Search results for "Methylation"
showing 10 items of 607 documents
Urea cycle dysregulation in non-alcoholic fatty liver disease.
2018
Background & Aims: In non-alcoholic steatohepatitis (NASH), the function of urea cycle enzymes (UCEs) may be affected, resulting in hyperammonemia and the risk of disease progression. We aimed to determine whether the expression and function of UCEs are altered in an animal model of NASH and in patients with non-alcoholic fatty liver disease (NAFLD), and whether this process is reversible. Methods: Rats were first fed a high-fat, high-cholesterol diet for 10 months to induce NASH, before being switched onto a normal chow diet to recover. In humans, we obtained liver biopsies from 20 patients with steatosis and 15 with NASH. Primary rat hepatocytes were isolated and cultured with free fatty …
Lack of neurofibromatosis type 2 gene promoter methylation in sporadic vestibular schwannomas.
2011
<i>Background:</i> Vestibular schwannomas (VS) are benign tumors of the nervous system that are usually sporadic but also occur in the inherited disorder neurofibromatosis type 2 (NF2). In VS, losses of chromosomal material and mutations of the NF2 gene have been established to be causative. For a subset of VS without detectable gene alterations, promoter inactivation by hypermethylation has been suggested. However, published data are very limited and contradictory. <i>Methods:</i> We analyzed NF2 gene promoter methylation in 35 sporadic VS by methylation-specific PCR. <i>Results:</i> Twenty-three of the tumors were informative, showing no promoter methyl…
Extent and patterns of MGMT promoter methylation in glioblastoma- and respective glioblastoma-derived spheres.
2010
Abstract Purpose: Quantitative methylation-specific tests suggest that not all cells in a glioblastoma with detectable promoter methylation of the O6-methylguanine DNA methyltransferase (MGMT) gene carry a methylated MGMT allele. This observation may indicate cell subpopulations with distinct MGMT status, raising the question of the clinically relevant cutoff of MGMT methylation therapy. Epigenetic silencing of the MGMT gene by promoter methylation blunts repair of O6-methyl guanine and has been shown to be a predictive factor for benefit from alkylating agent therapy in glioblastoma. Experimental Design: Ten paired samples of glioblastoma and respective glioblastoma-derived spheres (GS), c…
Demethylation treatment restores hic1 expression and impairs aggressiveness of head and neck squamous cell carcinoma.
2010
Promoter hypermethylation of tumor suppressor genes is a common feature of primary cancer cells. However, at date the somatic epigenetic events that occur in head and neck squamous cell carcinoma (HNSCC) tumorigenesis are not yet been well defined. In the present study we analysed the methylation status of the gene hypermethylated in cancer-1 (hic1), a gene located on chromosome 17p13.3, a region frequently lost in HNSCC. We analysed 22 HNSCC samples and three cell lines using methylation specific PCR (MSP). We found hic1 methylated in 21 out of 22 samples and in all three cell lines. Treatment of the cell lines with the demethylating agent 5-Azacytidin (5-Aza) resulted in the demethylation…
Leisure-time physical activity and DNA methylation age-a twin study.
2018
Background Epigenetic clocks may increase our understanding on human aging and how genetic and environmental factors regulate an individual aging process. One of the most promising clocks is Horvath’s DNA methylation (DNAm) age. Age acceleration, i.e., discrepancy between DNAm age and chronological age, tells us whether the person is biologically young or old compared to his/her chronological age. Several environmental and lifestyle factors have been shown to affect life span. We investigated genetic and environmental predictors of DNAm age in young and older monozygotic (MZ) and dizygotic (DZ) twins with a focus on leisure time physical activity. Results Quantitative genetic modeling revea…
Characterization of lacrimal proline-rich protein 4 (PRR4) in human tear proteome
2014
This study was initiated considering the lack of comprehensive characteristics profile of PRR4 in tears of healthy subjects. Therefore, detailed characterizations of PRR4 from basal tears employing in-gel and in-solution digestions for MS systems are presented herein. First, pooled tear samples (n = 10) were utilized to identify PRR4-rich region/spots in 1DE/2DE gels employing LC-MALDI-MS and 1DE-LC-ESI-LTQ-Orbitrap-MS systems. PRR4-rich region and ten spots with vast polymorphisms (Mr : 17-30 kDa, pI: 3.0-6.6) were identified in 1DE and 2DE gels, respectively. In addition, combinations of four types of PTMs, which are methylation, acetylation, oxidation, and pyroglutamate formation, were i…
Cadmium, Smoking, and Human Blood DNA Methylation Profiles in Adults from the Strong Heart Study
2020
The epigenetic effects of individual environmental toxicants in tobacco remain largely unexplored. Cadmium (Cd) has been associated with smoking-related health effects, and its concentration in tobacco smoke is higher in comparison with other metals. We studied the association of Cd and smoking exposures with human blood DNA methylation (DNAm) profiles. We also evaluated the implication of findings to relevant methylation pathways and the potential contribution of Cd exposure from smoking to explain the association between smoking and site-specific DNAm. We conducted an epigenome-wide association study of urine Cd and self-reported smoking (current and former vs. never, and cumulative smoki…
Epigenetic modifications precede molecular alterations and drive human hepatocarcinogenesis
2021
Development of primary liver cancer is a multistage process. Detailed understanding of sequential epigenetic alterations is largely missing. Here, we performed Infinium Human Methylation 450k BeadChips and RNA-Seq analyses for genome-wide methylome and transcriptome profiling of cirrhotic liver (n = 7), low- (n = 4) and high-grade (n = 9) dysplastic lesions, and early (n = 5) and progressed (n = 3) hepatocellular carcinomas (HCC) synchronously detected in 8 patients with HCC with chronic hepatitis B infection. Integrative analyses of epigenetically driven molecular changes were identified and validated in 2 independent cohorts comprising 887 HCCs. Mitochondrial DNA sequencing was further em…
Chemoradiotherapy of Newly Diagnosed Glioblastoma With Intensified Temozolomide
2009
Purpose To evaluate the toxicity and efficacy of chemoradiotherapy with temozolomide (TMZ) administered in an intensified 1-week on/1-week off schedule plus indomethacin in patients with newly diagnosed glioblastoma. Patients and Methods A total of 41 adult patients (median Karnofsky performance status, 90%; median age, 56 years) were treated with preirradiation TMZ at 150 mg/m 2 (1 week on/1 week off), involved-field radiotherapy combined with concomitant low-dose TMZ (50 mg/m 2 ), maintenance TMZ starting at 150 mg/m 2 using a 1-week on/1-week off schedule, plus maintenance indomethacin (25 mg twice daily). Results The median follow-up interval was 21.7 months. Grade 4 hematologic toxicit…
MGMT promoter methylation status and prognosis of patients with primary or recurrent glioblastoma treated with carmustine wafers
2013
The prognostic role of O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastoma patients treated with carmustine (BCNU) wafer implantation is unclear. Here, we report on a retrospective study of 47 patients with either newly diagnosed (30 patients) or recurrent (17 patients) glioblastoma (WHO grade IV) treated with BCNU (bis-chloroethylnitrosourea) wafers. Thirteen of the newly diagnosed patients received local BCNU and irradiation only (first-line BCNU), while 17 patients additionally received concomitant and adjuvant temozolomide (TMZ) radiochemotherapy (first-line BCNU + TMZ). Of the 17 patients treated for recurrent glioblastoma (second-line BCNU), 16 had rec…