Katie L. Bailey

University of Nebraska Medical Center

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Mark A. Carlson

University of Nebraska Medical Center

Sara Cartwright

University of Nebraska Medical Center

Pinaki Mondal

University of Nebraska Medical Center

Michael A. Hollingsworth

University of Nebraska Medical Center

Neeley Remmers

University of Nebraska Medical Center

T.A. Wyatt

McLaren Greater Lansing

Audrey J. Lazenby

University of Nebraska Medical Center

Neesha Patel

University of Nebraska Medical Center

Sanjib Chowdhury

Janssen (United States)

Todd A. Wyatt

University of Nebraska Medical Center

Cooperative Institutions

University of Nebraska Medical Center

Nebraska Medical Center

University of Nebraska at Omaha

Omaha VA Medical Center

VA Nebraska Western Iowa Health Care System

University of Colorado Denver

University of Colorado Anschutz Medical Campus

University of Nebraska–Lincoln

Fred and Pamela Buffett Cancer Center

RELX Group (Netherlands)

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Understanding the Relationship between TGF-Beta and IGF-1R Signaling in Colorectal Cancer

Katie L. Bailey

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Porcine Models of Pancreatic Cancer

Frontiers in Oncology (2019)

Katie L. Bailey Mark A. Carlson

Pancreatic cancer is the fourth most common cause of cancer-related deaths in both men and women. The 5-year survival rate for metastatic pancreatic cancer is only 8%. There remains a need for improved early diagnosis and therapy for pancreatic cancer. Murine models are the current standard for preclinical study of pancreatic cancer. However, mice may not accurately reflect human biology because of a variety of differences between the two species. Remarkably, only 5-8% of anti-cancer drugs that have emerged from preclinical studies and entered clinical studies have ultimately been approved for clinical use. The cause of this poor approval rate is multi-factorial, but may in part be due to use of murine models that have limited accuracy with respect to human disease. Murine models also have limited utility in the development of diagnostic or interventional technology that require a human-sized model. So, at present, there remains a need for improved animal models of pancreatic cancer. The rationale for a porcine model of pancreatic cancer is (i) to enable development of diagnostic/therapeutic devices for which murine models have limited utility; and (ii) to have a highly predictive preclinical model in which anti-cancer therapies can be tested and optimized prior to a clinical trial. Recently, pancreatic tumors were induced in transgenic Oncopigs and porcine pancreatic ductal cells were transformed that contain oncogenic KRAS and p53-null mutations. Both techniques to induce pancreatic tumors in pigs are undergoing further refinement and expansion. The Oncopig currently is commercially available, and it is conceivable that other porcine models of pancreatic cancer may be available for general use in the near future.

10.3389/fonc.2019.00144

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Citations (40)

Alcohol causes inhibition of histone deacetylase (HDAC) 3, 4 and 10 in the airway epithelium

Alcohol (2012)

Katie L. Bailey Marsha R. Wilderdyke James E. Robinson Joseph H. Sisson Todd A. Wyatt

Histone deacetylase 5

HDAC11

Histone deacetylase 2

10.1016/j.alcohol.2011.09.005

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Amino Acid Metabolism Is Associated With Balance of mTOR and Autophagy Signaling in Airway Mucous Metaplasia

John D. Dickinson Katrina M. Kudrna Paul G. Thomes Rohit Gaurav Katie L. Bailey

Metaplasia

10.1164/ajrccm-conference.2023.207.1_meetingabstracts.a1259

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Porcine pancreatic ductal epithelial cells transformed with KRASG12D and SV40T are tumorigenic

Scientific Reports (2021)

Katie L. Bailey Sara Cartwright Neesha Patel Neeley Remmers Audrey J. Lazenby

Abstract We describe our initial studies in the development of an orthotopic, genetically defined, large animal model of pancreatic cancer. Primary pancreatic epithelial cells were isolated from pancreatic duct of domestic pigs. A transformed cell line was generated from these primary cells with oncogenic KRAS and SV40T. The transformed cell lines outperformed the primary and SV40T immortalized cells in terms of proliferation, population doubling time, soft agar growth, transwell migration and invasion. The transformed cell line grew tumors when injected subcutaneously in nude mice, forming glandular structures and staining for epithelial markers. Future work will include implantation studies of these tumorigenic porcine pancreatic cell lines into the pancreas of allogeneic and autologous pigs. The resultant large animal model of pancreatic cancer could be utilized for preclinical research on diagnostic, interventional, and therapeutic technologies.

