徳島大学脳神経外科

脳腫瘍研究

徳島大学医歯薬学研究部脳神経外科研究室

脳腫瘍研究

診療において正確で高度な画像誘導手術を行うためナビゲーションシステムや覚醒下開頭術、神経内視鏡手術、電気生理学的モニタリング技術、蛍光診断技術（5-ALA）、光線力学療法（PDT）等の最先端の脳腫瘍手術を行い、放射線・化学療法等の補助療法を含めた集学的治療を行っています。しかし、脳腫瘍のうち最も悪性度の高い神経膠腫（グリオブラストーマ）においては、集学的治療を施しても生存期間中央値は約2年と極めて予後不良です。その原因としてグリオブラストーマは浸潤性が高いため、完全に摘出するのは難しく、治療に難渋します。この状況をなんとか克服するため、各種の新規治療法の開発に向けて、他大学研究機関や学内医工連携研究を行っています。

近年、連携研究先（應義塾大学医学部内先端医 科学研究所遺伝子制御研究部門、佐谷教授ら）において確立された浸潤性の高いグリオブラストーマに近いマウスグリオーマ幹細胞移植脳腫瘍モデルを用いて超音波療法 (SDT)と薬物併用により抗腫瘍効果が増強された（左下図）ことから、産学連携研究に発展させ、反復可能なSDTの開発計画を準備しています。一方、脳腫瘍近傍に発現するchemokines（CCL2, CxCL10）（右下図）およびその受容体（CcR2, CcR10）の増加が脳腫瘍増大に関与し、その抑制が抗腫瘍効果に有用であることを見出し、医工連携研究により、創製化合物による治療効果の評価も継続しています。

