Development of an ultra-early detection method for recurrence of hepatocellular carcinoma using a microcavity array liquid biopsy system

• Project/Area Number: 26670379
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: University of Fukui
• Principal Investigator: Nakamoto Yasunari 福井大学, 学術研究院医学系部門, 教授 (40293352)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 癌 / 細胞・組織 / 蛋白 / ゲノム / 内科

Outline of Final Research Achievements

A method for efficient enrichment of circulating tumor cells (CTCs) was evaluated in the blood of patients with hepatocellular carcinoma (HCC) using a microcavity array system. When HCC cell lines HepG2, Huh7 and PLC/PRF/5 were mixed in heathy blood, the detection rates were 65%, 77% and 99%, respectively. In 3mL blood of 19 HCC patients, 8.8±8.7 and 125.0±176.3 of CTCs were isolated in stages I-III and IV (P<0.05), respectively, indicating that the numbers of CTCs may be correlated with the progression of HCC. The results demonstrate the establishment of a novel liquid biopsy method for CTCs in HCC and suggest its clinical significance on the disease development.

Research Products

• [Journal Article] Identification of novel variants in HLA class II region related to HLA DPB1 expression and disease progression in patients with chronic hepatitis C. (2017)
  • Author(s): Hiramatsu K, Matsuda H, Nemoto T, Nosaka T, Saito Y, Naito T, Takahashi K,Ofuji K, Ohtani M, Suto H, Yasuda T, Hida Y, Kimura H, Soya Y, Nakamoto Y.
  • Journal Title: J Med Virol. Volume: in press Issue: 9 Pages: 1574-1583
  • DOI: 10.1002/jmv.24814
  • Peer Reviewed / Open Access
• [Journal Article] Perioperative plasma glypican-3 level may enable prediction of the risk of recurrence after surgery in patients with stage I hepatocellular carcinoma. (2017)
  • Author(s): Ofuji K, Saito K, Suzuki S, Shimomura M, Shirakawa H, Nobuoka D, Sawada Y, Yoshimura M, Tsuchiya N, Takahashi M, Yoshikawa T, Tada Y, Konishi M, Takahashi S, Gotohda N, Nakamoto Y, Nakatsura T.
  • Journal Title: Oncotarget. Volume: in press Issue: 23 Pages: 37835-37844
  • DOI: 10.18632/oncotarget.14271
  • Peer Reviewed / Open Access
• [Journal Article] Promising new strategies for hepatocellular carcinoma. (2016)
  • Author(s): Nakamoto Y.
  • Journal Title: Hepatol. Res. Volume: 47 Issue: 4 Pages: 251-265
  • DOI: 10.1111/hepr.12795
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Long-Term Endoscopic Follow-Up of Patients with Chronic Radiation Proctopathy after Brachytherapy for Prostate Cancer (2016)
  • Author(s): M. Ohtani, H. Suto, T. Nosaka, Y. Saito, Y. Ozaki, R. Hayama, T. Naito, K. Takahashi, K. Ofuji, H. Matsuda, K. Hiramatsu, T. Nemoto, H. Shioura, H. Kimura, Y. Aoki, O. Yokoyama, Y. Nakamoto
  • Journal Title: Diagn Ther Endosc Volume: 2016:1414090 Pages: 1-7
  • DOI: 10.1155/2016/1414090
  • Peer Reviewed / Open Access
• [Journal Article] 1.Effect of green tea catechins on gastric mucosal dysplasia in insulin-gastrin mice. (2016)
  • Author(s): Ohno T, Ohtani M, Suto H, Ohta M, Imamura Y, Matsuda H, Hiramatsu K, Nemoto T, Nakamoto Y.
  • Journal Title: Oncol. Rep. Volume: 35 Issue: 6 Pages: 3241-3247
  • DOI: 10.3892/or.2016.4717
  • Peer Reviewed / Open Access
• [Journal Article] Preoperative diagnosis of cavernous hemangioma presenting with melena using wireless capsule endoscopy of the small intestine. (2016)
  • Author(s): Akazawa Y, Hiramatsu K, Nosaka T, Saito Y, Ozaki Y, Takahashi K, Naito T, Ofuji K, Matsuda H, Ohtani M, Nemoto T, Suto H, Yamaguchi A, Imamura Y, Nakamoto Y.
  • Journal Title: Endosc. Int. Open Volume: 4 Issue: 03 Pages: E249-E251
  • DOI: 10.1055/s-0041-111321
