| Project/Area Number |
18591571
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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 |
Thoracic surgery
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| Research Institution | Tazuke Kofukai Medical Research Institute |
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Principal Investigator |
MASAYUKI Miyake Tazuke Kofukai Medical Research Institute, 5th division, Medical Research Institute, Researcher (80343755)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAKI Masayuki The Tazuke Kofukai, 5th division, Medical Research Institute, Researcher (90250076)
HIROTA Kiichi Kyoto University, Graduate School of Medicine, Associate Professor (00283606)
MITSUDOMI Tetsuya Aichi Cancer Center, Research Institute, Researcher (70209807)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Aminomotidase N / CD13 / Angiogenesis / Human Monoclonal Antibody / Metastasis Inhibition / アミノペプチダーゼN |
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| Research Abstract |
We established the human type monoclonal antibody (MAb) suppressing angiogenesis and the cloning of this antibody reveals Aminopeptidase N (APN)/CD13. The APN gained a potential ability of metastasis to the lung. Using the actual clinical specimens of lung cancer, colon cancer and pancreatic cancer, we found that the expression of APN had an association with angiogenesis, and was a significant factor of poor prognosis. After establishment in human type monoclonal antibody, we used assay of Trenswell and sorted the antibody that inhibited cell motility. In particular, MT95-4 and MT19-12 antibody significantly inhibited activity of APN among several kinds of antibody that recognized APN/CD13. We reported that human anti-APN monoclonal antibody MT95-4 and MT19-12 suppressed metastases to lung and lymph node. l)The number of lung tumors was reduced in mice that received anti APN antibody MT95-4 in intravenously metastatic model (96.7±14.3 vs 22.5±13.1, p<0.001). 2) There was no significant difference between Anti APN antibody MT95-4 treated tumors and control PBS tumors in orthotopically implantation model (211.1±31.1mm3 vs 204.4±32.1=3). 3) Consistent with qualitative observations, the lymph node weights were reduced in mice that received anti APN antibody MT95-4 (475.6, ±94.2mg vs 116.7±25.9mg, p<0.001). The modification of the sugar chain resulted in such changes, thus currently it is studied which kinds of sugar chain changes might associate with the tumor metastasis. The function of effect has been unclear yet, but there are relationships between the modification of the sugar chain and Angiogenesis. This modality to suppress lymphatic metastasis could be applied to clinical therapy of cancers, especially for the prevention of metastasis during radiotherapy.
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