Development of treatment strategy for rhabdomyosarcoma based on control of cancer stem cell proliferation

• Project/Area Number: 26670766
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatric surgery
• Research Institution: Keio University
• Principal Investigator: Kuroda Tatsuo 慶應義塾大学, 医学部, 教授 (60170130)
• Co-Investigator(Kenkyū-buntansha): HIYAMA Eisou 広島大学, 学内共同利用施設等, 教授 (00218744) ; TAKITA Junko 東京大学, 医学部附属病院, 准教授 (00359621) ; IKEDA Hitoshi 獨協医科大学, 医学部, 教授 (10326928) ; FUCHIMOTO Yasushi 慶應義塾大学, 医学部, 講師(非常勤) (40219077) ; MORIKAWA Yasuhide 慶應義塾大学, 医学部, 講師(非常勤) (90124958)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 小児外科学 / 小児腫瘍学 / 小児がん / 腫瘍幹細胞 / 横紋筋肉腫

Outline of Final Research Achievements

Either PAX3-FKHR or PAX7-FKHR gene was positive in 76% of alveolar type rhabomyosarcoma, whereas never detected in embryonal type tumor. Survival rate was significantly lower in alveolar type cases with positive chimeric gene (44.2±7.3％) compared to those with negative chimeric gene (75.0±12.5％) , which was similar to that of embryonal cases (76.3±4.9％) . ALL mixed type cases were alive regardless of chimeric gene positivity.
CD44, a stem cell marker, was positive in all rhabdomyosarcoma cell line examined, whereas, CD44v was negative in all the cell lines. Positivity rate of CD133 was 25% in RD cell line, whereas, less than 2% in other cell lines such as Rh30, KYM-1, RMS-YM. However, CD133 positive cells are chemotherapy resistant, and rapidly formed tumor after administrated in mice. Novel treatment strategy may be stratified according to the genotype and expression of the stem cell makers in rhabdomyosarcoma.

Research Products

• [Journal Article] Secondary cancers after a childhood cancer diagnosis: a nationwide hospital-based retrospective cohort study in Japan (2015)
  • Author(s): Ishida Y, Qiu D, Maeda M, Fujimoto J, Kigasawa H, Kobayashi R, Sato M, Okamura J, Yoshinaga S, Rikiishi T, Shichino H, Kiyotani C, Kudo K, Asami K, Hori H, Kawaguchi H, Inada H, Adachi S, Manabe A, Kuroda T
  • Journal Title: Int J Clin Oncol Volume: - Issue: 3 Pages: 506-516
  • DOI: 10.1007/s10147-015-0927-z
  • Peer Reviewed
• [Journal Article] Integrated genetic and epigenetic analysis defines novel molecular subgroups in rhabdomyosarcoma. (2015)
  • Author(s): Seki M, Nishimura R, Yoshida K, Shimamura T, Shiraishi Y, Sato Y, Kato M, Chiba K, Tanaka H, Hoshino N, Nagae G, Shiozawa Y, Okuno Y, Hosoi H, Tanaka Y, Okita H, Miyachi M, Souzaki R, Taguchi T, Koh K, Hanada R, Kato K, Nomura Y, Akiyama M, Oka A, Igarashi T, Miyano S, Aburatani H, Hayashi Y, Ogawa S, Takita J.
  • Journal Title: Nat Commun. Volume: 6 Issue: 1 Pages: 7557-7557
  • DOI: 10.1038/ncomms8557
  • NAID: 120005623266
  • Peer Reviewed / Open Access
• [Journal Article] Application of nuclear medicine to achieve less invasive surgery for malignant solid tumors in children (2014)
  • Author(s): Hotta R, Fujimura T, Shimojima N, Nakahara T, Fuchimoto Y, Hoshino K, Morikawa Y, Matsufuji H, Kuroda T.
  • Journal Title: Pediatr Int. Volume: 56 Issue: 6 Pages: 896-901
  • DOI: 10.1111/ped.12368
  • Peer Reviewed
• [Journal Article] 当院での進行・再発神経芽腫に対する外科的治療の検討 (2014)
  • Author(s): 高橋 信博(慶応義塾大学 医学部小児外科), 富田 紘史, 石濱 秀雄, 藤村 匠, 加藤 源俊, 藤野 明浩, 星野 健, 嶋田 博之, 高橋 孝雄, 黒田 達夫
  • Journal Title: 日本小児外科学会雑誌 Volume: 50 Pages: 645-645
  • Peer Reviewed
• [Journal Article] 小児がん診断後の二次がん発症に関する疫学研究 15病院における後ろ向きコホート(Secondary cancers after cancer diagnosis in childhood: A hospital-based retrospective cohort study in Japan) (2014)
  • Author(s): 石田 也寸志(愛媛県立中央病院 小児医療センター), 邱 冬梅, 前田 美穂, 藤本 純一郎, 気賀沢 寿人, 小林 良二, 佐藤 真穂, 岡村 純, 吉永 信治, 力石 健, 七野 浩之, 清谷 知賀子, 工藤 寿子, 浅見 恵子, 堀 浩樹, 川口 浩史, 稲田 浩子, 足立 壮一, 真部 淳, 黒田 達夫
  • Journal Title: 日本小児血液・がん学会雑誌 Volume: 51 Pages: 261-261
  • Peer Reviewed
• [Journal Article] 横紋筋肉腫治療後26年で発症した放射線誘発性軟骨肉腫の1例 (2014)
  • Author(s): 宇高 徹(慶応義塾大学 医学部整形外科), 須佐 美知郎, 中山 ロバート, 渡部 逸央, 堀内 圭輔, 星野 健, 黒田 達夫, 佐々木 文, 向井 万起男, 戸山 芳昭, 森岡 秀夫
  • Journal Title: 臨床整形外科 Volume: 49 Pages: 723-728
  • Peer Reviewed
• [Journal Article] 小児悪性固形腫瘍の臨床研究グループの現状と今後 日本横紋筋肉腫研究グループ(JRSG)の展開と臨床試験の今後の課題 (2014)
  • Author(s): 黒田 達夫(慶応義塾大学 小児外科), 森川 康英, 池田 均, 大植 孝治, 木下 義晶, 仁尾 正記, 檜山 英三
  • Journal Title: 日本小児外科学会雑誌 Volume: 50 Pages: 396-396
  • Peer Reviewed