@article{6e9beeaa5da24b4eb26ae5df0f048980,
title = "Development and comprehensive characterization of porcine hepatocellular carcinoma for translational liver cancer investigation",
abstract = "Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. New animal models that faithfully recapitulate human HCC phenotypes are required to address unmet clinical needs and advance standard-of-care therapeutics. This study utilized the Oncopig Cancer Model to develop a translational porcine HCC model which can serve as a bridge between murine studies and human clinical practice. Reliable development of Oncopig HCC cell lines was demonstrated through hepatocyte isolation and Cre recombinase exposure across 15 Oncopigs. Oncopig and human HCC cell lines displayed similar cell cycle lengths, alpha-fetoprotein production, arginase-1 staining, chemosusceptibility, and drug metabolizing enzyme expression. The ability of Oncopig HCC cells to consistently produce tumors in vivo was confirmed via subcutaneous (SQ) injection into immunodeficient mice and Oncopigs. Reproducible development of intrahepatic tumors in an alcohol-induced fibrotic microenvironment was achieved via engraftment of SQ tumors into fibrotic Oncopig livers. Whole-genome sequencing demontrated intrahepatic tumor tissue resembled human HCC at the genomic level. Finally, Oncopig HCC cells are amenable to gene editing for development of personalized HCC tumors. This study provides a novel, clinically-relevant porcine HCC model which holds great promise for improving HCC outcomes through testing of novel therapeutic approaches to accelerate and enhance clinical trials.",
keywords = "Interventional radiology, Large animal model, Liver cancer, Personalized medicine, Transgenic pigs",
author = "Gaba, {Ron C.} and Lobna Elkhadragy and {Edward Boas}, F. and Sulalita Chaki and Chen, {Hanna H.} and Mohammed El-Kebir and Garcia, {Kelly D.} and Giurini, {Eileena F.} and Grace Guzman and LoBianco, {Francesca V.} and Neto, {Mario F.} and Newson, {Jordan L.} and Aisha Qazi and Maureen Regan and Rund, {Lauretta A.} and Schwind, {Regina M.} and Stewart, {Matthew C.} and Thomas, {Faith M.} and Whiteley, {Herbert E.} and Jiaqi Wu and Schook, {Lawrence B.} and Schachtschneider, {Kyle M.}",
note = "Funding Information: Ron C. Gaba receives research support from Guerbet USA LLC, Janssen Research & Development LLC, the United States Department of Defense, and the United States National Institutes of Health. F. Edward Boas is a co-founder of Claripacs, LLC. He received research funding (investigator-initiated) from Guerbet. He received research support (investigator-initiated) from GE. He received research supplies (investigator-initiated) from Bayer. He received a research grant and speaker fees from Society of Interventional Oncology, which were sponsored by Guerbet. He attended research meetings sponsored by Guerbet. He is an investor in Labdoor, Qventus, CloudMedx, Notable Labs, and Xgenomes. He is the inventor and assignee on US patent 8233586, and is an inventor on US provisional patent applications 62/754,139 and 62/817,116. Regina M. Schwind receives research support from Guerbet USA LLC and Janssen Research & Development LLC. Lawrence B. Schook research support from Guerbet USA LLC, Janssen Research & Development LLC, the United States Department of Defense, and the United States National Institutes of Health. Kyle M. Schachtschneider receives research support from Guerbet USA LLC, Janssen Research & Development LLC, and the United States National Institutes of Health. The remaining authors—Lobna Elkhadragy, Sulalita Chaki, Hanna H. Chen, Mohammed El-Kebir, Kelly D. Garcia, Eileena F. Giurini, Grace Guzman, Francesca V. LoBianco, Mario F. Neto, Jordan L. Newson, Aisha Qazi, Maureen Regan, Lauretta A. Rund, Matthew C. Stewart, Faith M. Thomas, Herbert E. Whiteley, and Jiaqi Wu—have no reported conflicts of interest. Funding Information: Histological services were provided by the Research Resources Center Research Histology and Tissue Imaging Core at the University of Illinois at Chicago, established with the support of the Vice Chancellor of Research. We acknowledge the UICentre for Drug Discovery at the University of Illinois at Chicago for consultation. Publisher Copyright: {\textcopyright} Gaba et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",
year = "2020",
month = jul,
day = "14",
doi = "10.18632/oncotarget.27647",
language = "English (US)",
volume = "11",
pages = "2686--2701",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "28",
}