Induction and characterization of pancreatic cancer in a transgenic pig model.
<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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0239391 |
| _version_ | 1819029117801070592 |
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| author | F Edward Boas Fuad Nurili Achiude Bendet Christopher Cheleuitte-Nieves Olca Basturk Gokce Askan Adam O Michel Sebastien Monette Etay Ziv Constantinos T Sofocleous Aaron W P Maxwell Lawrence B Schook Stephen B Solomon David P Kelsen Avigdor Scherz Hooman Yarmohammadi |
| author_facet | F Edward Boas Fuad Nurili Achiude Bendet Christopher Cheleuitte-Nieves Olca Basturk Gokce Askan Adam O Michel Sebastien Monette Etay Ziv Constantinos T Sofocleous Aaron W P Maxwell Lawrence B Schook Stephen B Solomon David P Kelsen Avigdor Scherz Hooman Yarmohammadi |
| author_sort | F Edward Boas |
| collection | DOAJ |
| description | <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-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.<h4>Results</h4>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.<h4>Conclusion</h4>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. |
| first_indexed | 2024-12-21T06:09:10Z |
| format | Article |
| id | doaj.art-608850cc806641efadc5030623de0300 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T06:09:10Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-608850cc806641efadc5030623de03002022-12-21T19:13:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01159e023939110.1371/journal.pone.0239391Induction and characterization of pancreatic cancer in a transgenic pig model.F Edward BoasFuad NuriliAchiude BendetChristopher Cheleuitte-NievesOlca BasturkGokce AskanAdam O MichelSebastien MonetteEtay ZivConstantinos T SofocleousAaron W P MaxwellLawrence B SchookStephen B SolomonDavid P KelsenAvigdor ScherzHooman Yarmohammadi<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-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.<h4>Results</h4>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.<h4>Conclusion</h4>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.https://doi.org/10.1371/journal.pone.0239391 |
| spellingShingle | F Edward Boas Fuad Nurili Achiude Bendet Christopher Cheleuitte-Nieves Olca Basturk Gokce Askan Adam O Michel Sebastien Monette Etay Ziv Constantinos T Sofocleous Aaron W P Maxwell Lawrence B Schook Stephen B Solomon David P Kelsen Avigdor Scherz Hooman Yarmohammadi Induction and characterization of pancreatic cancer in a transgenic pig model. PLoS ONE |
| title | Induction and characterization of pancreatic cancer in a transgenic pig model. |
| title_full | Induction and characterization of pancreatic cancer in a transgenic pig model. |
| title_fullStr | Induction and characterization of pancreatic cancer in a transgenic pig model. |
| title_full_unstemmed | Induction and characterization of pancreatic cancer in a transgenic pig model. |
| title_short | Induction and characterization of pancreatic cancer in a transgenic pig model. |
| title_sort | induction and characterization of pancreatic cancer in a transgenic pig model |
| url | https://doi.org/10.1371/journal.pone.0239391 |
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