The central purpose of the Clinical/Experimental Radiation Research Interface Studies (CERRIS) grant is to develop more optimal radiation treatment through the integration of advances in basic science research and clinical investigation leading to the development of a more favorable therapeutic ratio. Although the foremost objective of radiation treatment is ablation of the primary tumor and its regional nodal deposits, thereby improving survival rates, there is a need to preserve vital normal tissues surrounding the cancer to assure high quality of life. Ideally, the therapist would like a predictive index to determine the tumor response as well as the potential for severe normal tissue injury which leads to morbid late effects. The major scientific themes an objectives are enumerated below. The focus in the clinical core section devoted to innovative clinical trials will be demonstrated as being derived from these laboratory themes. A. To define the molecular mechanisms of radiation pathophysiology in critical normal tissues organs such as lung and brain, and thereby identify biochemical events that could serve as early markers for late effects. B. To study the role of intrinsic factors such as intracellular glutathione, thiol depletion and potential lethal repair capacity in tumor radiosensitivity and to determine if, by their manipulation, one can overcome tumor cell radioresistance. C. To evaluate the dynamic cytokinetic parameters in irradiated cancers such as flow cytometric DNA, IudR and K67 to determine potential doubling time, DNA synthesis time and to be able to predict the radiosensitivity of tumor cells, particularly in quiescent phase and the kinetics of their recruitment and proliferative capacities. D. To assess tumor hypoxia, oxygen transport and the manipulation of pathophysiological parameters such as blood flow and hemoglobin affinity for potential therapeutic applications. E. To further define the potential beneficial therapeutic effects of beta interferon by simulating through in vitro experimental models the basis for clinical studies. F. To translate through innovative clinical trials the aforementioned radiobiologic research themes into protocol designs that produce more favorable therapeutic ratios and optimal combined modality therapy with an emphasis on organ preservation and quality of life.
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