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Lower Host Immune Response against Invasion and Metastasis of Gastric Carcinoma and its Dissolution.

Research Project

Project/Area Number 09670508
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, Assistant Professor., 臨床医学系, 講師 (00110502)

Co-Investigator(Kenkyū-buntansha) 野末 睦  筑波大学, 臨床医学系, 講師 (00237843)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
KeywordsGastric Cencer / Immune response / B7-1&B7-2 / CD44v6 / CD44v9 / Fas receptor / Fas ligand / Tumor immune evasion / B7-1(CD80) / B7-2(CD86) / 食道癌 / CD44v6分子 / CD44v9分子 / Fas抗原(CD95) / Fasリガンド(CD95L) / 消化器癌 / IL-12 / TGFα / EGFR
Research Abstract

1).To evaluate the potential of interleukin 12(IL- 12) in combination with interleukin2 (IL-2) as an inducer of enhanced-killer cells against human tumors in in vitro system. 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). Expression of costimulatory molecules, such as B7-1(CD80 antigen) and B7-2 (CD86 antigen) was determined in carcinoma of the primary focus in the stomach (24 cases) and in carcinoma of the metastatic lesion in the malignant ascites (20 cases) by the method of two-color flow cytometry. The B7- 1 molecule on the gastric carcinoma bearing CD80+CD86+ was abrogated during rumor invasion and/or metastasis, and the tumor finally acquired the CD80-CD86+ phenotype. Consequently, inadequ … More ate B7-1 costimulation may contribute to the escape of tumors from destruction by the 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.
4) Increased expression of EGFR and CD44v9 molecules on gastric carcinomas, particularly metastatic carcinomas, and decreased expression of EGFR and CD44v6 molecules on irradiated esophageal carcinomas plays an important roles of tumor growth and tumor progression and can be useful as a potential metastatic and/or prognostic marker for upper GI carcinomas, although CD44v6 molecule are not detectable on adenocarcinoma of the stomach, at least.
5) FasL was constitutively expressed in primary locus and metastatic lesion from malignant ascites in patients with gastric carcinoma, although FasR expression on the cells was hardly detectable. In addition, significantly increased expression of FasL was observed in metastatic cancer cells as compared with that in primaly locus of the gastric carcinoma. However, the FasR and FasL were commonly and highly coexpressed by tumor-infiltrative lymphocytes (TIL) from metastatic carcinoma, although TIL from primary lesion of the stomach revealed consistently very low or undetectable levels of expression of the FasR and FasL.In conclusion, the results suggest that FasL expressiion on cancer and TIL could conceivably facilitate the FasR counterattack & paracrine fratricide, followed by playing a important role in the escape of tumor cells from destruction by the host' s immune systems. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Koyama S et al: "Transforming growth factor-alpha (TGF α)-producing gastric carcinoma with acanthosis nigricans" J.Gastroenterology. 32. 71-77 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Koyama S: "Augmented human-tumor-cytolytic activity of peripheral blood lymphocytes and cells from a mixed lymphocytes/tumor culture" J Cancer Res Clin Oncol. 123. 478-484 (1977)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 小山 捷平: "結腸・直腸癌のスクリーニング" Medicina. 35. 425-427 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Koyama S et al: "Expression of costimulatory molecules,B7-1 and B7-2 on human gastriccarcinoma." J Cancer Res Clin Oncol. 124. 383-388 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Koyama S et al: "Expression of epidermal growth factor receptor and CD44 splicing variants sharing exon 6 and 9 on gastric and esophageal carcinomas" J Cancer Res Clin Oncol. 125. 47-54 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shohei Koyama, et al: "Transforming growth factor-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 (1). 71-77 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shohei Koyama: "Augmented human-tumor-cytolytic activity of peripheral blood lymphocytes and cells from a mixed lymphocyte/tumor culture activated by interleukin-12 and interleukin-2, and phenotypic characterization of the cells in patients with advanced carcinoma." J Cancer Res Clin Oncol. 123 (9). 478-484 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shohei Koyama, et al: "Expressio of costimulatory molecules, B7-1 and B7-2 on human gastric carcinoma." J Cancer Res Clin Oncol.124 (7). 383-388 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shohei Koyama, et al: "Expression of epidermal growth factor receptor and CD44 splicing variants sharing exons 6 and 9 on gastric and esophageal carcinomas : a two-color flow-cytometric analysis." J Cancer Res Clin Oncol. 125 (1). 47-54 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 小山 捷平: "結腸・直腸癌のスクリーニング" Medicina. 35(3). 425-427 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Koyama et al.: "Expression of costimulatory molecules,B7-1 and B7-2 on human gastric carcinoma." J.Cancer Res.& Clin Oncology. 124(7). 383-388 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Koyama et al.: "Expression of epidermal growth factor receptor and CD44 splicing variants sharing exons 6 and 9 on gastric and esiphageal carcinoma." J.Cancer Res.& Clin Oncology. 125(1). 47-54 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Koyama,S et al.: "Transforming growth factor-alpha-producing gastric carcinoma with acanthosis nigricans:An endocrine・・・" J.Gastroenterology. 32(1). 32-77 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Koyama,S.: "Augmented human-tumor-cytolytic activity of periphen blood lymphocytes and cells from mixedlymphocytes・・・" J.Cancer Res. & Clin Oncology. 123. 478-484 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Koyama,S et al.: "Expression of costimulatory molecules,B7-1 and B7-2 on human gastric carcinoma." J.Cancer Res. & Clin.Oncology. 124(in press). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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