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Utilization of a preclinical model for chemoprevention of esophageal cancer employing a food-based and single- agent approach

Aziz, Robeena M
http://rave.ohiolink.edu/etdc/view?acc_num=osu1086122566

Abstract Details

2004, Doctor of Philosophy, Ohio State University, Public Health.
Cancer incidence estimates for 2003 indicate that 18% of all cancers diagnosed originate in the aerodigestive tract, including the larynx, lung and bronchus, oral cavity, pharynx and esophagus. Specifically esophageal squamous cell carcinoma represents over 90% of all esophageal cancer cases. It is the 8th leading cause of cancer and the 5th leading cause of cancer death. Our laboratory has evaluated the chemopreventive potential of certain foods and a variety of single agents, including food-derived and synthetic compounds, in animal models of lung, colon and esophageal cancer. The goal of these studies was to determine the efficacy of food based and single agents for future use in human chemoprevention trials in individuals at high risk for esophageal cancer. Certain foods, particularly fruits and vegetables, contain a number of complex mixtures that possess preventative properties which may be active at multiple stages of carcinogenesis and / or have additive or synergistic effects. Following a food-based approach for cancer chemoprevention, we initially conducted a study to determine if a freeze-dried preparation of blueberries would inhibit N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis. A single-agent strategy for cancer chemoprevention typically involves the use of an agent which targets a specific process in carcinogenesis. Earlier studies have demonstrated that elevated polyamines may play an important role in the development of tumors in the human esophagus. Based on our findings, our second study evaluated the effect of difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, on post-initiation events in NMBA-induced rat esophageal tumorigenesis. Since black raspberries are effective at inhibiting tumors in both during the initiation and promotion / progression stages of carcinogenesis, our third study evaluated whether black raspberries might also exhibit therapeutic effects against esophageal cancer. The results of our studies indicated that freeze-dried blueberries were ineffective as inhibitors of esophageal tumorigenesis in the rat esophagus. Although the black raspberries may be effective during initiation and promotion / progression stages of carcinogenesis, they did not appear to exhibit any therapeutic value in NMBA-treated rats with fully developed esophageal tumors. However, DFMO appears to be an effective chemopreventive agent when administered in the diet during the promotion / progression stages of NMBA-induced tumorigenesis. Together, these findings illustrate the potential of certain chemopreventives to produce diverse effects among animal model systems, and suggest the importance of developing synergistic-based chemopreventives which inhibit multiple processes during carcinogenesis.
Gary Stoner (Advisor)
170 p.
Health Sciences, Public Health
chemoprevention; N-nitrosmethylbenzylamine; freeze-dried berries

Recommended Citations

Citations

  • Aziz, R. M. (2004). Utilization of a preclinical model for chemoprevention of esophageal cancer employing a food-based and single- agent approach [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1086122566

    APA Style (7th edition)

  • Aziz, Robeena. Utilization of a preclinical model for chemoprevention of esophageal cancer employing a food-based and single- agent approach. 2004. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1086122566.

    MLA Style (8th edition)

  • Aziz, Robeena. "Utilization of a preclinical model for chemoprevention of esophageal cancer employing a food-based and single- agent approach." Doctoral dissertation, Ohio State University, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=osu1086122566

    Chicago Manual of Style (17th edition)

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This open access ETD is published by The Ohio State University and OhioLINK.