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子宮内膜細胞の老化逸脱へのゲノム多様性の関与

Research Project

Project/Area Number 23249075
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKyushu University

Principal Investigator

和氣 徳夫  九州大学, 学内共同利用施設等, 研究員 (60091584)

Co-Investigator(Kenkyū-buntansha) 浅野間 和夫  九州大学, 医学(系)研究科(研究院), 准教授 (30380413)
劉 格  九州大学, 学内共同利用施設等, 研究員 (50647998)
恒松 良祐  九州大学, 医学(系)研究科(研究院), 助教 (20380529)
高尾 知佳  九州大学, 環境発達医学研究センター, 学術研究員 (40612429)
井上 貴史  九州大学, 大学病院, 助教 (70380417)
Project Period (FY) 2011-11-18 – 2016-03-31
Project Status Declined (Fiscal Year 2015)
Budget Amount *help
¥30,160,000 (Direct Cost: ¥23,200,000、Indirect Cost: ¥6,960,000)
Fiscal Year 2015: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2014: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2013: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2012: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
KeywordsGenome diversity / Endometrial cancer / MDM2 309 G/T SNP / AhR -130bp C/T SNP / AhR transcription / serum IL24 concentration / MDM2 / SNP / AHR / NF1C / 子宮体癌 / MDM2型 / シグナロソーム / -130C/T多型 / NFIC
Outline of Annual Research Achievements

1)子宮内膜細胞の老化逸脱へのゲノム多様性の関与
MDM2 SNP309 G/G+G/TとTP53コドン72Arg/Argの組み合わせは子宮体癌発症odds比2.53(1.03-6.21)と両遺伝子間に統計学的有意な相互作用を示し、子宮体癌発症リスクを増大する。
2)AhR-130 C/T SNPによる転写制御
AhR-130 T/T遺伝子型はC/C遺伝子型に比しmRNAレベルで1.7倍、蛋白レベルで2倍のAhR発現亢進を示した。NF1C転写抑制因子結合サイトがC/C型では維持されT/T型で消失するためである。AhR T/T型の頻度は全体の10%程度であるが進行子宮体癌で有意に高頻度に検出される。AhRが癌細胞にEpithelial Mesenchymal Transition(EMT)を誘発し癌の進展に関与するためである。
マイクロアレイ法にてAhR下流でTCDD応答性発現変化する遺伝子を同定した。そのうちIL24遺伝子はT/T遺伝子型でC/C遺伝子型に比しTCDD非存在下の発現が有意に亢進しており、TCDD非存在性、AhR依存性AhR転写制御の存在が強く示唆された。TCDD存在下でのIL24発現もT/T型で有意に高値であった。ダイオキシン類高濃度被曝例として、油症患者の血中IL24濃度を測定した。T/T遺伝子型油症患者の血中IL24濃度はC/C遺伝子型と比較し有意に高値であった。これらの結果から、AhR-130bp C/T SNP及びIL24血中濃度はダイオキシン類による病態発症を予知出来るバイオマーカーとして使用可能であることが示唆された。

Research Progress Status

翌年度、交付申請を辞退するため、記入しない。

Strategy for Future Research Activity

翌年度、交付申請を辞退するため、記入しない。

Report

(4 results)
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (31 results)

All 2015 2014 2013 2012 2011

All Journal Article (30 results) (of which Peer Reviewed: 24 results,  Open Access: 2 results) Presentation (1 results)

  • [Journal Article] Aryl hydrocarbon receptor SNP -130 C/T associates with dioxins susceptibility through regulating its receptor activity and downstream effectors including interleukin 242015

    • Author(s)
      Liu G, Asanoma K, Takao T, Tsukimori K, Uchi H, Furue M, Kato K, Wake N
    • Journal Title

      Toxicology Letters.

