0000000000920757

AUTHOR

Chris Simpson

Phase I Assessment of New Mechanism-Based Pharmacodynamic Biomarkers for MLN8054, a Small-Molecule Inhibitor of Aurora A Kinase

Abstract The mitotic kinase Aurora A is an important therapeutic target for cancer therapy. This study evaluated new mechanism-based pharmacodynamic biomarkers in cancer patients in two phase I studies of MLN8054, a small-molecule inhibitor of Aurora A kinase. Patients with advanced solid tumors received MLN8054 orally for 7 consecutive days in escalating dose cohorts, with skin and tumor biopsies obtained before and after dosing. Skin biopsies were evaluated for increased mitotic cells within the basal epithelium. Tumor biopsies were assessed for accumulation of mitotic cells within proliferative tumor regions. Several patients in the highest dose cohorts showed marked increases in the ski…

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The impact from survey depth and resolution on the morphological classification of galaxies

We consistently analyse for the first time the impact of survey depth and spatial resolution on the most used morphological parameters for classifying galaxies through non-parametric methods: Abraham and Conselice-Bershady concentration indices, Gini, M20moment of light, asymmetry, and smoothness. Three different non-local data sets are used, Advanced Large Homogeneous Area Medium Band Redshift Astronomical (ALHAMBRA) and Subaru/XMMNewton Deep Survey (SXDS, examples of deep ground-based surveys), and Cosmos Evolution Survey (COSMOS, deep space-based survey). We used a sample of 3000 local, visually classified galaxies, measuring their morphological parameters at their real redshifts (z ~ 0)…

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