Identification of genes related with malignant transformation of hepatocellular carcinoma using alpha 1-6 fucosyltransferaseconditional knock-out mice

• Project/Area Number: 23659395
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Niigata University
• Principal Investigator: AOYAGI Yutaka 新潟大学, 医歯学系, 教授 (00142266)
• Co-Investigator(Kenkyū-buntansha): SUDA Takeshi 新潟大学, 医歯学総合病院, 講師 (10361916) ; TAMURA Yasushi 新潟大学, 医歯学総合病院, 医員 (80467076)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: FUT8 / Cre-loxP / conditional knockout mouse / AFP-L3 / 肝細胞癌 / 糖鎖転移酵素 / コンディショナルノックアウトマウス / FUT8遺伝子 / 発癌

Research Abstract

Fucosylated fraction of alpha-fetoprotein is the product of α1-6 fucosyltransferase (FUT8) and is an indicator of unfavorable prognosis in patients with hepatocellular carcinoma. We have produced liver specific FUT8 conditional knockout mouse (FUT8loxP/loxP‐ AlbCre+/- mouse) for investigation of physiological function of FUT8 gene in hepatocarcinogenesis. A specific DNA fragment by cre-recombinase was seen in the liver tissue from FUT8loxP/loxP‐AlbCre+/- mouse. Real-time PCR analysis showed the FUT8 mRNA level in liver tissue was knocked down. On the other hand, we found no significant decrease of FUT8 activity in the liver tissue from FUT8loxP/loxP‐Alb Cre+/- mouse. No significant change in signal intensities of lectins associated with α1-6 fucosylation was observed in the liver tissue by sugar chain profiling analysis using lectin microchip.

Research Products

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• [Journal Article] Phase I study of miriplatin combined with transarterial chemotherapy using CDDP powder in patients with hepatocellular carcinoma. (2012)
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• [Journal Article] Contributing Factors to Gastric Ulcer Healing After Endoscopic Submucosal Dissection Including the Promoting Effect of Rebamipide (2012)
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• [Journal Article] Failure to achieve 2-log10 viral decrease in first four weeks ofpeg-IFNalpha-2b plus ribavirin therapy for chronic hepatitis C with genotype 1b and high viral titer is useful in predicting non-response: evaluation of response-guided therapy. (2011)
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• [Journal Article] History and recent progress in evaluation of the fucosylated alpha-fetoprotein fraction (2011)
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• [Journal Article] Hepatocellular carcinoma with progenitor cell features distinguishable by the hepatic stem/progenitor cell marker NCAM (2011)
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• [Journal Article] Characterization of elevated alanine aminotransferase levels during pegylated-interferon α-2b plus ribavirin treatment for chronic hepatitis C (2011)
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• [Journal Article] Aoyagi Y Multicentric occurrence of hepatocellular carcinoma with nonalcoholic steatohepatitis (2011)
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• [Journal Article] Multicentric occurrence of hepatocellular carcinoma with nonalcoholic steatohepatitis (2011)
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• [Journal Article] Usefulness of magnifying narrow band imaging for assessing lateral tumor extent of early gastric cancer: a case report. (2011)
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• [Journal Article] Failure to achieve 2-log10 viral decrease in first four weeks of peg-IFNalpha-2b plus ribavirin therapy for chronic hepatitis C with genotype 1b and high viral titer is useful in predicting non-response: evaluation of response-guided therapy. (2011)
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• [Journal Article] The efficacy of endoscopic triamcinolone injection for the prevention of esophageal stricture after endoscopic submucosal dissection (2011)
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• [Presentation] Hydrodynamics-based Gene Transfer to Large Animals (2013)
  • Author(s): Kamimura K, Suda T, Zhang G, Aoyagi Y, Liu D.
  • Organizer: Genetic Transformation Technologies
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  • Year and Date: 2013-02-12
• [Presentation] Hydrodynamics-based Gene Transfer to Large Animals (2013)
  • Author(s): 上村 顕也
  • Organizer: Genetic Transformation Technologies
  • Place of Presentation: University of Vienna Vienna, Austria
• [Presentation] Presence of antibodies againstself-HLA class II molecules inautoimmune hepatitis (2012)
  • Author(s): Yamagiwa S, Takamura M, Matsuda Y, Geneda T,Takahashi T, Ichida T, Aoyagi Y.
