I will transfer the principles of Chronobiology as they apply to the prevention, diagnosis and treatment of cancer from the nonhuman experimental arena to the cancer patients' bedside. Chronobiologic principles consider the ful spectrum of endogenous biologic rhythms and the interaction of these rhythms with one another as well as with cyclic and noncyclic environmental influences. Time specified experimental designs and measurements, their """"""""microscopic"""""""" rhythmometric analysis and subsequent time specified therapeutic, diagnostic and preventive interventions are apropot to the human cancer problem. I will attempt to increase the effectiveness and decrease the toxicity of presently available anti-cancer therapeis.
This aim entails addressing the basic question of whether spontaneous human malignancies participate in the circadian and other cytokinetic and metabolic rhythms which govern all normal tissues. It also entails accurately gauging the internal time structure of the individual experimental animal or cancer patient, then properly time qualifying the most appropriate hormonal, immunologic or chemotherapeutic treatment program within several time scales and finally employing time qualified observation and analysis of therapeutic pharmacologic and toxologic endpoints. Concurrently, I will attempt to make cancer diagnosis and follow-up more precise by the time qualification of biologic samplings and by the chronobiologic analysis of specific tumor marker substances or tumor altered host properties. Additionally, I plan to pursue practical methods of pharmacologically manipulating pertinent biologic rhythms in order to be able to make any clock hour and season predictably the optimal time for administering cancer chemotherapy. I will accomplish these aims by the use of chronobiologic methodologies which use the concepts of: multiple equispaced time qualified sampling, observation spans inversely proportional in length to the amplitude of the rhythm being observed and the degree of synchronization of individuals studied and bioergodicity. Rhythmometric analysis will consider the interaction of several concurrent rhythms of different period lengths. The consideration of such """"""""spectral solutions"""""""" will allow even greater biologic precision.
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