Temozolomide (TMZ) is the first-line chemotherapy drug for glioma, but whether TMZ should be withheld from patients with GBMs that lack O6-methylguanine-DNA methyltransferase (<i>MGMT</i>) promoter methylation is still under debate.
Prognostic significance of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation and isocitrate dehydrogenase-1 (IDH-1) mutation in glioblastoma multiforme patients: A single-center experience in the Middle East region.
Methylation of the O<sup>6</sup>-methylguanine DNA methyltransferase (MGMT) promoter has emerged as strong prognostic factor in the therapy of glioblastoma multiforme.
Independent overall survival predictors were MGMT promoter methylation (adjusted HR 0.35; 95% CI 0.23-0.55) and a RTV of <3.50 cc (adjusted HR 0.53; 95% CI 0.29-0.95), but not EOR for incompletely resected glioblastomas.
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.
Combined analysis of MGMT methylation and dynamic-susceptibility-contrast MRI for the distinction between early and pseudo-progression in glioblastoma patients.
Instead, a difference in survival outcomes was confirmed in unmethylated-MGMTGB patients with better survival for patients undergoing to SDRT, particularly in sub-total resection.
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.
Interestingly, PTEN deletion had poor prognostic value in astrocytomas IDH-wildtype (p = 0.015), while in GBM IDH-wildtype was associated with better overall survival (p = 0.042) as well as MGMT promoter methylation (p = 0.009).
This was not the case in glioblastoma cells expressing the repair protein MGMT, suggesting that the primary DNA lesion responsible for triggering HIPK2-mediated apoptosis is <i>O<sup>6</sup></i> -methylguanine.
The methylation status of the O<sup>6</sup>-methylguanine DNA methyltransferase (<i>MGMT</i>) gene promoter is predictive for benefit from temozolomide in glioblastoma (GBM).
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.
Studies examining the synergy between Dihydrotanshinone and Temozolomide against MGMT+ glioblastoma cells in vitro: Predicting interactions with the blood-brain barrier.
The phase II GLARIUS trial assigned patients with newly diagnosed, O-6-methylguanine-DNA methyltransferase promoter non-methylated glioblastoma to experimental bevacizumab/irinotecan (BEV/IRI) or standard temozolomide (TMZ).
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.