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Metabolic Profiling of Urine, Fecal, and Serum Samples and Pancreatic Tumors and Evaluation of HMGA1 Expression Levels in Pancreatic Intraepithelial Neoplasia Cells in the Ptf1a-Cre; LSL-KrasG12D Transgenic Mouse Model of Pancreatic Cancer

Schmahl, Michelle Jordan
http://orcid.org/0000-0001-5410-2545
http://rave.ohiolink.edu/etdc/view?acc_num=miami1523977530802748

Abstract Details

2018, Doctor of Philosophy, Miami University, Chemistry and Biochemistry.
Pancreatic cancer is the third leading cause of cancer related deaths. Individuals inflicted with this cancer are typically asymptomatic until advanced stages are reached. Surgical procedures provide the greatest chance of survival; nevertheless, pancreatic cancer is rarely detected in early stages where surgery would be effective. This is primarily due to the lack of dependable tests for early detection and diagnosis. Current diagnostic methods are extremely invasive or are deemed inadequate by general consensus, and population screening for pancreatic cancer with these methods is not feasible. Urine and fecal excrements have been shown to encompass potentially useful biomarkers in pancreatic cancer. In this dissertation, potential early biomarkers in serum, urine, and blood were identified through the use of the mouse model Ptf1aCre; LSL-KrasG12D of pancreatic cancer and nuclear magnetic resonance spectroscopy (NMR). Additionally, a histology atlas of pancreatic tissue was produced to aid in the evaluation of the precancerous stages, referred to as pancreatic intraepithelial neoplasia (PanIN). Due to the existence of multiple classification systems being in use, discrepancies among the field exist. The generated atlas will promote discussion and clarification of the PanIN stages. In order to acquire images, removal of the pancreas had to be performed. Due to the lack of peer-reviewed and high quality videos and instructions available, a manuscript accompanied by a video were produced to show the proper procedures to successfully remove the pancreas by dissection from a mouse. Also, high-mobility growth A1 protein (HMGA1), that has been linked to tumor progression in many cancers, had not been examined with the Ptf1aCre; LSL-KrasG12D mouse model until now. Elevated levels of HMGA1 have been shown to be present in as young as 5-months in the PanIN mice and in as old as 15-months when compared to normal un-transitioned pancreatic tissue. This dissertation encompasses many tools, platforms, and analyses assisting in the progression of early diagnostic pancreatic cancer research.
Michael Kennedy (Advisor)
Christopher Makaroff (Committee Chair)
Michael Crowder (Committee Member)
David Tierney (Committee Member)
Michael Robinson (Committee Member)
311 p.
Biochemistry; Chemistry
pancreas, pancreatic cancer, pancreatic ductal adenocarcinoma, adenocarcinoma, pancreatic intraepithelial neoplasia, PanIN, pancreas dissection, mouse pancreas dissection, mouse, HMGA1, high-mobility group A protein, atlas, histology

Recommended Citations

Citations

  • Schmahl, M. J. (2018). Metabolic Profiling of Urine, Fecal, and Serum Samples and Pancreatic Tumors and Evaluation of HMGA1 Expression Levels in Pancreatic Intraepithelial Neoplasia Cells in the Ptf1a-Cre; LSL-KrasG12D Transgenic Mouse Model of Pancreatic Cancer [Doctoral dissertation, Miami University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=miami1523977530802748

    APA Style (7th edition)

  • Schmahl, Michelle. Metabolic Profiling of Urine, Fecal, and Serum Samples and Pancreatic Tumors and Evaluation of HMGA1 Expression Levels in Pancreatic Intraepithelial Neoplasia Cells in the Ptf1a-Cre; LSL-KrasG12D Transgenic Mouse Model of Pancreatic Cancer. 2018. Miami University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=miami1523977530802748.

    MLA Style (8th edition)

  • Schmahl, Michelle. "Metabolic Profiling of Urine, Fecal, and Serum Samples and Pancreatic Tumors and Evaluation of HMGA1 Expression Levels in Pancreatic Intraepithelial Neoplasia Cells in the Ptf1a-Cre; LSL-KrasG12D Transgenic Mouse Model of Pancreatic Cancer." Doctoral dissertation, Miami University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=miami1523977530802748

    Chicago Manual of Style (17th edition)

miami1523977530802748
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© 2018, all rights reserved.
This open access ETD is published by Miami University and OhioLINK.