Clinical Application and Functional Analysis of Colorectal Cancer CTCs by New Telomescan F35

• Project/Area Number: 17K10653
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Juntendo University
• Principal Investigator: Ochiai Takumi 順天堂大学, 医学部, 客員准教授 (10626815)
• Co-Investigator(Kenkyū-buntansha): 小見山 博光 順天堂大学, 医学部, 非常勤講師 (30348982) ; 十合 晋作 順天堂大学, 医学部, 准教授 (80365634)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 大腸癌 / テロメスキャン / CTC / 採血診断 / CTC-chip / 転移予測 / 血中循環腫瘍細胞 / テロメラーゼ / 腫瘍マーカー / 治療効果判定 / 予後予測因子 / 血中循環癌細胞 / 大腸がん / 転移能評価 / 薬剤感受性

Outline of Final Research Achievements

The purpose of this study is the first clinical application of a blood circulating cancer cell (CTC) capture system in colorectal cancer using the telomerescan method in Japan. The telomeScan developed in Japan is a highly efficient cancer detection method using telomerase, which is highly expressed in cancer cells, as an indicator. In this study, we further improved the TelomeScan F35 system to detect CTCs with high efficiency and accuracy, and demonstrated that it is an innovative method for colorectal cancer diagnosis. We also aim to apply this system to the development of diagnostic and therapeutic methods that take advantage of the features of the telomeScan method, and to realize the world's first innovative system for clinical application.

Academic Significance and Societal Importance of the Research Achievements

CTC は次世代の採血診断マーカーとして期待されてきたが，従来の分析方法では検出率の低さなどが課題とされてきた．本研究ではpolymeric CTC-chip を用いた新システムを用いたCTC捕捉システムにより，採血検体による鋭敏な大腸癌の診断が可能であることを示した．さらに癌細胞で高発現を呈するテロメラーゼを指標とするテロメスキャンF35システムを用い，他法では検出しにくいEpCAM（上皮細胞接着分子）低発現の細胞も逃すことなく検出可能なことが確認された．以上，日本で開発された2つのシステムの適用によって，感度の高いCTC検出が可能となり，大腸癌の診断・治療の進展に寄与すると考えられる．

Research Products

• [Journal Article] Usefulness of an IL-6 Semi-Quantification Kit in Patients with Perforative Peritonitis (2021)
  • Author(s): Ichikawa R, Sugimoto K, Kure K, Honjo K, Takahashi R, Okazawa Y, Kawai M, Munakata S,Komiyama H, Sakamoto K et al..
  • Journal Title: Juntendo Medical Journal Volume: 67 Issue: 2 Pages: 158-164
  • DOI: 10.14789/jmj.2021.67.JMJ20-OA09
  • NAID: 130008032136
  • ISSN: 2187-9737, 2188-2126
  • Peer Reviewed / Open Access
• [Journal Article] Identification of MicroRNA 15b-3p as a Diagnostic Marker for Early Stage of Colorectal Cancer Through Comprehensive RNA Analysis (2021)
  • Author(s): Tsukamoto R, Hosoya M, Fukaya M, Yokoyama N, Kawano S, Sugimoto K, Takahashi M, Sakamoto K, Komiyama H,
  • Journal Title: Juntendo Medical Journal Volume: 67 Issue: 3 Pages: 272-281
  • DOI: 10.14789/jmj.JMJ20-OA12
  • NAID: 130008059636
  • ISSN: 2187-9737, 2188-2126
  • Peer Reviewed / Open Access
• [Journal Article] Antitumor effects of novel mAbs against cationic amino acid transporter 1 (CAT1) on human CRC with amplified CAT1 gene (2021)
  • Author(s): Okita K, Hara Y, Okura H, Hayashi H, Sasaki Y, Masuko S, Kitadai E, Masuko K, Yoshimoto S, Komiyama H, Sakamoto K, Masuko T.et al
  • Journal Title: Cancer Sci Volume: 112 Pages: 563-574
  • Peer Reviewed / Open Access
• [Journal Article] Using the polymeric circulating tumor cell chip to capture circulating tumor cells in blood samples of patients with colorectal cancer (2020)
  • Author(s): Kure K, Hosoya M, Ueyama T, Fukaya M, Sugimoto K, Tomiki Y,Ohnaga T, Sakamoto K, Komiyama H.
