Research on inhibition of anti-cancer treatment-induced EMT and fibrosis in the background liver and hepatocellular carcinoma

• Project/Area Number: 23591981
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kanazawa University
• Principal Investigator: TAJIMA HIDEHIRO 金沢大学, 大学病院, 助教 (00436825)
• Co-Investigator(Kenkyū-buntansha): OHTA Tetsuo 金沢大学, 医学系, 教授 (40194170)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 上皮間葉転換 / 癌幹細胞 / 肝星細胞 / 癌間質 / 肝癌 / EMT / 胆道癌 / HDAC阻害剤 / paclitaxel / 原発性肝癌 / 胆管細胞癌 / Paclitaxel / パクリタキセル / 線維化

Research Abstract

Epithelial-mesenchymal transition (EMT) in tissue fibrosis and cancer metastasis and invasion has been noted, but the EMT is induced in cancer cells by anti-cancer therapy itself has become a hot topic in recent years. It is well known that tissue fibrosis and EMT are inhibited by low dose administered taxan and histone deacetylase (HDAC) inhibitor. It has been shown that paclitaxel suppresses the induction of EMT in primary liver cancer (intrahepatic cholangiocarcinoma) cell line in the current study, HDAC inhibitors (sodium valproate) and paclitaxel inhibited activation of hepatic stellate cells.

