Expression and role of volume-activated anion channels in gastric cancer
Project/Area Number |
20K09084
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 55020:Digestive surgery-related
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Research Institution | Kyoto Prefectural University of Medicine |
Principal Investigator |
Toma Atsushi 京都府立医科大学, 医学(系)研究科(研究院), 特任講師 (30516191)
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Co-Investigator(Kenkyū-buntansha) |
大辻 英吾 京都府立医科大学, 医学(系)研究科(研究院), 教授 (20244600)
塩崎 敦 京都府立医科大学, 医学(系)研究科(研究院), 講師 (40568086)
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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 |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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Keywords | 胃癌 / 胃十二指腸外科学 / イオンチャネル / 低浸透圧 |
Outline of Research at the Start |
本研究では、胃癌における容積活性化アニオンチャネル(VAAC)の構成蛋白であるLRRC8A、SLCO2A1の発現機能解析を行うとともに、"癌細胞のVAAC発現を制御すると調節性容積減少が抑制され、低浸透圧細胞破壊が促進される"という実験仮説の検証を行う。その結果から、VAACを分子標的とした低浸透細胞破壊療法という、術中遊離胃癌細胞・腹膜播種性転移に対する斬新な治療概念の構築を目指す。
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Outline of Final Research Achievements |
The depletion of LRRC8A using siRNA decreased cell proliferation and cellular movement, and promoted the induction of apoptosis in human gastric cancer (GC) cells. The microarray analysis showed the up- or down-regulated expression of genes related to the p53 signaling pathway (JNK, p53, p21, Bcl-2, and FAS) in LRRC8A-knockdown cells. An immunohistochemical analysis revealed a correlation between the expression of LRRC8A and the pT status, and multivariate analysis identifed the strong expression of LRRC8A as an independent prognostic factor for 5-year survival in GC patients. Further, the depletion of SLCO2A1 using siRNA decreased cell proliferation, and promoted the induction of apoptosis in human GC cells. The present results indicate that volume-activated anion channels functions as a mediator of and/or biomarker for GC.
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Academic Significance and Societal Importance of the Research Achievements |
LRRC8Aが胃癌組織において高発現し、そのRNA干渉が癌細胞に抑制効果を示すことを新たに見出した。LRRC8Aのp53 signaling pathwayを介する新たな腫瘍進展制御機構や、予後因子としての意義を明らかにし、バイオマーカーや治療標的としての可能性を示した。また、SLCO2A1のアポトーシス制御機構を解明し、容積活性化アニオンチャネルを標的とした新規治療への応用が期待される。
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Report
(4 results)
Research Products
(53 results)
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[Journal Article] ANO9 regulates PD-L2 expression and binding ability to PD-1 in gastric cancer.2021
Author(s)
Katsurahara K, Shiozaki A, Kosuga T, Shimizu H, Kudou M, Arita T, Konishi H, Komatsu S, Kubota T, Fujiwara H, Okamoto K, Kishimoto M, Konishi E, Otsuji E.
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Journal Title
Cancer Science
Volume: 112
Issue: 3
Pages: 1026-1037
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinical safety and efficacy of neoadjuvant combination chemotherapy of tranilast in advanced esophageal squamous cell carcinoma: Phase I/II study (TNAC).2020
Author(s)
Shiozaki A, Kudou M, Fujiwara H, Konishi H, Shimizu H, Arita T, Kosuga T, Yamamoto Y, Morimura R, Ikoma H, Kuriu Y, Kubota T, Okamoto K, Otsuji E.
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Journal Title
Medicine
Volume: 99
Issue: 50
Pages: e23633-e23633
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] ANO9 Regulated Cell Cycle in Human Esophageal Squamous Cell Carcinoma.2020
Author(s)
Katsurahara K, Shiozaki A, Kosuga T, Kudou M, Shoda K, Arita T, Konishi H, Komatsu S, Kubota T, Fujiwara H, Okamoto K, Kishimoto M, Konishi E, Marunaka Y, Otsuji E.
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Journal Title
Ann Surg Oncol.
