While no significant increase of REST RNA levels was found in HD cellular and mouse models, they demonstrated that loss of Htt function leads to nuclear translocation of REST in various HD cellular models, thereby causing a REST-mediated repression of several neuronal genes and contributing to neuronal dysfunction.
In another study, while they showed increased TCF7L2 mRNA expression levels in the islets of various rodent T2D models, they demonstrated that TCF7L2 protein levels were actually decreased [ 17].
Given that these curves are adjusted for the covariates as in the models, they demonstrate that the subsequent breast cancer rates were similar for the switchers as those who used AIs exclusively.
Importantly, using in vivo models they demonstrate that tyrosine kinase inhibitors which target RET can block primary tumour growth of ER-positive breast cancers with an efficiency that is comparable with endocrine agents, the current standard of care for this subset of tumours.
In their substrate-bound models, they demonstrate that in the Fe(II -ARD form the substrate can coordII -ARDia its adjacent oxygen moieties O1 and O2 without steric restriction, while in the Ni(II)-enzyme the steric interformnce of the162 (Fig. 25) makesubstrateO3 binding stericanly more favorable.
In an animal model they demonstrated that exercise is beneficial to reduce atherosclerosis only when combined with dietary intervention [ 36].
Using this same injury model, they demonstrated that a fibrinolytic agent, tissue plasminogen activator, decreased pulmonary edema, airway obstruction and airway pressures and improved gas exchange [ 68].
By using conditional knockout mice for Dicer crossed with a K-Ras driven lung cancer model they demonstrated that a global reduction of miRNA biogenesis leads to reduced survival in affected mice.
In a mouse model, they demonstrated that ABCA1, a membrane transporter regulating the transbilayer distribution of PS at the outer leaflet of the plasma membrane, contributes to the pathogenesis of cerebral malaria by affecting MP shedding.
39 These data have been confirmed by Daydé et al who reported that in mice rituximab concentrations were inversely correlated with tumor burden, and using a pharmacokinetic pharmacodynamic model, they demonstrated that tumor burden significantly influenced rituximab efficacy.
In a mammary cancer model they demonstrated that although estradiol and the antiandrogen tamoxifen increased mRNA and intracellular VEGF protein, the secreted VEGF to the extracellular phase, and thereby angiogenesis, was decreased by the latter substance.
