Development of revolutionary markers to select drugs for advanced hepatocellular carcinoma

• Project/Area Number: 15K09000
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Okayama University
• Principal Investigator: Nouso Kazuhiro 岡山大学, 医学部, 客員研究員 (10314668)
• Co-Investigator(Kenkyū-buntansha): 白羽 英則 岡山大学, 大学病院, 講師 (40379748) ; 中村 進一郎 岡山大学, 大学病院, 講師 (70514230)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 進行肝細胞癌 / 分子標的薬 / サイトカイン / 糖鎖 / リキッドバイオプシー / 肝細胞癌 / 化学療法 / 効果予測 / 癌診断 / 薬剤感受性

Outline of Final Research Achievements

The aim of this study was to elucidate the predictive ability of cytokines, glycans, and circulating tumor DNA for the treatment effect of chemotherapies in patients with advanced hepatocellular carcinoma.
Predictive ability of cytokines were weak; however, serum angiopoietin2 level was closely related to overall survival of the patients. In addition, the level at progressive disease could determine the post progression survival. We also found out that serum levels of some glycans were correlated with the presence of the tumor and with overall survival. In examination of resected tumor, gene mutation related to cancer immortalization was found out to be the marker of short progression free survival and might be useful as the target of circulating tumor DNA.

Research Products

• [Journal Article] Modified radiofrequency ablation for the treatment of hepatocellular carcinoma. (2016)
  • Author(s): Nouso K, Oonishi A, Wakuta A, Kariyama K.
  • Journal Title: Hepatology Research Volume: 印刷中 Issue: 11 Pages: 1158-1161
  • DOI: 10.1111/hepr.12683
  • Peer Reviewed
• [Journal Article] Loss of Runt-related transcription factor 3 induces resistance to 5-fluorouracil and cisplatin in hepatocellular carcinoma. (2016)
  • Author(s): Kataoka J, Shiraha H, Horiguchi S, Sawahara H, Uchida D, Nagahara T, Iwamuro M, Morimoto H, Takeuchi Y, Kuwaki K, Onishi H, Nakamura S, Takaki A, Nouso K, Yagi T, Yamamoto K, Okada H.
  • Journal Title: Oncology Reports Volume: 35 Issue: 5 Pages: 2576-2582
  • DOI: 10.3892/or.2016.4681
  • Peer Reviewed / Open Access
• [Journal Article] Potential of alpha-fetoprotein as a prognostic marker after curative radiofrequency ablation of hepatocellular carcinoma. (2015)
  • Author(s): Dohi C, Nouso K, Miyahara K, Morimoto Y, Wada N, Kinugasa H, Takeuchi Y, Kuwaki K, Onishi H, Ikeda F, Nakamura S, Shiraha H, Takaki A, Okada H.
  • Journal Title: Hepatology Researvh Volume: 1 Issue: 9 Pages: 1-2
  • DOI: 10.1111/hepr.12636
  • Peer Reviewed / Open Access
• [Journal Article] Percutaneous Radiofrequency Ablation for Intermediate-Stage Hepatocellular Carcinoma. (2015)
  • Author(s): Kariyama K, Wakuta A, Nishimura M, Kishida M, Oonishi A, Ohyama A, Nouso K, Kudo M.
  • Journal Title: Oncology Volume: 89 supple2 Issue: Suppl. 2 Pages: 19-26
  • DOI: 10.1159/000440627
  • Peer Reviewed
• [Journal Article] Alpha-fetoprotein before and after pegylated interferon therapy for predicting hepatocellular carcinoma development. (2015)
