Purpose: Prospective trials have reported isotoxicity and improved oncologic outcomes with external beam radiation therapy (EBRT) microboost to a dominant intraprostatic lesion. There is often variability in the rate of adoption of new treatments, and current microboost practice patterns are unknown. We leveraged prospectively collected data from the multicenter Michigan Radiation Oncology Quality Consortium to understand the current state of microboost usage for localized prostate cancer.
View Article and Find Full Text PDFThe glioblastoma (GBM) microenvironment is enriched in immunosuppressive factors that potently interfere with the function of cytotoxic T lymphocytes. Cancer cells can directly impact the immune system, but the mechanisms driving these interactions are not completely clear. Here we demonstrate that the polyamine metabolite spermidine (SPD) is elevated in the GBM tumor microenvironment.
View Article and Find Full Text PDFCell death frequently occurs in the pathogenesis of obesity and metabolic dysfunction-associated fatty liver disease (MAFLD). However, the exact contribution of core cell death machinery to disease manifestations remains ill-defined. Here, we show via the direct comparison of mice genetically deficient in the essential necroptotic regulators, receptor-interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like (MLKL), as well as mice lacking apoptotic caspase-8 in myeloid cells combined with RIPK3 loss, that RIPK3/caspase-8 signaling regulates macrophage inflammatory responses and drives adipose tissue inflammation and MAFLD upon high-fat diet feeding.
View Article and Find Full Text PDFApoptotic cell death is regulated by the BCL-2 protein family, with clusters of BAK or BAX homodimers driving pore formation in the mitochondrial outer membrane via a poorly understood process. There is growing evidence that, in addition to BAK and BAX, lipids play an important role in pore formation. Towards a better understanding of the lipidic drivers of apoptotic pore formation in isolated mitochondria, two complementary approaches were taken.
View Article and Find Full Text PDFIntroduction: Multidisciplinary care (MDC) for late-stage chronic kidney disease (CKD) has been associated with improved patient outcomes compared with traditional nephrology care; however, the optimal MDC model is unknown. In 2015, we implemented a novel MDC model for patients with late-stage CKD informed by the Chronic Care Model conceptual framework, including an expanded MDC team, care plan meetings, clinical risk prediction, and a patient dashboard.
Methods: We conducted a single-center, retrospective cohort study of adults with late-stage CKD (estimated glomerular filtration rate [eGFR] < 30 ml/min per 1.