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Trial of novel thermo-gene therapy for malignant brain tumors-Aiming for enhancement of hyperthermia using p53 introduction-

Research Project

Project/Area Number 15390430
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionNiigata University

Principal Investigator

TANAKA Ryuichi  Niigata University, Brain Research Institute, Professor, 脳研究所, 教授 (30018816)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Hideaki  Niigata University, Medical & Dental Hospital, Lecturer, 医歯学総合病院, 講師 (70236305)
YAMANAKA Yuma  Niigata University, Brain Research Institute, Lecturer, 脳研究所, 講師 (20323991)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2004: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 2003: ¥8,800,000 (Direct Cost: ¥8,800,000)
Keywordsp53 / adenoviral vector / hyperthermia / gene therapy / glioma
Research Abstract

We evaluated combination effect of p53 introduction and hyperthermia on malignant glioma cells. Cell lines used are U251-MG, U373-MG (mutant p53), and D54, U87-MG (wild-type p53). 1)First, optimal MOl of Ad/p53 vector was determined. 2)Heat shock was applied at 43℃ for 2h using liquid incubator. 3)In in vitro experiment, additive effect of both treatments was observed in all the cell lines used. 4)In cell cycle analysis, no change of distribution was observed by heat shock alone in either U373-MG or D54 cells. However, there was an increase in both sub-G1 and G1 by p53 introduction alone. The effect of combination treatment was similar to that of p53 introduction alone. 5)In DNA fragmentation assay, apoptosis was induced by p53 introduction alone but not by heat shock alone. Higher percentage of apoptosis was induced by the combination treatment, which was likely to be caused by heat shock. This enhancing effect by heat shock was observed regardless of p53 status of tumor cells. 6)Apoptosis induction was caspase-dependent in U373-MG and U251-MG cells, but was caspase-independent in D54 cells. 7)p21 protein was over-expressed only after p53 introduction. 8)As in vivo experiment, we established U373-MG subcutaneous tumor model using nude mice. 9)Treatments were given to the following four groups. A)control-vector(CTR) and 37℃ heat shock(HS), b)CTR and 43℃ HS, c)p53-vector(p53V) and 37℃ HS, d)p53V and 43℃ HS. Results showed that no significant inhibitory effect on tumor growth was observed in groups (b),(c),and (d)compared with control-group (a).For future experiments, to achieve more efficient hyperthermia, A)repeating of heat shock, and B)heating with needle electrode, should be considered. Regarding gene transfer, C)gene expression under the control of tetracycline, and D) use of liposome with higher transfer efficiency, should be also be considered.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (6 results)

All 2004 Other

All Journal Article (4 results) Publications (2 results)

  • [Journal Article] Mild heat shock induces autophagic growth arrest, but not apoptosis in U251-MG and U87-MG human malignant glioma cells2004

    • Author(s)
      Komata T
    • Journal Title

      J Neuro-Oncol 68

      Pages: 101-111

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Mild heat shock induces autophagic growth arrest, but not apoptosis in U251-MG and U87-MG human malignant glioma cells.2004

    • Author(s)
      Komata T
    • Journal Title

      J Neuro-Oncol Vol.68

      Pages: 101-111

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Histone deacetylase inhibitors, N-butyric acid and trichostatin A, induce caspase-8-dependent but not caspase-9-dependent apoptosis in human malignant glioma cells

    • Author(s)
      Komata T
    • Journal Title

      Int J of Oncology (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Histone deacetylase inhibitors, N-butyric acid and trichostatin A, induce caspase-8-dependent but not caspase-9-dependent apoptosis in human malignant glioma cells.

    • Author(s)
      Komata T
    • Journal Title

      Int J of Oncology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Komata T: "Mild heat shock induces autophagic growth arrest, but not apoptosis in U251-MG and U87-MU human malignant glioma cells"J Neuro-Oncol. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] 田中 隆一: "脳腫瘍の温熱治療-最近の進歩"Annual Review 神経 2003. 163-168 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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