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Local differences in juvenile development of hepatocellular carcinoma in multi-racial Myanmar; focusing on the effect of iron and arsenic

Research Project

Project/Area Number 16H05813
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section海外学術
Research Field General anatomy (including histology/embryology)
Research InstitutionNagasaki University

Principal Investigator

KOJI Takehiko  長崎大学, 医歯薬学総合研究科(医学系), 教授 (30170179)

Co-Investigator(Kenkyū-buntansha) 柴田 恭明  長崎大学, 医歯薬学総合研究科(医学系), 講師 (80253673)
遠藤 大輔  長崎大学, 医歯薬学総合研究科(医学系), 助教 (90516288)
穐山 直太郎  東京慈恵会医科大学, 医学部, 助教 (90554238)
Research Collaborator Kyaw Soe  
Kyaw Myat Phone  
Kyaw Zin Thant  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Keywords肝癌 / 若年発症 / 鉄過剰摂取 / ヒ素 / 組織化学的解析 / Bcl9 / 居住地域性 / ミャンマー / 変異型p53 / p15INK4b / 若年性肝癌発症 / 鉄 / 民族差 / 地域的部族的差異 / ミャンマー
Outline of Final Research Achievements

We have attempted to clarify the cause of juvenile development of hepatocellular carcinoma (HCC) in Myanmar. Our previous study revealed that iron overload could be one possible reason. Since now arsenic contaminated to water is known to be a big risk for cancers in South-Asian countries, we examined HCC specimens from various races living in different locations for the exposure to iron and arsenic. When 56 HCC tissues were analyzed for the markers of iron deposition and arsenic exposure, we found a significant variation in Prussian blue staining and 5-hydroxymethylcytosine level in DNA, indicating those specimens were more or less exposed to these toxic metals. Moreover, we found that Bcl9, which regulates the function of β-catenin, was lost in the cytoplasm of juvenile HCC. These results indicate that our future approach focusing on Bcl9 as a target of iron and arsenic toxicity will be useful to clarify the influences of these toxic metals on the juvenile development of HCC.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、今後更に民族間での若年性肝癌発症の差異を病理検体に基づき解析することにより、地域的な鉄及びヒ素の影響を明らかにでき、ひいてはその除去による発症リスクの除去を可能とすることを示している。また民族間での生活環境の違いによるこれら毒性物質の無毒化につながる伝統食の発掘への期待も膨らむ。特に今後の検討に於いて、若年性肝癌発症に関連する具体的な解析対象分子Bcl9を同定できたこともこれら毒性物質の作用機構を解明する上で大きな貢献と思われる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (26 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (10 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 10 results,  Open Access: 10 results,  Acknowledgement Compliant: 5 results) Presentation (13 results) (of which Int'l Joint Research: 2 results,  Invited: 6 results) Book (1 results) Remarks (1 results)

  • [Int'l Joint Research] 医学研究局(DMR)/医科学局(ヤンゴン第一医科大学)/医科学局(ヤンゴン第二医科大学)(ミャンマー)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Immunohistochemical Mapping of Bcl9 Using Two Antibodies that Recognize Different Epitopes Is Useful to Characterize Juvenile Development of Hepatocellular Carcinoma in Myanmar2019

    • Author(s)
      Myat Thu Soe, Shibata Y, Myo Win Htun, Abe K, Kyaw Soe, Nay Win Than, Thann Lwin, Myat Phone Kyaw, Koji T
    • Journal Title

      ACTA HISTOCHEMICA ET CYTOCHEMICA

      Volume: 52 Issue: 1 Pages: 9-17

    • DOI

      10.1267/ahc.18045

    • NAID

      130007605029

    • ISSN
      0044-5991, 1347-5800
    • Year and Date
      2019-02-28
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Histone deacetylase inhibitors suppress transdifferentiation of gonadotrophs to prolactin cells and proliferation of prolactin cells induced by diethylstilbestrol in male mouse pituitary.2019

