Development of CTC capture chip for head and neck cancer patients

• Project/Area Number: 17K19718
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Surgery related to the biological and sensory functions and related fields
• Research Institution: Kanazawa University
• Principal Investigator: Yoshizaki Tomokazu 金沢大学, 医学系, 教授 (70262582)
• Co-Investigator(Kenkyū-buntansha): 中西 庸介 金沢大学, 医学系, 助教 (20623648)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 末梢血循環腫瘍細胞 / CTCチップ / 頭頸部癌 / 悪性度 / 末梢循環癌細胞 / 抗EpCAM 抗体 / CTC 捕捉システム / 培養細胞 / 癌 / トランスレーショナルリサーチ / 末梢循環腫瘍細胞

Outline of Final Research Achievements

Malignant potential of the tumor is defined by the cancer cell fraction with highly malignant potential. Circulating tumor cells (CTC) are considered to contain tumor cells with metastatic property. And thus, they represent metastatic potential of the parental tumor tissue. We developed polymeric CTC capture microchip by combining antibodies and micro fluid device. And we analyzed the efficacy of these chips. Global standard anti-EpCAM antibody chip showed high affinity for head and neck squamous cell carcinoma (HNSCC) cell lines. However, it showed quite low affinity for the CTC in HNSCC patients. Moreover, the reproducibility was not stable. These results suggest that improvement of CTC capturing system is required for clinical application of CTC capture system.

Academic Significance and Societal Importance of the Research Achievements

国内で市販されていたEpCAM発現細胞を標的としたFDA認可のCTC定量システムは正確に頭頸部扁平上皮癌の悪性度を反映しないことが判明した。その理由として、頭頸部癌のCTCがEpCAMを発現していない可能性と頭頸部癌患者においてはCTCが少ない可能性の２つが考えられた。今日期待されている採決による腫瘍悪性度評価において、CTCは体内の腫瘍組織における悪性度の高い細胞集団と考えられているので、今後はビメンチンなどの間葉系のマーカーを組み合わせたマイクロチップによる捕捉、もしくはサイズによるソーティングなどの捕捉システムの改良と検体採取法の最適化に向けた研究が必要であることが示唆された。

