2.50
Hdl Handle:
http://hdl.handle.net/10755/158052
Type:
Presentation
Title:
The Role of GP130 Cytokines in Prostate Cancer
Abstract:
The Role of GP130 Cytokines in Prostate Cancer
Conference Sponsor:Western Institute of Nursing
Conference Year:2006
Author:FitzGerald, Leah, PhD, RN
P.I. Institution Name:University of California Los Angeles
Title:Assistant Professor
Contact Address:8838 Villanova Avenue, Los Angeles, CA, 90045, USA
Contact Telephone:310-206-1065
Co-Authors:Otoniel Martinez-Maza, PhD; and Elizabeth CrabBreen, PhD
Objective: Serum IL-6 levels are a significant prognostic factor for prostate cancer (CaP). As IL-6-like cytokines share biological activities, and receptor elements, with IL-6, it is important to define the relationship between serum in vivo levels of IL-6, IL-11, sgp130, and sIL6R and the development of CaP. In prior work, IL-6, gp80 and gp130 genotype has been associated with increased in vivo and in vitro levels of IL-6 and IL-6 super family cytokines, as well as with the development of IL-6-associated cancers. As IL-6 is thought to play a role in the pathogenesis of CaP, we will define the relationship between IL-6/gp130 coding/promoter SNPs, in vivo IL-6 and IL-6 super family cytokine levels, and the development of CaP. The objectives of this study are to (1) define serum levels of gp130 cytokines and soluble receptors preceding the development of CaP and (2) define the association of IL-6, gp80 and gp130 genotype/phenotype and the development of CaP. Methods: This longitudinal study will be composed of men who are enrolled in the Multicenter AIDS Cohort Study (MACS) cohort, (a natural history study of AIDS) and who have developed CaP. Currently, there are 24 such subjects in the entire MACS. A group of 72 control subjects will be matched on age and HIV status for serum analysis. Design: Serum levels of IL-6 and IL-6 like cytokines and activation molecules will be measured in sera that has been previously collected at the following MACS study visits: 1) the visit preceding, but closest to, the diagnosis of CaP, 2) 12 months pre CaP diagnosis, 3) 1-3 years pre CaP diagnosis, 4) 3-5 years pre CaP diagnosis, and 5) 10 years pre CaP diagnosis. DNA (cell pellet or B-LCL) and serum will be analyzed in the patient and matched controls for a total of "n" of 96 (case: control ratio of 1:3). SNPs related to IL-6 gene expression and IL-6 receptor subunits (the IL-6 promoter -174 G/C SNP, gp80 & gp130 SNP) will be examined. DNA samples will be genotyped by use of the 5' nuclease (TaqMan) system. Serum Cytokine evaluations: Duplicate determinations will be done on all specimens. All serum cytokine levels will be measured using ultrasensitive Biosource ELISA. Results: Work currently in process. Conclusions: In summary, elevated serum levels of IL6 are associated with CaP, and IL6 can contribute to the pathogenesis of CaP, with elevated serum IL6 correlating with a poorer clinical outcome. IL6 is produced by activated macrophages in inflammatory responses, as well as by fat cells and other cell types. We postulate that IL6 and related cytokines signal via the gp130 receptor element to maintain STAT3 in an activated state, thus helping to drive the malignant phenotype in CaP, enhance inflammation. Together, these observations suggest that IL6 (and IL6 type cytokines) produced in inflammatory responses may contribute to the development and progression of CaP.
