Role of hepatoma-derived growth factor in the tumor angiogenesis and the growth of the hepatocellular carcinoma

• Project/Area Number: 24590998
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hyogo Medical University
• Principal Investigator: Enomoto Hirayuki 兵庫医科大学, 医学部, 准教授 (40449880)
• Co-Investigator(Kenkyū-buntansha): IMANISHI HIROYASU 兵庫医科大学, 医学部, 准教授 (60340957) ; NISHIGUCHI SHUHEI 兵庫医科大学, 医学部, 教授 (10192246)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: HDGF / 肝細胞癌 / 血管新生 / Sorafenib / IFN / Xenograft model / DNA チップ / 細胞増殖

Outline of Final Research Achievements

In the present study, we showed the possibility that IFN treatment amplifies the antitumor effects of sorafenib for hepatocellular carcinoma (HCC). Down-regulation of HDGF shows antitumor effects for HCC through the inhibition of cancer cell proliferation and angiogenesis. We also found that VEGF treatment did not induce HDGF expression, while HDGF induced VEGF expression. These findings revealed new roles of HDGF in HCC growth and angiogenesis, and should contribute to the development of a new therapy for HCC by inhibiting the HDGF function.

Research Products

• [Journal Article] Hepatoma-Derived Growth Factor: Its Possible Involvement in the Progression of Hepatocellular Carcinoma. (2015)
  • Author(s): Enomoto H, Nakamura H, Liu W, Nishiguchi S
  • Journal Title: International Journal of Molecular Sciences Volume: 16 Issue: 6 Pages: 14086-14097
  • DOI: 10.3390/ijms160614086
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Down-regulation of HDGF Inhibits the Growth of Hepatocellular Carcinoma Cells In Vitro and In Vivo (2015)
  • Author(s): Enomoto H, Nakamura H, Nishiguchi S, et al.
  • Journal Title: Anticancer Research Volume: 35 Pages: 6475-6480
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Role of hepatoma-derived growth factor in anti-angiogenic therapy for hepatocellular carcinoma. (2014)
  • Author(s): Enomoto H, Nakamura H, Nishiguchi S
  • Journal Title: Current Research in Gastroenterology and Hepatology Volume: 8 Pages: 13-18
  • Acknowledgement Compliant
• [Journal Article] Regulation of hepatoma-derived growth factor (HDGF) for anti-cancer (2014)
  • Author(s): Enomoto H, Nakamura H, Nishiguchi S
  • Journal Title: Current Research in Cancer Volume: in press
• [Journal Article] Hepatoma-derived growth factor (HDGF) in liver disease (2013)
  • Author(s): Enomoto H, Nakamura H, Nishiguchi S
  • Journal Title: Current Research in Hepatology Volume: 5 Pages: 1-6
• [Journal Article] Hepatoma-derived growth factor (HDGF) as a potential target for cancer therapy (2013)
  • Author(s): Enomoto H, Nakamura H, Nishiguchi S
  • Journal Title: Current Research in Cancer Volume: 7 Pages: 1-12
  • Peer Reviewed
• [Journal Article] Suppression of hepatoma cell proliferation by vitamin K (2012)
  • Author(s): Enomoto H, Nishiguchi S
  • Journal Title: Current Research in Cancer Volume: 6 Pages: 9-16
  • Peer Reviewed
• [Presentation] C型慢性肝炎SVR後の問題点 (2015)
  • Author(s): 會澤信弘、榎本平之、西口修平
  • Organizer: 第41回日本肝臓学会西部会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-12-03
• [Presentation] ペグインターフェロンα・リバビリン・プロテアーゼ阻害薬3剤併用療法とIFN-free治療についての比較：抗IFNα中和抗体陽性例の成績を含めての検討 (2015)
  • Author(s): 榎本平之、楊和典、西口修平
  • Organizer: 第19回日本肝臓学会大会
  • Place of Presentation: グランドプリンスホテル新高輪（東京都・港区）
  • Year and Date: 2015-10-08
• [Presentation] The pivotal role of anti-angiogenic activity in the in vivo antitumor effects of type I interferon. (2014)
  • Author(s): Enomoto H, Tsujimura T, Nishiguchi S, et al.
  • Organizer: The 65th Annual Meeting of the American Association for the Study of Liver Diseases（AASLD2014）
  • Place of Presentation: Boston (USA)
  • Year and Date: 2014-11-10
• [Presentation] Hepatoma-derived growth factorの発現抑制による肝癌増殖抑制効果：Sorafenibとの関係を含めての検討 (2013)
  • Author(s): 榎本平之、中村秀次、今西宏安 他
  • Organizer: 第49回日本肝臓学会総会
  • Place of Presentation: 東京
• [Presentation] Hepatoma-derived growth factorはsorafenibと異なる機序で肝癌増殖を抑制する (2013)
  • Author(s): 榎本平之、中村秀次、今西宏安 他
  • Organizer: 第8回日本肝がん分子標的治療研究会
  • Place of Presentation: 石川
• [Presentation] 肝癌症例におけるHepatoma-derived growth factor(HDGF)の血中濃度測定に関する検討 (2013)
  • Author(s): 榎本平之、中村秀次、西口修平
  • Organizer: 第17回日本肝臓学会大会(JDDW2013)
  • Place of Presentation: 東京
• [Presentation] HDGF(hepatoma-derived growth factor)-silencing inhibit the proliferation of hepatoma cells through the sorafenib-independent pathway. (2013)
  • Author(s): Enomoto H, Nakamura H, Imanishi H, et al.
  • Organizer: The 64th Annual Meeting of the American Association for the Study of Liver Diseases（AASLD2013）
  • Place of Presentation: Washington, USA
• [Presentation] インターフェロンとSorafenibの併用療法に関する基礎的検討 (2013)
  • Author(s): 榎本平之、今西宏安、長谷川国大 他
  • Organizer: 第7回日本肝がん分子標的治療研究会
  • Place of Presentation: 岐阜
• [Presentation] インターフェロンの血管新生抑制による抗腫瘍効果に関する検討 (2012)
  • Author(s): 榎本平之、由利幸久、長谷川国大 他
  • Organizer: 第77回日本インターフェロン・サイトカイン学会学術集会
  • Place of Presentation: 神戸
• [Presentation] 肝細胞癌を標的としたSorafenibとインターフェロンの併用療法に関する検討 (2012)
  • Author(s): 榎本平之、由利幸久、長谷川国大 他
  • Organizer: 第77回日本インターフェロン・サイトカイン学会学術集会
  • Place of Presentation: 神戸
• [Presentation] 肝細胞癌に対する分子標的薬とインターフェロンの併用療法に関する基礎的検討 (2012)
  • Author(s): 榎本平之
  • Organizer: 第12回肝疾患フォーラム学術集会
  • Place of Presentation: 大阪
  • Invited
• [Presentation] Sorafenibとインターフェロンの併用療法に関する検討 (2012)
  • Author(s): 榎本平之、由利幸久、長谷川国大 他
  • Organizer: 第16回日本肝臓学会大会(JDDW2012)
  • Place of Presentation: 神戸
• [Presentation] Hepatoma-derived growth factor as a possible target molecule for the treatment of hepatocellular carcinoma (2012)
  • Author(s): Enomoto H, Nakamura H, Yoh K, et al.
  • Organizer: The 10th JSH Single Topic Conference
  • Place of Presentation: 東京