| Project/Area Number |
02454337
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
UEDA Satoshi Kyoto Prefectural University of Medicine, Neurosurgery, Professor, 医学部, 教授 (40094411)
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| Co-Investigator(Kenkyū-buntansha) |
IMAHORI Yoshio Kyoto Pretectural University of Medicine, Neurosurgery, Research associate, 医学部, 助手 (80191899)
NARUSE Shouji Kyoto Prefectural University of Medicine, Neurosurgery, Associate professor, 医学部, 講師 (50106407)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1991: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1990: ¥5,300,000 (Direct Cost: ¥5,300,000)
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| Keywords | Signal transduction / Cell proliferation / Phosphoinositide turnover / Phospholipase C / Diacylglycerol / Protein Kinase C / PDGF / EGF / グリオ-マ / 細胞内情報伝達 / 1,2ー[ ^<11>C]ジアシルグリセロ-ル / Protein kinase C |
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| Research Abstract |
1. The major advance in cell biology in recent has been the clarification of a series of intracellular signaling pathways that link to the cell surface receptors. One of the most extensively studied signaling pathways is the phospholipase C dependent hydrolysis of membrane phosphoinositides to form inositol polyphosphate and diacylglycerols. We studied the tumor signal transduction mechanism regarding tumor proliferation and we found the metabolic difference in phospholipid turnover between the CNS and the glioma. Carbon-11-labeled 1, 2-diacylglycerol(DAG) uptake was observed in rat brain and transplanted rat glioma (C_6 glioma) using in vivo autoradiographic technique. Marked DAG uptake was shown in the transplanted cells, suggesting that phospholipid turnover in the glioma was prompted than the CNS. Chromatographic studies also showed the difference in the metabolic fraction, in which glioma cells simultaneously produced radioactive phosphatidylcholine (PC) and phosphatidylethanolamine (PE) accompanied with phosphatidic acids (PA), phosphatidylinositols(PI) and phosphoinositides(PIP and PIP_2). This suggest specific feature of the tumor signal transduction system represented by the dissociation of PI-PKC (protein kinase C) system.
2. In our studies with using growth factors, we found the fact that the many responses were observed in the tumor signal transduction in each stimulation. There was obvious difference in the response between PDGF and EGF. Platelet derived growth factor predominantly activated PC-PLD(phospholipase D) system, suggesting the PI-PKC dissociation, based on analogy to TPA. We conclude that the tumor signal transduction should be regulated by "dual phospholipid turnover system", i. e. PI-PCL and PC-PLD, positioned in te higher signaling hierarchy.
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