Gene expression profiling of patient derived glioblastoma tumor tissues
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ABSTRACT: To study the gene expression profile of patient derived glioblastoma tissues and perform cross platform analysis with metabolite data derived from matching tissues
Project description:Dendritic cell (DC)-based immunotherapy against glioblastoma multiforme is a novel treatment hope. Glioblastoma stem-like cells are, however, potentially causing immunoresistance. Glioblastoma cells cultured as gliomaspheres show a stem-like phenotype as opposed to classical adherent culture. They are thus a promising antigen source to specifically target glioblastoma stem-like cells via DC therapy and so overcome immunoresistance. Here we study the importance of gliomasphere-specific. Methodologically, we used 7 gliomaspheres, 3 of them patient-derived, as model system. Gliomasphere-specific protein expression was explored via quantitative proteomics.
Project description:The transcriptome of human glioblastoma stem cells (GSCs) isolated from brain tumours of four patients (#5, #7, #8, #9) was comparatively analysed among them and in respect to common established human glioblastoma cell lines (U87MG, U373MG) and non-transformed human neural stem cells (NSCs). Cells were grown under optimal culture conditions, total RNA carefully isolated form the seven cell samples, and then subjected to global transcriptomic analysis in Array
Project description:Gene expression microarray profiling on glioblastoma intra-tumour regions, where the study hypothesis states that the infiltrative tumour margin harbours a distinct transcriptomic profile from all non-infiltrative tumour regions. Data is from three patients (patient 9, 14 and 15) where regions 1-4 per patient were obtained from non-infiltrative intra-tumour regions, and region 5 was obtained from the infiltrative margin. All patients underwent craniotomy with intra-operative image guidance and visualization of 5ALA induced fluorescence to obtain infiltrative margin biopsies.
Project description:Here, we analyzed patient-derived glioblastoma xenografts generated in the mouse brain that give rise to three different histological phenotypes: (i) a highly invasive phenotype (ii) a highly angiogenic phenotype and (iii) an intermediate phenotype. Cell type-specific transcriptomic profiles of tumor and stromal endothelial cells were analyzed to reveal phenotype-specific gene expression patterns and the reciprocal crosstalk between tumor and stromal endothelial cells. This part of the study contains the analysis of the patient-derived tumor cells. The analysis of the stromal endothelial cells of the host mice is found under E-MTAB-3949.
Project description:Here, we analyzed patient-derived glioblastoma xenografts generated in the mouse brain that give rise to three different histological phenotypes: (i) a highly invasive phenotype (ii) a highly angiogenic phenotype and (iii) an intermediate phenotype. Cell type-specific transcriptomic profiles of tumor and stromal endothelial cells were analyzed to reveal phenotype-specific gene expression patterns and the reciprocal crosstalk between tumor and stromal endothelial cells. This part of the study contains the analysis of the stromal endothelial cells of the host mice. The analysis of the patient-derived tumor cells is found under E-MTAB-3948.
Project description:The gene expression profiles of two groups of triplicate human glioblastoma (GBM) xenografts grown in immunodeficient rats were compared. The first group of xenografts was derived from a patient biopsy with Epidermal Growth Factor Receptor (EGFR) amplification which grows highly invasive and is independent of angiogenesis. The second group was obtained by introducing a dominant-negative EGFR mutant into the tumor cells, leading to a progression of the tumors to an angiogenic phenotype associated with a transition from a proneural to a mesenchymal GBM molecular subtype.
Project description:We found that RPL22L1 isoform switch is regulated by SRSF4 protein and identified a small molecule compound FG1059, that inhibits this process and decreases tumor growth. To confirm that FG1059 affects RPL22L1 due to the inhibition of SRSF protein phosphorylation we studied the phosphoproteome of patient-derived GBM neurospheres treated with FG1059 for 0, 3, 6 and 12 hours.
Project description:Treatment of cancer cells with anti-cancer drugs often fails to achieve complete remission. Yet, such drug treatments may induce alteration in the tumor’s gene expression patterns, including those of Cancer/Testis Antigens (CTA). The degradation products of such antigens can be presented as HLA peptides on the surface of the tumor cells and be developed into anti-cancer immunotherapeutics. For example, the DNA methyl transferase inhibitor, 5-aza-2'-deoxycytidine (Decitabine) has limited anti-tumor efficacy, yet it induces the expression of many genes, including CTAs that are normally silenced in the healthy adult tissues. In this study, the presentation of many new HLA peptides derived from CTAs and induced by Decitabine was demonstrated in three human Glioblastoma cell lines. Such presentation of CTA-derived HLA peptides can be exploited for development of new treatment modalities, combining drug treatment with anti-CTA targeted immunotherapy. The Decitabine-induced HLA peptidomes include many CTAs that are not normally detected in healthy tissues or in cancer cells, unless treated with the drug. In addition, the study included large-scale analyses of the simultaneous effects of Decitabine on the transcriptomes, proteomes and HLA peptidomes of the human Glioblastoma cells. It demonstrates the poor correlations between these three levels of gene expression, both in their total levels and in their response to the drug.
Project description:Glioblastomas grow in a rich neurochemical mileu, but targeting neurochemical signaling as a potential therapeutic avenue for these incurable tumors has been underexplored. Thus, we probed patient derived glioblastoma stem cells with a focused library of neurochemicals, to identify new therapeutic targets. Dopaminergic, serotonergic and cholinergic pathways were found to be active against glioblastoma. In particular, dopamine receptor D4 (DRD4) antagonists selectively inhibited glioblastoma growth in vitro and in vivo, in addition to showing synergistic effect with temozolomide. Small molecule or genetic antagonism of DRD4 suppressed ERK1/2 signaling and impaired autophagic flux causing accumulation of autophagic vacuoles and ubiquitinated proteins, associated with G0/G1 cell cycle arrest. These data suggest a new mechanism for treating glioblastoma through modulating dopamine DRD4 signaling. We used Affymetrix microarrays to characterize the mechanism of action for dopamine receptor D4 antagonist (PNU 96415E) in human glioblastoma derived neural stem cells. We treated the human glioblastoma derived neural stem cells (GNS cells) with PNU 96415E for period of 0h, 24h and 48h and extracted RNA for hybridaization on Affymetrix microarrary (Human gene 1.0 ST array) on two GNS lines.
Project description:To identify proneural, neural, classical and mesenchymal gene expression signature (Verhaak's classification) in human glioblastoma, a microarray analysis on 16 patient-derived glioblastoma stem cell cultures was performed.