Faculty of Health Sciences (Research Outputs)

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Browsing Faculty of Health Sciences (Research Outputs) by Author "Augustine, T. N."

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    Tamoxifen induces hypercoagulation and alterations in ERα and ERβ dependent on breast cancer sub‑phenotype ex vivo
    (Nature, 2020-11-06) Pather, Kyrtania; Augustine, T. N.
    Tamoxifen shows efficacy in reducing breast cancer-related mortality but clinically, is associated with increased risk for thromboembolic events. We aimed to determine whether breast tumour subphenotype could predict propensity for thrombosis. We present two ex vivo Models of Tamoxifentherapy, Model 1 in which treatment recapitulates accumulation within breast tissue, by treating MCF7 and T47D cells directly prior to exposure to blood constituents; and Model 2 in which we recreate circulating Tamoxifen by treating blood constituents prior to exposure to cancer cells. Blood constituents included whole blood, platelet-rich plasma and platelet-poor plasma. Hypercoagulation was assessed as a function of thrombin activity, expression of CD62P and CD63 activation markers defined as an index of platelet activation, and platelet morphology; while oestrogen receptor expression was assessed using immunocytochemistry with quantitative analysis. We determined, in concert with clinical studies and contrary to selected laboratory investigations, that Tamoxifen induces hypercoagulation, dependent on sub-phenotypes, with the T47D cell line capacity most enhanced. We determined a weak positive correlation between oestrogen receptor expression, and CD62P and CD63; indicating an association between tumour invasion profiles and hypercoagulation, however, other yet unknown factors may play a predictive role in defining hypercoagulation.