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Deferasirox induces mesenchymal-epithelial transition in crocidolite-induced mesothelial carcinogenesis in rats.
MedLine Citation:
PMID:  24027214     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 based on 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 performed 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 6 weeks, and the preventive measures were via repeated oral administration of 25-50 mg/kg/day deferasirox or weekly to bimonthly phlebotomy of 4-10 ml/kg/day. The animals were observed till 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.
Authors:
Hirotaka Nagai; Yasumasa Okazaki; Shan Hwu Chew; Nobuaki Misawa; Hiroyuki Yasui; Shinya Toyokuni
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-9-11
Journal Detail:
Title:  Cancer prevention research (Philadelphia, Pa.)     Volume:  -     ISSN:  1940-6215     ISO Abbreviation:  Cancer Prev Res (Phila)     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-9-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101479409     Medline TA:  Cancer Prev Res (Phila)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine.
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