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Analysis of the function of Aminopeptidase N and neutral and peptidase and application of its cancer therapy.

Research Project

Project/Area Number 14571169
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

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)

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)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
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)
Keywordsangiogenesis / APN / CD13 / NEP / CD10
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.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Ikeda, N. et al.: "Clinical Significance of Aminopeptidase N/CD13 Expression in Human Pancreatic Carcinoma."Clinical Cancer Research. 9. 1503-1508 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hashida, H, et al.: "Clinical Significance of Transmembrane 4 Superfamily in Colon Cancer."British Journal of Cancer. 89. 158 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ding, Y. et al.: "Association of CC cChemokine Receptor 7 with Lymph Node Metastasis of Esophageal Squamous Cell Carcinoma."Clinical Cancer Research. 9. 242-245 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kim, KK., et al.: "A plasminogen activator inhibitor-1 promoter polymorphism and idiopathic interstitial pneumonia."Molecular Medicine. 9. 52-56 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 石田久雄 et al.: "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."外科治療. 90. 85-86 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hattori N, et al.: "The plasminogen activation system reduces fibrosis in the lung by a hepatocyte growth factor-dependent mechanism."American Journal of Pathology. 164. 1091-1098 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 三宅正幸 et al.: "これだけは知っておきたい-遺伝子医学の基礎知識"メデイカル ドゥ. 7 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimizu, K., Chin, K., Nakarnura, T., Masuzaki, H., Ogawa, Y, Hosokawa, R., Niimi, A., Hattori, N., Sasayama, S., Nakao, K., Mishima, M., Nakamura, T., Ohi, M.: "Plasma leptin levels and cardiac sympathetic function in patients with obstructive sleep apnoea-hypopnoea syndrome."THORAX. 57. 429-434 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sisson, TH., Hanson, IKE., Subbotina, N., Patwardhan, A., Hattori, N., Simon, RH.: "Inducible lung-specific urokinase expression reduces fibrosis and mortality after lung injury in mice."Am J Physiol Lung Cell Mol Physiol. 283. L1023-L1032 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hashida, H., Takabayashi, A., Tokuhara, T, Taki, T., Kondo, K., Kohno, N., Yamaoka, Y., Miyake M.: "Integrin α3 Expression as a Prognostic Factor in Colon Cancer : Association with MiRP-1/CD9 and KAI1/CD82."INT J CANCER. 97. 518-525 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kohno, M., Hasegawa, H., Miyake, M., Yamamoto, T., Fujita, S.: "CD151 Enhances Cell Motility and Metastasis of Cancer Cells in the Presence of Focal Adhesion Kinase."INT J CANCER. 97. 336-343 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hashida, H., Takabayashi, A., Kanai, M., Adachi, M., Kondo, K., Kohmo, N., Yamaoka, Y., Miyake, M.: "Aminopeptidase N Is Involved in Cell Motility and Angiogenesis : Its Clinical Significance in Human Colon Cancer."GASTRORNTEROLOGY. 122. 376-386 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kim, KK., Flaherty, KR., Long, Q., Hattori, N., Sisson, TH., Colby, TV., Travis, WD., Martinex, FJ., Murray, S., Simon, RH.: "A plasnimogen activator inhibitor-1 promoter polymorphism and Idiopathic interstitial pneumonia."Mol Med. 9. 52-56 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda, N., Nakajima, Y, Tokuhara, T., Hattori, N., Sho, M., Kanehiro, H, Miyake, M.: "Clinical Significance of Aminopeptidase N/CD13 Expression in Human Pancreatic Carcinoma."CLIN CANCER RES. 9. 1503-1508 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Chin, K., Nakamura, T., Takahashi, K., Sunu, K., Ogawa, Y, Masuzaki, H., Muro, S., Hattori, N., Matsumoto, H., Niimi, A., Chiba, T., Nakao, K., Mishima, M., Ohi, M., Nakarnura, T.: "Effects of obstructive sleep apnea syndrome on serum aminotransferase Levels in obese patients."Am J Med. 114. 