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Mechanisms of Goiter Development in Patients with Thyroglobulin Mutations

Research Project

Project/Area Number 19590569
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory medicine
Research InstitutionDokkyo Medical University

Principal Investigator

IEIRI Tamio  Dokkyo Medical University, 医学部, 教授 (80049220)

Co-Investigator(Kenkyū-buntansha) 菱沼 昭  獨協医科大学, 医学部, 准教授 (40201727)
Co-Investigator(Renkei-kenkyūsha) HISHINUMA Akira  獨協医科大学, 医学部, 准教授 (40201727)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsサイログロブリン異常症 / 甲状腺ホルモン合成障害 / びまん性甲状腺腫 / 細胞内輸送障害 / 定量RT-PCR / 遺伝子発現 / 細胞増殖 / MEK-MAPK経路 / アポトーシス / サイログロブリン / 遺伝子異常症 / 甲状腺腫 / 小胞体貯蔵病 / 分子シャペロン
Research Abstract

One of the major causes of congenital thyroid dyshormonogenesis is thyroglobulin gene. Until recently mutations of Tg gene were believed rare. However, upon understanding of clinical characteristics, an increasing number of Tg mutations were identified. Adult patients present huge goiter with normal or subclinical hypothyroidism and frequently develop thyroid cancer. We studied gene expression profile of surgically removed patients' thyroid tissues and cultured cells expressing abnormal thyroglobulin in vitro. Several genes were identified which play a significant role in cell proliferation.

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (41 results)

All 2010 2009 2008 2007

All Journal Article (12 results) (of which Peer Reviewed: 6 results) Presentation (24 results) Book (5 results)

  • [Journal Article] サイログロブリン遺伝子異常-細胞内輸送異常と甲状腺癌-2009

    • Author(s)
      菱沼昭, 家入蒼生夫
    • Journal Title

      ホルモンと臨床 秋季増刊号

      Pages: 73-79

    • Related Report
      2009 Annual Research Report
  • [Journal Article]2009

    • Author(s)
      菱沼昭
    • Journal Title

      甲状腺疾患診療マニュアル(診断と治療社)

      Pages: 82-83

    • Related Report
      2009 Annual Research Report
  • [Journal Article]2009

    • Author(s)
      菱沼昭, 家入蒼生夫
    • Journal Title

      内分泌病理学 最近の進歩2008(医学の世界社)

      Pages: 73-79

    • Related Report
      2009 Annual Research Report
  • [Journal Article] 特集 臨床検査:現状と展望トピックスII. 各論-実地医家に必要な新しい検査と重要な検査項目- 6. 内分泌・代謝疾患2008

    • Author(s)
      家人蒼生夫, 菱沼 昭, 竹越一博
    • Journal Title

      日本内科学会雑誌 97(12)

      Pages: 2983-2990

    • Related Report
      2009 Final Research Report
  • [Journal Article] 家系内に集積したサイログロブリン(Tg)遺伝子異常症2008

    • Author(s)
      深田修司, 菱沼 昭, 窪田純久, 隈 寛二、網野信行, 宮内 昭
    • Journal Title

      日本内分泌学会雑誌 84(Suppl)

      Pages: 38-41

    • NAID

      10021263018

    • Related Report
      2009 Final Research Report
  • [Journal Article] A novel homozygous missense mutation of the dual oxidase 2 (DUOX2) gene in an adult patient with large goiter.2008

    • Author(s)
      Ohye H, Fukata S, Hishinuma A, Kudo T, Nishihara E, ItoM, Kubota S, Amino N, Ieiri T, Kuma K, Miyauchi A
    • Journal Title

      Thyroid 10(5)

      Pages: 561-566

    • Related Report
      2009 Final Research Report
  • [Journal Article] A NOVEL HOMOZYGOUS MISSENSE MUTATION OF THE DUAL OXIDASE 2(DU0X2)GENE IN AN ADULT PATIENT WITH LARGE GOITER.2008