  • Journal Title: Oncl Lett Volume: 19 Pages: 2286-2294
  • DOI: 10.3892/ol.2020.11335
  • Peer Reviewed / Open Access
• [Journal Article] Angiopoietin-2 as a prognostic factor in patients with incurable stage IV colorectal cancer. (2020)
  • Author(s): Munakata S, Ueyama T, Ishihara H, Komiyama H, Tsukamoto R, Kawai M, Takahashi M, Kojima Y, Tomiki Y,
  • Journal Title: J Gastrointest Cancer. Volume: 2020 Online ahead of print Issue: 1 Pages: 000-000
  • DOI: 10.1007/s12029-020-00392-1
  • Peer Reviewed / Open Access
• [Journal Article] Metastatic seeding of human colon cancer cell clusters expressing the hybrid epithelial/mesenchymal state. (2019)
  • Author(s): Mizukoshi K, Okazawa Y, Haeno H, Koyama Y, Sulidan K, Komiyama H, Saeki H, Ohtsuji N, Ito Y, Kojima Y, Goto M, Habu S, Hino O, Sakamoto K, Orimo A.
  • Journal Title: Int J Cancer Volume: 146 Issue: 9 Pages: 2547-2562
  • DOI: 10.1002/ijc.32672
  • Peer Reviewed / Open Access
• [Journal Article] Pirfenidone attenuates lung fibrotic fibroblast responses to transforming growth factor-β1. (2019)
  • Author(s): Jin J, Togo S, Kadoya K, Tulafu M, Namba Y, Iwai M, Watanabe J, Nagahama K, Okabe T, Hidayat M, Kodama Y, Kitamura H, Ogura T, Kitamura N, Ikeo K, Sasaki S, Tominaga S, Takahashi K.
  • Journal Title: Respir Res Volume: 20:119 Issue: 1 Pages: 1-14
  • DOI: 10.1186/s12931-019-1093-z
  • Peer Reviewed
• [Journal Article] Specific features of fibrotic lung fibroblasts highly sensitive to fibrotic processes mediated via TGF-β-ERK5 interaction. (2019)
  • Author(s): Kadoya K, Togo S, Tulafu M, Namba Y, Iwai M, Watanabe J, Okabe T, Jin J, Kodama Y, Kitamura H, Ogura T, Kitamura N, Ikeo K, Takeda T, Kondo N, Takahashi K.
  • Journal Title: Cell Physiol Biochem Volume: 52 Issue: 4 Pages: 822-837
  • DOI: 10.33594/000000057
  • Peer Reviewed / Open Access
• [Journal Article] Impact of primary tumor location as a predictive factor in patients suffering from colorectal cancer treated with cytotoxic anticancer agents based on the collagen gel droplet-embedded drug sensitivity test. (2019)
  • Author(s): Ochiai T, Nishimura K, Watanabe T, Kitajima M, Nakatani A, Nagayasu K, Sakuyama N, Sato T, Kishine K, Abe Y, Nagaoka I
  • Journal Title: Oncol Lett Volume: 17 Pages: 1842-1850
  • DOI: 10.3892/ol.2018.9805
  • Peer Reviewed / Open Access
• [Journal Article] Pharmacological targeting of neutrophil serine proteases prevents lethality in dextran sulfate sodium (DSS)-induced colitis in mice (2018)
  • Author(s): Ro H, Munakata S, Ueyama T, Komiyama H, Takahashi M, Kojima Y, Tomiki Y, Sakamoto K
  • Journal Title: Journal of Gastrointestinal & Digestive System Volume: 8 Issue: 01 Pages: 551-551
  • DOI: 10.4172/2161-069x.1000551
  • Peer Reviewed / Open Access
• [Journal Article] High-sensitivity detection of micrometastases generated by GFP lentivirus-transduced organoids cultured from a patient-derived colon tumor. (2018)
  • Author(s): OkazawaY, Mizukoshi K, KoyamaY, Okubo S, Komiyama H, Kojima Y, Goto M, Habu S, Hino O, Sakamoto K, Orimo A.
  • Journal Title: J Vis Exp Volume: 136(e57374) Issue: 136 Pages: 463-473
  • DOI: 10.3791/57374
  • Peer Reviewed / Open Access
• [Journal Article] Tumor suppressor functions of DAXX through histone H3.3/H3K9me3 pathway in pancreatic NETs. (2018)
  • Author(s): Ueda H, Akiyama Y, Shimada S, Mogushi K, Serizawa M, Matsumura S, Mitsunori Y, Aihara A, Ban D, Ochiai T, Kudo A, Tanabe M, Tanaka S.
