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  <Article>
    <Journal>
      <PublisherName>MDPI</PublisherName>
      <JournalTitle>Acta Medica Okayama</JournalTitle>
      <Issn>2072-6694</Issn>
      <Volume>11</Volume>
      <Issue>2</Issue>
      <PubDate PubStatus="ppublish">
        <Year>2019</Year>
        <Month/>
      </PubDate>
    </Journal>
    <ArticleTitle>A Novel Combination Cancer Therapy with Iron Chelator Targeting Cancer Stem Cells via Suppressing Stemness</ArticleTitle>
    <FirstPage LZero="delete">177</FirstPage>
    <LastPage/>
    <Language>EN</Language>
    <AuthorList>
      <Author>
        <FirstName EmptyYN="N">Yuki</FirstName>
        <LastName>Katsura</LastName>
        <Affiliation>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Toshiaki</FirstName>
        <LastName>Ohara</LastName>
        <Affiliation>Department of Pathology and Experimental MedicineOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Kazuhiro</FirstName>
        <LastName>Noma</LastName>
        <Affiliation>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Takayuki</FirstName>
        <LastName>Ninomiya</LastName>
        <Affiliation>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Hajime</FirstName>
        <LastName>Kashima</LastName>
        <Affiliation>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Takuya</FirstName>
        <LastName>Kato</LastName>
        <Affiliation>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Hiroaki</FirstName>
        <LastName>Sato</LastName>
        <Affiliation>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Satoshi</FirstName>
        <LastName>Komoto</LastName>
        <Affiliation>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Toru</FirstName>
        <LastName>Narusaka</LastName>
        <Affiliation>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Yasuko</FirstName>
        <LastName>Tomono</LastName>
        <Affiliation> Shigei Medical Research Institute</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Boyi</FirstName>
        <LastName>Xing</LastName>
        <Affiliation>Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Yuehua</FirstName>
        <LastName>Chen</LastName>
        <Affiliation>Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Hiroshi</FirstName>
        <LastName>Tazawa</LastName>
        <Affiliation> Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Shunsuke</FirstName>
        <LastName>Kagawa</LastName>
        <Affiliation> Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Yasuhiro</FirstName>
        <LastName>Shirakawa</LastName>
        <Affiliation> Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Tomonari</FirstName>
        <LastName>Kasai </LastName>
        <Affiliation>School of Bioscience and Biotechnology, Tokyo University of Technology</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Masaharu</FirstName>
        <LastName>Seno</LastName>
        <Affiliation> Laboratory of Nano-Biotechnology, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Akihiro</FirstName>
        <LastName>Matsukawa</LastName>
        <Affiliation> Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Toshiyoshi</FirstName>
        <LastName>Fujiwara</LastName>
        <Affiliation>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</Affiliation>
      </Author>
    </AuthorList>
    <PublicationType/>
    <ArticleIdList>
      <ArticleId IdType="doi"/>
    </ArticleIdList>
    <Abstract> Excess iron causes cancer and is thought to be related to carcinogenesis and cancer progression including stemness, but the details remain unclear. Here, we hypothesized that stemness in cancer is related to iron metabolism and that regulating iron metabolism in cancer stem cells (CSCs) may be a novel therapy. In this study, we used murine induced pluripotent stem cells that expressed specific stem cell genes such as Nanog, Oct3/4, Sox2, Klf4, and c-Myc, and two human cancer cell lines with similar stem cell gene expression. Deferasirox, an orally available iron chelator, suppressed expression of stemness markers and spherogenesis of cells with high stemness status in vitro. Combination therapy had a marked antitumor effect compared with deferasirox or cisplatin alone. Iron metabolism appears important for maintenance of stemness in CSCs. An iron chelator combined with chemotherapy may be a novel approach via suppressing stemness for CSC targeted therapy.</Abstract>
    <CoiStatement>No potential conflict of interest relevant to this article was reported.</CoiStatement>
    <ObjectList>
      <Object Type="keyword">
        <Param Name="value">cancer stem cells</Param>
      </Object>
      <Object Type="keyword">
        <Param Name="value">combination therapy</Param>
      </Object>
      <Object Type="keyword">
        <Param Name="value">iron</Param>
      </Object>
      <Object Type="keyword">
        <Param Name="value">stemness</Param>
      </Object>
    </ObjectList>
    <ReferenceList/>
  </Article>
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