UTMB Department of Pathology

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Hyperthermia and Cancer

My long-term goal is to develop an effective therapy for patients with lung cancer. My current interest is in investigating the effects of hyperthermia (exogenously induced heat to a temperature of 42.5-43°C) on cancer cells in tissue culture. I am approaching my long-term goal on five different fronts. Initially, lung-cancer cell heat sensitivity is being quantified and studied in cell culture in Dr. Paul Boor’s lab. When an accurate quantitation of lung cancer cell thermosensitivity is identified, it will be duplicated in nude mice with both ectopic and orthotopic human lung tumors (Department of Surgery’s Nude Mouse facility). Mathematical modeling of the therapeutic dose will be conducted in Dr. Deyo’s lab (Department of Anesthesiology.) This “dose" of heat will then be studied for its effect on healthy swine, and if found to be acceptable in terms of induced pathophysiological changes, will be duplicated under the auspices of the FDA in phase I clinical trials in humans (J.B. Zwischenberger, M.D. is PI). The therapeutic efficiency of the “dose" will also be studied for effectiveness in nude rats with human lung tumors. Cell culture experiments include mass culture, and clonogenic assays of the effect of heat on overall cell survival. Effects of heat on mRNA transcription and protein expression is being studied for three intracellular signaling cascades—heat shock, mitogen-activated and stress-activated. Additionally, methods of inducing apoptosis in lung cancer cells by hyperthermia are also being studied. The effect of heat on cells in various stages of the cell cycle is currently being planned. Additional studies will focus on the combined effects of heat and chemotherapeutic agents. Human lung tumors have successfully been grown in both the ectopic and orthotopic position in nude mice, where we have shown the pre-heating of lung cancer cells prevents malignancy from occurring.

Future studies will focus on continuing these experiments with the eventuality of heat-treating human tumors in mice. Mathematical modeling has allowed for the safe implementation of systemic hyperthermia in patients.

I am currently developing ways of expressing the amount of heat delivered to various sites within the body, with the goal of defining a “thermal dose." A phase I study in patients was approved by the FDA and is currently ongoing. I have completed eight of the 10 patients. All of the patients have survived this trial. Tumor response, as expected, has been mixed. Studies in nude rats have not started, but design and construction of the apparatus necessary for these experiments have begun.