Date of Award

January 2013

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Robert Weiss

Subject Area(s)

Medicine

Abstract

Bladder cancer is the fourth most commonly diagnosed malignancy and is the eighth leading cause of cancer death among men in the United States of America. Furthermore, it is the seventh and seventeenth most common cancer among males and females, respectively with increasing incidence among Caucasian compared with other ethnicities. Thus it is of utmost importance to develop strategies to improve our ability to early diagnose as well improve treatments by developing new drugs or develop novel treatments. We hypothesized that improving drug potency by enhancing their uptake into tumors will improve their clinical efficacy and enhance tumor killing. We investigated the efficacy of hypothermia in synergizing the effect of various chemical therapeutic agents using different cell bladder types. The combination of hyperthermia and chemotherapeutic agents showed promising results. Hyperthermia enhanced the effect of drugs in reducing the amount of drug required to decrease the number of cells by 50% (LD50). However, the effect was variable depending on cell type and the drug tested. We also showed that hyperthermia alone increased the depth of penetration and density at which nanoparticles could penetrate the bladder. Thus, combination hyperthermia and chemotherapy holds promise for the treatment of superficial bladder cancer both as an initial therapy and as a salvage therapy.

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