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Integrins in hepatocellular carcinoma and antimetastatic therapies

Research Project

Project/Area Number 10670519
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKansai Medical University

Principal Investigator

NAITOH Yuji  Kansai Medical University, School of medicine, Assistant professor, 医学部, 講師 (30198014)

Co-Investigator(Kenkyū-buntansha) NAKAHASHI Yoshitsugu  Kansai Medical University, School of medicine, Assistant professor, 医学部, 助手 (70247930)
MATSUZAKI Koichi  Kansai Medical University, School of medicine, Assistant professor, 医学部, 講師 (70278638)
SEKI Toshihito  Kansai Medical University, School of medicine, Associate professor, 医学部, 助教授 (70163087)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordshepatocellular carcinoma / integrin / metastasis
Research Abstract

The progression of a tumor cells from one of benign delimited proliferation to invasive and metastatic growth is the major cause of poor clinical outcome in the patients with cancer. During the process of invasion and metastasis, cancer cells are known to interact with extracellular matrices (ECM), endothelial cells, platelets and other organ-specific structure. The integrins are heterodimeric molecules which mediate cell-ECM and cell-cell interactions, and are likely to be important for cancer cell survival and dissemination.
Recent findings from our laboratory have indicated that the types and levels of integrins in human hepatocellular carcinoma (HCC) cell lines are required during the following steps in the generation of distant metastases : a) angiogenesis ; b) detachment from the primary site ; c) migration ; d) intra- and extra-vasation (adhesion to vascular endothelium), and e) proliferation. We next investigated the expression of integrins in the specimens obtained from the pat … More ients with HCC, and found that notable changes in several integrin subunits occurred during tumor progression and invasion. These changes included increased or decreased expression, or changes in distribution from a polarized to a dispersed pattern, and were well correlated with malignant phenotypes of human HCC such as poor differentiation, size of tumor, absence of capsule, invasion to portal veins, and distant metastasis. Alterations in the integrin expression are useful as cancer invasion markers for prognostic and for diagnostic purpose.
Once invading cancer cells have gained access to the circulation, adhesion to the endothelia and other tissue components facilitates the establishment of tumor colonies at distant sites. Angiogenic endothelial cells in tumor vessels depend on the alpha v family of integrins for survival. Interfering with cancer cell attachment with integrin-binding cyclic peptides, and inhibiting angiogenesis with compounds that block the activity of alpha v subunits have been shown to be an effective anti-metastatic strategy. Ongoing efforts to develop specific pharmacological agonists and antagonists for integrins hold great promise in clinical medicine. Less

Report

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

    (37 results)

All Other

All Publications (37 results)

