Development of a new lung cancer treatment strategies that target isolated cancer cells

• Project/Area Number: 21390388
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Osaka University
• Principal Investigator: NORIYOSHI Sawabata 大阪大学, 医学系・研究科, 准教授 (50403184)
• Co-Investigator(Kenkyū-buntansha): OKAMURA Meinoshin 大阪大学, 医学系・研究科, 教授 (40252647) ; INOUE Masayoshi 大阪大学, 医学系・研究科, 講師 (10379232) ; NAKAGIRI Tomoyuki 大阪大学, 医学系・研究科, 助教 (70528710) ; SUSAKI Yoshiyuki 大阪大学, 医学部附属病院, 医員 (10528649) ; FUNAKI Soichirou 大阪大学, 医学系・研究科, 助教 (50464251) ; KADATA Yoshihisa 大阪大学, 医学系・研究科, 助教 (50464243)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2011: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
• Keywords: 呼吸器外科学 / 肺癌 / 遊離癌細胞 / 間質反応 / 転移 / 胸腔鏡 / 断端細胞診

Research Abstract

We revealed the importance of isolated tumor cells(ITCs) in surgical patients with lung cancer using ITCs at the surgical margin of limited lung resection and in the blood of the pulmonary vein of the resected lung. In addition the morphological appearance of the ITCs is associated with the degree of stromal reaction in the original lesion and with relapse free survival rate.
According to a finding that ITCs at the surgical margin is a predictor of margin recurrence father examination regarding survival was carried out to reveal that the ITC at the surgical margin was a prognostic indicator. This is because ITCs at the surgical margin seems an ideal model to investigate the behavior of cancer cells in a microenvironment.
In addition, scattering of ITCs into the blood by the surgical manipulation was shown, by way of the CD45 negative selection method using the pulmonary vein blood which provided the native morphology of ITCs, to be the positive ratio of presenting ITC was 73% and the morphology was a predictor of recurrence-cluster was deeply associated with relapse. Furthermore, this feature was related to serum CEA level, tumor vessel invasion(TVI) and stage of the tumor, of them TVI was the most reliable predictor of a presence of cluster cells in the PV-blood. Besides, late relapse case often revealed cytokeratin negative ITCs which may be a milestone to father investigation with respect to epithelial mesemchymal transition(EMT).

