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Searching for molecular markers of postoperative recurrence after surgery for lung cancer and its clinical application

Research Project

Project/Area Number 17K10803
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory surgery
Research InstitutionKanazawa Medical University

Principal Investigator

URAMOTO Hidetaka  金沢医科大学, 医学部, 教授 (90389445)

Co-Investigator(Kenkyū-buntansha) 薄田 勝男  金沢医科大学, 医学部, 教授 (00324046)
本野 望  金沢医科大学, 医学部, 講師 (30634901)
上田 善道  金沢医科大学, 医学部, 教授 (50271375)
町田 雄一郎  金沢医科大学, 金沢医科大学氷見市民病院, 助教 (50460366)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords肺癌 / 術後再発 / TSHZ2 / PRDX4 / biomarker / 手術 / 再発 / 診断 / 肺外科
Outline of Final Research Achievements

Surgery has reduced relapse, new tumors and deaths in patients with lung adenocarcinoma, but survival rate was still lower due to it’s characteristics of early metastasis and recurrence. we performed a microarray expression analysis using a combination of tumor tissues and cell lines based on recurrence or no-recurrence cases.We demonstrated the tumor-suppressive function of TSHZ2 in lung adenocarcinoma. TSHZ2 was found to be highly expressed in most lung adenocarcinoma cell lines and tumor tissues of lung adenocarcinoma patients. The overexpressed plasmids of TSHZ2 led to the dramatic inhibition of cell proliferation, colony formation ability, migration and apoptosis induction in lung adenocarcinoma cells. Notably, the high TSHZ2 expression patients with lung adenocarcinoma was inclined to have less EGFR mutations,but had preferable prognosis. Increased TSHZ2 could restrain EGFR and p-Erk1/2 expression, simultaneously activate p-SAPK/Jnk and p-P38 expression in vitro.

Academic Significance and Societal Importance of the Research Achievements

完全切除はすなわち、完治、つまり再発がない根治ということを意味する。しかし、実際には種々の固形腫瘍で一定の割合で再発する。しかも肺癌の術後再発率は決して低くはない。しかし、病理組織学的評価、腫瘍マーカーなどの臨床的パラメーターはそれなりの再発の予測になるが、それらをもってしても全貌を説明可能ではない。また現在、肺癌では再発率を少しでも減らすために、術後補助化学療法が施行されているが、その真の恩恵を得るのは約5%にすぎない。つまり、再発するであろう、かつ、その薬剤の効果を期待できる母集団に限定される。本研究はその再発するであろう集団の特定につながると思われる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (30 results)

All 2020 2019 2018 2017 2016

All Journal Article (15 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 15 results,  Open Access: 11 results) Presentation (15 results) (of which Int'l Joint Research: 5 results,  Invited: 4 results)

  • [Journal Article] Detection of Mediastinal Lymph Node Metastases Using Indocyanine Green (ICG) Fluorescence Imaging in an Orthotopic Implantation Model.2020

    • Author(s)
      Zhao S, Guo X, Taniguchi M, Kondo K, Yamada S, Gu C, Uramoto H.
    • Journal Title

      Anticancer Res.

      Volume: 40 Issue: 4 Pages: 1875-1882

    • DOI

      10.21873/anticanres.14141

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The impact of PRDX4 and the EGFR mutation status on cellular proliferation in lung adenocarcinoma. Mizutani K, Guo X, Shioya A, Zhang J, Zheng J, Kurose N, Ishibashi H, Motono N, U2019

    • Author(s)
      Mizutani K, Guo X, Shioya A, Zhang J, Zheng J, Kurose N, Ishibashi H, Motono N, Uramoto H, Yamada S.
    • Journal Title

      Int J Med Sci.

      Volume: 16 Issue: 9 Pages: 1199-1206

    • DOI

      10.7150/ijms.36071

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Diffusion-Weighted Imaging Can Differentiate between Malignant and Benign Pleural Diseases2019

    • Author(s)
      Usuda Katsuo、Iwai Shun、Funasaki Aika、Sekimura Atsushi、Motono Nozomu、Matoba Munetaka、Doai Mariko、Yamada Sohsuke、Ueda Yoshimichi、Uramoto Hidetaka
    • Journal Title

      Cancers

      Volume: 11 Issue: 6 Pages: 811-811

    • DOI

      10.3390/cancers11060811

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] What is the allowed volume threshold for chest tube removal after lobectomy: A randomized controlled trial2019

    • Author(s)
      Motono Nozomu、Iwai Shun、Funasaki Aika、Sekimura Atsushi、Usuda Katsuo、Uramoto Hidetaka
    • Journal Title

      Annals of Medicine and Surgery

      Volume: 43 Pages: 29-32

    • DOI

      10.1016/j.amsu.2019.05.011

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Thoracoscopic small pulmonary nodule detection using computed tomography-guided cutaneous marking and pleural marking2019

    • Author(s)
      Sekimura Atsushi、Funasaki Aika、Iwai Shun、Motono Nozomu、Usuda Katsuo、Uramoto Hidetaka
    • Journal Title

