Strategy to overcome chemoresistance of cancer stem cells by regulating cancer microenvironment and intracellular redox state

• Project/Area Number: 24591965
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: The Tazuke Kofukai
• Principal Investigator: UEDA Shugo 公益財団法人田附興風会, 医学研究所 第1研究部, 主任研究員 (80372580)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 癌幹細胞 / CD44 / レドックス / 抗癌剤感受性 / 消化器癌 / ガレクチン / 固形癌 / 低酸素 / レチノイン酸 / ガレクチン-7 / 腫瘍幹細胞 / 活性酸素 / 抗癌剤抵抗性

Outline of Final Research Achievements

Gastrointestinal cell lines expressing several amount of CD44, an important marker for cancer stem cell, were investigated. There was no difference in susceptibility of hydrogen peroxide-induced cell death and intracellular reactive oxygen species (ROS) between normoxia and hypoxia in HCT116 and HT-29 that express higher levels of CD44. All-trans retinoic acid, a clinically effective inducer of differentiation in acute promyelocytic leukemia cells, induced cell death by increasing intracellular ROS but had no effect on differentiation in these cell lines.
Expression of galectin-7 was lower in cancer cells than non-cancer tissues in clinical esophageal cancer. The epigenetic regulation of galectin-7 expression is under investigation.

