A major theme of the program is to develop the foundations for rational application to clinical oncology of the metabolic and physiochemical information obtainable by NMR. To that end, this project will use ex vivo, 31P-, 13C and 1H-NMR spectroscopy to characterize and study the metabolism of a series of 3 animal tumors of varying malignancy (Morris hepatomas 7787, 5123C, and 7777), as well as 2 control tissues (normal and post- partial hepatectomized liver). A unique feature of the study is the use of isolated, arterially perfused solid tumor preparations, analogous to perfused organs. This will permit a variety of NMR experiments not easily performed on either cultured tumor cells or animal tumors in situ. The fundamental issue that this proposal addresses is: Are there NMR detectable markers, or dynamic features of tumor metabolism, which correlate with degree of malignancy or responses to therapy? The specific issued addressed include: 1) Are there NMR detectable markers of tumor metabolism which correlate with the degree of malignancy or responses to therapy. 2) Are there dynamic features of tumor metabolism (ie. responses to changes of metabolic substrates, hormones, etc.) which correlate with the degree of malignancy or responses to therapy. 3) Is the interaction between metabolism and tissue pH different in normal vs. malignant issue? Thus, this study will address fundamental issues in the biology of solid tumors, as well as provide an experimental framework for the eventual application of in vivo NMR measurements to clinical diagnosis and therapeutic monitoring of cancer.
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