Anti-tumor activity of synthetic alkyllysophospholipids and glycolipids
| Project/Area Number |
59870076
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KUDO Ichiro (1985-1986) The University of Tokyo, 薬学部, 助教授 (30134612)
野島 庄七 (1984) 東京大学, 薬学部, 教授
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| Co-Investigator(Kenkyū-buntansha) |
津島 進 武田薬品工業株式会社, 中央研究所, 主任研究員
野村 容朗 武田薬品工業株式会社, 中央研究所, 主席研究員
NOJIMA Shoshichi Teikyo University, 薬学部, 教授 (70090470)
INOUE Keizo The University of Tokyo, 薬学部, 教授 (30072937)
NOMURA Hiroaki Takeda Chemical Industry Ltd.
TSUSHIMA Susumu Takeda Chemical Industry Ltd.
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| Project Period (FY) |
1984 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 1986: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1985: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1984: ¥9,700,000 (Direct Cost: ¥9,700,000)
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| Keywords | Alkylphospholipids / glyceroglycolipids / macrophage / platelet activating factor / 抗腫瘍活性 / リゾリン脂質 / 糖脂質 |
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| Research Abstract |
(1) Alkylphospholipids
1-0-Octadecyl-2-0-methyl-glycero-3-phosphocholine (ET18-0Me) has been reported to prossess difine anti-tumor effect in vivo. Lysophospholipid analogs were chemically synthesized and their anti-tumor activity against mouse experimental tumor (Sarcoma 180, MM46) were examined. Among them, 1-0-octadecy-2-0-acetoacetyl-glycero-3-phosphocholine was found to show anti-tumor activity similar to ET18-0Me, with less acute toxicity.
Intravenous injection of the ET18-0Me with sn-3 configuration retarded the subcutaneous growth of Sarcoma 180 cells effectively, while the growth inhibition by the sn-1 isomer was much less effective. This stereospecificity was similar to that observed in their activities as PAF agonist. The acetoacetyl compound, another PAF aganist, showed similar stereospecific anti-tumor action in vivo. These findings suggest that some alkyl lysophospholipids may activate host cells to a cytostatic stage against tumor cells in vivo through binding to a PAF rec
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eptor. Our preliminary result indicated that the responsible cells under these conditions might primarily be immature macrophages present in the bone-marrow.
On the other hand, under some conditions, the in vivo anti-tumor activity of ET18-0Me may be revealed through direct cytotoxicity and/or modulation of host defense system by 'non-specific' mechanisms.
(2) Glycolipids
Liposomes composed of chemically synthesized glyceroglycolipids, such as 1,2-dipalmityl-[ <beta> -cellobiosyl-(1'->3)]-glycerol (Cel-DAG), were found to enhance protective immunity against transplatable tumor cells (sarcoma 180) in ICR mice. Peritoneal exudate cells prepared from mice treated in vivo with Cel-DAG showed cytostatic activity in vivo against the mouse leukemia cell line, EL-4. Adherent cells separated from this preparation showed similar activity.
The adherent cell fraction alone showed rather weak cytostatic activity when pretreated with the glyceroglycolipids, and full activity was restored by supplementing with the non-adherent cell fraction. The ability of glycolipids to induce tumoricidal effects was affected by cholesterol content: with increasing cholesterol content, the activities decreased. Less
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Research Products
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