Understanding and control of pathophysiology of thoracic surgical disease by autophagy

• Project/Area Number: 15K10235
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: Niigata University
• Principal Investigator: TSUCHIDA Masanori 新潟大学, 医歯学系, 教授 (60293221)
• Co-Investigator(Kenkyū-buntansha): 白石 修一 新潟大学, 医歯学総合病院, その他 (00422600) ; 佐藤 征二郎 新潟大学, 医歯学系, 助教 (40646931) ; 小池 輝元 新潟大学, 医歯学系, 講師 (90635723)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: オートファジー / 肺癌 / 大動脈疾患 / 血管内皮 / 肺扁平上皮癌 / 血管内皮障害 / ｐ62

Outline of Final Research Achievements

1. Analysis in lung cancer cells: Changes after glutaminolysis suppression regarding glutamine-dependent proliferation, mTORC1 activity, autophagy induction ability were analyzed using a lung cancer cell line. LC3 - II level was measured as an index of autophagy induction ability. It was found that cell proliferation was suppressed via mTORC1 signal suppression and autophage induction by suppressing glutaminolysis.
2. Vascular endothelial damage model: In the mouse model, expression of p53 was found to be enhanced when the vascular endothelium was exposed to stress such as ischemia and aging. It is thought that p62 is involved in autophagy, but the direct association between P53 and P62 is unknown, and further study is required.

Research Products

• [Journal Article] Impact of Concurrent Genomic Alterations Detected by Comprehensive Genomic Sequencing on Clinical Outcomes in East-Asian Patients with EGFR-Mutated Lung Adenocarcinoma (2018)
  • Author(s): Sato Seijiro、Nagahashi Masayuki、Koike Terumoto、Ichikawa Hiroshi、Shimada Yoshifumi、Watanabe Satoshi、Kikuchi Toshiaki、Takada Kazuki、Nakanishi Ryota、Oki Eiji、Okamoto Tatsuro、Akazawa Kouhei、Lyle Stephen、Ling Yiwei、Takabe Kazuaki、Okuda Shujiro、Wakai Toshifumi、Tsuchida Masanori
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 1-10
  • DOI: 10.1038/s41598-017-18560-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical and Genetic Implications of Mutation Burden in Squamous Cell Carcinoma of the Lung (2018)
  • Author(s): Okamoto Tatsuro、Takada Kazuki、Sato Seijiro、Toyokawa Gouji、Tagawa Tetsuzo、Shoji Fumihiro、Nakanishi Ryota、Oki Eiji、Koike Terumoto、Nagahashi Masayuki、Ichikawa Hiroshi、Shimada Yoshifumi、Watanabe Satoshi、Kikuchi Toshiaki、Akazawa Kouhei、Lyle Stephen、Takabe Kazuaki、Okuda Shujiro、Sugio Kenji
  • Journal Title: Annals of Surgical Oncology Volume: 25 Issue: 6 Pages: 1564-1571
  • DOI: 10.1245/s10434-018-6401-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Progerin impairs vascular smooth muscle cell growth via the DNA damage response pathway. (2017)
  • Author(s): Kinoshita D, Nagasawa A, Shimizu I, Ito T, Yohko Y, Tsuchida M, Iwama A, Hayano T and Minamino T.
  • Journal Title: Oncotarget Volume: 印刷中 Issue: 21 Pages: 34045-34056
  • DOI: 10.18632/oncotarget.15973
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A highly specific and sensitive massive parallel sequencer-based test for somatic mutations in non-small cell lung cancer. (2017)
  • Author(s): Inoue Y, Shiihara J, Miyazawa H, Ohta H, Higo M, Nagai Y, Kobayashi K, Saijo Y, Tsuchida M, Nakayama M, Hagiwara K.
  • Journal Title: PLoS One Volume: 12(4) Issue: 4 Pages: 1-14
  • DOI: 10.1371/journal.pone.0176525
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of Glutaminolysis Inhibits Cell Growth via Down-regulating Mtorc1 Signaling in Lung Squamous Cell Carcinoma (2016)
  • Author(s): Ye X, Zhou Q2, Matsumoto Y, Moriyama M, Kageyama S, Komatsu M, Satoh S, Tsuchida M, Saijo Y.
  • Journal Title: Anticancer Res. Volume: 36 Issue: 11 Pages: 6021-6029
  • DOI: 10.21873/anticanres.11191
  • Peer Reviewed
• [Journal Article] Effects of fibrotic tissue on liver-targeted hydrodynamic gene delivery. (2016)
  • Author(s): Kobayashi Y, Kamimura K, Abe H, Yokoo T, Ogawa K, Shinagawa Y, Goto R, Inoue R, Ohtsuka M, Miura H, Kanefuji T, Suda T, Tsuchida M, Aoyagi Y, Zhang G, Liu D, Terai S.
  • Journal Title: Mol Ther Nucleic Acids Volume: . 5: e359. Pages: 1-8
  • DOI: 10.1038/mtna.2016.63
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ホルマリン固定後パラフィン包埋肺腺癌検体からのDNA抽出濃度について 次世代シーケンサーによる網羅的遺伝子解析のために (2016)
  • Author(s): 佐藤 征二郎, 市川 寛, 島田 能史, 永橋 昌幸, 若井 俊文, 土田 正則, 井筒 浩, 兒玉 啓輔, 中田 光隆
  • Journal Title: 新潟医学会雑誌 Volume: 130 Pages: 601-611
  • NAID: 120006761707
• [Presentation] 次世代シーケンサーを用いた併存遺伝子変異の影響 (2017)
  • Author(s): 佐藤 征二郎, 後藤 達哉, 北原 哲彦, 小池 輝元, 高田 和樹, 岡本 龍郎, 土田 正則
  • Organizer: 日本肺癌学会
• [Presentation] 喫煙量が肺扁平上皮癌の腫瘍生物学に及ぼす影響 (2017)
  • Author(s): 岡本 龍郎, 高田 和樹, 佐藤 征二郎, 松原 太一, 上妻 由佳, 原武 直紀, 高森 信吉, 赤嶺 貴紀, 桂 正和, 豊川 剛司, 庄司 文裕, 土田 正則, 前原 喜彦
  • Organizer: 日本外科学会定期学術集会
• [Presentation] Safety of Simultaneous TEVAR and Combined Aortic Wall Resection at the Time of Lung Resection for T4 Lung Cancer Infiltrating the Aorta (2017)
  • Author(s): M tsuchida, Y shimizu, A Nakamura, H Kitahara, T Goto, S Sato, T Okamoto, T Koike
  • Organizer: 18th World Conference on Lung Cancer
• [Presentation] 次世代シーケンサーを用いた原発性肺腺癌切除例の網羅的遺伝子発現解析に基づく治療 (2016)
  • Author(s): 佐藤 征二郎,後藤 達哉, 北原 哲彦, 小池 輝元, 高田 和樹, 岡本 龍郎, 前原 喜彦, 土田 正則
  • Organizer: 日本肺癌学会
  • Place of Presentation: 福岡国際会議場（福岡県・福岡市）
  • Year and Date: 2016-12-19
• [Presentation] Comprehensive gene alterations identified by next-generation sequencing of lung adenocarcinoma in Japanese population (2016)
  • Author(s): S Sato, M Nagahashi, T Goto, A Kitahara, T Koike, K Takada, T Okamoto, Hi Izutsu, K Kodama, M Nakada, Y Maehara, T Wakai, M Tsuchida
  • Organizer: World Conferance on Lung Cancer
  • Place of Presentation: ウィーン（オーストリア）
  • Year and Date: 2016-12-04
  • Int'l Joint Research