This proposed study is to evaluate the significant observation that tumors which could not be controlled by constant-temperature hyperthermia regressed fully after step-down heating (SDH). Regrowth after an apparently complete regression in most of these tumors implies that not all tumor cells were killed by SDH; we hypothesize that peripheral tumor cells survived and that these should be sensitive to X-radiation. We propose to use the RIF tumor model for the SDH study based on the low or nonimmunogenic status of the tumor with commercially available hosts, its high heat resistance which we believe to be representative of many spontaneous tumors, and its propensity to grow both in vivo and in vitro with acceptably high plating efficiency. The parallel studies of SDH in vivo and in vitro, coupled with blood flow measurements will define the relative contributions of cellular versus physiological factors to tumor control in vivo and will also extend in vitro phenomenology to an in vivo tumor model. Specific combinations of SDH and X-radiation will be evaluated both in tumors and in adjacent normal tissue for a quantitation of therapeutic gains that can be achieved by this new way of combining hyperthermia and X-radiation.
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| Monson, T P; Henle, K J; Nagle, W A et al. (1991) Tumor-targeted delivery of 8-hydroxyquinoline. Int J Radiat Oncol Biol Phys 20:1263-71 |
| Henle, K J; Shmookler Reis, R J; Lumpkin, C K (1991) Modulation of cellular glycosidase activity by hyperthermia. Int J Hyperthermia 7:531-7 |
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| Mansouri, A; Henle, K J; Nagle, W A et al. (1990) Tumor cell drug resistance and its reversal. SAAS Bull Biochem Biotechnol 3:91-6 |
| Henle, K J; Monson, T P; Stone, A (1990) Enhanced glycosyltransferase activity during thermotolerance development in mammalian cells. J Cell Physiol 142:372-8 |
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