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

Gene therapy of salivary gland carcinoma with virus vector

Research Project

Project/Area Number 10557192
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field Surgical dentistry
Research InstitutionOsaka University (2000)
The University of Tokushima (1998-1999)

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) KUSAKA Jun  Tokushima University Dental hospital Research Associate, 歯学部・附属病院, 助手 (80304541)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥4,500,000 (Direct Cost: ¥4,500,000)
Keywordsherpes simplex virus / salivary gland carcinoma / gene therapy / mutant virus / cell fusion / 欠損ウイルス / チミジンキナーゼ
Research Abstract

Recurrence and regional and systemic metastases of salivary gland carcinoma occur frequently, and this condition is generally refractory to chemotherapy and radiotherapy. In order to treat these advanced cases, novel therapy is required. Gene therapy is one of the approaches for the treatment of these cases. Although viruses used for gene therapy are usually genetically modified to deliver therapeutic transgenes and prevent viral infection, replication-competent herpes simplex virus type 1 (HSV-1) may be also used for cancer therapy because replication of HSV-1 within cancer cells can result in their destruction.
hrR3 virus has a lacZ insertion into the HSV-1 ICP6 gene. The ICP6 gene encodes the large subunit of HSV ribonucleotide reductase, and loss of its expression decreases the ability of the hrR3 to replicate in nondividing cells and increases specificity for tumor cell lysis. To obtain more effective HSV-1 mutant for the treatment of salivary gland carcinoma, we selected a fusion-inducing mutant hrR3f after repeated passages of hrR3 in Vero cells and human salivary gland adenocarcinoma HSY cells. When HSY cells were infected with hrR3 or hrR3f at a low input MOI, hrR3f could degenerate tumor cells more efficiently as compare with hrR3, because cells adjacent to hrR3f-infected cells were readily involved in polykaryocyte formation. Xenograft tumors were established in the subcutaneous tissue of the franks of nude mice, using HSY cells. A schedule consisting of multiple repeated percutaneous injection of hrR3f virus, to a total of three doses, was well tolerated and found inhibit tumor growth completely in the nude mouse model.
These studies have demonstrated the ability of theHSV-1 mutants to inhibit salivary gland carcinomas.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] 由良義明 他: "ヘルペスウイルスの細胞外放出に対するサイトカラシンDの促進作用"口腔組織培養学会誌. 8(1). 47-48 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsujimoto H, et al.: "Effect of epidermal growth factor administration on the development of mouse salivary gland carcinomas"Journal of Oral Pathology and Medicine. 28(1). 30-36 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 由良義明 他: "ヘルペスウイルスの細胞外放出とウイルス糖タンパクgDの細胞内分布に対するサイトカラシンDの効果"口腔組織培養学会誌. 9(1). 13-26 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yura Y, et al.: "Enhancement of herpes simplex virus-induced polykaryocyte formation by 12-o-teradecanoyl phorbol 13-acetate"Intervirology. 43(3). 129-138 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yura 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. 159-167 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yura Y, Kusaka J, Yoshioka Y, Yamamoto S, Yoshida H, Sato M: "Enhancing effect of cytochalasin D on the release of herpes simplex virus."The Journal of Tissue Culture Society for Dental Research. 8(1). 47-48 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsujimoto H, Yura Y, Yoshioka Y, Kusaka J, Yoshida H, Sato M: "Effect of epidermal growth factor administration on the development of mouse salivary gland carcinomas"Journal of Oral Pathology and Medicine. 28(1). 30-36 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yura Y, Kusaka J, Yamakawa R, Yamamoto S, Bando T, Yoshida H, Sato M: "Effects of cytochalasin D on the release of herpes simplex virus and the distribution of viral glycoprotein D."The Journal of Tissue Culture Society for Dental Research. 9(1). 13-26 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yura Y, Kusaka J, Yamakawa R, Bando T, Yoshida H, Sato M: "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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yura Y, Kusaka J, Bando T, Yamamoto S, Yoshida H, Sato M: "Enhancement of herpes simplex virus-induced polykaryocyte formation by 12-o-teradecanoyl phorbol 13-acetate"Intervirology. 43(3). 129-138 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yura Y, Yoshioka Y, Yamamoto S, Kusaka J, Bando T, Yoshida H, Sato M: "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. 159-167 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hitoshi Tsujimoto et al.: "Effect of epidermal growth factor-administration on the development of mouse salivary gland carcinomas"Journal of Oral Pathology and Medicine. 28. 30-36 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yura Y: "Enhancement of herpes simplex virus-induced polykaryocyte formation by 12-o-tetradecanoyl phorbol13 acetate : association with the reorganization of actin filaments and cell motility."Intervirology. 43・3. 129-138 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yura Y: "Enhancing effect of fibroblast growth factor on the proliferation of salivary gland carcinoma cells and salivary gland carcinogenesis"J Oral Pathol and Med, in press.

    • Related Report
      2000 Annual Research Report
  • [Publications] Yura Y: "Mental nerve neuropathy as a result of herpes simplex virus infection in the oral cavity"Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 90・3. 306-309 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 由良義明: "ヘルペスウイルスの細胞外放出とウイルス糖タンパクgDの細胞内分布に対するサイトカラシンDの効果"口腔組織培養学会. 9・1. 13-26 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 由良義明: "ホルボールエステルのヘルペスウイルス細胞変性促進効果に対するアクチン線維再配列の関与"口腔組織培養研究会誌. 7・2. 121-134 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hitoshi Tsujimoto: "Effect of epidermal growth factor administration on the development of mouse salivary gland carcinomas"Journal of Wral Pathology and Medicine. 28. 30-36 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 由良義明: "ヘルペスウイルスの細胞外放出に対するサイトカラシンDの促進作用"口腔組織培養学会誌. 8・1. 47-48 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 由良義明: "口腔顔面領域におけるαヘルペスウイルス感染症"日本臨床. 58・4(印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 由良義明: "上皮増殖因子の唾液腺発癌と培養細胞増殖に及ぼす影響" 口腔組織培養研究会誌. 7・1. 77-78 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 由良義明: "マウス顎下腺発癌における上皮増殖因子の役割" 口腔組織培養研究会誌. 7・2. 109-120 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 由良義明: "ホルボールエステルのヘルペスウイルス細胞変性促進効果に対するアクチン線維再配列の関与" 口腔組織培養研究会誌. 7・2. 121-134 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hitoshi Tsujimoto: "Effect of epidermal growth factor administration on the development of mouse salivary gland carcinomas." Journal of Oral Pathology and Medicine. 28. 30-36 (1999)

    • Related Report
      1998 Annual Research Report

URL: 

Published: 1998-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi