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• W2018717541 abstract "Abstract Background ABT‐751, an orally bioavailable sulfonamide, binds β‐tubulin to inhibit microtubule polymerization. We described response and event‐free survival (EFS) in children with neuroblastoma and other solid tumors receiving ABT‐751, assessed in vitro cytotoxicity of ABT‐751 and evaluated the effect of ABT‐751 on tubulin polymerization in peripheral blood mononuclear cells (PBMC) and pediatric tumor cell lines. Procedure Patients with neuroblastoma (n = 50) or other solid tumors (n = 26) enrolled on the ABT‐751 pediatric phase I and pilot trials were reviewed. The sulforhodamine B (SRB) and ACEA Real‐Time Cell Electronic Sensing (RT‐CES) assays were used to determine the in vitro cytotoxicity. Pharmacodynamic effects on tubulin polymerization/depolymerization were assessed by Western blot and confocal microscopy using antibodies specific for post‐translational modifications of polymerized tubulin. Results Forty‐five patients with neuroblastoma were evaluated for anti‐tumor response. No complete or partial responses were documented. The median EFS was 9.3 weeks for children with neuroblastoma and 3.3 weeks for children other solid tumors ( P < 0.0001). The ABT‐751 IC 50 was 0.6–2.6 mcM in neuroblastoma and 0.7–4.6 mcM in other solid tumor cell lines. Following drug exposure, polymerized tubulin decreased in a concentration‐ and time‐dependent manner in cell lines. Conclusions In children treated with ABT‐751, the EFS is longer in children with neuroblastoma as compared to other diagnoses. In vitro, ABT‐751 was cytotoxic at concentrations tolerable in children. Effects of ABT‐751 on polymerization and microtubule structure were time‐ and dose‐dependent but not dependent on tumor type. Pediatr Blood Cancer 2010; 54:47–54. © 2009 Wiley‐Liss, Inc." @default.
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• W2018717541 date "2009-09-03" @default.
• W2018717541 modified "2023-10-16" @default.
• W2018717541 title "Clinical outcome in children with recurrent neuroblastoma treated with ABT-751 and effect of ABT-751 on proliferation of neuroblastoma cell lines and on tubulin polymerization in vitro" @default.
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• W2018717541 doi "https://doi.org/10.1002/pbc.22267" @default.
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