8 research outputs found

    Reversal of P-glycoprotein-mediated multidrug resistance by a synthetic α-aminoxy peptidomimetic

    No full text
    The lack of selectivity and adequate potency of currently known P-glycoprotein (P-gp) inhibitors obscured their further development for clinical use to circumvent P-gp-mediated multidrug resistance (MDR), which necessitates the investigation of novel ones with higher potency and better specificity. The present study investigated the reversal effect of a new synthetic α-aminoxy lysine-peptidomimetic (Lys-P) on P-gp-mediated MDR. Effects of Lys-P on cytotoxicity of P-gp substrate doxorubicin (Dox) and intracellular accumulation of another P-gp substrate rhodamine 123 were examined in HEK293 cells. Its interaction mechanism and effect on P-gp expression were further investigated using ATPase assay and Western blot in Caco-2 cells, respectively. Lys-P restored the cytotoxicity of Dox toward the resistant MDR1-transfected HEK293 and MCF-7 TX400 cells without affecting their corresponding parental cells. It also significantly increased intracellular accumulation (21-fold) of rhodamine 123 in HEK293 MDR1 cells. Further mechanistic studies demonstrated that in the Caco-2 cell monolayer model, Lys-P abolished the P-gp-mediated efflux of Dox due to uncompetitive inhibition of P-gp ATPase without altering P-gp expression. Our findings demonstrated that Lys-P can be used as a promising lead compound for further development into selective and efficient MDR reversing agents for combination use with P-gp substrate drugs in cancer chemotherapy. © 2012 Elsevier B.V. All rights reserved.link_to_subscribed_fulltex

    Review on Physiotherapy Service for Stroke Patients of the Extended Rehabilitation Ward in Princess Margaret Hospital

    No full text
    HAC 2017 will focus on the Hospital Authority’s core values, viz. "People-centred Care", "Professional Service", "Committed Staff" and "Teamwork'

    Physiotherapy Service Review for Stroke Patients of the Extended Rehabilitation Ward of Princess Margaret Hospital

    No full text
    HAC 2017 will focus on the Hospital Authority’s core values, viz. "People-centred Care", "Professional Service", "Committed Staff" and "Teamwork'
    corecore