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You searched for +publisher:"University of Alabama – Birmingham" +contributor:("Diasio, Robert B.<br>Posey, James A.<br>Tollefsbol, Trygve O.<br>Wang, Hui"). One record found.

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1. Rayburn, Elizabeth R. Novel immunomodulatory oligonucleotides for cancer therapy.

Degree: PhD, 2007, University of Alabama – Birmingham

Prostate and colon cancer are two of the most prevalent cancers in the United States. Cancer therapy, including surgery, chemotherapy, radiotherapy and biological therapy, often results in severe side effects. New therapies are urgently needed to improve patient survival and quality of life. A new immunotherapy is being developed that makes use of Toll-like receptor 9, which recognizes certain sequences of bacterial and synthetic DNA. TLR9 agonists stimulate the immune system, and have been suggested to have anti-cancer effects. The objective of my dissertation research was to investigate the anti-cancer effects and mechanisms of action of an immunomodulatory oligonucleotide (IMO) agonist of TLR9 that has novel structural and chemical modifications. The anti-tumor activity of the IMO was evaluated in models of prostate and colon cancer alone and in combination with conventional therapies. The expression of TLR9 in cancer cells was also examined, as were the in vitro effects of the IMO. Major discoveries of the dissertation research include: 1) treatment with the IMO led to potent anti-tumor effects, inhibiting tumor growth in all in vivo models of prostate and colon cancer; 2) combination with the IMO led to enhanced effects following treatment with chemotherapeutic agents or radiation; 3) both TLR9 mRNA and protein were expressed in these cancer cells; 4) the IMO increased apoptosis, and decreased proliferation and survival in prostate and colon cancer cells and 5) the IMO is effective against tumors regardless of their p53 or hormone receptor status. Additional studies have shown that the IMO has anti-cancer effects in models of breast and lung cancer, further demonstrating that TLR9 agonism presents a viable new option for cancer therapy. Future studies of TLR9 agonism focused on determining its mechanism(s) of action in cancer cells, and studies in other models of cancer would be of interest. In summary, the IMO has potent anti-tumor effects both as monotherapy and in combination with conventional chemotherapeutic agents and radiation, and appears to act directly on cancer cells via TLR9, suggesting that TLR9 agonism may supply the much-needed new therapeutic strategy that would improve survival and quality of life for patients.

xii, 153 p. : ill., digital, PDF file

Pharmacology and Toxicology

Joint Health Sciences

Immunomodulator Oligonucleotide Toll-like Receptor 9 Chemotherapy CpG Cancer

UNRESTRICTED

Advisors/Committee Members: Zhang, Ruiwen, Diasio, Robert B.<br>Posey, James A.<br>Tollefsbol, Trygve O.<br>Wang, Hui.

Subjects/Keywords: Adenocarcinoma  – drug therapy<; br>; Antineoplastic Agents  – therapeutic use<; br>; Antineoplastic Combined Chemotherapy Protocols  – therapeutic use<; br>; Apoptosis  – drug effects<; br>; Colonic Neoplasms  – drug therapy<; br>; Deoxycytidine  – analogs & derivatives<; br>; Immunologic Factors  – therapeutic use<; br>; Oligonucleotides  – therapeutic use<; br>; Prostatic Neoplasms  – drug therapy<; br>; Taxoids  – therapeutic use<; br>; Toll-Like Receptor 9  – agonists<; br>; Tumor Suppressor Protein p53  – metabolism

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Rayburn, E. R. (2007). Novel immunomodulatory oligonucleotides for cancer therapy. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,463

Chicago Manual of Style (16th Edition):

Rayburn, Elizabeth R. “Novel immunomodulatory oligonucleotides for cancer therapy.” 2007. Doctoral Dissertation, University of Alabama – Birmingham. Accessed October 22, 2019. http://contentdm.mhsl.uab.edu/u?/etd,463.

MLA Handbook (7th Edition):

Rayburn, Elizabeth R. “Novel immunomodulatory oligonucleotides for cancer therapy.” 2007. Web. 22 Oct 2019.

Vancouver:

Rayburn ER. Novel immunomodulatory oligonucleotides for cancer therapy. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2007. [cited 2019 Oct 22]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,463.

Council of Science Editors:

Rayburn ER. Novel immunomodulatory oligonucleotides for cancer therapy. [Doctoral Dissertation]. University of Alabama – Birmingham; 2007. Available from: http://contentdm.mhsl.uab.edu/u?/etd,463

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