The clarification of pathogenesis and medical treatment of functional pituitary adenoma using iPS cells

• Project/Area Number: 26670459
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Endocrinology
• Research Institution: Kobe University
• Principal Investigator: Takahashi Yutaka 神戸大学, 医学(系)研究科(研究院), 准教授 (70301281)
• Co-Investigator(Kenkyū-buntansha): FUKUOKA Hidenori 神戸大学, 医学部附属病院, 助教 (80622068)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 下垂体 / 腫瘍 / 原因 / 疾患特異的iPS細胞 / 下垂体疾患 / 先天性下垂体低形成 / 下垂体腫瘍 / iPS細胞

Outline of Final Research Achievements

To clarify the pathogenesis and medical treatment of functional pituitary adenoma, we have performed a comprehensive genetic analysis of the GH-producing pituitary adenoma. Regarding Cushing’s disease, we performed a microarray analysis and screened molecular targeted therapy using primary culture tumor cells. We have further established a protocol for the differentiation from human iPS cells into pituitary in vitro. We have published 15 English papers and 13 Japanese papers.

Research Products

• [Journal Article] Accelerated telomere shortening in Acromegaly; IGF-I induces telomere shortening and cellular senescence. (2015)
  • Author(s): Matsumoto R, Fukuoka H, Iguchi G, Odake Y, Yoshida K, Bando H, Suda K, Nishizawa H, Takahashi M, Yamada S, Ogawa W, Takahashi Y
  • Journal Title: PLoS One. Volume: 10 Issue: 10 Pages: e0140189-e0140189
  • DOI: 10.1371/journal.pone.0140189
  • NAID: 120005668933
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The quality of life in acromegalic patients with biochemical remission by surgery alone is superior to that in those with pharmaceutical therapy without radiotherapy, using the newly developed Japanese version of the AcroQoL (2015)
  • Author(s): Yoshida K, Fukuoka H, Matsumoto R, Bando H, Suda K, Nishizawa H, Iguchi G, Ogawa W, Webb SM, Takahashi Y.
  • Journal Title: Pituitary Volume: 18 Issue: 6 Pages: 876-883
  • DOI: 10.1007/s11102-015-0665-2
  • Peer Reviewed / Open Access
• [Journal Article] Median-lower normal levels of serum thyroxine are associated with low triiodothyronine levels and body temperature in patients with central hypothyroidism. (2015)
  • Author(s): Hirata Y, Fukuoka H, Iguchi G, Iwahashi Y, Fujita Y, Hari Y, Iga M, Nakajima S, Nishimoto Y, Mukai M, Hirota Y, Sakaguchi K, Ogawa W, Takahashi Y.
  • Journal Title: Europian Journal of Endocrinology Volume: 173 Issue: 2 Pages: 247-256
  • DOI: 10.1530/eje-15-0130
  • Peer Reviewed / Open Access
• [Journal Article] A diagnostic pitfall in IgG4-related hypophysitis: infiltration of IgG4-positive cells in the pituitary of granulomatosis with polyangiitis. (2015)
  • Author(s): Bando H, Iguchi G, Fukuoka H, Taniguchi M, Kawano S, Saitoh M, Yoshida K, Matsumoto R, Suda K, Nishizawa H, Takahashi M, Morinobu A, Kohmura E, Ogawa W, Takahashi Y.
  • Journal Title: Pituitary Volume: 18 Issue: 5 Pages: 722-730
  • DOI: 10.1007/s11102-015-0650-9
  • Peer Reviewed / Open Access
• [Journal Article] The prevalence and associated factors of colorectal neoplasms in acromegaly: a single center based study. (2015)
  • Author(s): Yamamoto M, Fukuoka H, Iguchi G, Matsumoto R, Takahashi M, Nishizawa H, Suda K, Bando H, Takahashi Y.
  • Journal Title: Pituitary Volume: 18 Issue: 3 Pages: 343-351
  • DOI: 10.1007/s11102-014-0580-y
  • Peer Reviewed / Open Access
• [Journal Article] Endoscopic endonasal transsellar approach for laterally extended pituitary adenomas -Volumetric analysis of cavernous sinus invasion-. (2015)
  • Author(s): Taniguchi M, Hosoda K, Akutsu N, Takahashi Y, Kohmura E
  • Journal Title: Pituitary Volume: 18 Pages: 518-24
  • Peer Reviewed
• [Journal Article] Ameliorating effect of the novel dipeptidyl peptidase-4 inhibitor teneligliptin on psoriasis: A report of two cases (2015)
  • Author(s): Nagai H, Fujiwara S, Takahashi Y, Nishigori C
  • Journal Title: J Dermatology Volume: 42 Pages: 1-4
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A missense single-nucleotide polymorphism in the sialic acid acetyl esterase gene is associated with anti–PIT-1 antibody syndrome. (2014)
  • Author(s): Yamamoto M, Iguchi G, Bando H, Fukuoka H, Suda K, Takahashi M, Nishizawa H, Matsumoto R, Tojo K, Mokubo A, Ogata T, Takahashi Y.
  • Journal Title: Endocrine J Volume: 61 Pages: 641-4
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Involvement of PIT-1-reactive cytotoxic T lymphocytes in anti-PIT-1 antibody syndrome. (2014)
  • Author(s): Bando H, Iguchi G, Fukuoka H, Yamamoto M, Matsumoto R, Hidaka-Takeno R, Okimura Y, Matsumoto R, Suda K, Nishizawa H, Takahashi M, Toji K, Takahashi Y.
  • Journal Title: J Clin Endocrinol Metab Volume: 99 Issue: 9 Pages: E1744-E1749
  • DOI: 10.1210/jc.2014-1769
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The prevalence and associated factors of colorectal neoplasms in acromegaly: a single center based study. (2014)
  • Author(s): Yamamoto M, Fukuoka H, Iguchi G, Matsumoto R, Takahashi M, Nishizawa H, Suda K, Bando H, Takahashi Y.
  • Journal Title: Pituitary Volume: 18 Pages: 343-351
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] D-dimer as a significant marker of DVT in Patients with Subclinical or Overt Cushing’s Syndrome. (2014)
  • Author(s): Fukuoka H, Takeuchi T, Matsumoto R, Bando H, Suda K, Nishizawa H, Takahashi M, Hirota Y, Iguchi G, Takahashi Y.
  • Journal Title: Endocrine J Volume: 61 Pages: 1003-10
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Diabetic osteopenia by decreased β-catenin signaling is partly induced by epigenetic derepression of sFRP-4 gene (2014)
  • Author(s): Mori K, Kitazawa R, Kondo T, Mori M, Hamada Y, Nishida M, Minami Y, Haraguchi R, Takahashi Y, Kitazawa S.
  • Journal Title: PLoS One Volume: 9 Issue: 7 Pages: e102797-e102797
  • DOI: 10.1371/journal.pone.0102797
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Long-Term Effects of Growth Hormone Replacement Therapy on Liver Function in Adult Patients with Growth Hormone Deficiency. (2014)
  • Author(s): Matsumoto M, Fukuoka H, Iguchi G, Nishizawa H, Bando H, Suda K, Takahashi M, Takahashi Y
  • Journal Title: Growth Hormone and IGF-I Research. Volume: 24 Issue: 5 Pages: 174-9
  • DOI: 10.1016/j.ghir.2014.07.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Autoimmune hypophysitis: new developments. (2014)
  • Author(s): Takahashi Y