10.1038/s41598-021-92852-2

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Porcine pancreatic ductal epithelial cells transformed with KRAS G12D and SV40T are tumorigenic

Research Square (Research Square) (2021)

Katie L. Bailey Sara Cartwright Neesha Patel Neeley Remmers Audrey J. Lazenby

Abstract We describe our initial studies in the development of an orthotopic, genetically-defined, large animal model of pancreatic cancer. Primary pancreatic epithelial cells were isolated from pancreatic duct of domestic pigs. A transformed cell line was generated from these primary cells with oncogenic KRAS and SV40T. The transformed cell lines outperformed the primary and SV40T immortalized cells in terms of proliferation, population doubling time, soft agar growth, transwell migration and invasion. The transformed cell line grew tumors when injected subcutaneously in nude mice, forming glandular structures and staining for epithelial markers. Future work will include implantation studies of these tumorigenic porcine pancreatic cell lines into the pancreas of allogeneic and autologous pigs. The resultant large animal model of pancreatic cancer could be utilized for preclinical research on diagnostic, interventional, and therapeutic technologies.

10.21203/rs.3.rs-268379/v1

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Citations (1)

TGFβ/Smad3 regulates proliferation and apoptosis through IRS-1 inhibition in colon cancer cells

PLoS ONE (2017)

Katie L. Bailey Ekta Agarwal Sanjib Chowdhury Jiangtao Luo Michael G. Brattain

In this study, we have uncovered a novel crosstalk between TGFβ and IGF-1R signaling pathways. We show for the first time that expression and activation of IRS-1, an IGF-1R adaptor protein, is decreased by TGFβ/Smad3 signaling. Loss or attenuation of TGFβ activation leads to elevated expression and phosphorylation of IRS-1 in colon cancer cells, resulting in enhanced cell proliferation, decreased apoptosis and increased tumor growth in vitro and in vivo. Downregulation of IRS-1 expression reversed Smad3 knockdown-mediated oncogenic phenotypes, indicating that TGFβ/Smad3 signaling inhibits cell proliferation and increases apoptosis at least partially through the inhibition of IRS-1 expression and activation. Additionally, the TGFβ/Smad3/IRS-1 signaling axis regulates expression of cyclin D1 and XIAP, which may contribute to TGFβ/Smad3/IRS-1-mediated cell cycle progression and survival. Given that loss of TGFβ signaling occurs frequently in colon cancer, an important implication of our study is that IRS-1 could be a potential therapeutic target for colon cancer treatment.

XIAP

10.1371/journal.pone.0176096

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Citations (34)

Large Animal Models of Breast Cancer

HAL (Le Centre pour la Communication Scientifique Directe) (2021)

Pinaki Mondal Katie L. Bailey Sara Cartwright Vimla Band Mark A. Carlson

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Upregulation of Oxidative Stress Genes in the Airway Epithelium in Alcohol Use Disorders

Katie L. Bailey Heather Smith Katerina Kechris Jonathan Huber Jonathan Cardwell

10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a1838

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Large Animal Models of Breast Cancer

Frontiers in Oncology (2022)

Pinaki Mondal Katie L. Bailey Sara Cartwright Vimla Band Mark A. Carlson

In this mini review the status, advantages, and disadvantages of large animal modeling of breast cancer (BC) will be discussed. While most older studies of large animal BC models utilized canine and feline subjects, more recently there has been interest in development of porcine BC models, with some early promising results for modeling human disease. Widely used rodent models of BC were briefly reviewed to give context to the work on the large animal BC models. Availability of large animal BC models could provide additional tools for BC research, including availability of human-sized subjects and BC models with greater biologic relevance.

Animal model

Human disease

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10.3389/fonc.2022.788038

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Citations (16)