Project/Area Number |
10672156
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
応用薬理学・医療系薬学
|
Research Institution | Kyoritsu University of Pharmacy |
Principal Investigator |
NAKASHIMA Emi Kyoritsu College of Pharmacy, Faculty of Pharmaceutical Sciences, Professor (90115254)
|
Co-Investigator(Kenkyū-buntansha) |
IIZASA Hisashi Kyoritsu College of Pharmacy, Faculty of Pharmaceutical Sciences, Research Associate (80306662)
HATTORI Kenji Kyoritsu College of Pharmacy, Faculty of Pharmaceutical Sciences, Research Associate (90306663)
TSUJI Akira Kanazawa University, Faculty of Pharmaceutical Sciences, Professor (10019664)
|
Project Period (FY) |
1998 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000)
|
Keywords | TUMOR IMMUNITY / BIOLOGICAL RESPONSE MODIFIER / GENE TRNSFECTION / CHEMOKINE / INDOMETHACIN / TUMOR / CYTOKINE / CONCOMITANT THERAPY |
Research Abstract |
The immune cells, such as T lymphocyte and the natural killer cell, act an important role in tumor regression. We studied monocyte chemotactic protein-1(MCP-1) and macrophage inflammatory protein- la(MIP-1a) those are chemotactic factor of memory T lymphocyte and the chemokine acting to monocyte which is the precursor cell of the macrophage, respectively. We have already reported that these genes-transfected tumor cells induced apoptosis of the transplanted tumor cells. Especially, MTP- la gene-transfected tumor were rejected by the mouse of about 30%. Here, we examined the influence on the host immune response by using the Colon26clone20 colon cancer cells (hereafter, C20) introduced the gene of MCAF/MCP-1, and the synergistic administration of biological response modifier (BRM) were investigated. When both indomethacin and BRM were administered to the mouse harbored the carcinoma cell, the number of mice that rejected, and a remarkable antitumor effect was obtained. This effect was not observed in the SCID mouse that did not have T cell and B cell. Inoculated C20 cells again were also rejected. It was confirmed that the mouse obtained the tumor immunity. The antitumor effect of synergistic administration of indomethacin and BRM tended to be weakened in the mouse transplanted the MCAF/MCP-1 gene-transfected C20. For the tumor that decreases host immunity, MCAF/MCP-1 urges the macrophage permeation into the tumor, however, the activation of enough macrophage were not induced. Moreover, it was shown that the synergistic antitumor effects were obtained by using together with the medicine that adjusted the macrophage.
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