| Project/Area Number |
16K11731
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Ehime University (2019)
Dokkyo Medical University (2016-2018) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
木内 誠 獨協医科大学, 医学部, 助教 (00759483)
内田 大亮 獨協医科大学, 医学部, 准教授 (20335798)
川又 均 獨協医科大学, 医学部, 教授 (70224847)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | mGluR 5 / CXCR 4 / mGluR5 / CXCR4 / ｍGluR5 / 口腔癌 / 歯学 / 腫瘍学 |
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| Outline of Final Research Achievements |
We could not demonstrate significant results with a novel orally bioavailable mGluR5 inhibitor, RG7090 on the metastasis of oral cancer cells. However, we focus only on minimally invasive and persistent control, continued our study with AMD 070, a novel oral inhibitor of CXCR4 that is upstream of mGluR5. Mice adminstrated with AMD 070 did not exhibit any side effects, such as hematotoxicity, allergic reactions or weight loss. Although treatment with AMD070 did not affect the anchorage-dependent growth of B88-SDF-1 cells, it significantly suppressed the anchorage-independent growth. Moreover, we performed an experimental therapy using AMD070 to prevent the distant metastasis of B88-SDF-1 cells in vivo. Daily oral administration of AMD070 significantly inhibited the lung metastasis of B88-SDF-1 cells in nude mice.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究では、mGluR5 特異的経口阻害剤での有意な結果は得られなかったが、その上流の CXCR4 特異的経口阻害剤による転移抑制効果および有害事象について確認し、新規経口害剤が、SDF-1/CXCR4システムを介した口腔癌の転移を、低侵襲かつ持続的に抑制できる可能性を示唆した。
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