| Project/Area Number |
19K23878
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0901:Oncology and related fields
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| Research Institution | Akita University |
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Principal Investigator |
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| Project Period (FY) |
2019-08-30 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 胃癌 / 腫瘍由来細胞外小胞 / 超高感度ISH法 / 細胞外小胞 / マクロファージ |
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| Outline of Research at the Start |
腫瘍由来細胞外小胞(tumor derived extracellular vesicles；TEVs)は光学顕微鏡の観察限界をこえる微小な構造物であるため光学顕微鏡下での評価はなされておらず、病理標本を用いた臨床病理学的検討はいまだなされていない。本研究ではTEVs含有mRNAに対する超高感度in situ hybridization法を用いてTEVsの光学顕微鏡下での可視化手法を確立する。さらに、この手法を用いて手術検体の病理組織標本(肺癌、胃癌)でのTEVsの評価を行い、その臨床病理学的意義を検証する。
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| Outline of Final Research Achievements |
Tumor-derived extracellular vesicles (TEVs) extracted from gastric cancer cell lines were confirmed to contain RNAs (HER2, UCA1) that are expressed relatively specifically in cancer cells by qPCR. Fluorescently labeled gastric cancer cell lines were implanted in mice, and tumor specimens were harvested to confirm dot-like structures around cancer foci as possible TEVs by ultra-sensitive ISH and confocal microscopy. Ultra-sensitive ISH for HER2 was performed on gastric cancer surgical specimens, and dotted structures were identified as TEVs in HER2 score 3 specimens, while almost none were found in score 0-2 specimens.
The results showed that TEVs could be observed by ultra-sensitive ISH using optical microscopy if cancer cell-specific RNAs are targeted.
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| Academic Significance and Societal Importance of the Research Achievements |
腫瘍由来細胞外小胞(TEVs)は様々な作用(腫瘍微小環境形成、転移促進、血管新生、腫瘍免疫抑制など)で、腫瘍促進性に働くことは徐々に明らかになってきているが、一方、TEVsは微小構造であり、通常の光学顕微鏡で観察することが難しく、臨床的に観察、応用することが困難とされている。今回、超高感度ISH法により、一般的なパラフィン切片上で、TEVｓと考えられる構造を観察できる可能性が示せた。TEVsの観察がより簡便になることで、TEVsとそれぞれの予後との関連、TEVsを標的とした新規治療法の可能性など、臨床的応用の可能性がでてくるものと考る。
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