Pancreatic cancer is a serious disease, one in which the survival rate over five years is less than 6%. (1) Often, malignant tumors will exhibit uncontrolled proliferation and it is postulated that they have high metabolic needs. One of the areas of interest in cancer metabolism is the unique need for large amounts of polyamines in order to sustain this uncontrolled proliferation. Polyamines are organic compounds that all cells need for proliferation and differentiation. (2) Cells obtain polyamines by manufacture of them directly or obtain them from the environment through their transport across the cell membrane. When cancer cells have limited access to polyamines they enter apoptosis, or controlled cell death. In animal models of cancer, cellular apoptosis can be tracked by measuring tumor weights as well as histological methods. It is known that difluromethylornithine (DFMO), a polyamine synthesis inhibitor, has shown some success in reducing tumor weights. (3) Cells deprived of the ability to manufacture polyamines will resort to transporting existing polyamines from the environment for their use. (3) It is believed that a polyamine transport inhibitor (PTI) can be designed and used in conjunction with DFMO to completely deprive cancer cells of polyamines and increase rates of apoptosis in tumor cells. Through this study the interaction of DFMO with newly identified PTI will be analyzed. A mouse model with tumor cells in the pancreas will give a picture of how cancer cells react to DFMO / PTI in vivo. The findings allow us to postulate how targeted compounds interact with protein signaling pathways that may be important for regulating response to inhibitors of polyamine synthesis and/or transport.
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Altomare, Deborah A.
Bachelor of Science (B.S.)
College of Medicine
Molecular Biology and Microbiology
Length of Campus-only Access
Honors in the Major Thesis
Hogan, Frederick, "Polyamine Transport Inhibitor Effects on Pancreatic Cancer Proliferation Cells in Vivo" (2015). HIM 1990-2015. 1900.