@entity2867 ( @entity2867 ) has a rapidly fatal clinical course, being resistant to multimodal treatments. Microtubules, a/b tubulin heterodimers, are crucial in cell signaling, division and mitosis and are among the most successful targets for anticancer therapy. Panobinostat ( @entity13537 ) is a potent deacetylase inhibitor acting both on histones and nonhistonic proteins, including a-tubulin. In vitro @entity13537 , evaluated in three @entity2867 cell lines (BHT-101, CAL-62 and 8305C), resulted in impairment of cell viability, inhibition of colony formation, cell cycle arrest and apoptosis induction. Mechanistically, we showed that @entity13537 not only affected the expression of @entity994 and @entity4910 , but markedly determined microtubule stabilization as evidenced by tubulin acetylation and increased tubulin polymerization. In a @entity915 xenograft model implanted with @entity1 cells, the cytotoxic properties of @entity13537 were confirmed. The drug at the dose of 20 mg/kg significantly impaired @entity5 growth ( @entity5 .5-fold smaller than in untreated animals); at this dose, no relevant side effects were observed. In @entity5 of treated animals, a significant reduction of Ki67, which was negatively correlated with tubulin acetylation, was observed. Moreover, @entity16374 -tubulin levels negatively correlated with @entity5 volume at sacrifice, reinforcing the opinion that tubulin acetylation has a role in the inhibition of @entity5 growth. In conclusion, @entity13537 , acting on both histones and nonhistonic proteins in @entity259 , appears to be a promising therapeutic agent for the treatment of this kind of @entity5 which is known not to respond to conventional therapy.

Cytotoxic activity of the histone deacetylase inhibitor panobinostat ( XXXX ) in @entity259 in vitro and in vivo.

@entity1 :: ('9606', 'Species') :: ['CAL-62'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'final tumor volume 2', 'cancer', 'tumors'] @entity16374 :: ('CHEBI:40574', 'Chemical') :: ['acetyl'] @entity4910 :: ('595', 'Gene') :: ['cyclin D1'] @entity915 :: ('MESH:D053632', 'Disease') :: ['SCID'] @entity13537 :: ('MESH:C496932', 'Chemical') :: ['LBH589'] @entity259 :: ('MESH:D013964', 'Disease') :: ['anaplastic thyroid cancer'] @entity2867 :: ('MESH:D065646', 'Disease') :: ['ATC', 'Anaplastic thyroid carcinoma'] @entity994 :: ('1026', 'Gene') :: ['p21']
@entity13537 :: (MESH:C496932,Chemical) :: ['LBH589']
