Analysis of abnormality for check point mechanism regulation by DNA damage with radiation therapy for Oral cancer treatment and molecular target therapy against this mechanism.
| Project/Area Number |
16390592
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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 | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Showa University (2006)
Ehime University (2004-2005) |
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Principal Investigator |
SHINTANI S. Showa-Univ, Dept.Oral & Maxillofac.Surg., Prof., 歯学部, 教授 (80294429)
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| Co-Investigator(Kenkyū-buntansha) |
HAMAKAWA H. Ehime Univ., Dept.Oral & Maxillofac.Surg., Prof, 医学部教授, 教授 (20127905)
NAKASHIRO K. Ehime Univ., Dept.Oral & Maxillofac.Surg., A.Prof, 医学部教授, 助教授 (90314880)
HINO S. Ehime Univ., Dept.Oral & Maxillofac.Surg., A.Prof, 医学部教授, 助手 (90359927)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2006: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2005: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2004: ¥6,400,000 (Direct Cost: ¥6,400,000)
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| Keywords | Oral caner / Molecular target therapy / Radiation / Microarray / Angiogenesis inhibitor / Heat Shock Protein 90 / Cox-2 / EGFR / 化学療法 / p53 / 17-AAG / 放射線治療 / 感受性 / 抵抗性 / Heat shock Protein 90 / EGFR -TK inhibitor / CDK inhibitor / Cox-2 inhibitor / HSP-90 inhibitor |
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| Research Abstract |
Radiation therapy continues to remain a major treatment modality for oral cancers. Molecular targeting therapy developed as new molecular approaches derived from the recent increase in the knowledge of cancer biology. A better understanding of cancer biology and in particular of tumor radiation resistance mechanisms led to the identification of new molecular targets that could used to increase the therapeutic ratio of radiation therapy. These approaches attempt to increase specifically tumor radiation response with little impact on normal tissue response. We described the current approach of combined radiation with molecular targeting agents relevant for the treatment of oral cancer. Molecular targeting agents (Inhibitors of EGFR, COX-2, CDK, HSP90 and angiogenesis) enhanced the radio-response of tumors. Because of tumor heterogeneity and the multiple radio-resistance pathways, the responses of tumors were varied. These results suggested that the selection of relevant molecular targeti
… More
ng agents based on molecular biological information will be necessary for improvement of radiation enhancement.
On the other hand, to determine genes that correlating with radiation sensitivity of oral cancer treatment, we evaluated radiation sensitivity assessed by a standard colony formation assay with a gene microarray system with 7 OSCC cell lines. We found significant associations between dozens of genes expression levels and radiation resistance of OSCC cell lines. We also evaluated the relationship between expression levels of some candidate proteins, i.e. fibroblast growth factor (FGF) 2, friend leukemia inserton (Fli)-1 and an interferon inducible gene 6-16, G1P3, and radiation therapeutic effectiveness in OSCC patients of treated with preoperative radiation therapy. The significant association between the response to preoperative radiation therapy and candidate proteins expressions were observed. These data should contribute useful information for identifying predictive markers for radiation sensitivity, and may lead to the development of alternative treatment modalities for radiation therapy. Less
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Report
(4 results)
Research Products
(23 results)
