The longterm objectives of this radiobiological study are centered upon finding combinations of radiation with cytotoxic drugs whose effects are superior to those of the constituent modalities alone or of their algebraic sums. There are 10 specific aims which include: To investigate schedule dependence for combinations of cis-dichlordiammine platinum II (c-DDP) and radiation, examining different fractionated radiation courses; to determine whether the addition of 5-FU to c-DDP and radiation can enhance therapeutic effect as a function of sequence and schedule; to investigate schedule dependence for combinations of cyclophosphamide (CY) with fractionated irradiation; to investigate whether specific electron- affinic sensitizers can further enhance optimal c-DDP and CY radiation combinations; to investigate the effectiveness of radiation combined with multiple drug regimens; to confirm the correlation between breathing rate and pulmonary fibrosis by studying post-treatment fibrogenesis; to investigate the kinetics of cell death in tumor cells by time lapse cinemicrography; to further define the protective effect of Interleukin-1 (IL-1) against whole body radiation lethality; to investigate protective effect of IL-1 against CY lethality; to investigate whether IL-1 affects the sensitivity of normal tissues other than the bone marrow, viz. intestinal mucosa; and to determine whether IL-I can improve the therapeutic effectiveness of chemotherapy/radiotherapy combinations. All experiments will be done in inbred SPF mice either with syngeneic tumors (RIF-I, SCCVII, EMT6, KHT) or on normal tissues. Tumor response will be assessed primarily by regrowth delay; lung response primarily by breathing rate; and intestinal response primarily by crypt survival. This health- related project is directly applicable to human cancer therapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA034544-07
Application #
3172259
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Project Start
1983-05-01
Project End
1992-11-30
Budget Start
1989-12-01
Budget End
1990-11-30
Support Year
7
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
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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