• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Gene therapy for oral squamous cell carcinoma with herpes simplex virus vector

Research Project

Project/Area Number 13470432
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 Testuro  Osaka University, Dental Hospital, Assistant Professor, 歯学部附属病院, 講師 (40252697)
道澤 雅裕  大阪大学, 歯学部・附属病院, 医員
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥11,600,000 (Direct Cost: ¥11,600,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2002: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2001: ¥6,800,000 (Direct Cost: ¥6,800,000)
Keywordsgene therapy / oral cancer / herpes simplex virus / mutant virus / HMBA / calponin / malignant histiocytoma / 複製可能型組換えウイルス / 三叉神経 / 神経再建 / 細胞融合
Research Abstract

Oncolytic herpes simplex virus (RSV) therapy with replication-competent HSV type 1(HSV-1) mutant is a promising approach for the treatment of oral cancer, because replication of HSV-1 within cancer cells can result in their destruction. For the treatment of cancer in the oral cavity, it is essential to determine how oral environmental factors could affect the replication of HSV-1 vector. We examined the effect of a calcium ionophore, ionomycin, and oxygen radicals and found that ionomycin increased entracellular virus, whereas it did not change the virus production. Furthermore, H2O2 elevated the level of intracellular calcium ([Ca2+]i) and then increased the extracellular HSV-1, suggesting that [Ca2+]i plays an important role in the release of HSV-1 vector. To eradicate solid tumor, HSV-1 vector must spread from inoculated site to neighboring tumor cells. A polar compound, hexamethylene bisacatamide (HMBA) was found to enhance the replication of γ34.5 mutant R849 in human oral squamous cell carcinoma (SCC) cells. This indicated that HMBA can potentiate the oncolytic effect of R849 on human oral SCC. Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma in adult. Nearly 70% of primary human MFH express calponin at various levels, The replication of a HSV-1 mutant d12 CALP in which calponin promoter derives expression of ICP4 was examined in oral MPH cells, Cytopathic effect of d12 CALP was demonstrated in oral MFH that expressed calponin. When nude mice xenografts of MFH were injected with the d12 CALP, a significant reduction of the tumor growth was observed. Furthermore, intravenous administration of the vector resulted in the replication of d12 CALP in lung metastatic lesions. This vector could be usedd for the treatment of distant metastasis of MFH.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Shiojiri T, et al.: "PPAR gamma ligands inhibit nitrotyrosine formation and inflammatory mediator expressions in adjuvant-induced rheumatoid arthritis mice."European Journal of Pharmacology. 448(2-3). 231-238 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Doi T, et al.: "Induction of instability of p34^<cdc2> expression by treatment with cisplatin (CDDP) in mouse teratocarcinoma F9 cells."Cancer Letters. 176. 75-80 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yura Y, et al.: "Effect of Ca^<2+>-dependent cell death on the release of herpes simplex virus."Archives of Virology. 148(2). 221-235 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Imai T, et al.: "Regeneration of periodontal Ruffini endings of rat lower incisors following nerve cross-anastomosis with mental nerve."Brain Research.. 992(1). 20-29 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Obayashi S, et al.: "Delivery of 10boron to oral squamous cell carcinoma using boronophenylalanine and borocaptate sodium for boron neutron capture therapy."Oral Oncology. 40(5). 474-482 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ogawa Y, et al.: "Adenoid cystic carcinoma associated with salivary duct cyst in the sublingual gland : a case report."Journal of Oral Pathology and Medicine.. 33. 311-313 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shiojiri T, et al.: "PPAR gamma ligands inhibit nitrotyrosine formation and inflammatory mediator expressions in adjuvant-induced rheumatoid arthritis mice."Eur J Pharmacol. 448(2-3). 231-238 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Doi T, et al.: "Induction of instability of p3^<cdc2> expression by treatment with cisplatin (CDDP) in mouse teratocarcinoma F9 cells."Cancer Letters. 176. 75-80 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yura Y, et al.: "Effect of Ca^<2+>-dependent cell death on the release of herpes simplex virus."Arch Virol. 148(2). 221-235 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Imai T, et al.: "Regeneration of periodontal Ruffini endings of rat lower incisors following nerve cross-anastomosis with mental nerve."Brain Res.. 992(1). 20-29 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Obayashi S, et al.: "Delivery of 10boron to oral squamous cell carcinoma using boronophenylalanine and borocaptate-sodium for boron neutron capture therapy."Oral Oncology. 40(5). 474-482 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ogawa Y, et al.: "Adenoid cystic carcinoma associated with salivary duct cyst in the sublingual gland a case report."J Oral Pathol Med.. 33. 311-313 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ogawa Y. et al.: "Adenoid cystic carcinoma associated with salivary duct in The sublingual gland : a case report"Journal of Oral Pathology and Medicine. in press.

    • Related Report
      2003 Annual Research Report
  • [Publications] Obayashi S, et al.: "Delivery of ^<10>boron to oral squamous cell carcinoma using boronophenylal-anine and borocaptate sodium for boron neutron capture therapy"Oral Oncology. 40・5. 474-482 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Imai T, et al.: "Regeneration of periodontal Ruffini endings of rat lower incisors following nerve cross-anastomosis with mental nerve"Brain Research. 992・1. 20-29 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 道澤雅裕他: "カルポニンプロモーターをもつ条件つき複製可能型単純ヘルペスウイルスベクターを用いた口腔悪性繊維性組織球腫に対する遺伝子治療法の開発"口腔組織培養学会誌. 12・1. 39-40 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yura Y, et al.: "Effect of Ca^<2+>-dependent cell death on the release of herpes simplex virus"Archives of Virology. 148・2. 221-235 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shiojiri T, et al.: "PPARγ ligands inhibit nitrotyrosine formation and inflammatory mediator expressions in adjuvant-induced rheumatoid arthritis mice"European Journal of Pharmacology. 448・2-3. 231-238 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yura Y, et al.: "Effect of Ca^<2+>-dependent cell death on the release of herpes simplex virus"Archives of Virology. 148. 221-235 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 松本理基, 他: "口腔細胞のヘルペスウイルス感染に対するイオノマイシンの効果"口腔組織培養学会誌. (印刷中).

    • Related Report
      2002 Annual Research Report
  • [Publications] 道澤雅裕, 他: "カルポニンプロモーターをもつ条件つき複製可能型単純ヘルペスウイルスベクターを用いた口腔悪性線維性組織球腫に対する遺伝子治療法の開発"口腔組織培養学会誌. (印刷中).

    • Related Report
      2002 Annual Research Report
  • [Publications] Yura Y, et al.: "Mental nerve neuropathy as a result of primary herpes simplex virus infection in the oral cavity"Oral Surgery Oral Medicine Oral Pathology Oral radiology Endodontics. 90・3. 306-309 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tura Y, et al.: "Enhancing effects of fibroblast growth factor on the proliferation of salivary gland carcinoma cells and salivary gland carcinogenesis"Journal of Oral Pathology and Medicine. 30・3. 159-167 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 由良義明, 他: "現在の口腔ヘルペスウイルス感染症の診断"四国歯学会雑誌. 13・2. 253-258 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 由良義明: "ヘルペスウイルスの病原性と有用性"大阪大学歯学雑誌. 46・1. 1-8 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 由良義明, 他: "ヘルペスウイルス感染に対するカルシウムイオノフォアの効果"口腔組織培養学会誌. 10・1. 35-36 (2001)

    • Related Report
      2001 Annual Research Report

URL: 

Published: 2001-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi