O(6)-Methylguanine DNA methyltransferase (MGMT) protects tumor cells from the cytotoxic effects of DNA-alkylating agents such as 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU). To improve the therapeutic index of BCNU, biochemical strategies to inhibit MGMT temporarily by systemic administration of small molecules, such as O(6)-benzylguanine, have been developed and are showing promise in clinica...

A DNA repair enzyme, O6-methylguanine-DNA methyltransferase (MGMT), plays an important role in the development of gastric cancers. However, the role of MGMT promoter methylation in the occurrence of gastric cancer and its relationships with clinicopathologic characteristics has not been fully clarified. Thus, we performed a meta-analysis to evaluate the associations between MGMT promoter methyl...

OBJECTIVE We analyzed the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter in World Health Organization (WHO) grade III gliomas in association with other molecular markers to evaluate their prevalence. METHODS The samples of a total of 36 newly WHO grade III glioma patients including 19 anaplastic oligodendrogliomas (AO), 7 anaplastic oligoastrocytomas (AO...

The methylation of the O(6)-methylguanine DNA methyltransferase (MGMT) promoter is frequently observed in several cancer types. The potential correlation between the C>T allele at SNP rs16906252 and methylation in MGMT are being actively investigated and remain largely elusive. We studied the allelic pattern of MGMT methylation through meta-analysis. All eligible studies were identified by sear...

Resistance of glioblastoma (GBM) to the front-line chemotherapeutic agent temozolomide (TMZ) continues to challenge GBM treatment efforts. The repair of TMZ-induced DNA damage by O-6-methylguanine-DNA methyltransferase (MGMT) confers one mechanism of TMZ resistance. Paradoxically, MGMT-deficient GBM patients survive longer despite still developing resistance to TMZ. Recent studies indicate that...

Purpose: To address the association between sequence variants within the MGMT (O-methylguanineDNA methyltransferase) promoter–enhancer region and methylation of MGMT in premalignant lesions from smokers and lung adenocarcinomas, their biological effects on gene regulation, and targetingMGMT

The methylation status of O-6-methylguanine-DNA methyltransferase (MGMT) is associated with the prognosis in gliomas and in other cancers. Recent studies showed that rs16906252, an SNP in the MGMT promoter, is associated with promoter methylation and is a predictor of the overall survival time (OST) and the response to temozolomide (TMZ) treatment. However, these findings haven't been systemati...

BACKGROUND The gene encoding the DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT) is transcriptionally silenced by promoter hypermethylation in several human cancers, including diffuse large B-cell lymphoma (B-DLCL). MGMT promoter hypermethylation is a favorable prognostic marker in patients with brain tumors treated with alkylating agents. METHODS In a retrospective cohort s...

BACKGROUND Temozolomide (TMZ) is important chemotherapy for glioblastoma multiforme (GBM), but the optimal dosing schedule is unclear. METHODS The efficacies of different clinically relevant dosing regimens were compared in a panel of 7 primary GBM xenografts in an intracranial therapy evaluation model. RESULTS Protracted TMZ therapy (TMZ daily M-F, 3 wk every 4) provided superior survival ...

Treatment of chloroethylnitrosourea-resistant cells with streptozotocin (STZ) prior to bis-chloroethylnitrosourea (BCNU) exposure has been shown to result in a depletion of O6-methylguanine DNA methyltransferase (MGMT) activity, increased BCNU-induced interstrand cross-linking, and a 2-3 log enhancement of BCNU cytotoxicity in vitro. The current study was undertaken to define the kinetics of re...