| Project/Area Number |
18K15758
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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 53010:Gastroenterology-related
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| Research Institution | Nagoya City University |
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Principal Investigator |
Nishie Hirotada 名古屋市立大学, 医薬学総合研究院(医学), 助教 (00812174)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
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)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | PDT / 一重項酸素 / アポトーシス / アセチル基 / 糖鎖連結光感受性物質 / 光線力学的治療 / 内科 |
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| Outline of Final Research Achievements |
In PDT, apoptosis and necrosis are said to be induced by ROS and singlet oxygen induced by photochemical reactions. It has also been reported that apoptosis is induced in the endoplasmic reticulum (ER) and Golgi apparatus through the disruption of ER-Ca+ channel, which is derived from singlet oxygen generated in the ER and Golgi apparatus, respectively. Our results show that AcN003HP generates more singlet oxygen than other light-sensitive substances, and that it is localized in the endoplasmic reticulum. It also delayed peak uptake by 60 minutes more than G-cholrin e6. Therefore, it is possible that AcN003HP showed a higher cell-killing effect than the second-generation TS.
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| Academic Significance and Societal Importance of the Research Achievements |
光線力学療法（PDT）は様々な領域で臨床応用されており，消化器領域では化学放射線療法後の遺残再発食道癌に対し，TSを用いたPDTが保険収載されている。我々は以前から癌細胞が正常細胞より多くの糖を取り込む性質(Warburg効果)を応用して糖を連結したPSの開発を行っており，代謝、抗腫瘍効果にすぐれたGcholrin e6を開発した。ただし代謝が非常に早く、十分な腫瘍集積を得られているとは考えにくい状況であった。今回我々はAcN003HPを用いた光線力学療法の抗腫瘍効果などについて検討を行った。今後もさらに研究をつづけ改良を重ねることにより、有効性・安全性の向上を計る。
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