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Development of novel heat-induced cytokine gene therapy against malignant gliomas

Research Project

Project/Area Number 12470286
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) MORI Hiroshi  Brain Research Institute Lecturer, 脳研究所, 講師 (70291359)
TAKAHASHI Hideaki  University Medical Hospital Lecturer, 医学部附属病院, 講師 (70236305)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsheat shock promoter / heat shock protein 70 / gene therapy / hyperthermia / glioma / interferon-gamma / interferon-pamma / heat shock protein / gene terapy
Research Abstract

1) First, we constructed LacZ gene expression vector under the control of heat shock protein 70 (hsp70) promoter (hsp70/LacZ). Then three human glioma cell lines (U251-MG, T98G, NP2) and one mouse glioma cell line (203) were transfected with hsp70/LacZ vector using lipofection method. After selection with G418, the stable transfectants were obtained. Using these transfectants, the expression of beta-galactosidase after heating was measured. The condition of heating was 41℃ for 2h, 42℃ for 1h, or 43℃ for 1h. The results showed that the peak of the beta-galactosidase expression was between 3h and 24h after heating, even though the degree of its expression varied among the cell lines. (In contrast to other cell lines, the expression was positive in U251-MG cells even with 37℃ heating as a negative control.)
2) As a next step, we constructed CD40 ligand (CD40L) gene expression vector under the control of hsp70 promoter (hsp70/CD40L). Then we transfected the vector into mouse 203 glioma cell … More or human NP2 glioma cell by lipofection method. After the selection with G418, we obtained stable transfectants, hsp70/CD40L-203 or hsp70/CD40L-NP2. Using each transfectants, we measured the expression of CD40L protein in the supernatant of the culture medium after heating using ELISA. The results revealed that the peak expression of CD40L protein was between 3h and 48h after heating.
3) Furthermore, we constructed IFN-gamma gene expression vector under the control of hsp70 (hsp70/IFN-gamma). The stable transfectant with this vector (hsp70/IFN-gamma-203) was established after the selection with G418. Using this transfectant, we measured the expression of IFN-gamma protein in the supernatant of the culture medium after heating at 42℃ for 1h using ELISA. The result showed that the expression peaked at 24h after the heating. There was no expression of IFN-gamma observed with the treatment of 37℃ heating as a negative control.
4) Taken together, in most of the glioma cell lines except for U251-MG cells, the peak expression of the inserted gene by heating was observed between 3h and 48h after heating, even though the expression pattern varied depending on each cell line. Therefore, this gene expression system using hsp70 promoter can be a good candidate for heat-inducible gene treatments. Less

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] H.Takahashi: "Successful Treatments of Malignant Glioma in the Elderly by Radiofrequency Interstitial Hyperthermia : A Report of Two Cases"Jpn J Hyperthermic Oncol. 18・3. 157-164 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H. Takahashi: "Successful Treatments of Malignant Glioma in the Elderly by Radiofrequency Interstitial Hyperthermia : A Report of Two Cases"Jpn J Hyperthermic Oncol. 18・3. 157-164 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 田中 隆一: "VIII.温熱療法悪性グリオーマの温熱療法"In : 脳神経外科Advanced Practice 5、神経膠腫. 136-141 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 田中 隆一: "脳腫瘍の温熱療法 : 悪性グリオーマのRF組織内加温法"In : 集学的癌治療の研究と臨床,監修. 305-313 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Takahashi: "Successful Treatments of Malignant Glioma in the Elderly by Radiofrequency Interstitial Hyperthemia: A Report of TWo Cases"Jpn J Hyperthermic Oncol. 18(3). 157-167 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 田中 隆一: "第7章 温熱療法 最近の進歩"In : 先端医療シリーズ18、脳腫瘍の最新医療. 227-231 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 高橋 英明: "第7章 温熱療法 RF組織内温熱療法"In : 先端医療シリーズ18、脳腫瘍の最新医療. 232-238 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 近 貴志: "悪性脳腫瘍に対するHSP70promoterを用いたheat regulated gene therapy - preliminary study -"ポストシークエンス時代における脳腫瘍の研究と治療. (in Press).

    • Related Report
      2001 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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