Deferasirox Induces Mesenchymal–Epithelial Transition in Crocidolite-Induced Mesothelial Carcinogenesis in Rats
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- Hirotaka Nagai
- Authors' Affiliations: 1Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya; and 2Division of Analytical and Physical Chemistry, Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto, Japan
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- Yasumasa Okazaki
- Authors' Affiliations: 1Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya; and 2Division of Analytical and Physical Chemistry, Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto, Japan
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- Shan Hwu Chew
- Authors' Affiliations: 1Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya; and 2Division of Analytical and Physical Chemistry, Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto, Japan
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- Nobuaki Misawa
- Authors' Affiliations: 1Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya; and 2Division of Analytical and Physical Chemistry, Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto, Japan
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- Hiroyuki Yasui
- Authors' Affiliations: 1Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya; and 2Division of Analytical and Physical Chemistry, Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto, Japan
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- Shinya Toyokuni
- Authors' Affiliations: 1Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya; and 2Division of Analytical and Physical Chemistry, Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto, Japan
書誌事項
- 公開日
- 2013-11-01
- 資源種別
- journal article
- DOI
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- 10.1158/1940-6207.capr-13-0244
- 公開者
- American Association for Cancer Research (AACR)
この論文をさがす
説明
<jats:title>Abstract</jats:title> <jats:p>Asbestos was used worldwide in huge quantities in the past century. However, because of the unexpected carcinogenicity to mesothelial cells with an extremely long incubation period, many countries face this long-lasting social problem. Mesothelioma is often diagnosed in an advanced stage, for which no effective therapeutic protocols are yet established. We previously reported on the basis of animal experiments that the major pathology in asbestos-induced mesothelial carcinogenesis is local iron overload. Here, we undertook to find an effective strategy to prevent, delay, or lower the malignant potential of mesothelioma during asbestos-induced carcinogenesis. We used intraperitoneal injections of crocidolite to rats. We carried out a 16-week study to seek the maximal-tolerated intervention for iron reduction via oral deferasirox administration or intensive phlebotomy. Splenic iron deposition was significantly decreased with either method, and we found that Perls' iron staining in spleen is a good indicator for iron reduction. We injected a total of 10 mg crocidolite at the age of six weeks, and the preventive measures were via repeated oral administration of 25 to 50 mg/kg/d deferasirox or weekly to bimonthly phlebotomy of 4 to 10 mL/kg/d. The animals were observed until 110 weeks. Deferasirox administration significantly increased the fraction of less malignant epithelioid subtype. Although we found a slightly prolonged survival in deferasirox-treated female rats, larger sample size and refinement of the current protocol are necessary to deduce the cancer-preventive effects of deferasirox. Still, our results suggest deferasirox serves as a potential preventive strategy in people already exposed to asbestos via iron reduction. Cancer Prev Res; 6(11); 1222–30. ©2013 AACR.</jats:p>
収録刊行物
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- Cancer Prevention Research
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Cancer Prevention Research 6 (11), 1222-1230, 2013-11-01
American Association for Cancer Research (AACR)
