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New Immunotherapy for hepatocellular carcinoma after hepatectomy

Research Project

Project/Area Number 05671066
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionYamaguchi University

Principal Investigator

OKA Masaaki  Yamaguchi University School of Medicine Associate Professor, 医学部, 助教授 (70144946)

Co-Investigator(Kenkyū-buntansha) HAZAMA Shoichi  Yamaguchi University School of Medicine Research Associate, 医学部, 助手 (50253159)
SUZUKI Takashi  Yamaguchi University School of Medicine Professor, 医学部, 教授 (20026834)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordshepatocellular carcinoma / hepatectomy / IL-2 / immunotherapy / intraarterial infusion / liver regeneration / apoptosis / prognosis / 細胞障害性T細胞 / 免疫組織染色 / リンパ球サブセット
Research Abstract

Experimental study : The influence of IL-2 on liver regeneration was examined using mitotic index (MI) and the bromodeoxyuridine (BrdU) labeling index (LI) in 70% hepatectomized Donryu rats. IL-2 (45,000 JRU/day) or saline was administered continuously via the portal vein immediately after hepatectomy using an infusion pump. No difference in the weight of the liver, serum Alb, GPT,or Bil was observed in any groups at 1,2, or 4 days after hepatectomy. Gap junctions began to disappear after hepatectomy and reached a minimum on day 2 in all groups. Four days after hepatectomy, the density of the reappearing gap junctions was markedly lower in groups treated with IL-2 than in those receiving saline. However, the density returned to close to preoperative levels 6 days after hepatectomy in all groups. Continuous portal infusion of LI-2 transiently disturbed gap junction reappearance during liver regeneration. However, no other parameters of liver regeneration or liver functions differed. The … More se results suggest that intrahepatic IL-2 administration can be performed without serious complications after hepatectomy.
Clinical Study : We performed intraarterial combined immunotherapy (ACIT) for 12 paticnts with hepatocellular carcinoma (HCC) 14 days after hepatectomy. ACIT consists of IL-2, OK-432, adriamycin, cyclophosphamide, and famotidine. The 3-year survial rate of treated patients was 100%, while, that of 38 untreated patiens was 60%. Thus, intraarterial combined immunotherapy following hepatectomy significantly improved the survival rate in patients with HCC.Three patients with HCC were treated with ACIT.Histological analysis using the resected specimen revealed massive invasion of lymphocytes around HCC lesions. Immunohistochemical analysis demonstrated that the major invaded lymphocytes were the CD8 positive and HLA-DR positive lymphocytes.Furthermore, in the lymphocyte infiltrating area, the Fas antigen in tumor cells were strongly expressed. In conclusion, the antitumor effect of ACIT may be related with the activation of tumor infiltrating lymphocytes. These lymphocytes may kill tumor cells in an apoptotic fashion. Less