  • Journal Title: Handb Clin Neurol. Volume: 124 Pages: 417-22
  • DOI: 10.1016/b978-0-444-59602-4.00029-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] The essential role of GH/IGF-I in liver. (2015)
  • Author(s): Takahashi Y.
  • Organizer: the 6th Annual European Meeting on the Management of Acromegaly
  • Place of Presentation: イスタンブール
  • Year and Date: 2015-09-25
  • Int'l Joint Research / Invited
• [Presentation] GH resistance under fasting conditions: the role of SIRT1 in endocrine adaptation. (2015)
  • Author(s): Takahashi Y.
  • Organizer: FASEB Scietific Research Conference Colorado
  • Place of Presentation: コロラド
  • Year and Date: 2015-07-12
  • Int'l Joint Research / Invited
• [Presentation] クッシング病の薬物療法～現況と今後の展望 (2014)
  • Author(s): 福岡秀規、井口元三、小川渉、高橋 裕
  • Organizer: 第24回臨床内分泌代謝Update 2014
  • Place of Presentation: 大宮ソニックシティ、埼玉
  • Year and Date: 2014-11-28
  • Invited
• [Presentation] 先端巨大症の病態と新たなメカニズム (2014)
  • Author(s): 高橋 裕
  • Organizer: 第14回日本内分泌学会北陸支部学術集会ランチョンセミナー
  • Place of Presentation: 金沢
  • Year and Date: 2014-11-09
  • Invited
• [Presentation] The Year 神経内分泌臨床編 (2014)
  • Author(s): 高橋 裕
  • Organizer: 第41回日本神経内分泌学会学術集会
  • Place of Presentation: 都市センターホテル
  • Year and Date: 2014-10-30
  • Invited
• [Presentation] トランジション期の肝臓におけるGHの大切な役割 (2014)
  • Author(s): 高橋 裕
  • Organizer: 第48回日本小児内分泌学会学術集会
  • Place of Presentation: アクトシティ浜松
  • Year and Date: 2014-09-25
  • Invited
• [Presentation] 成長ホルモン、IGF-Iの肝臓における新たな作用と治療応用 (2014)
  • Author(s): 高橋 裕
  • Organizer: 第15回日本内分泌学会関東甲信越支部学術集会
  • Place of Presentation: ラフレさいたま 大宮
  • Year and Date: 2014-09-06
  • Invited
• [Presentation] Oxidative stress, telomere, and cellular senescence: New pathophysiological insights in acromegaly. (2014)
  • Author(s): Takahashi Y
  • Organizer: The 3rd Pituitary Expert Meeting in Asia
  • Place of Presentation: Tokyo
  • Year and Date: 2014-08-31
  • Invited
• [Presentation] 多腺性自己免疫症候群に伴う下垂体炎と抗PIT-1抗体症候群のトピックス (2014)
  • Author(s): 高橋 裕、坂東弘教、山本雅昭、福岡秀規、井口元三
  • Organizer: 第87回日本内分泌学会学術総会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-04-26
  • Invited
• [Book] 内科学第11版 (2016)
  • Author(s): 高橋 裕
  • Total Pages: 2
  • Publisher: 朝倉書店
• [Book] Endocrine Immunology; A novel clinical entity of autoimmune endocrinopathy: Anti-PIT-1 antibody syndrome (2015)
  • Author(s): Iguchi G, Bando H, Takahashi Y
  • Total Pages: 7
  • Publisher: Karger
• [Book] 医学大事典 (2015)
  • Author(s): 高橋 裕
  • Total Pages: 7
  • Publisher: 南山堂
• [Book] 今日の小児治療指針 (2015)
  • Author(s): 高橋 裕
  • Total Pages: 1
  • Publisher: 医学書院
• [Book] 第3版アンチエイジング医学の基礎と臨床 (2015)
  • Author(s): 高橋 裕
  • Total Pages: 2
  • Publisher: メジカルビュー社
• [Book] 内科学第11版 (2015)
  • Author(s): 高橋 裕
  • Publisher: 朝倉書店
• [Book] 難治性内分泌代謝疾患Update (2015)
  • Author(s): 高橋 裕
  • Publisher: 診断と治療社
• [Book] 内科外来基本処方Navi (2014)
  • Author(s): 高橋 裕
  • Total Pages: 222
  • Publisher: 中外医学社
• [Book] 内分泌代謝クリニカルクエスチョン (2014)
  • Author(s): 高橋 裕
  • Total Pages: 183
  • Publisher: 診断と治療社
• [Remarks] 神経内分泌研究グループ
  • URL: http://www.med.kobe-u.ac.jp/im2/doctor/activity/acti-04.html
• [Remarks] 神戸大学大学院 糖尿病内分泌内科学 神経内分泌グループ
  • URL: http://www.med.kobe-u.ac.jp/im2/doctor/activity/acti-04.html