More than 80% of DMGs carry specific mutations in histone H3, which causes a substitution of lysine 27 to methionine (H3K27M), initiating an oncogenic signaling cascade. These tumors show little sensitivity to classical chemotherapeutic agents, and radiotherapy only has limited impact on disease progression. Survival time is less than one year for most patients. Diffuse midline glioma (DMG formerly called diffuse intrinsic pontine glioma 1) is an incurable pediatric glioma localized in the brainstem. Controlling histone function by histone deacetylase inhibitors (HDACi) such as panobinostat (PS) (Farydak/LBH-589) is a promising therapeutic option for hematological and solid malignancies. These two proteins could be potential targets for future treatment in combination with PS.ĭuring cancer growth, changes in gene expression by alteration of epigenetic events including histone modifications are thought to have major impact on prognosis and therapeutic outcome. Combination of chemical inhibitor of EBP50 and panobinostat leads to a decrease in tumor proliferation. A new DMG model based on chick chorioallantoic membrane assay has been used to study the effects of the inhibition of EBP50 on tumor growth. This paper describes an oncogenic role of these scaffolding proteins in vitro and in vivo. To date, the role of EBP50 or IRSp53 in pediatric gliomas has not been investigated. Proteomic analysis revealed upregulation of 2 scaffolding proteins after treatment of DMG cells. Panobinostat is in clinical trials for the treatment of DMG patients.
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