Research Products

• [Journal Article] Low-dose paclitaxel inhibits the induction of epidermal-mesenchymal transition in the human cholangiocarcinoma CCKS-1 cell line. (2013)
  • Author(s): ATSUSHI HIROSE, HIDEHIRO TAJIMA, TETSUO OHTA, TOMOYA TSUKADA, KOICHI OKAMOTO, SHINICHI NAKANUMA, SEISHO SAKAI, JUN KINOSHITA, ISAMU MAKINO, HIROYUKI FURUKAWA, HIRONORI HAYASHI, KEISHI NAKAMURA, KATSUNOBU OYAMA, MASAFUMI INOKUCHI, HISATOSHI NAKAGAWARA, TOMOHARU MIYASHITA, HIROYUKI TAKAMURA, ITASU NINOMIYA, et al.
  • Journal Title: ONCOLOGY LETTERS Volume: 6 Issue: 4 Pages: 915-920
  • DOI: 10.3892/ol.2013.1494
  • Peer Reviewed
• [Journal Article] Angiotensin II enhances epithelial-to-mesenchymal transition through the interaction between activated hepatic stellate cells and the stromal cell-derived factor-1/CXCR4 axis in intrahepatic cholangiocarcinoma (2012)
  • Author(s): Okamoto K, et al, Ohta T
  • Journal Title: Int J Oncol Volume: 41 (2) Issue: 2 Pages: 573-82
  • DOI: 10.3892/ijo.2012.1499
  • NAID: 120006380697
  • Peer Reviewed
• [Journal Article] Successful treatment of unresectable gallbladder cancer with low-dose paclitaxel as palliative chemotherapy after failure of gemcitabine and oral S-1:A case report (2012)
  • Author(s): Tajima H, Ohta T, Shinbashi H
  • Journal Title: Oncology Letters Volume: 4 Issue: 6 Pages: 1281-1284
  • DOI: 10.3892/ol.2012.909
  • Peer Reviewed
• [Journal Article] Neoadjuvant chemotherapy with gemcitabine for pancreatic cancer increases insitu expressions of the apoptosis marker M30 and stem cell marker CD44 (2012)
  • Author(s): HIDEHIRO TAJIMA
  • Journal Title: Oncology Letters Volume: 3 Issue: 6 Pages: 1186-1190
  • DOI: 10.3892/ol.2012.657
  • Peer Reviewed
• [Journal Article] Sodium valproate blocks the transforming growth factor (TGF)-β1 autocrine loop and attenuates the TGF-β1-induced collagen synthesis in a human hepatic stellate cell line. (2011)
  • Author(s): Watanabe T, Ohta T, et al
  • Journal Title: Int J Mol Med Volume: 28 (6) Pages: 919-25
  • DOI: 10.3892/ijmm.2011.768
  • NAID: 120006380695
  • Peer Reviewed
• [Presentation] 胆道癌に対するlow dose Paclitaxel療法の基礎的検討 (2013)
  • Author(s): 田島秀浩、真橋宏幸、廣瀬淳史、渡邊利史、岡本浩一、中沼伸一、正司政寿、牧野勇、林泰寛、尾山勝信、中川原寿俊、宮下知治、高村博之、北川裕久、太田哲生
  • Organizer: 第51回日本癌治療学会学術集会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2013-10-24
• [Presentation] 胆道癌に対するlow dose Paclitaxel療法の上皮間葉転換(EMT)抑制に関する実験的検討および臨床的効果 (2013)
  • Author(s): 田島秀浩、太田哲生、中沼伸一、岡本浩一、酒井清祥、牧野勇、林泰寛、尾山勝信、中川原寿俊、宮下知治、高村博之、二宮致、北川裕久、伏田幸夫、藤村隆
  • Organizer: 第49回日本胆道学会学術集会
  • Place of Presentation: ヒルトン東京ベイ(千葉県)
  • Year and Date: 2013-09-20
• [Presentation] Experimental research on effect of low-dose paclitaxel for fibrosis in human hepatic stellate cells (2013)
  • Author(s): 真橋宏幸、田島秀浩、廣瀬淳史、渡邉利史、岡本浩一、中沼伸一、酒井清祥、林泰寛、中川原寿俊、高村博之、二宮致、北川裕久、伏田幸夫、藤村隆、太田哲生
  • Organizer: 第22回日本がん転移学会学術集会
  • Place of Presentation: ホテルブエナビスタ(長野県)
  • Year and Date: 2013-07-12
• [Presentation] Low-dose paclitaxel inhibits the induction of EMT in a human cholangiocarcinoma cell line, CCKS-1 (2012)
  • Author(s): 廣瀬淳史、田島秀浩、牧野勇、中村慶史、林泰寛、尾山勝信、井口雅史、中川原寿俊、藤田秀人、高村博之、二宮致、北川裕久、藤村隆、太田哲生
  • Organizer: 第21回日本がん転移学会学術集会/総会
  • Place of Presentation: オリエンタルホテル広島(広島県)
  • Year and Date: 2012-07-12
• [Presentation] Low-dose paclitaxel inhibits the induction of EMT in a human cholangiocarcinoma cell line, CCKS-1 (2012)
  • Author(s): 廣瀬淳史
  • Organizer: 第21回日本がん転移学会学術集会/総会
  • Place of Presentation: オリエンタルホテル広島（広島県）
• [Presentation] ヒストン脱アセチル化酵素阻害薬の膵線維化治療薬としての可能性 (2011)
  • Author(s): 渡邊 利史
  • Organizer: 日本膵臓学会大会
  • Place of Presentation: 弘前 ホテルニューキャッスル
• [Presentation] 術前化学療法が膵癌組織に与える影響に関する免疫組織学的検討 (2011)
  • Author(s): 田島秀浩
  • Organizer: 日本がん転移学会学術集会・総会
  • Place of Presentation: アクトシティ浜松 コングレスセンター(静岡）
• [Presentation] Experimental research on effect of Low-dose paclitaxel for fibrosis in human hepatic stellate cells
  • Author(s): HIROYUKI SHINBASHI, Hidehiro Tajima, Atsushi Hirose, Toshihumi Watanabe, Kouichi Okamoto,
  • Organizer: 日本がん転移学会
  • Place of Presentation: ホテルブエナビスタ（長野県）
• [Presentation] 胆道癌に対する3rd line化学療法としてのlow dose Paclitaxel療法の有用性
  • Author(s): 田島秀浩、太田哲生、北川裕久、廣瀬淳史、正司政寿、渡邉利史、中沼伸一、岡本浩一、酒井清祥、牧野 勇、林 泰寛、中村慶史、尾山勝信、中川原寿俊、宮下知治、高村博之
  • Organizer: 日本肝胆膵外科学会
  • Place of Presentation: 和歌山県民文化会館（和歌山県）
• [Presentation] 胆道癌に対するlow dose Paclitacel療法の上皮間葉転換(EMT)抑制に関する実験的検討および臨床的効果
  • Author(s): 田島秀浩、太田哲生、中沼伸一、岡本浩一、酒井清祥、牧野 勇、林 泰寛、尾山勝信、中川原寿俊、宮下知治、高村博之、二宮 致、北川裕久、伏田幸夫、藤村 隆
  • Organizer: 日本胆道学会
  • Place of Presentation: ヒルトン東京ベイ（千葉県）
• [Presentation] 胆道癌に対するlow dose Paclitaxel療法の基礎的検討
  • Author(s): 田島秀浩、真橋宏幸、廣瀬淳史、渡邊利史、岡本浩一、中沼伸一、正司政寿、牧野 勇、林 泰寛、尾山勝信、中川原寿俊、宮下知治、高村博之、北川裕久、太田哲生
  • Organizer: 日本癌治療学会
  • Place of Presentation: 京都国際会議場（京都府）