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Masaaki Oka, et al.: "Intraarterial combined immunochemotherapy for unresectable hepatocellular carcinoma : preliminary study." Cancer Immunology Immunotherapy. 38. 194-200 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masaaki Oka, et al.: "Depression of cytotoxicity of nonparenchymal cells on the liver after surgery" Surgery. 116. 877-882 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Norio Iizuka, Masaaki Oka, et al.: "NM23-H1 and NM23-H2 messenger RNA abundance in human hepatocellular carcinoma." Cancer Research. 55. 652-657 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masaaki Oka, Shoichi Hazama, et al.: "Histological analysis of hepatocellular carcinoma treated by intraarterial combined immunochemotherapy." Hepato-Gastroenterology. 42. 561-566 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masaaki Oka, et al.: "Immunological evaluation of responders of intraarterial combined immunochemotherapy for unresectable hepatocellular carcinoma." Cancer Detection and Prevention,. (in Press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kenji Wadamori, Masaaki Oka, et al.: "Influence of continuous Interleukin-2 administration via the portal vein on liver regeneration following partial hepatectomy in rats." Hepatology,. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masaaki Oka, et al.: "Intraarterial combined immunochemotherapy for unresectable hepatocellular carcinoma : preliminary study." Cancer Immunology Immunotherapy. 38. 194-200 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masaaki Oka, et al.: "Depression of cytotoxicity of nonparenchymal cells on the liver after surgery" Surgery. 116. 877-882 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Norio Iizuka, Masaaki Oka, et al.: "NM23-H1 and NM23-H2 messenger RNA abundance in human hepatocellular carcinoma." Cancer Reaesrch. 55. 652-657 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masaaki Oka, Shoichi Hazama, et al.: "Histological analysis of hepatocellular carcinoma treated by intraarterial combined immunochemotherapy." Hepato-Gastroenterology. 42. 561-566 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masaaki Oka, et al.: "Immunological evaluation of responders of intraarterial combined immunochemotherapy for unresectable hepatocellular carcinoma." Cancer Detection and Prevention. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kenji Wadamori, Masaaki Oka, et al.: "Influence of continuous Interleukin-2 administration via the portal vein on liver regeneration following partial hepatectomy in rats." Hepatology. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Norio Iizuka,Masaaki Oka,et al.: "NM23-H1 and NM23-H2 messenger RNA abundance in human hepatocellular carcinoma." Cancer Research. 55. 652-657 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Masaaki Oka,Shoichi Hazama,et al: "Histological analysis of hepatocelullar carcinoma treated by intraarterial combined immunochemotherapy." Hepato-Gastroenterology. 42. 561-566 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Masaaki Oka,et al.: "Immunological evaluation of responders of intraarterial combined immunochemotherapy for unresectable hepatocellular carcinoma." Cancer Detection and Prevention. (in Press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Kenji Wadamori,Masaaki Oka, et al.: "Influence of continuous Interleukin-2 administration via the portal vein on liver regeneration following partial hepatectomy in rats." Hepatology,. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Masaaki,Oka: "Intraarterial combined immunochemotherapy for unresectable hepatocellular carcinoma: Preliminary results" Can cer Immunology Immunotherapy. 38. 194-200 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Masaaki,Oka: "The depression of cytotoxicity of nonparenchymal cells in the liver" Surgery. 116. 877-882 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Masaaki,Oka: "Prostaglandin E2 levels and lymphocyte subsets in portal venous drainage of colorectal cancers" American J Surgery. 167. 264-267 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Masaaki,Oka: "Adoptive immunotherapy for unresectable or recurrent pancreatic cancer using lymphokine-activated killer cells or cytotoxic T-cells" J.Hepato-Biliary-Pancreatic Surgery. 2. 163-167 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Masaaki,Oka: "Interleukin-6 and Granulocytic Elastase Levels Following Laparoscopic Cholecystectomy" J.Hepato-Biliary-Pancreatic Surgery. (In press). (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Masaaki,Oka: "Change of lymphocyte subsets following various surgical strss" Bulletin Yamaguchi Med.School. 40. 29-35 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Masaaki,Oka: "Intraarterial combined immunochemotherapy for unresectable hepatocellular carcinoma:Preliminary results" Cancer Immunology Immunotherapy. (In press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Masaaki,Oka: "The depression of cytotoxicity of nonparenchymal cells in the liver" Surgery. (In press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Masaaki,Oka: "Prostaglandin E2 levels and lymphocyte subsets in portal venous drainage of colorectal cancers" American J Surgery. (In press). (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Masaaki,Oka: "Adoptive immunotherapy for unresectable or recurrent pancreatic cancer using lymphokine-activated killer cells or cytotoxic T-cells" J.Hepato-Biliary-Pancreatic Surgery. 2. 163-167 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Masaaki,Oka: "Interleukin-6 and Granulocytic Elastase Levels Following Laparoscopic Cholecystectomy" J.Hepato-Biliary-Pancreatic Surgery. (In press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Masaaki,Oka: "Change of lymphocyte subsets following various surgical stress" Bulletin Yamaguchi Med.School. 40. 29-35 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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