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Isolation of circulating tumor cells (CTC) and peritoneal tumor cells (PTC) by cytology-based filtration platform and its application to monitoring therapeutic effect

Research Project

Project/Area Number 16K10524
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionAichi Cancer Center Research Institute

Principal Investigator

ITO Seiji  愛知県がんセンター(研究所), 分子腫瘍学分野, 研究員 (50393129)

Research Collaborator ITO yuichi  
NAKANISHI hayao  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords血液中循環がん細胞(CTC) / 腹腔洗浄液中がん細胞(PTC) / 細胞診 / フィルター型デバイス / 自動分離装置 / 薬物治療 / Liquid biopsy / CTC細胞診 / CTCマウス / 分子標的治療 / CTC / スライドグラス標本 / 胃十二指腸外科学 / 微小転移
Outline of Final Research Achievements

In the present study, we newly developed a cytology-based, automated CTC/PTC isolation device for liquid biopsy. This platform consists of three steps; enrichment of CTCs with filter, transfer of CTCs to glass slide and staining with Pap and immunocytochemistry. CTC (PTC) are identified under light microscopy as cytokeratin (CEA)-positive cells with atypical morphology. Some genetic analysis such as FISH is also possible. Pilot clinical study showed that CTC number was higher in drainage vein blood (DVB) than peripheral blood, suggesting that CTCs in DVB are potential source for genetic analysis. Furthermore, using gastric cancer mouse CTC model, we demonstrated transient increase in CTC number early after T-DM1 therapy, suggesting mobilization of CTCs in rapid response to drug therapy. These results indicate that current CTC (PTC) detection platform would be a powerful diagnostic tool for early detection of metastasis and monitoring drug sensitivity in clinical setting.

Academic Significance and Societal Importance of the Research Achievements

本研究でCTCの同定を迅速、低コストに光学顕微鏡下で行うことが可能なデバイスを新たに開発し、市中病院でもCTCの測定をルチーン検査として行うことができる可能性が示唆された。デバイスのFilter径を大きくすることにより従来の洗浄細胞診に比べ高感度かつ半定量的なPTCの検出が可能となった。またDVBを用いることにより一定数以上のCTCの回収が可能となりCTCの遺伝子解析の可能性が示唆された。一方、ヒト胃癌のCTCマウスモデルを確立し、T-DM1治療後早期に一過性にCTC数が増加すること、すなわちCTCが動員される可能性を見出した。CTCモニターによる抗がん剤感受性評価の可能性が示唆された。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (30 results)

All 2019 2018 2017 2016

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Open Access: 11 results,  Acknowledgement Compliant: 1 results) Presentation (13 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Prognostic significance of perioperative tumor marker levels in stage II/III gastric cancer2019

    • Author(s)
      Suenaga Yasuhito、Kanda Mitsuro、Ito Seiji、Mochizuki Yoshinari、Teramoto Hitoshi、Ishigure Kiyoshi、Murai Toshifumi、Asada Takahiro、Ishiyama Akiharu、Matsushita Hidenobu、Tanaka Chie、Kobayashi Daisuke、Fujiwara Michitaka、Murotani Kenta、Kodera Yasuhiro
    • Journal Title

      World Journal of Gastrointestinal Oncology

      Volume: 11 Issue: 1 Pages: 17-27

    • DOI

      10.4251/wjgo.v11.i1.17

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of circulating tumor cells in drainage venous blood from colorectal cancer patients using a new filtration and cytology-based automated platform2019

    • Author(s)
      Tsutsuyama Masayuki、Nakanishi Hayao、Yoshimura Mayumi、Oshiro Taihei、Kinoshita Takashi、Komori Koji、Shimizu Yasuhiro、Ichinosawa Yoshiyuki、Kinuta Seichin、Wajima Kentaro、Sakakibara Yasufumi、Yatabe Yasushi、Ito Seiji、Kodera Yasuhiro
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 2 Pages: e0212221-e0212221

    • DOI

      10.1371/journal.pone.0212221

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proposal of a Scoring Scale to Estimate Risk of the Discontinuation of S-1 Adjuvant Monotherapy in Patients with Stage II to III Gastric Cancer: A Multi-Institutional Dataset Analysis2019

