MT3.1 MGMT (O6-Methylguanine-DNA Methyltransferase)
- Known as:
- MT3.1 MGMT (O6-Methylguanine-Desoxyribonucleic acid Methyltransferase)
- Catalog number:
- mc-380
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Kamiya biomedical company
- Gene target:
- MT3.1 MGMT (O6-Methylguanine-DNA Methyltransferase)
Related genes to: MT3.1 MGMT (O6-Methylguanine-DNA Methyltransferase)
- Gene:
- MGMT NIH gene
- Name:
- O-6-methylguanine-DNA methyltransferase
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 10q26.3
- Locus Type:
- gene with protein product
- Date approved:
- 1989-10-16
- Date modifiied:
- 2016-10-05
Related products to: MT3.1 MGMT (O6-Methylguanine-DNA Methyltransferase)
Related articles to: MT3.1 MGMT (O6-Methylguanine-DNA Methyltransferase)
- Glioblastoma (GBM) is an immunologically cold brain tumor with poor outcome, characterized by a myeloid-driven immunosuppressive microenvironment. Here we report an interim analysis of a first-in-human phase 1/2a dose-escalation study evaluating Temferon-a genetically engineered autologous stem cell transplant designed to deliver interferon-α2 by means of myeloid progeny recruited to the GBM TME and locally activate antitumor immunity. Twenty-four newly diagnosed patients with GBM and unmethylated MGMT promoter were treated across eight cohorts following surgical resection and radiotherapy, testing Temferon doses ranging from 0.5 × 10 to 4.0 × 10 CD34 cells kg and different conditioning regimens (BCNU or busulfan, with or without thiotepa). The primary endpoint was safety and tolerability within 90 days after infusion. Secondary endpoints included long-term safety, dose and conditioning regimen selection, Temferon engraftment, clinical response, quality of life and survival. No dose-limiting toxicities were observed up to the highest dose level of temferon tested. Busulfan conditioning was selected for further development. Adverse events included laboratory abnormalities, cytopenias and infections consistent with autologous stem cell transplant. Median overall survival and progression-free survival were 16.7 months and 8.1 months from diagnosis, respectively, with most patients maintaining good performance status and quality of life. Genetically engineered cells were detected long term in the bone marrow and the blood, where minimal amounts of interferon-α were measured. Temferon is a safe and tolerable immunotherapeutic strategy in patients with newly diagnosed GBM. ClinicalTrials.gov: NCT03866109 . - Source: PubMed
Publication date: 2026/06/01
Gentner BernhardEoli MaricaFarina FrancescaBarcella MatteoCapotondo AlessiaMazzoleni StefaniaBrambilla ValentinaFrancavilla AntonioGarramone MariagraziaCarrabba Matteo GFerla ValeriaBruno AlessandroAlvisi GiorgiaColtella NadiaMontini EugenioHadadi LeilaCapt CharlotteCuccarini ValeriaBruzzone Maria GraziaDi Meco FrancescoLegnani Federico GFerroli PaoloAcerbi FrancescoPallini RobertoD'Alessandris Quintino GiorgioOlivi AlessandroGagliardi FilippoSnider SilviaMortini PietroPatanè MonicaFiocchi AmletoBerno ValeriaPoliani Pietro LuigiFinocchiaro GaetanoRusso CarloCiceri FabioNaldini Luigi - Arsenic poisoning significantly elevates the risk of cancer and other chronic illnesses. The goal of this research is to identify important genes whose expression changes in response to arsenic toxicity, and the molecular pathways affected by arsenic, using computational analysis of arsenic toxicity profiles. This approach will computationally identify and analyze genes whose expression changes in response to arsenic, thereby elucidating the heightened risk of carcinogenesis in arsenic-exposed individuals. This work employed high-throughput arsenic toxicity profiles to computationally identify and analyze expressed genes (DEGs) differentially in Affymetrix microarray datasets from the Gene Expression Omnibus (GEO) database, which were screened using the GEO2R program. A protein-protein interaction (PPI) network was constructed using STRING to elucidate the functional links between these DEGs and DNA repair genes. Interactions between the seven central genes (E2F1, EXO1, EZH2, FEN1, HIST1H3A, POLA1, and TIMELESS) and the repair genes PARP1, NBN, PMS1, MSH3, XRCC5, XRCC6, MGMT, and MLH1 were discovered. We employed the DAVID and Enrichr-KG platforms to investigate the functions of these genes and their associations with cellular and molecular processes in greater detail. Two hundred eighty-one non-synonymous single-nucleotide polymorphisms (nsSNPs) in the 07 genes linked to arsenic toxicity were found using the COSMIC database. Based on our analysis, mutations in E2F1, EXO1, EZH2, FEN1, HIST1H3A, POLA1, and TIMELESS can hinder DNA repair mechanisms, ultimately leading to cancer. Our computational analysis demonstrated that these non-synonymous SNPs can affect gene function, potentially altering protein stability and activity. Furthermore, according to Metal-Protein docking and protein-protein docking, these genes and their mutations appear to affect interactions with repair proteins substantially. Specific dietary consumption may lessen the detrimental effects of arsenic poisoning on protein function. We hypothesized that the mutations might be reversed by attaching particular molecules to these mutants. The protective effects of six curcumin compounds were examined using molecular docking with AutoDock 4.2.6 to assess protein dynamics and binding interactions. Optimal complexes were selected for dynamics simulation using GROMACS, and potential strategies for long-term cancer prevention related to arsenic exposure were identified. - Source: PubMed
