Data from 34 studies showed that MGMT methylated patients had better OS, compared to GBM unmethylated patients (pooled HRs, 0.494; 95%CI 0.412-0.591; p = 0.001).
U87MG and U251MG (MGMT negative), as well as T98G (MGMT positive), were subcutaneously injected in nude mice, whereas luciferase positive U251MG cells and patient-derived GBM stem cell line (CSCs-5) were evaluated the orthotopic intra-brain in vivo experiments.
Methylation of the O<sup>6</sup>-methylguanine-DNA methyltransferase (MGMT) gene promoter is a well-established predictor of response to the DNA-alkylating agent temozolomide in patients with glioblastoma.
In other experiments, four glioblastoma cell lines synchronized at the G1/S phase using either double thymidine or thymidine-mimosine blocks and subsequent cycling consistently showed a loss of MGMT protein at mid- to late S-phase, irrespective of the cell line, suggesting such a downregulation is fundamental to cell cycle control.
For this purpose, tumor samples from newly diagnosed and untreated GBM patients with methylated (n = 22) or unmethylated (n = 17) MGMT promoter were simultaneously analyzed for integrin α<sub>v</sub>β<sub>3</sub> expression by an automated immunohistochemical staining platform.
Although methylation of the O<sup>6</sup>-methylguanine-DNA methyltransferase (MGMT) gene promoter predicts response to temozolomide in patients with glioblastoma, no consensus exists as to which assay is best for its detection.
The methylation status of oxygen 6-methylguanine-DNA methyltransferase (MGMT) promoter has been associated with treatment response in glioblastoma(GBM).
In this retrospective analysis of treatment-naïve samples of the OSAG 101-BSA-05 trial cohort, we identify the EGFR signaling activity markers phosphorylated PRAS40 and phosphorylated ribosomal protein S6 as predictive markers for treatment efficacy of the EGFR-blocking antibody nimotuzumab in MGMT promoter unmethylated GBs.
In our cohort of 51 GBM patients treated with radiation therapy with concurrent and adjuvant temozolomide, ABCA13 overexpression is associated with a decreased progression free survival in univariate (p < 0.01) and multivariate analyses including MGMT promoter methylation (p = 0.05) suggesting reduced sensitivity to temozolomide in ABCA13 overexpressing GBM.
Wild-type IDH was present in 89.8% of the adult glioblastoma samples, and TERT promoter mutations and MGMT promoter methylation were observed in 66.42% and 38.49% of all adult primary glioblastomas, respectively.
A drug screening aimed at evaluating the potential recycling and repurposing of known drugs was conducted in TMZ-resistant GBM cell lines and primary cultures of newly diagnosed GBM with different MGMT promoter methylation status, phenotypic/genotypic background and subtype, and validated with sphere formation, cell migration assays, and quantitative invasive orthotopic in vivo models.
Patients diagnosed with MGMT promoter unmethylated GBM from 2010 to 2012 who received radiation (RT) or chemoradiation (CRT) were identified in the National Cancer Database.
Correlation Between the Residual Tumor Volume, Extent of Tumor Resection, and O<sup>6</sup>-Methylguanine DNA Methyltransferase Status in Patients with Glioblastoma.