      Volume: 232 Issue: 2 Pages: 384-392

    • DOI

      10.1016/j.toxlet.2014.11.025

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A definitive haplotype of structural variations determined by microarray analysis of duplicated haploid genomes.2014

    • Author(s)
      Tomoko T, Koji Y, Yoji K, Koichiro H, Kiyoko K, Norio W, Kenshi H
    • Journal Title

      Genoomics Data

      Volume: 2 Pages: 55-59

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide parent-of-origin DNA methylation analysis reveals the intricacies of the human imprintome and suggests a germline methylation independent establishment of imprinting.2014

    • Author(s)
      Court F, Tayama C, Romanelli V, Martin-Trujillo A, Iglesias-Platas I, Okamura K, Sugahara N, Simon C, Moore H, Harness J, Keirstead H, Vicente Sanchez-Mut J, Kaneki E, Lapunzina P, Soejima H, Wake N, Esteller M, Ogata T, Hata K, Nakabayashi K, Monk D*
    • Journal Title

      Genome Res

      Volume: in press Issue: 4 Pages: 554-569

    • DOI

      10.1101/gr.164913.113

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Correlation between regular mouthing movements and hear rate patterns during non-rapid eye movement periods in normal human fetuses between 32 and 40 weeks of gestation2013

    • Author(s)
      Yuka O, Seiichi M, Kotaro F, Norio W, Kiyoko K,
    • Journal Title

      Early Human Development

      Volume: 89(6) Issue: 6 Pages: 381-386

    • DOI

      10.1016/j.earlhumdev.2012.12.007

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of MDM2 SNP309 and TP53 Arg72Propolymorphisms with risk of endometrial cancer.2013

    • Author(s)
      Tomoko Y, Ayumi K, Kiyoko K, Tatsuhiro O, Kanako O, Toshiaki S, and Norio W,
    • Journal Title

      Oncology Reports.

      Volume: 30 Issue: 1 Pages: 25-34

    • DOI

      10.3892/or.2013.2433

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Establishment of a new diagnostic method for hydropic villi by using TSSC3 antibody.2013

    • Author(s)
      Wake N, Takao T, Asanoma K, Kato H
    • Journal Title

      J Obstet Gynaecol Res.

      Volume: 39(7) Issue: 7 Pages: 1230-1235

    • DOI

      10.1111/jog.12100

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical utility of augmentation index as a new parameter of peripheral circulation in human fetuses.2013

    • Author(s)
      Fujita Y, Satoh S, Sugitani M, Yumoto Y, Fukushima K, Wake N,
    • Journal Title

      Early Hum Dev.

      Volume: 89(8) Issue: 8 Pages: 601-605

    • DOI

      10.1016/j.earlhumdev.2013.03.004

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Doppler sonographic evaluation of arteriovenous shunt flow in a fetus with dural sinus malformation.2013

    • Author(s)
      Sato Y, Fujita Y, Anami A, Yumoto Y, Fukushima K, Wake N.
    • Journal Title

      J Obstet Gynaecol Res.

      Volume: 39(5) Issue: 5 Pages: 1081-1084

    • DOI

      10.1111/jog.12023

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Well-differentiated villoglandular adenocarcinoma of the uterine cervix: assessment of cytological features by histological subtypes.2013

    • Author(s)
      Hagiwara T, Kaku T, Kobayashi H, Wake N, Saito T.
    • Journal Title

      Acta Cytol.

      Volume: 57(1) Issue: 1 Pages: 61-68

    • DOI

      10.1159/000342917

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oxidative stress produced by xanthine oxidase induces apoptosis in human extravillous trophoblast cells.2013

    • Author(s)
      Murata M, Fukushima K, Takao T, Seki H, Takeda S, Wake N.
    • Journal Title

      J Reprod Dev.

      Volume: 59(1) Pages: 7-13

    • NAID

      10031156805

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Successful management of cervico-isthmic pregnancy delivered at term.2013

    • Author(s)
      Sakai A, Fujita Y, Yumoto Y, Fukushima K, Kobayashi H, Wake N.
    • Journal Title

      10.1111/j.1447-0756.2012.01967.x. Epub 2012 Jul 29.

