The purpose of the research is to characterize a sharp thermotropic transition that has been demonstrated to occur in the membranes of mammalian cells. The effect of heating on plasma and nuclear membranes will be studied using a variety of biochemical, biophysical, and immunological techniques. Order parameters are to be obtained using spin label electron paramagnetic resonance techniques. Selected labels and fluorescent probes will characterize specific membrane regions and components. Values of lateral diffusion coefficients will be obtained by photo-bleaching experiments. Distribution, density and lateral mobility of H-2 and HLA antigens is to be determined using radiolabeled and fluorescent monoclonal antibodies. The effect of heating on cholesterol content of plasma membranes will be related to antibody binding. The information to be obtained from this research should suggest new approaches in clinical hyperthermia, suggest ways of improving drug delivery to solid tumors in chemotherapy, and to perhaps provide a rational, cellular basis for heat-immunotherapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA032827-08
Application #
3170671
Study Section
Radiation Study Section (RAD)
Project Start
1982-08-01
Project End
1990-11-30
Budget Start
1989-12-01
Budget End
1990-11-30
Support Year
8
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Ning, S; Hahn, G M (1994) Formation of tight junctions and desmosomes protects MDCK cells against hyperthermic killing. J Cell Physiol 160:249-54
Koong, A C; Giaccia, A J; Hahn, G M et al. (1993) Activation of potassium channels by hypoxia and reoxygenation in the human lung adenocarcinoma cell line A549. J Cell Physiol 156:341-7
Saad, A H; Hahn, G M (1992) Activation of potassium channels: relationship to the heat shock response. Proc Natl Acad Sci U S A 89:9396-9
Anderson, R L; Kraft, P E; Bensaude, O et al. (1991) Binding activity of glucocorticoid receptors after heat shock. Exp Cell Res 197:100-6
Mehdi, S Q; Hahn, G M (1990) Effects of hyperthermic temperatures and the synthesis of heat-shock proteins on the lateral diffusion of H-2Kk. Int J Hyperthermia 6:553-61
Gonzalez-Mendez, R R; Hahn, G M (1989) Effects of hyperthermia on the intracellular pH and membrane potential of Chinese hamster ovary cells. Int J Hyperthermia 5:69-84
Lin, P P; Hahn, G M (1988) Growth factors and hyperthermia. II. Viability of Chinese hamster ovary HA-1 cells during serum starvation and hyperthermia. Radiat Res 113:513-25
Woo, S Y; Rice, G C; Kapp, D S et al. (1988) A predictive assay for human tumor cellular response to hyperthermia using dansyl lysine staining and flow cytometry. Int J Radiat Oncol Biol Phys 14:361-5
Lin, P P; Hahn, G M (1988) Growth factors and hyperthermia. I. The relationship between hyperthermic cell killing and the mitogenic response to serum and growth factors. Radiat Res 113:501-12
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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