Epigenetic drug discovery for gastrointestinal cancer stem cells

• Project/Area Number: 25670577
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Osaka University
• Principal Investigator: SATOH Taroh 大阪大学, 医学(系)研究科(研究院), 寄附講座教授 (40368303)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 癌 / シグナル伝達 / トランスレーショナルリサーチ / 発現制御 / バイオテクノロジー

Outline of Final Research Achievements

Although histone modification is shown to be an essential factor for normal stem cell maintenance, the involvement of histone modification factors in cancer initiation and progression has been poorly understood. Using gastrointestinal cancer cells, we elucidated the functional roles of the histone demethylase, an essential epigenetic regulator. Knockdown resulted in the suppression of cancer growth in vitro and in vivo. Using this system, the screening allowed the identification of several compounds as candidates. They justify the rationale for studying the effects of the epigenetic factors in gastrointestinal cancer.

Research Products

• [Journal Article] EpCAM-Targeted therapy for human hepatocellular carcinoma. (2014)
  • Author(s): Katsuta E
  • Journal Title: Ann Surg Oncol Volume: 21 Issue: 3 Pages: 1314-1322
  • DOI: 10.3892/or.2013.2952
  • Peer Reviewed
• [Journal Article] Safety and pharmacokinetics of S-1 in a recurrent colon cancer patient with chronic myeloid leukemia treated with dasatinib: A case report. (2014)
  • Author(s): Sueda T., Kudo T., Sakai D., Uemura M., Nishimura J., Hata T., Takemasa I., Mizushima T., Yamamoto H., Ezoe S., Matsumoto K., Doki Y., Mori M., Satoh T.
  • Journal Title: Cancer Chemother Pharmacol. Volume: 74 Issue: 6 Pages: 1321-1324
  • DOI: 10.1007/s00280-014-2620-8
  • Peer Reviewed
• [Journal Article] Incidence and clinical features of drug-induced lung injury in patients with advanced colorectal cancer receiving cetuximab: results of a prospective multicenter registry. (2014)
  • Author(s): Satoh T, Gemma A, Kudoh S, Sakai F, Yamaguchi K, Watanabe T, Ishiguro M, Inoshiri S, Izawa M, Sugihara K, Sakata Y.
  • Journal Title: Jpn J Clin Oncol. Volume: 44(11) Issue: 11 Pages: 1032-9
  • DOI: 10.1093/jjco/hyu128
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Eradication of therapy-resistant cancer cells in gastrointestinal organs. (2013)
  • Author(s): Nishikawa, S., Konno, M., Hamabe, A., Hasegawa, S., Ogawa, H., Kano, Y., Fukusumi, T., Ohta, K., Noguchi, Y., Ozaki, M., Kudo, T., Sakai, D., Haraguchi, N., Satoh, T., Doki, Y., Mori, M., Ishii, H.
  • Journal Title: Mol. Clin. Oncol. Volume: 1 Pages: 15-17
  • Peer Reviewed
• [Journal Article] Adipose-derived mesenchymal stem cells and regenerative medicine. (2013)
  • Author(s): Konno, M., Hamabe, A., Hasegawa, S., Ogawa, H., Fukusumi, T., Nishikawa, S., Ohta, K., Kano, Y., Ozaki, M., Noguchi, Y., Sakai, D., Kudoh, T., Kawamoto, K., Eguchi, H., Satoh, T., Tanemura, M., Nagano, H., Doki, Y., Mori, M., Ishii, H.
  • Journal Title: Dev. Growth Differ. Volume: 55 Issue: 3 Pages: 309-318
  • DOI: 10.1111/dgd.12049
  • Peer Reviewed
• [Journal Article] Aldehyde dehydrogenase high gastric cancer stem cells are resistant to chemotherapy. (2013)
  • Author(s): Nishikawa, S., Konno, M., Hamabe, A., Hasegawa, S., Kano, Y., Ohta, K., Fukusumi, T., Sakai, D., Kudo, T., Haraguchi, N., Satoh, T., Takiguchi, S., Mori, M., Doki,Y., Ishii, H.
  • Journal Title: Int. J. Oncol. Volume: 42 Pages: 1437-1442
  • Peer Reviewed
• [Journal Article] Jumonji/Arid1b (Jarid1b) protein modulates human esophageal cancer cell growth. (2013)
  • Author(s): Kano, Y., Konno, M., Ohta, K., Haraguchi, N., Nishikawa, S., Kagawa, Y., Hamabe, A., Hasegawa, S., Ogawa, H., Fukusumi, T., Noguchi, Y., Ozaki, M., Kudo, T., Sakai, D., Satoh, T., Ishii, M., Mizohata, E., Inoue, T., Mori, M., Doki, Y., Ishii, H.
  • Journal Title: Mol. Clin. Oncol. Volume: 1 Pages: 753-757
  • Peer Reviewed
• [Journal Article] Depletion of Jarid1b induces cellular senescence in human colorectal cancer. (2013)
  • Author(s): Ohta, K., Haraguchi, N., Kano, Y., Kagawa, Y., Konno, M., Nishikawa, S., Hamabe, A., Hasegawa, S., Ogawa, H., Fukusumi, T., Uemura, M., Nishimura, J., Hata, T., Takemasa, I., Nishimura, T., Noguchi, Y., Ozaki, M., Kudo, T., Sakai, D., Satoh, T., Fukami, M., Ishii, M., Yamamoto, H., Doki, Y., Mori, M., Ishii, H.
  • Journal Title: Intern. J. Oncol. Volume: 42 Issue: 4 Pages: 1212-1218
  • DOI: 10.3892/ijo.2013.1799
  • Peer Reviewed
• [Presentation] A Japanese subgroup analysis of the lapatinib for gastric cancer (TyTAN) study (2013)
  • Author(s): 佐藤 太郎、土井 俊彦、辻 晃仁、小室 泰司、三輪 洋人、仁科 智裕、藤井 博文、向山 亮平、小林 幹朗、大津 敦
  • Organizer: 第１１回日本臨床腫瘍学会学術集会
  • Place of Presentation: 仙台国際センター(宮城県）