Publications by authors named "R O Bash"
Key molecular regulators of acquired radiation resistance in recurrent glioblastoma (GBM) are largely unknown, with a dearth of accurate preclinical models. To address this, we generated 8 GBM patient-derived xenograft (PDX) models of acquired radiation therapy-selected (RTS) resistance compared with same-patient, treatment-naive (radiation-sensitive, unselected; RTU) PDXs. These likely unique models mimic the longitudinal evolution of patient recurrent tumors following serial radiation therapy.
View Article and Find Full Text PDFRiverine floods are among the most costly natural disasters in the United States, and floods are generally projected to increase in frequency and magnitude with climate change. Faced with these increasing risks, improved information is needed to direct limited resources toward the most cost-effective adaptation actions available. Here we leverage a newly available flood risk dataset for residential properties in the conterminous United States to calculate expected annual damages to residential structures from inland/riverine flooding at a property-level; the cost of property-level adaptations to protect against future flood risk; and the benefits of those adaptation investments assuming both static and changing climate conditions.
View Article and Find Full Text PDFBackground: Glioblastoma-associated macrophages and microglia (GAMs) are the predominant immune cells in the tumor microenvironment. Activation of MerTK, a receptor tyrosine kinase, polarizes GAMs to an immunosuppressive phenotype, promoting tumor growth. Here, the role of MerTK inhibition in the glioblastoma microenvironment is investigated in vitro and in vivo.
View Article and Find Full Text PDFArticle Synopsis
- Glioblastoma (GBM) is a common and aggressive brain tumor with poor prognosis, and specific mutations in the PIK3CA gene are believed to play a crucial role in tumor growth and reaction to treatment.
- Researchers examined the effects of PIK3CA mutations in both normal human astrocytes and mouse models to understand their role in gliomagenesis and treatment response using targeted inhibitors.
- Findings showed that specific mutations in the PIK3CA gene influence tumor formation differently; while they didn't affect sensitivity to single inhibitors, mutations in the helical domain enhanced the effectiveness of combined PI3K and MEK inhibitors, suggesting a potential targeted therapy approach for patients with these mutations.
Background: Glioma-associated macrophages and microglia (GAMs) are components of the glioblastoma (GBM) microenvironment that express MerTK, a receptor tyrosine kinase that triggers efferocytosis and can suppress innate immune responses. The aim of the study was to define MerTK as a therapeutic target using an orally bioavailable inhibitor, UNC2025.
Methods: We examined MerTK expression in tumor cells and macrophages in matched patient GBM samples by double-label immunohistochemistry.