Research Products

• [Journal Article] Long-term quality-of-life comparison of total gastrectomy and proximal gastrectomy by Postgastrectomy Syndrome Assessment Scale (PGSAS-45): a nationwide multi-institutional study (2015)
  • Author(s): Takiguchi N, Takahashi M, Ikeda M, Inagawa S, Ueda S, Nobuoka T, Ota M, Iwasaki Y, Uchida N, Kodera Y, Nakada K.
  • Journal Title: Gastric Cancer Volume: 18 Pages: 407-416
  • DOI: 10.1007/s10120-014-0377-8
  • Peer Reviewed
• [Journal Article] Adoptive Transfer of MAGE-A4 T-cell Receptor Gene-Transduced Lymphocytes in Patients with Recurrent Esophageal Cancer (2015)
  • Author(s): Kageyama S, Ikeda H, Miyahara Y, Imai N, Ishihara M, Saito K, Sugino S, Ueda S, Ishikawa T, Kokura S, Naota H, Ohishi K, Shiraishi T, Inoue N, Tanabe M, Kidokoro T, Yoshioka H, Tomura D, Nukaya I, Mineno J, Takesako K, Katayama N, Shiku H.
  • Journal Title: Clin Cancer Res Volume: 21
  • Peer Reviewed
• [Journal Article] Overcoming regulatory T-cell suppression by a lyophilized preparation of Streptococcus pyogenes. (2013)
  • Author(s): Hirayama M, Nishikawa H, Nagata Y, Tsuji T, Kato T, Kageyama S, Ueda S, Sugiyama D, Hori S, Sakaguchi S, Ritter G, Old LJ, Gnjatic S, and Shiku H
  • Journal Title: Eur J Immunol. Volume: 43 (4) Pages: 989-1000
  • DOI: 10.1002/eji.201242800
  • Peer Reviewed
• [Journal Article] Effects of rikkunshito, a kampo medicine, on quality of life after proximal gastrectomy (2013)
  • Author(s): Gunji S, Ueda S, Yoshida M, Kanai M, Terajima H, Takabayashi A
  • Journal Title: J Surg Res Volume: 185 Pages: 575-580
  • DOI: 10.1016/j.jss.2013.06.010
  • Peer Reviewed
• [Journal Article] Dose-dependent effects of NY-ESO-1 protein vaccine complexed with cholesteryl pullulan (CHP-NY-ESO-1) on immune responses and survival benefits of esophageal cancer patients. (2013)
  • Author(s): Kageyama S, Wada H, Muro K, Niwa Y, Ueda S, Miyata H, Takiguchi S, Sugino SH, Miyahara Y, Ikeda H, Imai N, Sato E, Yamada T, Osako M, Ohnishi M, Harada N, Hishida T, Doki Y, Shiku H
  • Journal Title: J Transl Med Volume: 5;11 Pages: 246-246
  • DOI: 10.1186/1479-5876-11-246
  • Peer Reviewed
• [Journal Article] Adrenal cavernous hemangioma with subclinical Cushing's syndrome: report of a case. (2012)
  • Author(s): Oishi M, Ueda S, Honjo S, Koshiyama H, Yuba Y, Takabayashi A.
  • Journal Title: Surg Today Volume: 42(10) Pages: 973-977
  • DOI: 10.1007/s00595-012-0203-z
  • NAID: 10031032865
  • Peer Reviewed
• [Presentation] Stage III胃癌に対する周術期化学療法の有用性 (2015)
  • Author(s): 上田修吾、松原弘侑、後藤 徹、岩村宣亜、井上善景、吉冨摩美、内田洋一朗、飯田 拓、金澤旭宣、寺嶋宏明
  • Organizer: 第87回日本胃癌学会学術総会
  • Place of Presentation: リーガロイヤルホテル広島他 (広島県広島市)
  • Year and Date: 2015-03-04 – 2015-03-06
• [Presentation] A randomized phase II factorial design trial of CPT-11 versus PTX versus each combination with S-1 in patients with advanced gastric cancer refractory to S-1: Final results of OGSG0701 (2015)
  • Author(s): Kazuhiro Nishikawa, Hiroshi Imamura, Tomono Kawase, Masahiro Gotoh, Yutaka Kimura, Shugo Ueda, Jin Matsuyama, Junji Kawada, Naotoshi Sugimoto, Junya Fujita, Takao Tamura, Norimasa Fukushima, Daisuke Sakai, Toshio Shimokawa, Yukinori Kurokawa, Taroh Satoh, Toshimasa Tsujinaka, Hiroshi Furukawa
  • Organizer: American Society of Clinical Oncology (ASCO) 2015 Gastrointestinal Cancers Symposium
  • Place of Presentation: San Francisco (USA)
  • Year and Date: 2015-01-15 – 2015-01-17
• [Presentation] S-1単独またはS-1/CDDP併用治療抵抗性進行・再発胃癌に対する二次治療のランダム化第Ⅱ相試験(OGSG0701) (2014)
  • Author(s): 上田 修吾、今村 博司、後藤 昌弘、木村 豊、松山 仁、西川 和宏、藤田 淳也、杉本 直俊、黒川 幸典、古河 洋
  • Organizer: 第69回日本消化器外科学会総会
  • Place of Presentation: 郡山市民文化センター他 (福島県郡山市)
  • Year and Date: 2014-07-16 – 2014-07-18
• [Presentation] Randomized phase II study of CPT-11 versus PTX versus each combination chemotherapy with S-1 in patients with advanced gastric cancer refractory to S-1 or S-1 plus CDDP (2014)
  • Author(s): Tomono Kawase, Hiroshi Imamura, Masahiro Gotoh, Yutaka Kimura, Shugo Ueda, Jin Matsuyama, Kazuhiro Nishikawa, Naotoshi Sugimoto, Junya Fujita, Takao Tamura, Norimasa Fukushima, Ryohei Kawabata, Yukinori Kurokawa, Toshio Shimokawa, Daisuke Sakai, Toshimasa Tsujinaka, Hiroshi Furukawa
  • Organizer: American Society of Clinical Oncology (ASCO) 2014 50th Annual Meeting
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2014-05-30 – 2014-06-03
• [Presentation] Induction chemotherapy followed by surgery for stage IV gastric cancer (2014)
  • Author(s): Shugo Ueda, Yoshikage Inoue, Mami Yoshitomi, Yoichiro Uchida, Taku Iida, Akiyoshi Kanazawa, Hiroaki Terajima
  • Organizer: 49th Congress of the European Society for Surgical Research
  • Place of Presentation: Budapest (Hungary)
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] Adoptive transfer of wild-type TCR gene transduced T lymphocytes targeting MAGE-A4 antigen to patients with refractory easophageal cancer (2014)
  • Author(s): Kageyama S, Ikeda H, Imai N, Ishihara M, Miyahara Y, Ueda S, Ishikawa T, Naota H, Ohishi K, Shiraishi T, Inoue N, Tanabe M, Kidokoro T, Yoshioka H, Tomura D, Nukaya I, Mineno J, Takesako K, Katayama N, Shiku H
  • Organizer: 105th American Association for Cancer Research (AACR) Annual Meeting 2014
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2014-04-05 – 2014-04-09
• [Presentation] 進行胃癌に対するS-1+シスプラチン療法の抗腫瘍効果予測のためのバイオマーカー探索 (2013)
  • Author(s): 上田修吾、後藤 徹、岩村宣亜、戸田 怜、川本浩史、井上善景、吉冨摩美、内田洋一朗、飯田 拓、寺嶋宏明
  • Organizer: 第51回日本癌治療学会
  • Place of Presentation: 京都市 国立京都国際会館
• [Presentation] 食道癌におけるgalectin-7発現 (2012)
  • Author(s): 上田修吾
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌市中央区 ホテルロイトン札幌他