Existence of Inhibitor of Apoptosis in Tumor Exosomes

<p>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.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Basic Sciences

Year

2015

Author dc:creator

• Valenzuela, Malyn May Asuncion

Contributors dc:contributor

• Wall, Nathan R.
• Buchholz, John N.
• Neidigh, Jonathan W.
• Payne, Kimberly J.
• Perry, Christopher C.

• Medical Biochemistry
• Medicine and Health Sciences
• 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
• Pancreatic Cancer; Metastatic Pancreatic Cancer; Tumor Exosomes; Antimetabolite Agents; Chemoresistance

Statement dc: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.

Language dc:language

English

Repository record dc:identifier

https://scholarsrepository.llu.edu/etd/267

OAI identifier oai:identifier

oai:scholarsrepository.llu.edu:etd-1276