      Volume: 39(1) Pages: 371-374

    • Related Report
      2013 Annual Research Report
  • [Journal Article] The predictive value of anti-SS-A antibodies titration in pregnant women with fetal congenital heart block.2013

    • Author(s)
      Anami A, Fukushima K, Takasaki Y, Sumida T, Waguri M, Wake N, Murashima A.
    • Journal Title

      Mod Rheumatol.

      Volume: 23(4) Issue: 4 Pages: 653-658

    • DOI

      10.1007/s10165-012-0704-z

    • NAID

      10031189158

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Characterization of placental transfer of polychlorinated dibenzo-p-dioxins, dibenzofurans and polychlorinated biphenyls in normal pregnancy2013

    • Author(s)
      Tsukimori K, Morokuma S, Hori T, Takahashi K, Hirata T, Otera Y, Fukushima K, Kawamoto T, Wake N
    • Journal Title

      The Journal of Obstetrics and Gynaecology Research

      Volume: 39(1) Issue: 1 Pages: 83-90

    • DOI

      10.1111/j.1447-0756.2012.01906.x

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ultrasound evaluation of fetal brain dysfunction based on behavioral patterns.2013

    • Author(s)
      Morokuma S, Fukushima K, Otera Y, Yumoto Y, Tsukimori K, Ochiai M, Hara T, Wake N.
    • Journal Title

      Brain Dev.

      Volume: 35(1) Issue: 1 Pages: 61-67

    • DOI

      10.1016/j.braindev.2012.01.007

    • NAID

      40017369136

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of placental transfer of polychlorinated dibenzo-p-dioxins, dibenzofurans and polychlorinated biphenyls in normal pregnancy.2013

    • Author(s)
      Kiyomi T, Seiichi M, Tsuguhide H, Koji T,Teruaki H, Yuka O, Kotaro F, Toshihiro K and Norio W
    • Journal Title

      Obstetrics and Gynaecology Research

      Volume: 39 Pages: 83-90

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibin-α and synaptophysin immunoreactivity in synovial sarcoma with granular cell features.2012

    • Author(s)
      Setsu N, Kohashi K, Endo M, Yamamoto H, Ohishi Y, Sueyoshi K, Iwamoto Y, Tsuneyoshi M, Motoi T, Kumagai A, Oda Y.
    • Journal Title

      Hum Pathol.

      Volume: 43(6) Pages: 850-857

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ultrasound and MR images of prenatally diagnosed bilateral congenital diaphragmatic hernia, a rare variation of CDH☆.2012

    • Author(s)
      Kana Ishibashi Hiasa, Yasuyuki Fujita, Kotaro Fukushima, Kouji Nagata, Tomoaki Taguchi, Norio Wake.
    • Journal Title

      Clinical Imaging.

      Volume: 36(5) Pages: 639-642

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Successful management of cervico-isthmic regnancy delivered at term.2012

    • Author(s)
      Atsuhiko Sakai, Yasuyuki Fujita, Yasuo Yumoto, Kotaro Fukushima, Hiroaki Kobayashi and Norio Wake.
    • Journal Title

      Obstetrics and Gynaecology Research.

      Volume: 39(1) Pages: 371-374

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A retrospective chart review of the perinatal period in 22 pregnancies of 16 women with Moyamoya disease.2012

    • Author(s)
      Fukushima K, Yumoto Y, Kondo Y, Fujita Y, Morokuma S, Tsukimori K, Wake N.
    • Journal Title

      Clinical neuroscience.

      Volume: 19(10) Pages: 1358-1362

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of placental transfer of polychlorinated dibenzo-p-dioxins, dibenzofurans and polychlorinated biphenyls in normal pregnancy.2012

    • Author(s)
      Tsukimori K, Morokuma S, Hori T, Takahashi K, Hirata T, Otera Y, Fukushima K, Kawamoto T, Wake N.
    • Journal Title

      Obstetrics and Gynaecology Research.

