Development od coagulopathy with vascular anomalies

• Project/Area Number: 18K15704
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Gifu University
• Principal Investigator: Endo Saori 岐阜大学, 医学部附属病院, 助教 (90816117)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 血管腫 / カサバッハメリット現象 / 血液 / 凝固異常 / 脈管腫瘍 / 小児科学

Outline of Final Research Achievements

Vascular anomalies are very rare diseases, which cause severe coagulopathy, thrombocytopenia and blood clot in vein.Kasabach-Merritt Phenomenon is caused by vascular tumors and have poor prognosis. Pathogenesis of these condition are not known. Considering the difference between vascular tumors and vascular anomalies, we examined the cytokine analysis to identify the pathogenesis of it. It is considered that the difference of origin lesion could cause some type of coagulophathy in these disease. We reported these results on the papers.

Academic Significance and Societal Importance of the Research Achievements

近年、これらの疾患は病理学や遺伝生物学的な研究の発展に伴い、原因や病態が徐々に解明されてきている。我々は小児科の中でも血液腫瘍学を専門としているため、脈管異常に起こっている凝固異常を、本体から理解し研究をすることが可能である。国内外においても、この点に注目して研究を行っている施設はほとんどなかった。一方で、ｍTOR阻害剤であるシロリムスの難治性脈管異常に対する有効性は極めて高く、ブレークスルーになると期待されている。その有効性を検証するための臨床試験は海外で行われてきつつあり、今後さらに注目されるだろう。また本薬の薬理作用に関する研究報告はほとんどないため、本研究は非常に意義深かったと考える。

Research Products

• [Journal Article] Fatal Progression of Gorham-Stout Disease with Skull Base Osteomyelitis and Lateral Medullary Syndrome (2019)
  • Author(s): 11.Nozawa A, Ozeki M, Hori T, Kato H, Ohe N, Fukao T.
  • Journal Title: Internal Medicine Volume: 58 Issue: 13 Pages: 1929-1933
  • DOI: 10.2169/internalmedicine.2118-18
  • NAID: 130007672112
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2019-07-01
  • Peer Reviewed / Open Access
• [Journal Article] The impact of sirolimus therapy on lesion size, clinical symptoms, and quality of life of patients with lymphatic anomalies. (2019)
  • Author(s): Ozeki M., Nozawa A., Yasue S., Endo S., Asada R., Hashimoto H., Fukao T.
  • Journal Title: Orphanet J Rare Dis. Volume: 14 Issue: 1 Pages: 141-141
  • DOI: 10.1186/s13023-019-1118-1
  • Peer Reviewed / Open Access
• [Journal Article] Perampanel Inhibits Neuroblastoma Cell Proliferation Through Down-regulation of AKT and ERK Pathways. (2019)
  • Author(s): 6.Nozawa A., Ozeki M., Matsuoka M., Nakama M., Yasue S., Endo S., Kawamoto N., Ohnishi H., Fukao T.
  • Journal Title: Anticancer Res Volume: 39 Issue: 7 Pages: 3595-3599
  • DOI: 10.21873/anticanres.13506
  • Peer Reviewed / Open Access
• [Journal Article] Detection of NRAS mutation in cell-free DNA biological fluids from patients with kaposiform lymphangiomatosis (2019)
  • Author(s): Ozeki Michio、Aoki Yoko、Nozawa Akifumi、Yasue Shiho、Endo Saori、Hori Yumiko、Matsuoka Kentaro、Niihori Tetsuya、Funayama Ryo、Shirota Matsuyuki、Nakayama Keiko、Fukao Toshiyuki
  • Journal Title: Orphanet Journal of Rare Diseases Volume: 14 Issue: 1 Pages: 215-215
  • DOI: 10.1186/s13023-019-1191-5
  • Peer Reviewed / Open Access
• [Journal Article] Proinflammatory Cytokine Secretion in a Patient With Recurrent Neuroblastoma Related to the Onset of Malignancy-associated Hemophagocytic Lymphohistiocytosis. (2019)
  • Author(s): 10.Nozawa A., Ozeki M., Yasue S., Endo S., Ohe N., Miyazaki T., Fukao T.
  • Journal Title: J Pediatr Hematol Oncol. Volume: 42 Issue: 4 Pages: e199-e201
  • DOI: 10.1097/mph.0000000000001617
  • Peer Reviewed / Open Access
• [Journal Article] Immunologic Effects of Sirolimus in Patients With Vascular Anomalies. (2019)
  • Author(s): Nozawa Akifumi、Ozeki Michio、Yasue Shiho、Endo Saori、Kawamoto Norio、Ohnishi Hidenori、Fumino Shigehisa、Furukawa Taizo、Tajiri Tatsuro、Maekawa Takanobu、Fujino Akihiro、Souzaki Ryota、Fukao Toshiyuki
  • Journal Title: Journal of Pediatric Hematology/Oncology Volume: e-pub Issue: 5 Pages: 1-1
  • DOI: 10.1097/mph.0000000000001650
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy and safety of sirolimus treatment for intractable lymphatic anomalies: A study protocol for an open-label, single-arm, multicenter, prospective study (SILA). (2019)
  • Author(s): Ozeki M, Asada R, Saito AM, Hashimoto H, Fujimura T, Kuroda T, Ueno S, Watanabe S, Nosaka S, Miyasaka M, Umezawa A, Matsuoka K, Maekawa T, Yamada Y, Fujino A, Hirakawa S, Furukawa T, Tajiri T, Kinoshita Y, Souzaki R, Fukao T
  • Journal Title: Regen Ther. Volume: 14 Pages: 84-91
  • DOI: 10.1016/j.reth.2018.12.001
  • Peer Reviewed / Open Access
• [Journal Article] Generalized lymphatic anomaly and Gorham-Stout disease: overview and recent insights. (2019)
  • Author(s): Ozeki M, Fukao T
  • Journal Title: Advance Wound Care. Volume: 1 Issue: 6 Pages: 230-245
  • DOI: 10.1089/wound.2018.0850
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of sirolimus in an infant with Kasabach-Merritt phenomenon. (2018)
  • Author(s): Kumagai C., Ozeki M., Nozawa A., Kakuda H., Fukao T.
  • Journal Title: Pediatr Int. Volume: 60 Issue: 9 Pages: 887-889
  • DOI: 10.1111/ped.13630
  • Peer Reviewed / Open Access
• [Presentation] Common lymphatic malformationに対するシロリムス療法. (2019)
  • Author(s): 14.遠渡 沙緒理, 野澤 明史, 安江 志保, 浅田 隆太, 橋本 大哉, 小関 道夫, 深尾 敏幸
  • Organizer: 日本血管腫血管奇形学術集会(第16回)
• [Presentation] Kasabach-Merritt phenomenonに対するmTOR阻害剤の有効性と安全性について. (2018)
  • Author(s): 遠渡沙緒理, 野澤明史, 安 志保, 木村豪, 小関道夫, 深尾敏幸.
  • Organizer: 日本血管腫血管奇形学会（第15回）
• [Presentation] Differences in clinical findings and plasma cytokine profiles between generalized lymphatic anomaly and kaposiform lymphangiomatosis. (2018)
  • Author(s): 16.Ozeki M, Nozawa A, Kawamoto N, Fujino A, Hirakawa S, Fukao T.
  • Organizer: The 22nd International Workshop of the International Society for the Study of Vascular Anomalies.
  • Int'l Joint Research