| Project/Area Number |
17592062
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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 |
Surgical dentistry
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| Research Institution | Hokkaido University |
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Principal Investigator |
OHIRO Yoichi Hokkaido University, Graduate School of Dental Medicine, Instructor, 大学院歯学研究科, 助手 (40301915)
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| Co-Investigator(Kenkyū-buntansha) |
SHINDOH Masanobu Hokkaido University, Graduate School of Dental Medicine, Professor, 大学院歯学研究科, 教授 (20162802)
KOBAYASHI Masanobu Hokkaido University, Institute for Genetic Medicine, Associate Professor, 遺伝子病制御研究所, 助教授 (80241321)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Oral Cancer / Radiation therapy / Chemotherapy / p53 / Genetic alteration / Hypoxia / 治療効果予測因子 |
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| Research Abstract |
The predictive value of tumor suppressor protein of p53 and related genes for the effect of chemoradiation therapy on oral squamous cell carcinoma is still controversial. Recently, it is clear that tumor tissues are exposed to low-oxygen environmental (hypoxic state) so tumor cells alter their gene expression profile to survive in a severe condition. We estimate the proteins expression for p53 and p53R2 (p53-dependent kinase gene) in biopsy specimen to examine these proteins are valuable predictors for concurrent chemoradiotherapy. We also examined hypoxia-inducible factor (HIF) responsible proteins, vascular endothelial growth factor (VEGF) and Angiopoietin-like4 (ANGPTL4) in vitro to understand their relation under hypoxic state.
Thirty five cases were enrolled in this study. Fifteen patients were received radiation therapy only and 20 patients were given concurrent chemoradiotherapy before the operation. Biopsy specimens were examined by immunohistochemistry. The positive rate of p53 was 80% and p53R was 73.3 in all patients. Statistical anaylysis revealed that the combination with p53 positive/negative and p53R positive/negative couldn't predict the sensitivity to preoperative concurrent chemoradiotherapy.
In vitro study, VEGF and hypoxic condition stimulate the expression for ANGPTL4. Under hypoxic condition, over expression of ANGPTL4 down-regulates the expression of VEGF. These results suggest that under hypoxic condition, VEGF expression is negatively regulated by ANGPLT4.
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