Hepatoblastoma (HB) is the most common pediatric primary liver tumor. About 20% of affected children have pulmonary metastasis at presentation. Survival rates for these children are dismal, not exceeding 25%. To study this subset of patients, we sequenced a metastatic HB cell line, HLM_2, and identified downregulation of the Liver X Receptor (LXR)/Retinoid X Receptor (RXR) pathway. LXR/RXRs function as transcriptional regulators that influence genes implicated in HB development, including the Wnt/β-catenin signaling pathway. We assessed the effects of a novel LXR/RXR agonist, UAB116, on metastatic HB, hypothesizing that this compound would affect genes governing the Wnt/β-catenin pathway, decreasing the metastatic phenotype of HLM_2 metastatic HB cells. We evaluated its effects on viability, proliferation, stemness, clonogenicity, and motility, and performed RNA sequencing to study differential gene regulation. Treatment with UAB116 for 72 h decreased HLM_2 proliferation, stemness, clonogenicity, and invasion. RNA sequencing identified an eight-fold increase in TRIM29, a gene known to inhibit β-catenin, in cells treated with UAB116. Administration of the LXR/RXR agonist, UAB116, reduces proliferation, stemness, and invasiveness of metastatic HB cells, potentially by upregulation of TRIM29, a known modulator of the Wnt/β-catenin pathway, providing support for further exploration of LXR/RXR agonism as a therapeutic strategy for metastatic HB.

Hospitalized patients are subject to overnight vital sign (OVS) monitoring which leads to subsequent sleep disturbance and contributes to adverse outcomes and negative hospital experiences. Studies in pediatric populations have shown that routine OVS checks infrequently detect significant events. We hypothesized that OVS monitoring in pediatric surgery patients rarely detects abnormalities resulting in meaningful interventions. We performed a retrospective chart review of patients ≥ 5 years old admitted to the pediatric surgery service at a stand-alone Children's Hospital from 2019 to 2021. ICU patients were excluded from analysis. Overnight vital signs were defined as those recorded every 4 h between 10:00 PM and 6:00 AM. Abnormal OVS and subsequent interventions were recorded. Analysis included 354 patients aged 5-19 years old. At least one OVS was abnormal in 62% of patients. Abnormal blood pressure was the most commonly flagged OVS (80%). The rate of intervention for flagged OVS was 58%. Medication administration was the most common intervention (54%). Unplanned operative intervention and transfer to the ICU were uncommon but did occur in this cohort (0.9% and 1.4%, respectively). The majority of pediatric surgery patients had at least one flagged OVS and, while rare, some serious complications were detected. While minimizing sleep disturbance and maximizing patient satisfaction is valuable, these results support prioritizing patient safety with routine vital sign assessments until we can determine if there are sub-populations that can be safely managed without sleep disruptions. Level 4. Retrospective chart review.

The primary goal in the treatment of pediatric malignancies is to maintain effective cancer control while minimizing toxicities and late effects. Radiotherapy is a component of standard therapy against many pediatric cancers, but tumor cell DNA damage repair mechanisms and the hypoxic tumor microenvironment may limit the effectiveness of this modality. Additionally, irradiated cancer cells often acquire resistance to radiotherapy that permits cancer cell survival or stimulates tumor regrowth after treatment, further limiting the efficacy of radiotherapy. Various preclinical studies have investigated the potential of combining chemotherapy or immunotherapy with radiotherapy, with the goal of inducing a more lethal amount of DNA damage and prohibiting cells from acquiring radiotherapy resistance. This review provides an overview of the current strategies to enhance cancer cell response to radiotherapy, providing a framework to improve outcomes for children with solid tumors.