1998 Fiscal Year Final Research Report Summary
Basic research for oral cancer therapy by anti-cancer drugs and apoptosis-inducing factor
| Project/Area Number |
09557171
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Surgical dentistry
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| Research Institution | Showa University |
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Principal Investigator |
NAGUMO Masao Showa university, School of Dentistry, Professor, 歯学部, 教授 (70013993)
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| Co-Investigator(Kenkyū-buntansha) |
KAMIJO Ryutaro Showa University, School of Dentistry, Assistant Professor, 歯学部, 講師 (70233939)
IWASE Masayasu Showa University, School of Dentistry, Assistant Professor, 歯学部, 講師 (50193743)
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| Project Period (FY) |
1997 – 1998
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| Keywords | CDDP / 5-Fu / NO donors / apoptosis / ICAM-1 / caspase / Fas / Fas L / TNF-alpha |
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| Research Abstract |
We investigated the effects of anti-cancer drugs (CDDP, 5-Fu) , IFN-y or NO donors(SNP, SNAP, NOC) on induction of apoptosis mainly in NA cells which had been established from a squamous cell carcinoma of the tongue. Further the effects of these agents on the expression of c-myc and c-myb, adhesion molecules including ICAM-1, Fas/Fas ligand, and soluble Fas were also studied in NA cells. The results obtained were as follows :
1. When NA cells were treated with NO donors, apoptosis of NA cells was induced together with the inhibition of the expression of c-myc and c-myb mRNA.
2. CDDP and 5-Eu induced apoptosis of NA cells and it was suggested that FLICE (caspase 8) might be concerned in the induction of apoptosis of NA cells. However, synergistic -effect was not observed when NA cells were treated both with these anti-cancer drugs.
3. ICAM-1 expression on NA cells was enhanced by the treatment of CDDP or 5- Eu, and simultaneous treatment with CDDP and 5-Eu exhibited synergistic effect on the induction of ICAM-1.
4. Apoptosis was induced when NA cells were treated with IEN-gamma or anti-Fas antibody (CH11). Then, membrane binding Fas was not altered, whereas soluble Eas in the medium was decreased.
5. The expression of Fas and Fas ligand on HL-60 cells, a leukemia cell line, was enhanced by the treatment with IEN-gamma or TNF-alpha, while the expression of bcl-2 protein and its mRNA was reduced by the treatment.
These results indicate that apoptosis is induced both by anti-cancer drugs or NO donors and that the induction of apoptosis is enhanced by IFN-gamma or TNF-alpha.
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