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2006 Fiscal Year Final Research Report Summary

Study of gene therapy for lymph node metastasis of oral squamous cell carcinoma

Research Project

Project/Area Number 16390586
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionOsaka University

Principal Investigator

YURA Yoshiaki  Osaka University, Graduate school of Dentistry, Professor, 大学院歯学研究科, 教授 (00136277)

Co-Investigator(Kenkyū-buntansha) SUMI Tetsuro  Osaka University, Dental Hospital, Assistant Professor, 歯学部附属病院, 講師 (40252697)
Project Period (FY) 2004 – 2006
Keywordsoral cancer / lymph node metastasis / gene therapy / herpes simplex virus mutant / differentiating agent / oxygen radicals
Research Abstract

Approximate 30 % of oral cancer patients have cervical lymph node metastasis. It is very hard to treat multiple metasatsis of superficial lymph nodes and regrowth of lymph node lesions. Oncolytic virotherapy with a replication-competent herpes simplex virus type 1 (HSV-1) is a promising approach for the treatment of such lymph node lesions, because HSV-1 strain HF10 was reported to be effective for lymph node metastasis of mammary cancer. We inoculated oral squamous cell carcinoma (SCC) cells derived from a metastatic lymph node subcutaneously into buccal area of nude mice and made a model system of cervical lymph node metastasis and lung metastasis. As agents for oncolytic virotherapy for oral SCC, γ_134.5-deficent mutant R849 and HF, the original strain of HF10, were tested for anti-tumor activity in oral SCC cells. Both R849 and HF could replicate and cell viability was decreased in a time-dependent manner. Cell rounding was observed in R849-infected cells, whereas HF induced multinuclear giant cells. However, the virus yield of R849 was higher than that of HF. When R849 was infected with R849 and cultured in the presence of hexamethylene bisacatamide (HMBA), a differentiating agent of leukemia, the virus production was increased markedly. The anti-tumor effect of R849 was also examined with the use of nude mouse model of oral SCC by injecting R849 into the tumors alone or in combination with intraperitoneal injection of HMBA. The tumor growth was suppressed by R849 treatment and the effect was further enhanced with HMBA. Inflammation response to HSV-1 infection produces oxygen radicals at the infection site. We demonstrated that hydrogen peroxide enhanced the release of HSV-1 from infected cells.

  • Research Products

    (12 results)

All 2006 2005 2004

All Journal Article (11 results) Book (1 results)

  • [Journal Article] Induction of endonuclease G-mediated apopotosis in human oral squamous cell carcinoma cells by protein kinase C inhibitor safingol.2006

    • Author(s)
      Hamada M. et al.
    • Journal Title

      Apoptosis 11(1)

      Pages: 47-56

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Enhancement of antitumor activity of herpes simplex virus γ_134.5-deficient mutant for oral squamous cell carcinoma cells by hexamethylene bisacetamide.2006

    • Author(s)
      Naito S, et al.
    • Journal Title

      Cancer Gene Therapy 13(8)

      Pages: 780-791

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effects of boron neutron capture therapy on human oral squamous cell carcinoma in a nude mouse model.2006

    • Author(s)
      Kamida A, et al.
    • Journal Title

      International Journal of Radiation and Biology 82(1)

      Pages: 21-29

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Involvement of intracellular free Ca^<2+> in enhanced release of herpes simplex virus by hydrogen peroxide.2006

    • Author(s)
      Arimoto E, et al.
    • Journal Title

      Virology Journal 3

      Pages: 62E

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Induction of endonuclease G-mediated apoptosis in human oral squamous cell carcinoma cells by protein kinase C inhibitor safingol.2006

    • Author(s)
      Hamada M, et al.
    • Journal Title

      Apoptosis 11(1)

      Pages: 47-56

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Enhancement of antitumor activity of herpes simplex virus γ_134.5-deficient mutant for oral squamous cell carcinoma cells by hexamethylene bisacetamide2006

    • Author(s)
      Naito S, et al.
    • Journal Title

      Cancer Gene Therapy 13

      Pages: 780-791

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effects of boron neutron capture therapy on human oral squamous cell carcinoma in a nude mouse model.2006

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

      International Journal of Radiation and Biology 82(1)

      Pages: 21-29

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Mutations of the APC, beta-catenin, and axin 1 genes and cytoplasmic accumulation of beta-catenin in oral squamous cell carcinoma.2005

    • Author(s)
      Iwai S, et al.
    • Journal Title

      Journal of Cancer Research Clinical Oncology 131(12)

      Pages: 773-782

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Mutations of the APC, beta-catenin, and axin 1 genes and cytoplasmic accumulation of beta- catenin in oral squamous cell carcinoma.2005

    • Author(s)
      Iwai-S, et al.
    • Journal Title

      Journal of Cancer Research Clinical Oncology 131(12)

      Pages: 773-782

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Delivery of ^<10>boron to oral squamous cell carcinoma using boronophenylalanine and borocaptate sodium for boron neutron capture therapy.2004

    • Author(s)
      Obayashi, et al.
    • Journal Title

      Oral Oncology 40 (5)

      Pages: 474-482

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Delivery of ^<10>boron to oral squamous cell carcinoma using boronophenylalanine and borocaptate sodium for boron neutron capture therapy.2004

    • Author(s)
      Obayashi S, et al.
    • Journal Title

      Oral Oncology 40(5)

      Pages: 474-482

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 先端歯科医学の創生2005

    • Author(s)
      由良 義明, 他
    • Total Pages
      14
    • Publisher
      大阪大学出版会
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2008-05-27  

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