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2001 Fiscal Year Final Research Report Summary

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

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
KeywordsAIP / angiogenesis / HUVEC / glycosylation
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.

Research Products

(29 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)

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  • [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)

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  • [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)

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

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [Publications] Tokuhara, T., et al.: "Clinical sibnificance of CD151 gene expression in non-small cell lung cancer"Clinical Cancer Research. 7. 4109-4114 (2001)

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  • [Publications] Inufusa, H., et al.: "Role of galectin-3 in adenocarcinoma liver metastasis"International Journal of Oncology. 19. 913-919 (2001)

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  • [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)

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  • [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)

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  • [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)

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  • [Publications] Hashida, H., et al.: "Cell-Surface Aminopeptidase : Base and Clinical Aspects"Elsevier Science B. V.. 167-170 (2001)

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  • [Publications] Y. Muneoka: "Comparative aspects of invertebrate neuropeptides"Acta Biologica Hungarica. 51(2-4). 111-132 (2000)

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  • [Publications] O. Matsushima: "Annelid bioactive peptides : a comparative view"Trends in Comp. Biochem. Physiol.. 7. 131-141 (2000)

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  • [Publications] T. Kawada: "Identification of multiple urechistachykinin peptides, gene expression, pharmacological activity, and detection using mas spectrometric analyses"Peptides.. 21(12). 1777-1783 (2000)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [Publications] E. Iwakoshi: "Isolation and characterization of a GnRH-like peptide from Octopus vulgaris."Bioshem. Biophys. Res. Commun.. 291. 1187-1193 (2002)

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  • [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)

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  • [Publications] K. Tsutsui: "A novel hypothalamic peptide inhibiting gonadotropin release."J. Th. Goos et al. (eds.), Monduzzi Editore, Sorrento, Italy. 481-487 (2001)

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  • [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)

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  • [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)

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Published: 2003-09-16  

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