    • Author(s)
      Ohye, H., et al.
    • Journal Title

      THYROID 10

      Pages: 561-566

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 家系内に集積したサイログロブリン(Tg)遺伝子異常症2008

    • Author(s)
      深田修司, 他
    • Journal Title

      日本内分泌学会雑誌 84

      Pages: 38-41

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel thyrotropin receptor germline mutation (Asp617Tyr) causing hereditary hyperthyroidism.2007

    • Author(s)
      NIshihara E, Nagayama Y, Amino N, Hishlnuma A, Takano T, Yoshida H, Kubota S, Fukata S, Kuma K, Miyauchi A
    • Journal Title

      Endocrlne J. 54(6)

      Pages: 927-934

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Letter to the Editor Endemic goiter due to thyroglobulin gene abnormality and social ostracism.2007

    • Author(s)
      Fukata S, Hishinuma A, Kuma K, Miyauchi A, Sugawara M
    • Journal Title

      Endocrine J. 54(3)

      Pages: 485-486

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Thyroglobulin gene mutations producing defective intracellular transport of thyroglobulin are associated with increased thyroldal type 2 10dothyronine delodinase activity.2007

    • Author(s)
      Kanou Y, Hishinuma A, Tsunekawa K, Seki K, MIzuno Y, Fujisawa H, Imai T, Miura Y, Nagasaka T, Yamada C, Ieiri T, Murakami A, Murata Y.
    • Journal Title

      J Clin EndocrinoI Metab 92(4)

      Pages: 1451-1457

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Thyroglobulin gene mutations producing defective intracellular transport of thyroglobulin are associated with increased thyroidal type 2 iodothyronine deiodinase activity2007

    • Author(s)
      Kanou Y, et. al.
    • Journal Title

      J Clin Endocrinol Metab 92

      Pages: 1451-1457

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Genomic microdeletion of 6, 675 nucleotides encompassing exon 28 and 29 0f thyroglobulin (Tg) gene was found with a compound heterozygous occurrence of single nucleotide deletion7890delT2010

    • Author(s)
      Hishinuma A, Fukata S, Ohmika N, Hayama N, Namatame T, Ieiri T
    • Organizer
      14th lntemational Congress of Endocrinology (ICE2010)
    • Place of Presentation
      Kyoto
    • Year and Date
      2010-03-30
    • Related Report
      2009 Final Research Report
  • [Presentation] Genomic microdeletion of 6,675 nucleotides encompassing exon 28 and 29 of thyroglobulin(Tg)gene was found with a compound heterozygous occurrence of single nucleotide deletion7890delT2010

    • Author(s)
      菱沼昭, et al.
    • Organizer
      14th International Congress of Endocrinology
    • Place of Presentation
      Kyoto
    • Year and Date
      2010-03-30
    • Related Report
      2009 Annual Research Report
  • [Presentation] Gitelman's syndrome and Graves' disease2010

    • Author(s)
      深田修司, et al.
    • Organizer
      14th International Congress of Endocrinology
    • Place of Presentation
      Kyoto
    • Year and Date
      2010-03-30
    • Related Report
      2009 Annual Research Report
  • [Presentation] Increased thyroidal type 2 iodothyronine deiodinase(D2)activity may account for serum T3 predominance over T4 in patients with abnormal thyroglobulin(Tg)or sodium/iodine symporter(NIS)2010

    • Author(s)
      Y.Murata, et al.
    • Organizer
      14th International Congress of Endocrinology
    • Place of Presentation
      Kyoto
    • Year and Date
      2010-03-27
    • Related Report
      2009 Annual Research Report
  • [Presentation] 硬い甲状腺種を触知したサイログロブリン(Tg)遺伝子異常症の一例2010

    • Author(s)
      深田修司, 他
    • Organizer
      第83回日本内分泌学会学術総会
    • Place of Presentation
      京都
    • Year and Date
      2010-03-26
    • Related Report
      2009 Annual Research Report
  • [Presentation] Dyshormonogenesis by thyroglobulin mutation in basic and clinical aspects2010

