Development of lung cancer specific fluorescent probe for post operative recurrence control

• Project/Area Number: 15K10252
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology (2018); The University of Tokyo (2015-2017)
• Principal Investigator: Jun-ichi Nitadori 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (40424486)
• Co-Investigator(Kenkyū-buntansha): 中島 淳 東京大学, 医学部附属病院, 教授 (90188954) ; 安樂 真樹 東京大学, 医学部附属病院, 特定研究員 (70598557) ; 長山 和弘 東京大学, 医学部附属病院, 助教 (00647935)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 肺癌 / 蛍光プローブ / 肺腺癌 / 組織亜型 / Micropapillary / 癌特異的蛍光プローブ / gGlu-HMRG / 腺癌

Outline of Final Research Achievements

Lung cancer prognostic factors have been studied and lung adenocarcinoma histologic variants have been noted. Among them, micropapillary adenocarcinoma has been found to be a particularly poor prognostic factor, but at present the operative procedure has not been examined by stepping into tissue subtypes.
As the cause, it is raised that the diagnosis of tissue subtypes can not be made by intraoperative rapid pathological examination. Therefore, if it is possible to diagnose and visualize lung cancer and tissue subtype diagnosis in real time using cancer specific fluorescent probes that can recognize cancer cells as fluorescence by direct dropping and spraying onto tissues, it is possible to prevent recurrence. It was thought that the prognosis would be good. We conducted experiments for searching and identifying highly practical lung cancer-specific fluorescent probes.

Academic Significance and Societal Importance of the Research Achievements

術中に迅速かつ簡易的に予後不良因子となり得る組織型、遺残癌細胞が同定できる癌特異的蛍光プローブの創製、活用は外科医にとって手術切除範囲決定の補助になりうると考える。これにより、わが国のがん死亡者数第一位の肺癌の予後改善が期待される。

