Development of secondary prevention for hepatocellular carcinoma by enhancement of anti-tumor immunity stimulated by chemokine agents.

2013 Fiscal Year Final Research Report

• Project/Area Number: 23790781
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Kanazawa University
• Principal Investigator: ARAI Kuniaki 金沢大学, 大学病院, 助教 (50436838)
• Project Period (FY): 2011 – 2013
• Keywords: 抗腫瘍免疫

Research Abstract

The aim of this study is development of secondary prevention for hepatocellular carcinoma (HCC) by enhancement of anti-tumor immunity stimulated by chemokine agents in radiofrequency ablation (RFA) therapy with dendritic cell (DC) injection into HCC. We analyzed cellular immune response of DC and various method of introduction of DC. We revealed that stimulation of OK-432 enhances antigen presentation activity and immunopotentiative action. We started clinical trial of OK-432 stimulated DC injection into HCC after RFA therapy. Progression free survival in the group treated with RFA + OK432 stimulated DC transfer was much better.

Research Products

• [Journal Article] Liver cancer : progress in diagnosis and treatments. Topics : IV. Progress in guideline on liver cancer; 3 (2014)
  • Author(s): Arai K, Yamashita T, Kaneko S
  • Journal Title: Guideline of surveillance]. Nihon Naika Gakkai Zasshi Volume: 103(1) Pages: 37-43
• [Journal Article] Liver cancer : progress in diagnosis and treatments. Topics : VI. Progress in treatments of liver cancer; 5 (2014)
  • Author(s): Yamashita T, Arai K, Kaneko S
  • Journal Title: Chemotherapy. Nihon Naika Gakkai Zasshi Volume: 103(1) Pages: 102-9
• [Journal Article] Feasibility and efficacy of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma after sorafenib (2013)
  • Author(s): Terashima T, Arai K, 他10名
  • Journal Title: Hepatol Res Volume: (Epub ahead of print)
  • DOI: 10.1111/hepr.12266
  • Peer Reviewed
• [Journal Article] Evaluation of eligibility criteria in living donor liver transplantation for hepatocellular carcinoma byα-SMA -positive cancer-associated fibroblasts (2013)
  • Author(s): Takamura H, Arai K, 他27名
  • Journal Title: Oncol Rep Volume: 30(4) Pages: 1561-74
  • DOI: 10.3892/or.2013.2616
  • Peer Reviewed
• [Journal Article] 進行肝癌治療Q69.わが国のソラフェニブ治療の実態と治療成績はどのくらいですか? (2013)
  • Author(s): 山下竜也,荒井邦明,金子周一
  • Journal Title: 肝癌診療Q&A Pages: 277-280
• [Journal Article] Increase in CD14+HLA-DR -/low myeloid -derived suppressor cells in hepatocellular carcinoma patients and its impact on prognosis (2013)
  • Author(s): Arihara F, Arai K, 他6名
  • Journal Title: Cancer Immunol Immunother Volume: 62(8) Pages: 1421-30
  • DOI: 10.1007/s00262-013-1447-1
  • Peer Reviewed
• [Journal Article] Peretinoin, an acyclic retinoid, improves the hepatic gene signature of chronic hepatitis C following curative therapy of hepatocellular carcinoma (2013)
  • Author(s): Honda M, Arai K, 他7名
  • Journal Title: BMC Cancer Volume: 13 Pages: 191
  • DOI: 10.1186/1471-2407-13-191
  • Peer Reviewed
• [Journal Article] Association of interleukin-28B genotype and hepatocellular carcinoma recurrence in patients with chronic hepatitis C (2013)
  • Author(s): Hodo Y, Arai K, 他12名
  • Journal Title: Clin Cancer Res Volume: 19(7) Pages: 1827-37
  • DOI: 10.1158/1078-0432.CCR-12-1641
  • Peer Reviewed
• [Journal Article] Enhancement of tumor-associated antigen -specific T cell responses by radiofrequency ablation of hepatocellular carcinoma (2013)
  • Author(s): Mizukoshi E, Arai K, 他8名
  • Journal Title: Hepatology Volume: 57(4) Pages: 1448-57
  • DOI: 10.1002/hep.26153
  • Peer Reviewed
