| Project/Area Number |
21K14789
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 38030:Applied biochemistry-related
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| Research Institution | National Institute of Advanced Industrial Science and Technology |
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Principal Investigator |
Ganbold Munkhzul 国立研究開発法人産業技術総合研究所, 材料・化学領域, 産総研特別研究員 (00882169)
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| Project Period (FY) |
2022-12-19 – 2025-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2023: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2022: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | isorhamnetin / pancreatic cancer / PDAC / flavonoid / CAF / CAFs / cell metabolism / natural compound / desmoplasia / remodeling / Isorhamnetin / quercetin derivative |
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| Outline of Research at the Start |
A wide range of in vitro studies using human PDAC cell lines and human immortalized CAFs derived from PDAC patients will be conducted to study the effect of isorhamnetin and its derivatives in a more realistic environment.
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| Outline of Annual Research Achievements |
Microarray analysis releaved top significant downregulated molecular pathways regulated by isorhamnetin treatment were G2M checkpoint, E2F targets and Mitotic spindle hallmarks. KEGG pathway analysis showed that Cell cycle and DNA replication pathways were downregulated, showing all genes associated with cell cycle process were affected by isorhamnetin. High quality images of mitochondria were taken using MitoTracker. Reduced mitochondrial footprint with elongated branch length was detected in isorhamnetin treated cells. Mitochondrial respiration and glycolysis were also performed. The spare respiratory capacity and glycolytic reserve were depleted in isorhamnetin treated CAFs. This indicates that isorhamnetin treated CAFs are likely more vulnerable to metabolic stress.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
After submission of manuscript, several comments requesting additional experiments and analyses of distinct CAF subtypes switch exerted by isorhamnetin treatment were received. Due to the request to perform additional experiments and revision, process of submitting to a journal is being delayed slightly.
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| Strategy for Future Research Activity |
Additional in vitro experiments were planned to support the finding of isorhamnetin effect on CAFs biology, especially in cell cycle arrest. Using microarray data, CAF subtype specific enrichment analysis will be carried out to emphasize potential CAF subtype switch and subtype-related hallmarks affected by isorhamnetin treatment. Inflammatory and myofibroblast CAFs specific markers will be evaluated in protein and gene expression level at different time points.
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