    • Author(s)
      Nandar Tun, Shibata Y, Myat Thu Soe, Myo Win Htun, Koji T
    • Journal Title

      Histochem Cell Biol

      Volume: 151 Issue: 4 Pages: 291-303

    • DOI

      10.1007/s00418-018-1760-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Analysis of H3K27me3 expression and DNA methylation at CCGG sites in smoking and non-smoking patients with non-small cell lung cancer and their clinical significance.2018

    • Author(s)
      Zhu K, Deng Y, Weng G, Hu D, Huang C, Matsumoto K, Nagayasu T, Koji T, Zheng X, Jiang W, Lin G, Cai Y, Weng G, Chen X
    • Journal Title

      Oncol Lett

      Volume: 15 Pages: 6179-6188

    • DOI

      10.3892/ol.2018.8100

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Changes in DNA Methylation of Oocytes and Granulosa Cells Assessed by HELMET during Folliculogenesis in Mouse Ovary2018

    • Author(s)
      Liu J, Zhang W, Wu Z, Dai L, Koji T
    • Journal Title

      ACTA HISTOCHEMICA ET CYTOCHEMICA

      Volume: 51 Issue: 2 Pages: 93-100

    • DOI

      10.1267/ahc.17039

    • NAID

      130006727960

    • ISSN
      0044-5991, 1347-5800
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of joint immobilization on changes in myofibroblasts and collagen in the rat knee contracture model2017

    • Author(s)
      Sasabe R, Sakamoto J, Goto K, Honda Y, Kataoka H, Nakano J, Origuchi T, Koji T, Okita M
    • Journal Title

      J Orthop Res

      Volume: in press Issue: 9 Pages: 1998-2006

    • DOI

      10.1002/jor.23498

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 5-aza-2'-deoxycytidine impairs mouse spermatogenesis at multiple stages through different usage of DNA methyltransferases.2016

    • Author(s)
      Song N, Endo D, Song B, Shibata Y, Koji T
    • Journal Title

      Toxicology

      Volume: 361-362 Pages: 62-72

    • DOI

      10.1016/j.tox.2016.07.005

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Regulation and Biological Significance of Formation of Osteoclasts and Foreign Body Giant Cells in an Extraskeletal Implantation Model2016

    • Author(s)
      Ahmed GJ, Tatsukawa E, Morishita K, Shibata Y, Suehiro F, Kamitakahara M, Yokoi T, Koji T, Umeda M, Nishimura M, Ikeda T
    • Journal Title

      ACTA HISTOCHEMICA ET CYTOCHEMICA

      Volume: 49 Issue: 3 Pages: 97-107

    • DOI

      10.1267/ahc.16007

    • NAID

      130005161006

    • ISSN
      0044-5991, 1347-5800
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Granular C3 Dermatosis.2016

    • Author(s)
      Hashimoto T, Tsuruta D, Yasukochi A, Imanishi H, Sekine H, Fujita T, Wanibuchi H, Gi M, Kárpáti S, Sitaru C, Zone JJ, Endo D, Abe S, Nishino T, Koji T, Ishii N.
    • Journal Title

      Acta Derm Venereol

      Volume: 00 Pages: 00-00

    • DOI

      10.2340/00015555-2379

    • NAID

      120006987674

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Chondroitin sulfate prevents peritoneal fibrosis in mice by suppressing NF-κB activation.2016

    • Author(s)
      Abe S, Obata Y, Oka S, Koji T, Nishino T, Izumikawa K
    • Journal Title

      Med Mol Morphol

      Volume: 49 Issue: 3 Pages: 144-153

    • DOI

      10.1007/s00795-016-0133-8

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Curcumin ameliorates nephrosclerosis via suppression of histone acetylation independent of hypertension.2016

    • Author(s)
      Muta K, Obata Y, Oka S, Abe S, Minami K, Kitamura M, Endo D, Koji T, Nishino T
    • Journal Title