Research Products

• [Journal Article] Clinical implications of margin cytology findings and margin tumor size ratio in patients who underwent pulmonary excision for peripheral non-small lung cancer (2012)
  • Author(s): SawabataN, Maeda H, Ohta M, Okumura M
  • Journal Title: Surgery Today Volume: 42 Pages: 238-244
  • Peer Reviewed
• [Journal Article] Clinical implications of margin cytology findings and margin tumor size ratio in patients who underwent pulmonary excision for peripheral non (2012)
  • Author(s): Sawabata N, et al
  • Journal Title: Surgery Today Volume: 42 Issue: 3 Pages: 238-244
  • DOI: 10.1007/s00595-011-0031-6
  • Peer Reviewed
• [Journal Article] Clinical implication of pulmonary excision for undiagnosedperipheral lung cancer (2011)
  • Author(s): Funakoshi Y, Sawabata N, Takeuchi Y, Kusumoto H, Kimura T, Maeda H
  • Journal Title: Interact Cardiovasc Thorac Surg Volume: 13 Pages: 485-489
  • Peer Reviewed
• [Journal Article] Validation of pN2 sub-classifications in patients with pathological stage IIIA N2 non-small cell lung cancer (2011)
  • Author(s): Nakagiri T, Sawabata N, Funaki S, InoueM, Kadota Y, Shintani Y, Okumura M.
  • Journal Title: InteractCardiovasc Thorac Surg Volume: 12 Pages: 733-738
  • Peer Reviewed
• [Journal Article] Novel approach for detection of isolated tumor cells in pulmonary vein using negative selection method : morphological classification and clinical implications (2011)
  • Author(s): Funaki S, Sawabata N, Nakagiri T, Shintani Y, Inoue M, Kadota Y, Minami M, Okumura M.
  • Journal Title: Eur J Cardiothorac Surg Volume: 40 Pages: 322-327
  • Peer Reviewed
• [Journal Article] Novel approach for detection of isolated tumor cells in pulmonary vein using negative selection method (2011)
  • Author(s): Funaki S, Sawabata N, et al
  • Journal Title: Eur J Cardiothorac Surg Volume: 40 Pages: 322-327
  • DOI: 10.1016/j.ejcts.2010.11.029
  • Peer Reviewed
• [Journal Article] Optimal sampling methods for margin cytology examination following lung excision (2010)
  • Author(s): Okumura M
  • Journal Title: Interact Cardiovasc Thorac Surg Volume: 9 Pages: 434-439
  • Peer Reviewed
• [Journal Article] Optimal sampling methods for margin cytology examination following lung excision (2010)
  • Author(s): Utsumi T, Sawabata N, Inoue M, Okumura M
  • Journal Title: Interact Cardiovasc Thorac Surg Volume: 9 Pages: 244-239
  • Peer Reviewed
• [Presentation] Tumor Vessel Invasion Assures Isolated Tumor Cells in the Pulmonary Veinof Non-Small Cell Lung Cancer (2012)
  • Author(s): Funaki S, Sawabata N, et al
  • Organizer: 48th Society of Thoracic Surgeons
  • Place of Presentation: Frolida, US
  • Year and Date: 2012-01-27
• [Presentation] OkumuraM Tumor Vessel Invasion Assures IsolatedTumor Cells in the Pulmonary VeinofNon-Small Cell Lung Cancer (2012)
  • Author(s): Funaki S, Sawabata N, Nakagiri T, Shintani Y, Inoue M, Minami M, Okumura M
  • Organizer: 48th Societyof Thoracic Surgeons us
  • Place of Presentation: FL US
  • Year and Date: 2012-01-16
• [Presentation] 原発性非小細胞肺癌における (2011)
  • Author(s): 舟木壮一郎、澤端章好中桐伴行, 新谷康, 井上匡美, 南正人, 奥村明之進
  • Organizer: 臨床的背景と病理像ならびに肺静脈血遊離癌細胞第64回日本胸部外科学会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-11
• [Presentation] 原発性非小細胞肺癌における、臨床的背景と病理像ならびに肺静脈血遊離癌細胞 (2011)
  • Author(s): 舟木壮一郎、澤端章好, 他
  • Organizer: 第64回日本胸部外科学会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-11
• [Presentation] O癌周術期の末梢血中遊離癌細胞: 5年以上の追跡結果ら見た臨床上の有用性の検討 (2011)
  • Author(s): Utsumi T, Sawabata N, Inoue M
  • Organizer: 第64回日本胸部外科学会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-10
• [Presentation] 肺癌周術期の末梢血中遊離癌細胞:5年以上の追跡結果から見た臨床上の有用性の検討 (2011)
  • Author(s): 澤端章好
  • Organizer: 第64回日本胸部外科学会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-10
• [Presentation] Novel approach for detectionof isolated tumor cells in the pulmonaryvein by a negative selection method : morphological classification and its clinicalimplication (2011)