  • Peer Reviewed / Open Access
• [Journal Article] High-dose cyclophosphamide induces specific tumor immunity with concomitant recruitment of LAMP1/CD107a-expressing CD4-positive T cells into tumor sites. (2015)
  • Author(s): Naito, T., Baba, T., Takeda, K., Sasaki, S., Nakamoto, Y. and Mukaida, N.
  • Journal Title: Cancer Letters Volume: 366 Issue: 1 Pages: 93-99
  • DOI: 10.1016/j.canlet.2015.06.009
  • NAID: 120005663501
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism: a case report. (2015)
  • Author(s): Tanaka T, Hiramatsu K, Nosaka T, Saito Y, Naito T, Takahashi K, Ofuji K, Matsuda H, Ohtani M, Nemoto T, Suto H, Yamamoto T, Kimura H, Nakamoto Y.
  • Journal Title: BMC Cancer Volume: 15 Issue: 1 Pages: 863-863
  • DOI: 10.1186/s12885-015-1831-7
  • Peer Reviewed / Open Access
• [Journal Article] Ruptured hepatic metastases of cutaneous melanoma during treatment with vemurafenib: an autopsy case report. (2015)
  • Author(s): Nosaka T, Hiramatsu K, Nemoto T, Saito Y, Ozaki Y, Takahashi K, Naito T, Ofuji K, Matsuda H, Ohtani M, Suto H, Imamura Y, Nakamoto Y.
  • Journal Title: BMC Clin. Pathol. Volume: 15 Issue: 1 Pages: 15-15
  • DOI: 10.1186/s12907-015-0015-3
  • Peer Reviewed / Open Access
• [Journal Article] A case of Helicobacter pylori-negative intramucosal well-differentiated gastric adenocarcinoma with intestinal phenotype. (2015)
  • Author(s): Ozaki Y, Suto H, Nosaka T, Saito Y, Naito T, Takahashi K, Ofuji K, Matsuda H, Ohtani M, Hiramatsu K, Nemoto T, Imamura Y, Nakamoto Y.
  • Journal Title: Clin J Gastroenterol Volume: 8 Issue: 1 Pages: 18-21
  • DOI: 10.1007/s12328-014-0543-x
  • Peer Reviewed / Open Access
• [Journal Article] In vivo immunological antitumor effect of OK-432-stimulated dendritic cell transfer after radiofrequency ablation. (2014)
  • Author(s): Nakagawa H, Mizukoshi E, Iida N, Terashima T, Kitahara M, Marukawa Y, KitamuraK, Nakamoto Y, Hiroishi K, Imawari M, Kaneko S
  • Journal Title: Cancer Immunol Immunother. Volume: 63(4) Issue: 4 Pages: 347-356
  • DOI: 10.1007/s00262-013-1514-7
  • NAID: 120005368239
  • Peer Reviewed / Open Access
• [Journal Article] Efficient generation of highly immunocompetent dendritic cells from peripheral blood of patients with hepatitis C virus-related hepatocellular carcinoma. (2014)
  • Author(s): Kitahara M, Mizukoshi E, Nakamoto Y, Mukaida N, Matsushima K, Kaneko S
  • Journal Title: Int. Immunopharmacol. Volume: 21(2) Issue: 2 Pages: 346-353
  • DOI: 10.1016/j.intimp.2014.05.023
  • NAID: 120005463368
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of hepatic arterial infusion chemotherapy and sorafenib in elderly patients with advanced hepatocellular carcinoma: A case series. (2014)
  • Author(s): Nemoto T, Matsuda H, Nosaka T, Saito Y, Ozaki Y, Hayama R, Naito T, Takahashi K, Ofuji K, Ohtani M, Hiramatsu K, Suto H, Nakamoto Y
  • Journal Title: Mol. Clin. Oncol. Volume: 2 (6) Pages: 1028-1034
  • Peer Reviewed / Open Access
• [Journal Article] A peptide antigen derived from EGFR T790M is immunogenic in non small cell lung cancer. (2014)
  • Author(s): Ofuji K, Tada Y, Yoshikawa T, Shimomura M, Yoshimura M, Saito K, Nakamoto Y, Nakatsura T
  • Journal Title: Int. J. Oncol. Volume: 46(2) Issue: 2 Pages: 497-504
  • DOI: 10.3892/ijo.2014.2787
  • Peer Reviewed / Open Access
• [Presentation] Development of a Novel Circulating Tumor Cells Isolation System in Patients with Hepatocellular Carcinoma Using a Microcavity Array. (2016)
  • Author(s): Takahashi K, Ofuji K, Nosaka T, Ozaki Y, Matsuda H, Ohtani M, Hiramatsu K, Nemoto T, Matsunaga Tatsuya Nakamoto Y.
