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In this Phase I trial, seven patients received gene-modified hematopoietic stem cells following myelo-suppressive conditioning, but with only transient low-level engraftment of MGMT(P140K) gene-modified cells detectable in four patients.
the T/T genotype of MGMT rs12917 is likely to be linked to an enhanced susceptibility to cancer overall, especially glioma, in the Caucasian population.
our results revealed the essential role of the MGMT-DUB3-MCL1 axis in the chemoresistance of ovarian cancer and identified that a combined treatment with HDACis and PaTrin-2 is an effective method for overcoming chemoresistance in ovarian cancer.
An important role of Fstl1 in the regulation of temozolomide resistance by modulation of DIP2A/MGMT signaling.
MGMT rs12917 and higher levels of methylation in the MGMT promoter are associated with the risk of lung cancer
this study, the relationship of base pairing interactions and repair by O-6-methylguanine-DNA methyltransferase was tested in the frequently mutated codon 12 of the KRAS gene with complementary sequences containing each canonical DNA base. The rate of O(6)-MeG repair decreased 2-fold when O(6)-MeG was paired with G, whereas all other canonical bases had no impact on the repair rate.
It may contribute to the pathogenesis of nonsyndromic orofacial clefts in Chinese populations.
Alkylator resistance of S cells is mainly promoted by over-expression of O(6) -methylguanine DNA methyltransferase which results from increased activity of the NF-kappaB pathway in this cell culture model of glioma stem-like cells.
Study demonstrates that MGMT promoter methylation is present from the early life of the carriers and transmitted from mother to daughter suggesting a possible demethylation of MGMT during pregnancy.
Spearman's rank correlation analysis and Bonferroni correction were used to compare the values of DKI and the expression levels of GFAP, Topo IIalpha, and MGMT between the 2 groups.
When divided at the median, glioblastoma patients with low expression of MGMT protein (AF-low) had the best prognosis
Low MGMT promoter methylation is associated with glioblastoma.
MGMT Gene Promoter Methylation Status - Assessment of Two Pyrosequencing Kits and Three Methylation-specific PCR Methods for their Predictive Capacity in Glioblastomas.
In patients with neuroendocrine neoplasms, response to therapy, progression free survival and overall survival was correlated to MGMT promoter methylation status
The first evidence for non-repair functions of MGMT in cell cycle and highlight the involvement of PCNA in MGMT downregulation, with p21 attenuating the process.
The methylation of the MGMT promoter is uncommon, or occurs at a low frequency in meningiomas. There is no convincing rationale to test such tumors for their MGMT methylation status in a clinical setting
Data revealed that MGMT gene methylation was higher in non-small-cell lung carcinoma (NSCLC) tissue samples than normal. Also advanced stage NSCLC patients showed higher methylation than early stage patients without impacting patients survival. These results provided clear evidence about the association of MGMT hypermethylation with increased risk of NSCLC. [review]
There is no difference in the expression of Integrin alphavbeta3 between tumor samples from glioblastomas patients with methylated or unmethylated promoter regions in the (6)O-methylguanine methyltransferase (MGMT).
Germline variants in MGMT gene are associated with prostate cancer.
Promoter Hypermethylation of MGMT Gene is associated with Colorectal Cancer.
This study shows that when cell death and cell cycle arrest pathways are inhibited, p53 can still mediate MGMT-dependent repair, to promote cell survival upon DNA damage.
Snell, GHKRO, and PAPPA-KO mice express high levels of two proteins involved in DNA repair, O-6-methylguanine-DNA methyltransferase (MGMT) and N-myc downstream-regulated gene 1 (NDRG1).
This study demonstrates for the first time a non-linear dose-response for alkylation-induced colorectal carcinogenesis and reveals DNA repair by MGMT, but not AAG, as a key node in determining a carcinogenic threshold.
Findings suggest that O6-methylguanine-DNA methyltransferase (MGMT)-mediated temozolomide resistance is associated with increased histone acetylation.
Loss of MGMT expression and high Ezrin protein expression leads to esophageal cancer.
Both base excision repair and O6-methylguanine-DNA methyltransferase protect against methylation-induced colon carcinogenesis.
ta indicate that Zik1 and Gja9 demonstrated cancer-specific aberrant DNA methylation, whereas, Cdkn2a/p16, Igfbp3, Mgmt, Id4, and Cxcr4 were methylated in both the AOM tumors and normal colon mucosa.
Roles of MGMT and MLH1 proteins in alkylation-induced apoptosis and mutagenesis.
Repression of MGMT is associated with precancerous conditions in hyperplastic mucosa adjacent to colon cancer
GAMT and AGAT mRNA are up-regulated 5.4- and 1.9-fold respectively in adult mdx muscle compared to C57
In vivo selection of MD9-P140K-transduced BM cells was more efficient following submyeloablative than myeloablative therapy.
MGMT-deficient cells would likely exhibit an increased mutational burden, but only following exposures to specific environmental mutagens such as the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).
Mgmt suppresses intestinal cancer associated with exogenous alkylating agents.
IFN-beta appears to sensitize neuroblastoma cells to the cytotoxic effects of temozolomide through attenuation of MGMT expression
In the fetal brain, mRNA expression of AGAT increased steadily across the second half of pregnancy. In the fetal kidney and liver, AGAT mRNA and protein expression were also relatively low until 34-37 days gestation.
Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) in DNA. Repairs alkylated guanine in DNA by stoichiometrically transferring the alkyl group at the O-6 position to a cysteine residue in the enzyme. This is a
, O6-methylguanine-DNA methyltransferase
, methylated-DNA--protein-cysteine methyltransferase
, methylguanine-DNA methyltransferase
, O-6-alkylguanine-DNA alkyltransferase
, 0-6-methylguanine-DNA methyltransferase
, O(6)-alkylguanine-DNA alkyltransferase
, O6-alkylguanine-DNA alkyltransferase
, O6-methylguanine-DNA methyltranferase