      Journal of Thoracic Disease

      Volume: 11 Issue: 7 Pages: 2745-2753

    • DOI

      10.21037/jtd.2019.06.68

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] What is the best drug as a front-line treatment for EGFR activating mutation?2018

    • Author(s)
      Uramoto H
    • Journal Title

      Precision Cancer Medicine

      Volume: 1 Pages: 1-6

    • DOI

      10.21037/pcm.2018.09.07

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Expression and Prognostic Impact of VEGF, CD31 and αSMA in Resected Primary Lung Cancers.2018

    • Author(s)
      Usuda K, Iwai S, Funasaki A, Sekimura A, Motono N, Ueda Y, Shimazaki M,Uramoto H.
    • Journal Title

      Anticancer Res

      Volume: 38 Issue: 7 Pages: 4057-4063

    • DOI

      10.21873/anticanres.12695

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The Association of Peroxiredoxin 4 with the Initiation and Progression of Hepatocellular Carcinoma.2018

    • Author(s)
      Guo X, Noguchi H, Ishii N, Homma T, Hamada T, Hiraki T, Zhang J, Matsuo K, Yokoyama S, Ishibashi H, Fukushige T, Kanekura T, Fujii J, Uramoto H, Tanimoto A,Yamada S.
    • Journal Title

      Antioxid Redox Signal.

      Volume: 30 Issue: 10 Pages: 1271-1284

    • DOI

      10.1089/ars.2017.7426

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Critical in vivo roles of WNT10A in wound healing by regulating collagen expression/synthesis in WNT10A-deficient mice.2018

    • Author(s)
      Wang KY, Yamada S, Izumi H, Tsukamoto M, Nakashima T, Tasaki , Guo X, Uramoto H, Sasaguri Y, Kohno K.
    • Journal Title

      PLoS One

      Volume: 13 Issue: 3 Pages: e0195156-e0195156

    • DOI

      10.1371/journal.pone.0195156

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Depletion of WNT10A Prevents Tumor Growth by Suppressing Microvessels and Collagen Expression.2018

    • Author(s)
      Kumagai M, Guo X, Wang KY, Izumi H, Tsukamoto M, Nakashima T, Tasaki T, Kurose N, Uramoto H, Sasaguri Y,Kohno K, Yamada S.
    • Journal Title

      International Journal of Medical Sciences

      Volume: 16 Issue: 3 Pages: 416-423

    • DOI

      10.7150/ijms.26997

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Routine genetic testing of lung cancer specimens derived from surgery, bronchoscopy and fluid aspiration by next generation sequencing2017

    • Author(s)
      Gou Yamamoto, Mari Kikuchi, Shiho Kobayashi, Yoshiko Arai, Kenji Fujiyoshi, Tomokazu Wakatsuki, Miho Kakuta, Yuki Yamane, Yoshihito Iijima, Hideaki Mizutani, Yuki Nakajima, Junko Sudo, Hiroyasu Kinoshita, Futoshi Kurimoto, Hirohiko Akiyama, Hidetaka Uramoto, Hiroshi Sakai, Yoshito Akagi, Kiwamu Akagi
    • Journal Title

      International journal of oncology

      Volume: 50 Issue: 5 Pages: 1579-1589

    • DOI

      10.3892/ijo.2017.3935

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Non-small cell lung cancer: Whole-lesion histogram analysis of the apparent diffusion coefficient for assessment of tumor grade, lymphovascular invasion and pleural invasion2017

    • Author(s)
      Tsuchiya Naoko、Doai Mariko、Usuda Katsuo、Uramoto Hidetaka、Tonami Hisao
    • Journal Title

      PLoS One

      Volume: 12 Issue: 2 Pages: 0172433-017243

    • DOI

      10.1371/journal.pone.0172433

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of Notch1 and Numb in small cell lung cancer.2017

    • Author(s)
      Kikuchi H, Sakakibara-Konishi J, Furuta M, Yokouchi H, Nishihara H, Yamazaki S, Uramoto H, Tanaka F, Harada M, Akie K, Sugaya F, Fujita Y, Takamura K, Kojima T, Harada T, Higuchi M, Honjo O, Minami Y, Watanabe N, Oizumi S, Suzuki H, Ishida T, Dosaka-Akita H, Isobe H, Munakata M, Nishimura M.
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 6 Pages: 10348-10358

    • DOI

      10.18632/oncotarget.14411

    • NAID

      120006219939

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The neuropilin 2 isoform NRP2b uniquely supports TGFβ-mediated progression in lung cancer2017

    • Author(s)
      Gemmill Robert M.、Nasarre Patrick、Nair-Menon Joyce、Cappuzzo Federico、Landi Lorenza、D’Incecco Armida、Uramoto Hidetaka、Yoshida Takeshi、Haura Eric B.、Armeson Kent、Drabkin Harry A.
    • Journal Title

      Sci Signal

      Volume: 10 Issue: 462 Pages: 0528-0528

    • DOI

      10.1126/scisignal.aag0528

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immunohistochemical profiling of receptor tyrosine kinases, MED12, and TGF-βRII of surgically resected small cell lung cancer, and the potential of c-kit as a prognostic marker2016

