Project/Area Number |
19K17224
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 52040:Radiological sciences-related
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Research Institution | Gunma University |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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Keywords | Gadolinium / GBCA / Gadolinium retention / GDD / NSF / choroid plexus / contrast agents / Transmetallation / Gadolinium deposition / neutrophil elastase / astroglioma / meduloblastoma / Contrast agents (GBCA) / Fe(II) / Purkinje cells / Gadolinium toxicity / Gadolinium distribution / Blood-brain barrier |
Outline of Research at the Start |
Previous studies showed that Gd retention may occur in the brain tissue of normal patients. The mechanism of how Gd can penetrate the brain barrier resulting in retention in the brain tissue is yet to be elucidated. Unchelated Gd at low concentration has been shown to increase cell proliferation, but these phenomenon on brain tumor cells is unknown. In this research proposal, our aims are 1) To investigate the mechanism of Gd retention in the brain tissue by in vivo and in vitro studies, and 2) To investigate the effect of GBCAs exposure on the brain cancer cell lines by in vitro analysis.
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Outline of Final Research Achievements |
We found no significant differences in Gd concentration when Gadolinium-based contrast agents (GBCA) were incubated with transferrin. Incubation with Fe(II) did not cause any changes to the Purkinje cell arborization compared the control neurons. Fe(II) increased the effect of gadopentetate to the dendrite arborization, but it did not increase the effect of gadobutrol. Fibrotic markers were increased in the skin on renal failure mouse model that was injected with gadodiamide, while only collagen 1α and TGF-β mRNA expression were higher in the gadopentetate group. NE activity in the blood serum and the expression of skin NE was significantly higher in the GBCA-treated mice compared to the control. We investigated the GBCA effect on the C6-astroglioma and TE761-medulloblastoma in-vitro. GBCAs significantly increase the C6 proliferation, but the effect was less significant in TE761 cells.
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Academic Significance and Societal Importance of the Research Achievements |
This project provides the information of: The effect of Gd to the Purkinje cells, provide a background to reveal the mechanism of Gd retention in the brain, involvement of NE Skin lesion development in the Nephrogenic systemic fibrosis, and the effect of Gd to the proliferation of cancer cell lines.
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