Inhibition of cisplatin resistance by HMGB1 targeting in gastric cancer
Project/Area Number |
20K17661
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 55020:Digestive surgery-related
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Research Institution | Nara Medical University |
Principal Investigator |
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | シスプラチン / 胃癌 / HMGB1 / 薬剤耐性 / 酸化HMGB1 / 糖化HMGB1 / CML-HMGB1 / タンシノン / エチルピルビン酸 / 酸化型HMGB1 / RAGE / デオキシコール酸 |
Outline of Research at the Start |
胃癌の化学療法においてシスプラチンは中心的な薬剤のひとつであるが、その感受性は症例により差異があり、感受性の予知および増強法を開発することは胃癌の予後改善に重要である。申請者は、シスプラチン耐性にHMGB1高発現が有意に相関することを見出したが、発現抑制やシグナル阻害では核内HMGB1のDNA修復機能を抑制できなかった。本研究では、DNA修復機能を有する核内HMGB1を選択的に阻害する方法を検討し、シスプラチン耐性を解除する補助的治療法の基礎的知見を得ることを目的とする。本研究の結果はシスプラチンの奏効性を高め、胃癌の治療成績の向上につながることが期待される。
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Outline of Final Research Achievements |
HMGB1 is an important factor in cisplatin resistance. In this study, we attempted to improve cisplatin resistance by targeting HMGB1. Post-translational modification of HMGB1 showed that oxidized HMGB1 was more active than naive HMGB1, and glycated HMGB1 (CML-HMGB1) was more active. In contrast, inhibition of HMGB1 secretion by ethylpyruvate or tanshinone suppressed CML-HMGB1-induced cisplatin resistance. These findings indicate that targeting HMGB1, especially CML-HMGB1, is important for overcoming cisplatin resistance.
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Academic Significance and Societal Importance of the Research Achievements |
胃癌の化学療法においてシスプラチンは中心的な薬剤のひとつであるが、その感受性は症例により差異があり、感受性の予知および増強法を開発することは胃癌の予後改善に重要である。申請者は、シスプラチン耐性にHMGB1高発現が有意に相関することを見出したが、発現抑制やシグナル阻害では核内HMGB1のDNA修復機能を抑制できなかった。本研究では、DNA修復機能を有する核内HMGB1を選択的に阻害する方法を検討し、シスプラチン耐性を解除する補助的治療法の基礎的知見を得ることを目的とする。本研究の結果はシスプラチンの奏効性を高め、胃癌の治療成績の向上につながることが期待される。
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Report
(4 results)
Research Products
(27 results)
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[Journal Article] Short telomere lesions with dysplastic metaplasia histology may represent precancerous lesions of Helicobacter pylori-positive gastric mucosa2023
Author(s)
Fujiwara-Tani R, Takagi T, Mori S, Kishi S, Nishiguchi Y, Sasaki T, Ikeda M, Nagai K, Bhawal UK, Ohmori H, Fujii K, Kuniyasu H
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Journal Title
International Journal of Molecular Sciences
Volume: 24(4)
Issue: 4
Pages: 3182-3182
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Role of Glycated High Mobility Group Box-1 in Gastric Cancer2021
Author(s)
Kishi Shingo、Nishiguchi Yukiko、Honoki Kanya、Mori Shiori、Fujiwara-Tani Rina、Sasaki Takamitsu、Fujii Kiyomu、Kawahara Isao、Goto Kei、Nakashima Chie、Kido Akira、Tanaka Yasuhito、Luo Yi、Kuniyasu Hiroki
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Journal Title
International Journal of Molecular Sciences
Volume: 22
Issue: 10
Pages: 5185-5185
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] BRAF Mutation Is Associated with Hyperplastic Polyp-Associated Gastric Cancer2021
Author(s)
Fujiwara-Tani Rina、Okamoto Ayaka、Katsuragawa Hiroyuki、Ohmori Hitoshi、Fujii Kiyomu、Mori Shiori、Kishi Shingo、Sasaki Takamitsu、Nakashima Chie、Kawahara Isao、Hojo Yudai、Nishiguchi Yukiko、Mori Takuya、Mizumoto Takeshi、Nagai Kenta、Luo Yi、Kuniyasu Hiroki
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Journal Title
International Journal of Molecular Sciences
Volume: 22
Issue: 23
Pages: 12724-12724
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Effect of Proton Pump Inhibitors on Colorectal Cancer2020
Author(s)
Sasaki Takamitsu、Mori Shiori、Kishi Shingo、Fujiwara-Tani Rina、Ohmori Hitoshi、Nishiguchi Yukiko、Hojo Yudai、Kawahara Isao、Nakashima Chie、Fujii Kiyomu、Luo Yi、Kuniyasu Hiroki
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Journal Title
International Journal of Molecular Sciences
Volume: 21
Issue: 11
Pages: 3877-3877
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Clostridium perfringens enterotoxin induced claudin-4 to activate YAP in oral squamous cell carcinomas.2020
Author(s)
Nakashima C, Yamamoto K, Kishi S, Sasaki T, Ohmori H, Fujiwara-Tani R Mori S, Kawahara I, Nishiguchi Y, Mori T, Kondoh M, Luo Y, Kirita T, Kuniyasu H
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Journal Title
Oncotarget
Volume: 11
Issue: 4
Pages: 309-321
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Role of glycated high mobility group box-1 in gastric cancer.2021
Author(s)
Nishiguchi Y, Kishi S, Mori S, Takagi T, Hojo Y, Sasaki T, Fujii K, Nakashima C, Luo Y, Fujiwara-Tani R, Kuniyasu H
Organizer
80th Annual Meeting of Japanese Association for Cancer
Related Report
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[Presentation] Role of glycated high mobility group box-1 in gastric cancer.2021
Author(s)
Nishiguchi Y, Kishi S, Mori S, Takagi T, Hojo Y, Sasaki T, Fujii K, Nakashima C, Luo Y, Fujiwara-Tani R, Kuniyasu H
Organizer
第32回日本消化器癌発生学会・第10回国際消化器癌発生学会
Related Report
Int'l Joint Research
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