Development of biomarkers target on exosomes which derived from stromal cells in premalignant microenvironment.
| Project/Area Number |
16K10601
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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 | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
白羽根 健吾 九州大学, 医学研究院, 共同研究員 (10529803)
当間 宏樹 九州大学, 医学研究院, 共同研究員 (80437780)
大内田 研宙 九州大学, 大学病院, 講師 (20452708)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | PDAC / ADM / exosome / micro RNA / biomarker / 膵癌 / バイオマーカー / エクソゾーム / miRNA / 膵液 / 膵星細胞 / 膵前癌病変 / 早期診断 |
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| Outline of Final Research Achievements |
Most PDAC patients are diagnosed with advanced stage. Identification of biomarkers for early and definitive PDAC diagnosis is crucial. ADM known as morphological change of acinar cells, occurs during pancreatitis and pancreatic cancer progression etc. It has been suggested that ADM may lead to precancerous lesion that precedes pancreatic cancer. We revealed characterization of the ADM phenotype associated with different pathological conditions by RNA sequencing of tissues which captured by laser capture microdissection.
To investigate whether exosomal microRNAs (ex-miRs) could be used as biomarkers for PDAC, we isolated exosomes from pancreatic juice from patients with PDAC and chronic pancreatitis (CP). Relative expression levels of exosomal miR-21 and miR-155, which were reported to overexpress in PDAC tissue and pancreatic juice, were significantly higher in PDAC patients compared with CP patients. Ex-miRs, including ex-miR-21 and ex-miR-155, may represent novel biomarkers of PDAC.
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| Academic Significance and Societal Importance of the Research Achievements |
膵癌の唯一の根治的治療は外科切除であるが、ほとんどの症例が切除不能の状態で診断される。よって、膵臓癌の治療成績改善のためには、画期的な早期診断法によって切除可能な段階で診断することが重要である。本研究において膵癌ハイリスク患者を模したマウスモデルを用いて微小環境内の細胞から早期診断のバイオマーカーとなりうる遺伝子候補を検索し、ヒト膵液由来のexosomeに含まれるマイクロRNAが優れた膵癌診断のバイオマーカーとなりうる可能性を示した。
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Report
(4 results)
Research Products
(6 results)
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[Journal Article] Pancreatic juice exosomal microRNAs as biomarkers for detection of pancreatic ductal adenocarcinoma2019
Author(s)
Nakamura S, Sadakari Y, Ohtsuka T, Okayama T, Nakashima Y, Gotoh Y, Saeki K, Mori Y, Nakata K, Miyasaka Y, Onishi H, Oda Y, Goggins M, Nakamura M.
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Journal Title
Ann Surg Oncol
Volume: 印刷中
Issue: 7
Pages: 2104-11
DOI
Related Report
Peer Reviewed
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[Journal Article] Pancreatic stellate cells reorganize matrix components and lead pancreatic cancer invasion via the function of Endo1802018
Author(s)
Koikawa K, Ohuchida K, Takesue S, Ando Y, Kibe S, Nakayama H, Endo S, Abe T, Okumura T, Horioka K, Sada M, Iwamoto C, Moriyama T, Nakata K, Miyasaka Y, Ohuchida R, Manabe T, Ohtsuka T, Nagai E, Mizumoto K, Hashizume M, Nakamura M.
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Journal Title
Cancer Letters
Volume: 412
Pages: 143-154
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Extra-pancreatic invasion induces lipolytic and fibrotic changes in the adipose microenvironment, with released fatty acids enhancing the invasiveness of pancreatic cancer cells.2017
Author(s)
Okumura T, Ohuchida K, Sada M, Abe T, Endo S, Koikawa K, Iwamoto C, Miura D, Mizuuchi Y, Moriyama T, Nakata K, Miyasaka Y, Manabe T, Ohtsuka T, Nagai E, Mizumoto K, Oda Y, Hashizume M, Nakamura M.
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Journal Title
Oncotarget
Volume: 8
Issue: 11
Pages: 18280-18295
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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