Anti-tumor effects of EGFR inhibitors via cell differentiation on esophageal cancer cells

• Project/Area Number: 25460926
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto University
• Principal Investigator: Ohashi Shinya 京都大学, 医学(系)研究科(研究院), 助教 (20435556)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); 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)
• Keywords: 食道癌 / EGFR阻害剤 / 分化誘導 / EGFRシグナル阻害 / 上皮系癌細胞 / 間葉系癌細胞 / 治療抵抗性 / 食道扁平上皮癌 / 細胞分化 / EGFR阻害 / 抗がん剤耐性

Outline of Final Research Achievements

Cytotoxic and anti-tumor effects of EGFR inhibitors on human (esophageal squamous cell carcinoma) ESCC cells (TE1, TE5, TE8, TE11R, and HCE4) as well as transformed esophageal epithelial cells (T-Epi, T-Mes) were investigated. EGFR inhibitors showed cytotoxic and anti-tumor effect on epithelial-like cells (TE1, TE5, TE11, TE11R, and T-Epi) in accompany with increased expression of cell differentiation markers, but not on mesenchymal-like cells (TE8, HCE4, and T-Mes). EGFR inhibitors are considered to be effective for epithelial-like ESCC cells through the induction of cell differentiation.

Research Products

• [Journal Article] ALDH2 modulates autophagy flux to regulate acetaldehyde-mediated toxicity thresfolds. (2016)
  • Author(s): Tanaka K, Whelan KA, Chandramouleeswaran PM, Kagawa S, Rustgi SL, Noguchi C, Guha M, Srinvasan S, Amanuma Y, Ohashi S, Muto M, Klein-Szanto AJ, Noguchi E, Avadhani NG, Nakagawa H.
  • Journal Title: Am J Cancer Res Volume: in press
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Novel EGFR-targeted strategy with hybrid peptide against oesophageal squamous cell carcinoma. (2016)
  • Author(s): Kikuchi, O, Ohashi, S, Horibe, T, Kohno, M, Nakai, Y, Miyamoto, S, Chiba, T, Muto, M and Kawakami, K
  • Journal Title: Scientific reports Volume: 6 Issue: 1 Pages: 22452-22452
  • DOI: 10.1038/srep22452
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Recent Advances from Basic and Clinical Studies of Esophageal Squamous Cell Carcinoma. (2015)
  • Author(s): Ohashi S, Miyamoto S, Kikuchi O, Goto T, Amanuma Y, Muto M.
  • Journal Title: Gastroenterology Volume: 149 Issue: 7 Pages: 1700-1715
  • DOI: 10.1053/j.gastro.2015.08.054
  • NAID: 120005848418
  • Peer Reviewed / Open Access
• [Journal Article] Protective role of ALDH2 against acetaldehyde-derived DNA damage in oesophageal squamous epithelium (2015)
  • Author(s): Amanuma Y, Ohashi S, Itatani Y, Tsurumaki M, Matsuda S, Kikuchi1 O, Naka Y, Miyamoto S, Oyama T, Kawamoto T, Whelan KA, Nakagawa H, Chiba T, Matsuda T, Muto M
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 14142-14142
  • DOI: 10.1038/srep14142
  • NAID: 120005678158
  • Peer Reviewed / Open Access
• [Journal Article] Novel 5-fluorouracil-resistant human esophageal squamous cell carcinoma cells with dihydropyrimidine dehydrogenase overexpression. (2015)
  • Author(s): Kikuchi O, Ohashi S, Nakai Y, Nakagawa S, Matsuoka K, Kobunai T, Takechi T, Amanuma Y, Yoshioka M, Ida T, Yamamoto Y, Okuno Y, Miyamoto S, Nakagawa H, Matsubara K, Chiba T, Muto M.
  • Journal Title: Am J Cancer Res Volume: 5 Pages: 2431-2440
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] PDTのメカニズム・・・とくに食道癌細胞株におけるアポトーシスについて (2015)
  • Author(s): 大橋真也、武藤学
  • Journal Title: G.I.Research Volume: 23 Pages: 297-302
• [Journal Article] Cellular senescence checkpoint function determines different Notch1-dependent oncogenic and tumor-suppressor activities. (2014)
