Establishment of a Liver Transplant Patient-derived Tumor Xenograft (PDX) Model Using Cryopreserved Pancreatic Ductal Adenocarcinoma

Abstract

Background/Aim: There is rapid progression and widespread use of patient-derived tumor xenografts (PDX) in translational pancreatic cancer research. This study aimed to establish a liver transplant PDX model using cryopreserved primary pancreatic ductal adenocarcinoma (PDAC). Patients and Methods: Primary PDAC from 10 patients were cryopreserved and transplanted into immunodeficient mice using the liver pocket method. H&E staining and immunohistochemical staining, such as p53, Smad4, and MUC1 were used to evaluate engraftment and histological similarities. Results: Patient-derived xenograft placement was successful in six cases (60%), and 10 mice (33.3%). The Ki-67 index of primary PDAC and the cryopreservation duration were significantly related to successful engraftment (p=0. 003 and p=0.007, respectively). Conclusion: In this study, we succeeded in establishing a liver transplant PDX mouse model as a preclinical platform. The successful engraftment was affected by the cryopreservation duration and could be detected by the Ki-67 index.

Safety and Feasibility of Contrast-Enhanced Computed Tomography with a Nanoparticle Contrast Agent for Evaluation of Diethylnitrosamine-Induced Liver Tumors in a Rat Model

“…ExiTron nano 12000 is a nanoparticle-based, non-iodinated contrast agent that provides both liver and spleen CT contrast (17). Previous reports revealed that mouse liver tumors can be identified by CT using ExiTron nano 12000 in pre-clinical translational research (17,(24)(25)(26). ExiTron nano 12000 subsequently has been used for CECT imaging of lymph node metastasis in a lung cancer model in rat (27).…”

A rat-based preclinical platform facilitating transcatheter hepatic arterial infusion in immunodeficient rats with liver xenografts of patient-derived pancreatic ductal adenocarcinoma

“…Using HE-stained slides, two experimenters evaluated the histopathological features of adenocarcinoma with comparisons between original tumors and xenografted tumors. Immunohistochemical analysis of Ki67 was performed using rabbit Ki67 (1:400; Cell Signaling Technology, Danvers, MA, USA) on paraffin-embedded sections to measure cell proliferative capacity 28 . Five fields of tumor tissues from a single specimen were arbitrarily photographed at 400 × magnification.…”

In vivo Mouse Models of Pancreatic Ductal Adenocarcinoma

“…PDAC PDX mouse models have been improved and/or expanded in a variety of ways. Cryopreserved PDAC was introduced into liver to generate a robust model of PDAC liver metastasis of tumors from 6 of 10 patient donors in one third of recipient mice (110). Another means of advancing PDX models was deriving cancer from a tissue source other than primary tumor.…”