Abstract

The effectiveness of combinations of cytostatic chemotherapeutic drugs with radiation will be determined for several endpoints. Drugs to be used include adriamycin, actinomycin D, cyclophosphamide, BCNU, cis-platinum, and bleomycin. Tumor response will be evaluated by the delay of growth of 3 tumors, EMT6 sarcoma, RIF-1 sarcoma, and MDAH/MCa4 carcinoma, tested in syngeneic mice; and by clonogenic survival of tumor cells, determined in vitro, from RIF-1 and EMT6 tumors after treatment in vivo. Changes in the fractions of proliferating (P) and non-proliferating (Q) clonogenic tumor cells will be studied in EMT6 and RIF-1 tumors, using the microcolony 3HTdR labeling method. Combined modality effects will also be studied in the spinal cord, lung, kidney, and skin. Treatment regimens will be evaluated for effects on the spread of lymphatic or blood-borne metastases from footpad-implanted KHT tumors. Cells grown in vitro will be used to test for potentially valuable cytostatic agents other than the 6 drugs listed, and to investigate mechanisms of enhanced effectiveness in combined modality regimens. Intensive investigation of fractionated drug/radiation regimens, as well as baseline single dose experiments, will be undertaken. Testing in the tumor and normal tissue systems is intended ultimately to provide information about the therapeutic ratio of different combinations of modalities, i.e., the effect of treatment on malignant cells relative to the effects on normal tissues.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA025990-08
Application #
3167137
Study Section
Experimental Therapeutics Subcommittee 2 (ET)
Project Start
1979-08-01
Project End
1987-07-31
Budget Start
1986-08-01
Budget End
1987-07-31
Support Year
8
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

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

  Publications

Brown, Martin (2010) Henry S. Kaplan Distinguished Scientist Award Lecture 2007. The remarkable yin and yang of tumour hypoxia. Int J Radiat Biol 86:907-17
Sasai, K; Brown, J M (1994) Discrepancies between measured changes of radiobiological hypoxic fraction and oxygen tension monitoring using two assay systems. Int J Radiat Oncol Biol Phys 30:355-61
Kim, I H; Brown, J M (1994) Reoxygenation and rehypoxiation in the SCCVII mouse tumor. Int J Radiat Oncol Biol Phys 29:493-7
Brown, J M; Giaccia, A J (1994) Tumour hypoxia: the picture has changed in the 1990s. Int J Radiat Biol 65:95-102
Horsman, M R; Chaplin, D J (1994) Enhancement of cyclophosphamide cytotoxicity in vivo by the benzamide analogue pyrazinamide. Br J Cancer 69:648-54
Kim, I H; Lemmon, M J; Brown, J M (1993) The influence of irradiation of the tumor bed on tumor hypoxia: measurements by radiation response, oxygen electrodes, and nitroimidazole binding. Radiat Res 135:411-7
Minchinton, A I; Brown, J M (1992) Enhancement of the cytotoxicity of SR 4233 to normal and malignant tissues by hypoxic breathing. Br J Cancer 66:1053-8
Stone, H B; Minchinton, A I; Lemmon, M et al. (1992) Pharmacological modification of tumor blood flow: lack of correlation between alteration of mean arterial blood pressure and changes in tumor perfusion. Int J Radiat Oncol Biol Phys 22:79-86
Koong, A C; Hirst, D G (1991) The influence of chronic anaemia on the radiosensitivity of two mouse tumours. Br J Cancer 63:499-502
Stone, H B; Hirst, V K; Cribbs, R et al. (1991) A comparison of radiosensitization by etanidazole and pimonidazole in mouse tumors. Int J Radiat Oncol Biol Phys 20:987-95

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