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SOD derivatives prevent metastatic tumor growth aggravated by tumor removal

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Abstract

Although surgical removal is the most aggressive strategy to treat removable tumors, it sometimes aggravates tumor growth in metastatic sites. Because surgical procedures generate reactive oxygen species (ROS), known promoters of tumor metastasis and growth, we examined whether the growth of micrometastasis is inhibited by superoxide dismutase (SOD) derivatives after surgical removal of tumors in mice. Murine melanoma B16-BL6 cells were inoculated into the footpad to establish spontaneous pulmonary metastasis. The removal of the footpad tumor significantly (P < 0.05) increased the level of plasma lipoperoxides and the number of tumor cells in the lung. An intravenous injection of SOD or its pegylated-SOD derivative significantly (P < 0.05) inhibited the peroxidation and metastatic tumor growth. It also extended the survival period of mice undergoing removal of the footpad tumor. These findings indicate that the removal of tumor produces ROS, which then aggravates the growth of tumor cells in micrometastases. SOD derivatives can effectively prevent this metastatic tumor growth by detoxifying ROS.

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Abbreviations

SOD:

Superoxide dismutase

PEG-SOD:

Pegylated superoxide dismutase

PEG-catalase:

Pegylated catalase

ROS:

Reactive oxygen species

HBSS:

Hank’s-balanced salt solution

FBS:

Fetal bovine serum

TBARS:

Thiobarbituric acid reactive substances

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Acknowledgements

This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, by Health and Labor Sciences Research Grants for Research on Hepatitis and BSE from the Ministry of Health, Labor and Welfare of Japan and by the 21st Century COE Program “Knowledge Information Infrastructure for Genome Science”.

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Authors and Affiliations

  1. Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan

    Kenji Hyoudou, Yuki Kobayashi, Mai Ikemura, Fumiyoshi Yamashita & Mitsuru Hashida

  2. Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan

    Makiya Nishikawa

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  1. Kenji Hyoudou
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  2. Makiya Nishikawa
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  3. Yuki Kobayashi
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  4. Mai Ikemura
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  5. Fumiyoshi Yamashita
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  6. Mitsuru Hashida
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Correspondence to Makiya Nishikawa.

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Hyoudou, K., Nishikawa, M., Kobayashi, Y. et al. SOD derivatives prevent metastatic tumor growth aggravated by tumor removal. Clin Exp Metastasis 25, 531–536 (2008). https://doi.org/10.1007/s10585-008-9165-3

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  • DOI: https://doi.org/10.1007/s10585-008-9165-3

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