      Nephrol Dial Transplant

      Volume: 96 Issue: 10 Pages: 748-753

    • DOI

      10.1093/ndt/gfw036

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] ミャンマー国肝細胞がん症例におけるBcl9発現の病理学的意義。2019

    • Author(s)
      柴田恭明、Myat Thu Soe、Myo Win Htun、小路武彦
    • Organizer
      第124回日本解剖学会総会・全国学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ミャンマー国の幹細胞がん症例におけるBcl9の発現。2018

    • Author(s)
      柴田恭明、Myat Thu Soe、Myo Win Htun、小路武彦
    • Organizer
      第50回日本臨床分子形態学会総会・学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Involvement of histone H3 acetylation in DES-induced transdifferentiation of LH to PRL cells in male mouse pituitary.2018

    • Author(s)
      Nandar Tun, Shibata Y, Myat Thu Soe, Koji T
    • Organizer
      第59回日本組織細胞化学会総会・学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] マウス雄性生殖細胞における核内pgk-1, pgk-2遺伝子座の位置変化と遺伝子発現の相関解析。2018

    • Author(s)
      柴田恭明、小路武彦
    • Organizer
      第59回日本組織細胞化学会総会・学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Influence of iron-overload on Sox9-positive liver progenitor cells after partial hepatectomy in rat.2018

    • Author(s)
      Myat Thu Soe, Shibata Y, Koji T
    • Organizer
      第59回日本組織細胞化学会総会・学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Population kinetics of Sox9 positive liver progenitor cells in normal and iron-overloaded rat liver: Effects of partial hepatectomy.2018

    • Author(s)
      Myat Thu Soe, Shibata Y, Nandar Tun, Endo D, Koji T
    • Organizer
      第123回日本解剖学会総会・全国学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Population kinetics of Sox9 positive liver progenitor cells in normal and iron-overloaded rat liver: Effects of partial hepatectomy.2018

    • Author(s)
      Myat Thu Soe, Shibata Y, Kyaw Soe, Nandar Tun, Endo D, Koji T
    • Organizer
      46th Myanmar Health Research Congress
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Changes in DNA methylation level during liver regeneration after partial hepatectomy in normal and iron-overloaded rats.2017

    • Author(s)
      Myat Thu Soe, Nandar Tun, Endo D, Shibata Y Koji T
    • Organizer
      第122回日本解剖学会総会・全国学術集会
    • Place of Presentation
      長崎大学坂本キャンパス(長崎県長崎市)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] 組織細胞化学的シグナルの適正評価-免疫組織化学からエピゲノム組織化学まで-。2017

    • Author(s)
      小路武彦
    • Organizer
      Kanagawa CytoPathology Seminar
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 分子組織細胞化学の最新の進歩と形態学の未来。2017

    • Author(s)
      小路武彦
    • Organizer
      神奈川歯科大学学会第52回総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Prothymosin alpha-derived peptid prevents cisplatin-induced AKI.2017

    • Author(s)
      Torigoe K, Obata Y, Torigoe M, Koji T, Ueda H, Nishino T
    • Organizer
      51rd Annual Meeting of ASN
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] プロサイモシン由来ペプチドによるシスプラチン誘発急性腎障害の抑制効果。2017

    • Author(s)
      鳥越健太、小畑陽子、鳥越未来、岡哲、小路武彦、植田弘師、西野友哉
    • Organizer
      第60回日本腎臓学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] エピジェネティック因子:細胞動態の新たな組織細胞化学的パラメーター。2017

    • Author(s)
      小路武彦
    • Organizer
      第36回分子病理学研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Book] 組織細胞化学20182018

    • Author(s)
      柴田恭明
    • Total Pages
      232
    • Publisher
      学際企画株式会社
    • ISBN
      9784906514939
    • Related Report
      2018 Annual Research Report
  • [Remarks] 組織細胞生物学分野ホームページ

    • URL

      http://www.med.nagasaki-u.ac.jp/anatomy3/index.html

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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