小児固形悪性腫瘍の非侵襲的診断と新規治療開発のためのトランスレーショナルリサーチ

2015 Fiscal Year Annual Research Report

• Project/Area Number: 25253095
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: 細井 創 京都府立医科大学, 医学(系)研究科(研究院), 教授 (20238744)
• Co-Investigator(Kenkyū-buntansha): 中川原 章 地方独立行政法人佐賀県医療センター好生館(医学研究所), その他部局等, その他 (50117181) ; 檜山 英三 広島大学, 学内共同利用施設等, 教授 (00218744) ; 瀧本 哲也 国立研究開発法人国立成育医療研究センター, その他部局等, その他 (40393178) ; 田尻 達郎 京都府立医科大学, 医学(系)研究科(研究院), 教授 (80304806) ; 家原 知子 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (20285266) ; 北條 洋 福島県立医科大学, 公私立大学の部局等, 教授 (90209213) ; 滝田 順子 東京大学, 医学部附属病院, 准教授 (00359621) ; 木下 義晶 九州大学, 大学病院, 准教授 (80345529) ; 大喜多 肇 慶應義塾大学, 医学部, 准教授 (50317260) ; 菱木 知郎 千葉県がんセンター(研究所), その他部局等, その他 (00375776) ; 土屋 邦彦 京都府立医科大学, 医学(系)研究科(研究院), 助教 (90381938) ; 宮地 充 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40584983)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 小児がん / 神経芽腫 / 横紋筋肉腫 / liquid biopsy / 免疫療法