    • Author(s)
      Iizuka Akimitsu、Kanda Mitsuro、Ito Seiji、Mochizuki Yoshinari、Teramoto Hitoshi、Ishigure Kiyoshi、Murai Toshifumi、Asada Takahiro、Ishiyama Akiharu、Matsushita Hidenobu、Tanaka Chie、Kobayashi Daisuke、Fujiwara Michitaka、Murotani Kenta、Kodera Yasuhiro
    • Journal Title

      World Journal of Surgery

      Volume: - Issue: 8 Pages: 2016-2024

    • DOI

      10.1007/s00268-019-04942-y

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Addition of Docetaxel to Oral Fluoropyrimidine Improves Efficacy in Patients With Stage III Gastric Cancer: Interim Analysis of JACCRO GC-07, a Randomized Controlled Trial2019

    • Author(s)
      Yoshida Kazuhiro、Kodera Yasuhiro、Kochi Mitsugu、Ichikawa Wataru、Kakeji Yoshihiro、Sano Takeshi、Nagao Narutoshi、Takahashi Masazumi、Takagane Akinori、Watanabe Takuya、Kaji Masahide、Okitsu Hiroshi、Nomura Takashi、Matsui Takanori、Yoshikawa Takaki、Matsuyama Jin、Yamada Makoto、Ito Seiji
    • Journal Title

      Journal of Clinical Oncology

      Volume: - Issue: 15 Pages: 1296-1304

    • DOI

      10.1200/jco.18.01138

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Four courses versus eight courses of adjuvant S-1 for patients with stage II gastric cancer (JCOG1104 [OPAS-1]): an open-label, phase 3, non-inferiority, randomised trial2019

    • Author(s)
      Yoshikawa Takaki、Terashima Masanori、Mizusawa Junki、Nunobe Souya、Nishida Yasunori、Yamada Takanobu、Kaji Masahide、Fukushima Norimasa、Hato Shinji、Choda Yasuhiro、Yabusaki Hiroshi、Yoshida Kazuhiro、Ito Seiji、Takeno Atsushi、Yasuda Takashi、Kawachi Yasuyuki、Katayama Hiroshi、Fukuda Haruhiko、Boku Narikazu
    • Journal Title

      The Lancet Gastroenterology & Hepatology

      Volume: 4 Issue: 3 Pages: 208-216

    • DOI

      10.1016/s2468-1253(18)30383-2

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment and validation of prognostic nomograms in first-line metastatic gastric cancer patients2018

    • Author(s)
      Narita Yukiya、Kadowaki Shigenori、Oze Isao、Kito Yosuke、Kawakami Takeshi、Machida Nozomu、Taniguchi Hiroya、Ura Takashi、Ando Masashi、Ito Seiji、Tajika Masahiro、Yatabe Yasushi、Yasui Hirofumi、Muro Kei
    • Journal Title

      Journal of Gastrointestinal Oncology

      Volume: 9 Issue: 1 Pages: 52-63

    • DOI

      10.21037/jgo.2017.11.08

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Survival after recurrence in patients with gastric cancer who receive S-1 adjuvant chemotherapy: exploratory analysis of the ACTS-GC trial2018

    • Author(s)
      Ito Seiji、Ohashi Yasuo、Sasako Mitsuru
    • Journal Title

      BMC Cancer

      Volume: 18 Issue: 1

    • DOI

      10.1186/s12885-018-4341-6

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Incidence and treatment of metachronous gastric cancer after proximal gastrectomy2018

    • Author(s)
      Iwata Yoshinori、Ito Seiji、Misawa Kazunari、Ito Yuichi、Komori Koji、Abe Tetsuya、Shimizu Yasuhiro、Tajika Masahiro、Niwa Yasumasa、Yoshida Kazuhiro、Kinoshita Taira
    • Journal Title

      Surgery Today

      Volume: 48 Issue: 5 Pages: 552-557

    • DOI

      10.1007/s00595-018-1632-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Number of retrieved lymph nodes is an independent prognostic factor after total gastrectomy for patients with stage III gastric cancer: propensity score matching analysis of a multi-institution dataset2018

