Induction and preliminary characterization of neoplastic pulmonary nodules in a transgenic pig model.

Autor: Ghosn M; Department of Interventional Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA., Elsakka AS; Department of Interventional Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA., Petre EN; Department of Interventional Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA., Cheleuitte-Nieves C; Center of Comparative Medicine and Pathology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York, NY, USA., Tammela T; Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Monette S; Laboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center, The Rockefeller University, Weill Cornell Medicine, New York, NY, USA., Ziv E; Department of Interventional Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA., Schachtschneider KM; Department of Radiology, University of Illinois at Chicago, Chicago, IL, USA; Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, USA; National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, IL, USA., Srimathveeravalli G; Department of Mechanical Engineering, Institute for Applied Life Sciences, University of Massachusetts Amherst, Life Sciences Laboratories, 240 Thatcher Road Amherst, MA, USA., Yarmohammadi H; Department of Interventional Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA., Edward Boas F; Department of Radiology, City of Hope Cancer Center, 1500 East Duarte Rd., Duarte, CA, USA., Solomon SB; Department of Interventional Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA. Electronic address: solomons@mskcc.org.
Jazyk: angličtina
Zdroj: Lung cancer (Amsterdam, Netherlands) [Lung Cancer] 2023 Apr; Vol. 178, pp. 157-165. Date of Electronic Publication: 2023 Feb 21.
DOI: 10.1016/j.lungcan.2023.02.013
Abstrakt: Objectives: Lung cancer models in large animals are lacking. Oncopigs are transgenic pigs that carry both KRAS G12D and TP53 R167H Cre-inducible mutations. This study aimed to develop and histologically characterize a swine model of lung cancer that could serve for preclinical studies evaluating locoregional therapies.
Materials and Methods: In two Oncopigs, an adenoviral vector encoding the Cre-recombinase gene (AdCre) was injected endovascularly through the pulmonary arteries or inferior vena cava. In two other Oncopigs, a lung biopsy was performed and incubated with AdCre, before reinjecting the mixture into the lungs percutaneously. Animals were clinically and biologically (complete blood count, liver enzymes and lipasemia) monitored. Obtained tumors were characterized on computed tomography (CT) and on pathology and immunohistochemistry (IHC).
Results: Neoplastic lung nodules developed following 1 (1/10, 10%) endovascular inoculation, and 2 (2/6, 33%) percutaneous inoculations. All lung tumors were visible at the 1-week CT, and appeared as well-circumscribed solid nodules, with a median longest diameter of 14 mm (range: 5-27 mm). Only one complication occurred: an extravasation of the mixture into the thoracic wall during a percutaneous injection that resulted in a thoracic wall tumor. Pigs remained clinically healthy during the entire follow-up (14-21 days). On histology, tumors consisted of inflammatory undifferentiated neoplasms composed of atypical spindle and epithelioid cells and/or a fibrovascular stroma and abundant mixed leukocytic infiltrate. On IHC, atypical cells diffusely displayed expression of vimentin and some showed expression of CK WSS and CK 8/18. The tumor microenvironment contained abundant IBA1 + macrophages and giant cells, CD3 + T cells, and CD31 + blood vessels.
Conclusion: Tumors induced in the lungs of Oncopigs are fast growing poorly differentiated neoplasms associated with a marked inflammatory reaction that can be easily and safely induced at site specific locations. This large animal model might be suitable for interventional and surgical therapies of lung cancer.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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