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

2012 Fiscal Year Final Research Report

• 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
• Keywords: FUT8 / Cre-loxP / conditional knockout mouse / AFP-L3

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

• [Journal Article] Involvement of liver-intestine cadherin in cancer progression. (2013)
  • Author(s): Takamura M, Yamagiwa S, Matsuda Y, Ichida T, Aoyagi Y.
  • Journal Title: Med Mol Morphol. Volume: 46 Pages: 1-7
  • DOI: doi:10.1007/s00795-012-0003-y
  • Peer Reviewed
• [Journal Article] Human T cell leukemia virus type 2 (HTLV-2) Tax2 has a dominant activity over HTLV-1 Tax1 to immortalize humanCD4(+) T cells. (2012)
  • Author(s): Imai M, Higuchi M, Kawamura H, YoshitaM, Takahashi M, Oie M, Matsuki H, Tanaka Y, Aoyagi Y, Fujii M.
  • Journal Title: Virus Genes. Volume: 46 Pages: 39-46
  • DOI: doi:10.1007/s11262-012-0831-9
  • Peer Reviewed
• [Journal Article] Phase I study of miriplatin combined with transarterial chemotherapy using CDDP powder in patients with hepatocellular carcinoma. (2012)
  • Author(s): Kamimura K, Suda T, Tamura Y, TakamuraM, Yokoo T, Igarashi M, Kawai H, Yamagiwa S, Nomoto M, Aoyagi Y.
  • Journal Title: BMCGastroenterol Volume: 12 Pages: 127
  • DOI: doi:10.1186/1471-230X-12-127
  • Peer Reviewed
• [Journal Article] Increased Susceptibility to Severe Chronic Liver Damage in CXCR4 ConditionalKnock-Out Mice. (2012)
  • Author(s): Tsuchiya A, Imai M, Kamimura H, Takamura M, Yamagiwa S, Sugiyama T,Nomoto M, Heike T, Nagasawa T, Nakahata T, Aoyagi Y.
  • Journal Title: Dig Dis Sci Volume: 57 Pages: 2892-900
  • DOI: doi:10.1007/s10620-012-2239-8
  • Peer Reviewed
• [Journal Article] Identification of cellular genes showing differential expression associated with hepatitisB virus infection. (2012)
  • Author(s): Fukuhara Y, Suda T, KobayashiM, Tamura Y, Igarashi M, Waguri N, Kawai H, Aoyagi Y
  • Journal Title: World J Hepatol. Volume: 4(4) Pages: 139-48
  • DOI: doi:10.4254/wjh.v4.i4.139
  • Peer Reviewed
• [Journal Article] Formula to Predict Platelet Count after Partial Splenic Arterial Embolization in Patients with Hypersplenism. (2012)
  • Author(s): Osaki A, Suda T, Waguri N, Ishikawa T, Yokoo T, Kamimura K, Tamura Y,Takamura M, Igarashi M, Kawai H, Yamagiwa S, Aoyagi Y.
  • Journal Title: J VascInterv Radiol. Volume: 23 Pages: 900-7
  • DOI: doi:10.1016/j.jvir.2012.03.008
  • Peer Reviewed
• [Journal Article] Reduced NKG2D ligand expression in hepatocellular carcinoma correlates with earlyrecurrence. (2012)
  • Author(s): Kamimura H, Yamagiwa S, Tsuchiya A, Takamura M, Matsuda Y, Ohkoshi S,Inoue M, Wakai T, Shirai Y, Nomoto M, Aoyagi Y.
  • Journal Title: J. Hepatol. Volume: 56(2) Pages: 381-8
  • DOI: doi:10.1016/j.jhep.2011.06.017. Epub2011 Jul 12.
  • Peer Reviewed
• [Journal Article] Phase I study of miriplatin combined with transarterial chemotherapy using CDDP powder in patients with hepatocellular carcinoma. (2012)
  • Author(s): Kamimura K, Suda T, Tamura Y, TakamuraM, Yokoo T, Igarashi M, Kawai H, Yamagiwa S, Nomoto M, Aoyagi Y.
  • Journal Title: BMCGastroenterol. Volume: 12 Pages: 127
  • DOI: doi:10.1186/1471-230X-12-1274.
  • Peer Reviewed
• [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)