  • Journal Title: Endocr Relat Cancer Volume: 25(6) Issue: 6 Pages: 619-631
  • DOI: 10.1530/erc-17-0328
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Survival benefit of lymph node dissection in surgery for colon cancer in elderly patients:multicenter propensity score-matched study in Japan. (2018)
  • Author(s): Takahashi M, Niitsu H, Sakamoto K, Hinoi T, Hattori M, Goto M, Bando H, Hazama S, Maeda K, Okita K, Horie H, Watanabe M; Japan Society of Laparoscopic Colorectal Surgery.
  • Journal Title: Asian J Endosc Surg Volume: 2018 Mar 30 Issue: 4 Pages: 1-9
  • DOI: 10.1111/ases.12474
  • Peer Reviewed
• [Journal Article] High-sensitivity detection of micrometastases generated by gfp lentivirus-transduced organoidscultured from a patient-derived colon tumor (2018)
  • Author(s): Okazawa Y, Mizukoshi K, Koyama Y, Okubo S, Komiyama H, Kojima Y, Goto M, Habu S, Hino O,Sakamoto K, Orimo A.
  • Journal Title: Journal of Visualized Experiments（JoVE） in press Volume: --
  • Peer Reviewed
• [Journal Article] Impact of the individualization of the first-line chemotherapy for advanced colorectal cancer based on collagen gel droplet-embedded drug sensitivity test. (2017)
  • Author(s): Ochiai T, Nishimura K, Watanabe T, Kitajima M, Nakatani A, Nagayasu K, Naito S, Sato T, Kishine K, Abe Y, Hara C, Yamada S, Mashiko S, Nagaoka I.
  • Journal Title: Oncol Lett. Volume: 14 Pages: 6045-6052
  • DOI: 10.3892/ol.2017.6960
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy and safety of neoadjuvant chemotherapy with oxaliplatin, 5-fluorouracil, and levofolinate for T3 or T4 stage II/III rectal cancer: the FACT trial. (2017)
  • Author(s): Koike J, Funahashi K, Yoshimatsu K, Yokomizo H, Kan H, Yamada T, Ishida H, Ishibashi K, Saida Y, Enomoto T, Katsumata K, Hisada M, Hasegawa H, Koda K, Ochiai T, Sakamoto K, Shiokawa H, Ogawa S, Itabashi M, Kameoka S.
  • Journal Title: Chemother Pharmacol Volume: 79 Issue: 3 Pages: 519-525
  • DOI: 10.1007/s00280-017-3243-7
  • Peer Reviewed / Open Access
• [Journal Article] ARID2 modulates DNA damage response in human hepatocellular carcinoma cells. (2017)
  • Author(s): Oba A, Shimada S, Akiyama Y, Nishikawaji T, Mogushi K, Ito H, Matsumura S, Aihara A, Mitsunori Y, Ban D, Ochiai T, Kudo A, Asahara H, Kaida A, Miura M, Tanabe M, Tanaka S.
  • Journal Title: Journal of Hepatology Volume: in press Issue: 5 Pages: 942-951
  • DOI: 10.1016/j.jhep.2016.12.026
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Propensity Score Analysis in the Comparison of Long-Term Outcomes for Locally Advanced Colon Cancer Between Laparoscopic Colectomy and Open Colectomy (2017)
  • Author(s): Sugimoto K, Sakamoto K, Ichikawa R, Kure K, Honjo K, Ro H, Takahashi R, Kawano, Niwa K, Ishiyama S, Kamiyama H, Komiyama H, Takahashi M, Kojima Y, Goto M, Okuzawa A, Ishibiki Y, Tomiki Y
  • Journal Title: Juntendo Medical Journal Volume: 63 Issue: 4 Pages: 264-272
  • DOI: 10.14789/jmj.63.264
  • NAID: 130006106309
  • ISSN: 2187-9737, 2188-2126
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Combination of glycopyrronium and indacaterol inhibits carbachol-induced ERK5 signal in fibrotic processes. (2017)
  • Author(s): Namba Y, Togo S, Tulafu M, Kadoya K, Nagahama KY, Taka H, Kaga N, Orimo A, Liu X, Takahashi K.
  • Journal Title: Respir Res. Volume: 18 Issue: 1 Pages: 46-46
  • DOI: 10.1186/s12931-017-0529-6
  • Peer Reviewed / Open Access
• [Journal Article] Sensitive detection of viable circulating tumor cells using a novel conditionally telomerase-selective replicating adenovirus in non-small cell lung cancer patients. (2017)
  • Author(s): Togo S, Katagiri N, Namba Y, Tulafu M, Nagahama K, Kadoya K, Takamochi K, Oh S, Suzuki K, Sakurai F, Mizuguchi H, Urata Y, Takahashi K.
