D14e9590-7910-4f17-ad5d-729244a94787 - samples
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ABSTRACT:
PROVIDER: EGAD00001010163 | EGA |
REPOSITORIES: EGA
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Project description:Temozolomide (TMZ) resistance may contribute to the treatment failure in patients with glioblastoma (GBM). Hence, understanding the underlying mechanisms and developing effective strategies against TMZ resistance are highly desired in the clinic. long non-coding RNAs (lncRNAs) have emerged as new regulatory molecules with diverse functions in biological processes and been deregulated in many pathologies, involved in the therapeutic resistance. It is urgent to elucidate the underlying lncRNA-based mechanisms of TMZ resistance in GBM patients.
2019-04-12 | GSE113510 | GEO
Project description:Glioblastoma (GBM) is the most common primary brain tumor in adults, characterized by an inherent aggressivity and resistance to treatment leading to poor prognoses. While some resistance mechanisms have been elucidated, a deeper understanding of these mechanisms is needed to increase therapeutic efficacy. In this study we first discovered glial-cell derived neurotrophic factor (GDNF) to be upregulated in patient-derived glioblastoma spheroid cultures after chemotherapeutic temozolomide (TMZ) treatment, through RNA-Seq experiments. Therefore, we investigated the role of the GDNF/GDNF receptor alpha 1 (GFRA1) signaling pathway as a resistance mechanism to chemotherapy with temozolomide and lomustine as well as irradiation using patient-derived glioblastoma spheroid cultures. With qPCR experiments we showed a consistent upregulation of GDNF and its primary receptor GFRA1 following all three lines of treatment. Moreover, CRISPR/Cas9 knock-outs of GDNF in two patient-derived models sensitized these cells to chemotherapy treatment, but not radiotherapy. The increased sensitivity was completely reversed by the addition of exogeneous GDNF, confirming the key role of this factor in chemoresistance. Finally, a CRISPR KO of GFRA1 demonstrated a similar increased sensitivity to temozolomide and lomustine treatment, as well as radiotherapy. Together, our findings support the role of the GDNF/GFRA1 signaling pathway in glioblastoma chemo and radioresistance.
2024-02-13 | GSE255581 | GEO
Project description:Combined model of in vitro and in vivo resistance to alkylating agents (BCNU and Temozolomide) in glioblastoma multiforme. Three matched pairs of surgical specimens from initial (DI, ME, LX) and repeat (DIR, MER, LXR) tumor resection were used to establish cell lines. Patients received BCNU chemotherapy between the two operations, which rendered the sublines from repeat surgery more resistant to BCNU than those from initial surgery. Each the pre-chemotherapeutic set and the post-chemotherapeutic set of cell lines was selected in vitro for resistance to either BCNU or Temozolomide. 9 in vitro selected sublines were established. Of those 4 (2 selected for BCNU [ME-BCNU, DI-BCNU] and 2 selected for Temozolomide [ME-TMZ, LX-TMZ) were generated from the parental/sensitive pre-chemotherapeutic set and 5 (2 selected for BCNU [DIR-BCNU, MER-BCNU] and 3 selected for Temozolomide [DIR-TMZ, MER-TMZ, LXR-TMZ) from the in vivo resistant post-chemotherapeutic set. The model included a total of 15 sublines. Genome-wide high-resolution gene copy number profiling was performed on each subline using 42,000-feature cDNA microarrays. Utilizing the same microarray platform genome-wide gene expression profiles were generated. Biostatistical tools were employed to identify signatures of resistance to alkylating agents both at the genetic as well as at the transcriptomic levels. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Series_type = Logical Set Keywords: other
2006-01-27 | GSE2221 | GEO
Project description:Patients diagnosed with glioblastoma (GBM) with sustained synthesis of the DNA repair enzyme, O6-methyl guanine DNA methytransferase (MGMT), are rendered resistant to Temozolomide (TMZ) chemotherapy. Here, we hypothesized that pretreatment with the proteasome inhibitor Bortezomib (BTZ, Velcade) might sensitize these GBM to TMZ by depleting MGMT.
