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2015 Fiscal Year Annual Research Report

内分泌器官としての肝臓病学の確立

Research Project

Project/Area Number 26253046
Research InstitutionKanazawa University

Principal Investigator

金子 周一  金沢大学, 医学系, 教授 (60185923)

Co-Investigator(Kenkyū-buntansha) 本多 政夫  金沢大学, 保健学系, 教授 (00272980)
井上 啓  金沢大学, 新学術創成研究機構, 教授 (50397832)
篁 俊成  金沢大学, 医学系, 教授 (00324111)
水腰 英四郎  金沢大学, 医学系, 准教授 (90345611)
太田 嗣人  金沢大学, 脳・肝インターフェースメディシン研究センター, 准教授 (60397213)
御簾 博文  金沢大学, 医学系, 准教授 (80447680)
竹下 有美枝  金沢大学, 大学病院, 助教 (40507042)
Project Period (FY) 2014-04-01 – 2019-03-31
Keywordsゲノム / 発現制御 / 肝臓 / 栄養 / 生活習慣病
Outline of Annual Research Achievements

本研究では、過剰に摂取される栄養による全身の影響、とくに、過栄養によって肝臓の機能が大きく障害されていることを、遺伝子・タンパク・脂質の系統的な解析から明らかにし、その病態を研究している。肝臓の過栄養状態を示す脂肪肝と、糖質代謝および脂質代謝に関する研究を行った。これまでヒトの脂肪肝における脂肪酸の分析は詳細に行われていなかった。脂肪肝における脂肪酸の動態と、単純性の脂肪肝から炎症が引き起こされる機序を解析した(Liver International 2015)。脂肪肝において低下する肝再生の機序を明らかにするとともに(Hepatology 2015)、脂肪肝がインスリン抵抗性と関連する機序について解析した(Journal of Diabetes Investigation 2015)。過栄養において、脳・肝臓連関が破綻することを明らかにし、さらに、肝臓細胞の障害が増強することを見出している。肝臓由来分泌タンパクであるセレノプロテインPの骨格筋ならびに運動感受性に対する作用を検討した。過剰なセレノプロテインPが骨格筋の受容体を介して“運動療法抵抗性”を惹起することを見出した。糖尿病との関連では薬物による糖尿病治療の研究が行われた(Journal of Diabetes Investigation 2015 2本、BMJ Open Diabetes Research & Care 2015)。肝細胞がんの悪性度をGd-EOB MRI所見と免疫組織学的所見から明らかにし、EOB-MRI所見が肝細胞癌の悪性度の視標となることを示唆した(Radiology 2015)。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

当初の計画どおりの研究を実行することができている。予定した成果を論文とした。

Strategy for Future Research Activity

計画どおり、ヘパトカインであるセレノプロテインPおよびLECT2の構造解析および機能解析をさらに進める。脂肪肝の意義について、動物モデル、臨床材料を進める。これらの研究計画に変更はない。

  • Research Products

    (22 results)

All 2015 Other

All Journal Article (16 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 16 results,  Open Access: 16 results) Remarks (1 results) Patent(Industrial Property Rights) (5 results) (of which Overseas: 2 results)

  • [Journal Article] Growth arrest and DNA damage-inducible 34 regulates liver regeneration in hepatic steatosis in mice.2015

    • Author(s)
      Y Inaba, T Furutani, K Kimura, H Watanabe, S Haga, Y Kido, M Matsumoto, Y Yamamoto, K Harada, S Kaneko, S Oyadomari, M Ozaki, M Kasuga, H Inoue.
    • Journal Title

      Hepatology

      Volume: 61 Pages: 1343-1356

    • DOI

      10.1002/hep.27619.

    • Peer Reviewed / Open Access
  • [Journal Article] Bending of a vertical cannula without alarm during insulin pump therapy as a cause of unexpected hyperglycemia: A Japanese issue?2015

    • Author(s)
      K Kuroda, Y Takeshita, S Kaneko, T Takamura.
    • Journal Title

      J Diabetes Investig

      Volume: 6 Pages: 739-740

    • DOI

      10.1111/jdi.12357.

    • Peer Reviewed / Open Access
  • [Journal Article] Sitagliptin versus mitiglinide switched from mealtime dosing of a rapid-acting insulin analog in patients with type 2 diabetes: a randomized, parallel-group study.2015

    • Author(s)
      Y Takeshita, T Takamura, Y Kita, A Takazakura, K Kato, Y Isobe, S Kaneko.
    • Journal Title

      BMJ Open Diabetes Res Care

      Volume: 3 Pages: e000122

    • DOI

      10.1136/bmjdrc-2015-000122.

