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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
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥10,800,000 (Direct Cost: ¥10,800,000)
Fiscal Year 2006: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2005: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2004: ¥5,200,000 (Direct Cost: ¥5,200,000)
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.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (30 results)

All 2006 2005 2004 Other

All Journal Article (28 results) Book (2 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
    • Related Report
      2006 Final Research Report Summary
  • [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
    • Related Report
      2006 Final Research Report Summary
  • [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
    • Related Report
      2006 Final Research Report Summary
  • [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

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [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
    • Related Report
      2006 Final Research Report Summary
  • [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
    • Related Report
      2006 Final Research Report Summary
  • [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
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 分子標的としてのプロテインキナ-ゼCファミリー2006

    • Author(s)
      由良義明, 他
    • Journal Title

      日本口腔科学会雑誌 55(2)

      Pages: 104-107

    • NAID

      10018827351

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A role of salivary carbonic anhydrase VI in dental plaque2006

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

      Archives of Oral Biology 51(2)

      Pages: 117-122

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Induction of endonuclease G-mediated apopotosis in human oral squamous cell carcinoma cells by protein kinase C inhibitor safingol2006

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

      Apoptosis 11(1)

      Pages: 47-56

    • Related Report
      2006 Annual Research Report
  • [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(8)

      Pages: 780-791

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effects of boron neutron capture therapy on human oral squamous cell carcinoma in a nude mouse model2006

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

      International Journal of Radiation and Biology 82(1)

      Pages: 21-29

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Involvement of intracellular free Ca^(2+) in enhanced release of herpes simplex virus by hydrogen peroxide2006

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

      Virology Journal 3

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 分子標的としてのプロテインキナーゼCファミリー2006

    • Author(s)
      由良義明 他
    • Journal Title

      日本口腔科学会雑誌 55(2)

      Pages: 104-107

    • NAID

      10018827351

    • Related Report
      2005 Annual Research Report
  • [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

    • Related Report
      2005 Annual Research Report
  • [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
    • Related Report
      2006 Final Research Report Summary
  • [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
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Mutations of the APC, beta-catenin, and axin 1 genes and cytoplasmic accumulation of beta-catenin in oral squamaous cell carcinoma.2005

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

      J Cancer Res Clin Oncol 131(12)

      Pages: 773-782

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Phase II study of a novel oral formation of 5-fluorouracil in combination with low-dose cisplatin as preoperative chemotherapy of oral squamous cell carcinoma.2005

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

      Int J Clin Pharmacol Res 25(3)

      Pages: 115-122

    • Related Report
      2005 Annual Research Report
  • [Journal Article] ヘルペスウイルス感染状態で活性酸素によって誘導される細胞死の形態2005

    • Author(s)
      有本絵美子 他
    • Journal Title

      口腔組織培養学会誌 14(1)

      Pages: 15-16

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Suppression by incadronate of invasion and growth of A-375 human melanoma in mandible in nude mice2005

    • Author(s)
      Kitagawa Y, et al.
    • Journal Title

      Oncology Reports 13(2)

      Pages: 211-216

    • Related Report
      2004 Annual Research Report
  • [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
    • Related Report
      2006 Final Research Report Summary
  • [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
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Anti-HER-2/neu immune response are induced before the development of clinical tumors but declined following tumorigenesis in HER-2/Neu transgenic mice2004

    • Author(s)
      Takeuchi N, et al.
    • Journal Title

      Cancer Research 64(20)

      Pages: 7588-7595

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Carbonic anhydrase VI in the mouse nasal gland2004

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

      Journal of Histochemistry & Cytochemistry 52(8)

      Pages: 1057-1062

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Effectiveness of BNCT for recurrent head and neck malignancies2004

    • Author(s)
      Kato I, et al.
    • Journal Title

      Applied radiation and Isotopes 61(5)

      Pages: 1069-1073

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ウイルス放出に対する活性酸素の効果2004

    • Author(s)
      有本絵美子, 他
    • Journal Title

      口腔組織培養学会誌 13(1)

      Pages: 29-30

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Effects of boron neutron capture therapy on human oral squamous cell carcinoma in a nude mouse model.

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

      Int J Radiat Biol (in press)

    • Related Report
      2005 Annual Research Report
  • [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
    • Related Report
      2006 Final Research Report Summary
  • [Book] 先端歯科医学の創生2005

    • Author(s)
      由良義明, 他
    • Total Pages
      273
    • Publisher
      大阪大学出版会
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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