• [Journal Article] 【肝細胞癌のすべて2012】肝がんの治療アルゴリズム海外(APASL, EASL/EORTC, AASLD)の診療ガイドライン (2012)
  • Author(s): 荒井邦明,山下竜也,金子周一
  • Journal Title: 肝・胆・膵 Volume: 65巻6号 Pages: 1199-1204
• [Journal Article] 【肝細胞癌のすべて2012】治療方別の治療効果判定の実際肝動注化学療法 (2012)
  • Author(s): 山下竜也,荒井邦明,金子周一
  • Journal Title: 肝・胆・膵 Volume: 65巻6号 Pages: 1364-1369
• [Journal Article] Expression of chondroitin-glucuronate C5-epimerase and cellular immune responses in patients with hepatocellular carcinoma (2012)
  • Author(s): Mizukoshi E, Arai K, 他4名
  • Journal Title: Liver Int Volume: 32(10) Pages: 1516-26
  • DOI: 10.1111/j.1478-3231.2012.02853.x
  • Peer Reviewed
• [Journal Article] 【肝・胆・膵腫瘍の薬物療法-最近の進歩】肝がんソラフェニブの新たな展開(適応承認後明らかになってきた治療成績、課題、新たな臨床試験など) (2012)
  • Author(s): 山下竜也,荒井邦明,金子周一
  • Journal Title: 腫瘍内科 Volume: 9巻6号 Pages: 641-650
• [Journal Article] 【肝胆膵悪性腫瘍に対する分子標的療法の近未来的展望】肝細胞癌Sorafenib (2012)
  • Author(s): 山下竜也,荒井邦明,金子周一
  • Journal Title: 肝・胆・膵 Volume: 64巻5号 Pages: 645-655
• [Journal Article] Randomized, Phase II Study Comparing Interferon Combined with Hepatic Arterial Infusion of Fluorouracil plus Cisplatin and Fluorouracil Alone in Patients with Advanced Hepatocellular Carcinoma (2011)
  • Author(s): Yamashita T, Arai K, 他9名
  • Journal Title: Oncology Volume: 81(5-6) Pages: 281-290
  • DOI: 10.1159/000334439
  • Peer Reviewed
• [Journal Article] Identification of a secretory protein c19orf10 activated in hepatocellular carcinoma (2011)
  • Author(s): Sunagozaka H, Arai K, 他7名
  • Journal Title: Int J Cancer Volume: 129(7) Pages: 1576-85
  • DOI: 10.1002/ijc.25830
  • Peer Reviewed
• [Journal Article] 【肝細胞癌の化学療法-分子標的治療の進歩と効果判定】各論肝細胞癌の化学療法の進歩肝細胞癌の動注化学療法の進歩と治療成績 (2011)
  • Author(s): 山下竜也,荒井邦明,金子周一
  • Journal Title: 肝胆膵画像(1882-5087) Volume: 13巻6号 Pages: 602-607
• [Journal Article] Frequency of CD45RO+ subset in CD4+CD25(high) regulatory T cells associated with progression of hepatocellular carcinoma (2011)
  • Author(s): Takata Y, Arai K, 他11名
  • Journal Title: Cancer Lett Volume: 307(2) Pages: 165-73
  • DOI: 10.1016/j.canlet.2011.03.029
  • Peer Reviewed
• [Journal Article] 【肝細胞がん診療の進歩 : Up-To-Date】治療肝細胞がんに対する肝動注化学療法の位置づけ (2011)
  • Author(s): 山下竜也,荒井邦明,金子周一
  • Journal Title: 最新医学(0370-8241) Volume: 66巻8号 Pages: 1804-1810
• [Journal Article] Comparative analysis of various tumor-associated antigen-specific t-cell responses in patients with hepatocellular carcinoma (2011)
  • Author(s): Mizukoshi E, Arai K, 他8名
  • Journal Title: Hepatology Volume: 53 (4) Pages: 1206-16
  • DOI: 10.1002/hep.24149
  • Peer Reviewed
• [Presentation] Assessment of the therapeutic response of hepatocellular carcinoma treated with radiofrequency ablation : comparison of contrast-enhanced ultrasonography and computed tomography (2013)
  • Author(s): K Arai, T Yamashita, E Mizukoshi, S Kaneko
  • Organizer: WFUMB 2013 PA03-004
  • Place of Presentation: Sao Paulo, Brazil
  • Year and Date: 20130502-05
• [Presentation] Contrast-enhanced ultra -sonography for evaluating treatment of sorafenib in hepatocellular carcinoma (2013)
  • Author(s): K Arai, T Yamashita, E Mizukoshi, S Kaneko
  • Organizer: WFUMB 2013 PA03-003
  • Place of Presentation: Sao Paulo, Brazil
  • Year and Date: 20130502-05
• [Presentation] The impact of post-progression survival on overall survival of patients with advanced hepatocellular carcinoma treated by sorafenib therapy (2013)
  • Author(s): T Terashima, T Yamashita, N Takata, H Nakagawa, K Arai, T Kagaya, E Mizukoshi, M Hondo, S Kaneko
  • Organizer: AASLD2013 2094
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2013-11-05
