In this integrated project the impact of effects of heterogeneity of responses of cells and tissues on response to hyperthermia in the clinic are explored. The goal is to arrive at diagnostic and therapeutic means to overcome the problems posed by various non-uniform heat responses. Two clinical projects examine aspects of multi-modality treatments: Radiation therapy and heat; chemotherapy and heat. In the former, the importance of scheduling of hyperthermia treatments (both number and temporal sequence) during a course of fractionated hyperthermia is tested. The latter is a randomized prospective trial in recurrent breast cancer patients of Cyclophosphamide, Adriamycin and 5 FU plus or minus hyperthermia. Two equipment development projects have as their objective the reduction of non-uniformity of heating. One deals with microwave equipment development for external applications of hyperthermia and the other with radiofrequency equipment for interstitial heating. The use of NMR, combining imaging and spectroscopy, to diagnose efficacy of hyperthermal treatment as well as mapping of bloodflow is the topic of another project. In project number six, several assays will be examined for their possible ability to predict tumor-to- tumor heterogeneity of response to heat. The final project deals with the biophysical and molecular basis of variations in heat responses, both as related to genetic heterogeneity and to induced thermotolerance.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA044665-02
Application #
3094134
Study Section
Clinical Cancer Program Project Review Committee (CCP)
Project Start
1988-04-01
Project End
1993-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Mivechi, N F; Shi, X Y; Hahn, G M (1995) Stable overexpression of human HSF-1 in murine cells suggests activation rather than expression of HSF-1 to be the key regulatory step in the heat shock gene expression. J Cell Biochem 59:266-80
Spielman, D M; Pauly, J M (1995) Spiral imaging on a small-bore system at 4.7T. Magn Reson Med 34:580-5
Kapp, D S; Cox, R S (1995) Thermal treatment parameters are most predictive of outcome in patients with single tumor nodules per treatment field in recurrent adenocarcinoma of the breast. Int J Radiat Oncol Biol Phys 33:887-99
Spielman, D M; Pauly, J M; Meyer, C H (1995) Magnetic resonance fluoroscopy using spirals with variable sampling densities. Magn Reson Med 34:388-94
Mivechi, N F; Koong, A C; Giaccia, A J et al. (1994) Analysis of HSF-1 phosphorylation in A549 cells treated with a variety of stresses. Int J Hyperthermia 10:371-9
Lee, E R; Kapp, D S; Lohrbach, A W et al. (1994) Influence of water bolus temperature on measured skin surface and intradermal temperatures. Int J Hyperthermia 10:59-72
Mivechi, N F; Ouyang, H; Monson, J M et al. (1994) Correlation of heat resistance and HSP-70A mRNA levels in human tumor cells measured by competitive quantitative polymerase chain reaction. Int J Radiat Oncol Biol Phys 30:141-9
Prionas, S D; Kapp, D S; Goffinet, D R et al. (1994) Thermometry of interstitial hyperthermia given as an adjuvant to brachytherapy for the treatment of carcinoma of the prostate. Int J Radiat Oncol Biol Phys 28:151-62
Mivechi, N F; Murai, T; Hahn, G M (1994) Inhibitors of tyrosine and Ser/Thr phosphatases modulate the heat shock response. J Cell Biochem 54:186-97
Mivechi, N F; Park, Y M; Ouyang, H et al. (1994) Selective expression of heat shock genes during differentiation of human myeloid leukemic cells. Leuk Res 18:597-608

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