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Status |
Public on Apr 27, 2022 |
Title |
Effect of Crenigacestat treatment in xenograft model of HUCCT1 intrahepatic cholangiocarcinoma |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Intrahepatic Cholangiocarcinoma (iCCA) is a difficult type of cancer to diagnose, extremely aggressive and resistant to therapeutic options with an increased incidence and mortality over time. The overexpression of Notch pathway is implicated in iCCA to create an ecosystem that drives the tumor aggressiveness. Specifically, Notch1 is overexpressed in iCCA tissue of patients, playing an important role on tumor growth. Our purpose was to investigate the effectiveness of Crenigacestat in in vivo experiments, using Hucct1 injected in CD1 mice to generate an iCCA xenograft mouse model. In the present study, in order to explore modulated factors and genes by treatment we performed a transcriptomic analysis validated by Western Blotting and qRT-PCR on iCCA tumor masses of xenograft mice. Our results indicate that the treatment significantly inhibited Notch1 and HES1 genes and proteins triggering a strong immune response. Nevertheless, moderate fibrosis was shown in this model which may have hindered response to therapy to promote tumor progression. We used microarray technology to understand the molecular mechanisms affected by Crenigacestat in HUCCT1 xenograft model of intraepatic cholangiocarcinoma.
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Overall design |
Expression profiling of HUCCT1 xenograft mice model of intrahepatic cholangiocarcinoma after and before Crenigacestat treatment.
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Contributor(s) |
Mancarella S, Serino G, Giannelli G |
Citation(s) |
35457006 |
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Submission date |
May 07, 2020 |
Last update date |
Apr 29, 2022 |
Contact name |
Grazia Serino |
E-mail(s) |
[email protected]
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Organization name |
National Institute of Gastroenterology “S. de Bellis”, Research Hospital
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Street address |
Via Turi, 27
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City |
Castellana Grotte (BA) |
ZIP/Postal code |
70013 |
Country |
Italy |
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Platforms (1) |
GPL17586 |
[HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [transcript (gene) version] |
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Samples (10)
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GSM4520792 |
Xenograft treated with Crenigacestat 4 |
GSM4520793 |
Xenograft treated with Crenigacestat 5 |
GSM4520794 |
Xenograft treated with Crenigacestat 6 |
GSM4520795 |
Xenograft untreated with Crenigacestat 1 |
GSM4520796 |
Xenograft untreated with Crenigacestat 2 |
GSM4520797 |
Xenograft untreated with Crenigacestat 3 |
GSM4520798 |
Xenograft untreated with Crenigacestat 4 |
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Relations |
BioProject |
PRJNA630916 |