title: Imaging multidimensional therapeutically relevant circadian relationships.
abstract: Circadian clocks gate cellular proliferation and, thereby, therapeutically target availability within proliferative pathways. This temporal coordination occurs within both cancerous and noncancerous proliferating tissues. The timing within the circadian cycle of the administration of drugs targeting proliferative pathways necessarily impacts the amount of damage done to proliferating tissues and cancers. Concurrently measuring target levels and associated key pathway components in normal and malignant tissues around the circadian clock provides a path toward a fuller understanding of the temporal relationships among the physiologic processes governing the therapeutic index of antiproliferative anticancer therapies. The temporal ordering among these relationships, paramount to determining causation, is less well understood using two- or three-dimensional representations. We have created multidimensional multimedia depictions of the temporal unfolding of putatively causative and the resultant therapeutic effects of a drug that specifically targets these ordered processes at specific times of the day. The systems and methods used to create these depictions are provided, as well as three example supplementary movies.
authors.affiliation: Medical Chronobiology Laboratory, WJB Dorn VA Medical Center, University of South Carolina, SC 29209, USA.
authors.forename: Jamil
authors.initials: J
authors.lastname: Singletary
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Wood
authors.forename: Jovelyn
authors.initials: J
authors.lastname: Du-Quiton
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yang
authors.forename: Shobhit
authors.initials: S
authors.lastname: Vishnoi
authors.forename: William J M
authors.initials: WJ
authors.lastname: Hrushesky
references.citation: J Clin Oncol. 1993 Jul;11(7):1403-17
references.pmid: 8315438
references.citation: Gastroenterology. 1991 Aug;101(2):410-5
references.pmid: 2065918
references.citation: Mol Cancer Ther. 2006 Aug;5(8):2023-33
references.pmid: 16928823
references.citation: J Comp Neurol. 1972 Sep;146(1):1-14
references.pmid: 4116104
references.citation: Nat Neurosci. 1998 Dec;1(8):693-700
references.pmid: 10196585
references.citation: Cell. 2002 May 3;109(3):307-20
references.pmid: 12015981
references.citation: Science. 1985 Apr 5;228(4695):73-5
references.pmid: 3883493
references.citation: Jpn J Clin Oncol. 2000 Dec;30(12):529-33
references.pmid: 11210161
references.citation: Physiol Rev. 1989 Jul;69(3):671-707
references.pmid: 2664825
references.citation: Science. 2003 Oct 10;302(5643):255-9
references.pmid: 12934012
references.citation: Arch Toxicol Suppl. 1979;(2):157-69
references.pmid: 157118
references.citation: J Natl Cancer Inst. 1998 Oct 7;90(19):1480-4
references.pmid: 9776414
references.citation: Science. 1977 Sep 9;197(4308):1089-91
references.pmid: 887940
references.citation: Lancet. 1997 Sep 6;350(9079):681-6
references.pmid: 9291901
references.citation: Science. 1984 Jun 1;224(4652):1001-4
references.pmid: 6372092
references.citation: Breast Cancer Res Treat. 2005 May;91(1):47-60
references.pmid: 15868431
references.citation: Brain Res. 1972 Jul 13;42(1):201-6
references.pmid: 5047187
references.citation: Nature. 2002 Aug 29;418(6901):935-41
references.pmid: 12198538
references.citation: Exp Hematol. 1998 Jun;26(6):523-33
references.pmid: 9620286
references.citation: Eur J Cancer. 1995 Jul-Aug;31A(7-8):1264-70
references.pmid: 7577034