| Project/Area Number |
14571169
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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 |
General surgery
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| Research Institution | The Tazuke Kofukai |
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Principal Investigator |
TOKUHARA Takahiro Kitano Hospital The Tazuke Kofukai Medical Research Institute., Fifth Department of Oncology, Researcher, 医学研究所・第5研究部, 研究員 (80343755)
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| Co-Investigator(Kenkyū-buntansha) |
HATTORI Noboru Kitano Hospital The Tazuke Kofukai Medical Research Institute., Fifth Department of Oncology, Chief-Researcher, 医学研究所・第5研究部, 主任研究員 (00283169)
MIYAKE Masayuki Kitano Hospital The Tazuke Kofukai Medical Research Institute., Fifth Department of Oncology, Director, 医学研究所・第5研究部, 部長 (90250076)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | angiogenesis / APN / CD13 / NEP / CD10 |
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| Research Abstract |
We have established the monoclonal antibody(MAb) MH8-11 suppressing angiogenesis and the cloning of this antibody reveals Aminopeptidase N(APN)/CD13. The APN transfected B16-F1 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. On the other hand, we suppose neutral endopeptidase (NEP)/CD10 has anything to do with APN, but the evaluation of clinical specimens showed that NEP is a significant factor for good prognosis. MH7-5 MAb which we have established also recognized APN. Western blotting with MH7-5 showed both l6OkDa and l2OkDa bands, but only 150kDa band was detected using NH8-11. 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. One of our aims was to identify regulator genes of APN gene, and it was only observed that expression of NEP was decreased in the NEP positive and APN negative cell lines. Therefore, the identification of the gene which regulates APN gene remains unknown. Using the F1cell line with highly metastatic potential to the lung, we investigated whether the anti-APN MAb could prevent the lung metastasis or not. The number of metastatic colony of MH8-11MAb injected group were 41.4±24.4, compared to 98.3ア41.8 in control. This experiment demonstrated that MH8-11MAb efficiently prevented the pulmonary metastasis of F1 (p=0.0043). Currently, as the molecular targeting therapy, we will investigate whether human MH8-11 MAb might suppress the cancer progression or metastasis. We also investigate whether the NEP itself has a suppression of progression or not.
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