Journal article
Development and translational imaging of a TP53 porcine tumorigenesis model
The Journal of clinical investigation, Vol.124(9), pp.4052-4066
09/02/2014
DOI: 10.1172/JCI75447
PMCID: PMC4151205
PMID: 25105366
Abstract
Cancer is the second deadliest disease in the United States, necessitating improvements in tumor diagnosis and treatment. Current model systems of cancer are informative, but translating promising imaging approaches and therapies to clinical practice has been challenging. In particular, the lack of a large-animal model that accurately mimics human cancer has been a major barrier to the development of effective diagnostic tools along with surgical and therapeutic interventions. Here, we developed a genetically modified porcine model of cancer in which animals express a mutation in
TP53
(which encodes p53) that is orthologous to one commonly found in humans (R175H in people, R167H in pigs).
TP53
R167H/R167H
mutant pigs primarily developed lymphomas and osteogenic tumors, recapitulating the tumor types observed in mice and humans expressing orthologous
TP53
mutant alleles. CT and MRI imaging data effectively detected developing tumors, which were validated by histopathological evaluation after necropsy. Molecular genetic analyses confirmed that these animals expressed the R167H mutant p53, and evaluation of tumors revealed characteristic chromosomal instability. Together, these results demonstrated that
TP53
R167H/R167H
pigs represent a large-animal tumor model that replicates the human condition. Our data further suggest that this model will be uniquely suited for developing clinically relevant, noninvasive imaging approaches to facilitate earlier detection, diagnosis, and treatment of human cancers.
Details
- Title: Subtitle
- Development and translational imaging of a TP53 porcine tumorigenesis model
- Creators
- Jessica C Sieren - Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa, USADavid K Meyerholz - Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa, USAXiao-Jun Wang - Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa, USABryan T Davis - Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa, USAJohn D Newell - Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa, USAEmily Hammond - Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa, USAJudy A Rohret - Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa, USAFrank A Rohret - Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa, USAJason T Struzynski - Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa, USAJ. Adam Goeken - Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa, USAPaul W Naumann - Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa, USAMariah R Leidinger - Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa, USAAgshin Taghiyev - Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa, USARichard Van Rheeden - Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa, USAJussara Hagen - Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa, USABenjamin W Darbro - Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa, USADawn E Quelle - Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa, USAChristopher S Rogers - Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.124(9), pp.4052-4066
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI75447
- PMID
- 25105366
- PMCID
- PMC4151205
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 09/02/2014
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Pathology; Medical Genetics and Genomics; Neuroscience and Pharmacology
- Record Identifier
- 9984040018502771
Metrics
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