Development of multiplex biomarker testing and drug sensitivity testing using transbronchial biopsy samples.

• Project/Area Number: 26462122
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Chiba University
• Principal Investigator: Nakajima Takahiro 千葉大学, 大学院医学研究院, 講師 (20400913)
• Co-Investigator(Kenkyū-buntansha): 金田 篤志 千葉大学, 大学院医学研究院, 教授 (10313024) ; 吉野 一郎 千葉大学, 大学院医学研究院, 教授 (40281547) ; 吉田 成利 千葉県がんセンター(研究所), その他部局等, その他 (90334200) ; 松下 一之 千葉大学, 医学部附属病院, 准教授 (90344994)
• Co-Investigator(Renkei-kenkyūsha): IWATA Takekazu 千葉大学, 医学部附属病院, 助教 (30586681) ; SUZUKI Hidemi 千葉大学, 医学部附属病院, 助教 (60422226) ; YAMAMOTO Takayoshi 千葉大学, 医学部附属病院, 医員 (20648349) ; INAGE Terunaga 千葉大学, 医学部附属病院, 医員 (40706909)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: バイオマーカー診断 / 抗がん剤感受性試験 / 超音波気管支鏡 / 肺がん / リンパ節転移 / 微小乳頭状腺癌 / 遺伝子増幅 / 蛍光 in situ ハイブリダイゼーション / 橋渡し研究 / 肺癌 / バイオマーカー / 経気管支肺生検 / 超音波気管支鏡ガイド下生検 / 抗癌剤感受性試験 / 網羅的遺伝子発現解析

Outline of Final Research Achievements

Multiplex gene mutation and amplification detection protocol was designed with original TaqMan probe. This protocol focused on currently available molecular targeted therapeutic agents. It was based on the real-time PCR technology, cost for detection is only 2,500JPY per one probe set. The drug sensitivity test for cytotoxic chemotherapeutic agents using endobronchial needle biopsy specimen was developed based on the CD-DST method. With the improvement of image analysis, the novel method only require >20,000 tumor cells for the test and the prediction for chemotherapeutic agents can be performed using the small biopsy specimen. We also identified the targeted miRNA for ultra-high sensitivity detection of lung cancer metastasis within lymph node. In addition, comprehensive gene expression and aberrant DNA methylation analysis was performed for micropapillary adenocarcinoma and found the several candidate gene sets for unique character of this adenocarcinoma subtype.

Research Products

• [Journal Article] Tumor spread through air space, the clinical implications for T factor and effects on the disease recurrence and prognosis (2018)
  • Author(s): Nakajima Takahiro、Morimoto Junichi、Yoshino Ichiro
  • Journal Title: J Thorac Dis. Volume: 10 Issue: 2 Pages: 539-543
  • DOI: 10.21037/jtd.2018.01.66
  • Peer Reviewed / Open Access
• [Journal Article] Specimen acquisition training with a new biosimulator in endobronchial ultrasound-guided transbronchial needle aspiration. (2017)
  • Author(s): Nakajima T, Fujiwara T, Saegusa F, Inage T, Sakairi Y, Wada H, Suzuki H, Iwata T, Yoshida S, Nakatani Y, Yoshino I.
  • Journal Title: Medicine (Baltimore). Volume: 96 Issue: 13 Pages: e6513-e6513
  • DOI: 10.1097/md.0000000000006513
  • Peer Reviewed / Open Access
• [Journal Article] Pathological diagnosis of pulmonary large cell neuroendocrine carcinoma by endobronchial ultrasound-guided transbronchial needle aspiration (2017)
  • Author(s): Inage Terunaga、Nakajima Takahiro、Fujiwara Taiki、Sakairi Yuichi、Wada Hironobu、Suzuki Hidemi、Iwata Takekazu、Chiyo Masako、Nakatani Yukio、Yoshino Ichiro
  • Journal Title: Thoracic Cancer Volume: 9 Issue: 2 Pages: 273-277
  • DOI: 10.1111/1759-7714.12576
  • Peer Reviewed / Open Access
• [Journal Article] Concomitant Interstitial Lung Disease Is a Risk Factor for Pleural Invasion in Lung Cancer. (2017)
  • Author(s): Hata A, Suzuki H, Nakajima T, Tanaka K, Fujiwara T, Wada H, Iwata T, Yoshida S, Yoshino I.
  • Journal Title: Ann Thorac Surg. Volume: 103 Issue: 3 Pages: 967-974
  • DOI: 10.1016/j.athoracsur.2016.08.074
  • Peer Reviewed
• [Journal Article] Impact of free tumor clusters on prognosis after resection of pulmonary adenocarcinoma. (2016)
  • Author(s): Morimoto J, Nakajima T, Suzuki H, Nagato K, Iwata T, Yoshida S, Fukuyo M, Ota S, Nakatani Y, Yoshino I.