  • Organizer: The 63rd Annual Meeting of the AASLD
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  • Year and Date: 2012-11-09
• [Presentation] Comparative proteomic analysis of the liver in a murine model of non-alcoholic steatohepatitis (2012)
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  • Organizer: The63rd Annual Meeting of the AASLD
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  • Year and Date: 2012-11-09
• [Presentation] Nutritional intervention in cirrhotic patients with hepatocellular carcinoma on the basis of energy state assessment (2012)
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  • Organizer: The 3rd Asian-Pacific Topic Conference.
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  • Year and Date: 2012-11-03
• [Presentation] APM2 は肝細胞癌のシスプラチン効果予測指標となりうる (2012)
  • Author(s): 上村顕也,須田剛士,兼藤努,田村康,高村昌昭,五十嵐正人,川合弘一,山際訓,野本実,青柳豊.
  • Organizer: 第71回日本癌学会学術集会
  • Place of Presentation: ロイトン札幌ほか(北海道札幌市)
  • Year and Date: 2012-09-20
• [Presentation] APM2は肝細胞癌に対するシスプラチンの効果予測マーカー候補である (2012)
  • Author(s): 上村顕也,須田剛士,大崎暁彦,五十嵐正人,野本実,青柳豊.
  • Organizer: 第48回日本肝癌研究会
  • Place of Presentation: 石川県立音楽堂ほか(石川県金沢市)
  • Year and Date: 2012-07-20
• [Presentation] Establishing Clinically Applicable, Image-Guided, and Computer-Controlled Hydrodynamic Gene Delivery forTreatment of Hemophilia B (2012)
  • Author(s): Kanefuji T, Kamimura K,Suda T, GaoM, Zhang G,Aoyagi Y,Liu D .
  • Organizer: 第18回日本遺伝子治療学会学術集会
  • Place of Presentation: ホテル熊本テルサ(熊本県熊本市)
  • Year and Date: 2012-06-28
• [Presentation] 自己免疫性肝炎急性発症時における抗HLAclassII抗体出現と肝細胞傷害への関与 (2012)
  • Author(s): 山際訓,高村昌昭,野本実,青柳豊.
  • Organizer: 第48回日本肝臓学会総会
  • Place of Presentation: ANAクラウンプラザホテル金沢(石川県金沢市)
  • Year and Date: 2012-06-06
• [Presentation] Long Term Transgene Expression in Rat Liver Using a Novel Electromotor-Driven Hydrodynamic Gene Injector (2012)
  • Author(s): Yokoo T,Kamimura K,Suda T,Kanefuji T, Oda M,Zhang G,Liu D,Aoyagi Y.
  • Organizer: The 15th Annual meeting of American Society of Gene Therapy
  • Place of Presentation: Pennsylvania Convention Center(Philadelphia,PA.USA)
  • Year and Date: 2012-05-16
• [Presentation] Image-Guided,Lobe-Specific Hydrodynamic Gene Delivery to Baboon Liver (2012)
  • Author(s): Kamimura K,Suda T,Kanefuji T, ZhangG, Aoyagi Y,Liu D.
  • Organizer: The 15th Annual meeting of American Society of Gene Therapy
  • Place of Presentation: Pennsylvania ConventionCenter(Philadelphia,PA.USA)
  • Year and Date: 2012-05-16
• [Presentation] C型肝炎に対するインターフェロン治療によるAFP値変動と肝発癌抑制 (2012)
  • Author(s): 田村康,上村顕也,兼藤努,五十嵐正人,高村昌昭,山際訓,須田剛士,野本実,青柳豊
  • Organizer: 第98回日本消化器病学会総会
  • Place of Presentation: 京王プラザホテル(東京都新宿区)
  • Year and Date: 2012-04-20
• [Presentation] 実験的NASHモデルマウス肝組織のプロテオーム解析 (2012)
  • Author(s): 高村昌昭,許波,嶋田修一郎,張螢,吉田豊,矢尾板永信,山際訓,松田康伸, 野本実,山本格,青柳豊.
