Histone Deacetylase Inhibitors Target DNA Replication Regulators and Replication Stress in Ewing Sarcoma Cells.

Unlabelled: Histone deacetylases (HDAC) regulate diverse pathways in cancer cells. Previously, we identified that Ewing sarcoma tumors, which are caused by a translocation between the EWSR1 and FLI1 genes (EWS::FLI1), are sensitive to drugs that target DNA replication, including the RRM1 and RRM2 subunits of ribonucleotide reductase, and the ATR-checkpoint kinase 1 (CHK1)-WEE1 signaling pathway. In this study, we identified that multiple HDAC inhibitors, including fimepinostat, romidepsin, and panobinostat, downregulate the levels of the RRM1, RRM2, CHK1, and WEE1 proteins in Ewing sarcoma cells and impair DNA replication.

PI3Kδ Inhibition Potentiates Glucocorticoids in B-lymphoblastic Leukemia by Decreasing Receptor Phosphorylation and Enhancing Gene Regulation.

Glucocorticoids are the cornerstone of B-lymphoblastic leukemia (B-ALL) therapy. Because response to glucocorticoids alone predicts overall outcomes for B-ALL, enhancing glucocorticoid potency should improve treatment. We previously showed that inhibition of the lymphoid-restricted PI3Kδ with idelalisib enhances glucocorticoid activity in B-ALL cells.

Deacylcortivazol-like pyrazole regioisomers reveal a more accommodating expanded binding pocket for the glucocorticoid receptor.

Glucocorticoids (GCs) are widely used, potent anti-inflammatory and chemotherapeutic drugs. They work by binding to the glucocorticoid receptor (GR), a ligand-activated transcription factor, inducing translocation to the nucleus and regulation of genes that influence a variety of cellular activities. Despite being effective for a broad number of conditions, GC use is limited by severe side effects.

Evaluation of Empiric Vancomycin for Fevers During High-dose Cytarabine Administration.

Background: Cytarabine is a nucleoside analog used in chemotherapy regimens for the treatment of multiple hematologic malignancies. One of the known adverse effects of cytarabine, particularly in patients receiving high-dose cytarabine (HDAC), is drug-induced fever. Multiple studies have demonstrated an increased risk of viridans group streptococcal bacteremia in patients who have received HDAC.