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Anti-tumor effect achieved by effective induction of ferroptosis utilizing non-transferrin-bound iron

Research Project

Project/Area Number 18K08347
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionAsahikawa Medical College

Principal Investigator

IKUTA KATSUYA  旭川医科大学, 医学部, 客員教授 (00396376)

Co-Investigator(Kenkyū-buntansha) 田中 宏樹  旭川医科大学, 医学部, 助教 (70596155)
土岐 康通  旭川医科大学, 医学部, 特任助教 (90596280)
齋藤 豪志  旭川医科大学, 大学病院, 医員 (80837930)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsフェロトーシス / 抗腫瘍効果 / 非トランスフェリン結合鉄(NTBI) / 鉄 / labile plasma iron (LPI) / 非トランスフェリン結合鉄
Outline of Final Research Achievements

The present study was performed to elucidate the precise mechanisms of iron involvement for ferroptosis by using molecular biological techniques and also to elucidate the effective methods for inducing ferroptosis by iron modulation. Various cell lines derived from such as hepatocellular carcinoma, hematological malignancies, pancreas cancers showed ferroptosis by ferroptosis inducing reagent erastin. The inhibitory effect for cell growth by erastin was increased by adding iron to cell culture medium. Especially, non-transferrin-bound iron (NTBI) and labile plasma iron (LPI) seemed to cause ferroptosis effectively than transferrin-bound iron. We consider that the present data showed the possibility of effective induction of ferroptosis by iron modulation.

Academic Significance and Societal Importance of the Research Achievements

本研究では、肝癌、血液腫瘍、膵癌など様々な腫瘍細胞において、新しい細胞死フェロトーシスが起こることが確認され、さらに誘導物質に少量の鉄負荷を行うと、より効率的に起こることが示された。加えて、トランスフェリンと結合していない非トランスフェリン結合鉄(NTBI)やNTBIによる酸化能labile plasma iron (LPI)が特に効率的に腫瘍細胞にフェロトーシスを惹起する可能性も見出し、指標としての意義も示唆された。各種難治性腫瘍に対する既存薬物とは全く異なる新規の治療アプローチに繋がる可能性が示され、今後の基礎および臨床研究にも寄与できる基盤となる意義深い結果を得られたと考えている。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (35 results)

All 2021 2020 2019 2018

All Journal Article (18 results) (of which Peer Reviewed: 13 results,  Open Access: 4 results) Presentation (12 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Book (5 results)

  • [Journal Article] Long-term phlebotomy successfully alleviated hepatic iron accumulation in a ferroportin disease patient with a mutation in SLC40A1: A case report.2021

    • Author(s)
      Nishina S, Tomiyama Y, Ikuta K, Tatsumi Y, Toki Y, Kato A, Kato K, Yoshioka N, Sasaki K, Hara Y, Hino K.
    • Journal Title

      BMC Gastroenterology

      Volume: 21(1) Issue: 1 Pages: 111-111

    • DOI

      10.1186/s12876-021-01674-z

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Type 4B hereditary hemochromatosis due to heterozygous p.D157A mutation in SLC40A1 complicated with hypopituitarism.2021

    • Author(s)
      Honma Y, Karasuyama T, Kumamoto K, Shimajiri S, Toki Y, Tatsumi Y, Sumida K, Koikawa K, Morino K, Oe S, Miyagawa K, Yamasaki M, Shibata M, Abe S, Ikuta K, Hayashi H, Harada M.
    • Journal Title

      Medical Molecular Morphology

      Volume: 54(1) Issue: 1 Pages: 60-67

    • DOI

      10.1007/s00795-020-00259-1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Juvenile Hemochromatosis: A Case Report and Review of the Literature2020

    • Author(s)
      Takami Akiyoshi、Tatsumi Yasuaki、Sakai Katsuhisa、Toki Yasumichi、Ikuta Katsuya、Oohigashi Yuka、Takagi Junko、Kato Koichi、Takami Kazuhisa
    • Journal Title

