難治性リンパ管腫に対する分子標的治療と光線力学療法を併用した新規低侵襲治療の開発

2016 Fiscal Year Research-status Report

• Project/Area Number: 16K11351
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: 文野 誠久 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40405254)
• Co-Investigator(Kenkyū-buntansha): 東 真弓 京都府立医科大学, 医学(系)研究科(研究院), 助教 (10380453) ; 古川 泰三 京都府立医科大学, 医学(系)研究科(研究院), 講師 (20515291) ; 田尻 達郎 京都府立医科大学, 医学(系)研究科(研究院), 教授 (80304806)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 小児外科 / リンパ管腫

Outline of Annual Research Achievements

リンパ管腫は，とくに頭頸部発生例では，良性疾患であるにも関わらず，難治性となり，生涯にわたり患者のQOLを著しく損なうことが少なくない．したがって，低侵襲でより効果的な新規治療の開発がこれまでの課題であった．本研究では，5-ALAと発光ダイオードを用いた光線力学療法（PDT）にmTOR阻害剤であるSirolimusを併用する，安全性が高く侵襲性の極めて低いリンパ管腫に対する新規治療法の開発を目的とする．リンパ管腫モデルラットに，Sirolimus投与とPDT併用治療を行い，その効果を組織学的に検討する．さらに既存の治療法と統合して，新たな治療戦略を確立することを最終目標とする．
現在は，、シロリムス誘導体であるエベロリムスを用いて，臨床例においての治療効果を検証しており，４例に投与を行い，症状改善あるいは病変縮小効果が確認された．
今後モデルマウスにて，実証及びPDT実験系の確立を目指す．

Current Status of Research Progress

4: Progress in research has been delayed.