    • Author(s)
      Yokouchi H, Nishihara H, Harada T, Ishida T, Yamazaki S, Kikuchi H, Oizumi S, Uramoto H, Tanaka F, Harada M, Akie K, Sugaya F, Fujita Y, Takamura K, Kojima T, Higuchi M, Honjo O, Minami Y, Watanabe N, Goto A, Suzuki H, Dosaka-Akita H, Isobe H, Nishimura M, Munakata M
    • Journal Title

      Oncotarget

      Volume: Dec 31 Issue: 24 Pages: 39711-39726

    • DOI

      10.18632/oncotarget.14410

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] How we identify ideas for research in Personal replacement?: Searching for molecular markers of postoperative recurrence.2019

    • Author(s)
      浦本秀隆
    • Organizer
      第72回日本胸部外科学会定期学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Postgraduate Course: Perioperative infectious disease and counterplan/Respiratory surgery2019

    • Author(s)
      浦本秀隆
    • Organizer
      第72回日本胸部外科学会定期学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 肺癌におけるがんゲノム医療の展望と外科的処置の介入による組織量確保の重要性2019

    • Author(s)
      本野 望、浦本 秀隆.
    • Organizer
      第44回日本外科系連合学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 過去10年間における肺癌切除例の患者背景と治療内容の変遷と予後解析:術後合併症の予後への影響.2019

    • Author(s)
      本野 望、岩井 俊、船崎 愛可、関村 敦、薄田 勝男、浦本 秀隆.
    • Organizer
      第60回日本肺癌学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Prospective study for usefulness of plasma DNA on prediction of third generation EGFR tyrosine kinase inhibitors; The intermediate analysis of S-PLAT study.2019

    • Author(s)
      H. Yoshida, C. Nakashima, N. Matsumoto, K. Iwanaga, N. Ebi, A. Nishiyama, K. Yatera, S. Kuyama, M. Fukuda, S. Ushijima, H. Umeguchi, D. Harada, K. Kashiwabara, T. Suetsugu, N. Fujimoto, F. Tanaka, H. Uramoto, C. Yoshii, K. Nakatomi, N. Sueoka-Aragane
    • Organizer
      ESMO
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Salvage Thoracic Surgery for Primary Lung Cancer:Comparison with Induction therapy followed by surgery2018

    • Author(s)
      Uramoto H.
    • Organizer
      第4回大連肺癌学会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Diffusion-Weighted Imaging can differentiate pleural dissemination from malignant pleural mesothelioma, empyema or pleural effusion.2018

    • Author(s)
      Usuda K, Iwai S, Funasaki A, Sekimura A, Motono N, Matoba M, Doai M, Yamada S, Ueda Y, Uramoto H.
    • Organizer
      International Cancer Imaging
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] MR拡散強調画像は肺癌の初期癌性胸膜炎・胸膜播種が検出できる2018

    • Author(s)
      薄田勝男, 船崎愛可, 本野望, 関村敦, 的場宗孝, 土合万里子, 上田善道, 浦本秀隆
    • Organizer
      第35回日本呼吸器外科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] A prospective randomized control trial of volume threshold for chest tube removal after pulmonary resection2018

    • Author(s)
      本野望,岩井俊,船崎愛可,関村敦,薄田勝男,浦本秀隆
    • Organizer
      第71回日本胸部外科学会定期学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 肺腺癌の予後因子に関する検討;亜型分類,SUVmax,EGFR遺伝子変異は独立した予後因子である2018

    • Author(s)
      本野望,岩井俊,船崎愛可,関村敦,薄田勝男,浦本秀隆
    • Organizer
      第59回日本肺癌学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Diagnostic Performance of Whole-Body Diffusion-Weighted Imaging Compared to PET-CT Plus Brain MRI in Staging Clinically Resectable Lung Cancer2017

    • Author(s)
      薄田勝男、本野望、松井琢真、町田雄一郎、浦本秀隆
    • Organizer
      European Cancer Congress (ECCO)2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 肺癌の集学的治療における呼吸器外科医の立ち位置と挑戦的手術2017

    • Author(s)
      浦本秀隆.
    • Organizer
      第5回臨床外科学会石川県支部学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] pN1非小細胞肺癌におけるリンパ節転移形式と予後の関係2017

    • Author(s)
      本野望、船崎愛可、松井琢真、町田雄一郎、前田亮、関村敦、薄田勝男、浦本秀隆
    • Organizer
      第34回日本呼吸器外科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 肺癌領域においてこの10年で進歩はあったのか?: 胸部外科医の視点2017

    • Author(s)
      浦本秀隆.
    • Organizer
      関西胸部外科学会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Sphingosine kinase1(SPHK1)promoters proliferation and surnival in non-small cell lung cancer.2017

    • Author(s)
      本野望、船﨑愛可、前田亮、関村敦、浦本秀隆
    • Organizer
      IASLC 18TH World conference on lung cancer
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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