    • Author(s)
      Hishinuma A
    • Organizer
      Thyroid Satellite Symposium of 14th lntemational Congress of Endocrinology (CE2010)
    • Place of Presentation
      Kyoto
    • Year and Date
      2010-03-25
    • Related Report
      2009 Final Research Report
  • [Presentation] Dyshormonogenesis by thyroglobulin mutation in basic and clinical aspects2010

    • Author(s)
      菱沼昭
    • Organizer
      Thyroid Satellite Symposium of 14th International Congress of Endocrinology
    • Place of Presentation
      Kyoto
    • Year and Date
      2010-03-25
    • Related Report
      2009 Annual Research Report
  • [Presentation] ペンドレッド症候群の基礎と臨床2009

    • Author(s)
      吉田明雄, 他
    • Organizer
      第52回日本甲状腺学会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-11-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] TPO遺伝子の異常対立遺伝子のみの発現を呈した先天性甲状腺機能低下症の一例2009

    • Author(s)
      深田修司, 他
    • Organizer
      第52回日本甲状腺学会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-11-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] TSH不適切分泌症候群(SITSH)あ1例2009

    • Author(s)
      西山充, 他
    • Organizer
      第52回日本甲状腺学会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-11-04
    • Related Report
      2009 Annual Research Report
  • [Presentation] Novel compound heterozygous occurrence of single nucleotide deletion 7890delT and genomlc microdeletion encompassing exon 28 and 29 0f thyroglobulin gene causes multinodular goiter.2009

    • Author(s)
      Hishinuma A, Fukata S, Ohmika N, HayamaN, NamatameT, Ieiri T
    • Organizer
      9th Asia and Oceania Thyroid Association Congress
    • Place of Presentation
      Nagoya
    • Year and Date
      2009-11-02
    • Related Report
      2009 Final Research Report
  • [Presentation] Novel compound heterozygous occurrence of single nucleotide deletion 7890delT and genomic microdeletion encompassing exon 28 and 29 of thyroglobulin gene causes multinodular goiter2009

    • Author(s)
      菱沼昭, et al.
    • Organizer
      9th Asia and Oceania Thyroid Association Congress
    • Place of Presentation
      Nagoya
    • Year and Date
      2009-11-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] 公募シンポジウム8甲状腺癌の分子生物学の新知見と応用サイログロブリン異常と甲状腺癌の特徴2009

    • Author(s)
      菱沼昭, 深田修司, 宮内昭, 家人蒼生夫
    • Organizer
      第82回日本内分泌学会学術総会
    • Place of Presentation
      前橋
    • Year and Date
      2009-04-24
    • Related Report
      2009 Final Research Report
  • [Presentation] サイログロブリン異常と甲状腺癌の特徴2009

    • Author(s)
      菱沼昭, 他
    • Organizer
      第82回日本内分泌学会学術総会
    • Place of Presentation
      前橋
    • Year and Date
      2009-04-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] 特異なサイログロブリン遺伝子変異発現が認められた濾胞腺腫の一例2009

    • Author(s)
      深田修司, 他
    • Organizer
      第82回日本内分泌学会学術総会
    • Place of Presentation
      前橋
    • Year and Date
      2009-04-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] 先天性非自己免疫性甲状腺機能亢進症の一例2009

    • Author(s)
      野口義彦, 他
    • Organizer
      第82回日本内分泌学会学術総会
    • Place of Presentation
      前橋
    • Year and Date
      2009-04-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] 正常アリルの甲状腺発現抑制によりクレチン症を発症したNIS遺伝子変異T354Pヘテロ接合体の一例2009

    • Author(s)
      武内陽子, 他
    • Organizer
      第82回日本内分泌学会学術総会
    • Place of Presentation
      前橋
    • Year and Date
      2009-04-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] クリニカルアワー4特殊な甲状腺機能克進症の治療小児におけるバセドゥ病2009

