Abstract

There are two overall objectives for this grant. The first is to obtain data on how hyperthermia kills cells, and the second is to develop information of specific views for clinical hyperthermia treatment.
The specific aims of the basic studies are: (1) mapping of membranes of heated and/or thermotolerant cells, (2) use of temperature-sensitive mutants to study the mechanism of thermotolerance, (3) determine the effects of glucose, oxygen concentration, pH, on ATP intracellular levels, and on heat-sensitivity, and (4) to measure intracellular pH as a function of extracellular pH. Our clinically-oriented studies will examine (1) the decay of thermotolerance both in vitro and in vivo, (2) quantification of heat damage of various pig tissues, examining the possibility of their protection by thermotolerance, (3) the effects of development of thermotolerance on X-ray and drug sensitivity in vitro and in vivo, and finally (4) the optimum number of heat treatments to be associated with a course of fractionated X-ray therapy. Techniques to be utilized include P31 NMR, ESR, competitive finding studies of lectins, hormones and antigens. The data should provide information regarding the advantageous use of hyperthermia against localized malignant lesions.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA004542-29
Application #
3163175
Study Section
Radiation Study Section (RAD)
Project Start
1978-04-01
Project End
1988-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
29
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Hiraoka, M; Hahn, G M (1990) Changes in pH and blood flow induced by glucose, and their effects on hyperthermia with or without BCNU in RIF-1 tumours. Int J Hyperthermia 6:97-103
Goffinet, D R; Prionas, S D; Kapp, D S et al. (1990) Interstitial 192Ir flexible catheter radiofrequency hyperthermia treatments of head and neck and recurrent pelvic carcinomas. Int J Radiat Oncol Biol Phys 18:199-210
Hahn, G M; Ning, S C; Elizaga, M et al. (1989) A comparison of thermal responses of human and rodent cells. Int J Radiat Biol 56:817-25
Anderson, R L; Van Kersen, I; Kraft, P E et al. (1989) Biochemical analysis of heat-resistant mouse tumor cell strains: a new member of the HSP70 family. Mol Cell Biol 9:3509-16
Hiraoka, M; Hahn, G M (1989) Comparison between tumor pH and cell sensitivity to heat in RIF-1 tumors. Cancer Res 49:3734-6
Sekiguchi, R; Rice, G C; Hahn, G M (1988) The use of dansyl lysine to assess heat damage and thermotolerance of normal tissues. Int J Radiat Oncol Biol Phys 14:983-8
Anderson, R L; Shiu, E; Fisher, G A et al. (1988) DNA damage does not appear to be a trigger for thermotolerance in mammalian cells. Int J Radiat Biol 54:285-98
Anderson, R L; Herman, T S; van Kersen, I et al. (1988) Thermotolerance and heat shock protein induction by slow rates of heating. Int J Radiat Oncol Biol Phys 15:717-25
Tobari, C; Van Kersen, I; Hahn, G M (1988) Modification of pH of normal and malignant mouse tissue by hydralazine and glucose, with and without breathing of 5% CO2 and 95% air. Cancer Res 48:1543-7
Lee, K J; Hahn, G M (1988) Abnormal proteins as the trigger for the induction of stress responses: heat, diamide, and sodium arsenite. J Cell Physiol 136:411-20

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