| 研究課題/領域番号 |
21K14789
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| 研究種目 |
若手研究
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| 配分区分 | 基金 |
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| 審査区分 |
小区分38030:応用生物化学関連
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| 研究機関 | 国立研究開発法人産業技術総合研究所 |
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研究代表者 |
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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| 研究期間 (年度) |
2022-12-19 – 2025-03-31
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| 研究課題ステータス |
交付 (2023年度)
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| 配分額 *注記 |
4,420千円 (直接経費: 3,400千円、間接経費: 1,020千円)
2023年度: 650千円 (直接経費: 500千円、間接経費: 150千円)
2022年度: 2,080千円 (直接経費: 1,600千円、間接経費: 480千円)
2021年度: 1,690千円 (直接経費: 1,300千円、間接経費: 390千円)
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| キーワード | isorhamnetin / pancreatic cancer / PDAC / flavonoid / CAF / CAFs / cell metabolism / natural compound / desmoplasia / remodeling / Isorhamnetin / quercetin derivative |
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| 研究開始時の研究の概要 |
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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| 研究実績の概要 |
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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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
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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| 今後の研究の推進方策 |
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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