  • Organizer: 第98回日本消化器病学会総会
  • Place of Presentation: 京王プラザホテル(東京都新宿区)
  • Year and Date: 2012-04-19
• [Presentation] 肝細胞癌(HCC)に対するラジオ波焼灼療法(RFA)の効果と限界 (2012)
  • Author(s): 須田剛士,上村顕也,青柳豊ほか
  • Organizer: 第109回日本内科学会総会・講演会
  • Place of Presentation: みやこめっせ(京都府京都市)
  • Year and Date: 2012-04-12
• [Presentation] 肝細胞癌(HCC)に対するラジオ波焼灼療法(RFA)の効果と限界 (2012)
  • Author(s): 須田 剛士
  • Organizer: 第109回日本内科学会総会・講演会
  • Place of Presentation: 京都府京都市 みやこめっせ
• [Presentation] 実験的NASHモデルマウス肝組織のプロテオーム解析 (2012)
  • Author(s): 高村 昌昭
  • Organizer: 第98回日本消化器病学会総会
  • Place of Presentation: 東京都新宿区 京王プラザホテル
• [Presentation] 高齢肝細胞癌症例に対する治療介入の是非 (2012)
  • Author(s): 須田 剛士
  • Organizer: 第98回日本消化器病学会総会
  • Place of Presentation: 東京都新宿区 京王プラザホテル
• [Presentation] C型肝炎に対するインターフェロン治療によるAFP値変動と肝発癌抑制 (2012)
  • Author(s): 田村 康
  • Organizer: 第98回日本消化器病学会総会
  • Place of Presentation: 東京都新宿区 京王プラザホテル
• [Presentation] 当科で経験した肝硬変に深部出血を合併した３例 (2012)
  • Author(s): 渡邉 順
  • Organizer: 第98回日本消化器病学会総会
  • Place of Presentation: 東京都新宿区 京王プラザホテル
• [Presentation] cryptogenic肝硬変とNASH肝硬変の臨床的比較検討 (2012)
  • Author(s): 川合 弘一
  • Organizer: 第98回日本消化器病学会総会
  • Place of Presentation: 東京都新宿区 京王プラザホテル
• [Presentation] Image-Guided,Lobe-Specific Hydrodynamic Gene Delivery to Baboon Liver (2012)
  • Author(s): 上村 顕也
  • Organizer: The 15th Annual meeting of American Society of Gene Therapy
  • Place of Presentation: Philadelphia,PA. Pennsylvania Convention Center, USA
• [Presentation] Long Term Transgene Expression in Rat Liver Using a Novel Electromotor-Driven Hydrodynamic Gene Injector (2012)
  • Author(s): 横尾 健
  • Organizer: The 15th Annual meeting of American Society of Gene Therapy
  • Place of Presentation: Philadelphia,PA. Pennsylvania Convention Center, USA
• [Presentation] 細胞外液性造影動態による認識が困難な超早期肝細胞性病変の近未来進展予測 (2012)
  • Author(s): 須田 剛士
  • Organizer: 第48回日本肝臓学会総会
  • Place of Presentation: 石川県金沢市 石川県立音楽堂
• [Presentation] 肝細胞癌患者における血清シスタチンCの腎機能マーカーとしての臨床的有用性 (2012)
  • Author(s): 川合 弘一
  • Organizer: 第48回日本肝臓学会総会
  • Place of Presentation: 石川県金沢市 ポルテ金沢
• [Presentation] 自己免疫性肝炎急性発症時における抗HLA class II抗体出現と肝細胞傷害への関与 (2012)
  • Author(s): 山際 訓
  • Organizer: 第48回日本肝臓学会総会
  • Place of Presentation: 石川県金沢市 ANAクラウンプラザホテル金沢
• [Presentation] Establishing Clinically Applicable, Image-Guided, and Computer-Controlled Hydrodynamic Gene Delivery for Treatment of Hemophilia B (2012)
  • Author(s): 兼藤 努
  • Organizer: 第18回日本遺伝子治療学会学術集会
  • Place of Presentation: 熊本県熊本市 ホテル熊本テルサ
• [Presentation] 医薬工連携による新規遺伝子導入装置の開発と今後の展開 (2012)
  • Author(s): 上村 顕也
  • Organizer: 第28回日本DDS学会学術集会
  • Place of Presentation: 北海道札幌市 札幌コンベンションセンター
• [Presentation] APM2は肝細胞癌に対するシスプラチンの効果予測マーカー候補である (2012)
  • Author(s): 上村 顕也
  • Organizer: 第48回日本肝癌研究会
  • Place of Presentation: 石川県金沢市 石川県立音楽堂
• [Presentation] 肝細胞癌に対する肝動注療法における安全で効果的なシスプラチン量の設定 (2012)
  • Author(s): 須田 剛士
  • Organizer: 第71回日本癌学会学術集会