  • Author(s): Takeuchi Y, Ikeda F, Osawa T, Araki Y, Takaguchi K, Morimoto Y, Hashimoto N, Sakaguchi K, Sakata T, Ando M, Makino Y, Matsumura S, Takayama H, Seki H, Nanba S, Moritou Y, Yasunaka T, Ohnishi H, Takaki A, Nouso K, Iwasaki Y, Yamamoto K.
  • Journal Title: World J Hepatol. Volume: 印刷中 Issue: 19 Pages: 2220-2220
  • DOI: 10.4254/wjh.v7.i19.2220
  • Peer Reviewed
• [Journal Article] Association of hepatic oxidative stress and iron dysregulation with HCC development after interferon therapy in chronic hepatitis C. (2015)
  • Author(s): Nanba S, Ikeda F, Baba N, Takaguchi K, Senoh T, Nagano T, Seki H, Takeuchi Y, Moritou Y, Yasunaka T, Ohnishi H, Miyake Y, Takaki A, Nouso K, Iwasaki Y, Yamamoto K.
  • Journal Title: J Clin Pathol. Volume: 69 Issue: 3 Pages: 226-33
  • DOI: 10.1136/jclinpath-2015-203215
  • Peer Reviewed
• [Journal Article] Local recurrence and complications after percutaneous radiofrequency ablation of hepatocellular carcinoma: a retrospective cohort study focused on tumor location. (2015)
  • Author(s): Toshimori J, Nouso K, Nakamura S, Wada N, Morimoto Y, Takeuchi Y, Yasunaka T, Kuwaki K, Ohnishi H, Ikeda F, Shiraha H, Takaki A, Yamamoto K.
  • Journal Title: Acta Med Okayama Volume: 69 Pages: 219-26
  • NAID: 120005647397
  • Peer Reviewed
• [Presentation] 進行肝細胞癌におけるソラフェニブ治療の長期生存症例と短期終了症例のそれぞれの特徴 (2018)
  • Author(s): 足立卓哉、能祖一裕、中村進一郎、白羽英則他
  • Organizer: 日本肝癌分子標的治療研究会
• [Presentation] Follistatin is a useful biomarker predicting the effect of sorafenib for the treatment of hepatocellular carcinoma with extrahepatic spread. (2017)
  • Author(s): Adachi S, Nouso K, Okada H.
  • Organizer: APDW
  • Int'l Joint Research
• [Presentation] 進行肝細胞癌に対するソラフェニブ治療における鉄マーカーとの関係性 (2017)
  • Author(s): 足立卓哉、能祖一裕、中村進一郎、白羽英則他
  • Organizer: 日本肝癌分子標的治療研究会
• [Presentation] 進行肝細胞癌(HCC)に対するソラフェニブ治療の予後予測マーカーとしてのFollistatinの有用性 (2017)
  • Author(s): 足立卓哉 能祖一裕 岡田裕之
  • Organizer: ＪＤＤＷ
• [Presentation] 進行肝細胞癌に対するソラフェニブ治療における鉄マーカーとの関係性 (2017)
  • Author(s): 足立卓哉、能祖一裕、和田望、森元裕貴、竹内康人、桑木 健志、大西 秀樹、中村 進一郎、白羽 英則、高木章乃夫、岡田裕之
  • Organizer: 第15回日本肝がん分子標的治療研究会
  • Place of Presentation: イイノホール（東京都千代田区）
• [Presentation] 肝動注化学療法から分子標的薬への切り替えのタイミング (2016)
  • Author(s): 大西秀樹、能祖一裕、中村進一郎、和田望、安中幸、竹内康人、安中哲也、桑木健志、白羽英則、高木章乃夫、岡田裕之
  • Organizer: ＪＤＤＷ２０１６
  • Place of Presentation: 神戸コンベンションセンター（兵庫県神戸市）
  • Year and Date: 2016-11-03
• [Presentation] Changes of Innunoglobulin-bound Glycans in Patients with Hepatocellular Carcinoma. (2016)
  • Author(s): Dohi C, Nouso K, Miyahara K, Ako S, Adachi T, Wada N, Takeuchi Y, Kuwaki K, Onishi H, Ikeda F, Nakamura S, Shiraha H, Takaki A, Okada H
  • Organizer: The 12th JSH Single topic conference
  • Place of Presentation: 金沢日航ホテル（石川県金沢市）
  • Year and Date: 2016-09-22
• [Presentation] Changes of Immunoglobulin-bound Glycans in Patients with Gastro-Intestinal Cancers. (2016)
  • Author(s): Dohi C, Nouso K, Ako S, Morimoto Y, Miyahara K, Kinugasa H, Wada N, Takeuchi Y, Kuwaki K, Onishi H, Ikeda F, Nakamura S, Shiraha H, Takaki A, Okada H
  • Organizer: Digestive Disease Week 2016
  • Place of Presentation: コンベンションセンター（サンディエゴ ＵＳＡ）