  • Author(s): Shingo Kagawa, Mitsuteru Natsuizaka, KA Whelan, N Facompre, Seiji Naganuma, Shinya Ohashi, Hiroaki Kinugasa, AM Egloff, D Basu, PA Gimotty, AJ Klein-Szanto, AJ Bass, KK Wong, JA Diehl, AK Rustgi, Hiroshi Nakagawa
  • Journal Title: Oncogene Volume: 34巻18号 Issue: 18 Pages: 2347-2359
  • DOI: 10.1038/onc.2014.169
  • Peer Reviewed
• [Journal Article] Impairment of aldehyde dehydrogenase 2 increases accumulation of acetaldehyde-derived DNA damage in the esophagus after ethanol ingestion (2014)
  • Author(s): Yoshiyuki Yukawa, Shinya Ohashi, Yusuke Amanuma, Yukie Nakai, Mihoko tsurumaki, Osamu Kikuchi, Shin'ichi Miyamoto, Tsunehiro Oyama, Toshihiro Kawamoto, Tsutomu Chiba, Tomonari Matsuda, Manabu Muto
  • Journal Title: Am J Cancer Res Volume: 未定
  • Peer Reviewed
• [Presentation] 食道癌化学放射線療法後の局所遺残再発例に対する新規光線力学療法 -基礎研究、臨床研究から薬事承認まで- (2015)
  • Author(s): 大橋真也、堀松高博、武藤学
  • Organizer: 日本消化器病学会近畿支部第103回例会
  • Place of Presentation: 大阪国際交流センター(大阪府、大阪市）
  • Year and Date: 2015-09-26
• [Presentation] 食道癌に対する内視鏡的PDT治療における追加照射の安全性に関する検討 (2015)
  • Author(s): 大橋真也、堀松高博、武藤学
  • Organizer: 第28回日本レーザー医学会関西地方会
  • Place of Presentation: TKPガーデンシティ京都（京都府、京都市）
  • Year and Date: 2015-07-25
• [Presentation] Notch3過剰発現による食道扁平上皮分化誘導は腫瘍増生能及び5-FU抵抗性を抑制する (2015)
  • Author(s): 菊池理、大橋真也、天沼裕介、横山顕礼、宮本心一、松本繁巳、武藤学
  • Organizer: 第69回日本食道学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県、横浜市）
  • Year and Date: 2015-07-02
• [Presentation] EGFR inhibition promotes differentiation of esophageal squmamous cancer cells through Notch signaling pathway (2015)
  • Author(s): Masahiro Yoshioka, Shinya Ohashi, Osamu Kikuchi, Yusuke Amanuma, Tomomi Ida, Yukie Nakai, Hiroshi Nakagawa, Tsutomu Chiba, Manabu Muto
  • Organizer: Digestive Disease Week 2015
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2015-05-16 – 2015-05-19
• [Presentation] EGFR inhibition activates Notch signaling pathway and induces esophageal squamous cancer cell differentiation (2015)
  • Author(s): Masahiro Yoshioka, Shinya Ohashi, Osamu Kikuchi, Yusuke Amanuma, Tomomi Ida, Yukie Nakai, Shin'ichi Miyamoto, Hiroshi Nakagawa, Tsutomu Chiba, Manabu Muto
  • Organizer: GAP 2015 conference
  • Place of Presentation: Houston, USA
  • Year and Date: 2015-04-14 – 2015-04-16
• [Presentation] Potent cytotoxicity of novel photodynamic therapy with talaporfin sodium for fluorouracil-resistant esophageal sqaumous cell carcinoma in vitro. (2013)
  • Author(s): Shinya Ohashi, Osamu Kikuchi, Yusuke Amanuma, Manabu Muto
  • Organizer: National Taiwan University and Kyoto University Symposium 2013
  • Place of Presentation: National Taiwan University, 台湾
• [Presentation] Photodynamic therapy induces apoptosis via reactive oxygen species in fluorouracil-resistant esophageal squamous cell carcinoma cells (2013)
  • Author(s): Shinya Ohashi, Mihoko Tsurumaki, Osamu Kikuchi, Daisuke Kuriyama, Yusuke Amanuma, Yukie Nakai, Takeshi Setoyama, Shin'ichi Miyamoto, Tsutomu Chiba, Manabu Muto
  • Organizer: Digestive Disease Week and the 114th annual meeting of the American Gastroenterological Association
  • Place of Presentation: Orange County Convention Center, Orland, FL, USA
• [Presentation] regulation of chemotherapy resistance through epithelial-mesenchymal transition by Zinc finger E-box-binding proteins ZEB1 in esophageal squamous cell carcinoma (2013)
  • Author(s): Shinya Ohashi, Osamu Kikuchi, Yasumasa Ezoe, manabu Muto
  • Organizer: Global Academic Program 2013 MD Anderson Cancer Center
  • Place of Presentation: MD Anderson Cancer Center, Houston, TX, USA