Importance of NK cells and intrahepatic immune responses for the acceleration of hepatitis C after liver transplantation

• Project/Area Number: 21590834
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Niigata University
• Principal Investigator: YAMAGIWA Satoshi 新潟大学, 医歯学系, 助教 (10419327)
• Co-Investigator(Kenkyū-buntansha): TAKAMURA Masaaki 新潟大学, 医歯学総合病院, 医員 (20422602) ; MATSUDA Yasunobu 新潟大学, 医歯学系, 准教授 (40334669) ; SATO Yoshinobu 新潟大学, 医歯学系, 講師 (20313538)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 肝臓学 / 肝移植 / C型肝肝炎 / NK細胞 / 移植・再生医療 / C型肝炎

Research Abstract

The activating receptor natural killer group 2, member D(NKG2D) and its ligands play a crucial role in immune response to infections and tumors. Among the human NKG2D ligands, ULBP1 is prevalently expressed in hepatocellular carcinoma(HCC), but loss of its expression correlates with tumor progression and early recurrence. Although we could not find any significant changes in the gene expression profiles among the recurrent hepatitis C patients and chronic hepatitis C patients yet, our results suggest that the status of intrahepatic NK cell subsets and NK cell receptor ligand expressions might be associated with the rapid progression of recurrent hepatitis C infection.