Repository Posting Date:
26-Oct-2011
Date of Publication:
17-Oct-2011
Sponsors:
Western Institute of Nursing

Full metadata record

DC FieldValue Language
dc.typePresentationen_GB
dc.titleThe Role of GP130 Cytokines in Prostate Canceren_GB
dc.identifier.urihttp://hdl.handle.net/10755/158052-
dc.description.abstract<table><tr><td colspan="2" class="item-title">The Role of GP130 Cytokines in Prostate Cancer</td></tr><tr class="item-sponsor"><td class="label">Conference Sponsor:</td><td class="value">Western Institute of Nursing</td></tr><tr class="item-year"><td class="label">Conference Year:</td><td class="value">2006</td></tr><tr class="item-author"><td class="label">Author:</td><td class="value">FitzGerald, Leah, PhD, RN</td></tr><tr class="item-institute"><td class="label">P.I. Institution Name:</td><td class="value">University of California Los Angeles</td></tr><tr class="item-author-title"><td class="label">Title:</td><td class="value">Assistant Professor</td></tr><tr class="item-address"><td class="label">Contact Address:</td><td class="value">8838 Villanova Avenue, Los Angeles, CA, 90045, USA</td></tr><tr class="item-phone"><td class="label">Contact Telephone:</td><td class="value">310-206-1065</td></tr><tr class="item-email"><td class="label">Email:</td><td class="value">lfitzger@sonnet.ucla.edu</td></tr><tr class="item-co-authors"><td class="label">Co-Authors:</td><td class="value">Otoniel Martinez-Maza, PhD; and Elizabeth CrabBreen, PhD</td></tr><tr><td colspan="2" class="item-abstract">Objective: Serum IL-6 levels are a significant prognostic factor for prostate cancer (CaP). As IL-6-like cytokines share biological activities, and receptor elements, with IL-6, it is important to define the relationship between serum in vivo levels of IL-6, IL-11, sgp130, and sIL6R and the development of CaP. In prior work, IL-6, gp80 and gp130 genotype has been associated with increased in vivo and in vitro levels of IL-6 and IL-6 super family cytokines, as well as with the development of IL-6-associated cancers. As IL-6 is thought to play a role in the pathogenesis of CaP, we will define the relationship between IL-6/gp130 coding/promoter SNPs, in vivo IL-6 and IL-6 super family cytokine levels, and the development of CaP. The objectives of this study are to (1) define serum levels of gp130 cytokines and soluble receptors preceding the development of CaP and (2) define the association of IL-6, gp80 and gp130 genotype/phenotype and the development of CaP. Methods: This longitudinal study will be composed of men who are enrolled in the Multicenter AIDS Cohort Study (MACS) cohort, (a natural history study of AIDS) and who have developed CaP. Currently, there are 24 such subjects in the entire MACS. A group of 72 control subjects will be matched on age and HIV status for serum analysis. Design: Serum levels of IL-6 and IL-6 like cytokines and activation molecules will be measured in sera that has been previously collected at the following MACS study visits: 1) the visit preceding, but closest to, the diagnosis of CaP, 2) 12 months pre CaP diagnosis, 3) 1-3 years pre CaP diagnosis, 4) 3-5 years pre CaP diagnosis, and 5) 10 years pre CaP diagnosis. DNA (cell pellet or B-LCL) and serum will be analyzed in the patient and matched controls for a total of &quot;n&quot; of 96 (case: control ratio of 1:3). SNPs related to IL-6 gene expression and IL-6 receptor subunits (the IL-6 promoter -174 G/C SNP, gp80 &amp; gp130 SNP) will be examined. DNA samples will be genotyped by use of the 5' nuclease (TaqMan) system. Serum Cytokine evaluations: Duplicate determinations will be done on all specimens. All serum cytokine levels will be measured using ultrasensitive Biosource ELISA. Results: Work currently in process. Conclusions: In summary, elevated serum levels of IL6 are associated with CaP, and IL6 can contribute to the pathogenesis of CaP, with elevated serum IL6 correlating with a poorer clinical outcome. IL6 is produced by activated macrophages in inflammatory responses, as well as by fat cells and other cell types. We postulate that IL6 and related cytokines signal via the gp130 receptor element to maintain STAT3 in an activated state, thus helping to drive the malignant phenotype in CaP, enhance inflammation. Together, these observations suggest that IL6 (and IL6 type cytokines) produced in inflammatory responses may contribute to the development and progression of CaP.</td></tr></table>en_GB
dc.date.available2011-10-26T20:27:42Z-
dc.date.issued2011-10-17en_GB
dc.date.accessioned2011-10-26T20:27:42Z-
dc.description.sponsorshipWestern Institute of Nursingen_GB
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