| Co-Investigator(Kenkyū-buntansha) |
NAKASHIRO Kouichi Ehime University, School of Medicine, Assistant Professor, 医学部附属病院, 講師 (90314880)
HAMAKAWA Hiroyuki Ehime University, School of Medicine, Professor, 医学部, 教授 (20127905)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2002: ¥11,900,000 (Direct Cost: ¥11,900,000)
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| Research Abstract |
We evaluated the expression of p27^<KIP1>, a cell cycle regulator, in Oral squamous cell carcinoma (OSCC). P27^<KIP1> expressein was reduced in OSCC. Inversely, Skp2 and Jab-1 that regulate p27^<KIP1>, was overexpressed (Oncology 65, 2003). Epidermal growth factor receptor (EGFR) are frequently overexpressed in OSCC. EGFR inhibitor suppressed the cell growth of OSCC cell lines with p27^<KIP1> expression and a complete arrest in the G1 phase. So, we investigated whether treatment with ZD1839 (Iressa), a selective EGFR-tyrosine kinase inhibitor, would inhibit the cell proliferation, metastatic spread, and enhance response to radiotherapy in OSCC cells. ZD1839 suppressed the cell growth of OSCC cell lines. Growth arrest was observed in OSCC xenografts when mice were treated with ZD1839. The mechanism for cell growth arrest was accompanied by increased p27^<KIP1> and decreased Skp2 (Oral Oncol.40,2004). ZD1839 also have antimetastatic activity, in OSCC xenograft cervival lymph node metastasis model (Cancer Lett 201,2003). We also observed the additive growth inhibitory effects of ZD 1839 to radiation. The same effects were confirmed in OSCC xerografts( Int J Cancer 107,2003). We also evaluated the possibility of the antitumor activity of flavopiridol, a CDK inhibitor. Flavopiridol inhibit cell growth of OSCC cell line with a G1 and S2/M phase arrest and induced apoprttosis (Oral Oncol 39,2003). From these results, the EGFR inhibitor and/or CDK inhibitor will be a effective molecular target therapy agent against oral cancer.
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