The purpose of these studies is to investigate and document the 1H NMR changes that occur after chemotherapy and hormonal therapy in animal and human tumors, and to investigate the biologic changes that contribute to these alterations. Based on prior NMR studies, performed by us, on both human and animal tumor models, these NMR changes may prove to be useful in rapidly assessing the efficacy of a particular treatment program, following the toxicology of treatment on normal tissues, and in designing time-sequential treatments based on the biology of NMR changes. The studies will include work with a large tumor mass model and a micrometactatic liver model, both of the M5076 tumor. Studies of tumor NMR in-vivo and in-vitro will be correlated with simultaneous studies of total water content, extracellular water, total lipids and cytokinetic measurements. Changes occuring during tumor growth and occuring during treatment will be analyzed, along with T1, T2 and spin density NMR changes. Sequential human in-vivo NMR studies of liver metastases, bone metastases, with measurements of T1 and other NMR parameters, following chemotherapy and hormonal therapy will be correlated with clinical and laboratory evidence of changes. Appropriate animal models describing similar changes will be used to identify the biologic reasons for the NMR changes, in preparation for using these parameters for non-invasive monitoring of patients and for designing treatment programs.
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