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• W4362478896 abstract "<div>Abstract<p>LY573636-sodium (tasisulam) is a small molecule antitumor agent with a novel mechanism of action currently being investigated in a variety of human cancers. <i>In vitro</i>, tasisulam induced apoptosis via the intrinsic pathway, resulting in cytochrome <i>c</i> release and caspase-dependent cell death. Using high content cellular imaging and subpopulation analysis of a wide range of <i>in vitro</i> and <i>in vivo</i> cancer models, tasisulam increased the proportion of cells with 4N DNA content and phospho-histone H3 expression, leading to G₂–M accumulation and subsequent apoptosis. Tasisulam also blocked VEGF, epidermal growth factor, and fibroblast growth factor–induced endothelial cell cord formation but did not block acute growth factor receptor signaling (unlike sunitinib, which blocks VEGF-driven angiogenesis at the receptor kinase level) or induce apoptosis in primary endothelial cells. Importantly, <i>in vivo</i> phenocopying of <i>in vitro</i> effects were observed in multiple human tumor xenografts. Tasisulam was as effective as sunitinib at inhibiting neovascularization in a Matrigel plug angiogenesis assay <i>in vivo</i> and also caused reversible, non G₂–M–dependent growth arrest in primary endothelial cells. Tasisulam also induced vascular normalization <i>in vivo.</i> Interestingly, the combination of tasisulam and sunitinib significantly delayed growth of the Caki-1 renal cell carcinoma model, whereas neither agent was active alone. These data show that tasisulam has a unique, dual-faceted mechanism of action involving mitotic catastrophe and antiangiogenesis, a phenotype distinct from conventional chemotherapies and published anticancer agents. <i>Mol Cancer Ther; 10(11); 2168–78. ©2011 AACR</i>.</p></div>" @default.
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• W4362478896 date "2023-04-03" @default.
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• W4362478896 title "Data from Tasisulam Sodium, an Antitumor Agent That Inhibits Mitotic Progression and Induces Vascular Normalization" @default.
• W4362478896 doi "https://doi.org/10.1158/1535-7163.c.6535222" @default.
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