  • Place of Presentation: 北海道札幌市 ロイトン札幌
• [Presentation] APM2は肝細胞癌のシスプラチン効果予測指標となりうる (2012)
  • Author(s): 上村 顕也
  • Organizer: 第71回日本癌学会学術集会
  • Place of Presentation: 北海道札幌市 ロイトン札幌
• [Presentation] 新たな診断基準に基づく急性肝不全に対する人工肝補助療法施行例の検討 (2012)
  • Author(s): 山際 訓
  • Organizer: JDDW2012
  • Place of Presentation: 兵庫県神戸市 神戸国際展示場
• [Presentation] ハイドロダイナミック法によるヒヒ肝臓への遺伝子導入 (2012)
  • Author(s): 上村 顕也
  • Organizer: JDDW2012 第16回日本肝臓学会大会
  • Place of Presentation: 兵庫県神戸市 神戸国際展示場
• [Presentation] アルコール性肝障害および非アルコール性脂肪性肝炎の組織学的鑑別の検討 (2012)
  • Author(s): 野本 実
  • Organizer: JDDW2012 第16回日本肝臓学会大会
  • Place of Presentation: 兵庫県神戸市 神戸国際展示場
• [Presentation] ミニマル肝性脳症の診断とその特徴 (2012)
  • Author(s): 須田 剛士
  • Organizer: JDDW2012
  • Place of Presentation: 兵庫県神戸市 神戸国際展示場
• [Presentation] 肝疾患治療における非タンパク呼吸商(npRQ)測定の重要性 (2012)
  • Author(s): 兼藤 努
  • Organizer: JDDW2012
  • Place of Presentation: 兵庫県神戸市 神戸国際展示場
• [Presentation] Nutritional intervention in cirrhotic patients with hepatocellular carcinoma on the basis of energy state assessment (2012)
  • Author(s): 須田 剛士
  • Organizer: The 3rd Asian-Pacific Topic Conference
  • Place of Presentation: 東京都港区 芝パークホテル
• [Presentation] Comparative proteomic analysis of the liver in a murine model of non-alcoholic steatohepatitis (2012)
  • Author(s): 高村 昌昭
  • Organizer: The 63ｒｄ Annual Meeting of the AASLD
  • Place of Presentation: Hynes Convention Center Boston, USA
• [Presentation] Presence of antibodies against self-HLA class II molecules in autoimmune hepatitis (2012)
  • Author(s): 山際 訓
  • Organizer: The 63ｒｄ Annual Meeting of the AASLD
  • Place of Presentation: Hynes Convention Center, Boston, USA
• [Presentation] 新たな診断基準に基づく急性肝不全例の検討 (2012)
  • Author(s): 山際 訓
  • Organizer: 第39回日本肝臓学会東部会
  • Place of Presentation: 東京都港区 グランドプリンスホテル新高輪・国際館パミール
• [Presentation] TVRを含む3剤併用療法困難例におけるPEG-IFNα-2a/RBV併用療法の有効性・安全性に関する臨床的検討 (2012)
  • Author(s): 山際 訓
  • Organizer: 第39回日本肝臓学会東部会
  • Place of Presentation: 東京都港区 グランドプリンスホテル新高輪・国際館パミール
• [Presentation] 音響放射圧を用いた肝内せん断弾性波速度測定による肝細胞癌発癌リスク評価 (2012)
  • Author(s): 高村 昌昭
  • Organizer: 第39回日本肝臓学会東部会
  • Place of Presentation: 東京都港区 グランドプリンスホテル新高輪・国際館パミール
• [Presentation] Reduced NKG2D ligand expression in hepatocellular carcinoma correlates with early recurrence (2011)
  • Author(s): Yamagiwa S, Kamimura H, Tsuchiya A, Takamura M,Matsuda Y,Shirai Y,Aoyagi Y.
  • Organizer: The 62nd AASLD2011 Annual Meeting
  • Place of Presentation: Moscone West Convention Center(San Francisco,California, USA)
  • Year and Date: 2011-11-03
• [Presentation] 肝細胞癌に対するミリプラチン使用経験とその治療効果について (2011)
  • Author(s): 田村康,土屋淳紀,上村顕也,矢野雅彦,高村昌昭,五十嵐正人,川合弘一,山際訓,須田剛士,大越章吾,野本実,青柳豊.
  • Organizer: 第53回日本消化器病学会大会
  • Place of Presentation: 福岡国際センター他(福岡県福岡市)
  • Year and Date: 2011-10-21
• [Presentation] ミラノ基準内HCC症候群における高感度化AFP-L3分画測定の臨床的意義 (2011)
  • Author(s): 田村康,須田剛士,青柳豊,若井俊文,黒崎功,白井良夫.
