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A Metalloporphyrin Antioxidant Alters Cytokine Responses after Irradiation in a Prostate Tumor Model
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A Metalloporphyrin Antioxidant Alters Cytokine Responses after Irradiation in a Prostate Tumor Model
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Journal Article
A Metalloporphyrin Antioxidant Alters Cytokine Responses after Irradiation in a Prostate Tumor Model
2010
Overview
The goal of this study was to evaluate cytokine secretion capacity in a mouse model of prostate cancer, both with and without metalloporphyrin antioxidant and radiation treatment. C57BL/6 mice with subcutaneous RM-9 tumors were treated daily for 12 days with MnTE-2-PyP5+ [Mn (III) tetrakis (N-ethylpyridinium-2-yl) porphyrin], beginning 1 day after injection of RM-9 cells; a 10-Gy tumor-localized dose of 60Co γ rays was administered in a single fraction on day 7. Spleen, tumors and plasma were collected on day 12. T cells in the spleen were activated with anti-CD3 antibody and supernatants were collected. Twenty-two cytokines were quantified in spleen supernatants, five in tumor homogenates, and three in plasma using multiplex bead array technology and ELISA. The presence of a tumor had significant effects on many of the cytokines quantified (P < 0.05). Tumor-induced depression was evident for eight spleen cytokines (TNF-α, G-CSF, GM-CSF, IFN-γ, IL10, IP-10, MIP-1α and mKC), whereas only three were enhanced (IL1β, IL6 and MCP-1). Radiotherapy resulted in enhanced splenocyte capacity to produce IL4 and IL13 and increased IL4, MCP-1 and VEGF in tumors (P < 0.05). Addition of MnTE-2-PyP5+ to radiation decreased the concentrations of IL4, IL13 and TGF-β1 in spleen supernatants and IL4 and VEGF in tumors (P < 0.05 compared to radiation alone). Some differences were also noted in plasma cytokines. Overall, the findings suggest that administration of MnTE-2-PyP5+ together with radiotherapy may enhance anti-tumor immune responsiveness and decrease the risk for radiation-induced normal tissue toxicities.
Publisher
The Radiation Research Society,Radiation Research Society
Subject
/ Animals
/ Antioxidants - administration & dosage
/ Cancer
/ Dose-Response Relationship, Drug
/ Dose-Response Relationship, Radiation
/ Male
/ Metalloporphyrins - administration & dosage
/ Mice
/ Prostatic Neoplasms - metabolism
/ Prostatic Neoplasms - therapy
/ Radiotherapy, Conformal - methods
/ Spleen
/ Tumors
