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Telomerase-specific fluorescent navigation system for lung cancer surgery

Research Project

Project/Area Number 17390381
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionOKAYAMA UNIVERSITY

Principal Investigator

FUJIWARA Toshiyoshi  Okayama University, Hospital, Associate Professor, 医学部・歯学部附属病院, 助教授 (00304303)

Co-Investigator(Kenkyū-buntansha) KAGAWA Shunsuke  Okayama University, Hospital, Assistant Professor, 医学部・歯学部附属病院, 助手 (00362971)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥15,400,000 (Direct Cost: ¥15,400,000)
Fiscal Year 2006: ¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 2005: ¥8,800,000 (Direct Cost: ¥8,800,000)
KeywordsTelomerase / Adenovirus / hTERT / Virotherapy / Gene therapy / Diagnostics
Research Abstract

Currently available methods for detection of tumors in vivo such as X-ray, computed tomography, and ultrasonography are noninvasive and well studied; the images, however, are not specific for tumors. Direct optical imaging of tumor cells in vivo that can clearly distinguish them from surrounding normal tissues may be clinically useful. Here, we describe a new approach to visualizing tumors whose fluorescence can be detected using telomerase-specific replication-competent adenovirus expressing green fluorescent protein (GFP) (OBP-401). OBP-401 contains the replication cassette, in which the human telomerase reverse transcriptase (hTERT) promoter drives expression of El genes, and the GFP gene for monitoring viral replication. The hTERT is the catalytic subunit of telomerase, which is highly active in cancer cells, but is quiescent in most normal somatic cells. When the human lung cancer cell line H1299 was infected with OBP-401, the virus replicated in tumor cells and showed strong green signals. In contrast, infection of OBP-401 did not show any signals in normal cells such as fibroblasts. We also found that established subcutaneous tumors could be visualized following intratumoral injection of OBP-401. H1299 human lung tumors transplanted into BALB/c nu/nu mice were intratumorally injected with 1 x 10^8 plaque forming units (PFU) of OBP-401. Within 24 hours of treatment, the fluorescence of the expressed GFP became visible by 3CCD camera in these tumors. Moreover, intrathoracic administration of OBP-401 could visualize disseminated A549 tumor nodules in mice following intrathoracic implantation. Our results indicate that intratumoral or intrathoracic injection of OBP-401 might be a useful diagnostic method that provides a foundation for future clinical application.

Report

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

    (11 results)

All 2006 2005

All Journal Article (11 results)

  • [Journal Article] Enhanced antitumor efficacy of telomerase-selective oncolytic adenoviral agent (OBP-401) with docetaxel : Preclinical evaluation of chemovirotherapy2006

    • Author(s)
      Fujiwara, T.
    • Journal Title

      International Journal of Cancer 119

      Pages: 432-440

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] In vivo imaging of lymph node metastasis with telomerase-specific replication-selective adenovirus.2006

    • Author(s)
      Kishimoto, H.
    • Journal Title

      Nature Medicine 12

      Pages: 1213-1219

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Enhanced antitumor efficacy of telomerase-selective oncolytic adenoviral agent (OBP-401) with docetaxel : Preclinical evaluation of chemovirotherapy.2006

    • Author(s)
      Fujiwara T., Kagawa S., Kishimoto H., Endo Y., Hioki M., Ikeda Y., Sakai R., Urata Y., Tanaka N., Fujiwara T.
    • Journal Title

      Int. J. Cancer 119

      Pages: 432-440

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] In vivo imaging of lymph node metastasis with telomerase-specific replication-selective adenovirus.2006

    • Author(s)
      Kishimoto H., Kojima T., Watanabe Y., Kagawa S., Fujiwara T., Uno F., Teraishi F., Kyo S., Mizuguchi H., Urata Y., Tanaka N., Fujiwara T.
    • Journal Title

      Nature Med. 12

      Pages: 1213-1219

    • NAID

      10024170197

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Enhanced antitumor efficacy of telomerase-selective oncolytic adenoviral agent (OBP-401)with docetaxel : Preclinical evaluation of chemovirotherapy2006

    • Author(s)
      Fujiwara, T.
    • Journal Title

      International Journal of Cancer 119

      Pages: 432-440

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Histone deacetylase inhibitor FR901228 enhances the antitumor effect of telomerase-specific replication-selective adenoviral agent OBP-301 in human lung cancer cells2006

    • Author(s)
      Watanabe, T.
    • Journal Title

      Experimental Cell Research 312

      Pages: 256-265

    • Related Report
      2006 Annual Research Report 2005 Annual Research Report
  • [Journal Article] 悪性腫瘍に対するウイルス製剤Telomelysinの臨床開発.2006

    • Author(s)
      藤原俊義
    • Journal Title

      Biotherapy 20

      Pages: 310-317

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Enhanced antitumor efficacy of telomerase-selective oncolytic adenoviral agent (OBP-401) with docetaxel : Preclinical evaluation of chemovirotherapy2006

    • Author(s)
      Fujiwara, T.
    • Journal Title

      International Journal of Cancer 118(掲載予定)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Enhanced oncolysis by a tropism-modified telomerase-specific replication selective adenoviral agent OBP-405 ("Telomelysin-RGD")2005

    • Author(s)
      Taki, M.
    • Journal Title

      Oncogene 24

      Pages: 3130-3140

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Enhanced oncolysis by a tropism-modified telomerase-specific replication selective adenoviral agent OBP-405 ("Telomelysin-RGD").2005

    • Author(s)
      Taki M., Kagawa S., Nishizaki M., Mizuguchi H., Hayakawa T., Kyo S., Nagai K., Urata Y., Tanaka N., Fujiwara T.
    • Journal Title

      Oncogene 24

      Pages: 3130-3140

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 悪性腫瘍に対するウイルス製剤:Telomelysinの開発と臨床応用の可能性2005

    • Author(s)
      藤原俊義
    • Journal Title

      Medical Technology 33

      Pages: 961-966

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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