The longterm objectives of this research are to explore and define the roles of reoxygenation and recruitment/redistribution in the response of primarily neoplastic cells to ionizing radiation.
Specific aims are to investigate the kinetics of reoxygenation during fractionated irradiation; to investigate reoxygenation during and after treatment of tumors with cytotoxic drugs; to determine whether the kinetics of reoxygenation are affected by radiation combined with drugs; to determine whether cell migration might be detected especially in heterotypic systems by immunofluorescent identification techniques; to determine the effect of radiation on net inward migration of cells into spheroids; to study by different methods migration of cells outward from the centers of spheroids and how this is affected by irradiation; to study the effects of inhibitors of cell motility on tumor cell migration; to complete the development of SACCAS (the Stanford Automated Cell/Colony Autoradiographic Scanner); to investigate the differential radiosensitivity of P and Q cell; to determine whether Q cells are recruited after irradiation, after chemotherapy, and after combinations of the two; to develop algorithms for the analysis of multifield time-lapse movies in order to extract data on cell generation times, colony abortion probabilities, and related statistics; and to correlate 2-dimensional with 3-dimensional migration of EMT6 and/or RIF-1 tumor cells. The methodology includes the use of the paired survival curve method for studying reoxygenation kinetics, the use of multicellular tumor cell spheroids in either homotypic or heterotypic combinations with indicator cells as an in vitro model in order to study migration and thereby assess its role in tumor reoxygenation (detecting the indicator cells either autoradiographically or by immunofluorescence), differentiating between P and Q cells by the ability of the former to incorporate 3HTdR and identifying P cells and their descendants autoradiographically using SACCAS, and producing multifield time-lapse movies of colony growth in vitro by a novel automated technique.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA003353-31
Application #
3163152
Study Section
Radiation Study Section (RAD)
Project Start
1978-12-01
Project End
1988-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
31
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Saad, A H; Kuo, S S; Koong, A C et al. (1994) Modulation of potassium channels by protein tyrosine kinase inhibitors. J Cell Physiol 161:142-8
Koong, A C; Chen, E Y; Lee, A S et al. (1994) Increased cytotoxicity of chronic hypoxic cells by molecular inhibition of GRP78 induction. Int J Radiat Oncol Biol Phys 28:661-6
Koong, A C; Chen, E Y; Kim, C Y et al. (1994) Activators of protein kinase C selectively mediate cellular cytotoxicity to hypoxic cells and not aerobic cells. Int J Radiat Oncol Biol Phys 29:259-65
Brown, J M; Giaccia, A J (1994) Tumour hypoxia: the picture has changed in the 1990s. Int J Radiat Biol 65:95-102
Koong, A C; Chen, E Y; Giaccia, A J (1994) Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues. Cancer Res 54:1425-30
Kallman, R F (1994) The importance of schedule and drug dose intensity in combinations of modalities. Int J Radiat Oncol Biol Phys 28:761-71
Koong, A C; Auger, E A; Chen, E Y et al. (1994) The regulation of GRP78 and messenger RNA levels by hypoxia is modulated by protein kinase C activators and inhibitors. Radiat Res 138:S60-3
Koong, A C; Chen, E Y; Mivechi, N F et al. (1994) Hypoxic activation of nuclear factor-kappa B is mediated by a Ras and Raf signaling pathway and does not involve MAP kinase (ERK1 or ERK2). Cancer Res 54:5273-9
Zaghloul, M S; Dorie, M J; Kallman, R F (1994) Interleukin 1 increases thymidine labeling index of normal tissues of mice but not the tumor. Int J Radiat Oncol Biol Phys 29:805-11
Zaghloul, M S; Dorie, M J; Kallman, R F (1993) Interleukin-1 modulatory effect on the action of chemotherapeutic drugs and localized irradiation of the lip, duodenum, and tumor. Int J Radiat Oncol Biol Phys 26:417-25

Showing the most recent 10 out of 20 publications