  • Organizer: The 67th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2016)
  • Place of Presentation: Boston, Massachusetts
  • Year and Date: 2016-11-13
  • Int'l Joint Research
• [Presentation] Perioperative plasma glypican-3 levels predict the risk of post-operative recurrence. (2016)
  • Author(s): Ofuji K, Saito K, Nosaka T, Takahashi K, Naito T, Matsuda H, Ohtani M, Hiramatsu K, Nemoto T, Nakamoto Y.
  • Organizer: The 67th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2016)
  • Place of Presentation: Boston, Massachusetts
  • Year and Date: 2016-11-11
  • Int'l Joint Research
• [Presentation] Comparison of patient characteristics and survival between elderly and younger patients with hepatocellular carcinoma related to hepatitis C virus infection. (2016)
  • Author(s): Nemoto T, Matsuda H, Ohtani M, Nakamoto Y.
  • Organizer: 23rd International Symposium on Hepatitis C Virus and Related Viruses Kyoto
  • Place of Presentation: Kyoto International Conference Center(Kyoto)
  • Year and Date: 2016-10-13
  • Int'l Joint Research
• [Presentation] Analysis of glypican-3 as a predictive marker for postoperative recurrence of HCV related hepatocellular carcinoma. (2016)
  • Author(s): Ofuji K, Saito K, Matsuda H, Ohtani M, Hiramatsu K, Nemoto T, Nakamoto Y, Nakatsura T.
  • Organizer: 23rd International Symposium on Hepatitis C Virus and Related Viruses Kyoto
  • Place of Presentation: Kyoto International Conference Center(Kyoto)
  • Year and Date: 2016-10-13
  • Int'l Joint Research
• [Presentation] High-dose cyclophosphamide Eradicates Hepatoma Cells by rapid recruitment of CD4+ cytolytic T cells into tumor sites via the CCL3/CCR5 axis. (2016)
  • Author(s): Naito T, Baba T, Takeda K, Sasaki S, Matsuda H, Ohtani M, Hiramatsu K, Nemoto T, Mukaida N, Nakamoto Y.
  • Organizer: The 12th JSH Single Topic Conference in Kanazawa
  • Place of Presentation: Hotel Nikko Kanazawa(Kanazawa)
  • Year and Date: 2016-09-23
  • Int'l Joint Research
• [Presentation] Influence of antithrombotic drugs on gastric ulcer healing after endoscopic submucosal dissection. (2016)
  • Author(s): Ohtani M, Suto H, Nosaka T, Saito Y, Ozaki Y, Hayama R, Naito T, Takahashi K, Ofuji K, Matsuda H, Hiramatsu K, Nemoto T, Nakamoto Y.
  • Organizer: Digestive Disease Week 2016
  • Place of Presentation: San Diego U.S.A.
  • Year and Date: 2016-05-21
  • Int'l Joint Research
• [Presentation] Endoscopic long-term follow-up of chronic radiation proctopathy after brachytherapy for prostate cancer. (2016)
  • Author(s): Takahashi K, Suto H, Nosaka T, Saito Y, Ozaki Y, Hayama R, Naito T, Ohtani M, Ofuji K, Matsuda H, Hiramatsu K, Nemoto T, Nakamoto Y.
  • Organizer: Digestive Disease Week 2016
  • Place of Presentation: San Diego U.S.A.
  • Year and Date: 2016-05-21
  • Int'l Joint Research
• [Presentation] Chemokine CCL3/CCR5-recruited, Cytotoxic CD4+ T Cells Eradicate Hepatoma Cells in a Model of Anticancer Chemotherapy with High-Dose Cyclophosphamide. (2015)
  • Author(s): Naito T, Baba T, Takeda K, Sasaki S, Mukaida N, Nakamoto Y.
  • Organizer: The 65th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2015)
  • Place of Presentation: San Francisco, U.S.A.
  • Year and Date: 2015-11-17
  • Int'l Joint Research
• [Presentation] Identification of Hypermethylation and Non-Synonymous Mutations in Genes Down-Regulated during the Process of Hepatocarcinogenesis in a Model of Chronic Hepatitis B. (2014)
  • Author(s): Nakamoto Y, Yamashita T, Hiramatsu K, Nemoto T, Suto H, Kaneko S
  • Organizer: The 65th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2014)
  • Place of Presentation: Boston, Massachusetts
  • Year and Date: 2014-11-09