Elucidation of the mechanism of radioresistance in cancer cells using trans-omics approach and development of clinical biomarkers for radiotherapy.

• Project/Area Number: 16K20909
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy; Medical Physics and Radiological Technology
• Research Institution: Tohoku University
• Principal Investigator: Kanemitsu Yoshitomi 東北大学, 薬学研究科, 助手 (30752943)
• Research Collaborator: TOMIOKA Yoshihisa 東北大学, 大学院薬学研究科, 教授 (00282062) ; MATSUMOTO Yotato 東北大学, 大学院薬学研究科, 講師 (90420041) ; TSUKAMOTO Hiroki 東北大学, 大学院薬学研究科, 助教 (70423605) ; FUKUMOTO Manabu 東京医科大学, 医学部, 特任教授 (60156809) ; KUWAHARA Yoshikazu 東北医科薬科大学, 医学部, 准教授 (00392225)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 放射線耐性 / プロテオミクス / メタボロミクス / 脂肪酸合成酵素 / がん細胞

Outline of Final Research Achievements

In this study, we aimed to identify the molecules involved in radioresistance of cancer cells and to elucidate its mechanism. Here, we quantitatively compared the proteomes and the metabolomes of clinically relevant radioresistant (CRR) cell lines and their parent strains. In CRR cells, the chaperones and the proteins involved in oxidative stress were higher than control cell lines. Pathways such as amino acid metabolism and fatty acid metabolism were found to be highly enriched in CRR cells. These molecules can be expected as radiation tolerance markers and/or new targets for cancer therapies.

Research Products

• [Journal Article] Canagliflozin reduces plasma uremic toxins and alters the intestinal microbiota composition in a chronic kidney disease mouse model (2018)
  • Author(s): Mishima Eikan、Fukuda Shinji、Kanemitsu Yoshitomi、Saigusa Daisuke、Mukawa Chikahisa、Asaji Kei、Matsumoto Yotaro、Tsukamoto Hiroki、Tachikawa Tatsuki、Tsukimi Tomoya、Fukuda Noriko N、Ito Sadayoshi、Soga Tomoyoshi、Tomioka Yoshihisa、Abe Takaaki
  • Journal Title: Am J Physiol Renal Physiol Volume: 印刷中 Issue: 4 Pages: 824-833
  • DOI: 10.1152/ajprenal.00314.2017
  • Peer Reviewed / Open Access
• [Journal Article] The Disease-modifying Drug Candidate, SAK3 Improves Cognitive Impairment and Inhibits Amyloid beta Deposition in App Knock-in Mice. (2018)
  • Author(s): Izumi H, Shinoda Y, Saito T, Saido TC, Sato K, Yabuki Y, Matsumoto Y, Kanemitsu Y, Tomioka Y, Abolhassani N, Nakabeppu Y, Fukunaga K.
  • Journal Title: Neuroscience. Volume: 377 Pages: 87-97
  • DOI: 10.1016/j.neuroscience.2018.02.031
  • Peer Reviewed
• [Journal Article] Evaluation of the impact of gut microbiota on uremic solute accumulation by a CE-TOFMS-based metabolomics approach (2017)
  • Author(s): †Mishima, E., †Fukuda, S. (†equally contributed), Mukawa, C., Yuri, A., Kanemitsu, Y., Matsumoto, Y., Akiyama, Y., Fukuda, NN., Tsukamoto, H., Asaji, K., Shima, H., Kikuchi, K., Suzuki, T., Tomioka, Y., Soga, T., Ito, S., Abe, T.
  • Journal Title: Kidney International Volume: 92 Issue: 3 Pages: 634-645
  • DOI: 10.1016/j.kint.2017.02.011
  • Peer Reviewed / Open Access
• [Journal Article] Simultaneous quantitative analysis of uremic toxins by LC-MS/MS with a reversed-phase/cation-exchange/anion-exchange tri-modal mixed-mode column (2017)
  • Author(s): Kanemitsu Yoshitomi、Asaji Kei、Matsumoto Yotaro、Tsukamoto Hiroki、Saigusa Daisuke、Mukawa Chikahisa、Tachikawa Tatsuki、Abe Takaaki、Tomioka Yoshihisa
  • Journal Title: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences Volume: 1068-1069 Pages: 1-8
  • DOI: 10.1016/j.jchromb.2017.10.009
  • Peer Reviewed
• [Journal Article] An inhibitory epitope of human Toll-like receptor 4 resides on leucine-rich repeat 13 and is recognized by a monoclonal antibody (2017)
  • Author(s): Tsukamoto Hiroki、Yamagata Yuki、Ukai Ippo、Takeuchi Shino、Okubo Misaki、Kobayashi Yohei、Kozakai Sao、Kubota Kanae、Mumasaki Muneo、Kanemitsu Yoshitomi、Matsumoto Yotaro、Tomioka Yoshihisa
  • Journal Title: FEBS Letters Volume: 591 Issue: 16 Pages: 2406-2416
  • DOI: 10.1002/1873-3468.12768
  • Peer Reviewed
• [Presentation] 多層オミクス手法による放射線耐性化関連分子の探索 (2018)
  • Author(s): 富岡佳久、金光祥臣、松本洋太郎、桑原 義和、福本 学、塚本宏樹
  • Organizer: 第3回 治療耐性がん細胞研究協議会セミナー
• [Presentation] ミックスドモード ODS カラムを用いた LC-MS/MS による尿毒症物質一斉定量系の構築 (2017)
  • Author(s): 金光祥臣、淺地圭、松本洋太郎、塚本宏樹、三枝大輔、阿部高明、富岡佳久
  • Organizer: 第56回日本薬学会東北支部大会
• [Presentation] LC-HDMS および IMS を用いたヒト肝癌組織メタボロミクスによる新規バイオマーカーの同定 (2017)
  • Author(s): 永井滉士、三枝大輔、山崎貴広、金光祥臣、塚本宏樹、池田均、矢冨裕、松本洋太郎 、富岡佳久
  • Organizer: 第56回日本薬学会東北支部大会