  • Journal Title: J Thorac Cardiovasc Surg. Volume: 152 Issue: 1 Pages: 64-72
  • DOI: 10.1016/j.jtcvs.2016.03.088
  • Peer Reviewed
• [Journal Article] Recent advances in endobronchial ultrasound-guided transbronchial needle aspiration (2016)
  • Author(s): Nakajima T, Yasufuku K, Fujiwara T, Yoshino I
  • Journal Title: Respiratory Investigation Volume: in press Issue: 4 Pages: 230-236
  • DOI: 10.1016/j.resinv.2016.02.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Effect of Perioperative Pirfenidone Treatment in Lung Cancer Patients With Idiopathic Pulmonary Fibrosis. (2016)
  • Author(s): Iwata T, Yoshida S, Fujiwara T, Wada H, Nakajima T, Suzuki H, Yoshino I.
  • Journal Title: Ann Thorac Surg. Volume: 102 Issue: 6 Pages: 1905-1910
  • DOI: 10.1016/j.athoracsur.2016.05.094
  • Peer Reviewed
• [Journal Article] Spectrum analysis of endobronchial ultrasound radiofrequency of lymph nodes in patients with lung cancer. (2016)
  • Author(s): Nakajima T, Shingyoji M, Anayama T, Kimura H, Yasufuku K, Yoshino I.
  • Journal Title: Chest. Volume: in press Issue: 6 Pages: 1393-1399
  • DOI: 10.1016/j.chest.2016.01.015
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Surgical treatment of mucoepidermoid carcinoma of the lung: 20 years' experience. (2016)
  • Author(s): Yamamoto T, Nakajima T, Suzuki H, Tagawa T, Iwata T, Mizobuchi T, Yoshida S, Nakatani Y, Yoshino I.
  • Journal Title: Asian Cardiovasc Thorac Ann. Volume: ２４ Issue: 3 Pages: 257-261
  • DOI: 10.1177/0218492316630494
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Elastography for predicting and localizing nodal metastasis during endobronchial ultrasound. (2015)
  • Author(s): Nakajima T, Inage T, Sata Y, Morimoto J, Tagawa T, Suzuki H, Iwata T, Yoshida S, Nakatani Y, Yoshino I.
  • Journal Title: Respiration Volume: 90 Issue: 6 Pages: 499-506
  • DOI: 10.1159/000441798
  • Peer Reviewed
• [Journal Article] Transbronchial biopsy needle rinse solution used for comprehensive biomarker testing in patients with lung cancer. (2014)
  • Author(s): Sakairi Y, Sato K, Itoga S, Saegusa F, Matsushita K, Nakajima T, Yoshida S, Takiguchi Y, Nomura F, Yoshino I.
  • Journal Title: J Thorac Oncol. Volume: 9(1) Issue: 1 Pages: 26-32
  • DOI: 10.1097/jto.0000000000000024
  • Peer Reviewed
• [Journal Article] Guideline for the Acquisition and Preparation of Conventional and Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Specimens for the Diagnosis and Molecular Testing of Patients with Known or Suspected Lung Cancer. (2014)
  • Author(s): van der Heijden EH, Casal RF, Trisolini R, Steinfort DP, Hwangbo B, Nakajima T, Guldhammer-Skov B, Rossi G, Ferretti M, Herth FF, Yung R, Krasnik M.
  • Journal Title: Respiration. Volume: ８８ Issue: 6 Pages: 500-517
  • DOI: 10.1159/000368857
  • Peer Reviewed / Open Access
• [Journal Article] Staging lung cancer: role of endobronchial ultrasound. (2014)
  • Author(s): Inage T, Nakajima T, Yoshino I.
  • Journal Title: Lung Cancer: Targets and Therapy. Volume: ５ Pages: 67-72
  • DOI: 10.2147/lctt.s46195
  • Peer Reviewed / Open Access
• [Presentation] microRNA発現定量解析による高感度肺癌リンパ節転移検出法の開発 (2017)
  • Author(s): 稲毛 輝長, 中島 崇裕, 藤原 大樹, 糸賀 栄, 石毛 崇之, 伊藤 祐輝, 小野里 優希, 松本 寛樹, 椎名 裕樹, 佐田 諭己, 畑 敦, 豊田 行英, 田中 教久, 坂入 祐一, 和田 啓伸, 鈴木 秀海, 岩田 剛和, 松下 一之, 千代 雅子, 吉野 一郎.
