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Analysis of human monoclonal antibody suppressing metastasis and the mechanism of metastasis.

Research Project

Project/Area Number 16591285
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionThe Tazuke Kofukai

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)

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)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
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)
KeywordsKM mouse / Aminopeptidase N / Human Monoclonal Antibody / Aminopeptidase N / ADCC効果 / Aminopeputidase N
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.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (37 results)

All 2005 2004 Other

All Journal Article (34 results) Book (3 results)

  • [Journal Article] 細胞運動の制御による癌移転の抑制 Suppression of metastasis by inhibition of cell motility2005

    • Author(s)
      徳原孝洋, 三宅正幸
    • Journal Title

      外科治療 93

      Pages: 221-222

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Circulating aminopeptidase N/CD13 is an independent prognostic factor inpatients with non-small celllung cancer2005

    • Author(s)
      Murakami.H.et al.
    • Journal Title

      Clin. Cancer Res. 11

      Pages: 8674-8679

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Two cases of hyperkalemia after administration of hypertonic mannitol during craniotomy.2005

    • Author(s)
      Hirota, K. et al.
    • Journal Title

      J Aflesth. 19

      Pages: 75-77

    • NAID

      10014429030

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of hypoxia-inducible factor 1 by prolyl and asparaginyl hydroxylases.2005

    • Author(s)
      Hirota, K. et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 338

      Pages: 610-616

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hypoxia reduces constitutive and TNF-alpha-induced Expression of monocyte chemoattractant protein-1 in human proximal renal tubular cells.2005

    • Author(s)
      Li, X.et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 335

      Pages: 1026-1034

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] KL-6, a human MUCI mucin, promotes proliferation and survival of lung fibroblasts.2005

    • Author(s)
      Ohshimo, S. et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 30

      Pages: 1845-1852

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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.
    • Journal Title

      Clin.Cancer Res 11

      Pages: 8674-8679

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Two cases of hyperkalemia after administration of hypertonic mannitol during craniotomy.2005

    • Author(s)
      Hirota, K., Hara, T., Hosoi, S., Hara, Y., Adachi, T.
    • Journal Title

      J.Anesth. 19

      Pages: 75-77

    • NAID

      10014429030

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of hypoxia-inducible factor 1 by prolyl and asparaginyl hydroxylases.2005

    • Author(s)
      Hirota, K., Semenza, G.
    • Journal Title

      Biochem.Biophys.Res.Commun. 338

      Pages: 610-606

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hypoxia reduces constitutive and TNF-alpha-induced expression of Monocyte chemoattractant protein-1 in human proximal renal tubular cells.2005

    • Author(s)
      Li, X., Kimura, H., Hirota, K., Sugimoto, H., Yoshida, H.
    • Journal Title

      Biochem.Biophys.Res.Commun. 335

      Pages: 1026-1034

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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.
    • Journal Title

      Biochem.Biophys.Res.Commun. 30

      Pages: 1845-1852

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Circulating aminopeptidase N/CD13 is an independent prognostic factor in patients with non-small celllung cancer.2005

    • Author(s)
      Murakami, H. et al.
    • Journal Title

      Clin.Cancer Res. 11

      Pages: 8674-8679

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Clinicopathological significance of Aminopeptidase N/CD13 expression in human gastric carcinoma.2005

    • Author(s)
      Kawamura, J. et al.
    • Journal Title

      Hapato-gastroenterol. (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Two cases of hyperkalemia after administration of hypertonic mannitol during craniotomy.2005

    • Author(s)
      Hirota, K. et al.
    • Journal Title

      J.Anesth. 19

      Pages: 75-77

    • NAID

      10014429030

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Regulation of hypoxia-inducible factor 1 by prolyl and asparaginyl hydroxylases.2005

    • Author(s)
      Hirota, K. et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 338

      Pages: 610-616

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hypoxia reduces constitutive and TNF-alpha-induced expression of monocyte chemoattractant protein-1 in human proximal renal tubular cells.2005

    • Author(s)
      Li, X.et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 335

