Basic research objected to establish the highly qualified assessment of hepatic reserve function by utilizing new molecular marker localized in liver

2009 Fiscal Year Final Research Report

• Project/Area Number: 19390353
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Sapporo Medical University
• Principal Investigator: HIRATA Koichi Sapporo Medical University, 医学部, 教授 (50136959)
• Co-Investigator(Kenkyū-buntansha): 澤田 典均 札幌医科大学, 医学部, 教授 (30154149) ; 三高 俊広 札幌医科大学, 医学部, 教授 (50231618) ; 小島 隆 札幌医科大学, 医学部, 准教授 (30260764) ; 水口 徹 札幌医科大学, 医学部, 講師 (30347174) ; 今村 将史 札幌医科大学, 医学部, 助教 (00404608) ; 信岡 隆幸 札幌医科大学, 医学部, 助教 (50404603) ; 川本 雅樹 札幌医科大学, 医学部, 兼任助教 (70404605) ; 中村 幸雄 札幌医科大学, 医学部, 研究員 (50516648) ; 孫 誠一 札幌医科大学, 医学部, 研究員 (60404612) ; 柴田 稔人 札幌医科大学, 医学部, 研究員 (80404622) ; 梶 晋輔 札幌医科大学, 医学部, 研究員 (90404623)
• Project Period (FY): 2007 – 2009
• Keywords: 肝予備能評価 / 新規分子 / 肝不全 / 胆汁うっ滞 / 接着装置 / 肝幹細胞 / 細胞移植

Research Abstract

The researches were composed of three kinds of contents as follows : (1) the studies about low localized molucules utilized for the assessments of hepatic function, (2) the regulation on isolation, identification and proliferation of hepatic stem cells recognized to have key roles and (3) the possibility of gene-transfected hepatocyte or heparic stem cell on the treatment for hepatic dysfunction. Our results showed (1) the logical significance of asialoglycoprotein receptor count method and the distribution of adhesion molecules (especially claudins) on hepatic cell function, (2) successful modification of hepatic stem cells in vitro, and (3) the clinical capability by the cell transplantation utilized gene-transfected hepatocytes or fresh hepatic stem cells.

Research Products

• [Journal Article] Prognostic impact of surgical complications and preoperative serum hepatocyte growth factor in hepatocellular carcinoma patients after initial hepatectomy. (2009)
  • Author(s): Mizuguchi T, Nagayama M, Meguro M, Shibata T, Kaji S, Nobuoka T, Kimura Y, Furuhata T, Hirata K
  • Journal Title: J Gastrointest Surg 13(2) Pages: 325-33
  • Peer Reviewed
• [Journal Article] Impaired liver regeneration with humoral and genetic disturbances in urinary trypsin inhibitor-deficient mice. (2009)
  • Author(s): Nobuoka T, Mizuguchi T, Oshima H, Shibata T, Kaji S, Nagayama M, Meguro M, Mitaka T, Hirata K
  • Journal Title: Liver Int 29(7) Pages: 979-87
  • Peer Reviewed
• [Journal Article] Knockdown of tight junction protein claudin-2 prevents bile canalicular formation in WIF-B9 cells. (2009)
  • Author(s): Son S, Kojima T, Decaens C, Yamaguchi H, Ito T, Imamura M, Murata M, Tanaka S, Chiba H, Hirata K, Sawada N
  • Journal Title: Histochem Cell Biol 131 Pages: 411-424
  • Peer Reviewed
• [Journal Article] Tight junction proteins and signal transduction pathways in hepatocytes. (2009)
  • Author(s): Kojima T, Murata M, Yamamoto T, Lan M, Son S, Takano K-I, Yamaguchi H, Ito T, Tanaka S, Chiba H, Hirata K, Sawada N
  • Journal Title: Histol Histopathol 24 Pages: 1463-1472
  • Peer Reviewed
• [Journal Article] Functional Expression of Organic Anion Transporters in Hepatic Organoids Reconstructed by Rat Small Hepatocytes. (2008)
  • Author(s): Oshima H, Kon J, Ooe H, Hirata K, Mitaka T
  • Journal Title: Cell Biochem 104(1) Pages: 68-81
  • Peer Reviewed
• [Journal Article] In vitro transformation of adult rat hepatic progenitor cells into pancreatic endocrine hormone-producing cell. (2008)
  • Author(s): Kawasaki H, Mizuguchi T, Kikkawa Y, Oshima H, Sasaki Y, Tokino T, Kokai Y, Miyazaki J, Mitaka T, Hirata K
  • Journal Title: J Hepatobiliary Pancreat Surg 5(3) Pages: 310-317
  • Peer Reviewed
• [Journal Article] Efficient transformation of small hepatocytes into insulin-expressing cells by forced expression of Pdx1. (2008)
  • Author(s): Kawasaki H, Mizuguchi T, Oshima H, Nobuoka T, Shibata T, Kaji S, Kokai Y, Katsuramaki T, Mitaka T, Hirata K
  • Journal Title: J Hepatobiliary Pancreat Surg 15(4) Pages: 403-409
  • Peer Reviewed
• [Journal Article] Proliferation of Hepatocyte Progenitor Cells Isolated from Adult Human livers in Serum-free Medium. (2008)
  • Author(s): Sasaki K, Kon J, Mizuguchi T, Chen J, Ooe H, Oshima H, Hirata K, Mitaka T
  • Journal Title: Cell Transplantation 17(10-11) Pages: 1221-1230
  • Peer Reviewed
• [Journal Article] Rapid Recovery of Postoperative Liver Function after Major Hepatectomy using Saline-linked Electric Cautery. (2008)
  • Author(s): Toru Mizuguchi, Tadashi Katsuramaki, Minoru Nagayama, Makoto Meguro, Toshihito Shibata, Shinsuke Kaji, Koichi Hirata
  • Journal Title: Hepato-Gastroenterology 55 Pages: 2188-2192
  • Peer Reviewed
• [Journal Article] Laminin alpha 5 mediates ectopic adhesion of hepatocellular carcinoma through integrins and/or Lutheran/ basal cell adhesion molecule. (2008)
  • Author(s): Kikkawa Y, Sudo R, Kon J, Mizuguchi T, Nomizu M, Hirata K, Mitaka T
  • Journal Title: Exp Cell Res 314(14) Pages: 2579-90
  • Peer Reviewed
• [Journal Article] Oncostatin M induces upregulation of claudin-2 in rodent hepatocytes coinciding with changes in morphology and function of tight junctions. (2007)
  • Author(s): Imamura M, Kojima T, Lan M, Son S, Murata M, Osanai M, Chiba H, Hirata K, Sawada N
  • Journal Title: Exp Cell Res 313 Pages: 1951-1962
  • Peer Reviewed
• [Journal Article] New strategy for the antifibrotic therapy with oral administration of FR260330 (a selective inducible nitric oxide synthase inhibitor) in rat experimental liver cirrhosis. (2007)
  • Author(s): Kikuchi H, Katsuramaki T, Kukita K, Taketani S, Meguro M, Nagayama M, Isobe M, Mizuguchi T, Hirata K
  • Journal Title: Wound Repair Regen 15(6) Pages: 881-8
  • Peer Reviewed
• [Journal Article] Analysis of the changes pattern of serum apolipoprotein A-1 after hepatectomy. (2006)
  • Author(s): Katsuramaki T, Mizuguchi T, Nagayama M, Kimura Y, Furuhata T, Yamaguchi K, Hata F, Hirata K
  • Journal Title: Hepatogastroenterology 53(72) Pages: 924-7
  • Peer Reviewed