UNASSIGNED: Compelling epidemiologic studies indicate that @entity28 is a risk factor for many @entity1 @entity5 , including @entity259 . In recent decades, the incidence of @entity259 has dramatically increased along with a marked rise in @entity28 prevalence. We previously demonstrated that a high fat diet (HFD) effectively induced the @entity28 phenotype in a @entity19 model of @entity259 (Thrb(PV/PV)Pten(+/-) @entity19 ). Moreover, HFD activates the @entity10433 signal pathway to promote more @entity146 phenotypes. The aim of the present study was to evaluate the effect of S3I-201, a specific inhibitor of @entity10433 activity, on HFD-induced aggressive @entity5 progression in the @entity19 model of @entity259 . WT and Thrb(PV/PV)Pten(+/-) @entity19 were treated with HFD together with S3I-201 or vehicle-only as controls. We assessed the effects of @entity45323 on HFD-induced @entity259 progression, the leptin- @entity16404 - @entity10433 signaling pathway, and key regulators of epithelial-mesenchymal transition (EMT). S3I-201 effectively inhibited HFD-induced aberrant activation of @entity10433 and its downstream targets to markedly inhibit @entity259 growth and to prolong survival. Decreased protein levels of cyclins @entity69006 , @entity11953 ( @entity11953 ), @entity11954 , and @entity995 protein led to the inhibition of @entity5 cell proliferation in S3I-201-treated Thrb(PV/PV)Pten(+/-) @entity19 . Reduced occurrence of vascular invasion and blocking of @entity4575 and lung metastasis in @entity259 of S3I-201-treated Thrb(PV/PV)Pten(+/-) @entity19 were mediated via decreased expression of @entity3111 and matrix metalloproteinases, two key effectors of EMT. The present findings suggest that inhibition of the @entity10433 activity would be a novel treatment strategy for @entity28 -induced @entity259 .

Inhibition of @entity10433 activity delays XXXX -induced thyroid carcinogenesis in a @entity19 model.

@entity1 :: ('9606', 'Species') :: ['human'] @entity16404 :: ('16452(Tax:10090)', 'Gene') :: ['JAK2'] @entity69006 :: ('13370;22344', 'Gene') :: ['D1 and B1'] @entity11954 :: ('12571(Tax:10090)', 'Gene') :: ['CDK6'] @entity28 :: ('MESH:D009765', 'Disease') :: ['obesity', 'obese'] @entity146 :: ('MESH:D001523', 'Disease') :: ['aggressive tumor'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancers', 'tumor', 'cancer'] @entity3111 :: ('22352(Tax:10090)', 'Gene') :: ['vimentin'] @entity10433 :: ('20848(Tax:10090)', 'Gene') :: ['STAT3'] @entity45323 :: ('MESH:C520337', 'Chemical') :: ['S3I-201'] @entity11953 :: ('12567(Tax:10090)', 'Gene') :: ['CDK4', 'cyclin dependent kinase 4'] @entity4575 :: ('MESH:D000708', 'Disease') :: ['anaplasia'] @entity259 :: ('MESH:D013964', 'Disease') :: ['thyroid tumors', 'thyroid tumor', 'thyroid cancer'] @entity995 :: ('MESH:D012175', 'Disease') :: ['phosphorylated retinoblastoma']
@entity28 :: (MESH:D009765,Disease) :: ['obesity']
