| Project/Area Number |
17592061
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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 |
ONO Mitsunobu Hokkaido University, Graduate School of Dental Medicine, Instructor, 大学院歯学研究科, 助手 (50281829)
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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)
HIGASHINO Fumihiro Hokkaido University, Graduate School of Dental Medicine, Lecturer, 大学院歯学研究科, 助教授 (50301891)
OHIRO Yoichi Hokkaido University, Graduate School of Dental Medicine, Instructor, 大学院歯学研究科, 助手 (40301915)
TOTSUKA Yasunori Hokkaido University, Graduate School of Dental Medicine, Professor, 大学院歯学研究科, 教授 (00109456)
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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 |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Oral carcinoma / Adrenomedullin / Gene targeting therapy |
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| Research Abstract |
Cancer cells are exposed to hypoxic state because of their high proliferation rate: however, cancer cells are resistant to hypoxia-induced cell death. Hypoxia Inducible Factor (HIF) was identified as the transcription factor which maintains the homeostasis of the cell in hypoxic state. We examined the downstream genes of HIF by DNA micro array and we found that adenomemedullin, a blood vessel expansive peptide encoding gene product.
Twenty-two cases of tongue squamous cell carcinoma who consulted the Hokkaido University Hospital were examined by immunohistochmistry. Adrenomedullin was detected in 11 of 22 cases examined. They were investigated clinico-pathologically. mong the 12 cases of cervical lymph node metastasis cases, 8 cases were positive for aderenomedullin. In contrast, only 3 cases were positive for adrenomedullin in 10 cases without lymph node metastasis.
We reconstruct two mutant expression plasmids of adrenomedullin that are thought to function as antagonist, AMA214 is deletion and mutant plasmid with 27-115 amino acid deletion and 116 threonine into serine..AMA224 has deletion of 95-115 amino acid and the same mutation in 116 amino acid. AMA214 and AMA224 injection induced the regression of transplanted tumors in SCID mouse. CD31-positive tumor endothelial cells were disappeared in these animals.
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