ABSTRACT
The incidence of cardiogenic shock is rising, patient complexity is increasing and patient survival has plateaued. Mirroring organisational innovations of elite military units, our multidisciplinary medical specialists at the INOVA Heart and Vascular Institute aim to combine the adaptability, agility and cohesion of small teams across our large healthcare system. We advocate for widespread adoption of our 'combat' methodology focused on: increased disease awareness, early multidisciplinary shock team activation, group decision-making, rapid initiation of mechanical circulatory support (as appropriate), haemodynamic-guided management, strict protocol adherence, complete data capture and regular after action reviews, with a goal of ending preventable death from cardiogenic shock.
ABSTRACT
The nitric oxide (NO) prodrug JS-K, a promising anti-cancer agent, consists of a diazeniumdiolate group necessary for the release of NO as well as an arylating ring. In this study, we research the mechanism by which JS-K kills a murine erythroleukemia cell line and determine the roles of NO and arylation in the process. Our studies indicate that JS-K inhibits the PI 3-kinase/Akt and MAP kinase pathways. This correlates with the activation of the tumor suppressor FoxO3a and increased expression of various caspases, leading to apoptosis. The arylating capability of JS-K appears to be sufficient for inducing these biological effects. Overall, these data suggest that JS-K kills tumor cells by arylating and inactivating signaling molecules that block the activation of a tumor suppressor.
