Validation of a Preclinical Model of Diethylnitrosamine-Induced Hepatic Neoplasia in Yucatan Miniature Pigs

Jennifer Mitchell; Peggy T. Tinkey; Rony Avritscher; Carolyn Van Pelt; Ghazaleh Eskandari; Suraj Konnath George; Lianchun Xiao; Erik Cressman; Jeffrey S. Morris; Asif Rashid; Ahmed O. Kaseb; Hesham M. Amin; Rajesh Uthamanthil

doi:10.1159/000446074

Validation of a Preclinical Model of Diethylnitrosamine-Induced Hepatic Neoplasia in Yucatan Miniature Pigs

Jennifer Mitchell, Peggy T. Tinkey, Rony Avritscher, Carolyn Van Pelt, Ghazaleh Eskandari, Suraj Konnath George, Lianchun Xiao, Erik Cressman, Jeffrey S. Morris, Asif Rashid, Ahmed O. Kaseb, Hesham M. Amin, Rajesh Uthamanthil

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

Objective: The purpose of this study was to reduce the time to tumor onset in a diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) swine model via partial liver embolization (PLE) and to characterize the model for use in translational research. Methods: Eight Yucatan miniature pigs were injected intraperitoneally with either saline (n = 2) or DEN (n = 6) solution weekly for 12 weeks. Three of the DEN-treated pigs underwent PLE. The animals underwent periodic radiological evaluation, liver biopsy, and blood sampling, and full necropsy was performed at study termination (∼29 months). Results: All DEN-treated pigs developed hepatic adenoma and HCC. PLE accelerated the time to adenoma development but not to HCC development. Biomarker analysis results showed that IGF1 levels decreased in all DEN-treated pigs as functional liver capacity decreased with progression of HCC. VEGF and IL-6 levels were positively correlated with disease progression. Immunohistochemical probing of HCC tissues demonstrated the expression of several important survival-promoting proteins. Conclusion: To our knowledge, we are the first to demonstrate an accelerated development of hepatic neoplasia in Yucatan miniature pigs. Our HCC swine model closely mimics the human condition (i.e., progressive disease stages and expression of relevant molecular markers) and is a viable translational model.

Original language	English (US)
Pages (from-to)	90-100
Number of pages	11
Journal	Oncology (Switzerland)
Volume	91
Issue number	2
DOIs	https://doi.org/10.1159/000446074
State	Published - Aug 1 2016

Keywords

Animal models
Diethylnitrosamine
Hepatocellular carcinoma
Preclinical studies
Yucatan miniature pigs

ASJC Scopus subject areas

Oncology
Cancer Research

MD Anderson CCSG core facilities

Biostatistics Resource Group

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10.1159/000446074

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Mitchell, J., Tinkey, P. T., Avritscher, R., Van Pelt, C., Eskandari, G., Konnath George, S., Xiao, L., Cressman, E., Morris, J. S., Rashid, A., Kaseb, A. O., Amin, H. M., & Uthamanthil, R. (2016). Validation of a Preclinical Model of Diethylnitrosamine-Induced Hepatic Neoplasia in Yucatan Miniature Pigs. Oncology (Switzerland), 91(2), 90-100. https://doi.org/10.1159/000446074

Mitchell, J, Tinkey, PT, Avritscher, R, Van Pelt, C, Eskandari, G, Konnath George, S, Xiao, L , Cressman, E, Morris, JS, Rashid, A , Kaseb, AO , Amin, HM & Uthamanthil, R 2016, 'Validation of a Preclinical Model of Diethylnitrosamine-Induced Hepatic Neoplasia in Yucatan Miniature Pigs', Oncology (Switzerland), vol. 91, no. 2, pp. 90-100. https://doi.org/10.1159/000446074

