Abstract

Pancreatic cancer is a deadly and aggressive disease. The only option for metastatic pancreatic cancer is chemotherapy where only the antimetabolites gemcitabine (Gem) and 5-fluorouracil (5FU) are used clinically. However, resistance to these antimetabolites remains a problem highlighting the need to discover and develop new antimetabolites that will improve a patient’s overall survival. Cancer is a disease that has acquired numerous molecular, biochemical and cellular changes. Resistance to apoptosis is one of the characteristics of cancer, of which the inhibitor of apoptosis (IAP) family of proteins plays an important role. It has also been shown that cancer cells secrete vesicles called tumor exosomes (TEX) which are loaded with bioactive molecules which strongly influences the tumor microenvironment. Both protein and mRNA of the IAP Survivin, cIAP1, cIAP2 and XIAP are released into the extracellular space by not only the pancreatic cancer cell line PANC-1, but also from other cancer and non-cancer cell lines. IAP release may play an important role in pancreatic cancer’s lack of response to antimetabolite agents and eventual progression to chemoresistance. These findings can be used to design and develop novel compounds that can be used in combination with Gem or 5FU which are designed to target exosomes, in particular IAP packaging, which may make a vital impact in the treatment for metastatic pancreatic cancer.

LLU Discipline

Biochemistry

Department

Basic Sciences

School

School of Medicine

First Advisor

Wall, Nathan R.

Second Advisor

Buchholz, John N.

Third Advisor

Neidigh, Jonathan W.

Fourth Advisor

Payne, Kimberly J.

Fifth Advisor

Perry, Christopher C.

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

2015

Date (Title Page)

3-2015

Language

English

Library of Congress/MESH Subject Headings

Neoplasms; Inhibitor of Apoptosis Proteins; Antigens - Neoplasm; Cell Line - Tumor; Cell Cycle; Exosomes; Vascular Endothelial Growth Factors; Equilibrative Nucleoside Transporter 1; RNA Interference; Matrix Metalloproteinases; Polymerase Chain Reaction

Subject - Local

Pancreatic Cancer; Metastatic Pancreatic Cancer; Tumor Exosomes; Antimetabolite Agents; Chemoresistance

Type

Dissertation

Page Count

114

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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