  • Author(s): Ohkoshi S, Yamagiwa S, Yano M, Takahashi H, Aoki YH, Waguri N,Igarashi K, Sugitani S, Takahashi T, Ishikawa T, Kamimura T, Wakabayashi H, Watanabe T, Matsuda Y, Aoyagi Y.
  • Journal Title: Hepatogastroenterology. Volume: 58(107-108) Pages: 965-70
  • Peer Reviewed
• [Journal Article] History and recent progress in evaluation of the fucosylated alpha-fetoprotein fraction (2011)
  • Author(s): Aoyagi Y, Tamura Y, Suda T, EDITORIAL
  • Journal Title: JGastroenterol Hepatol Volume: 26(4) Pages: 615-6
  • DOI: doi:10.1111/j.1440-1746.2011.06671.x.
  • Peer Reviewed
• [Journal Article] Hepatocellular carcinoma with progenitor cell features distinguishable by the hepatic stem/progenitor cell marker NCAM. (2011)
  • Author(s): Tsuchiya A, Kamimura H, Tamura Y, Takamura M, Yamagiwa S, Suda T, NomotoM, Aoyagi Y.
  • Journal Title: Cancer Lett. Volume: 309(1) Pages: 95-103
  • DOI: doi:10.1016/j.canlet.2011.05.021. Epub2011 Jun 12.
  • Peer Reviewed
• [Journal Article] The initial phase of chromosome condensation requires Cdk1-mediated phosphorylation of the CAP-D3 subunit of condensin II. (2011)
  • Author(s): Abe S, Nagasaka K, Hirayama Y, Kozuka-Hata H, Oyama M, Aoyagi Y,Obuse C, Hirota T.
  • Journal Title: Genes Dev. Volume: 25(8) Pages: 863-74
  • DOI: doi:10.1101/gad.2016411.
  • Peer Reviewed
• [Journal Article] Characterization of elevated alanine aminotransferase levels duringpegylated-interferon α-2b plus ribavirin treatment for chronic hepatitis C. (2011)
  • Author(s): Aoki YH, Ohkoshi S, Yamagiwa S, YanoM, Takahashi H, Waguri N, Igarashi K, Sugitani S, Takahashi T, Ishikawa T, Kamimura T, Wakabayashi H, Watanabe T, Matsuda Y, Nomoto M, Aoyagi Y.
  • Journal Title: Hepatol Res. Volume: 41(2) Pages: 118-25
  • DOI: doi:10.1111/j.1872-034X.2010.00749.x.
  • Peer Reviewed
• [Journal Article] Aoyagi Y Multicentric occurrence of hepatocellular carcinoma with nonalcoholic steatohepatitis (2011)
  • Author(s): Kawai H, Nomoto M, Suda T, Kamimura K, Tsuchiya A, Tamura Y, Yano M, TakamuraM, Igarashi M, Wakai T, Yamagiwa S, Matsuda Y, Ohkoshi S, Kurosaki I, Shirai Y, Okada M
  • Journal Title: World JHepatol Volume: 3(1) Pages: 15-23
  • DOI: doi:10.4254/wjh.v3.i1.15.
  • Peer Reviewed
• [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
  • Place of Presentation: University of Vienna(Vienna,Austria)
  • Year and Date: 2013-02-12
• [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
  • Place of Presentation: Hynes Convention Center(Boston,USA)
  • Year and Date: 2012-11-09
• [Presentation] Comparative proteomic analysis of the liver in a murine model of non-alcoholic steatohepatitis (2012)
  • Author(s): Takamura M, Xu B,Yamagiwa S,Matsuda Y,Shimada S,Zhang Y,Yoshida Y,Yaoita E, Nomoto M, Yamamoto T,Aoyagi Y.
  • Organizer: The63rd Annual Meeting of the AASLD
  • Place of Presentation: Hynes ConventionCenter(Boston,USA)
  • Year and Date: 2012-11-09
• [Presentation] Nutritional intervention in cirrhotic patients with hepatocellular carcinoma on the basis of energy state assessment (2012)
  • Author(s): Suda T,Kanefuji T,Aoyagi Y.
  • Organizer: The 3rd Asian-Pacific Topic Conference.
  • Place of Presentation: ShibaPark Hotel(Tokyo)
  • 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] 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