Development of a novel small-molecule compounds targeting cancer stem cells derived from malignant glioma

• Project/Area Number: 24501362
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Clinical oncology
• Research Institution: Shizuoka Cancer Center Research Institute
• Principal Investigator: ASHIZAWA Tadashi 静岡県立静岡がんセンター(研究所), その他部局等, その他 (10443441)
• Co-Investigator(Kenkyū-buntansha): AKIYAMA Yasuto 静岡県立静岡がんセンター研究所 (70222552) ; ANDO Takayuki 静岡県環境衛生科学研究所 (40402226) ; 小郷 尚久 静岡県立大学, 薬学研究科(研究院), 講師 (20501307)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); 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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: がん幹細胞治療薬 / 国際情報交換

Outline of Final Research Achievements

Despite of an intensive therapy, the prognosis of malignant gliomas is still poor, and average overall survival is only about a year. Therefore, the development of new drugs against gliomas has been required. In recent years, the novel therapeutic regimens against cancer stem cells have been investigated. In the current study, We established a small-molecule compound library screening system consisting of in silico study and in vitro proliferation assay using glioma patients-derived stem cell lines in a collaboration with Shizuoka Institute of Environment and Hygiene. So far we found that five promising compounds which have potent inhibitory activity on stem cell proliferation, and even a few compounds showed anti-stem cell tumor activity in vivo. In the future, through preclinical safety and drug delivery study of identified compounds, we are planning to pursue the possibility of a new therapeutic agent against glioma stem cell.

Research Products

• [Journal Article] Effect of the STAT3 inhibitor STX-0119 on the proliferation of temozolomide-resistant glioblastoma cell line (2014)
  • Author(s): Ashizawa T, Akiyama Y, Miyata H, Iizuka A, Komiyama M, Kume A, Omiya M, Sugino T, Asai A, Hayashi N, Mitsuya K, Nakasu Y, Yamaguchi K
  • Journal Title: Int. J. Oncology Volume: 45 Pages: 411-418
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] YKL-40 downregulation is a key factor to overcome temozolomide resistance in a glioblastoma cell line. (2014)
  • Author(s): Akiyama Y, Ashizawa T, Komiyama M, Miyata H, Oshita C, Omiya M, Iizuka A, Kume A, Sugino T, Hayashi N, Mitsuya K, Nakasu Y, Yamaguchi K.
  • Journal Title: Oncol Rep Volume: 32 (1) Issue: 1 Pages: 159-166
  • DOI: 10.3892/or.2014.3195
  • Peer Reviewed
• [Journal Article] Novel cancer-testis antigen expression on glioma cell lines derived from high-grade glioma patients. (2014)
  • Author(s): Akiyama Y, Komiyama M, Miyata H, Yagoto M, Ashizawa T, Iizuka A, Oshita C, Kume A, Nogami M, Ito I, Watanabe R, Sugino T, Mitsuya K, Hayashi N, Nakasu Y, Yamaguchi K.
  • Journal Title: Oncol Rep. Volume: 31 Issue: 4 Pages: 1683-1690
  • DOI: 10.3892/or.2014.3049
  • Peer Reviewed / Open Access
• [Journal Article] Anti-vascular endothelial growth factor receptor (VEGFR) 2 autoantibody identification in glioblastoma patient using single B cell-based antibody gene cloning (2014)
  • Author(s): Iizuka A, Komiyama M, Oshita C, Kume A, Ashizawa T, Mitsuya K, Hayashi N, Nakasu Y, Yamaguchi K and Akiyama Y
  • Journal Title: Immunol Lett. Volume: 159 Pages: 15-22
  • Peer Reviewed
• [Journal Article] Effect of the STAT3 inhibitor STX-0119 on the proliferation of cancer stem-like cells derived from recurrent glioblastoma (2013)
  • Author(s): Tadashi Ashizawa, Haruo Miyata, Akira Iizuka, Masaru Komiyama, Chie Oshita, Akiko Kume, Masahiro Nogami, Mika Yagoto, Ichiro Ito, Takuma Oishi, Reiko Watanabe, Koichi Mitsuya, Kenji Matsuno, Toshio Furuya, Tadashi Okawara, Masami Otsuka, Naohisa Ogo, Akira Asai, Yoko Nakasu, Ken Yamaguchi Yasuto Akiyama
  • Journal Title: International Journal of Oncology Volume: 43 Issue: 1 Pages: 219-227
  • DOI: 10.3892/ijo.2013.1916
  • Peer Reviewed
• [Journal Article] α-type-1 polarized dendritic cell-based vaccination in recurrent high-grade glioma: a phase I clinical trial. (2012)
  • Author(s): Akiyama Y, Oshita C, Kume A, Iizuka A, Miyata H, Komiyama M, Ashizawa T, Yagoto M, Abe Y, Mitsuya K, Watanabe R, Sugino T, Yamaguchi K, Nakasu Y.
  • Journal Title: BMC Cancer Volume: 27;12 Issue: 1 Pages: 623-623
  • DOI: 10.1186/1471-2407-12-623
  • Peer Reviewed
• [Journal Article] Identification of novel MAGE-A6- and MAGE-A12-derived HLA-A24-restricted cytotoxic T lymphocyte epitopes using an in silico peptide-docking assay (2012)
  • Author(s): Akiyama Y, Komiyama M, Nakamura Y, Iizuka A, Oshita C, Kume A, Nogami M, Miyata H, Ashizawa T, Yoshikawa S, Kiyohara Y and Yamaguchi K
  • Journal Title: Cancer Immunol Immunother Volume: 61 Issue: 12 Pages: 2311-9
  • DOI: 10.1007/s00262-012-1298-1
  • Peer Reviewed
• [Journal Article] Dendritic cell-based vaccination in metastatic melanoma patients: phase II clinical trial (2012)
  • Author(s): Oshita C, Takikawa M, Kume A, Miyata H, Ashizawa T, Iizuka A, Kiyohara Y, Yoshikawa S, Tanosaki R, Yamazaki N, Yamamoto A, Takesako K, Yamaguchi K and Akiyama Y
  • Journal Title: Oncol Rep Volume: 28 Issue: 4 Pages: 1131-8
  • DOI: 10.3892/or.2012.1956
  • Peer Reviewed
• [Journal Article] Identification of novel kynurenine production-inhibiting benzenesulfonamide derivatives in cancer cells (2012)
  • Author(s): Nakano S, Takai K, Isaka Y, Takahashi S, Unno Y, Ogo N, Matsuno K, Takikawa O, Asai A.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 419 Issue: 3 Pages: 556-561
  • DOI: 10.1016/j.bbrc.2012.02.059
  • Peer Reviewed
• [Presentation] テモゾロミド耐性神経膠芽腫細胞に対するSTAT3阻害剤STX-0119のin vitro及びin vivo抗腫瘍効果 (2014)
  • Author(s): 芦澤 忠、飯塚 明、小宮山 勝、浅井 章良、山口 建、秋山 靖人
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 神経膠芽腫患者由来のがん性幹細胞の増殖に及ぼすSTAT3阻害剤STX-0119の効果 (2013)
  • Author(s): 芦澤 忠、飯塚 明、小宮山 優、浅井章良、山口 建、秋山靖人
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 悪性グリオーマ患者より樹立したグリオーマ初代培養細胞株での腫瘍抗原の発現
  • Author(s): 小宮山 優、飯塚 明、芦沢 忠、久米 亜希子、三矢 幸一、中洲 庸子、山口 建、秋山 靖人
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