Imaging multidimensional therapeutically relevant circadian relationships.
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.
Singletary
Jamil
J
Medical Chronobiology Laboratory, WJB Dorn VA Medical Center, University of South Carolina, SC 29209, USA.
Wood
Patricia A
PA
Du-Quiton
Jovelyn
J
Wang
Song
S
Yang
Xiaoming
X
Vishnoi
Shobhit
S
Hrushesky
William J M
WJ
J Clin Oncol. 1993 Jul;11(7):1403-17
8315438
Gastroenterology. 1991 Aug;101(2):410-5
2065918
Mol Cancer Ther. 2006 Aug;5(8):2023-33
16928823
J Comp Neurol. 1972 Sep;146(1):1-14
4116104
Nat Neurosci. 1998 Dec;1(8):693-700
10196585
Cell. 2002 May 3;109(3):307-20
12015981
Science. 1985 Apr 5;228(4695):73-5
3883493
Jpn J Clin Oncol. 2000 Dec;30(12):529-33
11210161
Physiol Rev. 1989 Jul;69(3):671-707
2664825
Science. 2003 Oct 10;302(5643):255-9
12934012
Arch Toxicol Suppl. 1979;(2):157-69
157118
J Natl Cancer Inst. 1998 Oct 7;90(19):1480-4
9776414
Science. 1977 Sep 9;197(4308):1089-91
887940
Lancet. 1997 Sep 6;350(9079):681-6
9291901
Science. 1984 Jun 1;224(4652):1001-4
6372092
Breast Cancer Res Treat. 2005 May;91(1):47-60
15868431
Brain Res. 1972 Jul 13;42(1):201-6
5047187
Nature. 2002 Aug 29;418(6901):935-41
12198538
Exp Hematol. 1998 Jun;26(6):523-33
9620286
Eur J Cancer. 1995 Jul-Aug;31A(7-8):1264-70
7577034