Abstract

The changes in vascular functions and related physiological factors such as pO2 and pH in experimental tumors and normal tissues by X-irradiation and heat, and the role of such changes in the treatment of tumors by radiotherapy and hyperthermia alone or in combination will be investigated. The SCK tumors of A/J mice and RIF-1 tumors of C3H mice will be used as tumor model and the skin muscle of C3H mice and SD rats will be used as normal tissue model. Blood flow and blood volume will be measured with radioactive microspheres and radioactive RBC, respectively. The temperature profiles in tumors and normal tissues during heating, which is directly influenced by the heat dissipation by blood perfusion, will be monitored. The changes in oxygenation status, as a result of vascular changes, in tumors and normal tissues will be assessed by measuring pO2 with microelectrode. The changes in hypoxic cell fraction in tumors will also be measured and correlation between the change in pO2 and hypoxic cell fraction will be anaylzed. The implication of changes in oxygenation status of tumors and normal tissues in sequencing radiotherapy and hyperthermia will be critically assessed. The changes in acidity in the tissues will be determined by measuring pH with microelectrode and by biochemical determination of acidic metabolities such as lactic acid and B-hydroxybutric acid. The potential difference in the development of thermotolerance in tumors and normal tissues due to difference in pH and other microenvironmental factors will be analyzed. The information to be obtained in this study should help clinicians devise optimal treatment protocol of radiotherapy and hyperthermia used alone or in combination.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA013353-12
Application #
3163749
Study Section
Radiation Study Section (RAD)
Project Start
1977-09-30
Project End
1988-07-30
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
12
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Song, C W; Shakil, A; Osborn, J L et al. (2009) Tumour oxygenation is increased by hyperthermia at mild temperatures. 1996. Int J Hyperthermia 25:91-5
Monzen, Hajime; Griffin, Robert J; Williams, Brent W et al. (2004) Study of arsenic trioxide-induced vascular shutdown and enhancement with radiation in solid tumor. Radiat Med 22:205-11
Griffin, R J; Monzen, H; Williams, B W et al. (2003) Arsenic trioxide induces selective tumour vascular damage via oxidative stress and increases thermosensitivity of tumours. Int J Hyperthermia 19:575-89
Griffin, Robert J; Williams, Brent W; Wild, Robert et al. (2002) Simultaneous inhibition of the receptor kinase activity of vascular endothelial, fibroblast, and platelet-derived growth factors suppresses tumor growth and enhances tumor radiation response. Cancer Res 62:1702-6
Song, C W; Park, H; Griffin, R J (2001) Improvement of tumor oxygenation by mild hyperthermia. Radiat Res 155:515-28
Park, H J; Lyons, J C; Ohtsubo, T et al. (2000) Cell cycle progression and apoptosis after irradiation in an acidic environment. Cell Death Differ 7:729-38
Griffin, R J; Ogawa, A; Song, C W (2000) A novel drug to reduce tumor perfusion: antitumor effect alone and with hyperthermia. Radiat Res 154:202-7
Ogawa, A; Griffin, R J; Song, C W (2000) Effect of a combination of mild-temperature hyperthermia and nicotinamide on the radiation response of experimental tumors. Radiat Res 153:327-31
Park, H; Lyons, J C; Griffin, R J et al. (2000) Apoptosis and cell cycle progression in an acidic environment after irradiation. Radiat Res 153:295-304
Peterson, M E; Schultz, D J; Reynolds, C et al. (1999) Outcomes in breast cancer patients relative to margin status after treatment with breast-conserving surgery and radiation therapy: the University of Pennsylvania experience. Int J Radiat Oncol Biol Phys 43:1029-35

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