{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Mancarella S"],"funding":["Associazione Italiana per la Ricerca sul Cancro"],"pagination":["2330-2343"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7370218"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["27(8)"],"pubmed_abstract":["Intrahepatic cholangiocarcinoma (iCCA) is a deadly disease with rising incidence and few treatment options. An altered expression and/or activation of NOTCH1-3 receptors has been shown to play a role in iCCA development and progression. In this study, we established a new CCA patient-derived xenograft model, which was validated by immunohistochemistry and transcriptomic analysis. The effects of Notch pathway suppression by the Crenigacestat (LY3039478)-specific inhibitor were evaluated in human iCCA cell lines and the PDX model. In vitro, LY3039478 significantly reduced Notch pathway components, including NICD1 and HES1, but not the other Notch receptors, in a panel of five different iCCA cell lines. In the PDX model, LY3039478 significantly inhibited the Notch pathway and tumor growth to "],"journal":["Cell death and differentiation"],"pubmed_title":["Crenigacestat, a selective NOTCH1 inhibitor, reduces intrahepatic cholangiocarcinoma progression by blocking VEGFA/DLL4/MMP13 axis."],"pmcid":["PMC7370218"],"funding_grant_id":["18737"],"pubmed_authors":["Dituri F","Mancarella S","Serino G","Chen X","Wang J","Calvisi DF","Giannelli G","Cigliano A","Ribback S"],"additional_accession":[]},"is_claimable":false,"name":"Crenigacestat, a selective NOTCH1 inhibitor, reduces intrahepatic cholangiocarcinoma progression by blocking VEGFA/DLL4/MMP13 axis.","description":"Intrahepatic cholangiocarcinoma (iCCA) is a deadly disease with rising incidence and few treatment options. An altered expression and/or activation of NOTCH1-3 receptors has been shown to play a role in iCCA development and progression. In this study, we established a new CCA patient-derived xenograft model, which was validated by immunohistochemistry and transcriptomic analysis. The effects of Notch pathway suppression by the Crenigacestat (LY3039478)-specific inhibitor were evaluated in human iCCA cell lines and the PDX model. In vitro, LY3039478 significantly reduced Notch pathway components, including NICD1 and HES1, but not the other Notch receptors, in a panel of five different iCCA cell lines. In the PDX model, LY3039478 significantly inhibited the Notch pathway and tumor growth to ","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Aug","modification":"2026-04-12T19:49:00.195Z","creation":"2025-06-01T02:53:33.597Z"},"accession":"S-EPMC7370218","cross_references":{"pubmed":["32042099"],"doi":["10.1038/s41418-020-0505-4"]}}