2019-08-20 | PXD007193 | Pride
Project description:Glioblastoma therapy relies on the alkylating drug temozolomide (TMZ) administered to irradiated patients post-neurosurgery, which increases overall survival but cannot prevent fatal disease relapse. Using clinical samples and glioblastoma models, we here identify TMZ-driven enrichment of ALDH1A1+ tumor subclones acquiring AKT-dependent drug resistance en route to relapse. We demonstrate that this recurrent phenotype switch is predictable and can be countered by a sequential rather than simultaneous combinatorial treatment approach.
2020-02-12 | GSE145128 | GEO
Project description:Acquired resistance of temozolomide (TMZ) is one of the major obstacle of glioblastoma clinical treatment and the mechanism of TMZ resistance is still not very clear. In the presented research we show that deletion of rs16906252-associated MGMT enhancer in MGMT negative glioma cells induced increase sensitivity to temozolomide and combination of RNA-seq and Capture HiC identified several long-range target genes of rs16906252-associated MGMT enhancer. In addition, HiC data shows alterations of chromatin structures in glioma cells survived from high-dosage TMZ treatment and changes of TADs influence rs16906252-associated MGMT enhancer’s long-range regulations of target genes. Our study suggests rs16906252-associated MGMT enhancer regulates glioma cells’ TMZ sensitivity by long-range regulations of several target genes, which is a novel mechanism of regulation of TMZ sensitivity in glioma cells.
2020-04-02 | GSE129476 | GEO
Project description:Glioblastoma multiforme(GBM) is the most common and lethal malignant primary brain tumor. Temozolomide (TMZ) is a promising chemo-therapeutic agent to treat GBM. However, resistance to TMZ develops quickly with a high frequency. The mechanisms underlying GBM cells’ resistance to TMZ are not fully understood. Non-coding RNAs are aberrantly expressed in many cancers and are highly involved in their pathogenesis including drug-resistence. In order to systematically study the role of miRNAs in GBM cells' resistence to TMZ , we built gene expression profiles of TMZ-resistant cell line and TMZ-sensitive cell line using miRNA gene expression microarrays.
2020-07-04 | GSE100775 | GEO
Project description:Genome wide DNA methylation profiling of glioblastoma tumor samples from the Nordic randomised, phase 3 trial. For this study samples were selected based on their good prognostic markers (type of surgery, performance status) from three treatment arms (temozolomide (TMZ) vs. hypofractionated radiation 34Gy vs. radiation 60Gy), and based on the MGMT methylation status. From each group half of the patients had short survival and the other half had long survival.
2022-08-20 | GSE207426 | GEO
Project description:Glioblastoma multiforme (GBM) is the most common and lethal malignant primary brain tumor. Temozolomide (TMZ) is a promising chemo-therapeutic agent to treat GBM. However, resistance to TMZ develops quickly with a high frequency. The mechanisms underlying GBM cells’ resistance to TMZ are not fully understood. Long non-coding RNAs (lncRNAs) are aberrantly expressed in many cancers and are highly involved in their pathogenesis including drug-resistence. In order to systematically study the role of lncRNAs in GBM cells' resistence to TMZ , we built gene expression profiles of TMZ-resistant cell line and TMZ-sensitive cell line using lncRNA and mRNA gene expression microarrays.
2020-07-03 | GSE100736 | GEO
Project description:The discovery of long non-coding RNAs (lncRNAs) has improved the understanding of development and progression in various cancer sub-types. However, the role of lncRNAs in temozolomide (TMZ) resistance in glioblastoma (GBM) remains largely undefined. In this present study, the differential expression of lncRNAs were identified between U87 and U87TR (TMZ-resistant) cells and to find potential therapeutic targets of GBM for improving the survival of patients.
2022-03-30 | GSE199689 | GEO