発表論文

  1. Yamaguchi I, Kanematsu Y, Mizobuchi Y, Tada Y, Miyamoto T, Sogabe S, Ishihara M, Kagusa H, Yamamoto Y, Matsuda T, Kitazato KT, Okayama Y, Takagi Y. Chronic subdural hematoma associated with dural metastasis leads to early recurrence and death: A single-institute, retrospective cohort study. J Clin Neurosci. 2021 Dec;94:244-249
  2. Shono K, Mizobuchi Y, Yamaguchi I, Nakajima K, Fujiwara Y, Fujihara T, Kitazato K, Matsuzaki K, Uto Y, Sampetrean O, Saya H, Takagi Y. Elevated cellular PpIX potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the Akt/NF-κB/MDR1 pathway. Sci Rep. 2021 Jul 23;11(1):15105
  3. Shono K, Yamaguchi I, Mizobuchi Y, Kagusa H, Sumi A, Fujihara T, Nakajima K, Kitazato KT, Matsuzaki K, Saya H, Takagi Y. Downregulation of the CCL2/CCR2 and CXCL10/CXCR3 axes contributes to antitumor effects in a mouse model of malignant glioma. Sci Rep. 2020 Sep 17;10(1):15286.
  4. Nakajima K, Mizobuchi Y, Fujihara T, Azumi M, Takagi Y. Continued-Maintenance Therapy with High-dose Methotrexate Improves Overall Survival of Patients with Primary Central Nervous System Lymphoma. J Med Invest. 2021;68(3.4):286-291.
  5. Mizobuchi Y, Nakajima K, Fujihara T, Matsuzaki K, Mure H, Nagahiro S, Takagi YThe risk of hemorrhage in stereotactic biopsy for brain J Med Invest. 2019;66(3.4):314-318
  6. Dolgorsuren EA, Harada M, Kanazawa Y, Abe T, Otomo M, Matsumoto Y, Mizobuchi Y, Nakajima K. Correlation and Characteristics of Intravoxel Incoherent Motion and Arterial Spin Labeling Techniques Versus Multiple Parameters Obtained on Dynamic Susceptibility Contrast Perfusion MRI for Brain J Med Invest. 2019;66(3.4):308-313. 
  7. Fujihara T, Mizobuchi Y, Nakajima K, Kageji T, Matsuzaki K, Kitazato KT, Otsuka R, Hara K, Mure H, Okazaki T, Kuwayama K, Nagahiro S, Takagi Y. Down-regulation of MDR1 by Ad-DKK3 via Akt/NFkappaB pathways augments the anti-tumoreffect of temozolomide in glioblastoma cells and a murine xenograft model. J Neurooncol. 2018 Sep;139(2):323-332
  8. Kageji T, Miyamoto T, Kotani Y, Kaji T, Bando Y, Mizobuchi Y, Nakajima K, Nagahiro S　.Congenital craniopharyngioma treated by radical surgery: case report and review of the literature.　Childs Nerv Syst. 2017 Feb;33(2):357-362. 
  9. Kageji T, Nagahiro S, Mizobuchi Y, Nakajima K.Postoperative Hematoma Requiring Recraniotomy in 1149 Consecutive Patients With Intracranial Tumors. Oper Neurosurg (Hagerstown). 2017 Jun 1;13(3):392-397
  10. Sato A, Mizobuchi Y, Nakajima K, Shono K, Fujihara T, Kageji T, Kitazato K, Matsuzaki K, Mure H, Kuwayama K, Sumi A, Saya H, Sampetrean O, Nagahirao S. Blocking COX-2 induces apoptosis and inhibits cell proliferation via the Akt/survivin- and Akt/ID3 pathway in low-grade-glioma. J Neurooncol. 2017 Apr;132(2):231-238
  11. Hara K, Kageji T, Mizobuchi Y, Kitazato KT, Okazaki T, Fujihara T, Nakajima K, Mure H, Kuwayama K, Hara T, Nagahiro S. Blocking of the interaction between Wnt proteins and their co-receptors contributes to the anti-tumor effects of adenovirus-mediated DKK3 in glioblastoma. Cancer Lett. 2015 Jan 28;356(2 Pt B):496-505.
  12. Mizobuchi Y, Kageji T, Tadashi Y, Nagahiro S. Craniotomy for cerebellar hemangioblastoma excision in a patient with von Hippel-Lindau disease complicated by uncontrolled hypertension due to pheochromocytoma. Int J Surg Case Rep. 2015;17:96-9.
  13. Abe T, Mizobuchi Y, Sako W, Irahara S, Otomi Y, Obama Y, Nakajima K, Khashbat D, Majigsuren M, Kageji T, Nagahiro S, Harada M. Clinical Significance of Discrepancy between Arterial Spin Labeling Images and Contrast-enhanced Images in the Diagnosis of Brain Tumors. Magn Reson Med Sci. 2015;14(4):313-9.
  14. Okazaki T, Kageji T, Mizobuchi Y, Miyamoto T, Nagahiro S. Nine-year interval recurrence after treatment of boron neutron capture therapy in a patient with glioblastoma: a case report.Appl Radiat Isot. 2014 Jun;88:28-31. 
  15. Kageji T, Mizobuchi Y, Nagahiro S, Nakagawa Y, Kumada H.Correlation between radiation dose and histopathological findings in patients with gliblastoma treated with boron neutron capture therapy (BNCT). Appl Radiat Isot. 2014 Jun;88:20-2. 
  16. Kurashiki Y, Kageji T, Mizobuchi Y, Satomi J, Satoh K, Hirose T, Nagahiro S.　Differential diagnosis of and therapy for anaplastic astroblastoma: case report and review of the literature No Shinkei Geka. 2013 Oct;41(10):891-9.
  17. Okazaki T, Kageji T, Kuwayama K, Kitazato KT, Mure H, Hara K, Morigaki R, Mizobuchi Y, Matsuzaki K, Nagahiro S. Up-regulation of endogenous PML induced by a combination of interferon-beta and temozolomide enhances p73/YAP-mediated apoptosis in glioblastoma. Cancer Lett. 2012 Oct 28;323(2):199-207.
  18. Kageji T, Mizobuchi Y, Nagahiro S, Nakagawa Y, Kumada H. Clinical results of boron neutron capture therapy (BNCT) for glioblastoma.Appl Radiat Isot. 2011 Dec;69(12):1823-5
  19. Kageji T, Mizobuchi Y, Nagahiro S, Nakagawa Y, Kumada H. Long-survivors of glioblatoma treated with boron neutron capture therapy (BNCT).Appl Radiat Isot. 2011 Dec;69(12):1800-2
  20. Mure H, Matsuzaki K, Kitazato KT, Mizobuchi Y, Kuwayama K, Kageji T, Nagahiro SAkt2 and Akt3 play a pivotal role in malignant gliomas. .Neuro Oncol. 2010 Mar;12(3):221-32
  21. Kuwayama K, Matsuzaki K, Mizobuchi Y, Mure H, Kitazato KT, Kageji T, Nakao M, Nagahiro S. Promyelocytic leukemia protein induces apoptosis due to caspase-8 activation via the repression of NFkappaB activation in glioblastoma. Neuro Oncol. 2009 Apr;11(2):132-41
  22. Nakagawa Y, Kageji T, Mizobuchi Y, Kumada H, Nakagawa YC linical results of BNCT for malignant braintumors in children. Appl Radiat Isot. 2009 Jul;67(7-8) Suppl):S27-30.
  23. Mizobuchi Y, Matsuzaki K, Kuwayama K, Kitazato K, Mure H, Kageji T, Nagahiro S REIC/Dkk-3 induces cell death in human malignant glioma. .Neuro Oncol. 2008;10:244-53. 
  24. Kageji T, Nagahiro S, Matsuzaki K, Mizobuchi Y, Toi H, Nakagawa Y, Kumada H. Boron neutron capture therapy using mixed epithermal and thermal neutron beams in patients with malignant glioma-correlation between radiation dose and radiation injury and clinical outcome. Int J Radiat Oncol Biol Phys. 2006 Aug 1;65(5):1446-55
  25. Kageji T, Nagahiro S, Toi H, Mizobuchi Y, Nakagawa Y.[Boron neutron capture therapy (BNCT) for malignant glioma-present status and the points at issue]. Nihon Rinsho. 2005 Sep;63 Suppl 9:442-6.
  26. Kageji T, Nagahiro S, Mizobuchi Y, Toi H, Nakagawa Y, Kumada H Radiation injury of boron neutron capture therapy using mixed epithermal- and thermal neutron beams in patients with malignant glioma..Appl Radiat Isot. 2004 Nov;61(5):1063-7. 
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