PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-2 (2)
 

Clipboard (0)
None
Journals
Authors
more »
Year of Publication
Document Types
1.  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.
doi:10.1155/2009/231539
PMCID: PMC2727657  PMID: 19688113
2.  Circadian Disruption, Per3, and Human Cytokine Secretion 
Integrative cancer therapies  2009;8(4):329-336.
Circadian disruption has been linked with inflammation, an established cancer risk factor. Per3 clock gene polymorphisms have also been associated with circadian disruption and with increased cancer risk. Patients completed a questionnaire and provided a blood sample prior to undergoing a colonoscopy (n = 70). Adjusted mean serum cytokine concentrations (IL-6, TNF-alpha, gamma-INF, IL-I ra, IL-I-beta, VEGF) were compared among patients with high and low scores for fatigue (Multidimensional Fatigue Inventory), depressive symptoms (Beck Depression Inventory II), or sleep disruption (Pittsburgh Sleep Quality Index), or among patients with different Per3 clock gene variants. Poor sleep was associated with elevated VEGF, and fatigue-related reduced activity was associated with elevated TNF-alpha concentrations. Participants with the 4/5 or 5/5 Per3 variable tandem repeat sequence had elevated IL-6 concentrations compared to those with the 4/4 genotype. Biological processes linking circadian disruption with cancer remain to be elucidated. Increased inflammatory cytokine secretion may playa role.
doi:10.1177/1534735409352029
PMCID: PMC2959170  PMID: 19926609
circadian rhythm; clock gene; cytokine; inflammation

Results 1-2 (2)