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Non-invasive in vivo analysis of early metastatic processes

Research Project

Project/Area Number 09470506
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionUniversity of Shizuoka

Principal Investigator

OKU Naoto  University of Shizuoka, School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (10167322)

Co-Investigator(Kenkyū-buntansha) TSUKADA Hideo  Hamamatsu Photonics K. K., Central Research Laboratory, Senior Researcher, 中央研究所, 専任部員
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥11,900,000 (Direct Cost: ¥11,900,000)
Fiscal Year 1999: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1997: ¥5,700,000 (Direct Cost: ¥5,700,000)
Keywordsmetastasis / positron emission tomography (PET) / cell trafficking / imaging / selectin / integrin / macrophage / metastasis suppresion / 転移標的組織 / 免疫監視機構 / ポジトロンCT (PET) / シアリルルイスA / NR細胞 / スルファチド / シアリルルイスX
Research Abstract

For elucidating early phase of tumor metastasis, we developed non-invasive method to determine metastatic tumor cell trafficking by PET. We have already observed the correlation between metastatic potential and metastatic cell accumulation in a target tissues. In the present study, we firstly clarified the involvement of selectins in the early tumor cell trafficking. We also observed sulfatide, a ligand for selectins, suppressed tumor metastasis. Secondly, we investigated the role of integrins in tumor metastatic process by using integrin transfectants. CHO cells were transfected with a chain of integrins, I.e., α2, α3, α4, α6, α9 and av. PET analysis indicated that integrin αvβ1 and α4β1 enhanced tumor cell accumulation in a target tissue. Furthermore, useful evidences were obtained about involvement of integrin avb3 in liver metastasis. Thirdly, we investigated the role of immune surveillance on the suppression of tumor metastasis. If small number of tumor cells were injected in experimental metastatic model, metastasis was not observed due to removal of tumor cells from target by immune defense system. In fact, metastasis was observed in mice which were pretreated for the depletion of macrophages even when small number of tumor cells were injected. And, in this case, removal of tumor cells from target tissues was suppressed by the determination of PET. Therefore, we clearly demonstrated that macrophage play an important role for suppressing metastasis in the early stage of metastatic processes.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Chieko Koike, et al: "Tumor Cells with Organ-specific Metastatic Ability Show Distinctive Trafficking in Vivo : Analyses by Positron Emission Tomography and Bioimaging"Cancer Res.. 57. 3612-3619 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Naoto Oku, et al.: "Application of Liposomes for Cancer Metastasis"Adv. Drug Delivery Rev.. 24. 215-223 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Naoto Oku, et al.: "Application of Long-circulating Liposomes to Cancer Photodynamic Therapy"Biol. Pharm. Bull.. 20. 670-673 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Chieko Koike, et al: "How Platelet Aggregation Affects B16BL6 Melanoma Cell Trafficking"FEBS Lett. 427. 286-290 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tomohiro Asai, et al.: "5'-O-dipalmitoylphosphatidyl 2'-C-Cyano-2'-deoxy-1-β-D-arabiono-pentofuranosyl-cytosine Is Enhanced by Long-circulating Liposomalization"Biol. Pharm. Bull.. 21. 766-771 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Dail Ishikawa, et al.: "GD1α-Replica peptides Functionally Mimic GD1 α, an Adhesion Molecule of Metastaric Tumor Cells, and Suppress the Tum or Metastasis"FEBS Lett.. 441. 20-24 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hironori Kikkawa, et al.: "Role of Sialylglycoconjugate(s) in the Initial Phase of Metastasis of Liver-metastatic RAW117 Lymphoma Cells"Jpn. J. Cancer Res.. 89. 1296-1305 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Naoto Oku: "Delivery of contrast agents for positron emission tomography imaging by liposomes"Adv. Drug Delivery Rev.. 37. 53-61 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Naoto Oku: "Anticancer Therapy Using Glucuronate Modified Long-circulating Liposomes"Adv. Drug Delivery Rev.. 40. 63-73 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshiko Fujimoto, et al.: "Magnetic Resonance Lymphography of Profundus Lymph Nodes with Liposomal Gadolinium-Diethylenetriamine Pentaacetic Acid"Biol. Pharm. Bull.. 23. 97-100 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masako Takikawa, et al.: "Suppression of GD1 α ganglioside-mediated tum or metastasis by liposomalized WHW-peptide"FEBS Lett.. 466. 381-384 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hironori Kikkawa, et al.: "Possible Role Immune Surveillance at the Initial Phase of Metastasis Produced by B16BL6 Melanoma Cell"FEBS Lett.. 467. 211-216 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Chieko Koike, Manabu Watanabe, Naoto Oku,Hideo Tsukada, Tatsuro Irimura and Shoji Okada: "Tumor Cells with Organ-specific Metastatic Ability Show Distinctive Trafficking in Vivo : Analyses by Positron Emission Tomography and Bioimaging."Cancer Res.. 1997. 