Abstract 4096: Stage-defined, transgenic immunocompetent mouse model (ASV-B) to investigate new drugs for hepatocellular carcinoma

Autor: Evelyne Dupuy, Clarisse Eveno, Annemilaï Tijeras-Raballand, Valérie Paradis, Patricia Hainaud, Armand de Gramont, Marc Pocard, Philippe Bonnin, Mohamed Bouattour, Eric Raymond, Sandrine Faivre, C. Hobeika
Rok vydání: 2018
Předmět:
Zdroj: Cancer Research. 78:4096-4096
ISSN: 1538-7445
0008-5472
Popis: Background: Hepatocellular carcinoma (HCC) is a complex multistep malignancy in need of new therapeutic options often arising on underlying chronic liver disease. HCC animal models relevant to clinical situations are crucial to investigate new anticancer drugs, alone or in combination. Mice bearing xenografts and transgenic mice are the two main models used for preclinical drug development, but most of them fail to mimic the different step of HCC observed in patients. In this study, we aim to describe a stage-defined, transgenic immunocompetent HCC mouse model. Methods: ASV-B is a transgenic mouse model that spontaneously develops, upon SV40 T-Ag oncogene expression in hepatocytes, a reproducible stage-defined HCC. Hyperplasia at week(W)8 is followed by nodular stage at W12 (multiple well-delimited tumor nodules of about 1 mm, growing progressively up to 1 cm), then diffuse carcinoma stage at W16-20. HCC is restricted to male, backcrossed with C57BL/6J mice, the female littermates being used as controls. Results: Liver volume assessed by ultrasound at each step of carcinogenesis showed a 2.7-, 2.7-, 3.9-, and 5.8-fold increase (p Conclusion: ASV-B transgenic mouse model mimics several characteristics of human HCC developing on healthy liver including multinodular disease, vessel abnormalities, and dedifferentiation toward mesenchymal phenotype. Further steps will consist of characterizing the adjacent nontumor liver, and developing nonalcoolic steatohepatitis (NASH) on ASV-B model using specific diets. Citation Format: Annemilaï Tijeras-Raballand, Patricia Hainaud, Christian Hobeika, Clarisse Eveno, Marc Pocard, Philippe Bonnin, Valérie Paradis, Mohamed Bouattour, Eric Raymond, Armand de Gramont, Evelyne Dupuy, Sandrine Faivre. Stage-defined, transgenic immunocompetent mouse model (ASV-B) to investigate new drugs for hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4096.
Databáze: OpenAIRE