  • Organizer: 第34回日本呼吸器外科学会
• [Presentation] 特発性肺線維症における肺発がん機序の解明：網羅的メチル化遺伝子解析による検討 (2017)
  • Author(s): 畑 敦, 中島 崇裕, 田中 教久, 坂入 祐一, 藤原 大樹, 和田 啓伸, 鈴木 秀海, 千代 雅子, 岩田 剛和, 松坂 恵介, 金田 篤志, 吉野 一郎.
  • Organizer: 第34回日本呼吸器外科学会
• [Presentation] EVALUATION OF NEW 25G NEEDLE IN EBUS-TBNA COMPARING CONVENTIONAL 22G NEEDLE IN DIAGNOSIS FOR NODAL METASTASIS OF LUNG CANCER (2017)
  • Author(s): Sakairi Y, Nakajima T, Yonemori Y, Kaiho T, Ohashi K, Sata Y, Shiina Y, Toyoda T, Hata A, Tamura H, Fujiwara T, Wada H, Suzuki H, Chiyo M, Yoshino I.
  • Organizer: IASLC 18th world conference on lung cancer
  • Int'l Joint Research
• [Presentation] 呼吸器内視鏡領域における超音波，これまでとこれから (2017)
  • Author(s): 中島 崇裕, 吉野 一郎.
  • Organizer: 日本超音波医学会第90回学術集会
  • Invited
• [Presentation] 困難症例への挑戦と工夫 (2017)
  • Author(s): 中島 崇裕.
  • Organizer: 第29回気管支鏡セミナー
  • Invited
• [Presentation] 超音波気管支鏡画像の周波数解析によるリンパ節転移予測システムの開発 (2017)
  • Author(s): 中島 崇裕, 藤原 大樹, 稲毛 輝長, 佐田 諭己, 椎名 裕樹, 畑 敦, 豊田 行英, 田中 教久, 坂入 祐一, 和田 啓仲, 鈴木 秀海, 岩田 剛和, 千代 雅子, 吉野一郎.
  • Organizer: 第40回日本呼吸器内視鏡学会学術集会
• [Presentation] EBUS-TBNA検体を用いたCD-DST法による抗癌剤感受性試験の開発 (2016)
  • Author(s): 中島 崇裕, 稲毛 輝長, 宮川 功，小林 昶運, 浅野 宏幸, 藤原 大樹, 坂入 祐一, 鈴木 秀海, 岩田 剛和, 岩澤 俊一郎, 多田 裕司, 滝口 裕ー, 巽 浩一郎, 吉野 一郎
  • Organizer: 第57回日本肺癌学会学術集会
  • Place of Presentation: 福岡、福岡国際会議場
  • Year and Date: 2016-12-19
• [Presentation] EBUS-TBNA 検体を用いたCD-DST 法による抗癌剤感受性試験の開発 (2016)
  • Author(s): 中島崇裕, 稲毛輝長, 多田裕司, 宮川功, 小林昶運, 浅野宏幸, 三枝文恵, 藤原大樹, 和田啓伸, 鈴木秀海, 岩田剛和, 吉田成利, 滝口裕一, 巽浩一郎, 吉野一郎
  • Organizer: 第39 回日本呼吸器内視鏡学会学術集会
  • Place of Presentation: 名古屋、名古屋国際会議場
  • Year and Date: 2016-06-24
• [Presentation] microRNA 発現定量解析による新しい肺癌リンパ節転移検出法の開発 (2016)
  • Author(s): 稲毛 輝長, 中島 崇裕, 石毛 崇之, 糸賀 栄, 海寶 大輔, 佐田 諭己, 畑 敦, 豊田 行英, 山本 高義, 田中 教久, 和田 啓伸, 藤原 大樹, 鈴木 秀海, 岩田 剛和, 松下 一之, 吉田 成利, 野村 文夫, 吉野 一郎
  • Organizer: 第39 回日本呼吸器内視鏡学会学術集会
  • Place of Presentation: 名古屋、名古屋国際会議場
  • Year and Date: 2016-06-23
• [Presentation] 肺癌治療経過中のEBUS-TBNA による縦隔・肺門リンパ節評価 (2016)
  • Author(s): 藤原 大樹, 中島 崇裕, 稲毛 輝長, 海寶 大輔, 佐田 諭己, 豊田 行英, 畑 敦, 山本 高義, 田中 教久, 和田 啓伸, 鈴木 秀海, 岩田 剛和, 吉田 成利, 吉野 一郎
  • Organizer: 第39 回日本呼吸器内視鏡学会学術集会
  • Place of Presentation: 名古屋、名古屋国際会議場
  • Year and Date: 2016-06-23
• [Presentation] 超音波内視鏡 EBUS-TBNA (2016)
  • Author(s): 中島 崇裕
  • Organizer: 第28回気管支鏡セミナー
  • Place of Presentation: 名古屋、名古屋国際会議場
  • Year and Date: 2016-06-22
  • Invited
• [Presentation] SHOULD ADDITIONAL SURGICAL STAGING BE PERFORMED ENSUING A NEGATIVE RESULT BY ENDOBRONCHIAL ULTRASOUND-GUIDED TRANSBRONCHIAL NEEDLE ASPIRATION? (2016)
  • Author(s): Nakajima T, Sata Y, Inage T, Fujiwara T, Wada H, H. Suzuki, Iwata T, Yoshida S,Yoshino I
  • Organizer: 2016 ESTS Annual Meeting
  • Place of Presentation: Naples, Italy
  • Year and Date: 2016-05-30
  • Int'l Joint Research
