Reducing sedated lumbar punctures in pediatric patients with acute lymphoblastic leukemia.

Background: Sedation for lumbar punctures (LPs) in pediatric acute lymphoblastic leukemia (ALL) patients has been the standard for decades to reduce pain and anxiety. Recent studies on the potential long-term neurocognitive effects of cumulative propofol exposure have raised concerns about this practice. The recent pandemic introduced additional burdens to patients, with the requirement of a negative COVID-19 test prior to each sedated procedure.

Eltrombopag inhibits the proliferation of Ewing sarcoma cells via iron chelation and impaired DNA replication.

Background: The treatment of Ewing sarcoma, an aggressive bone and soft tissue sarcoma, is associated with suboptimal outcomes and significant side-effects. Consequently, there is an urgent need to identify novel therapies that will improve outcomes for children and adults with Ewing sarcoma tumors while also decreasing treatment-related toxicities.

Methods: We analyzed data from the PRISM drug repurposing screen, which tested the activity of 4518 drugs across 578 cancer cell lines, to identify drugs that selectively inhibit the growth of Ewing sarcoma cell lines.

The translational repressor 4E-BP1 regulates RRM2 levels and functions as a tumor suppressor in Ewing sarcoma tumors.

Ribonucleotide reductase (RNR), which is a heterodimeric tetramer composed of RRM1 and RRM2 subunits, is the rate-limiting enzyme in the synthesis of deoxyribonucleoside triphosphates (dNTPs) and essential for both DNA replication and the repair of DNA damage. The activity of RNR is coordinated with the cell cycle and regulated by fluctuations in the level of the RRM2 subunit. Multiple cancer types, including Ewing sarcoma tumors, are sensitive to inhibitors of RNR or a reduction in the levels of either the RRM1 or RRM2 subunits of RNR.