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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, p53, CAN, Id1
Papers on Methylguanine-DNA Methyltransferase
Nimotuzumab enhances temozolomide-induced growth suppression of glioma cells expressing mutant EGFR in vivo.
Nagane et al., Tokyo, Japan. In Cancer Med, Feb 2016
Methylation status of promoter region of O(6) -methylguanine-DNA methyltransferase (MGMT) was detected by methylation-specific PCR.
Glioblastoma care in the elderly.
Plotkin et al., Boston, United States. In Cancer, Feb 2016
In addition, temozolomide chemotherapy is safe and extends the survival of patients with tumors that harbor O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation.
Prognostic significance of histomolecular subgroups of adult anaplastic (WHO Grade III) gliomas: applying the 'integrated' diagnosis approach.
Santosh et al., Bengaluru, India. In J Clin Pathol, Feb 2016
Clinical, histological and molecular parameters, including 1p/19q codeletion, isocitrate dehydrogenase gene (IDH1)-R132H positivity, α thalassemia/mental retardation syndrome X-linked gene (ATRX) expression and O(6)-methylguanine-DNA-methyltransferase gene (MGMT) promoter methylation (mMGMT), were correlated with overall survival (OS) and recurrence-free survival (RFS).
Expression and prognostic value of the WEE1 kinase in gliomas.
Kristensen et al., Odense, Denmark. In J Neurooncol, Feb 2016
This was confirmed in multivariate analysis (HR 0.60, p = 0.003) even when adjusted for MGMT status (HR 0.60, p = 0.005).
Stress Response Leading to Resistance in Glioblastoma-The Need for Innovative Radiotherapy (iRT) Concepts.
Multhoff et al., München, Germany. In Cancers (basel), Dec 2015
Further molecular alterations and prognostic markers like the DNA-repair protein O6-methylguanine-DNA methyltransferase (MGMT), anti-apoptotic molecular chaperones, and/or the activity of aldehyde dehydrogenase 1 (ALDH1) have also been identified to play a role in the sensitivity to cytostatic agents.
Investigating molecular alterations to profile short- and long-term recurrence-free survival in patients with primary glioblastoma.
Naccarato et al., Pisa, Italy. In Oncol Lett, Dec 2015
The 19 samples were molecularly characterized for mutations in the isocitrate dehydrogenase 1 (IDH1) gene, amplification of the epidermal growth factor receptor (EGFR) gene, presence of the EGFR variant III, and methylation of the promoter region of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene.
MGMT testing allows for personalised therapy in the temozolomide era.
Marignol et al., Dublin, Ireland. In Tumour Biol, Nov 2015
Silencing of the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter is thought to induce chemosensitivity, and testing for methylation may allow for patient stratification; however, this has yet to become routine clinical practice despite an abundance of literature on the subject.
Management of diffusely infiltrating glioma in the elderly.
Weller et al., Zürich, Switzerland. In Curr Opin Oncol, Nov 2015
Histopathologically, these are mostly astrocytic tumors and treatment is guided by the methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter.
Expression and clinical significance of P53, O6-methylguanine-dna methyltransferase and epidermal growth factor receptor in glioma.
Chang et al., Zhengzhou, China. In J Biol Regul Homeost Agents, Oct 2015
The objective of the present investigation was to explore the expression and clinical significance of tumor suppressor gene (P53), O6-methylguanine-DNA methyltransferase (MGMT) and epidermal growth factor receptor (EGFR) in glioma.
Adenosquamous carcinoma of the pancreas: Molecular characterization of 23 patients along with a literature review.
Von Hoff et al., Scottsdale, United States. In World J Gastrointest Oncol, Oct 2015
Molecular characterization revealed overexpression in MRP1 (80%), MGMT (79%), TOP2A (75), RRM1 (42%), TOPO1 (42%), PTEN (45%), CMET (40%), and C-KIT (10%) among others.
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, 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).
Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial.
Mehta et al., Houston, United States. In J Clin Oncol, 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, 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, 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, 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.
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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