    • Author(s)
      Hayashi Shogo、Kanda Mitsuro、Ito Seiji、Mochizuki Yoshinari、Teramoto Hitoshi、Ishigure Kiyoshi、Murai Toshifumi、Asada Takahiro、Ishiyama Akiharu、Matsushita Hidenobu、Tanaka Chie、Kobayashi Daisuke、Fujiwara Michitaka、Murotani Kenta、Kodera Yasuhiro
    • Journal Title

      Gastric Cancer

      Volume: - Issue: 4 Pages: 853-863

    • DOI

      10.1007/s10120-018-0902-2

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pathological tumor infiltrative pattern and sites of initial recurrence in stage II/III gastric cancer: Propensity score matching analysis of a multi-institutional dataset2018

    • Author(s)
      Nakagawa Nobuhiko、Kanda Mitsuro、Ito Seiji、Mochizuki Yoshinari、Teramoto Hitoshi、Ishigure Kiyoshi、Murai Toshifumi、Asada Takahiro、Ishiyama Akiharu、Matsushita Hidenobu、Tanaka Chie、Kobayashi Daisuke、Fujiwara Michitaka、Murotani Kenta、Kodera Yasuhiro
    • Journal Title

      Cancer Medicine

      Volume: 7 Issue: 12 Pages: 6020-6029

    • DOI

      10.1002/cam4.1868

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A phase III trial to confirm modified S-1 adjuvant chemotherapy for pathological stage II/III vulnerable elderly gastric cancer patients who underwent gastric resection (JCOG1507, BIRDIE)2018

    • Author(s)
      Mizutani Tomonori、Yamaguchi Kazuya、Mizusawa Junki、Ito Seiji、Nishida Yasunori、Yabusaki Hiroshi、Boku Narikazu、Sano Takeshi、Yoshida Kazuhiro、Sasako Mitsuru、Yoshikawa Takaki、Terashima Masanori、Stomach Cancer Study Group/Japan Clinical Oncology Group
    • Journal Title

      Japanese Journal of Clinical Oncology

      Volume: 48 Issue: 12 Pages: 1101-1104

    • DOI

      10.1093/jjco/hyy152

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intraoperative Blood Loss is Associated with Shortened Postoperative Survival of Patients with Stage II/III Gastric Cancer: Analysis of a Multi-institutional Dataset2018

    • Author(s)
      Ito Yuki、Kanda Mitsuro、Ito Seiji、Mochizuki Yoshinari、Teramoto Hitoshi、Ishigure Kiyoshi、Murai Toshifumi、Asada Takahiro、Ishiyama Akiharu、Matsushita Hidenobu、Tanaka Chie、Kobayashi Daisuke、Fujiwara Michitaka、Murotani Kenta、Kodera Yasuhiro
    • Journal Title

      World Journal of Surgery

      Volume: 43 Issue: 3 Pages: 870-877

    • DOI

      10.1007/s00268-018-4834-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 胃癌術後補助化学療法においてS-1後発医薬品内服時のみ好中球減少が軽快した一例2018

    • Author(s)
      重吉到、三澤一成、伊藤誠二.
    • Journal Title

      癌と化学療法

      Volume: 45

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] A phase II study of preoperative chemotherapy with docetaxel, cisplatin, and S-1 followed by gastrectomy with D2 plus para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis: JCOG1002.2017

    • Author(s)
      Ito S, Sano T, Mizusawa J, Takahari D, Katayama H, Katai H, Kawashima Y,
    • Journal Title

      Gastric Cancer

      Volume: 20 Issue: 2 Pages: 322-331

    • DOI

      10.1007/s10120-016-0619-z

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 【Stage IV胃癌に対する外科治療戦略】 切除可能なStage IV胃癌に対する外科治療 腹部大動脈周囲リンパ節転移例に対する外科治療2016

    • Author(s)
      伊藤 誠二, 伊藤 友一, 三澤 一成, 清水 泰博, 木下 平
    • Journal Title

      外科

      Volume: 78 Pages: 353-356

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] 高度 リンパ節転移陽性胃癌に対する集学的治療開発2019

