• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The analysis of the structure and the funtion of AIP and gene therapy using AIP

Research Project

Project/Area Number 11557087
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field General surgery
Research InstitutionTazuke Kofukai Medical Research Institute

Principal Investigator

ISHIDA Hisao (2000-2001)  Tazuke Kofukai Medical reserch Insutitute Dep. V of Oncology, 医学研究所・第5研究部, 研究員 (40322771)

足立 匡司 (1999)  財団法人 田附興風会, 医学研究所・第5研究部, 研究員 (20291015)

Co-Investigator(Kenkyū-buntansha) TAKI Toshihiko  Tazuke Kofukai Medical reserch Insutitute Dep. V of Oncology, 第5研究部, 主幹 (60135605)
MIYAKE Masayuki  Tazuke Kofukai Medical reserch Insutitute Dep. V of Oncology, 第5研究部, 部長 (90250076)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2001: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1999: ¥6,400,000 (Direct Cost: ¥6,400,000)
KeywordsAIP / angiogenesis / HUVEC / glycosylation / 糖鎖 / metastasis / 血管新生 / 血管新生因子
Research Abstract

The molecular basis of cell motility is obviously highly complex and is believed to be controlled by a number of molecular systems, while angiogenesis is an important biological component of fumor progression. 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. The present study utilized an approach based on the selection of HUVEC, which showed motility. We have addressed this study using functional monoclonal antibodies (MAbs), which inhibit HUVEC motility is probes The monoclonal antibody HM7 3 was established after immunization of mice with HUVEC, and was selected on the basis of its ability to inhibit HUVEC migration in a malrigel transwell penetration assay and tube formation. HM7-3 inhibited augiogenesis using eggs and cornea of rats. cDNA cloning revealed that HM7-3 recognizes a new specific protein structure and we named this protein Angiogenesis Inhibiting Protein (AlP). However, the extent of suppression of angiogenesis of malignant tumors is not directly related to the level of ALP expression. A repIication-deficient adenovirus vector was used for the in vivo transfer of All cDNA. Intratumor injection of an adenovirus vector (rAd-AIP) expressing AlP resulted in no inhibition of tumor angiogenesis. As ALP has several N-glycosyIation sites, the function of ALP may be, in general, highly controlled by N-glycosylation. De-N-glycosyltion of ALP results in the loss of functions. The terminal structure, sialic acid might have an important role on angiogenesis. On the other hand, ALP inhibits angiogenesis of the cornea of the rat, but cannot inhibit angiogenesis of malignant cells. The hypothesis may be considered that ALP may have an effect on angiogenesis of normal cells. The further examination will be necessary for the analysis of the mechanism of ALP.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report

Research Products

(50 results)

All Other

All Publications

  • [Publications] Huang, C., et al.: "p16 protein expression is associated with a poor prognosis in squamous cell carcinoma of the lung"British Journal of Cancer. 82. 374-380 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hirasawa, Y., et al.: "Natural autoantibody to MUC1 is a prognostic indicator for non-small cell lung cancer"American Journal of Respiratory and Critical Care Medicine. 161. 589-594 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Adachi, M., et al.: "Significance of integrin α5 gene expression as a prognostic factor in node negative non-small cell lung cancer"Clnical Cancer Research. 15. 96-101 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hamada, H., et al.: "A novel monoclonal antibody, H9, directed against the core protein of MUC1 Mucin"Oncology Report. 7. 225-232 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Konishi, T., et al.: "The K-ras gene regulates vascular endothelial growth factor gene expression in non-small cell lung cancers"International Journal of Oncology. 16. 501-511 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yagita, M., et al.: "A novel natural killer cell line (KHYG-1) from a patient with aggressive natural killer cell leukemia carrying a p53 point mutation"Leukemia. 14. 922-930 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miyake, M., et al.: "Suppression of pulmonary metastasis using adenovirally motility related protein-1 (MRP-1/CD9) gene delivery"Oncogene. 19. 5221-5226 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hashida, H., et al.: "The novel monoclonal antibody MH8-4 inhibiting cell motility recognizes integrin α3 : inverse of its expression with metastases in colon cancer"International Journal of Oncology. 18. 89-95 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ikeda, N., et al.: "The association of K-ras gene mutation and vascular endothelial growth factor gene expression in pancreatic cancers"Cancer. 92. 488-499 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tokuhara.T., et al.: "Neutral endopeptidase/CD1O and aminopeptidase N/CD13 gene expression as a nrncrnostic factorin non-small cell lung cancer"Japanese Journal of Thoracic and Cardiovascular Surgery. 49. 489-496 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tokuhara, T., et al.: "Clinical sibnificance of CD151 gene expression in non-small cell lung cancer"Clinical Cancer Research. 7. 4109-4114 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Inufusa, H., et al.: "Role of galectin-3 in adenocarcinoma liver metastasis"International Journal of Oncology. 19. 913-919 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hashida, H., et al.: "Aminopeptidase N is involved in cell motility and angiogenesis : its clinical significance in human colon cancer"Gastroenterology. 122. 376-386 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hashida, H., et al.: "Cell-Surface Aminopeptidase : Base and Clinical Aspects"Elsevier Science B. V.. 167-170 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Muneoka: "Comparative aspects of invertebrate neuropeptides"Acta Biologica Hungarica. 51(2-4). 111-132 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] O. Matsushima: "Annelid bioactive peptides : a comparative view"Trends in Comp. Biochem. Physiol.. 7. 131-141 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Kawada: "Identification of multiple urechistachykinin peptides, gene expression, pharmacological activity, and detection using mas spectrometric analyses"Peptides.. 21(12). 1777-1783 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. In: "Functional analysis fo C-terminal amide in bioactivity of endomorphin-2 : Conformational comparison with its unamidated peptide in DMSO solution."Peptide Science 2000. 313-316 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Satake: "Characterization of a cDNA encoding a novel avian hypothalamic neuropeptide exerting an inhibitory effect on gonadotropin release."Biochemical J.. 354(2). 379-385 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. In: "Conformational comparison of ? -selective endomorphin-2 with its C-terminal free acid in DMSO solutoin, by 1^HNMR spectroscopy and molecular modeling calculation."J. Peptide Res.. 58(5). 399-412 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Furukawa: "The enterins : a novel family of neuropeptides isolated from the enteric nerous sysem and CNS of Aplysia."J. Neurosci.. 21(20). 8247-8261 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Ukena: "A novel rat hypothalamic Rfamide-related peptide identified by immunoaffinity chromatography and mass spectrometry."FEBS Lett.. 512(1-3). 255-258 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] E. Iwakoshi: "Isolation and characterization of a GnRH-like peptide from Octopus vulgaris."Bioshem. Biophys. Res. Commun.. 291. 1187-1193 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] X. Wang: "A candidate for fish prolactin-releasing peptide isolated from Japanese crucian carp."Recent Advances in Comparative Endocrinology, J. Y. L. Yu (eds.). Taipei, Taiwan. 29-38 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Tsutsui: "A novel hypothalamic peptide inhibiting gonadotropin release."J. Th. Goos et al. (eds.), Monduzzi Editore, Sorrento, Italy. 481-487 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] E. Iwakoshi: "Isolation and characterization of a GnRH-like peptide from Octopus vulgaris."J. Th. Goos et al. (eds.), Monduzzi Editore, Sorrento, Italy. 585-590 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] O. Matsushima: "The GGNG-peptide family : annelid myoactive peptides"Perspective in Comparative Endocrinology, H. J. Th. Goos et al. (eds.), Monduzzi Editore, Sorrento, Italy. 905-909 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hashida H, et al.: "The Novel Monoclonal Antibody MH8-4 Inhibiting Cell Motility Recognizes Integrin α3 : Inverse of Its Expression with Metastases in Colon Cancer"Int.J.Oncol.. 18. 89-95 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ikeda N, et al.: "The Association of K-ras Gene Mutation and Vascular Endothelial Growth Factor Gene Expression in Pancreatic Cancers"Cancer. 92. 488-499 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tokuhara T, et al.: "Neutral Endopeptidase/CD 10 and Aminopeptidase N/CD13 Gene Expression as a Prognostic Factor in Non-Small Cell Lung Cancer"Jpn.J.Thorac.Cardiov.Surg. 49. 489-496 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tokuhara T, et al.: "Clinical Significance of CD151 Gene Expression in Non-Small Cell Lung Cancer"Clin.Cancer Res.. 7. 4109-4114 (2001)

    • Related Report
      2001 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"Int.J.Cancer. 97. 518-525 (2002)

    • Related Report
      2001 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. 122. 376-386 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hashida H, et al.: "Cell-Surface Aminopeptidase : Base and Clinical Aspects"S.Mizutani et al. Elsevier Science B.V.. 4 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Huang,C., et al.: "p16 protein expression is associated with a poor prognosis in squamous cell carcinoma of the lung."British Journal of Cancer. 82. 374-380 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hirasawa,Y., et al.: "Natural autoantibody to MUC1 is a prognostic indicator for non-small cell lung cancer."American Journal of Respiratory and Critical Care Medicine. 161. 589-594 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Adachi,M., et al.: "Significance of integrin α5 gene expression as a prognostic factor in node negative non-small cell lung cancer."Clinical Cancer Research. 15. 96-101 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hamada,H., et al.: "A novel monoclonal antibody, H9, directed against the core protein of MUC1 Mucin."Oncology Report. 7. 225-232 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Konishi,T., et al.: "The K-ras gene regulates vascular endothelial growth factor gene expression in non-small cell lung cancers."International Journal of Oncology. 16. 501-511 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yagita,M., et al.: "A Novel Natural Killer Cell Line (KHYG-1) from A Patient with Aggressive Natural Killer Cell Leukemia Carrying A p53 Point Mutation."Leukemia. 14. 922-930 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ikeda N.et al.: "Prognostic Significance of Angiogenesis in Human Pancreatic Cance"British Journal of Cancer. 79. 1564-1571 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Miyake M.et al.: "A Novel Molecular Staging Protocol for Non-small Cell Lung Cancer"Journal of Clinical Oncology. 18. 2397-2404 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Huang C.et al.: "Overexpression of Bax Associated with Mutations in the Loop-Sheet-Helix Motif of p53"American Journal of Pathology. 155. 955-965 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Huang C.et al.: "p16 Protein Expression Is Associated with a Poor Prognosis in Squamous Cell Carcinoma of the Lung"British Journal of Cancer. 82. 374-380 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Adachi M.et al.: "Significance of Integrin α5 Gene Expression as a Prognostic Factor in Node Negative Non-small Cell Lung Cancer"Clinical Cancer Research. 6. 96-101 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Konishi T.et al.: "The K-ras Gene Regulates Vascular Endothelial Growth Factor Gene Expression in Non-small Cell Lung Cancer"International Journal of Oncology. 16. 501-511 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 三宅正幸: "肺がんにおける糖鎖抗原の発現,がんの浸潤・転移 基礎研究の臨床応用"北島政樹(医学書院). 8 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 三宅正幸: "Key Word 1999-2000 呼吸器疾患"山木戸道郎,日和田邦男,小倉剛(先端医学社). 2 (1999)

    • Related Report
      1999 Annual Research Report

URL: 

Published: 1999-03-31   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi