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Pharmacokinetics, Pharmacodynamics and Bioavailability of ACM-001.1 (S-Pindolol Benzoate) in Healthy Volunteers.
J Cachexia Sarcopenia Muscle
February 2025
Quotient Sciences, Nottingham, UK.
Background: S-pindolol has metabolic effects of potential benefit in cancer cachexia: reduced catabolism through nonselective β-blockade; increased anabolism through partial β2 receptor agonism; and increased appetite and reduced fatigue through central 5-hydroxytryptamine/serotonin receptor activity. A Phase 2a clinical trial demonstrated that S-pindolol can reverse weight loss and improve fat-free mass in patients with cancer-related weight loss. A comparative phase I bioavailability study of S-pindolol and racemic pindolol was performed to support the development of S-pindolol in cancer cachexia.
View Article and Find Full Text PDFMHC class I upregulation contributes to the therapeutic response to radiotherapy in combination with anti-PD-L1/anti-TGF-β in squamous cell carcinomas with enhanced CD8 T cell memory-driven response.
Cancer Lett
January 2025
Department of Pathology, University of California, Davis, CA, USA; Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; VA Northern California Health Care System, Sacramento, CA, USA. Electronic address:
Radiation therapy (RT), a mainstay treatment for head and neck squamous cell carcinoma (HNSCC), kills cancer cells and modulates the tumor immune microenvironment. We sought to assess the effect of RT in combination with PD-L1/TGF-β dual blockade in squamous cell carcinomas (SCC) and analyze the underlying mechanisms. We transplanted mouse SCC cells derived from keratin-15 (K15) stem cells harboring Kras/Smad4 mutations into syngeneic recipients and irradiated tumors followed by PD-L1/TGF-β dual blockade.
View Article and Find Full Text PDFThe Effect of Early Beta-Blockade with Esmolol on Therapy Intensity Level in Adults with Severe Traumatic Brain Injury.
Neurotrauma Rep
October 2024
Consultant in Intensive Care Medicine, Southmead Hospital, North Bristol NHS Trust, Bristol, UK.
Following severe traumatic brain injury (TBI), elevated catecholamine levels are associated with worsened secondary brain injury and poorer clinical outcomes. The mechanisms are uncertain but may include cerebral ischemia and blood-brain barrier disruption, with consequent cerebral edema manifesting as intracranial hypertension. Early beta-blockade (EBB) may mitigate these detrimental hyperadrenergic effects.
View Article and Find Full Text PDFVascular limitations in blood pressure regulation with age in women: Insights from exercise and acute cardioselective β-blockade.
Exp Physiol
January 2025
Integrative and Biomedical Physiology, Intercollege Graduate Degree Program, The Pennsylvania State University, University Park, Pennsylvania, USA.
Younger women rely on altering cardiac output ( ) to regulate blood pressure (BP). In contrast, older women rely more on altering vascular tone. However, evidence suggests that the ability to alter systemic vascular conductance (SVC) is diminished in older women.
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