  • Year and Date: 2016-05-21
  • Int'l Joint Research
• [Presentation] Characteristics of HCC patients with hTERT promoter mutation. (2016)
  • Author(s): Ako S, Nouso K, Kinugasa H, Adachi T, Dohi C, Morimoto Y, Wada N, Takeuchi Y, Kuwaki K, Onishi H, Ikeda F, Nakamura S, Shiraha H, Takaki A, Okada H.
  • Organizer: Digestive Disease Week 2016
  • Place of Presentation: コンベンションセンター（サンディエゴ ＵＳＡ）
  • Year and Date: 2016-05-21
  • Int'l Joint Research
• [Presentation] Recent advancement of tumor ablation in patients with HCC (2015)
  • Author(s): Nouso K
  • Organizer: Asian conference of tumor ablation
  • Place of Presentation: 福岡
  • Year and Date: 2015-10-30
  • Int'l Joint Research / Invited
• [Presentation] Serum N-glycan was useful for the prediction of the prognosis in patients with HCC (2015)
  • Author(s): Nouso K, Miyahara K, Yamamoto K
  • Organizer: 日本消化器病週間インターナショナルシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2015-10-08
  • Int'l Joint Research
• [Presentation] 肝動注化学療法の効果と問題点 (2015)
  • Author(s): 大西秀樹 能祖一裕 山本和秀
  • Organizer: 第51回日本肝癌研究会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-23
• [Presentation] TACE不応進行肝細胞癌の治療戦略についての検討 (2015)
  • Author(s): 和田 望、 能祖 一裕、 山本 和秀
  • Organizer: 第51回日本肝癌研究会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-23
• [Presentation] Characteristics of the patients with hepatocellular carcinoma treated with sorafenib over one year. (2015)
  • Author(s): Adachi T, Nouso K, W Nozomu
  • Organizer: Asia-Pacific Primary Liver Cancer Expert Meeting 2015
  • Place of Presentation: 大阪
  • Year and Date: 2015-07-03
  • Int'l Joint Research
• [Presentation] Prediction of the recurrence of hepatocellular carcinoma by alpha-fetoprotein after radiofrequency ablation (2015)
  • Author(s): Dohi C, Nouso K, Miyahara K,
  • Organizer: Asia-Pacific Primary Liver Cancer Expert Meeting 2015
  • Place of Presentation: 大阪
  • Year and Date: 2015-07-03
  • Int'l Joint Research
• [Presentation] 腫瘍マーカーの推移から見た肝動注化学療法の早期治療効果予測 (2015)
  • Author(s): 大西秀樹 能祖一裕 中村進一郎 和田 望 竹内康人 桑木健志 白羽英則 山本和秀
  • Organizer: 第51回日本肝臓学会総会
  • Place of Presentation: 熊本
  • Year and Date: 2015-05-21
• [Presentation] Alteration of serum N-glycan profile in patients with hepatocellular carcinoma and their clinical application (2015)
  • Author(s): Nouso K, Miyahara K, Dohi C, Morimoto Y, Kinugasa H, Wada N, Takeuchi Y, Kuwaki K, Onishi H, Ikeda F, Nakamura S, Shiraha H, Takaki A, Amano M, Nishimura S, and Yamamoto K.
  • Organizer: DDW2015
  • Place of Presentation: ワシントンDC
  • Year and Date: 2015-05-16
  • Int'l Joint Research
• [Presentation] Local Recurrences and Complications After Percutaneous Radiofrequency Ablation of Hepatocellular Carcinoma: Analysis Focused on Tumor Locations. (2015)
  • Author(s): Toshimori J, Nouso K, Nakamura S
  • Organizer: DDW2015
  • Place of Presentation: ワシントンDC
  • Year and Date: 2015-05-16
  • Int'l Joint Research
• [Presentation] 病態別に見た進行肝細胞癌に対する化学療法の効果 (2015)
  • Author(s): 大西秀樹 能祖一裕 山本和秀
  • Organizer: 第101回日本消化器病学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2015-04-23