The effect of CCL1 antisense ODN for monocytes from patients with hepatocellular Carcinoma on tumor progression

• Project/Area Number: 26860533
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Osaka Medical College
• Principal Investigator: Asai Akira 大阪医科大学, 医学部, 講師 (30622146)
• Research Collaborator: Suzuki Fujio University of Texas Medical Branch, Internal Medicine/Infectious Diseases, Professor
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 単球 / 肝細胞癌 / CCL1 / マクロファージ

Outline of Final Research Achievements

Despite major advances in curative and palliative approaches, hepatocellular carcinoma (HCC) is still the third leading cause of cancer-related death worldwide. M1 monocytes play a key role in host antitumor defenses in HCC. The majority of monocytes from early HCC stage patients switched to the M1 phenotype (IL-12+IL-10－iNOS+cells), whereas the majority of monocytes from advanced HCC stage patients did not switch to the M1 phenotype and continued to express M2b phenotypic properties (IL-12－IL-10+CCL1+iNOS－cells). Monocytes from advanced HCC stage patients showed M1 polarization after treatment with CCL1 antisense oligodeoxynucleotide (ODN). Therefore, our study indicates that anti-HCC defenses of advanced HCC stage patients may be improved after CCL1 antisense ODN treatment.

Research Products

• [Journal Article] Host antitumor resistance improved by the macrophage polarization in a chimera model of patients with HCC (2017)
  • Author(s): Akira Asai, Yusuke Tsuchimoto, Hideko Ohama, Shinya Fukunishi, Yasuhiro Tsuda, Makiko Kobayashi, Kazuhide Higuchi, Fujio Suzuki
  • Journal Title: Oncoimmunology Volume: 6 Issue: 4 Pages: e1299301-e1299301
  • DOI: 10.1080/2162402x.2017.1299301
  • Peer Reviewed / Int'l Joint Research
• [Presentation] CCL1 antisense ODN gene therapy for monocytes is prevented for the progression of hepatocellular carcinoma in humanized chimeric mice. (2015)
  • Author(s): Yusuke Tsuchimoto, Akira Asai, Hideko Ohama, Shinya Fukunishi, Yasuhiro Tsuda, Kazuhide Higuchi, Makiko Kobayashi, Fujio Suzuki
  • Organizer: Digestive Diesases Week 2015
  • Place of Presentation: Washington D.C.
  • Year and Date: 2015-05-17
  • Int'l Joint Research
• [Presentation] Suppression of tumor progression in patients with advanced stage of hepatocellular carcinoma by M1 macrophage induction (2015)
  • Author(s): Yusuke Tsuchimoto, Akira Asai, Hideko Ohama, Shinya Fukunishi, Yasuhiro Tsuda, Kazuhide Higuchi, Makiko Kobayashi, Fujio Suzuki
  • Organizer: Digestive Diesases Week 2015
  • Place of Presentation: Washington D.C.
  • Year and Date: 2015-05-17
  • Int'l Joint Research
• [Presentation] Suppression of tumor growth by a M2b macrophage reverter in humanized murine chimeras created with peripheral blood monocytes of patients with advanced stage hepatocellular carcinoma (2015)
  • Author(s): Yusuke Tsuchimoto, Akira Asai, Hideko Ohama, Shinya Fukunishi, Yasuhiro Tsuda, Makiko Kobayashi, Kazuhide Higuchi, Fujio Suzuki
  • Organizer: Immunology 2015
  • Place of Presentation: New orleans
  • Year and Date: 2015-05-08
  • Int'l Joint Research
• [Presentation] 進行期肝細胞癌患者に対するCCL1 antisense ODNを用いた遺伝子治療について (2014)
  • Author(s): 朝井 章、津田 泰広、樋口 和秀
  • Organizer: 第40回肝臓学会東部会
  • Place of Presentation: 京王プラザホテル、東京
  • Year and Date: 2014-11-27 – 2014-11-28
• [Presentation] 進行期肝細胞癌患者における単球の役割について (2014)
  • Author(s): 朝井 章、津田 泰広、樋口 和秀
  • Organizer: 第50回日本肝臓学会総会
  • Place of Presentation: ホテルニューオータニ、東京
  • Year and Date: 2014-05-29 – 2014-05-30
• [Presentation] Two different types of macrophages were detected in patients with different stages of HCC (2014)
  • Author(s): Yusuke Tsuchimoto, Akira Asai, Keisuke Yokohama, Hideko Ohama, Tetsuya Sujishi, Shinya Fukunishi, Yasuhiro Tsuda, Kazuhide Higuchi, Makiko Kobayashi, Fujio Suzuki
  • Organizer: AAI Annual Meeting 2014
  • Place of Presentation: David L. Lawrence Convention Center、Pittsburgh, Pennsylvania
  • Year and Date: 2014-05-02 – 2014-05-06