• [Presentation] Serum Dickkopf-1 as a biomarker for the diagnosis of hepatocellular carcinoma with stem cell features (2013)
  • Author(s): H Sunagozaka, T Yamashita, N Oishi, T Hayashi, H Takatori, T Shimakami, K Kitamura, K Arai, T Kagaya, Y Sakai, T Yamashita, E Mizukoshi, M Hondo, S Kaneko
  • Organizer: AASLD2013 1792
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2013-11-05
• [Presentation] Phase I Trial of Alpha-Fetoprotein-Derived Peptides in the Treatment of Hepatocellular Carcinoma (2013)
  • Author(s): E Mizukoshi, T Yamashita, K Arai, H Sunagozaka, K Fushimi, H Nakagawa, K Yamada, K Kaji, M Kitahara, S Kaneko
  • Organizer: AASLD2013 251
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2013-11-05
• [Presentation] Therapeutic Efficacy and Safety of OK432-Stimulated Monocyte-Derived Dendritic Cell Injection into Hepotocellular Carcinoma after Radiofrequency Ablation (2013)
  • Author(s): M Kitahara, E Mizukoshi, K Kaji, K Yamada, H Nakagawa, H Sunagozaka, K Arai, T Yamashita, S Kaneko
  • Organizer: AASLD2013 1265
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2013-11-04
• [Presentation] Cellular immune responses for human homologue of Prp24p-derived peptides in patients with Hepatocellular Carcinoma (2013)
  • Author(s): K Kaji, E Mizukoshi, T Yamashita, K Arai, H Sunagozaka, K Fushimi, H Nakagawa, K Yamada, M Kitahara, S Kaneko
  • Organizer: AASLD2013 1262
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2013-11-04
• [Presentation] The Study Group on New Liver Cancer Therapies (NLCT) in Japan. Efficacy and safety of miriplatin for hepatocellular carcinoma : a multi‐center retrospective study in Japan (2012)
  • Author(s): K Arai, S Kaneko, T Yamashita, K Ikeda, J Furuse, M Kudo
  • Organizer: AASLD 2012
  • Place of Presentation: Boston, USA
  • Year and Date: 2012-11-10
• [Presentation] A phase I study of vaccination with human telomerase reverse transcriptase-derived peptide in patients with hepatocellular carcinoma (2012)
  • Author(s): E Mizukoshi,T Yamashita, K Arai, H Sunagozaka, K Fushimi, S Kaneko
  • Organizer: AASLD2012
  • Place of Presentation: Boston, USA
  • Year and Date: 2012-11-10
• [Presentation] Efficacy and safety of hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma (2012)
  • Author(s): T Yamashita,T Terashima, K Arai, H Sunagozaka, E Mizukoshi, A Sakai, M Honda, S Kaneko
  • Organizer: AASLD2012
  • Place of Presentation: Boston, USA
  • Year and Date: 2012-11-09
• [Presentation] Increase of CD14+HLA-DR-/low myeloid-derived suppressor cells in hepatocellular carcinoma and its impact for prognosis of patients (2011)
  • Author(s): F Arihara,E Mizukoshi, M Kitahara, Y Takada, K Arai, T Yamashita, Y Nakamoto, S Kaneko
  • Organizer: AASLD2011
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2011-11-08
• [Presentation] Enhancement of tumor-associated antigen-specific T cell responses by radiofrequency ablation of hepatocellular carcinoma (2011)
  • Author(s): E Mizukoshi,F Arihara, T Yamashita, K Arai, H Sunagozaka, T Ueda, T Kagaya, T Yamashita, S Kaneko
  • Organizer: AASLD2011
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2011-11-08
• [Presentation] Distinct Liver Cancer Stem Cells defined by EpCAM and CD90 in Human Hepatocellular Carcinoma (2011)
  • Author(s): T Yamashita,M Honda, Y Nakamoto, E Mizukoshi, T Yamashita, K Arai, K Nio, Y Hara, X W.Wong, S Kaneko
  • Organizer: AASLD2011
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2011-11-07
• [Book] 肝腫瘍, 臨床病態学 (2013)
  • Author(s): 荒井邦明,金子周一
  • Total Pages: 151-157
  • Publisher: ヌーヴェルヒロカワ