Research Products

• [Journal Article] Modified meatotympanoplasty for external auditory canal stenosis and lateralized tympanic membrane: a preliminary study (2020)
  • Author(s): Kase Kina、Ito Makoto、Hatano Miyako、Sugimoto Hisashi、Shimada Mari、Yoshizaki Tomokazu
  • Journal Title: Acta Oto-Laryngologica Volume: 140 Issue: 4 Pages: 327-332
  • DOI: 10.1080/00016489.2020.1714723
  • Peer Reviewed / Open Access
• [Journal Article] Microglial activation in the cochlear nucleus after early hearing loss in rats. (2019)
  • Author(s): Noda M, Hatano M, Hattori T, Takarada-Iemata M, Shinozaki T, Sugimoto H, Ito M, Yoshizaki T, Hori O.
  • Journal Title: Auris Nasus Larynx. Volume: 印刷中 Issue: 5 Pages: 716-723
  • DOI: 10.1016/j.anl.2019.02.006
  • Peer Reviewed / Open Access
• [Journal Article] Expression of estrogen receptor alpha is associated with pathogenesis and prognosis of human papillomavirus‐positive oropharyngeal cancer (2019)
  • Author(s): Kano Makoto、Kondo Satoru、Wakisaka Naohiro、Wakae Kosho、Aga Mituharu、Moriyama‐Kita Makiko、Ishikawa Kazuya、Ueno Takayoshi、Nakanishi Yosuke、Hatano Miyako、Endo Kazuhira、Sugimoto Hisashi、Kitamura Kouichi、Muramatsu Masamichi、Yoshizaki Tomokazu
  • Journal Title: International Journal of Cancer Volume: 145 Issue: 6 Pages: 1547-1557
  • DOI: 10.1002/ijc.32500
  • Peer Reviewed / Open Access
• [Journal Article] Bone invasion‐targeted chemotherapy with a novel anionic platinum complex (3Pt) for oral squamous cell carcinoma (2019)
  • Author(s): Kasahara Yoshiya、Endo Kazuhira、Ueno Takayoshi、Ueno Haruna、Moriyama‐Kita Makiko、Odani Akira、Yoshizaki Tomokazu
  • Journal Title: Cancer Science Volume: 110 Issue: 10 Pages: 3288-3295
  • DOI: 10.1111/cas.14145
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of UCH-L1 Deubiquitinating Activity with Two Forms of LDN-57444 Has Anti-Invasive Effects in Metastatic Carcinoma Cells (2019)
  • Author(s): Kobayashi Eiji、Hwang Duhyeong、Bheda-Malge Anjali、Whitehurst Christopher B.、Kabanov Alexander V.、Kondo Satoru、Aga Mitsuharu、Yoshizaki Tomokazu、Pagano Joseph S.、Sokolsky Marina、Shakelford Julia
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 15 Pages: 3733-3733
  • DOI: 10.3390/ijms20153733
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Third Epidemiological Analysis of Nasopharyngeal Carcinoma in the Central Region of Japan from 2006 to 2015 (2019)
  • Author(s): Kanno M, Narita N, Fujimoto Y, Wakisaka N, Yoshizaki T, Kodaira T, Makita C, Sato Y, Yamazaki K, Wakaoka T, Shimode Y, Tsuji H, Kito R, Ishinaga H, Hosokawa S, Takakura H, Nishimura K, Matoba T, Fujieda S.
  • Journal Title: Cancers Volume: 11 Issue: 8 Pages: 1180-1180
  • DOI: 10.3390/cancers11081180
  • Peer Reviewed / Open Access
• [Journal Article] Effects of l-carnitine administration on health-related quality of life during cisplatin-based chemoradiotherapy in patients with head and neck squamous cell carcinoma (2019)
  • Author(s): Endo Kazuhira、Ueno Takayoshi、Ishikawa Kazuya、Nakanishi Yosuke、Kondo Satoru、Wakisaka Naohiro、Yoshizaki Tomokazu
  • Journal Title: Auris Nasus Larynx Volume: 46 Issue: 3 Pages: 431-436
  • DOI: 10.1016/j.anl.2018.10.007
  • Peer Reviewed / Open Access
• [Journal Article] Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study (2019)
  • Author(s): Burtness B, Harrington KJ, Greil R, Soulieres D, Tahara M, de Castro G Jr, Psyrri A, Basté N, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Hong RL, Gonzalez Mendoza R, Roy A, Zhang Y, Gumuscu B, Cheng JD, Jin F, Rischin D; KEYNOTE-048 Investigators.
  • Journal Title: The Lancet Volume: 394 Issue: 10212 Pages: 1915-1928
  • DOI: 10.1016/s0140-6736(19)32591-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Superior mediastinal lymphadenopathy by silicosis mimicking metastasis of papillary thyroid carcinoma ? Case report and literature review (2019)
  • Author(s): Tsukatani Toshiaki、Niwa Hideki、Komori Takeshi、Yoneyama Tatsuya、Tsuji Hiroyuki、Michigishi Takatoshi、Yokoyama Kunihiko、Yoshizaki Tomokazu
  • Journal Title: Auris Nasus Larynx Volume: - Issue: 6 Pages: 1054-1057
  • DOI: 10.1016/j.anl.2019.12.003
  • Peer Reviewed / Open Access
• [Journal Article] Detection of sentinel lymph node using contrast-enhanced agent, Sonazoid?, and evaluation of its metastasis with superb microvascular imaging in oral and oropharyngeal cancers: a preliminary clinical study (2019)
  • Author(s): Wakisaka Naohiro、Endo Kazuhira、Kitazawa Tomohiro、Shimode Yuzo、Kato Koroku、Moriyama-Kita Makiko、Koda Wataru、Ikeda Hiroko、Ishikawa Kazuya、Ueno Takayoshi、Nakanishi Yosuke、Kondo Satoru、Sugimoto Hisashi、Yoshimura Kenichi、Tsuji Hiroyuki、Kawashiri Shuichi、Omoto Kiyoka、Yoshizaki Tomokazu
  • Journal Title: Acta Oto-Laryngologica Volume: 139 Issue: 1 Pages: 94-99
  • DOI: 10.1080/00016489.2018.1535193
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Inhibition of autophagy by chloroquine makes chemotherapy in nasopharyngeal carcinoma more efficient (2019)