Parida LuckyPatel Trupti N - Ortho-coumaric acid (o-CA) derivatives, specifically butyl, isobutyl, propyl, ethyl, and methyl-o-coumarate, have emerged as potential therapeutic agents for glioblastoma multiforme (GBM). This study investigates their effects on drug resistance, proliferation, migration, maturation, cell cycle regulation, and autophagy in stem-like glioblastoma cells (SLGCs). We evaluated the biological activity of o-CA derivatives using an in vitro GBM cell model by assessing spheroid and colony formation, cell migration, autophagy marker induction, DNA damage repair protein expression, cell cycle alterations, and the expression of stemness and differentiation markers. Treatment with o-CA derivatives, particularly butyl and isobutyl, resulted in a decreased self-renewal capacity of SLGCs, as indicated by reduced spheroid and colony formation compared to temozolomide (TMZ). Additionally, butyl o-CA impaired cell migration. Cell cycle analysis revealed an increased proportion of cells in the G0/G1 phase following treatment with butyl and isobutyl o-CA, accompanied by a reduction in the S and G2/M phases. Furthermore, we observed increased expression of the autophagy marker microtubule-associated protein 1 light-chain 3B (LC3-B) in cells treated with propyl and butyl o-CA. The expression of the drug resistance marker O6-methylguanine DNA methyltransferase (MGMT) was significantly reduced, particularly in cells treated with Butyl o-CA. Moreover, butyl o-CA-treated cells demonstrated lower expression levels of the stemness markers CD133 and Nestin, in conjunction with elevated expression of the differentiation markers GFAP and NeuN. Overall, these findings suggest that o-CA derivatives, especially butyl and Isobutyl o-CA, may effectively modulate stem-like characteristics in an in vitro GBM model. - Source: PubMed
Publication date: 2026/05/29
Reséndiz-Castillo Luis JavierGutiérrez-Mercado Yanet KarinaMateos-Díaz Juan CarlosCarranza-Aranda Ahtziri SocorroReza-Zaldivar Edwin EstefanHernández-Sapiéns Mercedes AzucuenaCanales-Aguirre Alejandro Arturo - MicroRNAs (miRNAs) play pivotal roles in glioblastoma (GBM) progression and therapy resistance. Among them, miR-25-3p has emerged as a key oncogenic miRNA that promotes tumor growth, invasiveness, and resistance to temozolomide (TMZ). In this study, we profiled miRNA expression in primary GBM specimens (n = 50) stratified by MGMT methylation and TP53 mutation status and assessed the functional impact of miR-25-3p inhibition in seven patient-derived GBM cell lines. Quantitative PCR analysis revealed upregulation of miR-135b in MGMT-methylated tumors and miR-10b in TP53-mutant cases. Both miR-25-3p and miR-10b were significantly elevated in 3D spheroid cultures compared to 2D monolayers. Notably, both miRNAs were secreted via tumor-derived extracellular vesicles, implicating a role in cell-cell communication. Inhibition of miR-25-3p in GBM cell lines consistently suppressed β-catenin and re-induced FBXW7 expression across all cases, correlating with inhibitor uptake. In four of seven cell lines, miR-25-3p inhibition enhanced TMZ sensitivity and reduced invasiveness, although the anti-invasive effect was not further potentiated by the addition of TMZ. In addition, RNA-Seq and methylome analyses revealed genetic and epigenetic reprograming toward a less aggressive, less invasive phenotype with reduced stemness potential. These findings highlight the interplay between tumor microenvironment and molecular heterogeneity in shaping miRNA dynamics in GBM. Collectively, our results identify miR-25-3p as a promising dual-action therapeutic target to mitigating both invasion and chemoresistance in GBM, warranting further translational investigation. - Source: PubMed
Publication date: 2026/05/30
Richter KatharinaMarkmann HannahKaps PhilippWolff AnnabellSimm StefanDubinski DanielGessler FlorianFreiman Thomas MKirschstein TimoJunghanss ChristianMaletzki ClaudiaSchneider Bjoern - In patients with glioblastoma (GBM), the presence of other primary malignancies in different organs appears to be associated with a reduced survival rate compared to patients with GBM alone. This study aimed to evaluate how the presence of additional simultaneous cancers affects the survival outcomes of patients newly diagnosed with GBM. - Source: PubMed
Publication date: 2026/05/28
Hong BujungChaib HindTsoy YuriyMoros GonzaloKipele MariaHeissler Hans EZiegenhardt GunterMawrin ChristianShiban Ehab