Comprehensive assessment of blood-brain barrier opening and sterile inflammatory response: unraveling the therapeutic window.

Microbubbles (MBs) combined with focused ultrasound (FUS) has emerged as a promising noninvasive technique to permeabilize the blood-brain barrier (BBB) for drug delivery into the brain. However, the safety and biological consequences of BBB opening (BBBO) remain incompletely understood. This study aims to investigate the effects of two parameters mediating BBBO: microbubble volume dose (MVD) and mechanical index (MI).

Development of Chromosome 1q+ Specific Treatment for Highest Risk Pediatric Posterior Fossa Ependymoma.

Purpose: There are no effective treatment strategies for children with highest-risk posterior fossa group A ependymoma (PFA). Chromosome 1q gains (1q+) are present in approximately 25% of newly diagnosed PFA tumors, and this number doubles at recurrence. Seventy percent of children with chromosome 1q+ PFA will die because of the tumor, highlighting the urgent need to develop new therapeutic strategies for this population.

Comprehensive Assessment of Blood-Brain Barrier Opening and Sterile Inflammatory Response: Unraveling the Therapeutic Window.

Unlabelled: Microbubbles (MBs) combined with focused ultrasound (FUS) have emerged as a promising noninvasive technique to permeabilize the blood-brain barrier (BBB) for drug delivery to the brain. However, the safety and biological consequences of BBB opening remain incompletely understood. This study investigates the effects of varying microbubble volume doses (MVD) and ultrasound mechanical indices (MI) on BBB opening and the sterile inflammatory response (SIR) using high-resolution ultra-high field MRI-guided FUS in mouse brains.

MRI-guided focused ultrasound blood-brain barrier opening increases drug delivery and efficacy in a diffuse midline glioma mouse model.

Background: Diffuse intrinsic pontine glioma (DIPG) is the most common and deadliest pediatric brainstem tumor and is difficult to treat with chemotherapy in part due to the blood-brain barrier (BBB). Focused ultrasound (FUS) and microbubbles (MBs) have been shown to cause BBB opening, allowing larger chemotherapeutics to enter the parenchyma. Panobinostat is an example of a promising in vitro agent in DIPG with poor clinical efficacy due to low BBB penetrance.

MRI-Guided Focused Ultrasound Blood-Brain Barrier Opening Increases Drug Delivery and Efficacy in a Diffuse Midline Glioma Mouse Model.

Unlabelled: Diffuse intrinsic pontine glioma (DIPG) is the most common and deadliest pediatric brainstem tumor and is difficult to treat with chemotherapy in part due to the blood-brain barrier (BBB). Focused ultrasound (FUS) and microbubbles (MBs) have been shown to cause BBB disruption (BBBD), allowing larger chemotherapeutics to enter the parenchyma. Panobinostat is an example of a promising agent in DIPG with poor clinical efficacy due to low BBB penetrance.

Senescence Induced by BMI1 Inhibition Is a Therapeutic Vulnerability in H3K27M-Mutant DIPG.

Diffuse intrinsic pontine glioma (DIPG) is an incurable brain tumor of childhood characterized by histone mutations at lysine 27, which results in epigenomic dysregulation. There has been a failure to develop effective treatment for this tumor. Using a combined RNAi and chemical screen targeting epigenomic regulators, we identify the polycomb repressive complex 1 (PRC1) component BMI1 as a critical factor for DIPG tumor maintenance in vivo.

Establishment of patient-derived orthotopic xenograft model of 1q+ posterior fossa group A ependymoma.

Background: Treatment for pediatric posterior fossa group A (PFA) ependymoma with gain of chromosome 1q (1q+) has not improved over the past decade owing partially to lack of clinically relevant models. We described the first 2 1q+ PFA cell lines, which have significantly enhanced our understanding of PFA tumor biology and provided a tool to identify specific 1q+ PFA therapies. However, cell lines do not accurately replicate the tumor microenvironment.

Quantitative NMR-Based Metabolomics on Tissue Biomarkers and Its Translation into In Vivo Magnetic Resonance Spectroscopy.

Nuclear magnetic resonance (NMR) spectroscopy is an established analytical platform for analyzing metabolic profiles of cells, tissues, and body fluids. There are several advantages in introducing an NMR-based study design into metabolomics studies, including a fast and comprehensive detection, characterization, and quantification of dozens of endogenous metabolites in a single NMR spectrum. Quantitative proton H-NMR is the most useful NMR-based platform for metabolomics.