The objective of this proposal is to answer the question, """"""""Is combined use of low dose rate brachytherapy and hyperthermia superior to low dose rate brachytherapy alone?"""""""". If so, what would be the optimum means to combine heat and brachytherapy? Since cell culture studies of the combined heat and low dose rate irra- diation have yielded important radiobiological clues, in vivo tumor and normal tissue studies are needed to address a number of specific issues relevant to clinical applications. There are four specific aims to achieve the overall objective of the study. They are: (i) an optimum radiation dose rate that would yield the maximum heat radiosensitization, (ii) an optimum temperature and duration of heat treatment, (iii) sequence and timing of heat and radiation, and (iv) the effects of critical normal tissues from the combined heat and radiation. We plan to use two tumor systems: RIF fibrosarcoma growing in the intramuscular site of C3H mice and 9L gliosarcoma growing in the brain of Fischer rats. The end points of ana- lysis for tumors include: (i) clonogenic assays, (ii) tumor growth delays, and (iii) tumor cure rates. The end points for normal tissues include semiquantitative skin scorings and histopathological changes of the tissues. Based on the foregoing end points, a quantitative estimate of thermal enhancement ratio and therapeutic gain will be made. The significance of the study would be two-fold: identification of radiobiological factors that might improve the therapeutic ratio of the combined hyperthermia and low dose rate radiotherapy, and application of the findings to the treatment of radioresistant human tumors, including malignant gliomas of the brain and soft tissue sarcomas.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA053114-01A1
Application #
3197900
Study Section
Radiation Study Section (RAD)
Project Start
1991-07-01
Project End
1995-05-31
Budget Start
1991-07-01
Budget End
1992-05-31
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Henry Ford Health System
Department
Type
DUNS #
073134603
City
Detroit
State
MI
Country
United States
Zip Code
48202
Khil, M S; Kim, J H; Mullen, C A et al. (1996) Radiosensitization by 5-fluorocytosine of human colorectal carcinoma cells in culture transduced with cytosine deaminase gene. Clin Cancer Res 2:53-7
Ryu, S; Brown, S L; Kim, S H et al. (1996) Preferential radiosensitization of human prostatic carcinoma cells by mild hyperthermia. Int J Radiat Oncol Biol Phys 34:133-8
Khil, M S; Kim, S H; Pinto, J T et al. (1996) Ethacrynic acid: a novel radiation enhancer in human carcinoma cells. Int J Radiat Oncol Biol Phys 34:375-80
Ryu, S; Brown, S L; Kolozsvary, A et al. (1996) Increased tumour response of a murine fibrosarcoma to low temperature hyperthermia and low dose rate brachytherapy. Int J Hyperthermia 12:635-43
Kim, J H; Kim, S H; Kolozsvary, A et al. (1995) Selective enhancement of radiation response of herpes simplex virus thymidine kinase transduced 9L gliosarcoma cells in vitro and in vivo by antiviral agents. Int J Radiat Oncol Biol Phys 33:861-8
Ryu, S; Gabel, M; Khil, M S et al. (1994) Estramustine: a novel radiation enhancer in human carcinoma cells. Int J Radiat Oncol Biol Phys 30:99-104
Lee, Y J; Erdos, G; Hou, Z Z et al. (1994) Mechanism of quercetin-induced suppression and delay of heat shock gene expression and thermotolerance development in HT-29 cells. Mol Cell Biochem 137:141-54
Kim, J H; Khil, M S; Kim, S H et al. (1994) Clinical and biological studies of estramustine phosphate as a novel radiation sensitizer. Int J Radiat Oncol Biol Phys 29:555-7
Kim, J H; Kim, S H; Brown, S L et al. (1994) Selective enhancement by an antiviral agent of the radiation-induced cell killing of human glioma cells transduced with HSV-tk gene. Cancer Res 54:6053-6
Lee, Y J; Berns, C M; Erdos, G et al. (1994) Effect of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) on HSP70 and HSP28 gene expression and thermotolerance development in human colon carcinoma cells. Biochem Pharmacol 48:2057-63

Showing the most recent 10 out of 11 publications