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Targetting chemotherapy of brain tumor using liposome encapsulated cisplatin and novel cisplatin derivative

Research Project

Project/Area Number 08671591
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

SHIBATA Shobu  Nagasaki University, School of Medicine, professor, 医学部, 教授 (50039517)

Co-Investigator(Kenkyū-buntansha) RYU Tobutoshi  Nagasaki University, School of Medicine, Assistant, 医学部, 助手 (20231706)
TOKUNAGA Yoshiharu  Nagasaki University, School of Medicine Hospital, Lecturer, 医学部・附属病院, 講師 (00207557)
YASUNAGA Akio  Nagasaki University, School of Medicine, Associated Professor, 医学部, 助教授 (90124841)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsBrain tumor / Lipsome encapulated cisplatin / Cisplatin derivative
Research Abstract

Antitumor effect of polysaccharide-coated liposome, 1-aminolactose pullulan-coated liposome encapsulated cisplatin and a newly synthesized cisplatin derivative, 4-pyridoxate diammine hydroxy platinum (Pypt), against brain tumours in vitro and in vivo were evaluated and compared with cisplatin.
(1)When pullulan-coated liposome labeled with ^<14>C was intracarotidly administrated into the 9L cells in planted brain tumour rats, brain tumours uptake of radioactivity increased 4.5 times and spleen uptake decrease compared with the neutral liposome. The cytotoxity of cisplatin against 9L-glioma cell was not inhibited by encapsulation of pullulan-coated liposomes. The median survival times for 9L glioma rat model following intracarotid administration of pullulan-coated liposome encapsulated cisplatin were 35.5 days and 20.3 days for control (P<0.05). The quantity of platinum of 1-aminolactose pullulan-coated liposome encapsulated cisplatin into the brain tumour was about 4 times as great as that of pullulan-coated liposome encapsulated cisplatin.
(2)Rat bran was inoculated with 9L glioma, and Pypt and cisplatin were administered as selective intracarotid infusions. A significant improvement in survival time compared with control animals was found. Platinum concentration in the brain tumours, 30 min after administration of Pypt, was 2.4 times significantly higher than with cisplatin. This suggest that drug delivery efficiency to the 9L glioma is greater for Pypt than cisplatin.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Anda T, et al.: "Effect of tumor necrosis factor-alpha on the permeability of bovine brain microvessel emdothelial cell monolayers" Neurol Res. 19・4. 369-376 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tokunaga Y, et al.: "Antitumor effects of 4-pyridoxate diammine hydroxyplatinum,a novel cisplatin derivative,against malignant gliomas in vitro and in-vivo:A comparison with cisplatin." Pharma Sci. 3. 353-356 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakashima M, et al.: "In-vivo microdialysis study of the distribution of cisplatin into brain tumor tissue after intracrotid infusion in rats with 9L malignant glioma." J Pharm Pharmacol. 49・8. 777-780 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Anda T,et al.: "Effect of tumor necrosis factor-alpha on the permeability of bovine brain microvessel emdothelial cell monolayrs" Neurol Res. 19(4). 369-376 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tokunaga Y,et al.: "Antitumor effects of 4-pyridoxate diammine hydroxyplatinum, a novel cisplatin derivative, against malignant gliomas in vitro and in-vivo : A comparison with cisplatin." Pharma Sci. 3. 353-356 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakashima M,et al.: "In-vivo microdialysis study of the distribution of cisplatin into brain tumor tissue after intracarotid iufusion in rats with 9L malignant glioma" J Pharm Pharmacol. 49(8). 777-780 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tokunaga Y,et al.: "Antitumor effects of 4-pyridoxate diammine hydroxyplatinum, a novel cisplatin derivative, against malignant gliomas in vitro and in-vivo : A comparison with cisplatin." Pharma Sci. 3. 1-4 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakashima M,et al.: "In-vivo microdialysis study of the distribution of cisplatin into brain tumor tissue after intracarotid infusion in rats with 9L malignant glioma." J.Pharmacol. 49. 779-780 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 案田岳夫: "牛脳微小血管内皮細胞を用いたin vitro BBBモデルにおけるliposome封入cisplatin透過性の基礎的検討" Drug Delivery System. 10(6). 425-430 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] 柴田尚武: "最近のグリオーマの治療法" 日本医事新報. 3651. 31-34 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] 柴田尚武: "脳腫瘍指向性リポソームの開発" Drug Delivery System. 7(2). 109-114 (1992)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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