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abstract = "Objective: The purpose of this study was to reduce the time to tumor onset in a diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) swine model via partial liver embolization (PLE) and to characterize the model for use in translational research. Methods: Eight Yucatan miniature pigs were injected intraperitoneally with either saline (n = 2) or DEN (n = 6) solution weekly for 12 weeks. Three of the DEN-treated pigs underwent PLE. The animals underwent periodic radiological evaluation, liver biopsy, and blood sampling, and full necropsy was performed at study termination (∼29 months). Results: All DEN-treated pigs developed hepatic adenoma and HCC. PLE accelerated the time to adenoma development but not to HCC development. Biomarker analysis results showed that IGF1 levels decreased in all DEN-treated pigs as functional liver capacity decreased with progression of HCC. VEGF and IL-6 levels were positively correlated with disease progression. Immunohistochemical probing of HCC tissues demonstrated the expression of several important survival-promoting proteins. Conclusion: To our knowledge, we are the first to demonstrate an accelerated development of hepatic neoplasia in Yucatan miniature pigs. Our HCC swine model closely mimics the human condition (i.e., progressive disease stages and expression of relevant molecular markers) and is a viable translational model.",

keywords = "Animal models, Diethylnitrosamine, Hepatocellular carcinoma, Preclinical studies, Yucatan miniature pigs",

author = "Jennifer Mitchell and Tinkey, {Peggy T.} and Rony Avritscher and {Van Pelt}, Carolyn and Ghazaleh Eskandari and {Konnath George}, Suraj and Lianchun Xiao and Erik Cressman and Morris, {Jeffrey S.} and Asif Rashid and Kaseb, {Ahmed O.} and Amin, {Hesham M.} and Rajesh Uthamanthil",

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month = aug,

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doi = "10.1159/000446074",

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AU - Mitchell, Jennifer

AU - Tinkey, Peggy T.

AU - Avritscher, Rony

AU - Van Pelt, Carolyn

AU - Eskandari, Ghazaleh

AU - Konnath George, Suraj

AU - Xiao, Lianchun

AU - Cressman, Erik

AU - Morris, Jeffrey S.

AU - Rashid, Asif

AU - Kaseb, Ahmed O.

AU - Amin, Hesham M.

AU - Uthamanthil, Rajesh

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Objective: The purpose of this study was to reduce the time to tumor onset in a diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) swine model via partial liver embolization (PLE) and to characterize the model for use in translational research. Methods: Eight Yucatan miniature pigs were injected intraperitoneally with either saline (n = 2) or DEN (n = 6) solution weekly for 12 weeks. Three of the DEN-treated pigs underwent PLE. The animals underwent periodic radiological evaluation, liver biopsy, and blood sampling, and full necropsy was performed at study termination (∼29 months). Results: All DEN-treated pigs developed hepatic adenoma and HCC. PLE accelerated the time to adenoma development but not to HCC development. Biomarker analysis results showed that IGF1 levels decreased in all DEN-treated pigs as functional liver capacity decreased with progression of HCC. VEGF and IL-6 levels were positively correlated with disease progression. Immunohistochemical probing of HCC tissues demonstrated the expression of several important survival-promoting proteins. Conclusion: To our knowledge, we are the first to demonstrate an accelerated development of hepatic neoplasia in Yucatan miniature pigs. Our HCC swine model closely mimics the human condition (i.e., progressive disease stages and expression of relevant molecular markers) and is a viable translational model.

AB - Objective: The purpose of this study was to reduce the time to tumor onset in a diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) swine model via partial liver embolization (PLE) and to characterize the model for use in translational research. Methods: Eight Yucatan miniature pigs were injected intraperitoneally with either saline (n = 2) or DEN (n = 6) solution weekly for 12 weeks. Three of the DEN-treated pigs underwent PLE. The animals underwent periodic radiological evaluation, liver biopsy, and blood sampling, and full necropsy was performed at study termination (∼29 months). Results: All DEN-treated pigs developed hepatic adenoma and HCC. PLE accelerated the time to adenoma development but not to HCC development. Biomarker analysis results showed that IGF1 levels decreased in all DEN-treated pigs as functional liver capacity decreased with progression of HCC. VEGF and IL-6 levels were positively correlated with disease progression. Immunohistochemical probing of HCC tissues demonstrated the expression of several important survival-promoting proteins. Conclusion: To our knowledge, we are the first to demonstrate an accelerated development of hepatic neoplasia in Yucatan miniature pigs. Our HCC swine model closely mimics the human condition (i.e., progressive disease stages and expression of relevant molecular markers) and is a viable translational model.

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KW - Preclinical studies

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Validation of a Preclinical Model of Diethylnitrosamine-Induced Hepatic Neoplasia in Yucatan Miniature Pigs

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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