Development of treatment strategy for patients with hepatocellular carcinoma using serum glycosylation modification

2011 Fiscal Year Final Research Report

• Project/Area Number: 20390205
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• 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): UCHIUMI Toshio 新潟大学, 自然科学系, 教授 (50143764) ; OHKOSHI Shogo 新潟大学, 医歯学系, 講師 (70231199) ; SUDA Takeshi 新潟大学, 医歯学系, 講師 (10361916)
• Project Period (FY): 2008 – 2011
• Keywords: 肝細胞癌 / 糖鎖 / α1-6フコース転位酵素(FUT8) / アルファフェトプロテイン

Research Abstract

Fucosylated fraction of alpha-fetoprotein, AFP-L3, is the product ofα1-6 fucosyltransferase(FUT8) in the presence of GDP-fucose and is an indicator of unfavorable prognosis in patients with hepatocellular carcinoma(HCC). The aim of this study is to investigate physiological function of the core fucose in HCC cell lines using not only small interfering RNA(siRNA) but a FUT8 conditional gene knockdown tool. Real-time PCR analysis showed that the FUT8 mRNA level was knocked down 48h after siRNA transfection. On the other hand, we found no significant change in cell growth and infiltration. And no significant reduction in producing intracellular fucosylated proteins was observed by sugar chain profiling analysis using lection microchip. Next, we established conditional FUT8 knockdown mice, and characterized their molecular background of FUT8. We plan to carry out the experiments of hepatocarcinogenesis on the FUT8 knockdown mice.