Research Products

• [Journal Article] Spread through air spaces is an independent predictor of recurrence in stage III (N2) lung adenocarcinoma. (2019)
  • Author(s): Terada Y, Takahashi T, Morita S, Kashiwabara K, Nagayama K, Nitadori JI, Anraku M, Sato M, Shinozaki-Ushiku A, Nakajima J.
  • Journal Title: Interact Cardiovasc Thorac Surg. Volume: 印刷中 Issue: 3 Pages: 442-448
  • DOI: 10.1093/icvts/ivz116
  • Peer Reviewed
• [Journal Article] A comparison between 2- and 3-dimensional approaches to solid component measurement as radiological criteria for sublobar resection in lung adenocarcinoma 2 cm in size. (2019)
  • Author(s): Yoshida Y, Manaka T, Nitadori JI, Shinozaki-Ushiku A, Doke T, Saito T, Sato J, Miyaji T, Yamaguchi T, Oyama H, Fukayama M, Nakajima Y, Nakajima J.
  • Journal Title: Surg Today. Volume: 印刷中 Issue: 10 Pages: 828-835
  • DOI: 10.1007/s00595-019-01806-9
  • Peer Reviewed
• [Journal Article] Procedure-Specific Risk Prediction for Recurrence in Patients Undergoing Lobectomy or Sublobar Resection for Small (2 cm) Lung Adenocarcinoma: An International Cohort Analysis. (2019)
  • Author(s): Bains S, Eguchi T, Warth A, Yeh YC, Nitadori JI, Woo KM, Chou TY, Dienemann H, Muley T, Nakajima J, Shinozaki-Ushiku A, Wu YC, Lu S, Kadota K, Jones DR, Travis WD, Tan KS, Adusumilli PS.
  • Journal Title: J Thorac Oncol. Volume: 1 Issue: 1 Pages: 72-86
  • DOI: 10.1016/j.jtho.2018.09.008
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Low truncal muscle area on chest computed tomography: a poor prognostic factor for the cure of early-stage non-small-cell lung cancer. (2018)
  • Author(s): Sun C, Anraku M, Karasaki T, Kuwano H, Nagayama K, Nitadori JI, Sato M, Nakajima J.
  • Journal Title: Eur J Cardiothorac Surg. Volume: 印刷中 Issue: 3 Pages: 414-420
  • DOI: 10.1093/ejcts/ezy324
  • Peer Reviewed
• [Journal Article] High CCR4 expression in the tumor microenvironment is a poor prognostic indicator in lung adenocarcinoma. (2018)
  • Author(s): Karasaki T, Qiang G, Anraku M, Sun Y, Shinozaki-Ushiku A, Sato E, Kashiwabara K, Nagayama K, Nitadori JI, Sato M, Murakawa T, Kakimi K, Fukayama M, Nakajima J.
  • Journal Title: J Thorac Dis Volume: 10 Issue: 8 Pages: 4741-4750
  • DOI: 10.21037/jtd.2018.07.45
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impact of the 8th Edition of the UICC-TNM Classification on Clinical Stage 0-IA Lung Adenocarcinoma: Does the New Classification Predict Postoperative Prognosis More Precisely than the Previous One? (2018)
  • Author(s): Wang L, Anraku M, Sato M, Nitadori JI, Nagayama K, Kitano K, Nakajima J.
  • Journal Title: Annals of Thoracic and Cardiovascular Surgery Volume: 24 Issue: 5 Pages: 223-229
  • DOI: 10.5761/atcs.oa.18-00051
  • NAID: 130007498736
  • ISSN: 1341-1098, 2186-1005
  • Peer Reviewed
• [Journal Article] Micropapillary histological subtype in lung adenocarcinoma of 2 cm or less: impact on recurrence and clinical predictors. (2017)
  • Author(s): Yoshida Y, Nitadori JI, Shinozaki-Ushiku A, Sato J, Miyaji T, Yamaguchi T, Fukayama M, Nakajima J.
  • Journal Title: Gen Thorac Cardiovasc Surg. Volume: 65 Issue: 5 Pages: 273-279
  • DOI: 10.1007/s11748-017-0747-3
  • Peer Reviewed
• [Journal Article] Rapid Cancer Fluorescence Imaging Using A γ-Glutamyltranspeptidase-Specific Probe For Primary Lung Cancer. (2016)
  • Author(s): Hino H, Kamiya M, Kitano K, Mizuno K, Tanaka S, Nishiyama N, Kataoka K, Urano Y, Nakajima J
  • Journal Title: Translational Oncology. Volume: 9 Issue: 3 Pages: 203-210
  • DOI: 10.1016/j.tranon.2016.03.007
  • Peer Reviewed / Open Access
• [Journal Article] International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification predicts occult lymph node metastasis in clinically mediastinal node-negative lung adenocarcinoma. (2016)
  • Author(s): Yeh YC, Kadota K, Nitadori J, Sima CS, Rizk NP, Jones DR, Travis WD, Adusumilli PS.
