Radiotherapy is an integral component in the treatment of many types of cancer, with approximately half of cancer patients receiving radiotherapy. Systemic therapy applies pressure that can select for resistant tumor subpopulations, underscoring the importance of understanding how radiation impacts tumor evolution to improve treatment outcomes. We integrated temporal genomic profiling of 120 spatially distinct tumor regions from 20 patients with undifferentiated pleomorphic sarcomas (UPS), longitudinal circulating tumor DNA (ctDNA) analysis, and evolutionary biology computational pipelines to study UPS evolution during tumorigenesis and in response to radiotherapy.
View Article and Find Full Text PDFBackground: Atrial fibrillation (AF) has been associated with thoracic radiotherapy, but the specific risk with irradiating different cardiac substructures remains unknown.
Objectives: This study sought to examine the relationship between irradiation of cardiac substructures and the risk of clinically significant (grade ≥3) AF.
Methods: We analyzed data from patients who underwent definitive radiotherapy for localized cancers (non-small cell lung, breast, Hodgkin lymphoma, or esophageal) at our institution between 2004 and 2022.
Diabetes is a major risk factor for cardiovascular disease, but the molecular mechanisms underlying diabetic vasculopathy have been elusive. Here we report that inositol hexakisphosphate kinase 1 (IP6K1) mediates hyperglycemia-induced endothelial senescence by rewiring the liver kinase B1 (LKB1) signaling from activating the adenosine monophosphate-activated protein kinase (AMPK) pathway to the p53 pathway. We found that hyperglycemia upregulated IP6K1, which disrupts the Hsp/Hsc70 and carboxyl terminus of Hsc70-interacting protein (CHIP)-mediated LKB1 degradation, leading to increased expression levels of LKB1.
View Article and Find Full Text PDFLong non-coding RNAs (lncRNAs) are essential components of innate immunity, maintaining the functionality of immune systems that control virus infection. However, how lncRNAs engage immune responses during influenza A virus (IAV) infection remains unclear. Here, we show that lncRNA USP30-AS1 is up-regulated by infection of multiple different IAV subtypes and is required for tuning inflammatory and antiviral response in IAV infection.
View Article and Find Full Text PDFBackground: Cognitive frailty (CF) is a major precursor to dementia, and multidomain interventions have the potential to delay, prevent or reverse its early onset. However, the successful translation and sustainability of such interventions in real-life settings remain uncertain. In this study, we aimed to explore the insights of older adults with CF and their caregivers regarding the impact and participation in the AGELESS multidomain intervention.
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