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Gene transfer of Endostatin and K1-5 suppresses the growth of hepatocellular carcinoma

Research Project

Project/Area Number 11670550
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKURUME UNIVERSITY

Principal Investigator

TORIMURA Takuji  Kurume University School of Medicine ・ Assistant professor, 医学部, 講師 (60197986)

Co-Investigator(Kenkyū-buntansha) HARADA Riko  Kurume University School of Medicine, 医学部, 助手 (50279155)
UENO Takato  Research Center for Innovative Cancer Therapy of Kurume University ・ Professor, 先端癌治療研究センター, 教授 (70176618)
金 基哲  久留米大学, 医学部, 助手 (30279145)
Project Period (FY) 1999 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsGene therapy / Endostatin / K1-5 / cDNA / Damage of endothelial cell / Liposome / Hepatoma / Nude mouse / Kringle1-5 / endostatin / 内皮細胞 / 遺伝子銃 / プラスミド / PCR
Research Abstract

We investigated anti-tumor effect of endostatin and K1-5, potent anti-angiogenc factors. We used KYN-2 cells, a human hepatoma cell line. KYN-2 cells(2 ×10^6 cells)were implanted in the liver of nude mice. Seven days after implantation, 100 μg of endostatin cDNA and K1-5 cDNA were transferred via tail vein by liposome method twice a week for 3weeks. For control mice, empty plasmid was injected. At day 28, the mice ware killed and tumor volume was calculated as length x width^2 × 0.52.
Of endostatin treated group, tumor growth was not observed in 2 of 6 cases. Average tumor volume was 69.5 ± 76mm^3. Of K1-5 treated group, tumor growth was not observed in 3 of 6 cases. Average tumor volume was 69.5 ± 76mm^3. On the otherhand, tumor development was detected in every case of control group. Average tumor volume was 2175 ± 1386mm^3(p<0.05). The expression of endostatin and K1-5 proteins was detected in pulmonary epithelial cells, hepatocytes, and hapatoma cells, respectively.
In addition, we investigated anti-tumor effect of adenovirus-mediated gene transfer of endostatin. Adenovirus-endostatin (1.5×10^9) was injected into the peritoneal cavity of nude mice 7days after implantation of KYN-2 cells (2 × 10^6 cells)into the liver. At day 28, mice ware killed and tumor volume was calculated. In endostatin treated group, average tumor volume was 180± 129mm^3. In control group, average tumor volume was 1797± 1228mm^3(p<0.05). These findings indicate that the gene therapy with endostatin and K1-5, potent anti-angiogenc factors significantly suppresses the growth of hepatocellular carcinoma.

Report

(5 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Takuji T: "Integrin α_6β_1 plays a sigmificant role in the attachment of hepatoma cells to laminin"Journal of Hepatology. 31. 734-740 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takuji T: "VEGF Partucipates in Neovascularization and Sinusoidal Capillarization in HCC"Springer-Verlag Tokyo. 274-287 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Riko O: "Increased Expression of Membrane Type 1 Dedifferentiation in Hepatocellular Carcinomas"HUMANPATHOLOGY. 30. 443-450 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takuji T: "Angiogenesis inhibitor TNP-470 suppression of experimentally-induced hapatpcellular carcinoma in rats"INTERNATIONAL JOURNAL OF ONCOLOGY. 16. 375-382 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takuji T: "Laminin deposition to type IV Collagen enhances haptotaxis, chemoklnesis, and adhesion of hapatoma cells through β1-integrins"Journal of Hepatology. 35. 245-253 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takuji T: "Autocrine Motility Factor Enhances Hepatoma Cell Invasion Across the Basement Membrane Through Activation of β1 Integrins"HEPATOLOGY. 62-71 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takato U: "Relation of type II transforming growth factor-β receptor to hepatic fibrosis and hepatocellular cercinoma"INTERNATIONAL JOURNAL OF ONCOLOGY. 18. 49-55 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 鳥村拓司: "肝細胞癌における血管新生の機序とその制御"肝胆膵. 45(4). 563-569 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 鳥村拓司: "肝細胞癌における血管新生の機序とその抑制"肝胆膵. 45. 563-569 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Motoaki Kin: "AngiogenesisinhibitorTNP-470 suppressesthe progressionof experimentally-induced hepatocellularcarcinomain rats."International Journal of Oncology. 16. 375-382 (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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