Abstract

The long term objectives of this plan are the investigation of specific aspects of tumor biology/radiobiology, namely reoxygenation, cell migration, cell recruitment, and the relationship between cell sensitivity and cell kinetics.
The specific aims under reoxygenation include determining kinetics within the SCCVII tumor and comparing these for tumor specificity with our earlier RIF-1 studies, investigating reoxygenation after hyperfractionated irradiation, and examining the effect of cytotoxic drugs on reoxygenation. Tumor cell migration studies will investigate tumor cell migration in spheroids that are implanted intraperitoneally; determine whether irradiation effects cell migration within and away from spheroids that rest on collagen sheets; compare the migratory ability of cells grown on glass or plastic culture surfaces with the same cells on collagen sheets; and examine the migratory ability of normal and neoplastic cells, using 10T1/2 and 3T3 cells, contrasted with our EMT6 and RIF-1 data. Cell recruitment, sensitivity, and kinetic studies will characterize the radiosensitivity of P and Q cells in EMT6, RIF-I and SCCVII tumors; investigate whether recruitment of Q cells into P cells is affected by irradiation and by cytotoxic drugs; determine microcolony abortion probabilities; determine whether the mode of X-ray dose fractionation affects growth kinetics of surviving clonogenic tumor cells; and provide data on the kinetics of cell death and the division delay dependence caused by chemotherapeutic drugs. All animal studies will be done with inbred SPF mice. Tumor response will be assayed either by regrowth delay or colony growth. This health-related project is directly applicable to human cancer therapy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA003353-36
Application #
2084460
Study Section
Radiation Study Section (RAD)
Project Start
1978-12-01
Project End
1994-11-30
Budget Start
1992-12-01
Budget End
1994-11-30
Support Year
36
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

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

  Publications

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

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