  • Journal Title: Oncotarget Volume: 4 Issue: 21 Pages: 16818-16818
  • DOI: 10.18632/oncotarget.16818
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Decrease in an anti-ageing factor, growth differentiation factor 11, in chronic obstructive pulmonary disease. (2017)
  • Author(s): Onodera K, Sugiura H, Yamada M, Koarai A, Fujino N, Yanagisawa S, Tanaka R, Numakura T, Togo S, Sato K, Kyogoku Y, Hashimoto Y, Okazaki T, Tamada T, Kobayashi S, Yanai M, Miura M, Hoshikawa Y, Okada Y, Suzuki S, Ichinose M.
  • Journal Title: Thorax Volume: 2017 Issue: 10 Pages: 893-904
  • DOI: 10.1136/thoraxjnl-2016-209352
  • Peer Reviewed / Open Access
• [Presentation] Detection of circulating tumor cellsin blood samples of colorectal cancer patients using the polymeric CTC chip (2020)
  • Author(s): Fukaya M, Kure K, Hosoya M, Sugimoto K, Ohnaga T, Sakamoto K, Komiyama H.
  • Organizer: 第79回日本癌学会学術総会
• [Presentation] 網羅的解析を用いた新規結腸癌診断マーカーの探索. (2019)
  • Author(s): 塚本亮一, 小見山博光, 河野眞吾, 河合雅也, 高橋玄, 小島豊, 冨木裕一, 坂本一博
  • Organizer: 第57回日本癌治療学会学術集会, 福岡.
• [Presentation] 患者大腸癌細胞集団の中間型上皮間葉移行を介した浸潤・転移機構. (2019)
  • Author(s): 水越幸輔，岡澤 裕，波江野 洋，小山 侑，大久保捷奇，Kaidiliavi Sulidan，伊藤恭彦，小見山博光，杉本起一，小島 豊，五藤倫敏，垣生園子，樋野興夫，折茂 彰，坂本一博:
  • Organizer: 第30回日本消化器癌発生学会総会，横浜.
• [Presentation] Complete Mesocolic Excision For Transverse Colon In Our Hospital. (2018)
  • Author(s): Shun Ishiyama, Kota Amemiya, Yuki Tsuchiya, Hirokazu Matsuzawa, Shingo Kawano, Masaya Kawai, Koichiro Niwa, Kiichi Sugimoto, Hirohiko Kamiyama, Makoto Takahashi, Hiromitsu Komiyama, Yutaka Kojima, Atsushi Okuzawa, Yuichi Tomiki, Tetsu Fukunaga, Yoshiaki Kajiyama, Seiji Kawasaki, Kazuhiro Sakamoto
  • Organizer: SAGES & CAGES 16TH WORLD CONGRESS OF ENDOSCOPIC SURGERY, Seattle, WA, USA
  • Int'l Joint Research
• [Presentation] Prognostic Factor For Locally Advanced Rectal Cancer After Surgery Following Chemoradiotherapy: Which Factor Is More Important To Predict The Long-term Outcome? (2018)
  • Author(s): Kosuke Mizukoshi, Hirokazu Matsuzawa, Masaya Kawai, Kiichi Sugimoto, Hiromitsu Komiyama, Yutaka Kojima, Yuichi Tomiki, Kazuhiro Sakamoto.
