Publications by authors named "W Tyrrell"

Mutations in the NRF2-KEAP1 pathway are common in non-small cell lung cancer (NSCLC) and confer broad-spectrum therapeutic resistance, leading to poor outcomes. Currently, there is no means to non-invasively identify NRF2 activation in living subjects. Here, we show that positron emission tomography imaging with the system x radiotracer, [F]FSPG, provides a sensitive and specific marker of NRF2 activation in orthotopic, patient-derived, and genetically engineered mouse models of NSCLC.

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The ability to image early treatment response to radiotherapy in head and neck squamous cell carcinoma (HNSCC) will enable the identification of radioresistant tumor volumes suitable for treatment intensification. Here, we propose the system x radiotracer (4)-4-(3-[F]fluoropropyl)-L-glutamate ([F]FSPG) as a non-invasive method to monitor radiation response in HNSCC. We assessed temporal changes in cell death, antioxidant status, and [F]FSPG retention following a single dose of 10 Gy irradiation in FaDU HNSCC cells.

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Background: Apparently healthy dogs of various breeds eating nontraditional, high-pulse diets can have larger left ventricular diameter, lower systolic function, and more ventricular premature complexes (VPCs) compared with dogs eating traditional, low-pulse diets. It is unknown whether Irish Wolfhounds eating high-pulse diets have similar cardiac abnormalities.

Hypothesis/objectives: To compare electrocardiographic and echocardiographic findings between Irish Wolfhounds eating high- or low-pulse diets.

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Mouse models are invaluable tools for radiotracer development and validation. They are, however, expensive, low throughput, and are constrained by animal welfare considerations. Here, we assessed the chicken chorioallantoic membrane (CAM) as an alternative to mice for preclinical cancer imaging studies.

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Mutations in the NRF2-KEAP1 pathway are common in non-small cell lung cancer (NSCLC) and confer broad-spectrum therapeutic resistance, leading to poor outcomes. The cystine/glutamate antiporter, system x, is one of the >200 cytoprotective proteins controlled by NRF2, which can be non-invasively imaged by ()-4-(3-F-fluoropropyl)-l-glutamate ([F]FSPG) positron emission tomography (PET). Through genetic and pharmacologic manipulation, we show that [F]FSPG provides a sensitive and specific marker of NRF2 activation in advanced preclinical models of NSCLC.

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