Reason

リンパ管腫モデルラットの開発において，技術的に困難がある．

Strategy for Future Research Activity

シロリムスのリンパ管腫に対する作用機序解析およびモデルマウス作成を行っていく．

Causes of Carryover

リンパ管腫モデルマウス作成に難渋しており，予定していた実験動物や試薬を購入しなかった．また学会発表も予定より少ない．

Expenditure Plan for Carryover Budget

動物実験について進めていく．また，これまでの研究成果について国際学会を含めて学会発表を精力的に行っていく予定である．

Research Products

• [Journal Article] Surgical intervention and perioperative risk factors of retroperitoneal teratomas in children: a single institution experience. (2016)
  • Author(s): Fumino S, Maniwa J, Takeuchi Y, Sakai K, Higashi M, Aoi S, Furukawa T, Kimura O, Tajiri T
  • Journal Title: Pediatr Surg Int Volume: 32 Pages: 661-666
  • DOI: 10.1007/s00383-016-3938-6
  • Peer Reviewed
• [Journal Article] MEK inhibitors as a novel therapy for neuroblastoma: Their in vitro effects and predicting their efficacy. (2016)
  • Author(s): Tanaka T, Higashi M, Kimura K, Wakao J, Fumino S, Iehara T, Hosoi H, Sakai T, Tajiri T
  • Journal Title: J Pediatr Surg Volume: 51 Pages: 2074-2079
  • DOI: 10.1016/j.jpedsurg.2016.09.043
  • Peer Reviewed
• [Presentation] Treatment strategies for different types of lymphangioma. 28-years experience in a single institution. (2016)
  • Author(s): 17)Kimura O, Furukawa T, Fumino S, Aoi S, Tajiri T
  • Organizer: 68th Annual Autum Congress of the Korean Surgical Society,
  • Place of Presentation: Seoul,Korea
  • Year and Date: 2016-11-03 – 2016-11-05
  • Int'l Joint Research
• [Presentation] Retroperitoneal teratomas in children: still challenging for surgeons. (2016)
  • Author(s): Fumino S, Maniwa J, Takeuchi Y, Sakai K, Higashi M, Aoi S, Furukawa T, Kimura O, Tajiri T
  • Organizer: 40th World Congress of the International College of Surgeons
  • Place of Presentation: 京都
  • Year and Date: 2016-10-24 – 2016-10-26
  • Int'l Joint Research
• [Presentation] JNK-STAT3 pathway in neuroblastoma. (2016)
  • Author(s): Higashi M, Sakai K, Fumino S, Aoi S, Furukawa T, Tajiri T
  • Organizer: 40th World Congress of the International College of Surgeons
  • Place of Presentation: 京都
  • Year and Date: 2016-10-24 – 2016-10-26
  • Int'l Joint Research
• [Presentation] Immunohistochemical staining of phosphorylated-ERK as a predictor of therapeutic effects of MEK inhibitors on neuroblastoma. (2016)
  • Author(s): Tanaka T, Higashi M, Wakao J, Kimura K Fumino S, Iehara T, Hosoi H, Sakai T, Tajiri T
  • Organizer: 40th World Congress of the International College of Surgeons,
  • Place of Presentation: 京都
  • Year and Date: 2016-10-24 – 2016-10-26
  • Int'l Joint Research
• [Presentation] Perioperative management and surgical intervention for retroperitoneal teratomas in children. (2016)
  • Author(s): Fumino S, Maniwa J, Takeuchi Y, Sakai K, Higashi M, Aoi S, Furukawa T, Kimura O, Tajiri T
  • Organizer: 48th Congress of the International Society of Paediatric Oncology (SIOP)
  • Place of Presentation: Dublin,Ireland
  • Year and Date: 2016-10-19 – 2016-10-22
  • Int'l Joint Research
• [Presentation] Postoperative bowel management for the patients with anorectal malformation associating spinal lesions: A single institute experience. (2016)
  • Author(s): Aoi S, Furukawa T, Higashi M, Sakai K, Fumino S, Kimura O, Tajiri T
  • Organizer: International Children's Continence Society
  • Place of Presentation: 京都
  • Year and Date: 2016-06-30 – 2016-07-02
  • Int'l Joint Research
• [Presentation] Thoracoscopic resection of ectopic mediastinal parathyroid adenoma utilizing gamma probe and intraoperative PTH monitoring in a child. (2016)
  • Author(s): Furukawa T, Fumino S, Sakai K, Higashi M, Aoi S, Tajiri T
  • Organizer: IPEG’s 25th Annual Congress for Endosurgery in Children
  • Place of Presentation: 福岡
  • Year and Date: 2016-05-26 – 2016-05-26
  • Int'l Joint Research
• [Presentation] MEK inhibitors as a novel therapy for neuroblastoma: Their in vitro effects & predicting their efficacy. (2016)
  • Author(s): Tanaka T, Higashi M, Kimura K, Wakao J, Fumino S, Iehara T, Hosoi H, Sakai T, Tajiri T
  • Organizer: 49th Annual Meeting of the Pacific Association of Pediatric Surgeons (PAPS)
  • Place of Presentation: Kauai,USA
  • Year and Date: 2016-05-17 – 2016-05-21
  • Int'l Joint Research
• [Presentation] Surgical management and perioperative risk factors of retroperitoneal teratomas in children: A single institution experience. (2016)
  • Author(s): Fumino S, Maniwa J, Takeuchi Y, Sakai K, Higashi M, Aoi S, Furukawa T, Kimura O, Tajiri T
  • Organizer: 49th Annual Meeting of the Pacific Association of Pediatric Surgeons (PAPS)
  • Place of Presentation: Kauai,USA
  • Year and Date: 2016-05-17 – 2016-05-21
  • Int'l Joint Research
• [Presentation] A clinical trial of low-dose mTOR inhibitor therapy for the treatment of children with refractory lymphatic anomaly. (2016)
  • Author(s): Furukawa T, Sakai K, Higashi M, Fumino S, Aoi S, Kimura O, Ozeki M, Tajiri T
  • Organizer: 49th Annual Meeting of the Pacific Association of Pediatric Surgeons (PAPS)
  • Place of Presentation: Kauai,USA
  • Year and Date: 2016-05-17 – 2016-05-21
  • Int'l Joint Research
• [Presentation] Tumor-homing effect of human mesenchymal stem cells in a TH-MYCN mouse model of neuroblastoma. (2016)
  • Author(s): Kimura K, Kishida T, Wakao J, Tanaka T, Higashi M, Fumino S, Aoi S, Furukawa T, Mazda O, Tajiri T
  • Organizer: 49th Annual Meeting of the Pacific Association of Pediatric Surgeons (PAPS)
  • Place of Presentation: Kauai,USA
  • Year and Date: 2016-05-17 – 2016-05-21
  • Int'l Joint Research
• [Book] 小児疾患診療のための病態生理 改訂第5版【Ⅶ．血液・腫瘍性疾患】性腺腫瘍 (2016)
  • Author(s): 文野誠久，田尻達郎
  • Total Pages: 4
  • Publisher: 東京医学社