  • [Publications] S. Yanagitani, et al.: "Ischemia induces metallothionein III expression in neurons of rat brain"Life Sciences. 64. 707-715 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. Miyazaki, et al.: "Induction of metallothionein isoforms in rat hepatoma cells by ... ..."J. Biochem.. 124. 65-71 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] N. Yamashiki, et al.: "Usefullness of AFP-L3 as a marker of distant metastasis from ... ..."Oncology Reports. 6. 1229-1232 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M. Matsushita, et al.: "Down-regulation of TGF-β receptors in human colorectal cancer"Br. J. Cancer. 80. 194-205 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Seki, et al.: "Percutaneous microwave coagulation therapy for patients with ... ..."Cancer. 85. 1694-1702 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M. Imamura, et al.: "Preliminary investigation of resistance of plasmid DNA to ... ..."Int. J. Mol. Med. 4. 57-59 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 内藤 雄二: "肝疾患研究の新しい展開"メディカルレビュー社. 183 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 関 寿人: "消化器疾患のIVR 肝・膵疾患のIVR治療"メジカルレビュー社. 181 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S. Yanagitani: "Ischemia induces metallothionein III expression in neurons of rat brain"Life Sci.. 64. 707-715 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. Miyazaki: "Induction of metallothionein isoforms in rat hepatoma cells by various anticancer drugs"J. Biochem.. 124. 65-71 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] A. Okajima: "Induction of hepatocyte growth factor activator messenger RNA in the liver following tissue injury and acute inflammation"J. Hepatology. 25. 97-102 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] N. Yamashiki: "Usefulness of Lens culinaris agglutinin A-reactive fraction of α-fetoprotein (AFP-L3) as a marker of distant metastasis from hepatocellular carcinoma"Oncology Reports. 4. 1229-1232 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M.. Imamura: "Preliminary investigation of resistance of plasmid DNA to neon ion beams using transformation into recipient Escherichia coli cells"Int. J. Mol. Med.. 6. 57-59 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M. Matsushita: "Down-regulation of TGF-β receptors in human colorectal cancer : Implications for cancer development"Br. J. Cancer. 80. 194-205 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Seki: "Percutaneous microwave coagulation therapy for patients with small hepatocellular carcinoma : Comparison with percutaneous ethanol injection therapy"Cancer. 85. 1694-1702 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Seki: "Percutaneous microwave coagulation therapy for solitary metastatic liver tumors from colorectal cancer : A pilot clinical study"Am. J. Gastroenterol.. 94. 322-327 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Seki: "Hepatic infarction following percutaneous ethanol injection therapy for hepatocellular carcinoma"Eur. J. Gastroenterol. Hepatol.. 10. 915-918 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M. Date: "Differential expression of transforming growth factor-β and its receptors in hepatocytes and nonparenchymal cells of rat liver after CC14 administration"J. Hepatol.. 28. 572-581 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M. Imamura: "Change of temperature in mouse tumor tissue immersed in a water bath at 44℃"Oncology Reports. 5. 1061-1064 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M. Imamura: "Enhancement by hyperthermia of the in vivo antitumor effect of doxorubicin hydrochloride (DOX) and buthioninesulfoximine (BSO)-hydroxyapatite (HAP) complex"Int. J. Oncol.. 10. 961-964 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Tamai: "Development of local necrosis, side effects and histopathological study after hepatic injection of acetic acid solution"Int. Hepatol. Commun.. 6. 153-157 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] A. Taniguchi: "Ligand-dependent and -independent interactions with the transforming growth factor type II and I receptor subunits reside in the aminosterminal portion of the ectodomain of the type III subunit"In Vitro Cell. Dev. Biol. Aminal. 34. 232-238 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] C. Yamamoto: "Immunolocalization of transforming growth factor β during wound repair in rat retina after laser photocoagulation"Graefe's Arch Clin. Exp. Ophthalmol.. 236. 41-46 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S.Yanagitani,et al: "Ischemia induces metallothionein III expression in neurons of rat brain"Life Sciences. 64. 707-715 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Miyazaki,et al: "Induction of metallothionein isoforms in rat hepatoma cells by ・・・ ・・・"J.Biochem.. 124. 65-71 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] N.Yamashiki,et al: "Usefullness of AFP-L3 as a marker of distant metastasis from ・・・ ・・・"Oncology Reports. 6. 1229-1232 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Matsushita,et al: "Down-regulation of TGF-β receptors in human colorectal cancer"Br.J.Cancer. 80. 194-205 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Seki,et al: "Percutaneous microwave coagulation therapy for patients with ・・・ ・・・"Cancer. 85. 1694-1702 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Imamura.at al: "Preliminary investigation of resistance of plasmid DNA to ・・・ ・・・"Int.J.Mol.Med. 4. 57-59 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 内藤 雄二: "肝疾患研究の新しい展開 第II巻"メディカルレビュー社. 183 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] 関 寿人: "消化器疾患のIVR 肝・膵疾患のIVR治療"メディカルレビュー社. 181 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Yanagitani,et al: "Ischania induces metalls thionein III expression in neurons of rat brain" Life Sciences. 64巻・8号. 707-715 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Miyazaki,et al: "Induction of metallothionein isoforms in rat hepatoma cells by various anticancer anup" J.Biochem.124. 65-71 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Date,et al: "Differential expression of transforming growth foctor-β and its receptors in hepatocytes and nonparenchymal cells of rat bitw after CCl_4 administration" J.Hepatol.28. 572-581 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Imamura,et al: "Chance of tempenatore in mouse tumor tissue immerdeal in a water-bath at 44゚C" Oncology Reports. 5. 1061-1064 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] A.Okajima,et al: "Induction of hepatocyte growth factor activator messenger RNA in the liver following tissue injury and acute inflowmation" Hepatology. 25. 97-102 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 内藤 雄二: "肝疾患研究の新しい展開 Vol.II" メディカルレビュー社(発行者,松岡光明), 183 (1997)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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