• [Presentation] Primary culture of cancer cells and chemosensitivity testing using samples obtained by EBUS-TBNA (2016)
  • Author(s): Takahiro Nakajima, Terunaga Inage, Yuji Tada, Isao Miyagawa, Hisayuki Kobayashi, Hiroyuki Asano, Fumie Saegusa, Taiki Fujiwara, Hironobu Wada, Hidemi Suzuki, Takekazu Iwata, Shigetoshi Yoshida, Yuichi Takiguchi, Koichiro Tatsumi, Ichiro Yoshino
  • Organizer: 19th WCBIP/WCBE World Congress
  • Place of Presentation: florence, Italy
  • Year and Date: 2016-05-09
  • Int'l Joint Research
• [Presentation] 微小検体からの肺癌細胞の初代培養法の確立と抗癌剤感受性試験 (2015)
  • Author(s): 中島崇裕
  • Organizer: 第56回日本肺癌学会学術集会
  • Place of Presentation: 神奈川県，横浜市，パシフィコ横浜
  • Year and Date: 2015-11-26
• [Presentation] The utility of liquid base cytology during endobronchial ultrasound-guided transbronchial needle aspiration (2015)
  • Author(s): 中島崇裕
  • Organizer: Chest annual meeting 2015
  • Place of Presentation: カナダ モントリオール、Convention Center
  • Year and Date: 2015-10-28
  • Int'l Joint Research
• [Presentation] 薬物治療の進歩と呼吸器内視鏡検体の評価 EBUS-TBNA検体処理における液状細胞診検体作成の有用性に関する検討 (2015)
  • Author(s): 中島崇裕
  • Organizer: 第38回日本呼吸器内視鏡学
  • Place of Presentation: 東京都，新宿区，京王プラザホテル
  • Year and Date: 2015-06-11
• [Presentation] EBUS-TBNA検体処理における液状細胞診検体作成の有用性に関する検討 (2015)
  • Author(s): 中島 崇裕
  • Organizer: 第38回日本呼吸器内視鏡学会学術集会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-06-11
• [Presentation] 局所進行非小細胞肺癌に対する拡大肺葉切除術による再建法(Extended lobectomy with reconstructive procedures for locally advanced non-small cell lung cancer)(英語) (2015)
  • Author(s): 中島崇裕
  • Organizer: 第32回日本呼吸器外科学会
  • Place of Presentation: 香川県，高松市，かがわ国際会議場
  • Year and Date: 2015-05-15
• [Presentation] 呼吸器疾患のBio-Imaging PET/CTによる肺癌の診断と治療効果判定の進歩 肺癌N診断における、CT・PET-CT、EBUS-TBNA、切除病理検討の対比 (2015)
  • Author(s): 中島崇裕
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 東京都，千代田区，東京国際フォーラム
  • Year and Date: 2015-04-18
• [Presentation] 臨床ⅢA期N2非小細胞肺癌に対する外科治療の現状 (2015)
  • Author(s): 中島崇裕
  • Organizer: 第115回日本外科学会定期学術集会
  • Place of Presentation: 愛知県，名古屋市，名古屋国際会議場
  • Year and Date: 2015-04-18
• [Presentation] Molecular biomarker testing using samples obtained by EBUS-TBNA (2014)
  • Author(s): Takahiro Nakajima
  • Organizer: World Congress of Bronchology and Interventional Pulmonology
  • Place of Presentation: 京都国際会館（京都府京都市）
  • Year and Date: 2014-04-14
  • Invited
• [Book] 気管支鏡ベストテクニック 改訂2版 (2017)
  • Author(s): 中島 崇裕.
  • Total Pages: 292
  • Publisher: 中外医学社
  • ISBN: 9784498032033
• [Book] Molecular Targeted Therapy of Lung Cancer (2017)
  • Author(s): Takahiro Nakajima, Ichiro Yoshino
  • Total Pages: 327
  • Publisher: Springer
  • ISBN: 9789811020001
• [Book] Molecular Targetted Therapy of Lung Cancer (2017)
  • Author(s): Takahiro Nakajima, Ichiro Yoshino
  • Total Pages: 327
  • Publisher: Springer