  • Organizer: 第47回日本肝癌研究会
  • Place of Presentation: 静岡県コンベンションアーツセンター「グランシップ」(静岡県静岡市)
  • Year and Date: 2011-07-29
• [Presentation] 高感度AFP-L3分画と肝細胞癌切除組織所見および予後との関連性についての検討 (2011)
  • Author(s): 田村康,須田剛士,五十嵐正人,土屋淳紀,上村顕也,山際訓,野本実,大越章吾,青柳豊.
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: ホテルグランパシフィックLEDAIBA(東京都港区)
  • Year and Date: 2011-06-03
• [Presentation] Gd-EOB-DTPA造影MRIで乏血性かつ肝細胞造影相で低信号を示す病変の自然経過 (2011)
  • Author(s): 須田剛士,土屋淳紀,上村顕也,矢野雅彦,田村康,高村昌昭,五十嵐正人,川合弘一,山際訓,青柳豊.
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: ホテルグランパシフィックLEDAIBA(東京都港区)
  • Year and Date: 2011-06-02
• [Presentation] 切除不能進行肝細胞癌に対するミリプラ/アイエーコール併用肝動注療法(第I相試験) (2011)
  • Author(s): 上村顕也,須田剛士,土屋淳紀,矢野雅彦,田村康,高村昌昭,五十嵐正人,川合弘一,山際訓,大越章吾,野本実,青柳豊.
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: ホテルグランパシフィックLEDAIBA(東京都港区)
  • Year and Date: 2011-06-02
• [Presentation] 自己免疫性肝炎急性発症時におけるAFPおよびAFP-L3分画の上昇 (2011)
  • Author(s): 山際訓,田村康,野本実,青柳豊.
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: ホテルグランパシフィックLEDAIBA(東京都港区)
  • Year and Date: 2011-06-02
• [Presentation] Optimization of Image-Guided Hydrodynamic Gene Delivery to Liver of Large Animals (2011)
  • Author(s): Kamimura K,Suda T,Kanefuji T, Zhang G, Liu D,Aoyagi Y.
  • Organizer: 第14回アメリカ遺伝子細胞治療学会
  • Place of Presentation: Washington State Convention& Trade Center(Seattle,WA,USA)
  • Year and Date: 2011-05-19
• [Presentation] Optimization ofImage-Guided Hydrodynamic Gene Delivery to Liver of Large Animals (2011)
  • Author(s): Suda T, Kamimura K,Kanefuji T, ZhangG, Liu D,Aoyagi Y.
  • Organizer: 第14回アメリカ遺伝子細胞治療学会
  • Place of Presentation: Washington State Convention& Trade Center(Seattle,WA,USA)
  • Year and Date: 2011-05-19
• [Presentation] APM2 is a Candidate of Predictive Marker for Cisplatin Sensitivity in HepatocellularCarcinoma (2011)
  • Author(s): Kamimura K,Suda T,Fukuhara Y,Osaki A, Aoyagi Y.
  • Organizer: The 3rd JCA-AACR SpecialJoint Conference
  • Place of Presentation: 東京ベイ舞浜ホテルクラブリゾート(千葉県舞浜市)
  • Year and Date: 2011-03-02
• [Presentation] Development of Electromotor-Driven Injector for Hydrodynamic Gene Delivery. (2011)
  • Author(s): Suda T
  • Organizer: 14th American Society og Gene & Cell Therapy Annual Meeting
  • Place of Presentation: Washington State Convention & Trade Center(米国）
• [Presentation] Development of Electromotor-Driven Injector for Hydrodynamic Gene Delivery. (2011)
  • Author(s): Yokoo K
  • Organizer: 14th American Society og Gene & Cell Therapy Annual Meeting
  • Place of Presentation: Washington State Convention & Trade Center（米国）
• [Book] 癌の臨床 (2011)
  • Author(s): 阿部聡司
  • Total Pages: 6
  • Publisher: 篠原出版新社
• [Book] 【非B非C型肝癌の現状と問題点】 Cryptogenic肝癌と他の非B非C型肝癌の臨床病理学的比較 消化器内科 (2011)
  • Author(s): 川合弘一
  • Total Pages: 7
  • Publisher: 科学評論社
• [Book] 【外来診療に有用な腫瘍マーカーの知識】 腫瘍マーカーの種類と特徴 AFP 臨牀と研究 (2011)
  • Author(s): 青柳 豊
  • Total Pages: 4
  • Publisher: 大道学館
• [Book] 【腫瘍マーカー-その今日的解釈(理解)と応用】 肝臓癌の腫瘍マーカー 成人病と生活習慣病 (2011)
  • Author(s): 青柳 豊
  • Total Pages: 6
  • Publisher: 東京医学社