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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA031635-05
Application #
3169730
Study Section
Experimental Therapeutics Subcommittee 2 (ET)
Project Start
1982-03-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
5
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Hrushesky, William J M; Sothern, Robert B; Du-Quiton, Jovelyn et al. (2011) Sunspot dynamics are reflected in human physiology and pathophysiology. Astrobiology 11:93-103
Grutsch, James F; Ferrans, Carol; Wood, Patricia A et al. (2011) The association of quality of life with potentially remediable disruptions of circadian sleep/activity rhythms in patients with advanced lung cancer. BMC Cancer 11:193
Retsky, Michael W; Hrushesky, William J M; Gukas, Isaac D (2009) Hypothesis: primary antiangiogenic method proposed to treat early stage breast cancer. BMC Cancer 9:7
Oh, Eun-Young; Wood, Patricia A; Yang, Xiaoming et al. (2009) Discovery of candidate genes and pathways that may help explain fertility cycle stage dependent post-resection breast cancer outcome. Breast Cancer Res Treat 118:345-59
Wood, Patricia A; Du-Quiton, Jovelyn; You, Shaojin et al. (2006) Circadian clock coordinates cancer cell cycle progression, thymidylate synthase, and 5-fluorouracil therapeutic index. Mol Cancer Ther 5:2023-33
Wood, Patricia A; Bove, Kathleen; You, Shaojin et al. (2005) Cancer growth and spread are saltatory and phase-locked to the reproductive cycle through mediators of angiogenesis. Mol Cancer Ther 4:1065-75
Bove, Kathleen; Lincoln, David W; Wood, Patricia A et al. (2002) Fertility cycle influence on surgical breast cancer cure. Breast Cancer Res Treat 75:65-72
Kobayashi, Minoru; Wood, Patricia A; Hrushesky, William J M (2002) Circadian chemotherapy for gynecological and genitourinary cancers. Chronobiol Int 19:237-51
Bjarnason, G A; Jordan, R C; Wood, P A et al. (2001) Circadian expression of clock genes in human oral mucosa and skin: association with specific cell-cycle phases. Am J Pathol 158:1793-801
Lincoln 2nd, D W; Hrushesky, W J; Wood, P A (2000) Circadian organization of thymidylate synthase activity in normal tissues: a possible basis for 5-fluorouracil chronotherapeutic advantage. Int J Cancer 88:479-85

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