Date of Award

Fall 2003

Document Type

Thesis

Degree Name

Master of Science in Computational Biology - (M.S.)

Department

College of Computing Sciences

First Advisor

Michael Recce

Second Advisor

Rosalyn D. Blumenthal

Third Advisor

Zaven S. Ariyan

Abstract

Circadian rhythms have been found in both plants and animals, in normal tissues as well as in most tumors and human cancers. By following these rhythms in healthy and cancerous tissue, it has been possible to find optimal times to deliver a dose of drug, such that efficacy is maximized and toxicity to normal tissues is minimized. In this study, the periodicity of several cell cycle and apoptotic regulatory proteins were studied in two prostate cancer models against a dietary therapeutic agent, Selenium. The ALVA-3 1 (androgen-independent) and PC-3 (androgen-independent) prostate cancer cell lines were grown in vivo, as a subcutaneous xenograft in mice and measured at seven different Hours After Light Onset (HALO). Measurements were taken at 3, 7, 10, 13, 17, 20 and 23 HALO, which is equivalent to 10 AM, 1 PM, 4 PM, 7 PM, 11 PM, 2 AM and 5 AM. The tumors were used to assess total expression of the protein of interest using an immunoblotting method, and the results were assessed by densitometry. Statistical analysis of the mice with the ANOVA and the COSiNOR methods showed that selenium treatment was most effective at HALO 13 at decreasing cell cycle and apoptosis-related proteins for ALVA-3 1. For PC-3 tumor lines, HALO 7 proved to be of highest expression while HALO 13 showed the lowest expression. The selenium treated tumors showed inhibitory effects via lower expression levels throughout both tumor trials.

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