An establishment of new tumor dormancy therapy based on regulation of radical scavenger

• Project/Area Number: 23591967
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Oita University
• Principal Investigator: INOMATA MASAFUMI 大分大学, 医学部, 准教授 (60315330)
• Co-Investigator(Kenkyū-buntansha): KITANO Seigou 大分大学, 法人本部, 学長 (90169871) ; MORIYAMA Masatsugu 大分大学, 医学部, 教授 (90239707) ; NOGUCHI Takayuki 大分大学, 医学部, 病院長 (90156183) ; ETOH Tsuyoshi 大分大学, 医学部, 講師 (00404369) ; HIRATSUKA Takahiro 大分大学, 医学部, 医員 (20600886) ; 萩原 聡 大分大学, 医学部, 講師 (50527661) ; 緒方 一美 大分大学, 医学部, 研究員 (70596048)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 小腸大腸肛門外科学 / 腫瘍学 / 抗酸化剤 / オートファジー / 腫瘍増殖 / 腹膜播種 / アポトーシス / 胃癌

Research Abstract

We investigated whether new antioxidants, alfa-lipoic acid (ALA) delivertives and vitamin E delivertives elicits its antiproliferative effects in vivo and in vitro by inducing apoptosis, autophagy or cell cycle arrest, and we analyzed the expression of proteins related to these phenomena and their phosphorylation in HT-29 human colon cancer cells. These new antioxidants inhibited the proliferation of HT-29 cells through the mechanisms of G2/M cell cycle arrest and autophagy but not that of apoptosis. The newly synthesized ALA derivative may be expected to become a novel cancer therapeutic strategy through its induction of autophagy.

Research Products

• [Journal Article] Bolus injection of newly synthesized vitamin E derivative ETS-GS for the treatment of acute severe ulcerative colitis in a mouse model. New vitamin E derivative for acute severe UC. (2013)
  • Author(s): Hiratsuka T, Inomata M, Hagiwara S, Kono Y, Shiraishi N, Noguchi T, Kitano S.
  • Journal Title: Int J colorectal Dis. Volume: 28(3) Issue: 3 Pages: 305-11
  • DOI: 10.1007/s00384-012-1502-y
  • Peer Reviewed
• [Journal Article] DHL-TauZnNa, a newly synthesized α-lipoic acid derivative, induces autophagy in human colorectal cancer cells (2013)
  • Author(s): Hiratsuka T, Inomata M, Kono Y, Yokoyama S, Shiraishi N, Kitano S.
  • Journal Title: Oncology Report Volume: 29（6） Issue: 6 Pages: 2140-2146
  • DOI: 10.3892/or.2013.2394
  • Peer Reviewed
• [Journal Article] Biological predictors of survival in stage II colorectal cancer (2013)
  • Author(s): Ueda Y, Yasuda K, Inomata M, Shiraishi N, Yokoyama K, Kitano S
  • Journal Title: Morecular and Clinical Oncology Volume: in press
  • Peer Reviewed
• [Journal Article] A newly synthetic vitamin E derivative, E-Ant-S-GS, attenuates lung injury caused by cecal ligation and puncrure-unduced sepsis in rats (2012)
  • Author(s): Kono Y, Inomata M, Hagiwara S, Shiraishi N, Noguchi T, Kitano S
  • Journal Title: Surgery Volume: 151(3) Issue: 3 Pages: 420-426
  • DOI: 10.1016/j.surg.2011.08.003
  • Peer Reviewed
• [Journal Article] Antiproliferative effects of a new α-lipoic acid derivative, DHL-HisZnNa, in HT29 human colon cancer cells in vitro (2012)
  • Author(s): Kono Y, Inomata M, Hagiwara S, Hiratsuka T, Suzuki K, Koga H, Shiraishi N, Noguchi T, Kitano S
  • Journal Title: Expert Opinion On Therapeutic Targets Volume: 16(S1) Issue: sup1 Pages: S103-S109
  • DOI: 10.1517/14728222.2011.640320
  • Peer Reviewed
• [Presentation] 新規αリポ酸誘導体DHLHZnのオキサプラチン誘導末梢神経障害に対する抑制効果;ラットモデルにおける検討 (2012)
  • Author(s): 杉田諭、二日市琢良、草野徹、中嶋健太郎、平塚孝宏、赤木智徳、柴田智隆、上田貴威、當寺ヶ盛学、白下英史、衛藤剛、猪股雅史、野口剛、白石憲男、北野正剛
  • Organizer: 第42回日本創傷治癒学会
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2012-12-03
• [Presentation] デキストラン硫酸ナトリウム大腸炎に対する光線照射の治療効果―炎症性腸疾患に対する光線を用いた新規治療法の開発― (2012)
  • Author(s): 平塚孝宏、井聖子、赤木智徳、當寺ヶ盛学、柴田智隆、白下英史、衛藤剛、猪股雅史、小山淑正、萩原聡、野口隆之、白石憲男、北野正剛
  • Organizer: 第3回癌・炎症とαリポ酸研究会プログラム
  • Place of Presentation: 大分県由布市
• [Presentation] 新規αリポ酸誘導体DHLHZｎのオキサプラチン誘導末梢神経障害に対する抑制効果；ラットモデルにおける検討 (2012)
  • Author(s): 杉田 諭、二日市琢良、草野徹、中嶋健太郎、平塚孝宏、赤木智徳、柴田智隆、上田貴威、當寺ヶ盛学、白下英史、衛藤剛、猪股雅史、野口剛、白石憲男、北野正剛
  • Organizer: 第42回日本創傷治癒学会
  • Place of Presentation: 北海道札幌市
• [Presentation] Antitumor effects of a newα-lipoic acid derivative,DHL-HisZnNa,are mediated by G1 cell cycle arrest in HT29 human colon cancer cells (2011)
  • Author(s): Yohei Kono, Masafumi Inomata, Takahiro Hiratsuka, Takashi Masuda, Teijiro Hirashita, Fumitaka Yoshizumi, Norio shiraishi, Seigo Kitano
  • Organizer: International Surgical Week 2011
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2011-08-29
• [Presentation] The alpha-lipoic acid derivative, sodium zinc dihydrolipoylhistidinate (DHLHZn), reduces chemotherapy- induced alopecia in a rat model (2011)
  • Author(s): Masafumi Inomata, Yohei kono, Takahiro Hiratsuka, Fumitaka Yoshizumi, Norio Shiraishi, Satoshi Hagiwara, Tsuyoshi Noguchi, Seigo Kitano
  • Organizer: International Surgical Week 2011
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2011-08-28
• [Presentation] Effect of A Newα-lipoic Acid Dervative, DHL-HisZn, on Cancer Cell Growth in HT29 Human Colon Cancer Cell (2011)
  • Author(s): Yohei Kono, Masafumi Inomata, Takahiro Hiratsuka, Kazumi Ogata, Seigo Kitano
  • Organizer: OOTR 7th Annual Conference
  • Place of Presentation: 香港
  • Year and Date: 2011-05-13
• [Presentation] The Effectiveness of A New Alpha-lipoic Acid Derivative, Sodium Zinc Dihydrolipoylhistidenate (DHLHZn), in Preventing Chemotherapy-induced Alopecia (2011)
  • Author(s): Masafumi Inomata, Yohei Kono, Takahiro Hiratsuka, Kazumi Ogata, Seigo Kitano
  • Organizer: OOTR 7th Annual Conference
  • Place of Presentation: 香港
  • Year and Date: 2011-05-13
• [Presentation] Antiproliferative Effect of Newly Synthetic Antioxidant,αLipoic Acid Derivatives (2011)
  • Author(s): Takahiro Hiratsuka, Masafumi Inomata, Yohei Kono, Kazumi Ogata, Seigo Kitano
  • Organizer: OOTR 7th Annual Conference
  • Place of Presentation: 香港
  • Year and Date: 2011-05-13
• [Presentation] Effect of A New α-lipoic Acid Dervative, DHL-HisZn, on Cancer Cell Growth in HT29 Human Colon Cancer Cell (2011)
  • Author(s): Yohei Kono, Masafumi Inomata, Takahiro Hiratuka, Kazumi Ogata, Seigo Kitano
  • Organizer: OOTR 7th Annual Conference
  • Place of Presentation: 香港
• [Presentation] The Effectiveness of A New Alpha-lipoic Acid Derivative, Sodium Zinc Dihydrolipoylhistidenate (DHLHZn), in Preventing Chemotherapy-induced Alopecia (2011)
  • Author(s): Masafumi Inomata, Yohei Kono, Takahiro Hiratsuka, Kazumi Ogata, Seigo Kitano
  • Organizer: OOTR 7th Annual Conference
  • Place of Presentation: 香港
• [Presentation] Antiproliferative Effect of Newly Synthetic Antioxidant, α Lipoic Acid Derivatives (2011)
  • Author(s): Takahiro Hiratsuka, Masafumi Inomata, Yohei Kono, Kazumi Ogata, Seigo Kitano
  • Organizer: OOTR 7th Annual Conference
  • Place of Presentation: 香港
• [Presentation] 新規抗酸化剤αリポ酸誘導体を用いた癌治療法の開発―新たな細胞死Autophagyへの誘導― (2011)
  • Author(s): 平塚孝宏、河野洋平、 杉田諭、草野徹、 中嶋健太郎、赤木智徳、萩原聡、衛藤剛、 安田一弘、猪股雅史、 野口剛、白石憲男、 野口隆之、北野正剛
  • Organizer: 第16回癌と遺伝子大分外科フォーラム
  • Place of Presentation: 大分
• [Presentation] Antitumor effects of a new α-lipoic acid derivative,DHL-HisZnNa,are mediated by G1 cell cycle arrest in HT29 human colon cancer cells (2011)
  • Author(s): Yohei Kono, Masafumi Inomata, Takahiro Hiratuka, Takashi Masuda, Teijiro Hirashita, Fumitaka Yoshizumi, Norio shiraishi, Seigo Kitano
  • Organizer: International Surgical Week 2011
  • Place of Presentation: 横浜
• [Presentation] The alpha-lipoic acid derivative, sodium zinc dihydrolipoylhistidinate (DHLHZn),reduces chemotherapy-induced alopecia in a rat model (2011)
  • Author(s): Masafumi Inomata, Yohei kono, Takahiro Hiratsuka, Fumitaka Yoshizumi, Norio Shiraishi, Satoshi Hagiwara, Tsuyoshi Noguchi, Seigo Kitano
  • Organizer: International Surgical Week 2011
  • Place of Presentation: 横浜
• [Presentation] 抗癌剤誘発脱毛に対するαリポ酸誘導体の軽減効果 (2011)
  • Author(s): 河野洋平, 吉住文孝, 猪股雅史, 北野正剛, 萩原聡, 野口隆之
  • Organizer: 第2回癌・炎症とαリポ酸研究会(招待講演)
  • Place of Presentation: 大分
• [Presentation] 大腸がんに対するαリポ酸誘導体DHLTauZnの抗腫瘍効果の検討 (2011)
  • Author(s): 平塚孝宏, 中嶋健太郎, 河野洋平, 猪股雅史, 白石憲男, 北野正剛
  • Organizer: 第2回癌・炎症とαリポ酸研究会(招待講演)
  • Place of Presentation: 大分
• [Presentation] αリポ酸誘導体（DHLHZn）の癌幹細胞様細胞を介した抗腫瘍効果の検討 (2011)
  • Author(s): 赤木智徳, 三森功士, 石橋正久, 澤田元太, 高橋佑典, 古後龍之介, 西田尚弘, 岩谷岳, 主藤朝也, 田中文明, 柴田浩平, 猪股雅史, 白石憲男, 北野正剛, 萩原聡, 野口隆之, 森正樹
  • Organizer: 第2回癌・炎症とαリポ酸研究会(招待講演)
  • Place of Presentation: 大分