      Volume: 39(1) Pages: 83-90

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] "Piling up" clear cells in müllerian-type mucinous and mixed cell-type borderline tumor do not represent concomitant clear cell neoplasms.2012

    • Author(s)
      Ohishi Y, Kurihara S, Aman M, Takeuchi T, Imamura H, Kaku T, Kobayashi H, Wake N, Oda Y.
    • Journal Title

      Human Pathology

      Volume: 43(10) Pages: 1618-1626

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A comparing the Effects of Kamishoyosan or HRT on Climacteric Disorders in Postmenopausal Women.2012

    • Author(s)
      Higuchi T, Iino K, Tarakida A, Abe K, Taniguchi R, Mizunuma H, Mikami Y, Katagiri S, Hashimoto T, Hasuo Y, et al
    • Journal Title

      Results from a Randomized Controlled Trial. Menopause & Women’s Health Jpn.

      Volume: 20 Pages: 305-312

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The maternally expressed gene Tssc3 regulates the expression of MASH2 transcription factor in mouse trophoblast stem cells through the AKT-Sp1 signaling pathway.2012

    • Author(s)
      Takao T, Asanoma K, Tsunematsu R, Kato K, Wake N.
    • Journal Title

      Journal of biological chemistry.

      Volume: 287(51) Pages: 42685-42694

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Maternal exposure to high levels of dioxins in relation to birth weightin women affected by Yusho disease2012

    • Author(s)
      Tsukimori K, Uchi H, Mitoma C, Yasukawa F, Chiba T, Todaka T, Kajiwara J, Yoshimura T, Hirata T, Fukushima K, Wake N, Furue M
    • Journal Title

      Environ Int

      Volume: 38(1) Pages: 79-86

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SATB Homeobox Protenis Regulate Trophoblast Stem Cell Renewal and Differentiation2012

    • Author(s)
      Asanoma K, Kubota K, Chakraborty D, Renaud SJ, Wake N, Fukushima K, Soares MJ, Rumi MA
    • Journal Title

      J Biol Chem

      Volume: 287(3) Pages: 2257-2268

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of the concentrations of polychlorinated biphenyls and dioxins in mothers affected by the Yusho incident and their children2011

    • Author(s)
      Tsukimori K, Uchi H, Mitoma C, Yasukawa F, Fukushima K, Kajiwara J, Yoshimura T, Hirata T, Wake N, Furue M
    • Journal Title

      Chemosphere

      Volume: 84(7) Pages: 928-935

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sodium butyrate inhibits the self-renewal capacity of endometrial tumor side-population cells by inducing a DNA damage response2011

    • Author(s)
      Kato K, Kuhara A, Yoneda T, Inoue T, Takao T, Ohgami T, Dan L, Kuboyama A, Kusunoki S, Takeda S, Wake N
    • Journal Title

      MolCancer Ther

      Volume: 10(8) Pages: 1430-1439

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lsolation and Characterization of Human Trophoblast Side-Population (SP) Cells in Primary Villous Cytotrophoblasts and HTR-8/SVneo Cell Line2011

    • Author(s)
      Takao T, Asanoma K, Kato K, Fukushima K, Tsunematsu R, Hirakawa T, Matsumura S, Seki H, Takeda S, Wake N
    • Journal Title

      PLoS One

      Volume: 6(7)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of S-equol and natural S-eqol supplement(SE5-OH) on the growth of MCF-7 in vitro and as tumors implanted into ovariectomized athymic mice2011

    • Author(s)
      Onda A, Ueno T, Uchiyama S, Hayashi S, Kato K, Wake N
    • Journal Title

      Food Chem Toxicol

      Volume: 49(9) Pages: 2279-2284

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FGF4-dependent stem cells derived from rat blastocycts differentiate alone the trophoblast lines2011

    • Author(s)
      Asanoma K, Rumi MA, Kent LN, Chakraborty D, Renaud SJ, Wake N, Lee DS, Kubota K, soares MJ,
    • Journal Title

      Dev Biol

      Volume: 351(1) Pages: 110-119

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] のう胞化絨毛の研究-基礎からの臨床-2011

    • Author(s)
      和気徳夫
    • Organizer
      日本産婦人科学会
    • Place of Presentation
      大阪(招待講演)
    • Year and Date
      2011-08-30
    • Related Report
      2011 Annual Research Report

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Published: 2013-05-15   Modified: 2019-07-29  

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