| Project/Area Number |
16K10531
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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 |
Digestive surgery
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| Research Institution | Nagoya University |
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Principal Investigator |
UEHARA KEISUKE 名古屋大学, 医学部附属病院, 病院講師 (50467320)
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| Co-Investigator(Kenkyū-buntansha) |
梛野 正人 名古屋大学, 医学系研究科, 教授 (20237564)
横山 幸浩 名古屋大学, 医学系研究科, 寄附講座教授 (80378091)
國料 俊男 名古屋大学, 医学部附属病院, 講師 (60378023)
山口 淳平 名古屋大学, 医学部附属病院, 助教 (00566987)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | TLR7 / Danger signal / 大腸癌 |
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| Outline of Final Research Achievements |
Imiquimod, a TLR7 agonist, suppressed proliferation, motility and invasion and induced cell death in a human cancer cell line (DLD1, KLM1, Panc1 and HuCCT1). The cell morphology was different in each cancer cell line after imiquimod treatment. In addition, imiquimod induced early apoptosis in the cancer cell lines after 12 hours of treatment. Immunoglobulin heavy chain-binding protein (BiP), which is a marker of endoplasmic reticulum stress, was highly expressed in cancer cells after imiquimod treatment. Therefore, endoplasmic reticulum stress was considered a cause of imiquimod-induced apoptosis. However, the expression of PKR-like ER kinase (PERK), which is another marker of endoplasmic reticulum stress, did not change. This result suggested that a mechanism different from endoplasmic reticulum stress was involved in imiquimod-induced apoptosis. Further investigations will be required for clinical applications.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、TLR7アゴニストであるイミキモドの抗腫瘍効果およびその作用機序として小胞体ストレスによるアポトーシスの関与を明らかにした。新たな知見が明らかになっただけでなく、臨床応用への可能性も示唆されており、本研究成果の学術的、社会的意義は大きい。
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