    • Author(s)
      伊藤 誠二、佐野 武、高張 大亮 、円谷 彰、寺島 雅典、笹子 三津留
    • Organizer
      第91回日本胃癌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 胃全摘-開腹vs腹腔鏡-2018

    • Author(s)
      伊藤 誠二、伊藤 友一、三澤 一成、檜垣 栄治、大城 泰平、植村 則久、木下 敬史、夏目 誠治、千田 嘉穀、安部 哲也、小森 康司、清水 泰博、木下 平
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 胃癌に対する腹部大動脈周囲リンパ節郭清の再考2018

    • Author(s)
      伊藤 誠二、伊藤 友一、三澤 一成、植村 則久、木下 敬史、千田 嘉穀、安部 哲也、小森 康司、清水 泰博、木下 平
    • Organizer
      第73回日本消化器外科学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 3Dフィルタ型CTC分離デバイスを用いたCTC細胞診の試みと大腸、肺, 乳がん血中循環癌細胞(CTC)に関する臨床的検討2018

    • Author(s)
      中西 速夫、筒山 将之、服部 正也、黒田 浩、谷田部 恭、伊藤 誠二
    • Organizer
      第77回日本癌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The value of PAND following NAC for gastric cancer with extensive lymph node metastasis2018

    • Author(s)
      Seiji Ito.
    • Organizer
      第90回日本胃癌学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] pStageⅡ/Ⅲ胃癌症例における術後合併症と長期予後の関連性の検討2018

    • Author(s)
      重吉到、三澤一成、伊藤誠二.
    • Organizer
      第90回日本胃癌学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] pStageⅠ胃癌症例における術後合併症と長期予後の関連性の検討2017

    • Author(s)
      重吉到、三澤一成、伊藤誠二.
    • Organizer
      第15回日本消化器外科学会大会(JDDW)
    • Related Report
      2017 Research-status Report
  • [Presentation] 胃癌に対する内視鏡的治療非治癒切除後の追加手術症例に関する検討2017

    • Author(s)
      伊藤友一、伊藤誠二.
    • Organizer
      第15回日本消化器外科学会大会(JDDW)
    • Related Report
      2017 Research-status Report
  • [Presentation] フィルタ型分離デバイスを用いたCTC 細胞診断法の開発とその前臨床並びに臨床応用2017

    • Author(s)
      中西 速夫、伊藤 誠二、伊藤 友一、坂尾 幸則、黒田 浩、岩田広治、服部 正也、安立 弥生、筒山 将之、谷田部 恭.
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 残胃癌におけるリンパ節転移と至適郭清範囲の検討2017

    • Author(s)
      伊藤友一、伊藤誠二.
    • Organizer
      第72回日本消化器外科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 当院に於ける胃亜全摘症例の術後短期成績と栄養評価2017

    • Author(s)
      重吉到、伊藤誠二.
    • Organizer
      第72回日本消化器外科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Novel therapeutic approach with PAM for peritoneal micrometastasisof gastric cancer2017

    • Author(s)
      H. Nakanishi, Y. Ikehara, S. Ito
    • Organizer
      第89回日本胃癌学会総会
    • Place of Presentation
      広島国際会議場(広島市)
    • Related Report
      2016 Research-status Report
  • [Presentation] 1.進行胃癌に対する化学療法後大動脈周囲リンパ節郭清の意義 高度リンパ節転移陽性胃癌の術前化療レジメと大動脈周囲リンパ節郭清術の意義2016

    • Author(s)
      伊藤 誠二, 佐野 武, 高張 大亮, 円谷 彰, 片山 宏, 笹子 三津留
    • Organizer
      第71回日本消化器外科学会総会
    • Place of Presentation
      あわぎんホール(徳島市)
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] 細胞のスライドグラス標本作製方法2016

    • Inventor(s)
      中西速夫、伊藤誠二
    • Industrial Property Rights Holder
      中西速夫、伊藤誠二
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016
    • Acquisition Date
      2019
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 細胞のスライドグラス標本作製方法及びDNA又はRNAの抽出方法2016

    • Inventor(s)
      中西速夫、伊藤誠二
    • Industrial Property Rights Holder
      中西速夫、伊藤誠二
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-145568
    • Filing Date
      2016-07-25
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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