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| Publications [#168884] of Mark W. Dewhirst
Papers Published
- DS Gridley, AY Makinde, X Luo, A Rizvi, JD Crapo, MW Dewhirst, BJ Moeller, RD Pearlstein, JM Slater, Radiation and a metalloporphyrin radioprotectant in a mouse prostate tumor model.,
Anticancer research, Greece, vol. 27 no. 5A
(November, 2007),
pp. 3101-9, ISSN 0250-7005
(last updated on 2009/12/31)
Abstract:
BACKGROUND: Antioxidants have the potential to protect normal tissues against radiation-induced damage, but must not protect tumor cells during radiotherapy. The major objectives were to determine whether a metalloporphyrin antioxidant affects prostate tumor response to radiation and identify possible mechanisms of interaction. MATERIALS AND METHODS: C57BL/6 mice with RM-9 tumor were treated with manganese (III) meso-tetrakis (1,3-diethylimidazolium-2-yl) porphyrin (MnTDE-2-ImP) and 10 gray (Gy) radiation. Tumor volume was quantified and a subset/group was evaluated for hypoxia-inducible factor-1alpha (HIF-1alpha), bone marrow-derived cell populations and cytokines. RESULTS: The addition of MnTDE-2-ImP transiently increased tumor response compared to radiation alone. The group receiving drug plus radiation had reduced intratumoral HIF-1alpha and decreased capacity to secrete TNF-alpha, whereas production of IL-4 was increased. There were no toxicities associated with combination treatment. CONCLUSION: The results demonstrate that MnTDE-2-ImP did not protect the RM-9 prostate tumor against radiation; instead, radiation effectiveness was modestly increased. Possible mechanisms include reduction of radiation-induced HIF-1alpha and an altered cytokine profile.
Keywords:
Animals • Antioxidants • B-Lymphocytes • Body Weight • Combined Modality Therapy • Disease Models, Animal • Hypoxia-Inducible Factor 1, alpha Subunit • Killer Cells, Natural • Leukocyte Count • Male • Metalloporphyrins • Mice • Mice, Inbred C57BL • Organ Size • Prostatic Neoplasms • Radiation-Protective Agents • Spleen • T-Lymphocytes • anatomy & histology • biosynthesis • blood • drug effects • drug therapy* • pathology • pharmacology • pharmacology* • radiation effects • radiotherapy*
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