Analysis of the function of Aminopeptidase N and neutral and peptidase and application of its cancer therapy.
| Project/Area Number |
16591284
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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 The Tazuke Kofukai, 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) |
MIYAKE Masayuki The Tazuke Kofukai, 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)
HATTORI Noboru Hiroshima University, Department of Molecular and Internal Medicine, Associated Professor, 大学院・医歯薬学総合研究科第2内科, 講師 (00283169)
HATTORI Kiichi Kyoto University, Graduate School of Medicine, Department of Anethesia, Associated Professor, 医学研究所麻酔科, 講師 (00283606)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Aminopeptidase N / CD13 / Human Monoclonal Antibody / metastasis inhibition / angiogenesis / ADCC効果 / Aminopeptidase N |
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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 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. However, there is a problem for the clinical application of mouse monoclonal antibody which produces HAMA (Human Anti-Mouse Antibody). We established the human type monoclonal antibody that recognized APN/CD13. I used the human type antibody production mouse "KM mouse" which Kirin Brewery developed. Thus, we established hybridoma by the same method as normal mouse monoclonal antibody by immunization by human fibrosarcoma cell line HT1080. After establishment in human type monoclonal antibody, we used assay of Transwell and sorted the antibody that inhibited cell motility. As the result, we established the human type monoclonal antibody that recognized APN/CD13. In particular, MT95-4 antibody significantly inhibited activity of APN among several kinds of antibody that recognized APN/CD13. 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. MT95-4 has a stronger ability suppressing APN enzyme activity than the mouse monoclonal antibody MH8-11. Using MT95-4 we might be able to treat the various kinds of cancers as a molecular targeting therapy.
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Report
(3 results)
Research Products
(38 results)
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[Journal Article] Circulating aminopeptidase N/CD13 is an independent prognostic factor in patients with non-small cell lung cancer2005
Author(s)
Murakami, H., Yokoyama, A., Kondo, K., Nakanishi, S., Kohno, N., Miyake, M.
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Journal Title
Clin.Cancer Res 11
Pages: 8674-8679
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] KL-6, a human NUC1 mucin, promotes proliferation and survival of Lung fibroblasts2005
Author(s)
Ohshimo, S., Yokoyama, A., Hattori, N., Ishikawa, N., Hirasawa, Y., Kohno, N
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Journal Title
Biochem.Biophys.Res.Commun 30
Pages: 1845-1852
Description
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[Journal Article] The Plasminogen activation system reduces fibrosis in the lung by a Hepatocyte growth factor-dependent mechanism.2004
Author(s)
Hattori, N., Mizuno, S., Yoshida, Y., Chin, K., Mishima, M., Sisson, TH., Simon, RH., Nakamura, T., Miyake, M.
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Journal Title
Am.J.Pathol. 164
Pages: 1091-1098
Description
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[Journal Article] MRP-1/CD9 gene transduction downregulates Wnt signal pathways.2004
Author(s)
Huang, C., Liu, D., Masuya, D., Kameyama, K., Nakashima, T., Yokomise, H., Ueno, M., Miyake, M.
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Journal Title
Oncogene 23
Pages: 7475-7483
Description
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[Journal Article] MRP-1/CD9 gene transduction regulates the actin cytoskeleton throug the down-regulation of WAVE2.
Author(s)
Huang, CL., Ueno, M., Liu, D., Masuya, D., Nakano, J., Yokomise, H., Nakagawa, T., Miyake, M.
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Journal Title
Description
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[Journal Article] Clinical significance of Aminopeptidase N in Non-Small Cell LungCancer.
Author(s)
Tokuhara, T., Hattori, N., Ishida, H., Hirai, T., Higashiyama, M., Kodama, K., Miyake, M
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Journal Title
Clin, Cancer, Res. (in press)
Description
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[Book] 呼吸器外科の最新医療2005
Author(s)
石原久雄, 三宅正幸
Total Pages
3
Publisher
先端医療技術研究所
Description
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[Book] 外科治療2005
Author(s)
徳原孝洋, 三宅正幸
Total Pages
2
Publisher
永井書店
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