The purpose of this project is to obtain clinical data, including skin samples, that will help investigators evaluate changes occurring in sun damaged human skin as a result of light that simulates sun exposure (Solar Simulated Light). Of specific interest are the molecular targets for cancer prevention. Molecular targets are the parts of the body's cells that have been shown to play a role in causing or preventing cancer and which scientists seek to affect in a way that may slow or eliminate the development of cancer.
The aim of this study is to assess TLR4 and TOPK/PRPK signaling in sun damaged human skin acutely exposed to solar simulated light and to validate this clinical model prior to intervention with therapeutic skin cancer prevention approaches. Acute solar simulated light exposure will be evaluated in sun damaged skin to determine the level of activation of the targeted pathways using reverse-phase protein array (LCM-RPPA) analysis and immunohistochemistry (IHC).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
31
Acute SSL will be delivered to sun damaged skin at a rate of two-times the minimal erythema dose of each individual subject. Minimal erythema dose is defined as the smallest dose of energy necessary to produce confluent erythema with four distinct borders at 22-26 hours post-exposure.
University of Arizona
Tucson, Arizona, United States
Number of TLR4 Signaling Pathway Analytes With a Significant Change in Expression From Baseline (Pre-solar Stimulated Light Exposure to 1 and 24 Hours Post Exposure)
The number of pre-specified Reverse Phase Protein Microarray Analysis (RPPA) analytes in the TLR4 signaling pathway (AKT S473, AKT T308, IkBa S32/36, IRAK2, IRF-3, IRF-3 S386, MyD88, TAK1 S412, TBK1/NAK, TLR4, TRAF3, TRAF6, TRIF, ERK 1/2 T202/Y204, c-Jun, c-Jun S63, c-Jun S73, NFkB p65 S536, and p38 MAPK T180/Y182) that had a significant change from pre-solar simulated light (pre-SSL) exposure (baseline) to 1hr and 24hr post-SSL in epidermis of sun damaged skin. This outcome will be used to test whether there was a change at the pathway level using the pathway analysis method based on a self-contained, subject-level permutation test: for each analyte a paired t-test is applied to compare the log2 expression level between baseline and the post-SSL time point, and the total number of analytes significantly different at the 0.05 level with change in the expected direction serves as the test statistic, with its null distribution to be estimated by subject-level permutation.
Time frame: Changes from baseline (pre-SSL exposure) to post-SSL exposure (at 1hr and 24hr post-exposure).
Number of TOPK/PRPK Signaling Pathway Analytes With a Significant Change in Expression From Baseline (Pre-solar Stimulated Light Exposure to 1 and 24 Hours Post Exposure)
The number of pre-specified Reverse Phase Protein Microarray Analysis (RPPA) analytes in the TOPK/PRPK signaling pathway (p90RSK S380, PBK/TOPK, PRPK, ERK 1/2 T202/Y204, c-Jun, c-Jun S63, c-Jun S73, NFkB p65 S536, and p38 MAPK T180/Y182) that had a significant change from pre-solar simulated light (pre-SSL) exposure (baseline) to 1hr and 24hr post-SSL in epidermis of sun damaged skin. This outcome will be used to test whether there was a change at the pathway level using the pathway analysis method based on a self-contained, subject-level permutation test: for each analyte a paired t-test is applied to compare the log2 expression level between baseline and the post-SSL time point, and the total number of analytes significantly different at the 0.05 level with change in the expected direction serves as the test statistic, with its null distribution to be estimated by subject-level permutation.
Time frame: Changes from baseline (pre-SSL exposure) to post-SSL exposure (at 1hr and 24hr post-exposure).
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