Analysis of human monoclonal antibody suppressing metastasis and the mechanism of metastasis.
| Project/Area Number |
16591285
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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 |
ISHIDA Hisao The Tazuke Kofukai, Kitano Hospital, The Tazuke Kofukai Medical Research Institute. Fifth Department of Oncology, Department of Thoracic Surgery, 医学研究所第5研究部, 研究員 (40322771)
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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 |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | KM mouse / Aminopeptidase N / Human Monoclonal Antibody / Aminopeptidase N / ADCC効果 / Aminopeputidase N |
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| Research Abstract |
The aims of this study were to systematically investigate the possible involvement of proteins at the cell surface in controlling cell motility and angiogenesis, and further identify the cell surface molecules involved in malignant tumors. We addressed these issues using functional human monoclonal antibodies (MAbs), which inhibit cell motility. In addition, we established human monoclonal antibodies using KM mice. We have established 11 monoclonal antibodies which suppress lung metastasis. Among them, 7 kinds of monoclonal antibodies have recognized proteins and the others were directed to sugar chains like glycoproteins and glycolipids. Previously, we established a murine MAb MH8-11, which inhibits cell motility and in vitro angiogenesis. This epitope was a 165-kD protein and the sequencing analysis revealed that it was almost identical to aminopeptidase N (APN)/cluster of differentiation 13 (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 a poor prognosis. Currently, as the molecular targeting therapy, we established the human monoclonal antibodies recognizing APN. MT95-4 has a stronger ability suppressing APN enzyme activity than the mouse monoclonal antibody MH8-11. Using the F1 cell line with highly metastatic potential to the lung, we demonstrated that MT95-4 MAb efficiently prevented the pulmonary metastasis of F1. 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
(37 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 fibroblasts.2005
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
「研究成果報告書概要(欧文)」より
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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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Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Clinical significance of Aminopeptidase N in Non-Small Cell Lung Cancer.
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
「研究成果報告書概要(欧文)」より
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[Book] 呼吸器外科の最新医療2005
Author(s)
石田久雄, 三宅正幸
Total Pages
3
Publisher
先端医療技術研究所
Description
「研究成果報告書概要(和文)」より
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