2000 Fiscal Year Final Research Report Summary
Chemotherapy of salivary gland carcinomas with tyrosine kinase inhibitors
| Project/Area Number |
11671869
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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 |
病態科学系歯学(含放射線系歯学)
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| Research Institution | Osaka University (2000)
The University of Tokushima (1999) |
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Principal Investigator |
YURA Yoshiaki Graduate school of Dentistry Osaka University Professor, 大学院・歯学研究科, 教授 (00136277)
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| Project Period (FY) |
1999 – 2000
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| Keywords | salivary gland carcinoma / acidic FGF / growth factor receptor / tyrosine kinase inhibitor |
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| Research Abstract |
Chemotherapy is required for the treatment of salivary gland carcinomas, because these tumors recur and metastasize to distant organs frequently. If tumor growth were dependent on the signal of a specific growth factor, interruption of such signal would result in growth inhibition of the tumors. Acidic fibroblast growth factor (aFGF) was been demonstrated in the mouse submandibular gland and was found to stimulate the growth of mouse submandibular gland undifferentiated carcinoma YT-12 cells. Furthermore, bovine brain aFGF promoted the development of 9, 10-dimethyl-1, 2-benzanthracene-induced submandibular gland carcinomas. Since aFGF and FGF receptors were demonstrated in the normal submandibular glands and carcinomas, autocrine and paracrine mechanisms may regulate the growth of the tumors.
Tyrphostins are artificial and low molecular weight compounds that specifically inhibit protein tyrosine kinases. Tyrphostins suppressed the growth of YT-12 cells ; tyrphostin 9 was the most potent inhibitor. Furthermore, the growth of nude mouse tumors induced by YT-12 cell inoculation was suppressed by intra-tumor administration of tyrphostin 9. It also inhibited tyrosine-phosphorylation of membrane proteins including FGF receptor-l in the aFGF-treated YT-12 cells. Flow cytometric analysis, DNA staining with Hochest 33258 and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method indicated that tyrpjostin 9 induced the arrest of cell cycle and apoptosis. These results suggest that aFGF play a role in the development of mouse submandibular gland carcinomas, and that tyrosine kinase inhibitor, tyrphostin 9, can be used as an inhibitor for the submandibular gland carcinoma.
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