Volume: ー
Issue: 9
Pages: 3218-3230
DOI
Related Report
Peer Reviewed
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[Presentation] 大腸癌幹細胞の低浸透圧ショックへの抵抗性2022
Author(s)
加藤俊治, 塩崎敦, 工藤道弘, 清水浩紀, 小菅敏幸, 木内純, 大橋拓馬, 有田智洋, 山本有祐, 小西博貴, 森村玲, 栗生宜明, 生駒久視, 窪田健, 藤原斉, 岡本和真, 大辻英吾
Organizer
第 122 回日本外科学会定期学術集会
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[Presentation] Amlodipine, voltage-gated Ca2+ channel inhibitor, suppressed the growth of cancer stem cells in hepatocellular carcinoma2022
Author(s)
Atsushi Shiozaki, Kento Kurashima, Michihiro Kudou, Hiroki Shimizu,Toshiyuki Kosuga, Takuma Ohashi, Tomohiro Arita, Yusuke Yamamoto, Hirotaka Konishi, Ryo Morimura, Yoshiaki Kuriu, Hisashi Ikoma, Takeshi Kubota, Hitoshi Fujiwara, Eigo Otsuji
Organizer
第81回日本癌学会学術総会
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[Presentation] Tranilast and furosemide suppressed the growth of cancer stem cells in esophageal adenocarcinoma2022
Author(s)
Hiroyuki Inoue, Atsushi Shiozaki, Toshiyuki Kosuga, Hiroki Shimizu, Michihiro Kudou, Takuma Ohashi, Tomohiro Arita, Hirotaka Konishi, Ryo Morimura, Takeshi Kubota, Hitoshi Fujiwara, Eigo Otsuji
Organizer
第81回日本癌学会学術総会
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[Presentation] Correlation between TRPV2 and PD-L1 expression in advanced gastric cancer and its clinical significance2022
Author(s)
Tomoyuki Fukami, Atsushi Shiozaki, Jun Kiuchi, Takuma Ohashi, Hiroki Shimizu, Tomohiro Arita, Yusuke Yamamoto, Hirotaka Konishi, Ryo Morimura, Yoshiaki Kuriu, Hisashi Ikoma, Takeshi Kubota, Hitoshi Fujiwara, Eigo Otsuji
Organizer
第81回日本癌学会学術総会
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[Presentation] The function analysis and clinical significance of CACNA2D1 in human gastric cancer2022
Author(s)
Naosuke Nakamichi, Atsushi Shiozaki, Hiroyuki Inoue, Toshiyuki Kosuga, Hiroki Shimizu, Michihiro Kudou, Takuma Ohashi, Tomohiro Arita, Yusuke Yamamoto, Hirotaka Konishi, Yoshiaki Kuriu, Hisashi Ikoma, Takeshi Kubota, Hitoshi Fujiwara, Eigo Otsuji
Organizer
第81回日本癌学会学術総会
Related Report
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[Presentation] Gastric cancer stem cells are suppressed by voltage-gated Ca2+ channel inhibitors2021
Author(s)
Atsushi Shiozaki, Keita Katsurahara, Toshiyuki Kosuga, Michihiro Kudou, Hiroki Shimizu, Takuma Ohashi, Tomohiro Arita, Yusuke Yamamoto, Hirotaka Konishi, Ryo Morimura, Yoshiaki Kuriu, Hisashi Ikoma, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Eigo Otsuji
Organizer
第80回日本癌学会学術総会
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[Presentation] The expression and role of CACNA2D1 in human gastric cancer2021
Author(s)
Hiroyuki Inoue, Atsushi Shiozaki, Toshiyuki Kosuga, Hiroki Shimizu, Michihiro Kudou, Tomohiro Arita, Yusuke Yamamoto, Hirotaka Konishi, Ryo Morimura, Yoshiaki Kuriu, Hisashi Ikoma, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Eigo Otsuji
Organizer
第80回日本癌学会学術総会
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[Presentation] Colorectal cancer stem cells have resistance to hypotonic shock2021
Author(s)
Shunji Kato, Atsushi Shiozaki, Hiroki Shimizu, Michihiro Kudou, Toshiyuki Kosuga, Tomohiro Arita, Yusuke Yamamoto, Hirotaka Konishi, Ryo Morimura, Yoshiaki Kuriu, Hisashi Ikoma, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Eigo Otsuji
Organizer
第80回日本癌学会学術総会
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[Presentation] ATP1A1 regulates tumor progression and affects postoperative prognosis in human gastric cancer2021
Author(s)
Kei Nakamura, Atsushi Shiozaki, Michihiro Kudou, Hiroki Shimizu, Toshiyuki Kosuga, Tomohiro Arita, Yusuke Yamamoto, Hirotaka Konishi, Ryo Morimura, Yoshiaki Kuriu, Hisashi Ikoma, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Mitsuo Kishimoto, Eigo Otsuji
Organizer
第80回日本癌学会学術総会
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