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Molecular analysis of flg and its products for targeted therapy on brain tumors

Research Project

Project/Area Number 06671373
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Cerebral neurosurgery
Research InstitutionUniversity of Tsukuba

Principal Investigator

TSUBOI Koji  Univ.of Tsukuba, Institute of clinical medicine, assistant professor, 臨床医学系, 講師 (90188615)

Co-Investigator(Kenkyū-buntansha) YOSHII Yoshihiko  Univ.of Tsukuba, Institute of clinical med., associate professor, 臨床医学系, 助教授 (50110507)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsGlioma / flg / anti-sense / Northern / Southern / FLG / Growth / 神経膠腫 / bFGF / 脳腫瘍 / 腫瘍増殖
Research Abstract

It has been reported that basic fibroblast growth factor (bFGF) plays an important role in the growth of glioma cells. The gene encoding receptor of bFGF,namely fms-like gene (flg), was analyzed in this study not only to clarify its biological activity in the growth of glioma cells but also to examine its potential to be a molecular target in treatment of malignant gliomas. First we analyzed expression of flg mRNA in brain tumor tissues obtained at surgery using RT-PCR technique. Sixty-five samples were studied, and it was indicated that expression of flg mRNA in glioma tissues were more enhanced than normal brain tissues. Moreover, it's expression was further enhanced in cases with malignant transformation or recurrence. Histopathologically, enchanced flg expression was in correlation with high cellularity in glioma tissues. Based on these facts, we made more detailed molecular analyzes by Southern and Northern blot techniques on cultured glioblastoma cell lines. flg gene amplification was not observed in Southern analysis, while its expression was increased in Northern, indicating its expression should be controlled by upstream unknown transcription factors. In addition, immunohistochemical analyzes indicated that the flg-product was detected more in glioblastoma cell lines than normal fibroblasts. Anti-sense oligo nucleotide effectively suppressed the growth of glioblastoma cells at concentration of 20 muM.All these results indicate that autocrine or paracrine loops of FGF-flg system is essential in glioma cell proliferation, which also indicates that flg can be a good candidate as a molecular target in treatment of gliomas.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Koji Tsuboi: "Leukoencephalopathy associated with intraarterial ACNU in patients with gliomas" J Neuro-Oncology. 23. 223-231 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoji Komatsu: "The correlation between flg expression and the progression of glioma" Brain Tummor Research and Therapy. 203-209 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Koji Tsuboi: "Role of flg in the growth of glioblastoma cells in vitro" Neurosurgery. (in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoji Komatsu, Koji Tsuboi, Yoshihiko Yoshii, and Tadao Nose: "The correlation between flg gene expression and the progression of glioma" Brain Tumor Researh Therapy.by Nagai (Ed.). Springer Verlag Tokyo. 203-209 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Koji Tsuboi, Yoji Komatsu, Yoshihiro Tsuchida, Yoshihiko Yoshii, and Tadao Nose: "Role of flg in growth of glioblastoma cell lines in vitro" Neurosurg.(in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Koji Tsuboi: "Leukoencephalopathy associated with intraarterinl ACNU in patients with glismas" J Neuro-Oncol. 23. 223-231 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Koji Tsuboi: "Non-radioactive mismotch analysis to detect small mutations in HPRT CDNA" Jup. J. Med Sci Biol. 48. 163-170 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yoji Komatsu: "Correlation between flg expression and progression of glioma" Brain Tumor Research and Therapy. 203-209 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tsuboi K.: "Growth Inhibition of Glioma cells by suppression of flg." Brain Tumor Pathology. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tsuboi K.: "Non-radioactive Mismatch analysis to Detect Small Mutations in Human HPRT cDNA" Jap. J. Med. Sci. Biol. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Komatsu Y.: "The correlation between flg gene expression and progrossion of glioma" Brain Tumor Research and Therapy. (in press). (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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