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O-6-methylguanine-DNA methyltransferase

Methylguanine-DNA Methyltransferase, MGMT, O6-methylguanine-DNA methyltransferase
This gene is expressed only in the liver and the encoded protein is localized mostly in the peroxisomes, where it is involved in glyoxylate detoxification. Mutations in this gene, some of which alter subcellular targetting, have been associated with type I primary hyperoxaluria. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: HAD, AGE, CAN, POLYMERASE, p53
Papers on Methylguanine-DNA Methyltransferase
Treatment Considerations for MGMT-Unmethylated Glioblastoma.
Schiff et al., San Francisco, United States. In Curr Neurol Neurosci Rep, 31 Jan 2015
Temozolomide, the most widely used alkylating agent in glioblastoma, is cytotoxic to cells by inducing DNA damage but can be rapidly repaired by the protein O (6)-methylguanine DNA methyltransferase (MGMT).
MGMT promoter methylation is associated with temozolomide response and prolonged progression-free survival in disseminated cutaneous melanoma.
Egyházi Brage et al., Stockholm, Sweden. In Int J Cancer, 15 Dec 2014
UNLABELLED: To investigate the predictive and prognostic value of O6-methylguanine DNA methyltransferase (MGMT) inactivation by analyses of promoter methylation in pre-treatment tumour biopsies from patients with cutaneous melanoma treated with dacarbazine (DTIC) or temozolomide (TMZ) were performed.
MGMT promoter methylation in non-neoplastic brain.
Ho et al., Taipei, Taiwan. In J Neurooncol, 13 Dec 2014
UNLABELLED: O(6)-methylguanine-DNA-methyltransferase (MGMT) is mainly regulated by cytosine-guanine island promoter methylation that is believed to occur only in neoplastic tissue.
Programmed death ligand 1 expression and tumor-infiltrating lymphocytes in glioblastoma.
Wick et al., Vienna, Austria. In Neuro Oncol, 29 Nov 2014
METHODS: We performed immunohistochemistry for CD3, CD8, CD20, HLA-DR, phosphatase and tensin homolog (PTEN), PD-1, and PD-L1 and pyrosequencing for assessment of the O6-methylguanine-methyltransferase (MGMT) promoter methylation status in 135 glioblastoma specimens (117 initial resection, 18 first local recurrence).
Multidisciplinary management of adult low grade gliomas.
- et al., In Chirurgia (bucur), Sep 2014
ABBREVIATIONS: LGG: low grade gliomas, WHO: World Health Organization, OS: overall survival, PFS: progression-free survival, MRI: Magnetic resonance imaging, MRS: Magnetic resonance spectroscopy, MPFS: malignant progression-free survival, rCBV: Relative Cerebral Blood Volume, QOL: quality of life, FLAIR: Fluid attenuated inversion recovery, MGMT: O6-methylguanine DNA methyltransferase enzyme, DSC MR imaging: Dynamic Susceptibility Contrast Perfusion MR imaging, 1H-MRS: Proton Magnetic Resonance Spectroscopy, IDH1: isocitrate dehydrogenase 1 gene, SPECT: Single-photon emission computed tomography, PET: Positron emission tomography, DTI-FT: Diffuse Tensor Imaging-fiber tracking technique, DES: direct electrical stimulation, EEG: Electroencephalography, EcoG: Electrocorticography, MEP: motor evoked potentials, EMG: Electromyography, AED: anti-epileptic drugs, TMZ: Temozolomide, EORTC: European Organization for Research and Treatment of Cancer, NCCTG: North Central Cancer Treatment Group, RTOG: Radiation Therapy Oncology Group, ECOG: Eastern Cooperative Oncology Group, EOR: extent of resection, Gy: Gray (unit), GyE: gray equivalent, RT: radiation therapy, IMRT: image-guided intensity modulated radiotherapy, FSRT: fractionated stereotactic radiotherapy, SRS: proton therapy or stereotactic radiosurgery, LET: high-linear energy transfer beams, RBE: relative biological effectiveness, CTCAE: Common Terminology Criteria for Adverse Events, PCV: procarbazine, lomustine, and vincristine chemotherapy.
Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial.
CENTRIC study team et al., Zürich, Switzerland. In Lancet Oncol, Sep 2014
Data from phase 2 trials suggest that it has antitumour activity as a single agent in recurrent glioblastoma and in combination with standard temozolomide chemoradiotherapy in newly diagnosed glioblastoma (particularly in tumours with methylated MGMT promoter).
Two DNA repair gene polymorphisms on the risk of gastrointestinal cancers: a meta-analysis.
Liu et al., Wuhan, China. In Tumour Biol, Mar 2014
PARP-1 and MGMT play an important role in the DNA repair system and therefore have been implicated in human carcinogenesis.
Radiation and concomitant chemotherapy for patients with glioblastoma multiforme.
Comas et al., Badalona, Spain. In Ai Zheng, Jan 2014
Elderly patients with tumors that exhibit methylation of the O-6-methylguanine-DNA methyltransferase promoter can benefit from TMZ alone.
Molecular biology of high-grade gliomas: what should the clinician know?
Marosi et al., Zürich, Switzerland. In Ai Zheng, Jan 2014
Recent practice-changing clinical trials have defined a role for routine assessment of O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastoma patients, especially in the elderly, and 1p and 19q codeletions in patients with anaplastic glial tumors.
Case comparison and literature review of glioblastoma: A tale of two tumors.
Ross et al., Portland, United States. In Surg Neurol Int, Dec 2013
The following markers were assessed: O (6)-methylguanine DNA methyltransferase (MGMT) methylation, isocitrate dehydrogenase (IDH) 1 and 2 status, epidermal growth factor receptor (EGFR) amplification, phosphatase and tensin homolog (PTEN) status, Ki-67, p53, and 1p/19q status.
Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial.
Mehta et al., Houston, United States. In J Clin Oncol, Dec 2013
O(6)-methylguanine-DNA methyltransferase (MGMT) methylation status may be an important determinant of treatment response.
The somatic genomic landscape of glioblastoma.
TCGA Research Network et al., New York City, United States. In Cell, Nov 2013
Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM.
Adenovirus-mediated gene therapy with sitimagene ceradenovec followed by intravenous ganciclovir for patients with operable high-grade glioma (ASPECT): a randomised, open-label, phase 3 trial.
ASPECT Study Group et al., Hamburg, Germany. In Lancet Oncol, Aug 2013
In a subgroup of patients with non-methylated MGMT, the HR was 1·72 (95% CI 1·15-2·56; p=0·008).
Intrinsic molecular subtypes of glioma are prognostic and predict benefit from adjuvant procarbazine, lomustine, and vincristine chemotherapy in combination with other prognostic factors in anaplastic oligodendroglial brain tumors: a report from EORTC study 26951.
French et al., Rotterdam, Netherlands. In J Clin Oncol, Feb 2013
They are prognostic for PFS independent of clinical (age, performance status, and tumor location), molecular (1p/19q loss of heterozygosity [LOH], IDH1 mutation, and MGMT methylation), and histologic parameters.
O6-methylguanine DNA methyltransferase as a promising target for the treatment of temozolomide-resistant gliomas.
Jiang et al., Xuzhou, China. In Cell Death Dis, 2012
One of the major mechanisms of cancer drug resistance is enhanced activity of a DNA repair enzyme, O(6)-methylguanine-DNA-methyltransferase (MGMT), which counteracts chemotherapy-induced DNA alkylation and is a key component of chemoresistance.
Uncoupling of eNOS causes superoxide anion production and impairs NO signaling in the cerebral microvessels of hph-1 mice.
Katusic et al., Rochester, United States. In J Neurochem, 2012
Reduced tetrahydrobiopterin bioavailability causes endothelial NOS uncoupling, increases superoxide anion production, inhibits eNOS/cGMP signaling, and imposes significant oxidative stress in the cerebral microvasculature.
Angiotensin-II and MARCKS: a hydrogen peroxide- and RAC1-dependent signaling pathway in vascular endothelium.
Michel et al., Boston, United States. In J Biol Chem, 2012
a critical role for H(2)O(2) in angiotensin-II signaling to the endothelial cytoskeleton in a novel pathway that is critically dependent on MARCKS, Rac1, and c-Abl.
The prolyl hydroxylase PHD3 identifies proinflammatory macrophages and its expression is regulated by activin A.
Corbí et al., Madrid, Spain. In J Immunol, 2012
These results indicate that EGLN3 gene expression in macrophages is dependent on activin A
Loss of the oxygen sensor PHD3 enhances the innate immune response to abdominal sepsis.
Schneider et al., Heidelberg, Germany. In J Immunol, 2012
It is concluded that impairment of PHD3 enzyme function aggravates the clinical course of abdominal sepsis
PHD3-dependent hydroxylation of HCLK2 promotes the DNA damage response.
Patterson et al., Chapel Hill, United States. In J Clin Invest, 2012
mice lacking PHD3 were resistant to the effects of ionizing radiation and had decreased thymic apoptosis, a biomarker of genomic integrity
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