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Author (up) Antonelli, A.; Bocci, G.; Fallahi, P.; La Motta, C.; Martina Ferrari, S.; Mancusi, C.; Fioravanti, A.; Di Desidero, T.; Sartini, S.; Corti, A.; Piaggi, S.; Materazzi, G.; Spinelli, C.; Fontanini, G.; Danesi, R.; Da Settimo, F.; Miccoli, P. url  doi
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  Title CLM3, a multitarget tyrosine kinase inhibitor with antiangiogenic properties, is active against primary anaplastic thyroid cancer in vitro and in vivo Type Journal Article
  Year 2014 Publication The Journal of Clinical Endocrinology and Metabolism Abbreviated Journal J Clin Endocrinol Metab  
  Volume Issue Pages jc20132321  
  Keywords  
  Abstract Context and Objective. We have studied the antitumor activity of a “pyrazolo[3,4-d]pyrimidine” compound (CLM3) proposed for a multiple signal transduction inhibition [including the RET tyrosine kinase, epidermal growth factor receptor, vascular endothelial growth factor (VEGF) receptor (VEGFR) and with antiangiogenic activity], in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C (undifferentiated thyroid cancer) and in an ATC-cell line (AF). Design and Main Outcome Measures. CLM3 was tested: in primary ATC cells at the concentrations of 5, 10, 30, 50 muM; in 8305C cells, and in AF cells, at 1, 5, 10, 30, 50 or 100 muM; in AF cells in CD nu/nu mice. Results. CLM3 significantly inhibited proliferation of 8305C and AF cells, inducing also apoptosis. A significant reduction of proliferation with CLM3 in ATC cells (P < 0.01, ANOVA) was shown. CLM3 increased the percentage of apoptotic ATC cells dose-dependently (P < 0.001, ANOVA) and inhibited migration (P < 0.01) and invasion (P < 0.001). AF-cell line was injected sc in CD nu/nu mice and tumor masses became detectable 15 days after. CLM3 (50 mg/kg/die) inhibited significantly tumor growth (starting 16 days after the beginning of treatment). CLM3 significantly decreased the VEGF-A expression and microvessel density in AF tumor tissues. Furthermore, CLM3 inhibited EGFR, AKT and ERK1/2 phosphorylation and down-regulated cyclin D1 in 8305C and AF cells. Conclusions. The antitumor and antiangiogenic activity of a “pyrazolo[3,4-d]pyrimidine” compound (CLM3) is very promising in anaplastic thyroid cancer, opening the way to a future clinical evaluation.  
  Address Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126, Pisa, Italy  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0021-972X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:24423321 Approved no  
  Call Number refbase @ admin @ Serial 35477  
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