Dataset Information

Induction and characterization of pancreatic cancer in a transgenic pig model.

ABSTRACT:

Background

Preclinical testing of new locoregional therapies for pancreatic cancer has been challenging, due to the lack of a suitable large animal model.

Purpose

To develop and characterize a porcine model of pancreatic cancer. Unlike small animals, pigs have similar physiology, drug dosing, and immune response to humans. Locoregional therapy in pigs can be performed using the same size catheters and devices as in humans.

Methods

The Oncopig is a transgenic pig with Cre-inducible TP53R167H and KRASG12D mutations. In 12 Oncopigs, CT-guided core biopsy of the pancreas was performed. The core biopsy was incubated with an adenoviral vector carrying the Cre recombinase gene. The transformed core biopsy was injected back into the pancreas (head, tail, or both). The resulting tumors (n = 19) were characterized on multi-phase contrast-enhanced CT, and on pathology, including immunohistochemistry. Angiographic characterization of the tumors was performed in 3 pigs.

Results

Pancreatic tumors developed at 19 out of 22 sites (86%) that were inoculated. Average tumor size was 3.0 cm at 1 week (range: 0.5-5.1 cm). H&E and immunohistochemical stains revealed undifferentiated carcinomas, similar to those of the pancreatobiliary system in humans. Neoplastic cells were accompanied by a major inflammatory component. 1 of 12 pigs only had inflammatory nodules without evidence of neoplasia. On multiphase CT, tumors were hypovascular compared to the normal pancreas. There was no pancreatic duct dilation. In 3 pigs, angiography was performed, and in all 3 cases, the artery supplying the pancreatic tumor could be catheterized using a 2.4 F microcatheter. Selective angiography showed the pancreatic tumor, without extra-pancreatic perfusion.

Conclusion

Pancreatic cancer can be induced in a transgenic pig. Intra-arterial procedures using catheters designed for human interventions were technically feasible in this large animal model.

SUBMITTER: Boas FE

PROVIDER: S-EPMC7505440 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Induction and characterization of pancreatic cancer in a transgenic pig model.

Boas F Edward FE Nurili Fuad F Bendet Achiude A Cheleuitte-Nieves Christopher C Basturk Olca O Askan Gokce G Michel Adam O AO Monette Sebastien S Ziv Etay E Sofocleous Constantinos T CT Maxwell Aaron W P AWP Schook Lawrence B LB Solomon Stephen B SB Kelsen David P DP Scherz Avigdor A Yarmohammadi Hooman H

PloS one 20200921 9

<h4>Background</h4>Preclinical testing of new locoregional therapies for pancreatic cancer has been challenging, due to the lack of a suitable large animal model.<h4>Purpose</h4>To develop and characterize a porcine model of pancreatic cancer. Unlike small animals, pigs have similar physiology, drug dosing, and immune response to humans. Locoregional therapy in pigs can be performed using the same size catheters and devices as in humans.<h4>Methods</h4>The Oncopig is a transgenic pig with Cre-in ...[more]

PMID: 32956389

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Dataset Information

Induction and characterization of pancreatic cancer in a transgenic pig model.

Background

Purpose

Methods

Results

Conclusion

Publications

Induction and characterization of pancreatic cancer in a transgenic pig model.

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