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  • 1
    Abstract: The SWI/SNF chromatin-remodeling complex regulates gene expression and alters chromatin structures in an ATP-dependent manner. Recent sequencing efforts have shown mutations in BRG1 (SMARCA4), one of two mutually exclusive ATPase subunits in the complex, in a significant number of human lung tumor cell lines and primary non-small cell lung carcinoma (NSCLC) clinical specimens. To determine how BRG1 loss fuels tumor progression in NSCLC, molecular profiling was performed after restoration of BRG1 expression or treatment with a histone deacetylase inhibitor or a DNA methyltransferase (DNMT) inhibitor in a BRG1-deficient NSCLC cells. Importantly, validation studies from multiple cell lines revealed that BRG1 reexpression led to substantial changes in the expression of CDH1, CDH3, EHF, and RRAD that commonly undergo silencing by other epigenetic mechanisms during NSCLC development. Furthermore, treatment with DNMT inhibitors did not restore expression of these transcripts, indicating that this common mechanism of gene silencing did not account for their loss of expression. Collectively, BRG1 loss is an important mechanism for the epigenetic silencing of target genes during NSCLC development. IMPLICATIONS: Inactivation of the SWI/SNF complex provides a novel mechanism to induce gene silencing during NSCLC development.
    Type of Publication: Journal article published
    PubMed ID: 24445599
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  • 2
    ISSN: 1432-1041
    Keywords: Intracranial hypertension ; dimethyl sulphoxide (DMSO) ; head injury treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten patients with closed head trauma and elevated intracranial pressure (ICP) ranging from 40–127 mm Hg were treated with intravenous dimethyl sulphoxide (DMSO) every 6 h for 1–10 days. Four patients received DMSO and intermittent oxygen. All patients showed a reduction of ICP after 24 h and 7 had normal ICP after 6 days of treatment. Two patients died of their injuries. Neurological assessment at the time of discharge showed 2 patients with severe neurological deficits and 6 patients with mild to no deficit. After a 3 month follow-up, 1 patient remained severely impaired and 7 patients showed mild to no deficit. It appears that intravenous DMSO can rapidly reduce elevated ICP in severe closed-head injury and that it improves neurological outcome.
    Type of Medium: Electronic Resource
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