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] Blockade of ataxia telangiectasia mutated sensitizes hepatoma cell lines to sorafenib by interfering with Akt signaling (2012)
  • Author(s): Fujimaki S, Matsuda Y, Wakai T, Sanpei A, Kubota M, Takamura M, Yamagiwa S, Yano M, Ohkoshi S, Aoyagi Y
  • Journal Title: Cancer Lett Volume: 319(1) Pages: 98-108
  • Peer Reviewed
• [Journal Article] Reduced NKG2D ligand expression in hepatocellular carcinoma correlates with early recurrence (2012)
  • Author(s): Kamimura H
  • Journal Title: J.Hepatol. Volume: 56 Issue: 2 Pages: 381-8
  • DOI: 10.1016/j.jhep.2011.06.017
  • Peer Reviewed
• [Journal Article] Blockade of ataxia telangiectasia mutated sensitizes hepatoma cell lines to sorafenib by interfering with Akt signaling (2012)
  • Author(s): Fujimaki S
  • Journal Title: Cancer Lett. Volume: 319 Issue: 1 Pages: 98-108
  • DOI: 10.1016/j.canlet.2011.12.043
  • Peer Reviewed
• [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)
  • 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] Characterization of elevated alanine aminotransferase levels during pegylated-interferonα-2b plus ribavirin treatment for chronic hepatitis C (2011)
  • Author(s): Aoki YH, Ohkoshi S, Yamagiwa S, Yano M, 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
  • 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: World J. Hepatol Volume: 3(1) Pages: 15-23
  • Peer Reviewed
• [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)
  • Author(s): Ohkoshi S, Yamagiwa S, et al.
  • Journal Title: Hepatogastroenterology Volume: 58(107-108) Pages: 965-970
  • Peer Reviewed
• [Journal Article] Characterization of elevated alanine aminotransferase levels during pegylated- interferon α-2b plus ribavirin treatment for chronic hepatitis C (2011)
  • Author(s): Aoki YH, Ohkoshi S, Yamagiwa S, et al.
  • Journal Title: Hepatology Research Volume: 41(2) Pages: 119-125
  • Peer Reviewed
• [Journal Article] Multicentric occurrence of hepatocellular carcinoma with nonalcoholic steato-hepatitis (2011)
  • Author(s): Kawai H, Nomoto M, Yamagiwa S, et al.
  • Journal Title: World Journal of Hepatology Volume: 3(1) Pages: 15-23
  • Peer Reviewed
• [Journal Article] Very-Low-Dose Pegylated Interferon a2a Plus Ribavirin Therapy for Advanced Liver Cirrhosis Type C : A Possible Therapeutic Alternative without Splenic Intervention (2010)
  • Author(s): Ohkoshi S, Yamagiwa S, Yano M, Takahashi H, Aoki YH, Matsuda Y, Aoyagi Y
  • Journal Title: Case Rep. Gastroenterol Volume: 4(2) Pages: 261-6
  • Peer Reviewed
• [Journal Article] Shear wave 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] The "Senobi" breathing exercise is recommended as first line treatment for obesity (2010)
  • Author(s): Sato K, Kawamura T, Yamagiwa S
  • Journal Title: Biomed. Res Volume: 31(4) Pages: 259-62
  • 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] Very-low-dose pegylated interferon α2a plus ribavirin therapy for advanced liver cirrhosis type C : a possible therapeutic alternative without splenic intervention (2010)
  • Author(s): Ohkoshi S, Yamagiwa S, et al.
  • Journal Title: Case Reports in Gastroenterology Volume: 4(2) Pages: 261-266
  • Peer Reviewed
• [Journal Article] Shear wave velocity is a useful marker of managing nonalcoholic steatohepatitis (2010)
  • Author(s): Osaki A, Kubota T, Yamagiwa S, et al.
  • Journal Title: World Journal of Gastroenterology Volume: 16(23) Pages: 2918-2925
  • Peer Reviewed
• [Journal Article] The "Senobi" breathing exercise is recommended as first line treatment for obesity (2010)
  • Author(s): Sato K, Kawamura T, Yamaeiwa S
  • Journal Title: Biomedical Research Volume: 31(4) Pages: 259-262
  • 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, et al.
  • Journal Title: International Journal of Oncology 36(1) Pages: 245-254
  • Peer Reviewed
• [Journal Article] Clinicopathological analysis of CD133^+and NCAM^+human hepatic stem/progenitor cells in damaged livers and hepatocellular carcinomas (2009)
  • Author(s): Tsuchiya A, Kamimura H, Takamura M, Yamagiwa S, Matsuda Y, Sato Y, Nomoto M, Ichida T, Aoyagi Y
  • Journal Title: Hepatol. Res Volume: 39(11) Pages: 1080-90
  • NAID: 10027405577
  • Peer Reviewed
• [Journal Article] The Niigata liver disease study group. 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
  • Journal Title: Dig. Dis. Sci Volume: 54(11) Pages: 2530-7
  • 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, et al.
  • Journal Title: Digestive Diseases and Sciences 54(11) Pages: 2530-2537
  • Peer Reviewed
• [Journal Article] Clinicopathological analysis of CD133^+ and NCAM^+ human hepatic stem/progenit or cells in damaged livers and hepatocellular carcinomas. (2009)
  • Author(s): Tsuchiya A, Kamimura H, Takamura M, Yamagiwa S, et al.
  • Journal Title: Hepatology Research 39(11) Pages: 1080-1090
  • Peer Reviewed
• [Presentation] Reduced NKG2D ligand expression in hepatocellular carcinoma correlates with early recurrence (2011)
  • Author(s): Yamagiwa S, et al
  • Organizer: The 62^<nd> annual meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: Moscone West Convention center(San Francisco,米国)
  • Year and Date: 2011-11-07
• [Presentation] Reduced NKG2D ligand expression in hepatocellular carcinoma correlate with early recurrence (2011)
  • Author(s): Yamagiwa S, et al.
  • Organizer: The 62^<nd> annual meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: Moscone West Convention center (San Francisco,米国)
  • Year and Date: 2011-11-07
• [Presentation] 肝細胞癌におけるNK細胞活性化レセプターリガンド発現低下とその臨床的意義 (2011)
  • Author(s): 山際訓, 他
  • Organizer: 第15回日本肝臓学会大会
  • Place of Presentation: マリンメッセ福岡(福岡市)
  • Year and Date: 2011-10-20
• [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, 他
  • 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LE DAIBA(東京都港区)
  • Year and Date: 2011-06-03
• [Presentation] C型慢性肝炎に対するPEG-IFNα-2a/Ribavirin併用療法における血清CXCL10値と治療効果の検討-新潟県多施設共同研究- (2010)
  • Author(s): 山際訓, 他
  • Organizer: 第14回日本肝臓学会大会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2010-10-13
• [Presentation] C型慢性肝炎に対するPEG-IFNa-2a/Ribavirin併用療法における血清CXCL10値と治療効果の検討-新潟県多施設共同研究- (2010)
  • Author(s): 山際訓, 他
  • Organizer: 第14回日本肝臓学会大会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2010-10-13
• [Presentation] 肝細胞癌におけるNK細胞活性化レセプターリガンド発現とその調節による抗腫瘍効果増強の可能性 (2010)
  • Author(s): 上村博輝,山際訓, 他
  • Organizer: 第42回日本臨床分子形態学会総会
  • Place of Presentation: 東レ総合研修センター(三島市)
  • Year and Date: 2010-09-25
• [Presentation] 肝細胞癌におけるNK細胞活性化レセプターリガンド発現とその調節による抗腫砺効果増強の可能性 (2010)
  • Author(s): 上村博輝, 山際訓, 他
  • Organizer: 第42回日本臨床分子形態学会総会
  • Place of Presentation: 東レ総合研修センター(三島市)
  • Year and Date: 2010-09-25
• [Presentation] 肝細胞癌における分子標的としてのNK細胞活性化レセプターリガンドとその発現調節による抗腫瘍効果 (2010)
  • Author(s): 上村博輝,山際訓, 他
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形国際ホテル(山形市)
  • Year and Date: 2010-05-27
• [Presentation] C型肝炎の持続感染と抗腫瘍免疫機構からの逃避に関与するNK細胞活性化レセプターリガンド (2010)
  • Author(s): 上村博輝,山際訓, 他
  • Organizer: 第96回日本消化器病学会総会
  • Place of Presentation: 朱鷺メッセ(新潟市)
  • Year and Date: 2010-04-23
• [Presentation] C型肝炎の持続感染と抗腫瘍免疫機構からの逃避に関与するNK細胞活性化レセブターリガンド (2010)
  • Author(s): 上村博輝, 山際訓, 他
  • Organizer: 第96回日本消化器病学会総会
  • Place of Presentation: 朱鷺メッセ(新潟市)
  • Year and Date: 2010-04-23
• [Presentation] 肝移植後C型肝炎再発例における肝内NK細胞亜分画 (2009)
  • Author(s): 山際訓, 他
  • Organizer: 第27回日本肝移植研究会
  • Place of Presentation: 東レ総合研修センター(三島市)
  • Year and Date: 2009-07-10