Outline of Annual Research Achievements

小児がんについての、わが国の先端的基礎研究を結集・統合し、次期臨床試験に実応用できるトランスレーショナルリサーチを推進することを目的として、本研究事業を行った。その結果、①血液から抽出できる小児がんの新規バイオマーカーを探索し、治療層別化へ応用可能なマーカーを抽出することが出来た、②低・中間リスク小児がん患者に対する副作用軽減を目指し、間葉系幹細胞を用いたドラッグデリバリーシステムの可能性について明らかにすることが出来た。③高リスク小児がん患者に対し、ペプチドワクチン、PD-1阻害剤、NKT細胞療法を用いた新規免疫療法の可能性について明らかにした。④超高リスク小児がんに対し、次世代ゲノム解析技術を用いた詳細な分子病態を解析し、新規層別化、新規分子標的の候補となるゲノム以上について明らかにした。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Antibody-dependent cellular cytotoxicity toward neuroblastoma enhanced by activated invariant natural killer T cells. (2016)
  • Author(s): Mise N, Takami M, Suzuki A, Kamata T, Harada K, Hishiki T, Saito T, Terui K, Mitsunaga T, Nakata M, Ikeuchi T, Nakayama T, Yoshida H, Motohashi S.
  • Journal Title: Cancer Sci Volume: 107 Pages: 233-241
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Molecular genetic and cytogenetic analysis of a primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma (2016)
  • Author(s): Kato K, Oh Y, Takita J, Gunji Y, Kobayashi C, Yoshimi A, Nakao T, Noma M, Koike K, Morimoto A, Iijima S, Hojo H, Tsuchida M.
  • Journal Title: Int J Hematol Volume: 103 Pages: 196-201
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Oncolytic viral therapy for neuroblastoma cells with Sindbis virus AR339 strain. (2015)
  • Author(s): Takenouchi A, Saito K, Saito E, Saito T, Hishiki T, Matsunaga T, Isegawa N, Yoshida H, Ohnuma N, Shirasawa H. Oncolytic viral therapy for neuroblastoma cells with Sindbis virus AR339 strain.
  • Journal Title: Pediatr Surg Int. Volume: 31 Pages: 1151-1159
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Radioguided localization of neuroblastomas in laparoscopic surgery using (123)I- radiolabeled metaiodobenzylguanidine (2015)
  • Author(s): Hishiki T, Saito T, Terui K, Mitsunaga T, Nakata M, Hayashi H, Yoshida H.
  • Journal Title: Pediatr Blood Cancer. Volume: 62 Pages: 1297-1299
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Glypican 3 Expression in Pediatric Malignant Solid Tumors. (2015)
  • Author(s): Kinoshita Y, Tanaka S, Souzaki R, Miyoshi K, Kohashi K, Oda Y, Nakatsura T, Taguchi T
  • Journal Title: Eur J Pediatr Surg Volume: 25 Pages: 138-144
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Circulating free DNA as non-invasive diagnostic biomarker for childhood solid tumors. (2015)
  • Author(s): Kurihara S, Ueda Y, Onitake Y, Sueda T, Ohta E, Morihara N, Hirano S, Irisuna F, Hiyama E
  • Journal Title: Journal of Pediatric Surgery. Volume: 50 Pages: 2094-2097
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Direct Lipido-Metabolomics of Single Floating Cells for Analysis of Circulating Tumor Cells by Live Single-cell Mass Spectrometry. (2015)
  • Author(s): Hiyama E, Ali A, Amer S, Harada T, Shimamoto K, Furushima R, Abouleila Y, Emara S, Masujima T.
  • Journal Title: Analytical Sciences. Volume: 1 Pages: 1215-1217
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Integrated genetic and epigenetic analysis defines novel molecular subgroups in rhabdomyosarcoma. (2015)
  • Author(s): 34.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: 3 Pages: 7557
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Comparison of chemotherapeutic agents as a myeloablative conditioning with TBI for pediatric ALL: a study from the pediatric ALL working group of the JSHCT. (2015)
  • Author(s): Kato M, Ishida H, Koh K, Inagaki J, Kato K, Goto H, Kaneko T, Cho Y, Hashii Y, Kurosawa H, Takita J, Hamamoto K, Inoue M, Sawada A, Suzuki R, Kato K.
  • Journal Title: Pediatr Blood Cancer. Volume: 62 Pages: 1844-1850
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Neonatal acute megakaryoblastic leukemia mimicking congenital neuroblastoma (2015)
  • Author(s): 37.Kawasaki Y, Makimoto M, Nomura K, Hoshino A, Hamashima T, Hiwatari M, Nakazawa A, Takita J, Yoshida T, Kanegane H.
  • Journal Title: Clin Case Rep Volume: 3 Pages: 145-149
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Upregulation of MAPK negative feedback regulators and RET in mutant ALK neuroblastoma: implications for targeted treatment. (2015)
  • Author(s): Lambertz I, Kumps C, Claeys S, Lindner S, Beckers A, Janssens E, Carter DR, Cazes A, Cheung BB, De Mariano M, De Bondt A, De Brouwer S, Delattre O, Gibbons J, Janoueix-Lerosey I, Laureys G, Liang C, Marshall GM, Porcu M, Takita J, et al.
  • Journal Title: Clin Cancer Res Volume: 21 Pages: 3327-3339
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Aggressive transformation of anaplastic large cell lymphoma with increased number of ALK-translocated chromosomes. (2015)
  • Author(s): Hoshino A, Nomura K, Hamashima T, Isobe T, Seki M, Hiwatari M, Yoshida K, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Ogawa S, Takita J, Kanegane H.
  • Journal Title: Int J Hematol. Volume: 101 Pages: 198-202
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Allogeneic haematopoietic stem cell transplantation for infant acute lymphoblastic leukaemia with KMT2A (MLL) rearrangements: a retrospective study from the paediatric acute lymphoblastic leukaemia working group of the Japan Society for Haematopoietic Cell Transplantation. (2015)
  • Author(s): Kato M, Hasegawa D, Koh K, Kato K, Takita J, Inagaki J, Yabe H, Goto H, Adachi S, Hayakawa A, Takeshita Y, Sawada A, Atsuta Y, Kato K.
  • Journal Title: Br J Haematol. Volume: 168 Pages: 564-570
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Early use of allogeneic hematopoietic stem cell transplantation for infants with MLL gene-rearrangement-positive acute lymphoblastic leukemia. (2015)
  • Author(s): Koh K, Tomizawa D, Moriya Saito A, Watanabe T, Miyamura T, Hirayama M, Takahashi Y, Ogawa A, Kato K, Sugita K, Sato T, Deguchi T, Hayashi Y, Takita J, Takeshita Y, Tsurusawa M, Horibe K, Mizutani S, Ishii E
  • Journal Title: Leukemia Volume: 29 Pages: 290-296
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Identification of a homozygous JAK3 V674A mutation caused by acquired uniparental disomy in a relapsed early T-cell precursor ALL patient (2015)
  • Author(s): 42.Kawashima-Goto S, Imamura T, Seki M, Kato M, Yoshida K, Sugimoto A, Kaneda D, Fujiki A, Miyachi M, Nakatani T, Osone S, Ishida H, Taki T, Takita J, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Ogawa S, Hosoi H
  • Journal Title: Int J Hematol. Volume: 101 Pages: 411-416
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Validity of image-defined risk factors in localized neuroblastoma: A report from two centers in Western Japan. (2015)
  • Author(s): Fumino S, Kimura K, Iehara T, Nishimura M, Nakamura S, Souzaki R, Nishie A, Taguchi T, Hosoi H, Tajiri T
  • Journal Title: J Pediatr Surg Volume: 50 Pages: 2012-2106
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant