The effect of suppression of NF kB activity on the radio-sensitivity of colon cancer cells and on the prevention of intestinal damage.

• Project/Area Number: 21591738
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Hyogo Medical University
• Principal Investigator: YOSHIDA Yasuhiko (2010-2011) 兵庫医科大学, 医学部, 研究生(研究員) (40434948); 王 孔志 (2009) Hyogo College of Medicine, 医学部, 助教 (80340967)
• Co-Investigator(Kenkyū-buntansha): FUJIMOTO Jiro 兵庫医科大学, 医学部, 教授 (90199373) ; IIMURO Yuji 兵庫医科大学, 医学部, 教授 (30252018) ; HIRANO Tadamichi 兵庫医科大学, 医学部, 講師 (90340968) ; OKADA Toshihiro 兵庫医科大学, 医学部, 講師 (70351799) ; UYAMA Naoki 兵庫医科大学, 医学部, 研究生(研究員) (70402873) ; 吉田 康彦 兵庫医科大学, 医学部, 助教 (40434948)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 放射性感受性 / 肝細胞増殖因子 / おとり型核酸 / 放射線障害 / 放躰性感受性 / 放射線感受性

Research Abstract

In a mouse model of radiation induced-chronic intestinal injury, fibrogenesis was seen in the submucosal layer. We investigated the effect of HGF administration and NF-kB decoy transfection on fibrogenesis of intestinal wall in a mouse model. HGF administration, but not NF-kB decoy transfection, inhibited the fibrogenesis in the intestinal wall. Next, we investigated the effect of low-dose HGF administration and NF-kB decoy transfection on proliferation ability of a cell line of human colon cancer. NF-kB decoy transfection, but not low-dose HGF administration, inhibited proliferation of cancer cells. Last, we investigated the relationship between NF-kB and EMT in cancer cells. Unfortunately, NF-kB transfection did not change the gene expression of EMT related molecules.

Research Products

• [Journal Article] Fascin, a novel marker of human hepatic stellate cells, may regulate their proliferation, migration, and collagen gene expression through the FAK-PI3K-Akt pathway (2012)
  • Author(s): Uyama N, Iimuro Y, Kawada N, Reynaert H, Suzumura K, Hirano T, Kuroda N, Fujimoto J.
  • Journal Title: Laboratory Investigation Volume: 92(1) Issue: 1 Pages: 57-71
  • DOI: 10.1038/labinvest.2011.150
  • Peer Reviewed
• [Journal Article] N-terminal kinase activation by oxidative stress suppresses retinoid signaling through proteasomal degradation of retinoic acid receptor α protein in hepatic cells (2011)
  • Author(s): Hoshikawa Y, Kanki K, Ashla AA, Arakaki Y, Azumi J, Yasui T, Tezuka Y, Matsumi Y, Tsuchiya H, Kurimasa A, Hisatome I, Hirano T, Fujimoto J, Kagechika H, Shomori K, Ito H, Shiota G.
  • Journal Title: Cancer Science Volume: 102(5) Issue: 5 Pages: 934-941
  • DOI: 10.1111/j.1349-7006.2011.01889.x
  • Peer Reviewed
• [Journal Article] Toll-like receptor signaling in liver regeneration, fibrosis and carcinogenesis (2011)
  • Author(s): Seki E, Park E, Fujimoto J.
  • Journal Title: Hepatology Research Volume: 41(7) Issue: 7 Pages: 597-610
  • DOI: 10.1111/j.1872-034x.2011.00822.x
  • NAID: 10031144129
  • Peer Reviewed
• [Journal Article] Preoperative estimation of asialoglycoprotein receptor expression in the remnant liver from CT/99mTc-GSA SPECT fusion images correlates well with postoperative liver function parameters (2010)
  • Author(s): Iimuro Y, Kashiwagi T, Yamanaka J, Hirano T, Saito S, Sugimoto T, Watanabe S, Kuroda N, Okada T, Asano Y, Uyama N, Fujimoto J.
  • Journal Title: J Hepatobiliary Pancreat Sci Volume: 17(5) Pages: 673-81
  • NAID: 10027663484
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/20703846
  • Peer Reviewed
• [Journal Article] The TLR4/TRIF-Mediated Activation of NLRP3 Inflammasome Underlies Endotoxin-Induced Liver Injury in Mice (2010)
  • Author(s): Tsutsui H, Imamura M, Fujimoto J, Nakanishi K.
  • Journal Title: Gastroenterol Res Pract Pages: 641865-641865
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/20634907
  • Peer Reviewed
• [Journal Article] In vivo effect of imatinib on progression of cecal GIST-like tumors in exon 17-type c-kit knock-in mice (2009)
  • Author(s): Ishikawa T, Nakai N, Liu NN, Shiba K, Isozaki K, Matsuda I, Ito T, Fujimoto J, Hatakeyama K, Kanda T, Hirota S.
  • Journal Title: Lab Invest Volume: 89(10) Pages: 1161-8
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/19636292
  • Peer Reviewed
• [Presentation] A novel small molecule inhibitor of FAK inhibits the ability of proliferation and invasion of human cholangiocarcinoma cell lines in vitro (2011)
  • Author(s): Uyama N, Iimuro Y, Kuroda N, Hirano T, Okada T, Asano Y, Suzumura K, Fujimoto J.
  • Organizer: International Surgical Week 2011
  • Place of Presentation: Yokohama
  • Year and Date: 2011-08-28
• [Presentation] A novel small molecule inhibitor of FAK inhibits the ability of proliferation and invasion of human cholangiocarcinoma cell lines in vitro (2011)
  • Author(s): Uyama N, Iimuro Y, Kuroda N, Hirano T, Okada T, Asano Y, Suzumura K, Fujimoto J
  • Organizer: International Surgical Week ISW 2011
  • Place of Presentation: Yokohama
  • Year and Date: 2011-08-28
• [Presentation] 肝内胆管癌組織におけるFAKの発現とその役割 (2011)
  • Author(s): 宇山直樹, 飯室勇二, 近藤祐一, 鈴村和大, 吉田康彦, 佐竹真, 麻野泰包, 岡田敏弘, 平野公通, 黒田暢一, 藤元治朗
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-04
• [Presentation] 肝癌外科切除における最終確認診断としての術中造影エコーの有用性 (2011)
  • Author(s): 飯室勇二, 近藤祐一, 宇多優吾, 鈴村和大, 吉田康彦, 宇山直樹, 麻野泰包, 岡田敏弘, 平野公通, 田中弘教, 飯島尋子, 西口修平, 藤元治朗
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-03
• [Presentation] Impact of preoperative 3D hepatectomy simulation system for liver resection and transplantation : Application to various kind of liver resection procedure (2011)
  • Author(s): Fujimoto J, Iimuro Y, Yada A, Kondo Y, Saito S, Sueoka H, Ohashi K.
  • Organizer: 46th Annual Congress of the European Society for Surgical Research
  • Place of Presentation: Aachen
  • Year and Date: 2011-05-25
• [Presentation] Fascin, an actin bundlling protein, can be a novel marker of human hepatic stellate cells and may regulate functions of HSCs through FAK-PI3K-AKT pathway (2011)
  • Author(s): Uyama N, Iimuro Y, Kawada N, Reynaert H, Suzumura K, Satake M, Okada T, Hirano T, Kuroda N, Fujimoto J.
  • Organizer: Digestive Disease Week 2011
  • Place of Presentation: Chicago
  • Year and Date: 2011-05-07
• [Presentation] Fascin, an actin bundlling protein, can be a novel marker of human hepatic stellate cells and may regulate functions of Hscs through FAK-PI3 K-AKT pathway (2011)
  • Author(s): Uyama N, Iimuro Y, Kawada N, Reynaert H, Suzumura K, Satake M, Okada T, Hirano T, Kuroda N, Fujimoto J
  • Organizer: Digestive Disease Week 2011
  • Place of Presentation: Chicago
  • Year and Date: 2011-05-07
• [Presentation] Analysis of unique liver regeneration in patients with giant liver cysts after fenestration of cysts without liver resection (2010)
  • Author(s): Iimuro Y, Okada T, Yada A, Kondo Y, Suzumura K, Yoshida Y, Uyama N, Fujimoto J.
  • Organizer: The 61st Annual Meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: Boston
  • Year and Date: 2010-10-30
• [Presentation] 肝細胞癌内線維化領域に存在する線維芽細胞の免疫組織学的検討 (2010)
  • Author(s): 宇山直樹, 飯室勇二, 中井紀博, 近藤祐一, 鈴村和大, 佐竹真, 吉田康彦, 杉本貴昭, 麻野泰包, 斉藤慎一, 王孔志, 岡田敏弘, 平野公通, 黒田暢一, 山中潤一, 藤元治朗
  • Organizer: 第14回日本肝臓学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2010-10-14
• [Presentation] 2年以上生存リンパ節転移陽性肝内胆管癌(ICC)切除症例の検討 (2010)
  • Author(s): 平野公通, 山中潤一, 麻野泰包, 飯室勇二, 黒田暢一, 岡田敏弘, 斉藤慎一, 杉本貴昭, 宇山直樹, 藤元治朗
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-04-10
• [Presentation] Application of computational portal flow dynamics simulation to liver regeneration analysis (2009)
  • Author(s): Iimuro Y, Uyama N, Sugimoto T, Saito S, Hirano T, Yamanaka J, Fujimoto J.
  • Organizer: The 43rd World Congress of the International Society of Surgery
  • Place of Presentation: Adelaide
  • Year and Date: 2009-09-07
• [Presentation] Heat shock protein 47 regulates expression of Collagen V and TIMP2 in pancreatic cancer cells (2009)
  • Author(s): Uyama N, Kuroda N, Ohashi K, Sugimoto T, Kondo Y, Suzumura K, Yoshida Y, Satake M, Asano Y, Saito S, Oh K, Okada T, Hirano T, Yamanaka J, Iimuro Y, Fujimoto J.
  • Organizer: Digestive Disease Week and the 110th Annual Meeting of the AGA Institute
  • Place of Presentation: Chicago
  • Year and Date: 2009-05-31
• [Presentation] 肝細胞癌に対する分子治療の基礎的検討 (2009)
  • Author(s): 藤元治朗
  • Organizer: (ワークショップ)第109回日本外科学会定期学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2009-04-02
• [Presentation] 肝再生制御因子としての肝内門脈血流動態の解析と肝内メカニカルストレス受容体の検索 (2009)
  • Author(s): 飯室勇二, 宇山直樹, 斉藤慎一, 麻野泰包, 杉本貴昭, 岡田敏弘, 平野公通, 黒田暢一, 山中潤一, 藤元治朗
  • Organizer: 第109回日本外科学会定期学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2009-04-02
• [Presentation] 肝細胞癌に対する遺伝子治療-臨床応用に向けての問題点 (2009)
  • Author(s): 平野公通, 山中潤一, 飯室勇二, 黒田暢一, 岡田敏弘, 斉藤慎一, 杉本貴昭, 麻野泰包, 吉田康彦, 鈴村和大, 藤元治朗
  • Organizer: 第109回日本外科学会定期学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2009-04-01
• [Book] 消化器外科学レビュー2011-最新主要文献と解説-第1版(肝胆膵の画像診断) (2011)
  • Author(s): 大橋浩一郎, 藤元治朗, 渡邊昌彦, 國土典宏, 土岐祐一郎
  • Publisher: 総合医学社
• [Book] 総胆管輪状狭窄症(井廻道夫編)肝・胆道系症候群-その他の肝・胆道系疾患を含めて- (2011)
  • Author(s): 飯室勇二
  • Publisher: 日本臨牀社
• [Book] 疾病と検査 (2010)
  • Author(s): 岡田敏弘, 藤元治朗, 松田暉, 荻原俊男, 難波光義, 鈴木久美, 林直子
  • Publisher: 南江堂