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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2025
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| _version_ | 1849927640203395072 |
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| author | Nicholas T. Younger (14956251) |
| author2 | Mollie L. Wilson (14956254) Anabel Martinez Lyons (14956257) Edward J. Jarman (9773166) Alison M. Meynert (14956260) Graeme R. Grimes (14160170) Konstantinos Gournopanos (14956263) Scott H. Waddell (14956266) Peter A. Tennant (14956269) David H. Wilson (14956272) Rachel V. Guest (14956275) Stephen J. Wigmore (14915943) Juan Carlos Acosta (14956278) Timothy J. Kendall (14956281) Martin S. Taylor (14956284) Duncan Sproul (13971883) Pleasantine Mill (256953) Luke Boulter (14956287) |
| author2_role | author author author author author author author author author author author author author author author author author |
| author_facet | Nicholas T. Younger (14956251) Mollie L. Wilson (14956254) Anabel Martinez Lyons (14956257) Edward J. Jarman (9773166) Alison M. Meynert (14956260) Graeme R. Grimes (14160170) Konstantinos Gournopanos (14956263) Scott H. Waddell (14956266) Peter A. Tennant (14956269) David H. Wilson (14956272) Rachel V. Guest (14956275) Stephen J. Wigmore (14915943) Juan Carlos Acosta (14956278) Timothy J. Kendall (14956281) Martin S. Taylor (14956284) Duncan Sproul (13971883) Pleasantine Mill (256953) Luke Boulter (14956287) |
| author_role | author |
| dc.creator.none.fl_str_mv | Nicholas T. Younger (14956251) Mollie L. Wilson (14956254) Anabel Martinez Lyons (14956257) Edward J. Jarman (9773166) Alison M. Meynert (14956260) Graeme R. Grimes (14160170) Konstantinos Gournopanos (14956263) Scott H. Waddell (14956266) Peter A. Tennant (14956269) David H. Wilson (14956272) Rachel V. Guest (14956275) Stephen J. Wigmore (14915943) Juan Carlos Acosta (14956278) Timothy J. Kendall (14956281) Martin S. Taylor (14956284) Duncan Sproul (13971883) Pleasantine Mill (256953) Luke Boulter (14956287) |
| dc.date.none.fl_str_mv | 2025-11-24T22:22:11Z |
| dc.identifier.none.fl_str_mv | 10.1158/0008-5472.30698865 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/figure/Figure_4_from_i_In_Vivo_i_Modeling_of_Patient_Genetic_Heterogeneity_Identifies_New_Ways_to_Target_Cholangiocarcinoma/30698865 |
| dc.rights.none.fl_str_mv | CC BY info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | 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 |
| dc.title.none.fl_str_mv | Figure 4 from <i>In Vivo</i> Modeling of Patient Genetic Heterogeneity Identifies New Ways to Target Cholangiocarcinoma |
| dc.type.none.fl_str_mv | Image Figure info:eu-repo/semantics/publishedVersion image |
| description | <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> |
| eu_rights_str_mv | openAccess |
| id | Manara_50374de4dd2f3569e771499e9c1cc607 |
| identifier_str_mv | 10.1158/0008-5472.30698865 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/30698865 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY |
| spelling | Figure 4 from <i>In Vivo</i> Modeling of Patient Genetic Heterogeneity Identifies New Ways to Target CholangiocarcinomaNicholas T. Younger (14956251)Mollie L. Wilson (14956254)Anabel Martinez Lyons (14956257)Edward J. Jarman (9773166)Alison M. Meynert (14956260)Graeme R. Grimes (14160170)Konstantinos Gournopanos (14956263)Scott H. Waddell (14956266)Peter A. Tennant (14956269)David H. Wilson (14956272)Rachel V. Guest (14956275)Stephen J. Wigmore (14915943)Juan Carlos Acosta (14956278)Timothy J. Kendall (14956281)Martin S. Taylor (14956284)Duncan Sproul (13971883)Pleasantine Mill (256953)Luke Boulter (14956287)CancerCancer BiologyMolecular and Cellular BiologyTherapeutic Research and DevelopmentMethods and TechnologyCell SignalingComputational MethodsSequence analysisDrug TargetsGastrointestinal CancersLiver cancerGene TechnologiesComparative genomicsOncogenes & Tumor SuppressorsKrasPreclinical ModelsAnimal models of cancer<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>2025-11-24T22:22:11ZImageFigureinfo:eu-repo/semantics/publishedVersionimage10.1158/0008-5472.30698865https://figshare.com/articles/figure/Figure_4_from_i_In_Vivo_i_Modeling_of_Patient_Genetic_Heterogeneity_Identifies_New_Ways_to_Target_Cholangiocarcinoma/30698865CC BYinfo:eu-repo/semantics/openAccessoai:figshare.com:article/306988652025-11-24T22:22:11Z |
| spellingShingle | Figure 4 from <i>In Vivo</i> Modeling of Patient Genetic Heterogeneity Identifies New Ways to Target Cholangiocarcinoma Nicholas T. Younger (14956251) 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 |
| status_str | publishedVersion |
| title | Figure 4 from <i>In Vivo</i> Modeling of Patient Genetic Heterogeneity Identifies New Ways to Target Cholangiocarcinoma |
| title_full | Figure 4 from <i>In Vivo</i> Modeling of Patient Genetic Heterogeneity Identifies New Ways to Target Cholangiocarcinoma |
| title_fullStr | Figure 4 from <i>In Vivo</i> Modeling of Patient Genetic Heterogeneity Identifies New Ways to Target Cholangiocarcinoma |
| title_full_unstemmed | Figure 4 from <i>In Vivo</i> Modeling of Patient Genetic Heterogeneity Identifies New Ways to Target Cholangiocarcinoma |
| title_short | Figure 4 from <i>In Vivo</i> Modeling of Patient Genetic Heterogeneity Identifies New Ways to Target Cholangiocarcinoma |
| title_sort | Figure 4 from <i>In Vivo</i> Modeling of Patient Genetic Heterogeneity Identifies New Ways to Target Cholangiocarcinoma |
| topic | 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 |