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Host Immune Response against Cancer Invasion and Metastasis of Digestive System.

Research Project

Project/Area Number 07670560
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionUniversity of Tsukuba

Principal Investigator

KOYAMA Shohei  Institute of Clinical Medicine University of Tsukuba, Assistant Professor., 臨床医学系, 講師 (00110502)

Co-Investigator(Kenkyū-buntansha) FUKAO Katashi  Institute of Clinical Medicine University of Tsukuba, Professor., 臨床医学系, 教授 (50091921)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsCancer of digestive system / Cancer metastastasis / Immune response / Antitumor immunity / Adhesion molecule / Cvtokine / Growth factor / Interleukin-12 (IL-12) / がん転移 / インターロイキン-12
Research Abstract

1).To evaluate the potential of interleukin 12 (IL-12) in combination with interleukin 2 (IL-2) as an inducer of enhanced-killer cells against human tumors in in vitro system, PBL from cancer patients (n=15) were cultivated with IL-2 or IL-12/IL-2 for 10 days (LAK generation), and PBL from cancer patients (n=16) were also stimulated with MMC-treated allogeneic tumor cells for 3 days, followed by further cultivation with IL-2 or IL-12/IL-2 for 7 days (CTL generation). The cytolytic activities of the cells cultured with IL-12/IL-2 combination were significantly increased as compared with those of IL-2 alone in both LAK and CTL generation systems (p<0.01). In LAK generation system, IL-12/IL-2 induced killer-effector cells showed NK cell type bearing CD8-CD11b+, CD8-CD16b+ and CD3-CD56+. While, in CTL generation systems, CD8+CD11b-T cells mixed with NK cell type bearing CD8-CD11b+, CD8-CD16b+ and CD3-CD56+ were cell population of killer-effector cells induced by IL-12/IL-2 combination.
2).E … More xpression of costimulatroy molecules, such as B7-1 (CD80 antigen) and B7-2 (CD86 antigen) was determined in carcinoma of the primary focus in the stomach (10 cases) and the esophagus (3 cases), and in carcinoma of the metastatic lesion in the malignant ascites (5 cases) by the method of two-color flow cytometry. Also, gastric normal mucosa (14 cases) was made to examine as a control. As a results, the mean positive rate of CD80 antigen-expression of normal gastric mucosa and the primary lesion of the stomach and the esophagus shows 50.1% and 43.8%, respectively. While, the mean positive rate of the metastatic lesion shows lower levels, revealing 11.8%. The CD86 antigen-expression of normal mucosa, primary and metastatic lesions shows 56.4%, 68.8% and 76.1%, respectively. Thus, CD86 antigen may be expressed on tumor cells at higher levels in accordance with cancer proliferation and metastasis. Lower level of expression of CD80 molecule on tumor cells, especially metastatic lesion results in inadequate B7-1 costimulation. This may contribute to the escape of tumors from destruction by the host's immune system.
3).Adenocarcinoma cells of the stomach showed intense immunoreactivity with both anti TGF alpha and anti EGF receptor antibodies. Coexpression of TGF alpha and EGFR in the tumor suggests an aberrant autocrine loop for autostimulation, which may play an important role in the further progression of gastric carcinoma toward invasive tumor growth and metastatic potential. EGFR expression was also noted on the paillomatous hyperplasia of the cutaneous verrucous papules lesion. Serum level of TGF alpha, determined by an ELISA was high 144 pg/ml (normal 22.0 <plus-minus> 16 pg/ml). Serum TGF alpha abruptly decreased to 49 pg/ml on day 7 after the total gastrectomy. Amelioration of the cutaneous lesions was observed after surgical resection of the gastric carcinoma. This suggests that TGF alpha stimulates the proliferation of keratinocytes involved with EGFG.Large amounts of circulating TGF alpha in the blood over a long period released by the primary tumor seem to act as an endocrine-like mechanism causing epidermal cells to proliferat Less

Report

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

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Ishikawa,M & Koyama,S et al.: "Venous tumor thrombosis and cavernous transformation of the portal vein in a patient with gastric carcinoma." J.Gastroenterology. 30. 529-533 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Koyama,S.et al.: "Primary tubular adenocarcinoma arising in the duodenal limb of reconstructed gastroduodenostomy for signet-ring cell ca. ‐‐‐‐‐‐‐" J.Gastroenterology. 30. 657-660 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Koyama,S.et al.: "Primary diaphragmatic schwannoma with a typical target appearance : Correlation of CT and MR imagings and histological findings." J.Gastroenterology. 31. 268-272 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Koyama,S et al.: "Transforming growth factor-alpha-producing gastric carcinoma with acanthosis nigricans : An endocrine effect of TGF in‐‐‐‐‐‐‐" J.Gastroenterology. 32. 71-77 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ishikawa M,Koyama S et al.: "Venous tumor thrombosis and cavernous transformation of the portal vein in a patient with gastric carcinoma" J.Gastroenterology. 30. 529-533 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Koyama S.et al.: "Primary tubular adenocarcinoma arising in the duodenal limb of reconstructed gastroduodenostomy for signet-ring cell carcinoma of the stomach" J.Gastroenterology. 30. 657-660 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Koyama S.et al.: "Primary diaphragmatic schwannoma with a typical target appearance : Correlaion of CT and MR imagings and histoligical findings" J.Gastroenterology. 31. 268-272 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Koyama S.et al.: "Transforming growth facor-alpha (TGF alpha) producing gastric carcinoma with acanthosis nigricans : An endocrine effect of TGF alpha in the pathogenesis of cutaneous paraneoplastic syndrome and epithelial hyperplasia of the esophagus" J.Gastroenterology. 32. 71-77 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ishikawa,M & Koyama,S et al.: "Vεлous tumor thrombosis and Cavernous transformation of the portal vein in a patient with gastric carcinoma." J.Gastroenterology. 30. 529-533 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Koyama,S et al.: "Primary tubular adenocarcinoma arising in the duodenal limb of reconstructed gastroduodenostomy for signet-ring cell ca.-------" J.Gastroenterology. 30. 657-660 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Koyama,S.et al.: "Primary diaphragmatic schwannoma with a typical target appearance : Correlation of CT and MR Imagings and histological findings." J.Gastroenterology. 31. 268-272 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Koyama,S et al.: "Transforming growth factor-alpha-producing gastric carcinoma with acanthosis nigricans : An endocrine effect of TGF in -------" J.Gastroenterology. 32. 71-77 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ishikawa, M. & Koyama, S. et al.: "Venous tumor thrombosis and cavernous transformation of the portal vein in a patient with gastric carcinoma." J. Gastroenterology. 30. 529-533 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Koyama, S. et al.: "Primary tubular adenocarcinoma arising in the duodenal limb of reconstructed gastroduodenostomy for signet-ring cell ca." J. Gastroenterology. 30. 657-660 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Koyama, S. et al: "Primary diaphragmatic schwannoma with a typical target appearance : Correlation of CT and MR imagings and histological findings." J. Gastroenterology. 31(in press.). (1996)

    • Related Report
      1995 Annual Research Report

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

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