      Pharmaceuticals

      Volume: 13 Issue: 8 Pages: 195-195

    • DOI

      10.3390/ph13080195

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] アルコール性肝障害を合併し遺伝子変異と異なる病態を呈したFerroportin病の1例.2020

    • Author(s)
      松岡直紀、林 学、高橋裕太、持丸友昭、熊川宏美、渡邉一男、巽 康彰、加藤宏一、生田克哉、右田清志、大平弘正.
    • Journal Title

      日本消化器病学会雑誌

      Volume: 117(12) Pages: 1100-1108

    • NAID

      130007952822

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 大きく変わったウイルス性肝炎の診療2020

    • Author(s)
      生田克哉、鈴木康秋、澤田康司、畑山真弓.
    • Journal Title

      日本内科学会雑誌

      Volume: 109(2) Pages: 308-316

    • NAID

      130007983352

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 鉄過剰症の新規マーカー、NTBIとLPI2020

    • Author(s)
      齋藤豪志、生田克哉.
    • Journal Title

      医学のあゆみ

      Volume: 275(8) Pages: 904-905

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 鉄欠乏性貧血の人は血小板が高値になる印象があるのですが、関連はあるのでしょうか?2020

    • Author(s)
      生田克哉
    • Journal Title

      Medical Technology

      Volume: 48(8) Pages: 888-889

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Identification of Heterozygous p.Y150C and p.V274M Mutations in the HJV Gene in a Japanese Patient With a Mild Phenotype of Juvenile Hemochromatosis: A Case Report2020

    • Author(s)
      Kawaguchi T, Ikuta K, Tatsumi Y, Toki Y, Hayashi H, Tonan T, Ohtake T, Hoshino S, Naito M, Kato K, Okumura T, Torimura T.
    • Journal Title

      Hepatology Research

      Volume: 50 (1) Issue: 1 Pages: 144-150

    • DOI

      10.1111/hepr.13423

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Successful Treatment of Nivolumab-related Cholangitis with Prednisolone: A Case Report and Review of the Literature2019

    • Author(s)
      Sawada K, Shonaka T, Nishikawa Y, Hasegawa K, Hayashi H, Hasebe T, Nakajima S, Ikuta K, Fujiya M, Furukawa H, Okumura T.
    • Journal Title

      Internal Medicine

      Volume: 58 Issue: 12 Pages: 1747-1752

    • DOI

      10.2169/internalmedicine.2330-18

    • NAID

      130007663632

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2019-06-15
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hepatitis B Virus (HBV) Reactivation in an Acute Lymphoblastic Leukemia Patient Despite Being Vaccinated Against HBV in Infancy2019

    • Author(s)
      Yamamoto M, Ikuta K, Sawada K, Shindo M, Torimoto Y, Okumura T.
    • Journal Title

      Digestive and Liver Disease

      Volume: 51 (10) Issue: 10 Pages: 1487-1488

    • DOI

      10.1016/j.dld.2019.07.003

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel Automated Measuring System for Evaluating Labile Plasma Iron in Serum2019

    • Author(s)
      Saito T, Ikuta K, Hatayama M, Shibusa K, Matsui K, Tanaka R, Toki Y, Kato D, Iizuka N, Okumura T.
    • Journal Title

      Annals of Clinical Biochemistry

      Volume: 56 (6) Issue: 6 Pages: 654-661

    • DOI

      10.1177/0004563219861413

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 長期間の赤血球輸血に伴う肝機能障害2019

    • Author(s)
      生田克哉、澤田康司.
    • Journal Title

      Medical Practice

      Volume: 第36巻第8号 Pages: 1307-1310

    • Related Report
      2019 Research-status Report
  • [Journal Article] 慢性炎症に伴う貧血2019

