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2007 Fiscal Year Final Research Report Summary

Genethraphy for the patients with metastatic or refractory osteosatcoma using Ad-OC-TK gene

Research Project

Project/Area Number 16390440
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionKobe University

Principal Investigator

AKISUE Toshihiro  Kobe University, Graduate School of Medicine, Assistant Professor (90379363)

Co-Investigator(Kenkyū-buntansha) NISHIDA Kotaro  Kobe University, Graduate School of Medicine, Assistant Professor (00379372)
GOTO Akinobu  Hyogo College of Medicine, 医学部, Professor (70283885)
SHIRAKAWA Toshiro  Kobe University, Graduate School of Medicine, Associate Professor (70335446)
Project Period (FY) 2004 – 2007
KeywordsGenetheraphy / Adenovirus / Osteocalcin / Clinical Trial / Gene Expression / Osteosarcoma
Research Abstract

We have established TNMY cell lines from the retrieved MFH. We tested the effects of PTK787 (inhibitor for VEGF receptors) on cell proliferation, invasion, angiogenesis of Nara H, Nara F, GBS-1, and TNMY.) We have not found the inhibitory effect of PTK787 on cell proliferation of MFH cell lines. Cell invasion of Nara H cells was inhibited by PTK787. All four cell lines showed inhibitory effects of PTK787 on angiogenesis. In the study of DcR3 decoy receptors related to apoptosis, inhibitory effect of siRNA on mRNA expression of DcR3 could be detected in osteosarcoma and MFH cell lines. The extent of protein expression in MFH cells was higher than that in osteosarcoma cells after siRNA treatment for DcR3. In osteosarcoma cells, the number of TUNEL positive cells after siRNA+FasL treatment was same as that after contral siRNA+FasL treatment, but the number of TUNEL positive cells after siRNA+FasL+adriamycin treatment was higher than that after contral siRNA+FasL+adriamycin treatment, indicating that siRNA+FasL+adriamycin treatment induced apoptosis in osteosarcoma cells. In the study of Sphingosine-1-posphate (S1P) and EDG receptors for S1P in sarcomas, we found that mRNA expression of EDG1, 3, and 5 in high-grade sarcomas was higher than that in low-grade sarcomas. Expression of Sphingosine kinase 2 (SPHK2) in low-grade sarcomas was higher that that in high-grade sarcomas, whereas we did not find the difference in mRNA expression of SPHK1 between low-grade and high-grade sarcomas
We produced Ad-OC-TK gene probes for clinical application at CPC cell culture center in Gene Medicine Japan and we tested the quality and security of probes for clinical use. The results of the tests were excellent for clinical use of Ad-OC-TK gene probes.

  • Research Products

    (16 results)

All 2008 2007 2006 2005

All Journal Article (12 results) (of which Peer Reviewed: 6 results) Presentation (4 results)

  • [Journal Article] Inhibition of PKC・activation in human bone and soft tissue sarcoma cells by selective PKC inhibitor PKC412.2008

    • Author(s)
      Kawamoto T, Akisue T, et. al.
    • Journal Title

      Anticancer Res

      Pages: 825-832

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Inhibition of PKCa activation in human bone and soft tissue sarcoma cells by selective PKC inhibitor PKC4122008

    • Author(s)
      Kawamoto, T, Akisue, T, et. al.
    • Journal Title

      Anticancer Res (In Press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Imanitib mesylate inhibits tumorigenicity of malignant fibrous histiocytoma cells in vivo.2007

    • Author(s)
      Irsan I, Akisue T, et. al.
    • Journal Title

      Anticancer Res 27

      Pages: 423-30

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] High level of ezrin mRNA expression in an osteosarcoma biopsy sample with lung metastasis.2007

    • Author(s)
      Ogino W, Takeshima Y, Mori T, Yanai T, Hayakawa A, Akisue T, at al.
    • Journal Title

      J Pediatr Hematol Onco 29

      Pages: 435-439

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Long-term outcome of phase I/II clinical trial of Ad-OC-TK/VAL gene therapy for hormone-refractory metastatic prostate cancer.2007

    • Author(s)
      Shirakawa T, Terao S, et. al.
    • Journal Title

      Hum Gene Ther 18

      Pages: 1225-1232

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Imanitib mesylate inhibits tumorigenicity of malignant fibrous histiocytoma cells in vivo2007

    • Author(s)
      Irsan, I, Akisue, T, et. al.
    • Journal Title

      Anticancer Res 27

      Pages: 423-30

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] High level of ezrin mRNA expression in an osteosarcoma biopsy sample with lung metastasis.2007

    • Author(s)
      Ogino, W, Takeshima, Y, Mori, T, Yanai, T, Hayakawa, A, Akisue, T, et. al.
    • Journal Title

      J Pediatr Hematol Onco 29

      Pages: 435-439

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Long-term outcome of phase I/II clinical trial of Ad-OC-TK/VAL gene therapy for hormone-refractory metastatic prostate cancer2007

    • Author(s)
      Shirakawa, T, Terao, S, Hinata, N, et. al.
    • Journal Title

      Hum Gene Ther 18

      Pages: 1225-1232

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expression of VEGF and its receptors and angiogenesis in bone and soft tissue tumors.2006

    • Author(s)
      Hara H, Akisue T, et. al.
    • Journal Title

      Anticancer Res 26

      Pages: 4307-11

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Expression of VEGF and its receptors and angiogenesis in bone and soft tissue tumors.2006

    • Author(s)
      Hara, H, Akisue, T, et. al.
    • Journal Title

      Anticancer Res 26

      Pages: 4307-11

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Establishment and characterization of a KIT-positive and stem cell factor-producing cell line, KTHOS, derived from human osteosarcoma.2005

    • Author(s)
      Hitora T, Yamamoto T, Akisue T, et. al.
    • Journal Title

      Pathol Int 55

      Pages: 41-47

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Establishment and characterization of a KIT-positive and stem cell factor-producing cell line, KTHOS, derived from human osteosarcoma.2005

    • Author(s)
      Hitora, T, Yamamoto, T, Akisue, T, et. al.
    • Journal Title

      Pathol Int 55

      Pages: 41-47

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Effect of angiogenesis inhibitor PTK787 for MFH in vitro.2008

    • Author(s)
      Hara H, Akisue T, et. al.
    • Organizer
      54th Annual Meeting of the Orthopaedic Research Society
    • Place of Presentation
      San Francisco USA
    • Year and Date
      2008-03-01
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Effect of angiogenesis inhibitor PTK787 for MFH in vitro2008

    • Author(s)
      Hara, H, Akisue, T, et. al.
    • Organizer
      54th Annual Meeting of the Orthopaedic Research Society
    • Place of Presentation
      San Francisco USA
    • Year and Date
      2008-03-01
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Inhibitory effect of pkc412 on cell proliferation of human bone and soft tissue sarcoma cell lines.2006

    • Author(s)
      Kawamoto T, Akisue T,
    • Organizer
      52th Annual Meeting of the Orthopaedic Research Society,
    • Place of Presentation
      Chicago USA
    • Year and Date
      2006-03-19
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Inhibitory effect of pkc412 on cell proliferation of human bone and soft tissue sarcoma cell lines2006

    • Author(s)
      Kawamoto, T, Akisue, T, et. al.
    • Organizer
      52th Annual Meeting of the Orthopaedic Research Society
    • Place of Presentation
      Chicago USA
    • Year and Date
      2006-03-19
    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2010-02-04  

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