  • Author(s): Aga Tomomi、Endo Kazuhira、Tsuji Akira、Aga Mitsuharu、Moriyama-Kita Makiko、Ueno Takayoshi、Nakanishi Yosuke、Hatano Miyako、Kondo Satoru、Sugimoto Hisashi、Wakisaka Naohiro、Yoshizaki Tomokazu
  • Journal Title: Auris Nasus Larynx Volume: 46 Issue: 3 Pages: 443-450
  • DOI: 10.1016/j.anl.2018.10.013
  • NAID: 130007936124
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Expression and subcellular localisation of AID and APOBEC3 in adenoid and palatine tonsils (2018)
  • Author(s): Seishima Noriko、Kondo Satoru、Wakae Kousho、Wakisaka Naohiro、Kobayashi Eiji、Kano Makoto、Moriyama-Kita Makiko、Nakanishi Yosuke、Endo Kazuhira、Imoto Tomoko、Ishikawa Kazuya、Sugimoto Hisashi、Hatano Miyako、Ueno Takayoshi、Koura Miki、Kitamura Koichi、Muramatsu Masamichi、Yoshizaki Tomokazu
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 918-918
  • DOI: 10.1038/s41598-017-18732-w
  • NAID: 120006602142
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] C-Terminal Farnesylation of UCH-L1 Plays a Role in Transport of Epstein-Barr Virus Primary Oncoprotein LMP1 to Exosomes (2018)
  • Author(s): Kobayashi E, Aga M, Kondo S, Whitehurst C, Yoshizaki T, Pagano J. S , Shackelford J
  • Journal Title: mShpere Volume: 3 Issue: 1
  • DOI: 10.1128/msphere.00030-18
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Glucocorticoid receptor expression in resident and hematopoietic cells in IgG4-related disease. (2018)
  • Author(s): Iguchi T, Takaori K, Mii A, Sato Y, Suzuki Y, Yoshifuji H, Seno H, Ogawa O, Omori K, Bessho K, Kondo S, Yoshizaki T, Nakashima H, Saito T, Mimori T, Haga H, Kawano M, Yanagita M.
  • Journal Title: Mod Pathol. Volume: - Issue: 6 Pages: 890-899
  • DOI: 10.1038/s41379-018-0036-4
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Expression of interferon regulatory factor 7 correlates with the expression of Epstein-Barr Virus latent membrane protein 1 and cervical lymph node metastasis in nasopharyngeal cancer (2017)
  • Author(s): Kondo S, Endo K, Wakisaka N, Aga M, Kano M, Seishima N, Imoto T, Kobayashi E, Moriyama-Kita M, Nakanishi Y, Murono S, Pagano JS, Yoshizaki T
  • Journal Title: Pathology International Volume: 67 Issue: 9 Pages: 461-466
  • DOI: 10.1111/pin.12561
  • Peer Reviewed
• [Presentation] CONCURRENT SUPERSELECTIVE INTRA-ARTERIAL CHEMORADIOTHERAPY FOR ADVANCED TEMPORAL BONE SQUAMOUS CELL CARCINOMA (2019)
  • Author(s): Yoshizaki Tomokazu, Ishikawa Eriko, Sugimoto Hisashi
  • Organizer: 32nd Politzer Society Meeting & 2nd World Congress of Otology
  • Int'l Joint Research
• [Presentation] Effects of L-carnitine administration on health-related quality of life during cisplatin-based chemoradiotherapy in patients with head and neck squamous cell carcinoma (2019)
  • Author(s): Endo Kazuhira, Ueno Takayoshi, Ishikawa Kazuya, Nakanishi Yosuke, Kondo Satoru, Wakisaka Naohiro, Yoshizaki Tomokazu
  • Organizer: 5th Congress of European ORL-HNS
  • Int'l Joint Research
• [Presentation] ROLE OF EPSTEIN-BARR VIRUS AND ALTERNATING CHEMORADIOTHERAPY IN NASOPHARYNGEAL CARCINOMA (2019)
  • Author(s): Yoshizaki Tomokazu
  • Organizer: AAO-HNSF Annual Meeting & OTO Experience
  • Int'l Joint Research
• [Presentation] THE INFLUENCE OF HUMAN PAPILLOMAVIRUS ON NASOPHARYNGEAL CARCINOMA IN JAPAN. (2019)
  • Author(s): Yoshizaki Tomokazu
  • Organizer: EUROGIN 2019
  • Int'l Joint Research
• [Presentation] HPV-status determines the efficacy of an oral fluoropyrimidine, S-1, in oropharyngeal carcinoma. (2019)
  • Author(s): Wakisaka Naohiro, Yoshizaki Tomokazu
  • Organizer: 15th Japan-Taiwan Conference on Otolaryngology-Head and Neck Surgery
  • Int'l Joint Research
• [Presentation] Distinct mode of invasion in HPV associate and non-associated oropharyngeal squamous cell carcinoma (2018)
  • Author(s): Tomokazu Yoshizaki
  • Organizer: 17th Japan KoreaJoint Mmeeting
  • Int'l Joint Research / Invited
• [Presentation] Role of Epstein-Barr virus and Alternating Chemoradiotherapy In Nasopharyngeal Carcinoma. (2018)
  • Author(s): Tomokazu Yoshizaki, Satoru Kondo, Yoshitaka Aoki, Harue Mizokam
  • Organizer: International conference on EBV & KSHV 2018
  • Int'l Joint Research
• [Presentation] Human papillomavirus genome integration is associated with the expression of ABOBEC3 in oropharyngeal carcinomas. (2018)
  • Author(s): Tomokazu Yoshizaki, Satoru Kondo
  • Organizer: 6th IFNOS
  • Int'l Joint Research
• [Presentation] 耳鼻咽喉科領域におけるIgG4関連疾患 嗅覚障害との関連も含めて (2018)
  • Author(s): 吉崎智一
  • Organizer: 第31回日本口腔咽頭科学会
  • Invited
• [Presentation] 頭頸部癌センチネルリンパ節生検術臨床試験 (2018)
  • Author(s): 吉崎智一、センチネルリンパ節生検術共同研究班
  • Organizer: 第20回SNNS研究会
  • Invited
• [Presentation] The Expression of APOBEC3A Associates with Human Papilloma Virus Genome Integration in Oropharyngeal Carcinomas (2017)
  • Author(s): Yoshizaki T
  • Organizer: 4th Congress of European ORL-HNS
  • Int'l Joint Research
• [Presentation] Relationship between APOBEC3 expression and viral genome hypermutation and integration in HPV-related oropharngeal cancers (2017)
  • Author(s): Kondo S, Wakisaka N, Yoshizaki T
  • Organizer: 第76回日本癌学会