Detailed Abstract
[E-poster - Basic Research (Basic Research)]
[EP 259] Title: Establishment of Extrahepatic Cholangiocarcinoma Mouse Model by Gene Engineered Organoids And Orthotopic Implantation
Junya TOYODA 1, Shingo KATO 2, Kentaro MIYAKE 1, Yasuhiro YABUSHITA 1, Yu SAWADA 1, Yuki HOMMA 1, Ryusei MATSUYAMA 1, Itaru ENDO 1
1 Department of Gastrological Surgery, Yokohama City University, JAPAN, 2 Department of Clinical Cancer Genomics, Yokohama City University Hospital, JAPAN
Background : Curative treatment of extrahepatic cholangiocarcinoma remains limited to surgical treatment. Animal models of extrahepatic cholangiocarcinoma that maintain normal immunity are essential for the development of new immunotherapies for extrahepatic cholangiocarcinoma. However, the orthotopic experimental animal model of extrahepatic cholangiocarcinoma has not been established.
Methods : In this study, we established mouse extrahepatic bile duct organoids and introduced KrasG12D mutant and trp53 knockout.
Results : These gene engineered organoids, when injected subcutaneously, formed a tumor with an adenocarcinoma histology. Using the “implantation organoid-derived tumor bud (IOTB)” method, a small piece of harvested subcutaneous tumor was implanted into the extrahepatic bile duct of another mouse, which showed invasion into the common bile duct and histological features of extrahepatic cholangiocarcinoma. This model is an allogeneic orthotopic transplantation model and does not require time to secure enough individuals. In addition, bile drainage for obstructive jaundice associated with tumor fragment invasion was performed, prolonging the survival of the model mice, and allowing drug delivery experiments.
Conclusions : This model is ideal for the development of novel therapies for extrahepatic cholangiocarcinoma. A brief description of the model creation process and prospects will be presented.
Methods : In this study, we established mouse extrahepatic bile duct organoids and introduced KrasG12D mutant and trp53 knockout.
Results : These gene engineered organoids, when injected subcutaneously, formed a tumor with an adenocarcinoma histology. Using the “implantation organoid-derived tumor bud (IOTB)” method, a small piece of harvested subcutaneous tumor was implanted into the extrahepatic bile duct of another mouse, which showed invasion into the common bile duct and histological features of extrahepatic cholangiocarcinoma. This model is an allogeneic orthotopic transplantation model and does not require time to secure enough individuals. In addition, bile drainage for obstructive jaundice associated with tumor fragment invasion was performed, prolonging the survival of the model mice, and allowing drug delivery experiments.
Conclusions : This model is ideal for the development of novel therapies for extrahepatic cholangiocarcinoma. A brief description of the model creation process and prospects will be presented.
SESSION
E-poster
E-Session 03/21 ALL DAY