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- W2113896257 abstract "We have studied the antitumoral activity of two new pyrazolo[3,4-d]pyrimidine compounds (CLM3 and CLM29) in primary papillary dedifferentiated thyroid cancer (DePTC) cells.The antiproliferative effect was tested in DePTC cells obtained at reoperation from patients with recurrence of the tumor. The concentrations of CLM3 and CLM29 used in the in vitro experiments were 1, 10, 30, and 50 μm.Proliferation assays in DePTC cells showed a significant reduction of proliferation by CLM3 and CLM29, which was by 12% with CLM3 (the most potent compound) 10 μm, 43% with CLM3 30 μm, and 60% with CLM3 50 μm. CLM3 and CLM29 increased the percentage of apoptotic cells in DePTC cells dose dependently (P < 0.001) and inhibited migration (P < 0.001). A DePTC cell line (AL) was injected sc in CD nu/nu mice, and tumor masses became detectable 10 d after xenotransplantation. CLM3 (40 mg/kg · die) significantly inhibited tumor growth and weight, and the therapeutic effect was significant starting on the 19th day after cell implantation (4 d after the beginning of treatment). The CLM3-treated group of animals did not show any appreciable toxicity. CLM3 and CLM29 increased thrombospondin-1 expression in the AL cell line. A significant reduction of microvessels and in the percentage of antivascular endothelial growth factor antibody immunoreactivity was observed in the CLM3 treated tumors, with a simultaneous increase of the percentage of necrosis.The antitumoral activity of two new pyrazolo[3,4-d]pyrimidine compounds (CLM3, CLM29) in vitro and CLM3 in vivo in DePTC has been shown, opening the way to a future clinical evaluation." @default.
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- W2113896257 date "2011-02-01" @default.
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- W2113896257 title "Novel Pyrazolopyrimidine Derivatives as Tyrosine Kinase Inhibitors with Antitumoral Activity in Vitro and in Vivo in Papillary Dedifferentiated Thyroid Cancer" @default.
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- W2113896257 doi "https://doi.org/10.1210/jc.2010-1905" @default.
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