Research Products

• [Journal Article] Reduced NKG2D ligand expression in hepatocellular carcinoma correlates with early recurrence (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
  • 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, Nomoto M, Aoyagi Y.
  • Journal Title: Cancer Lett. Volume: 309(1) Pages: 95-103
  • 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
  • Journal Title: J Gastroenterol Hepatol Volume: 26(4) Pages: 615-6
  • 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
  • Peer Reviewed
• [Journal Article] 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, Takamura M, Igarashi M, Wakai T, Yamagiwa S, Matsuda Y, Ohkoshi S, Kurosaki I, Shirai Y, Okada M, Aoyagi Y
  • Journal Title: Polyhedron Volume: 3(1) Pages: 15-23
  • Peer Reviewed
• [Journal Article] Clinical Advantage of Highly Sensitive On-Chip Immunoassay for Fucosylated Fraction of Alpha-Fetoprotein in Patients with Hepatocellular Carcinoma. (2010)
  • Author(s): Tamura Y, Igarashi M, Kawai H, Suda T, Satomura S, Aoyagi Y.
  • Journal Title: Dig Dis Sci. Volume: 55(12) Pages: 3576-83
  • Peer Reviewed
• [Journal Article] Fucosylated fraction of alpha-fetoprotein as a predictor of prognosis in patients with hepatocellular carcinoma after curative treatment (2010)
  • Author(s): Tamura Y, Igarashi M, Suda T, Wakai T, Shirai Y, Umemura T, Tanaka T, Kakizaki S, Takagi H, Hiasa Y, Onji M, Aoyagi Y.
  • Journal Title: Dig Dis Sci. Volume: 55(7) Pages: 2095-101
  • Peer Reviewed
• [Journal Article] Shearwave velocity is a useful marker for managing nonalcoholic steatohepatitis (2010)
  • Author(s): Osaki A, Kubota T, Suda T, Igarashi M, Nagasaki K, Tsuchiya A, Yano M, Tamura Y, Takamura M, Kawai H, Yamagiwa S, Kikuchi T, Nomoto M, Aoyagi Y.
  • Journal Title: World J Gastroenterol. Volume: 16(23) Pages: 2918-25
  • Peer Reviewed
• [Journal Article] Clonally expanding thymocytes having lineage capability ingamma-ray-induced mouse atrophic thymus (2010)
  • Author(s): Yamamoto T, Morita S, Go R, Obata M, Katsuragi Y, Fujita Y, Maeda Y, Yokoyama M, Aoyagi Y, Ichikawa H, Mishima Y, Kominami R.
  • Journal Title: Int J Radiat Oncol Biol Phys. Volume: 77(1) Pages: 235-43
  • Peer Reviewed
• [Journal Article] Clonally expanding thymocytes having lineage capability in gamma-ray-induced mouse atrophic thymus (2010)
  • Author(s): Yamamoto T, Morita S, Go R, Obata M, Katsuragi Y, Fujita Y, Maeda Y, Yokoyama M, Aoyagi Y, Ichikawa H, Mishima Y, Kominami R.
  • Journal Title: Int J Radiat Oncol Biol Phys. Volume: 77(1) Pages: 235-43
  • Peer Reviewed
• [Journal Article] The PDZ domain binding motif(PBM) of human T-cell leukemia virus type 1 Tax can be substituted by heterologous PBMs from viral oncoproteins during T-cell transformation (2010)
  • Author(s): Aoyagi T, Takahashi M, Higuchi M, Oie M, Tanaka Y, Kiyono T, Aoyagi Y, Fujii M.
  • Journal Title: Virus Genes. Volume: 40(2) Pages: 193-9
  • Peer Reviewed
• [Journal Article] Loss of liver-intestine cadherin in human intrahepatic cholangiocarcinoma promotes angiogenesis by up-regulating metal-responsive transcription factor-1 and placental growth factor (2010)
  • Author(s): Takamura M, Yamagiwa S, Wakai T, Tamura Y, Kamimura H, Kato T, Tsuchiya A, Matsuda Y, Shirai Y, Ichida T, Ajioka Y, Aoyagi Y.
  • Journal Title: Int J Oncol. Volume: 36(1) Pages: 245-54
  • Peer Reviewed
• [Journal Article] Serum alpha-fetoprotein levels during and after interferon therapy and the development of hepatocellular carcinoma in patients with chronic hepatitis C (2009)
  • Author(s): Tamura Y, Yamagiwa S, Aoki Y, Kurita S, Suda T, Ohkoshi S, Nomoto M, Aoyagi Y.
  • Journal Title: Dig Dis Sci. Volume: 54(11) Pages: 2530-7
  • Peer Reviewed
• [Journal Article] Oxidative stress induces anti-hepatitis C virus status via the activation of extracellular signal-regulated kinase (2009)
  • Author(s): Yano M, Ikeda M, Abe KI, Kawai Y, Kuroki M, Mori K, Dansako H, Ariumi Y, Ohkoshi S, Aoyagi Y, Kato N.
  • Journal Title: Hepatology. Volume: 50(3) Pages: 678-88
  • Peer Reviewed
• [Journal Article] Progress toward liver-based gene therapy (2009)
