Induction and characterization of pancreatic cancer in a transgenic pig model

• DOI: 10.1371/journal.pone.0239391
• Publication Date: 2020-09-21T18:14:10Z
• Authors: F. Edward Boas; Fuad Nurili; Achiude Bendet; Christopher Chele...; Olca Basturk; Gokce Askan; Adam O. Michel; Sebastien Monette; Etay Ziv; Constantinos T. S...; Aaron W. P. Maxwell; Lawrence B. Schook; Stephen B. Solomon; David P. Kelsen; Avigdor Scherz; Hooman Yarmohammadi
• Keywords: Pancreatic tumor; Pancreatic Disease

Background Preclinical testing of new locoregional therapies for pancreatic cancer has been challenging, due to the lack a suitable large animal model. Purpose To develop and characterize porcine model cancer. Unlike small animals, pigs have similar physiology, drug dosing, immune response humans. Locoregional therapy in can be performed using same size catheters devices as Methods The Oncopig is transgenic pig with Cre-inducible TP53R167H KRASG12D mutations. In 12 Oncopigs, CT-guided core biopsy pancreas was performed. incubated an adenoviral vector carrying Cre recombinase gene. transformed injected back into (head, tail, or both). resulting tumors (n = 19) were characterized on multi-phase contrast-enhanced CT, pathology, including immunohistochemistry. Angiographic characterization 3 pigs. Results Pancreatic developed at 19 out 22 sites (86%) that inoculated. Average tumor 3.0 cm 1 week (range: 0.5–5.1 cm). H&E immunohistochemical stains revealed undifferentiated carcinomas, those pancreatobiliary system Neoplastic cells accompanied by major inflammatory component. only had nodules without evidence neoplasia. On multiphase hypovascular compared normal pancreas. There no duct dilation. pigs, angiography performed, all cases, artery supplying could catheterized 2.4 F microcatheter. Selective showed tumor, extra-pancreatic perfusion. Conclusion induced pig. Intra-arterial procedures designed human interventions technically feasible this