      Pages: 1026-1034

    • Related Report
      2005 Annual Research Report
  • [Journal Article] KL-6, a human MUC1 mucin, promotes proliferation and survival of lung fibroblasts.2005

    • Author(s)
      Ohshimo, S. et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 30

      Pages: 1845-1852

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The Plasminogen activation system reduces fibrosis in the lung by a Hepatocyte growth factor-dependent mechanism.2004

    • Author(s)
      Hattori, N., et al.
    • Journal Title

      Am. J. Pathol 164

      Pages: 1091-1098

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] MRP-1/CD9 gene transduction downregulates Wnt signal pathways.2004

    • Author(s)
      Huang, C. et al.
    • Journal Title

      Oncogene 23

      Pages: 7475-7483

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 癌の封じ込めによる肺切除適応の拡大 Enlargement of application for lung cancer surgery based on metastasis prevention.2004

    • Author(s)
      石田久雄 et al.
    • Journal Title

      外科治療 90

      Pages: 85-86

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 多変量解析による膵癌の進展・予後に関与する遺伝子異常の検索2004

    • Author(s)
      池田直也 e tal.
    • Journal Title

      病理と臨床 22

      Pages: 819-825

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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.
    • Journal Title

      Am.J.Pathol. 164

      Pages: 1091-1098

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Gene therapy for pulmonary diseases.2004

    • Author(s)
      Hattori, N., Miyake, M.
    • Journal Title

      Frontiers in Immuno-gene Therapy

      Pages: 209-225

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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.
    • Journal Title

      Oncogene 23

      Pages: 7475-7483

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The plasminogen activation system reduces fibrosis in the lung by a hepatocyte growth factor-dependent mechanism.2004

    • Author(s)
      Hattori, N. et al.
    • Journal Title

      American Jpurnal of Pathology 164

      Pages: 1091-1098

    • Related Report
      2004 Annual Research Report
  • [Journal Article] MRP-1/CD9 gene transduction downregulates Wnt signal patyhways.2004

    • Author(s)
      Huang, C. et al.
    • Journal Title

      Oncogene 23

      Pages: 7475-7483

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Response shift in perception of sleepiness in obstructive sleep apnes-hypopnea syndrome before and after treatment with nasal CPAP.2004

    • Author(s)
      Chin, K. et al.
    • Journal Title

      Sleep 27

      Pages: 490-493

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The intravenous anesthetic propofol inhibits hypoxia-inducible factor 1 activity in an oxygen tension-dependent manner.2004

    • Author(s)
      Takabuchi, S. et al.
    • Journal Title

      FEBS Lett 577

      Pages: 434-438

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The inhibitory effect of sodium nitroprusside on HIT-1 activation is not dependent on nitric oxide-soluble guanylyl cyclase pathway.2004

    • Author(s)
      Takabuchi, S. et al.
    • Journal Title

      Biochemical and Biophysical Research Communications 324

      Pages: 417-423

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Induction of hypoxia-inducible factor 1 activity by muscarinic acetylcholine receptor-signaling.2004

    • Author(s)
      Hirota, K. et al.
    • Journal Title

      Journal of Biological Chemistry 279

      Pages: 41521-41528

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Clinical significance of Aminopeptidase N in Non-Small Cell LungCancer.

    • Author(s)
      Tokuhara.T.et al.
    • Journal Title

      Clin. Cancer Res. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] MRP-1/CD9 gene transduction regulates the actin cytoskeleton through the down-regulation of WAVE2.

    • Author(s)
      Huang, CL. et al.
    • Journal Title

      Oncogene (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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.
    • Journal Title

      Oncogene (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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.
    • Journal Title

      Clin, Cancer, Res. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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
    • Related Report
      2005 Final Research Report Summary
  • [Book] Frontiers in lmmuno-gene Therapy2004

    • Author(s)
      Hattori.N., Miyake, M.
    • Total Pages
      16
    • Publisher
      Research Signpost
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Frontiers in Immuno-gene Therapy2004

    • Author(s)
      Hattori, N, Miyake, M.
    • Total Pages
      16
    • Publisher
      Osamu Mazda
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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