  • Author(s): Funaki S, Sawabata N, Nakagiri T, Shintani Y, Inoue M, Kadota Y, Minami M, Okumura M
  • Organizer: 24th European Association of Cardio-Thoracic Surgery
  • Place of Presentation: Geneve Switzerland
  • Year and Date: 2011-10-05
• [Presentation] Clinical implication of isolated tumor cells at the surgical margin of lung excision for non-small cell lung cancer (2011)
  • Author(s): Sawabata N, et al
  • Organizer: 8th International symposium of minimally residual cancer
  • Place of Presentation: Osaka
  • Year and Date: 2011-09-22
• [Presentation] Clinical and pathological analyses of isolated tumor cells in non-small cell lung cancer (2011)
  • Author(s): Funaki S, Sawabata N, et al
  • Organizer: 8th International symposium of minimally residual cancer
  • Place of Presentation: Osaka
  • Year and Date: 2011-09-22
• [Presentation] Clinical and pathological analyses of isolated tumor cells in non-small cell lung cancer 8th International symposium of minimally residual cancer (2011)
  • Author(s): Funaki S, Sawabata N Nakagiri T Shintani Y, Inoue M, Minami M, Okumura M
  • Organizer: 8th International symposium of minimally residual cancer
  • Place of Presentation: Osaka Japan
  • Year and Date: 2011-09-21
• [Presentation] Clinical implication of isolated tumor cells at the surgical margin of lung excision for non-small cell lung cancer (2011)
  • Author(s): Sawabata N, Funaki S, Inoue M Shintani Y, Nakagiri T, Minami M, Okumura M
  • Organizer: 8th International symposium of minimally residual cancer
  • Place of Presentation: Osaka Japan
  • Year and Date: 2011-09-20
• [Presentation] Clinical and pathological analyses of isolated tumor cells in non small cell lung cancer-Clinicopathological parameters affecting isolated tumor cell morphology in non small cell lung cancer (2011)
  • Author(s): Funaki S, Sawabata N, Abulamity A Nakagiri T, Shintani Y, Inoue M, Kadota Y, Minami M, Okumura M
  • Organizer: 14th World Congress of Lung Cancer
  • Place of Presentation: Amsterdam Nederland
  • Year and Date: 2011-08-17
• [Presentation] 癌周囲微小環境を標的とした肺癌治療 (2011)
  • Author(s): 新谷康、澤端章好, 他
  • Organizer: 第111回日本外科学会総会国際シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2011-05-26
• [Presentation] 癌周囲微小環境を標的とした肺癌治療IS-10国際シンポジウム(10) Treatment of lung cancer in the 21st century : From bench to bedside, further to the OR (2011)
  • Author(s): 新谷康, 中桐伴行, 門田嘉久, 井上匡美, 澤端章好, 南正人, 奥村明之進
  • Organizer: 第111回日本外科学会定期学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-25
• [Presentation] Novel approach for detection of isolated tumor cells in the pulmonary vein by a negative selection method : morphological classification and its clinical implication (2010)
  • Author(s): 舟木壮一郎、澤端章好, 他
  • Organizer: 24^<th> European Association of Cardio-Thoracic
  • Place of Presentation: Geneve Switerland
  • Year and Date: 2010-10-04
• [Presentation] リンパ節転移様式を基にした病期IIIA N2非小細胞肺癌(NSCLC)に対する外科治療の検討:今後のTNM分類を見据えて肺外科治療-2,一般口演 (2010)
  • Author(s): 中桐伴行, 澤端章好, 内海朝喜, 舟木壮一郎, 南正人, 井上匡美, 門田嘉久, 須崎剛志, 奥村明之進
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2010-03-05
• [Presentation] 肺癌手術摘出肺肺静脈内遊離癌細胞 : 新規同定法による臨床的意義の探索 (2009)
  • Author(s): 澤端章好
  • Organizer: 第62回日本胸部外科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-11
• [Presentation] Isolated tumor cells in pulmonary vein blood of resected lung with non-small cell lung cancer : a pilot study of morphological qualification (2009)
  • Author(s): Noriyoshi Sawabata
  • Organizer: 13th World Congress of Lung Cancer
  • Place of Presentation: サンフランシスコ 米国
  • Year and Date: 2009-08-02
• [Presentation] 肺部分切除+断端細胞診の実際:切離マージン確認の方法と長期成績肺癌に対するsublobar resectionの適応と評価,ビデオワークショップ (2009)
  • Author(s): 内海朝喜, 澤端章好, 南正人, 井上匡美, 門田嘉久, 重村周文, 前田元, 竹内幸康, 船越康信, 松村晃秀, 奥村明之進
  • Organizer: 第109回日本外科学会定期学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2009-02-25