PURPOSE: @entity817 ( @entity8554 ) may play a role in the progression from @entity3557 to @entity259 ( @entity259 ). We tested the effects of a highly selective @entity817 ( @entity8554 ) inhibitor, @entity17169 , on proliferation, migration, and invasion both in @entity1 @entity259 cell lines (8505c(B-Raf @entity8554 ) and @entity15293 ( @entity8958 / @entity2750 and wild-type @entity817 )) and in primary @entity1 normal thyroid (NT) follicular cells engineered with or without @entity817 ( @entity8554 ). EXPERIMENTAL DESIGN: Large-scale genotyping analysis by mass spectrometry was performed in order to analyze >900 gene mutations. Cell proliferation and migration/invasion were performed upon @entity17169 treatment in 8505c, @entity15293 , and NT cells. Orthotopic implantation of either 8505c or @entity15293 cells into the thyroid of severe combined @entity465 @entity19 was performed. Gene validations were performed by quantitative polymerase chain reaction and immunohistochemistry. RESULTS: We found that @entity17169 reduced in vitro cell proliferation and migration and invasion of 8505c cells, causing early downregulation of genes involved in @entity5 progression. @entity17169 -treated NT cells overexpressing @entity817 ( @entity8554 ) (heterozygous wild-type @entity817 / @entity817 ( @entity8554 )) showed significantly lower cell proliferation, migration, and invasion. @entity17169 treatment did not block cell invasion in @entity15293 cells with wild-type @entity817 , which showed very low and delayed in vivo @entity5 growth. In vivo, @entity17169 treatment of 8505c orthotopic @entity259 inhibited @entity146 and significantly upregulated the thyroid differentiation markers @entity7457 and paired box gene 8. CONCLUSIONS: Here, we have shown that @entity17169 preferentially inhibits migration and invasion of @entity817 ( @entity8554 ) @entity259 cells and @entity146 . Normal thyroid cells were generated to be heterozygous for wild-type @entity817 / @entity817 ( @entity8554 ), mimicking the condition found in most @entity1 @entity259 . @entity17169 was effective in reducing cell proliferation, migration, and invasion in this heterozygous model. @entity17169 therapy should be tested and considered for a phase I study for the treatment of @entity1 with @entity817 ( @entity8554 ) @entity259 .

Targeting BRAFV600E with XXXX displays potent antimigratory and anti-invasive activity in preclinical models of @entity1 @entity259 .

@entity3557 :: ('MESH:C536915', 'Disease') :: ['papillary thyroid cancer'] @entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity8958 :: ('5979', 'Gene') :: ['RET'] @entity146 :: ('MESH:D001523', 'Disease') :: ['tumor aggressiveness'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity17169 :: ('MESH:C528407', 'Chemical') :: ['PLX4720'] @entity465 :: ('MESH:D007153', 'Disease') :: ['immunodeficient'] @entity8554 :: ('p|SUB|V|600|E', 'ProteinMutation') :: ['V600E'] @entity15293 :: ('53373', 'Gene') :: ['TPC-1'] @entity817 :: ('673', 'Gene') :: ['B-Raf'] @entity259 :: ('MESH:D013964', 'Disease') :: ['thyroid tumors', 'ATC', 'anaplastic thyroid cancer', 'thyroid cancer', 'thyroid cancers'] @entity7457 :: ('7080', 'Gene') :: ['thyroid transcription factor 1'] @entity2750 :: ('5727', 'Gene') :: ['PTC-1']
@entity17169 :: (MESH:C528407,Chemical) :: ['PLX4720']