    • Peer Reviewed / Open Access
  • [Journal Article] Renoprotective effects of atorvastatin compared with pravastatin on progression of early diabetic nephropathy.2015

    • Author(s)
      A Takazakura, M Sakurai, Y Bando, H Misu, Y Takeshita, Y Kita, A Shimizu, T Hayakawa, K Kato, S Kaneko, T Takamura.
    • Journal Title

      J Diabetes Investig

      Volume: 6 Pages: 346-353

    • DOI

      10.1111/jdi.12296.

    • Peer Reviewed / Open Access
  • [Journal Article] Vildagliptin vs liraglutide as a second-line therapy switched from sitagliptin-based regimens in patients with type 2 diabetes: A randomized, parallel-group study.2015

    • Author(s)
      Y Takeshita, T Takamura, Y Kita, T Otoda, K Kato, H Wakakuri, M Yamada, H Misu, Y Matsushima, S Kaneko.
    • Journal Title

      J Diabetes Investig

      Volume: 6 Pages: 192-200

    • DOI

      10.1111/jdi.12269.

    • Peer Reviewed / Open Access
  • [Journal Article] Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: A comparison with vitamin E.2015

    • Author(s)
      Y Ni, M Nagashimada, F Zhuge, L Zhan, N Nagata, A Tsutsui, Y Nakanuma, S Kaneko, T Ota.
    • Journal Title

      Sci Rep

      Volume: 5 Pages: 17192

    • DOI

      10.1038/srep17192.

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Phase I trial of multidrug resistance-associated protein 3-derived peptide in patients with hepatocellular carcinoma.2015

    • Author(s)
      E Mizukoshi, H Nakagawa, M Kitahara, T Yamashita, K Arai, H Sunagozaka, N Iida, K Fushimi, S Kaneko.
    • Journal Title

      Cancer Lett

      Volume: 369 Pages: 242-249

    • DOI

      10.1016/j.canlet.2015.08.020.

    • Peer Reviewed / Open Access
  • [Journal Article] Defeating EpCAM+ liver cancer stem cells by targeting chromatin remodeling enzyme CHD4 in human hepatocellular carcinoma.2015

    • Author(s)
      K Nio, T Yamashita, H Okada, M Kondo, T Hayashi, Y Hara, Y Nomura, SS Zeng, M Yoshida, T Hayashi, H Sunagozaka, N Oishi, M Honda, S Kaneko.
    • Journal Title

      J Hepatol

      Volume: 63 Pages: 1164-1172

    • DOI

      10.1016/j.jhep.2015.06.009.

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inhibition of microRNA-214 ameliorates hepatic fibrosis and tumor incidence in platelet-derived growth factor C transgenic mice.2015

    • Author(s)
      H Okada, M Honda, JS Campbell, K Takegoshi, Y Sakai, T Yamashita, T Shirasaki, R Takabatake, M Nakamura, T Tanaka, S Kaneko.
    • Journal Title

      Cancer Sci

      Volume: 106 Pages: 1143-1152

    • DOI

      10.1111/cas.12730.

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immunological features of T cells induced by human telomerase reverse transcriptase-derived peptides in patients with hepatocellular carcinoma.2015

    • Author(s)
      E Mizukoshi, H Nakagawa, M Kitahara, T Yamashita, K Arai, H Sunagozaka, K Fushimi, E Kobayashi, H Kishi, A Muraguchi, S Kaneko.
    • Journal Title

      Cancer Lett

      Volume: 364 Pages: 98-105

    • DOI

      10.1016/j.canlet.2015.04.031.

    • Peer Reviewed / Open Access
  • [Journal Article] Response to Importance of confounding factors in assessing fatty acid compositions in patients with non-alcoholic steatohepatitis.2015

    • Author(s)
      K Yamada, E Mizukoshi, H Sunagozaka, K Arai, T Yamashita, Y Takeshita, H Misu, T Takamura, S Kitamura, Y Zen, Y Nakanuma, M Honda, S Kaneko.
    • Journal Title

      Liver Int

      Volume: 35 Pages: 1773

    • DOI

      10.1111/liv.12755.