  • Journal Title: European Journal Cardio-Thoracic Surgery Volume: 49(1) Issue: 1 Pages: e9-e15
  • DOI: 10.1093/ejcts/ezv316
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Tumor Spread through Air Spaces is an Important Pattern of Invasion and Impacts the Frequency and Location of Recurrences after Limited Resection for Small Stage I Lung Adenocarcinomas. (2015)
  • Author(s): Kadota K, Nitadori J, Sima CS, Ujiie H, Rizk NP, Jones DR, Adusumilli PS, Travis WD.
  • Journal Title: Journal of Thoracic Oncology Volume: 10(5) Issue: 5 Pages: 806-14
  • DOI: 10.1097/jto.0000000000000486
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] TNM 分類 第 8 版 に おける 病理病期 StageIA1 肺腺癌 の 予後 因子の 検討 (2019)
  • Author(s): 中尾啓太 、 似鳥 純一、 唐崎 隆弘、 北野 健太郎、 長山 和弘、 佐藤 雅昭、 中島 淳
  • Organizer: 第36回日本呼吸器外科学会学術集会
• [Presentation] Necrosis is a Predictor of Recurrence in Patients with Stage I Lung Adenocarcinoma (2017)
  • Author(s): Yuriko Terada, Jun-ichi Nitadori, Shigeki Morita, Tsuyoshi Takahashi, Takuma Yotsumoto, Yutaka Sawai, Takahiro Karasaki, Kentaro Kitano, Kazuhiro Nagayama, Masaki Anraku, Masaaki Sato, Aya Shinozaki-Ushiku, Masashi Fukayama, Jun Nakajima
  • Organizer: IASLC 18th World Conference on Lung Cancer
  • Int'l Joint Research
• [Presentation] New Clinical T Classification Is Associated with Small Invasive Adenocarcinoma with Solid Histologic Component (2017)
  • Author(s): Yutaka Sawai, Jun-ichi Nitadori, Tsuyoshi Takahashi, Kentaro Kitano, Kazuhiro Nagayama, Masaki Anraku, Masaaki Sato, Jun Nakajima
  • Organizer: IASLC 18th World Conference on Lung Cancer
  • Int'l Joint Research
• [Presentation] Is sublobar resection for stage I invasive adenocarcinoma with solid histological subtype enough for cure? (2017)
  • Author(s): Tsuyoshi Takahashi, Jun-ichi Nitadori, Shigeki Morita, Mitsuaki Kawashima, Hideki Kuwano, Kazuhiro Nagayama, Masaki Anraku, Aya Shinozaki-Ushiku, Masaaki Sato, Masashi Fukayama, Jun Nakajima
  • Organizer: 25 th European Conference on General Thoracic Surgery
  • Int'l Joint Research
• [Presentation] A Retrospective Analysis of Patients with Small Lung Adenocarcinoma(<2cm) by New World Health Organization Classification (2016)
  • Author(s): Keita Nakao, Jun-ichi Nitadori, Shigeki Morita, Hideki Kuwano, Kazuhiro Nagayama, Masaki Anraku, Aya Shinozaki-Ushiku, Masaaki Sato, Masashi Fukayama, Jun Nakajima
  • Organizer: 17th World Conference on Lung Cancer
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2016-12-04
  • Int'l Joint Research
• [Presentation] Impact of Histologic Subtype and Spread through Air Spaces (STAS) in Stage III (N2) Lung Adenocarcinoma (2016)
  • Author(s): Yuriko Terada, Jun-ichi Nitadori, Shigeki Morita, Hideki Kuwano, Kazuhiro Nagayama, Masaki Anraku, Masaaki Sato, Aya Shinozaki-Ushiku, Masashi Fukayama, Jun Nakajima
  • Organizer: 17th World Conference on Lung Cancer
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2016-12-04
  • Int'l Joint Research
• [Presentation] 小型肺腺癌におけるFDG-PET とMicropapillary pattern に関する検討 (2015)
  • Author(s): 似鳥純一、吉田幸弘、牛久綾、篠原義和、吉田大介、柳谷昌弘、川島峻、川島光明、土屋武弘、村山智紀、 長山和弘、安樂真樹、佐藤雅昭、深山正久、中島淳
  • Organizer: 第68回日本胸部外科学会定期学術集会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2015-10-17
• [Presentation] A comparative study of micropapillary pattern and computed tomographic findings in the patients with small lung adenocarcinoma (&#8804;2cm) (2015)
  • Author(s): Jun-ichi Nitadori, Yukihiro Yoshida1, Aya Shinozaki-Ushiku2, Hideki Kuwano1, Kazuhiro Nagayama1, Masaki Anraku1, Masaaki Sato1, Masashi Fukayama2, Jun Nakajima1&#160;
  • Organizer: 16th World Conference on Lung Cancer
  • Place of Presentation: Denver, Co, USA
  • Year and Date: 2015-09-06
  • Int'l Joint Research
• [Presentation] 小型肺腺癌におけるMicropapillary patternとCT画像所見との関係 (2015)
  • Author(s): 似鳥純一、吉田幸弘、牛久綾、川島光明、土屋武弘、村山智紀、一瀬淳二、日野春秋、長山和弘、安樂真樹、村川知弘、深山正久、中島淳
  • Organizer: 第32回日本呼吸器外科学会
  • Place of Presentation: 香川県高松市
  • Year and Date: 2015-05-14