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molecular therapeutic approach for human papillomavirus infections

Research Project

Project/Area Number 13671746
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKeio University

Principal Investigator

FUJII Takuma  Keio Univ. of Med. Assistant Professor, 医学部, 助手 (10218969)

Co-Investigator(Kenkyū-buntansha) TSUKAZAKI Katsumi  Keio Univ. of Med. Associate professor, 医学部, 助教授 (40118972)
TODA Masahiro  Keio Univ. of Med. Assistant Professor, 医学部, 助手 (20217508)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordstranscriptional factor / virus / phage / peptides / genome / transcriptional activity / anti-viral agents / cervical cancer
Research Abstract

We have been investigating the possibility of molecular diagnosis of cancer of the uterine cervix by using HPV infection as a marker. First, we demonstrated that there are cases of advanced cancer of the cervix in which HPV16 type DNA is isolated in which it is possible to isolate antibody to HPV16 E7 protein from the patient's serum (Fujii et al.: Jpn J Cancer Res 86:28-34, 1995). We also collected cells by scraping the uterine cervix of patients in whom precancerous lesions of cervical cancer had been found and showed that the rate of detection of E6/E7 transcription products by RT-PCR rose as the lesions became more advanced (Fujii et al.: Gynecol Oncol 58:210-215, 1995). These findings showed that E6/E7 gene products greatly contribute to the development and maintenance of cancer clinically as well. Since E2 protein is a DNA-binding protein that modulates expression of the E6/E7 genes, it can be concluded to be a very important protein in terms of analyzing the mechanism of viral c … More arcinogenesis. The purpose of the present study was therefore to isolate a peptide that binds to E2 protein and inhibits its transcription function. HPV16 E2 protein was expressed in E. coli, and the protein was purified. The E2 protein was converted to the solid phase on plates, and a phage clone that binds to E2 protein was isolated by using a library in which random amino acid sequences were expressed in phage fiber proteins. A peptide sequence containing tryptophan was isolated as a result, and when the tryptophan was replaced with alanine, comparison of binding to E2 protein showed that binding was decreased with the mutant peptide. We also prepared a synthetic peptide in which the nuclear translocation signal was added to the peptide sequence that was isolated, and assessment of its effect on E2 protein transcription activity by the luciferase assay showed a reduction in transcription activity. These findings demonstrated that the peptide that had been isolated binds to E2 protein and suppresses its transcription activity Less

Report

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

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Fujii T, Brandsma JL, Peng X, et al.: "High and low level of cottontail rabbit papillomavirus E2 protein generate opposite effects on gene expression"J Biol Chem. 276. 867-874 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakagawa H, Sugano K, Fujii T, et al.: "Frequent detection of human papilloma viruses in cervical dysplasia by PCR single-strand DNA-conformational polymorphism analysis"Anticancer Res. 22. 1655-1660 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishikawa M, Fujii T, Trunk-Gehmacher M et al.: "Association between HPV infection and overexpression of P16INK4a in cervical adenocarcinoma"Int J Gynecol Cancer. 12. 594 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 藤井多久麿, 塚崎克己, 野澤志朗: "ヒトパピローマウイルス感染症の新しい分子標的治療への展望-E2蛋白質をターゲットとして"産婦人科の実際. 50. 105-114 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Peng XY, Won JH, Rutherford T, Fujii T et al.: "The use of the L-plastin promoter for adenoviral-mediated, tumor-specific gene expressionin ovarian and bladder cancer cell lines"Cancer Res. 61. 4405-4413 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 舛本暢生, 藤井多久麿, 野澤志朗: "Sentinel Node Navigation -癌治療への新しい展開-"金原出版. 296 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujii,T, Brandsma,JL, Peng,X et al.: "High and low level of cottontail rabbit papillomavirus E2 protein generate opposite effects on gene expression."J Biol Chem. 276. 867-874 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakagawa,H, Sugano,K, Fujii,T et al: "Frequent detection of human papilloma viruses in cervical dysplasia by PCR single-strand DNA-conformational polymorphism analysis"Anticancer Res,. 22. 1655-1660 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishikawa,M, Fujii,T, Trunk-Gehmacher,M et al: "Association between HPV infection and overexpression of P16INK4a in cervical adenocarcinoma"Int J Gynecol Cancer. 12. 594 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Peng,XY, Won,JH, Rutherford,T, Fujii,T et al: "The use of the L-plastin promoter for adenoviral-mediated, tumor-specific gene expressionin ovarian and bladder cancer cell lines"Cancer Res. 61. 4405-4413 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujii T, Brandsma JL, Peng X, et al.: "High and low level of cottontail rabbit papillomavirus E2 protein generate opposite effects on gene expression"J Biol Chem. 276. 867-874 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakagawa H, Sugano K, Fujii T et al.: "Frequent detection of human papilloma viruses in cervical dysplasia by PCR single-strand DNA-conformational polymorphism analysis"Anticancer Res. 22. 1655-1660 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishikawa M, Fujii T, Trunk-Gehmacher M et al.: "Association between HPV infection and overexpression of P16INK4a in cervical adenocarcinoma"Int J Gynecol Cancer. 12. 594 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 藤井多久磨, 塚崎克己, 野澤志朗: "ヒトパピローマウイルス感染症の新しい分子標的治療への展望-E2蛋白質をターゲットとして"産婦人科の実際. 50(1). 105-114 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Peng XY, Won JH, Rutherford T, Fujii T et al.: "The use of the L-plastin promoter for adenoviral-mediated, tumor-specific gene expressionin ovarian and bladder cancer cell lines"Cancer Res. 61. 4405-4413 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 舛本暢生, 藤井多久磨, 野澤志朗: "Sentinel Node Navigation-癌治療への新しい展開-"金原出版. 296 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujii T, Brandsma JL, et al.: "High and low level of cottontail rabbit papillomavirus E2 protein generate opposite effects on gene expression"J Biol Chem. 276. 867-874 (2001)

    • Related Report
      2001 Annual Research Report

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

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