3612-3619 (57)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Naoto Oku, Chieko Koike, Yoshihiro Tokudome, Shoji Okada, Naoyuki Nishikawa, Hideo Tsukada, Makoto Kiso, Akira Hasegawa, Hideki Fujii, Jun Murata and Ikuo Saiki: "application of Liposomes for Cancer Metastasis."Adv. Drug Delivery Rev.. 24. 215-223 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Naoto Oku, Nobuko Saito, Yukihiro Namba, Hideo Tsukada, David Dolphin, and Shoji Okada: "Application of Long-circulating Liposomes to Cancer Photodynamic Therapy."Biol. Pharm. Bull.. 20. 670-673 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Chieko Koike, Manabu Watanabe, Atsushi Isoai, Hiromichi Kumagai, Hideo Tsukada, Tatsuro Irimura, Shoji Okada and Naoto Oku: "How Platelet Aggregation Affects B16BL6 Melanoma Cell Trafficking."FEBS Lett.. 427. 286-290 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tomohiro Asai, Kohta Kurohane, Satoshi Shuto, Hirokazu Awano, Akira Matsuda, Hideo Tsukada, Yukihiro Namba, Shoji Okada and Naoto Oku: "Antitumor Activity of 5'-O-Dipalmitoylphosphatidyl 2'-C-Cyano-2'-deoxy-1-b-D-arabiono-pentofuranosylcytosine Is Enhanced by Long-circulating Liposomalization."Biol. Pharm. Bull.. 21. 766-771 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Dai Ishikawa, Hironori Kikkawa, Koichi Ogino, Yoshio Hirabayashi, Naoto Oku and Takao Taki: "GD1a-Replica Peptides Functionally Mimic GD1a, and Adhesion Molecule of Metastatic Tumor Cells, and Suppress the Tumor Metastasis."FEBS Lett.. 441. 20-24 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hironori Kikkawa, Daisei Miyamoto, Hidetoshi Imafuku, Chieko Koike, Yasuno Suzuki, Shoji Okada, Hideo Tsuka, Tatsuro Irimura and Naoto Oku: "Role of Sialylglycoconjugate(s) in the Initial Phase of Metastasis of Liver-metastatic RAW117 Lymphoma Cells."Jpn. J. Cancer Res.. 89. 1296-1305 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Naoto Oku: "Delivery of contrast agents for positron emission tomography imaging by liposomes."Adv. Drug Delivery Rev.. 37. 53-61 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Naoto Oku: "Anticancer Therapy Using Glucuronate Modified Long-circulating Liposomes."Adv. Drug Delivery Rev.. 40. 63-73 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshiko Fujimoto, Yoshitaka Okuhata, Shia Tyngi, Yukihiro Namba and Naoto Oku: "Magnetic Resonance Lymphography of Profundus Lymph Nodes with Liposomal Gadolinium-Diethylenetriamine Pentaacetic Acid."Biol. Pharm. Bull.. 23. 97-100 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masako Takikawa, Hironori Kikkawa, Tomohiro Asai, Naoto Yamaguchi, Dai Ishikawa, Michinori Takao, and Naoto Oku: "Suppression of GD1a ganglioside-mediated tumor metastasis by liposomalized WHW-peptide."FEBS Lett.. 466. 381-384 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hironori Kikkawa, Hidetoshi Imafuku, Hideo Tsukada and Naoto Oku: "Possible Role Immune Surveillance at the Initial Phase of Metastasis Produced by B16BL6Melanoma Cell."FEBS Lett.. 467. 211-216 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Naoto Oku: "Delivery of contrast agents for positron emission tomography imaging by liposomes"Adv.Drug Delivery Rev.. 37. 53-61 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Naoto Oku: "Anticancer therapy using glucuronate modified long-circulating liposomes"Adv.Drug Delivery Rev.. 40. 63-73 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshiko Fujimoto,et al.: "Magnetic resonance lymphography of profundus lymph nodes with liposomal gadolinium-diethylenetriamine pentaacetic Acid"Bio.Pharm.Bull.. 23. 97-100 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Masako Takikawa,et al.: "Suppression of GD1 α ganglioside-mediated tumor metastasis by liposomalized WHW-peptide"FEBS Lett.. 466. 381-384 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hironori Kikkawa,et al.: "Possible role immune surveillance at the initial phase of metastasis produced by B16BL6 melanoma cell"FEBS Lett.. 467. 211-216 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Chieko Koike,et.al: "How Platelet Aggregation Affects B16BL6 Melanoma Cell Trafficking." FEBS Lett.,. 427. 286-290 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Dai Ishikawa,et.al: "GD1α-replica Peptides Functionally Mimic GD1α,an adhesion molecule of metastatic tumor cells,and suppress the tumor metastasis." FEBS Lett.,. 441. 20-24 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hironori Kikkawa,et.al: "Role of Sialylglycoconjugate(s) in the Initial Phase of Metastasis of Liver-metastatic RAW117 Lymphoma Cells." Jpn.J.Cancer Res. 89. 1296-1305 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Chieko Koike, et.al: "Tumor Cells with Organ-specific Metastatic Ability Show Distinctive Trafficking in Vivo:Analyses by Positron Emission Tomography and Bioimaging" Cancer Res.57. 3612-3619 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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