    • Author(s)
      生田克哉
    • Journal Title

      Medical Practice

      Volume: 第36巻第8号 Pages: 1249-1254

    • Related Report
      2019 Research-status Report
  • [Journal Article] Autofluorescence Imaging Reflects the Nuclear Enlargement of Tumor Cells as well as the Cell Proliferation Ability and Aberrant Status of the p53, Ki-67, and p16 Genes in Colon Neoplasms2019

    • Author(s)
      Moriichi K, Fujiya M, Kobayashi Y, Murakami Y, Iwama T, Kunogi T, Sasaki T, Ijiri M, Takahashi K, Tanaka K, Sakatani A, Ando K, Nomura Y, Ueno N, Kashima S, Ikuta K, Tanabe H, Mizukami Y, Saitoh Y, Okumura T.
    • Journal Title

      Molecules

      Volume: 24 Issue: 6 Pages: 1106-1106

    • DOI

      10.3390/molecules24061106

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Safety and efficacy of intravenous ferric carboxymaltose in Japanese patients with iron-deficiency anemia caused by digestive diseases: an open-label, single-arm study.2019

    • Author(s)
      Ikuta K, Ito H, Takahashi K, Masaki S, Terauchi M, Suzuki Y.
    • Journal Title

      International Journal of Hematology

      Volume: 109(1) Issue: 1 Pages: 50-58

    • DOI

      10.1007/s12185-018-2529-9

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comparison of efficacy and safety between intravenous ferric carboxymaltose and saccharated ferric oxide in Japanese patients with iron-deficiency anemia due to hypermenorrhea: a multi-center, randomized, open-label noninferiority study.2019

    • Author(s)
      Ikuta K, Hanashi H, Hirai K, Ota Y, Matsuyama Y, Shimura A, Terauchi M, Momoeda M.
    • Journal Title

      International Journal of Hematology

      Volume: 109(1) Issue: 1 Pages: 41-49

    • DOI

      10.1007/s12185-018-2501-8

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pharmacokinetics, pharmacodynamics, safety, and tolerability of intravenous ferric carboxymaltose: a dose-escalation study in Japanese volunteers with iron-deficiency anemia.2018

    • Author(s)
      Ikuta K, Shimura A, Terauchi M, Yoshii K, Kawabata Y.
    • Journal Title

      International Journal of Hematology

      Volume: 107 Issue: 5 Pages: 519-527

    • DOI

      10.1007/s12185-018-2400-z

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 生体内の鉄代謝制御メカニズム2018

    • Author(s)
      生田克哉
    • Journal Title

      日本医事新報

      Volume: 4921 Pages: 28-33

    • Related Report
      2018 Research-status Report
  • [Presentation] 血清中フリー鉄による酸化活性(Labile Plasma Iron)の自動分析装置対応測定2020

    • Author(s)
      齋藤豪志、生田克哉、田中利輝、奥村利勝.
    • Organizer
      第67回日本臨床検査医学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] わが国の全血採血基準と献血者ヘモグロビン値・赤血球恒数の推移2020

    • Author(s)
      紀野修一、生田克哉.
    • Organizer
      第67回日本臨床検査医学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 輸血医療と関連した各種検査(シンポジウム)2020

    • Author(s)
      齋藤豪志、生田克哉.奥村利勝.
    • Organizer
      第68回日本輸血・細胞治療学会学術総会(誌上開催)
    • Related Report
      2020 Annual Research Report
  • [Presentation] 輸血医療と鉄代謝(特別講演)2020

    • Author(s)
      生田克哉.
    • Organizer
      第64回日本輸血・細胞治療学会北海道支部例会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Homozygous I281T mutation in HJV causing indolent juvenile hemochromatosis with a middle to late onset.2019

    • Author(s)
      Takami A, Tatsumi Y, Sakai K, Toki Y, Ikuta K, Kato K, Takami K.
    • Organizer
      24th European Hematology Association Congress
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Zinc-bound ceruloplasmin (Cp) interacts with trasnferrin (Tf), resulting in safe transfer of Fe (III) from Cp to Tf.2019

    • Author(s)
      Sakajiri T, Nakatsuji M, Teraoka Y, Ikuta K, Inui T, Yamamura T.
    • Organizer
      8th Congress of the International BioIron Society
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 糖尿病診療を契機に診断された遺伝性ヘモクロマトーシス(Ferroportin病)の一例.2019

    • Author(s)
      仁科惣治、富山恭行、巽 康彰、生田克哉、加藤宏一、大海宏暢、佐々木恭、吉岡奈穂子、原 裕一、日野啓輔.
    • Organizer
      第43回日本肝臓学会西部会
    • Related Report
      2019 Research-status Report
  • [Presentation] Hereditary Hemochromatosis-related gene mutation analysis in Japan.2019

    • Author(s)
      Saito T, Toki Y, Tamamura N, Funayama T, Igarashi S, Ishioh M, Hatayama M, Shindo M, Ikuta K, Torimoto Y, Tatsumi Y, Kato A, Hayashi H, Kato K, Okumura T.
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] セルロプラスミン(Cp)への亜鉛への結合はCpとトランスフェリンとの結合を可能にする.2019

    • Author(s)
      山村堯樹、坂尻徹也、中辻匡俊、寺岡佳晃、吉田航祐、生田克哉、渋佐琴恵、菅野江里子、冨田浩史、乾 隆.
    • Organizer
      第43回日本鉄バイオサイエンス学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Oral iron adiministration (OIA) transiently increased serum malondialdehyde modified low-density lipoprotein (MDA-LDL) and non-transferrin-bound iron (NTBI) in hemodialysis (HD) patients.2018

    • Author(s)
      Saito N, Saito K, Morioka T, Shimada H, Ikuta K, Kohgo Y, Miyazaki S.
    • Organizer
      American Society of Nephrology Kidney Week 2018 (Annual Meeting)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 血清の酸化活性能の新規測定系構築2018

    • Author(s)
      齋藤豪志、生田克哉、畑山真弓、土岐康通、進藤基博、鳥本悦宏、松井康蔵、飯塚直美、奥村勝利.
    • Organizer
      第42回日本鉄バイオサイエンス学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 鉄代謝異常と貧血2018

    • Author(s)
      生田克哉
    • Organizer
      第63回日本透析医学会学術集会・総会
    • Related Report
      2018 Research-status Report
  • [Book] 今日の治療指針第8版(担当:鉄欠乏性貧血 p1077-1078)2020

    • Author(s)
      生田克哉
    • Total Pages
      2114
    • Publisher
      医学書院
    • ISBN
      9784260038089
    • Related Report
      2020 Annual Research Report
  • [Book] 輸血後鉄過剰症 診療の参照ガイド令和1年改訂版(担当:鉄過剰症総論 p109-111)2020

    • Author(s)
      生田克哉
    • Total Pages
      52
    • Publisher
      厚生労働省科学研究費補助金(難治性疾患政策研究事業)特発性造血障害に関する調査研究班編集
    • Related Report
      2020 Annual Research Report
  • [Book] 輸血後鉄過剰症 診療の参照ガイド令和1年改訂版(担当:日本における原発性(遺伝性)鉄過剰症の種類と疫学 p133-136) p109-111)2020

    • Author(s)
      土岐康通、生田克哉
    • Total Pages
      52
    • Publisher
      厚生労働省科学研究費補助金(難治性疾患政策研究事業)特発性造血障害に関する調査研究班編集
    • Related Report
      2020 Annual Research Report
  • [Book] 血液専門医テキスト改訂第3版(担当:鉄欠乏性貧血)2019

    • Author(s)
      生田克哉
    • Total Pages
      635
    • Publisher
      南江堂
    • Related Report
      2019 Research-status Report
  • [Book] EBM血液疾患の治療2019-2020(担当:輸血後鉄過剰症に対する介入によって得られる効果 p468-472)2018

    • Author(s)
      生田克哉
    • Total Pages
      567
    • Publisher
      中外医学社
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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