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Author (up) Chan, D.; Zheng, Y.; Tyner, J.W.; Chng, W.J.; Chien, W.W.; Gery, S.; Leong, G.; Braunstein, G.D.; Koeffler, H.P. url  doi
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  Title Belinostat and panobinostat (HDACI): in vitro and in vivo studies in thyroid cancer Type Journal Article
  Year 2013 Publication Journal of Cancer Research and Clinical Oncology Abbreviated Journal J Cancer Res Clin Oncol  
  Volume Issue Pages  
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  Abstract PURPOSE: Advanced thyroid cancer responds poorly to most therapies. New therapies and combinations are needed. The aim of this study was to examine both in vitro and in vivo activity of two relatively new histone deacetylase inhibitors (HDACIs), belinostat and panobinostat, and a variety of tyrosine kinase inhibitors (TKIs) against a panel of nine human thyroid cancer cell lines. METHODS: The anti-proliferative activity and the effects of HDACIs, TKIs and their combinations on thyroid cancer cells were determined by cytotoxicity assays, microarray and immunoblot analyses. Synergism between HDACIs and TKIs was assessed by the median effects model of Chou-Talalay (Calcusyn(R)). RESULTS: Belinostat and panobinostat were active against the thyroid cancer cell lines irrespective of their mutational composition, and belinostat was effective in preventing growth of human thyroid cancer xenografts in immunodeficient mice. Further studies showed that both HDACIs induced apoptosis. HDACI also elevated acetylated histone 3, p21Waf, and PARP, and decreased levels of phosphorylated ERK and AKT (Ser473). RNA assay analysis suggested both HDACIs modulated genes associated with the cell cycle, DNA damage and apoptosis. Most of the TKI (pazopanib, motesanib, sorafenib and dasatinib) were either inactive in vitro or were active only at high doses. However, the novel combinations of either pazopanib or dasatinib TKIs with either belinostat or panobinostat synergistically inhibited cell growth of thyroid cancer cells in vitro. CONCLUSIONS: In summary, these HDACIs either alone or combined with selected TKIs may have a role in treatment of aggressive thyroid cancer.  
  Address National University Hospital, National University Cancer Institute Singapore, 1E Kent Ridge Road, Singapore, 119228, Singapore  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0171-5216 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:23824064 Approved no  
  Call Number @ @ Serial 40810  
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