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| Publications [#168924] of Mark W. Dewhirst
Papers Published
- BJ Moeller, I Batinic-Haberle, I Spasojevic, ZN Rabbani, MS Anscher, Z Vujaskovic, MW Dewhirst, A manganese porphyrin superoxide dismutase mimetic enhances tumor radioresponsiveness.,
International journal of radiation oncology, biology, physics, United States, vol. 63 no. 2
(October, 2005),
pp. 545-52, ISSN 0360-3016
(last updated on 2009/12/31)
Abstract:
Purpose: To determine the effect of the superoxide dismutase mimetic Mn(III) tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP(5+)) on tumor radioresponsiveness. Methods and Materials: Various rodent tumor (4T1, R3230, B16) and endothelial (SVEC) cell lines were exposed to MnTE-2-PyP(5+) and assayed for viability and radiosensitivity in vitro. Next, tumors were treated with radiation and MnTE-2-PyP(5+)in vivo, and the effects on tumor growth and vascularity were monitored. Results:In vitro, MnTE-2-PyP(5+) was not significantly cytotoxic. However, at concentrations as low as 2 mumol/L it caused 100% inhibition of secretion by tumor cells of cytokines protective of irradiated endothelial cells. In vivo, combined treatment with radiation and MnTE-2-PyP(5+) achieved synergistic tumor devascularization, reducing vascular density by 78.7% within 72 h of radiotherapy (p < 0.05 vs. radiation or drug alone). Co-treatment of tumors also resulted in synergistic antitumor effects, extending tumor growth delay by 9 days (p < 0.01). Conclusions: These studies support the conclusion that MnTE-2-PyP(5+), which has been shown to protect normal tissues from radiation injury, can also improve tumor control through augmenting radiation-induced damage to the tumor vasculature.
Keywords:
Animals • Blood Vessels • Cell Line, Tumor • Culture Media, Conditioned • Drug Screening Assays, Antitumor • Female • Metalloporphyrins • Mice • Mice, Inbred BALB C • Neoplasms • Radiation Tolerance • Radiation-Protective Agents • Radiation-Sensitizing Agents • Rats • Rats, Inbred F344 • Rodentia • blood supply • drug effects • drug effects* • pharmacology • pharmacology* • radiation effects • radiotherapy*
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