Figure 4 from <i>In Vivo</i> Modeling of Patient Genetic Heterogeneity Identifies New Ways to Target Cholangiocarcinoma

Figure 4 from <i>In Vivo</i> Modeling of Patient Genetic Heterogeneity Identifies New Ways to Target Cholangiocarcinoma

<p>Therapeutic coinhibition of Wnt and PI3K signaling reduces tumor growth in ICC. <b>A,</b> RNA-seq data of human ICC demonstrating a positive correlation between the activity of canonical Wnt signaling and Akt signaling. <b>B,</b> Schematic representation of the KPPTo...

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গ্রন্থ-পঞ্জীর বিবরন
প্রধান লেখক: Nicholas T. Younger (14956251) (author)
অন্যান্য লেখক: Mollie L. Wilson (14956254) (author), Anabel Martinez Lyons (14956257) (author), Edward J. Jarman (9773166) (author), Alison M. Meynert (14956260) (author), Graeme R. Grimes (14160170) (author), Konstantinos Gournopanos (14956263) (author), Scott H. Waddell (14956266) (author), Peter A. Tennant (14956269) (author), David H. Wilson (14956272) (author), Rachel V. Guest (14956275) (author), Stephen J. Wigmore (14915943) (author), Juan Carlos Acosta (14956278) (author), Timothy J. Kendall (14956281) (author), Martin S. Taylor (14956284) (author), Duncan Sproul (13971883) (author), Pleasantine Mill (256953) (author), Luke Boulter (14956287) (author)
প্রকাশিত: 2025
বিষয়গুলি:
Cancer
Cancer Biology
Molecular and Cellular Biology
Therapeutic Research and Development
Methods and Technology
Cell Signaling
Computational Methods
Sequence analysis
Drug Targets
Gastrointestinal Cancers
Liver cancer
Gene Technologies
Comparative genomics
Oncogenes & Tumor Suppressors
Kras
Preclinical Models
Animal models of cancer
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সংক্ষিপ্ত:<p>Therapeutic coinhibition of Wnt and PI3K signaling reduces tumor growth in ICC. <b>A,</b> RNA-seq data of human ICC demonstrating a positive correlation between the activity of canonical Wnt signaling and Akt signaling. <b>B,</b> Schematic representation of the KPPTom cholangiocarcinoma model where Cre<sup>ERT</sup> expression in Keratin-19–positive cholangiocytes results in the inactivation of <i>Trp53</i> and <i>Pten</i>, whereas labeling transformed cells with tdTomato. <b>C,</b> Representative IHC staining of KPPTom model following tamoxifen administration (day 0) and following 4 and 8 weeks of thioacetamide administration. tdTomato (red) denotes recombined cholangiocytes (denoted by Keratin-19; green). Blue, DNA. Top, whole mount FUNGI images; bottom, 2D histologic sections. Scale bar, 200 μm. White arrows, tdTomato-positive cells. <b>D,</b> Quantification of liver tissue occupied by tumor in the KPPTom ICC model. <b>E,</b> IHC showing that KPPTom ICC has activated canonical Wnt signaling [by staining for dephosphorylated (active) β-catenin] and PI3K activity (through pAKT<sup>Ser647</sup> positivity). Red arrows, positive cells. Scale bar, 100 μm. <b>F,</b> A schematic representation of how the KPPTom model was used to test the effectiveness of Wnt and Pi3K inhibitor combinations on ICC progression. <b>G,</b> IHC staining for tdTomato-positive cancer cells in vehicle-treated animals compared with those treated with a combination of LGK974 and pictilisib. Scale bar, 100 μm. <b>H,</b> Number of tdTomato-positive cells in KPPTom animals given vehicle or LGK974 and pictilisib in combination<b>. I,</b> Proportion of KPPTom animals containing macroscopic tumors in KPPTom animals treated with vehicle versus combination treatment. b.d., bile duct; p.v., portal vein.</p>

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