inhibition of ALDH1A3 is achieved with MCI-INI-3. Further development is warranted to characterize the role of ALDH1A3 and retinoic acid biosynthesis in glioma stem cell growth and differentiation.
Project description:Glioblastoma multiforme (GBM), the most common and malignant type of glioma, is characterized by a poor prognosis and the lack of an effective treatment, which are due to a small sub-population of cells with stem-like properties, termed glioma stem cells (GSCs). The term M-bM-^@M-^\multiformeM-bM-^@M-^] describes the histological feature of this tumor, i.e. the cellular and morphological heterogeneity. At the molecular level multiple layers of alterations may reflect this heterogeneity providing together the driving force of tumor initiation and development. In order to decipher the common M-bM-^@M-^\signatureM-bM-^@M-^] of the ancestral GSC population, we examined 5 already characterized GSC lines evaluating their copy number alterations using a genome-wide approach. Genomic DNA was isolated from 5 Glioma Stem Cell (GSC) lines. Each sample was labeled with Cy3 dye and then hybridized against the same commercial reference DNA labeled in Cy5.