Histological examination confirmed a wild-type (WT) IDH1/2, MGMT (DNA repair enzyme O6-methylguanine-DNA methyltransferase) methylated glioblastoma with a proliferative index focally as high as 20%.
The CpG methylation status of the MGMT promoter strongly correlates with clinical outcome and, therefore, is used as prognostic marker during glioblastoma therapy.
In addition to its benefits for molecular subgrouping and copy number analysis of brain tumors, DNA-methylation based classification is a highly reliable tool for the assessment of MGMT promoter methylation status in glioblastoma patients.
The purpose of this study was to determine the effect of disulfiram (DSF), an aldehyde dehydrogenase inhibitor, on in vitro radiosensitivity of glioblastoma cells with different methylation status of O6-methylguanine-DNA methyltransferase (MGMT) promoter and the underlying mechanism of such effect.
Clinical data (age, sex, extent of surgical resection), O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and pre-operative T2WI of 113 pathologically confirmed glioblastoma patients (from our institution, n = 61; from the Cancer Imaging Archive, n = 52) were retrospectively reviewed.
Although the two classical molecular markers of glioblastoma including isocitrate dehydrogenase 1 or 2 (IDH1/2) mutation and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation are associated with overall survival rate of glioblastoma patients, they are not specific to the survival outliers.
The absence of systematic and clinically relevant changes in HRQOL and neurocognitive function combined with the survival benefit of lomustine-temozolomide versus temozolomide alone suggests that a long-term net clinical benefit exists for patients with newly diagnosed glioblastoma with methylation of the MGMT promoter and supports the use of lomustine-temozolomide as a treatment option for these patients.
Studies examining the synergy between Dihydrotanshinone and Temozolomide against MGMT+ glioblastoma cells in vitro: Predicting interactions with the blood-brain barrier.
In addition, because temozolomide did not cause phosphorylation of cPLA<sub>2</sub> in MGMT high-expressing glioblastoma T98G cells, phosphorylation of cPLA<sub>2</sub> may be caused by DNA alkylation of temozolomide.
GTR and MGMT promoter methylation are independent prognosticators for improved overall and progression-free survival in a homogeneous cohort of newly diagnosed patients with IDH wild-type glioblastoma.
Data from a previous unrandomised phase 2 trial suggested that lomustine-temozolomide plus radiotherapy might be superior to temozolomide chemoradiotherapy in newly diagnosed glioblastoma with methylation of the MGMT promoter.
To determine whether there is a threshold for the TMZ-induced DNA damage response and exploring the factors regulating the switch between p53 dependent survival and death, the glioblastoma lines LN-229 (deficient in MGMT) and LN-229MGMT (stably transfected with MGMT) were exposed to different doses of TMZ. p53 protein expression and phosphorylation levels of p-p53ser15 and p-p53ser46 were determined by Western blotting.
Patients with glioblastoma without O6-methylguanine-DNA methyltransferase (MGMT) promoter hypermethylation are unlikely to benefit from alkylating chemotherapy with temozolomide (TMZ).
Epigallocatechin Gallate Preferentially Inhibits O<sup>6</sup>-Methylguanine DNA-Methyltransferase Expression in Glioblastoma Cells Rather than in Nontumor Glial Cells.
Enrichment analyses of intragenic DNA methylation profiles with epigenetic signatures prioritized the intragenic DNA methylation of ZMIZ1 as a possible glioblastoma prognostic marker that is independent of MGMT methylation in IDH1 wild-type patients.