  • Author(s): Suda T, Kamimura K, Kubota T, Tamura Y, Igarashi M, Kawai H, Aoyagi Y, Liu D.
  • Journal Title: Hepatol Res. Volume: 39(4) Pages: 325-40
  • Peer Reviewed
• [Journal Article] Progression of hypermethylation of the p16(INK4A) gene from normal liver to nontumorous liver and hepatocellular carcinoma : an evaluation using quantitative PCR analysis (2009)
  • Author(s): Kurita S, Ohkoshi S, Yano M, Yamazaki K, Suzuki K, Aoki YH, Matsuda Y, Wakai T, Shirai Y, Ichida T, Aoyagi Y.
  • Journal Title: Dig Dis Sci. Volume: 54(1) Pages: 80-8
  • Peer Reviewed
• [Journal Article] Featuresof hepatocellular carcinoma in cases with autoimmune hepatitis and primary biliary cirrhosis (2009)
  • Author(s): Watanabe T, Soga K, Hirono H, Hasegawa K, Shibasaki K, Kawai H, Aoyagi Y.
  • Journal Title: J Gastroenterol. Volume: 15(2) Pages: 231-9
  • Peer Reviewed
• [Journal Article] Sustained response to interferon-alpha plus ribavirin therapy for chronic hepatitis C is closely associated with increased dynamism of intrahepatic natural killer and natural killer T cells (2008)
  • Author(s): Yamagiwa S, Matsuda Y, Ichida T, Honda Y, Takamura M, Sugahara S, Ishikawa T, Ohkoshi S, Sato Y, Aoyagi Y.
  • Journal Title: Hepatol Res. Volume: 38(7) Pages: 664-72
  • Peer Reviewed
• [Journal Article] Sca-1+endothelial cells(SPECs) reside in the portal area of the liver and contribute to rapid recovery from acute liver disease (2008)
  • Author(s): Tsuchiya A, Heike T, Baba S, Fujino H, Umeda K, Matsuda Y, Nomoto M, Ichida T, Aoyagi Y, Nakahata T.
  • Journal Title: Biochem Biophys Res Commun. Volume: 365 Pages: 595-601
  • Peer Reviewed
• [Journal Article] Rearranged NF-kappa B2 gene in an adult T-cell leukemia cell line (2008)
  • Author(s): Isogawa M, Higuchi M, Takahashi M, Oie M, Mori N, Tanaka Y, Aoyagi Y, Fujii M.
  • Journal Title: Cancer Sci. Volume: 99(4) Pages: 792-8
  • Peer Reviewed
• [Presentation] Development of Electromotor-Driven Injector for Hydrodynamic Gene Delivery. (2011)
  • Author(s): Suda T, Yokoo K, Kamimura K, Oda M, Zhang G, Liu D, Aoyagi Y.
  • Organizer: 14^<th> American Society og Gene & Cell Therapy Annual Meeting
  • Place of Presentation: WashingtonStateConv ention & Trade Center.
  • Year and Date: 2011-05-19
• [Presentation] Interferon-B Prevents HBX-Triggered Hepatococarcinogenesis By Down-Regulating Cytoplasmic P21 Over expression. (2011)
  • Author(s): Yano M, Ohkoshi S, Aoki Y, Matsuda Y, Aoyagi Y
  • Organizer: 46^<th> Annual Meeting Of The European Association For The Study Of The Liver(EASL 2011)
  • Place of Presentation: 国際会議場122ベルリン
  • Year and Date: 2011-03-29
• [Presentation] APM2 is a Candidate of Predictive Marker for Cisplatin Sensitivity in Hepatocellular Carcinoma. (2011)
  • Author(s): Kamimura K, Suda T, Fukuhara Y, Osaki A, Aoyagi Y.
  • Organizer: 3^<rd> JCA-AACR Special Joint Conference
  • Place of Presentation: 東京ベイ舞浜ホテルクラブリゾート
  • Year and Date: 2011-03-02
• [Presentation] Oxidative Stress Induces Anti-HCV Status via the Activation of MEK-ERK1/2 Signaling Pathway. (2009)
  • Author(s): Yano M, Matsuda K, Ohkoshi S, Aoyagi Y.
  • Organizer: 2009 AASLD.
  • Place of Presentation: Hynes Convention Center
  • Year and Date: 2009-10-30
• [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,田村康,五十嵐正人,川合弘一,須田剛士
  • Total Pages: 941-944
  • 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,田村康,五十嵐正人,川合弘一,須田剛士
  • Total Pages: 648-653
  • Publisher: 東京医学社
• [Book] 【肝疾患における血液生化学検査、肝炎ウイルスマーカー、腫瘍マーカーの見方】腫瘍マーカーAFP濃度、AFP L3分画、PIVKA-II肝・胆・膵 (2010)
  • Author(s): 青柳豊,田村康,五十嵐正人,川合弘一,須田剛士
  • Total Pages: 669-679
  • Publisher: アークメディア
• [Book] 【早期肝細胞癌の診断ストラテジー】肝細胞癌診断、予後予測における高感度AFP-L3測定法の臨床的有用性消化器内科 (2010)
  • Author(s): 田村康,五十嵐正人,川合弘一,須田剛士,青柳豊
  • Total Pages: 504-510
  • Publisher: 科学評論社
• [Book] 肝癌バイオマーカー研究の現在血液(血漿・血清)からの探索The Liver Cancer Journal (2009)
  • Author(s): 田村康,五十嵐正人,川合弘一,須田剛士,青柳豊
  • Total Pages: 97-103
  • Publisher: メディカルレビュー社
• [Book] 【肝細胞癌の治療2009～2011】肝細胞癌の血液診断コンセンサス癌治療 (2009)
  • Author(s): 青柳豊,須田剛士
  • Total Pages: 131-133
  • Publisher: へるす出版