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Serum DHCR24 Auto-antibody as a new Biomarker for Progression of Hepatitis C.2015

    • Author(s)
      S Ezzikouri, K Kimura, H Sunagozaka, S Kaneko, K Inoue, T Nishimura, T Hishima, M Kohara, K Tsukiyama-Kohara.
    • Journal Title

      EBioMedicine

      Volume: 2 Pages: 604-612

    • DOI

      10.1016/j.ebiom.2015.04.007.

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Small tRNA-derived RNAs are increased and more abundant than microRNAs in chronic hepatitis B and C.2015

    • Author(s)
      SR Selitsky, J Baran-Gale, M Honda, D Yamane, T Masaki, EE Fannin, B Guerra, T Shirasaki, T Shimakami, S Kaneko, RE Lanford, SM Lemon, P Sethupathy.
    • Journal Title

      Sci Rep

      Volume: 5 Pages: 7675

    • DOI

      10.1038/srep07675.

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Relationship between Serum Uric Acid Levels and Chronic Kidney Disease in a Japanese Cohort with Normal or Mildly Reduced Kidney Function.2015

    • Author(s)
      T Toyama, K Furuichi, M Shimizu, A Hara, Y Iwata, N Sakai, V Perkovic, M Kobayashi, T Mano, S Kaneko, T Wada.
    • Journal Title

      PLoS One

      Volume: 10 Pages: e0137449

    • DOI

      10.1371/journal.pone.0137449.

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hepatocellular Carcinoma with β-Catenin Mutation: Imaging and Pathologic Characteristics.2015

    • Author(s)
      A Kitao, O Matsui, N Yoneda, K Kozaka, S Kobayashi, J Sanada, W Koda, T Minami, D Inoue, K Yoshida, T Yamashita, T Yamashita, S Kaneko, H Takamura, T Ohta, H Ikeda, Y Nakanuma, R Kita, T Gabata.
    • Journal Title

      Radiology

      Volume: 275 Pages: 708-717

    • DOI

      10.1148/radiol.14141315.

    • Peer Reviewed / Open Access
  • [Journal Article] Autoantibody status and histological variables influence biochemical response to treatment and long-term outcomes in Japanese patients with primary biliary cirrhosis.2015

    • Author(s)
      M Nakamura, H Kondo, A Tanaka, A Komori, M Ito, K Yamamoto, H Ohira, M Zeniya, E Hashimoto, M Honda, S Kaneko, Y Ueno, K Kikuchi, S Shimoda, K Harada, K Arai, Y Miyake, M Abe, M Taniai, T Saibara, S Sakisaka, H Takikawa, M Onji, H Tsubouchi, Y Nakanuma, H Ishibashi.
    • Journal Title

      Hepatol Res

      Volume: 45 Pages: 846-855

    • DOI

      10.1111/hepr.12423.

    • Peer Reviewed / Open Access
  • [Remarks] 金沢大学医学部付属病院内科(旧第一内科)恒常性制御学講座

    • URL

      http://www.m-kanazawa.jp/

  • [Patent(Industrial Property Rights)] オリゴヌクレオチドが結合したビーズの作製方法2015

    • Inventor(s)
      橋本真一、金子周一
    • Industrial Property Rights Holder
      金沢大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      PCT/JP2015/075760
    • Filing Date
      2015-04-07
    • Overseas
  • [Patent(Industrial Property Rights)] 2型糖尿病患者の治療薬選択の補助方法,治療薬の効果予測方法及び検査方法2015

    • Inventor(s)
      御簾博文、竹下有美枝、篁 俊成、金子周一
    • Industrial Property Rights Holder
      金沢大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      PCT/JP2015/075760
    • Filing Date
      2015-09-10
    • Overseas
  • [Patent(Industrial Property Rights)] 抗DHCR24自己抗体検出による病態診断系2015

    • Inventor(s)
      金子周一、小原恭子、小原道法、木村公則
    • Industrial Property Rights Holder
      金沢大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-142360
    • Filing Date
      2015-07-16
  • [Patent(Industrial Property Rights)] 細胞障害性T細胞の作製方法2015

    • Inventor(s)
      金子周一、水腰英四郎、中河秀俊、村口 篤、岸 裕幸、小林栄治
    • Industrial Property Rights Holder
      金沢大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-209372
    • Filing Date
      2015-10-23
  • [Patent(Industrial Property Rights)] 抗B型肝炎ウイルス薬2015

    • Inventor(s)
      橋本真一、金子周一、本多政夫、白崎尚芳、山下太郎
    • Industrial Property Rights Holder
      金沢大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-219183
    • Filing Date
      2015-11-09

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Published: 2017-01-06  

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