1998 Fiscal Year Final Research Report Summary
Lower Host Immune Response against Invasion and Metastasis of Gastric Carcinoma and its Dissolution.
| Project/Area Number |
09670508
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
KOYAMA Shohei Institute of Clinical Medicine, Assistant Professor., 臨床医学系, 講師 (00110502)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Gastric Cencer / Immune response / B7-1&B7-2 / CD44v6 / CD44v9 / Fas receptor / Fas ligand / Tumor immune evasion |
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| 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
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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
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