370-376 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hashida, H., Takabayashi, A., Tokuhara, T., Hattori, N., Taki, T., Hasegawa, H., Satoh, S., Kobayashi, N., Yamaoka, Y., Miyake, M.: "Clinical Significance of Transmenbrane 4 Superfamily in Colon Cancer."BRIT J CANCER. 89. 158-167 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hattori, Y, Nerusu, KC., Bhagavathula, N., Brennan, M., Hattori, N., Murphy, HS., Su, LD., Wang, TS., Johnson, TM., Varani, J.: "Vascular expression of matrix metalloproteinase-13 (collagenase-3) In basal cell carcinoma."Exp Mol Pathol... 74. 230-237 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Chuang-Tsai, S., Sisson, TH., Hattori, N., Tsai, CG, Subbotina, NM., Hanson, KE., Simon, RH.: "Reduction in fibrotic tissue formation in mice genetically deficient in Plasminogen avtivator inhibitor-1."AM J PATHOL. 163. 445-452 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ding, Y., Shimada, Y., Maeda, M., Kawabe, A., Kaganoi, J., Komoto, I., Hashimoto Y., Miyake, M., Hashida, H., Imamura, M.: "Association of CC cChemokine Receptor 7 with Lymph Node Metastasis of Esophageal Squamous Cell Carcinoma."CLIN CANCER RES. 9. 3406-3412 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hattori, N., Mizuno, S., Yoshida, Y, Chin, K., Mishima, M., Sisson, TH., Simon, RH., Nakamura, T., Miyake M.: "The Plasminogen activation system reduces fibrosis in the lung by a Hepatocyte growth factor-dependent mechanism."AM J PATHOL. 164. 1091-1098 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hattori, N., Miyake M.: "Gene therapy for pulmonary diseases."Frontiers in Immuno-gene Therapy. 209-225 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda, N. et al.: "Clinical Significance of Aminopeptidase N/CD13 Expression in Human Pancreatic Carcinoma."Clinical Cancer Research. 9. 1503-1508 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hashida H, et al.: "Clinical Significance of Transmenbrane 4 Superfamily in Colon Cancer."British Journal of Cancer. 89. 158 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ding, Y. et al.: "Association of CC cChemokine Receptor 7 with Lymph Node Metastasis of Esophageal Squamous Cell Carcinoma."Clinical Cancer Research. 9. 242-245 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kim, KK., et al.: "A plasminogen activator inhibitor-1 promoter polymorphism and idiopathic interstitial pneumonia."Molecular Medicine. 9. 52-56 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 石田久雄 et al.: "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."外科治療. 90. 85-86 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hattori, N. et al.: "The plasminogen activation system reduces fibrosis in the lung by a hepatocyte growth factor-dependent mechanism."American Journal of Pathology. 164. 1091-1098 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 三宅正幸 et al.: "これだけは知っておきたい-遺伝子医学の基礎知識"メディカル ドゥ. 7 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hashida, H. et al.: "Integrin α3 Expression as a Prognostic Factor in Colon Cancer : Association with MRP-1/CD9 and KAI1/CD82"International Journal of Cancer. 97. 518-525 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kohno, M. et al.: "CD151 Enhances Cell Motility and Metastasis of Cancer Cells in the Presence of Focal Adhesion Kinase"International Journal of Cancer. 97. 336-343 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hashida, H. et al.: "Aminopeptidase N Is Involved in Cell Motility and Angiogenesis : Its Clinical Significance in Human Colon Cancer"Gastroenterology. 112. 376-386 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ikeda, N. et al.: "Clinical Significance of Aminopeptidase N/CD13 Expression in Human Pancreatic Carcinoma"Clinical Cancer Research. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] 服部 登: "線溶系-呼吸器疾患とのかかわり"分子呼吸器病. 6. 58-60 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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