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Grant Details

Grant Number: 5R01CA100243-03 Interpret this number
Primary Investigator: Glaser, Ronald
Organization: Ohio State University
Project Title: Stress, the Immune System and Basal Cell Carcinoma
Fiscal Year: 2007


Abstract

DESCRIPTION (provided by applicant): Skin cancer, the most common cancer in the U.S., is more prevalent than all other malignancies combined. Basal cell carcinoma (BCC), the most common form of human cancer, shows evidence for spontaneous regression in approximately 44% of the tumors. Importantly, both spontaneous regression of tumors and appearance of new tumors appear to be related to the immune response to the tumor. Focusing on the microenvironment within BCC tumors, this study addresses the interplay between psychological factors and immune function, and how this interplay may be related to immune/molecular markers associated with histopathological characteristics of BCC tumors that are relatively higher or lower in their immunoreactivity. We will recruit 320 patients who have recently had a BCC removed (the "index" tumor). Two pathologists will evaluate the tumors and assess their immunoreactivity as measured by the level of immune cells trafficking to the tumor and the expression of immune and apoptotic markers expressed by these cells; they will also determine the tumor subtype. We will evaluate cross-sectional relationships between the immunogenic status of the BCC tumors and the influence of age, gender, severe life stressors, and depressive symptoms. Accordingly, we have the following specific aims: 1) Using the index BCC, we will determine if depressive symptoms and severe life stressors are related to markers shown to be reflective of immunoreactivity to a BCC, i.e., tumors showing differences in the level of CD3+ and CD68+ cells that traffic to the BCC tumor and surrounding stroma (quantitative measures) and the expression of cell markers, including CD25, ICAM-1, IFN-gamma, and IL-10, reflecting the activation of these cells (qualitative measures) and bcl-2, an apoptosis marker associated with tumor regression. 2) We will determine if the relationships between depressive symptoms and severe life stressors and tumor immunoreactivity are more pronounced among older adults.



Publications

Stress-induced Norepinephrine Downregulates CCL2 in Macrophages to Suppress Tumor Growth in a Model of Malignant Melanoma.
Authors: Steinberger K.J. , Bailey M.T. , Gross A.C. , Sumner L.A. , Voorhees J.L. , Crouser N. , Curry J.M. , Wang Y. , DeVries A.C. , Marsh C.B. , et al. .
Source: Cancer prevention research (Philadelphia, Pa.), 2020 Sep; 13(9), p. 747-760.
EPub date: 2020-06-09.
PMID: 32518084
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Gender specific association of child abuse and adult cardiovascular disease in a sample of patients with basal cell carcinoma.
Authors: Hosang G.M. , Johnson S.L. , Kiecolt-Glaser J. , Di Gregorio M.P. , Lambert D.R. , Bechtel M.A. , Hearne D.W. , Herron J.B. , Glaser R. .
Source: Child abuse & neglect, 2013 Jun; 37(6), p. 374-9.
EPub date: 2013-01-21.
PMID: 23347911
Related Citations

Basal cell carcinoma: stressful life events and the tumor environment.
Authors: Fagundes C.P. , Glaser R. , Johnson S.L. , Andridge R.R. , Yang E.V. , Di Gregorio M.P. , Chen M. , Lambert D.R. , Jewell S.D. , Bechtel M.A. , et al. .
Source: Archives of general psychiatry, 2012 Jun; 69(6), p. 618-26.
PMID: 22664550
Related Citations

β-Blockers and survival among Danish patients with malignant melanoma: a population-based cohort study.
Authors: Lemeshow S. , Sørensen H.T. , Phillips G. , Yang E.V. , Antonsen S. , Riis A.H. , Lesinski G.B. , Jackson R. , Glaser R. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2011 Oct; 20(10), p. 2273-9.
EPub date: 2011-09-20.
PMID: 21933972
Related Citations

Tumor site immune markers associated with risk for subsequent basal cell carcinomas.
Authors: Glaser R. , Andridge R. , Yang E.V. , Shana'ah A.Y. , Di Gregorio M. , Chen M. , Johnson S.L. , De Renne L.A. , Lambert D.R. , Jewell S.D. , et al. .
Source: PloS one, 2011; 6(9), p. e25160.
EPub date: 2011-09-29.
PMID: 21980389
Related Citations

Glucocorticoids activate Epstein Barr virus lytic replication through the upregulation of immediate early BZLF1 gene expression.
Authors: Yang E.V. , Webster Marketon J.I. , Chen M. , Lo K.W. , Kim S.J. , Glaser R. .
Source: Brain, behavior, and immunity, 2010 Oct; 24(7), p. 1089-96.
EPub date: 2010-05-11.
PMID: 20466055
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Role for catecholamines in tumor progression: possible use for β-blockers in the treatment of cancer.
Authors: Yang E.V. .
Source: Cancer biology & therapy, 2010-07-01; 10(1), p. 30-2.
EPub date: 2010-07-06.
PMID: 20505322
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Norepinephrine upregulates VEGF, IL-8, and IL-6 expression in human melanoma tumor cell lines: implications for stress-related enhancement of tumor progression.
Authors: Yang E.V. , Kim S.J. , Donovan E.L. , Chen M. , Gross A.C. , Webster Marketon J.I. , Barsky S.H. , Glaser R. .
Source: Brain, behavior, and immunity, 2009 Feb; 23(2), p. 267-75.
EPub date: 2008-10-21.
PMID: 18996182
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VEGF is differentially regulated in multiple myeloma-derived cell lines by norepinephrine.
Authors: Yang E.V. , Donovan E.L. , Benson D.M. , Glaser R. .
Source: Brain, behavior, and immunity, 2008 Mar; 22(3), p. 318-23.
EPub date: 2007-11-05.
PMID: 17981009
Related Citations

Chronic herpesvirus reactivation occurs in aging.
Authors: Stowe R.P. , Kozlova E.V. , Yetman D.L. , Walling D.M. , Goodwin J.S. , Glaser R. .
Source: Experimental gerontology, 2007 Jun; 42(6), p. 563-70.
EPub date: 2007-01-30.
PMID: 17337145
Related Citations

Norepinephrine up-regulates the expression of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, and MMP-9 in nasopharyngeal carcinoma tumor cells.
Authors: Yang E.V. , Sood A.K. , Chen M. , Li Y. , Eubank T.D. , Marsh C.B. , Jewell S. , Flavahan N.A. , Morrison C. , Yeh P.E. , et al. .
Source: Cancer research, 2006-11-01; 66(21), p. 10357-64.
PMID: 17079456
Related Citations

Stress, age, and immune function: toward a lifespan approach.
Authors: Graham J.E. , Christian L.M. , Kiecolt-Glaser J.K. .
Source: Journal of behavioral medicine, 2006 Aug; 29(4), p. 389-400.
EPub date: 2006-05-19.
PMID: 16715331
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