  • Organizer: The 29th ISUCRS Biennial Congress
  • Int'l Joint Research
• [Presentation] SLC7A1に対するモノクローナル抗体 大腸癌組織における遺伝子発現評価と,抗体の癌細胞株に対する傷害活性(Monoclonal antibodies against SLC7A1: assessment of gene expression and cytotoxicity in colorectal cancer) (2018)
  • Author(s): 深谷 緑, 小見山 博光, 杉本 起一, 神山 博彦, 益子 高, 坂本 一博
  • Organizer: 第77回日本癌学会学術総会
  • Int'l Joint Research
• [Presentation] 腹腔鏡下大腸癌手術における癒着防止吸収性バリアの挿入法の工夫 (2018)
  • Author(s): 塚本 亮一, 土谷 祐樹, 茂木 俊介, 河合 雅也, 石山 隼, 杉本 起一, 神山 博彦, 小見山 博光, 高橋 玄, 小島 豊, 冨木 裕一, 福永 哲, 梶山 美明, 川崎 誠治, 坂本 一博
  • Organizer: 第43回日本外科系連合学会学術集会
• [Presentation] 後期研修医によるTAPP法とスキルアップトレーニング (2018)
  • Author(s): 小針 文, 土谷 祐樹, 松澤 宏和, 河野 眞吾, 丹羽 浩一郎, 石山 隼, 杉本 起一, 小見山 博光, 高橋 玄, 小島 豊, 冨木 裕一, 福永 哲, 梶山 美明, 川崎 誠治, 坂本 一博
  • Organizer: 第43回日本外科系連合学会学術集会
• [Presentation] 網羅的解析を用いた新規結腸癌診断マーカーの探索 (2018)
  • Author(s): 塚本 亮一, 小見山 博光, 細谷 理樹, 河野 眞吾, 河合 雅也, 高橋 玄, 小島 豊, 冨木 裕一, 坂本 一博
  • Organizer: 第118回日本外科学会定期学術集会
• [Presentation] 大腸癌化学療法における5FUの血中濃度測定の有用性に関する検討 (2018)
  • Author(s): 安部 雄，柵山 尚紀，藤原 憲太郎，原 千紘，佐藤 剛，根岸 健二，永易 希一，中谷 晃典，北島 政幸，渡部 智雄，落合 匠，西村 和彦，長岡 功
  • Organizer: 第118回日本外科学会定期学術集会
• [Presentation] Production of monoclonal antibodies against amino acid transporter SLC7A1 to develop novel therapy for colorectal cancer. (2017)
  • Author(s): Fukaya M, Komiyama H, Sugimoto K, Kamiyama H, Sakamoto K:
  • Organizer: 第76回日本癌学会学術総会,
• [Presentation] Identification of a novel diagnostic marker for colon cancer through comprehensive microRNA analysis. (2017)
  • Author(s): Tsukamoto R, Komiyama H, Hosoya M, Kure K, Okazawa Y, Mizukoshi K, Fukaya M, Sugimoto K, Kamiyama H, Tomiki Y, Sakamoto K:
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] Kawano S, Amemiya K, Tsuchiya Y, Hagiwara T, Matsuzawa H, Makino Y, Motegi S, Tsukamoto R, Ichikawa R, Kure K, Honjo K, Ro H, Ito S, Okazawa Y, Takahashi R, Mizukoshi K, Kawai M, Munakata S, Niwa K, Ishiyama S, Sugimoto K, Kamiyama H, Komiyama H, Takahashi M, Kojima Y, Goto M, Okuzawa A, Tomiki Y, Kojima M, Ochiai A, Sakamoto K: (2017)
  • Author(s): Semaphorin 3C has a possibility of a new prognostic marker in colorectal cancer.
  • Organizer: 110th AACR, Washington DC,
  • Int'l Joint Research
• [Presentation] Postoperative adjuvant chemotherapy improves survival in stage II colon cancer ? a propensity score matching analysis. (2017)
  • Author(s): Tsukamoto R, Matsuzawa M, Hagiwara T, Tsuchiya Y, Amemiya K, Motegi S, Makino Y, Kawano S, Honjo K, Kure K, Ichikawa R, Ro H, Ito S, Takahashi R, Niwa K, Ishiyama S, Sugimoto K, Kamiyama H, Takahashi M, Kojima Y, Goto M, Okuzawa A, Tomiki Y, Fukunaga T, Kajiyama Y, Kawasaki S, Sakamoto K:
  • Organizer: 110th AACR, Washington DC
• [Remarks] 順天堂大学下部消化管外科学(消化器外科学講座)
  • URL: https://www.juntendo.ac.jp/graduate/laboratory/labo/kabusyoukakan/
• [Remarks] 順天堂大学下部消化管外科学（消化器外科学講座）
  • URL: https://www.juntendo.ac.jp/graduate/laboratory/labo/kabusyoukakan/
• [Remarks] 消化器外科学講座（下部消化管外科学）
  • URL: https://www.juntendo.ac.jp/med/labo/kabusyoukakan.html
• [Remarks] 順天堂大学大学院 下部消化管外科学
  • URL: https://www.juntendo.ac.jp/graduate/laboratory/labo/kabusyoukakan/
• [Remarks] 順天堂大学 下部消化管外科学 (消化器外科学講座)
  • URL: https://www.juntendo.ac.jp/graduate/laboratory/labo/kabusyoukakan/