    • Author(s)
      菱沼昭
    • Organizer
      第19回臨床内分泌代謝Update
    • Place of Presentation
      東京
    • Year and Date
      2009-03-14
    • Related Report
      2009 Final Research Report
  • [Presentation] シンポジウム4遺伝子異常による甲状腺疾患甲状腺ホルモン合成障害をきたす遺伝子異常2008

    • Author(s)
      菱沼昭
    • Organizer
      第81回日本内分泌学会
    • Place of Presentation
      青森
    • Year and Date
      2008-05-17
    • Related Report
      2009 Final Research Report
  • [Presentation] シンポジウム4 遺伝子異常による甲状腺疾患甲状腺ホルモン合成障害をきたす遺伝子異常2008

    • Author(s)
      菱沼 昭
    • Organizer
      第81回日本内分泌学会
    • Place of Presentation
      青森
    • Year and Date
      2008-05-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] 国際分子甲状腺学シンポジウムGenetic thyroid diseases in Japan featured by thyroglobulin mutations2007

    • Author(s)
      菱沼昭
    • Organizer
      第50回日本甲状腺学会
    • Place of Presentation
      神戸
    • Year and Date
      2007-11-15
    • Related Report
      2009 Final Research Report
  • [Presentation] Symposium (II)-Update ln Clinical Thyroidology- New Aspects of Thyroglobulin Mutations-Clinical Features2007

    • Author(s)
      Hishinuma A
    • Organizer
      Pathogenesis, and High Incidence of Cancer- Autum Meeting of Korean Endocrine Soclety
    • Year and Date
      2007-11-03
    • Related Report
      2009 Final Research Report
  • [Presentation] シンポジウム「甲状腺疾患の病理と臨床のさらなる融合-」サイログロブリン遺伝子異常症一細胞内輸送異常と甲状腺癌2007

    • Author(s)
      菱沼昭, 家人蒼生夫
    • Organizer
      第11回日本内分泌病理学会
    • Place of Presentation
      札幌
    • Year and Date
      2007-10-19
    • Related Report
      2009 Final Research Report
  • [Presentation] サイログロブリン遺伝子異常症-細胞内輸送異常と甲状腺癌2007

    • Author(s)
      菱沼 昭, 他
    • Organizer
      第11回日本内分泌病理学会
    • Place of Presentation
      札幌
    • Year and Date
      2007-10-19
    • Related Report
      2007 Annual Research Report
  • [Book] 内分泌病理学 最近の進歩2008 ホルモンと臨床 2009秋季増刊号(上條桂一編, サイログロブリン遺伝子異常一細胞内輸送異常と甲状腺癌-2009

    • Author(s)
      菱沼 昭, 家人蒼生夫
    • Publisher
      医学の世界社
    • Related Report
      2009 Final Research Report
  • [Book] 甲状腺疾患診療マニュアル(田上哲也、西川光重、伊藤公一、成瀬光栄 編, 先天性甲状腺疾患)2009

    • Author(s)
      菱沼 昭
    • Publisher
      診断と治療社
    • Related Report
      2009 Final Research Report
  • [Book] 甲状腺疾患診療マニュアル(田上哲也、西川光重、伊藤公一、成瀬光栄 編, 小児Basedow病)2009

    • Author(s)
      菱沼 昭
    • Publisher
      診断と治療社
    • Related Report
      2009 Final Research Report
  • [Book] 臨床検査 増刊号 ホルモンの病態異常と臨床検査 52(ll)(サイログロブリン遺伝子異常と甲状腺腫)2008

    • Author(s)
      菱沼 昭, 家人蒼生夫
    • Total Pages
      1183
    • Publisher
      医学書院
    • Related Report
      2009 Final Research Report
  • [Book] Hot Thyroidology(Emerging new features of patients with thyroglobulin mutations, including increased incidence of thyroid cancer.)2007

    • Author(s)
      Hishinuma A, Fukata S, Ieiri T.
    • Publisher
      European Thyroid Associatlon
    • Related Report
      2009 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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