The longterm objectives of this radiobiological study are centered upon finding commbinations of radiation with cytotoxic drugs whose effects are superior to those of the constituent modalities alone or of their algebraic sums. The 5 specific aims are: to investigate the generality of the supraadditive effect produced when cis-Pt is added to fractionated radiation (5 daily doses); to investigate the mechanism of this supra-additive response; to investigate whether supra-additive responses occur also in important normal tissues and thus to derive therapeutic gain factors; to investigate whether tumor response is improved using cytotoxic drugs (notably but not exclusively cis-Pt) combined with fractionated radiation schedules other than 5 daily doses; to determine whether supra-additivity is related to the productive recruitment of non-cycling tumor cells (RIF-1 and EMT6 tumors); and if this is the case, to determine the optimum times for treatment with different modalities. All experiments will be done in mice (C3H/Km or BALB/c/Ka) either on syngeneic tumors (RIF-1, EMT6, KHT, or SCC VII/St) or on normal tissues. Tumor response will assessed by regrowth delay, TCD50, or in vivo/in vitro excision assay. Q cell recruitment will be studied by the labeled microcolony method using SACCAS to analyze autoradiographs. Normal tissues and endpoints include spinal cord/myelitis, lung/LD50/160 days, kidney/LD50 2.5 mos. after unilateral nephrectomy, duodenum and colon/crypt survival, and acute macroscopically visible response of the skin. The results of this project should be applicable to human cancer therapy. Disciplines most directly involved: radiobiology, radiation therapy and medical oncology.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA034544-03
Application #
3172256
Study Section
Radiation Study Section (RAD)
Project Start
1983-05-01
Project End
1988-04-30
Budget Start
1985-05-01
Budget End
1986-04-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
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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
Kallman, R F; Bedarida, G; Rapacchietta, D (1992) Experimental studies on schedule dependence in the treatment of cancer with combinations of chemotherapy and radiotherapy. Front Radiat Ther Oncol 26:31-44
Dorie, M J; Kallman, R F; Cebulska-Wasilewska, A (1991) Interleukin-1 modification of the effects of cyclophosphamide and fractionated irradiation. Int J Radiat Oncol Biol Phys 20:311-4
Kallman, R F; Rapacchietta, D; Zaghloul, M S (1991) Schedule-dependent therapeutic gain from the combination of fractionated irradiation plus c-DDP and 5-FU or plus c-DDP and cyclophosphamide in C3H/Km mouse model systems. Int J Radiat Oncol Biol Phys 20:227-32
Dorie, M J; Allison, A C; Zaghloul, M S et al. (1989) Interleukin 1 protects against the lethal effects of irradiation of mice but has no effect on tumors in the same animals. Proc Soc Exp Biol Med 191:23-9
Kanazawa, H; Rapacchietta, D; Kallman, R F (1988) Schedule-dependent therapeutic gain from the combination of fractionated irradiation and cis-diamminedichloroplatinum (II) in C3H/Km mouse model systems. Cancer Res 48:3158-64
Tanabe, M; Godat, D; Kallman, R F (1987) Effects of fractionated schedules of irradiation combined with cis-diamminedichloroplatinum II on the SCCVII/St tumor and normal tissues of the C3H/KM mouse. Int J Radiat Oncol Biol Phys 13:1523-32