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ROLE OF CYTOKINES AND CELL ADHESION MOLECULE ON MECHANISM OF GROWTH OF LIVER TUMORS AND DECLATION OF IMMUNE-RESPONCES IN PATIENTS WITH LIVER TUMORS

Research Project

Project/Area Number 07671431
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionTOHO UNIVERSITY

Principal Investigator

NAKAZAKI Haruhiro  TOHO UNIVERSITY instructor, 医学部・第一外科, 講師 (00207747)

Co-Investigator(Kenkyū-buntansha) KAKIUCHI Terutaka  TOHO UNIVERSITY profassor, 免疫学, 教授 (40126024)
YOSHIO Tishifumi  TOHO UNIVERSITY,professor, 医学部・第一外科, 教授 (80057497)
OKADA Yayoi  TOHO UNIVERSITYaAssistant, 医学部・免疫学, 助手 (60256758)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Keywordsliver tumor / cytokines / cell adhesion molecule / killer activity / キラー伝性
Research Abstract

Growth of tumor cells is caused by unbalance of immune responces. In patients with tumor, cellular immunoresponce of peripheral blood is declined compared with healthy controls, and this low-immunoresponse is thought to cause tumor growth. Recently, we reported that cytokines (TNF-alpha, GM-CSF,IL-6 et.a1 ) were related with the generation, metastasis and invasion of liver tumor, especially TNF-alpha rised according to progress of tumor. In this study, (we investigated whether cytokines and cellular adhesion molecules (ICAM-1) interacted with tumor metastasis and invasion, and low immunoresponse of patitnts with liver tumor.
1) Serum levels of TNF-alpha, GM-CSF,IL-1,2,6 were high in patients with liver tumor. The levels of TNF-alpha, GM-CSF and ICAM-1 in tumor tissue, IL-1,2,6 and
ICAM-1 in non-tumor tissue were also high. ICAM-1 was detected in supernatant of established tumor cell line (MS-1), and surprisingly the production of ICAM-1 was increased by stimulation with TNF-alpha, GM-CSF … More ,IFN-gamma or IL-1. Moreover, ICAM-1 (CD54) levels on cell surface of MS-1 was also increased by the stimulation with these cytokines. These increase were verified by immuno-staining in liver tumor tissue.
Growth of tumor cells were related with the Ievels of cell surface B7-1 and B7-2, so we investigated the change of these cell surface markers in MS-1 by treatment with cytokines.
B7-1 level of MS-1 was increased by treatment of TNF-alpha and GM-CSF,and these increase were related with the concentration of cytokines. Though, on the contrary, B7-2 was decreased by these treatment.
2) Tne function of peripheral and tumor-infilated lymphocyte (PBL and TIL,respectively) were declined in patients with tumor compared with healthy controls. But, the response of TPA was increased in patients.
MS-1 was cultured more than two years without transformation, and fortunately, auto-lymphocytes were able to obtain by patient orginated of this cell line. So, we compared killar activity to MS-1 between auto- and allo lymphocytes.
Anto-lymphocytes had 34% of killar activity, and this activity was increased by the treatment of TNF-alpha, IFN-gamma and IL-6.
From these results, TNF-alpha, GM-CSF,IL-6 et.a1.induced co-stimulatory factor on tumor cell surface, and these induction was related to the activation of CTL in patients with liver tumor. Less

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] 中崎 晴弘: "大腸癌肝転移における血清サイトカイン値測定の意義" 日本大腸肛門病学会雑誌. 48・3. 212-216 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 中崎 晴弘: "肝細胞癌のオートクリン増殖におけるサイトカインの意義,特にTNF-αについて" 東邦医学会雑誌. 42-2. 140-144 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 下島 裕寛: "原発性肝癌患者術前末梢血および摘出癌部浸潤リンパ球に対する各種サイトカイン、レクチン反応性に関する検討" 東邦医学会雑誌. 42-5. 520-529 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Haruhiro Nakazaki: "SIGNIFICANCE OF CYTOKINES IN SERUM OF PATIENTS WITH LIVER METASTASIS-COMPLICATED COLORECTAL CARCINOMA" 48.3. 212-216 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Haruhiro Nakazaki: "CYTOKINES AS AUTOCRINE GROWTH FACTOR IN HEPATOCELLULAR CARCINOMA" J.Med Soc Toho Japan. 42,2. 140-144 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yasuhiro Shimojima: "EFFECT OF CYTOKINE AND LECTIN ON PERIPHERAL MONONUCLEARCYTES AND TUMOR-INFILTRATION LYMPHOCYTES IN HEPATOCELLULAR CARSINOMA" J.Med Soc Toho Japan. 42,5. 520-529 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 中崎晴弘: "大腸癌肝転移における血清サイトカイン値測定の意義" 日本大腸肛門病学会雑誌. 48・3. 212-216 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] 中崎晴弘: "肝細胞癌のオートクリン増殖におけるサイトカインの意義、特にTNF-αについて" 東邦医学会雑誌. 42・2. 140-144 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] 下島裕寛: "原発性肝癌患者術前末梢血および摘出癌部浸潤リンパ球に対する各種サイトカイン・レクチン反応性に関する検討" 東邦医学会雑誌. 42・5. 520-529 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 中崎晴弘: "肝細胞癌のオートクリーン増殖におけるサイトカインの意義,特にTNF-αについて" 東邦医会誌. 42・2. 140-146 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] 下島裕寛: "原発性肝癌患者術前末梢血,および摘出癌部浸潤リンパ球に対する各種サイトカイン,レクチン反応性に関する検討" 東邦医会誌. 42・5. 520-529 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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