Toda, Masahiro

写真a

Affiliation

School of Medicine, Department of Neurosurgery （Shinanomachi）

Position

Professor
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Academic Degrees 【 Display / hide 】

  • 博士（医学）, 慶應義塾大学

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Books 【 Display / hide 】

  • Stem cell research for the treatment of malignant glioma.

    Tamura R and Toda M, Brain Tumor, InTech, Croatia, 2017

  • Glioma Antigen Glioma: Immunotherapeutic approaches

    Toda M, R Yamanaka (Ed.), In Landes Bioscience, 2012

  • Brain tumor stem cells and anti-angiogenetic therapy

    Saito K, Yoshida K, Toda M, Cancer Stem Cells, The Cutting　Edge Stanley Shostak (Ed.), InTech, Croatia, 2011

    Contact page： 229-246

  • Immunotherapy targeted at brain cancer stem cells

    Toda M, Brain Tumor Immunotherapy, The Open Cancer Immunology Journal Terry Lichtor (Ed.), Bentham open,, 2010

    Contact page： 48-50

  • Treatment of metastatic brain tumors with a replication-competent multi-mutated herpes simplex virus-1.

    Toda M, Uyemura K, Kawase T, Rabkin SD, Martuza RL, Neural Development, Springer-Verlag, 1999

    Contact page： 521-525

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Papers 【 Display / hide 】

  • Cone-beam computed tomography fusion technique for vascular assessment of skull base meningiomas

    Yoshida K, Akiyama T, Takahashi S, Miwa T, Horiguchi T, Sasaki H, Toda M

    World Neurosurg S1878-8750 （ 21 ）  2021.04

    Research paper (scientific journal), Joint Work

  • A novel histopathological classification of meningiomas based on dural invasion

    Murase M, Tamura R, Kuranari Y, Sato M, Ohara K, Morimoto Y, Yoshida K, Toda M

    J Clin Path 74 （ 4 ） 238 - 243 2021.04

    Research paper (scientific journal), Joint Work, Accepted

    　View Summary

    Aims Histological invasion into the adjacent brain parenchyma is frequently investigated in meningioma because it is an important morphological criterion for grade II meningioma according to the 2016 WHO classification. However, few studies have focused on dural invasion of meningiomas. Herein, we propose a novel histopathological classification based on dural invasion of meningiomas. Methods Forty-nine cases with WHO grade I meningiomas who underwent Simpson grade I removal were collected. After the meningeal layer (ML) and periosteal layer (PL) of dura mater were visualised by Masson's trichrome stain, we evaluated the depth (to the ML and PL) and the patterns (1, expanding; 2, infiltrating) of dural invasion of meningiomas using serial paraffin sections. Invasion-associated markers, including Ki-67, matrix metalloproteinase (MMP)-1, MMP-9 and MMP-13, aquaporin 1 and Na-K-2Cl cotransporter, were quantitatively analysed by immunohistochemistry. Results Thirty-five cases (71.4%) showed the dural invasion. In 27 of these 35 cases (77.1%), dural invasion was localised in ML. Type 1 (expanding type) and type 2 (infiltrating type) invasions were observed in 23 and 12 cases, respectively. The recurrence rate in cases with type 2 invasion was significantly higher than that in cases with type 1 invasion. The percentage of MMP-1-positive tumour cells was also significantly higher in cases with dural invasion than those without, suggesting involvement of MMP-1 in dural invasion. Conclusions We quantitatively evaluated the depth and patterns of dural invasion in meningiomas. The patterns of dural invasion were associated with meningioma recurrence.

  • Angio-anatomical study of the pterygovaginal artery based on cone-beam computed tomography

    Yoshida K, Akiyama T, Raz E, Kamamoto D, Ozawa H, Toda M

    Neruoradiology （Neuroradiology)   2021.02

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  00283940

    　View Summary

    Purpose: To investigate the anatomical characteristics and clinical implications of the pterygovaginal artery (PtVA), a recurrent branch from the distal internal maxillary artery (IMA), which courses through the pterygovaginal canal that connects the pterygopalatine fossa and nasopharynx. Methods: Eighty-two patients with 90 sides of cone-beam computed tomography (CBCT) reconstructed from rotational angiography of the external or common carotid artery with a field of view covering the pterygopalatine fossa were retrospectively reviewed. The origin from the IMA, branching type, distribution, and anastomoses was evaluated. The underlying lesions were 36 hypervascular lesions with possible supply from PtVA (17 cavernous sinus arteriovenous fistulas (AVFs), 6 anterior condylar AVFs, and 13 nasopharyngeal, parasellar, or paraclival tumors) and 46 other diseases. Results: PtVA was identified in 75 sides (83%). It originated from the pterygopalatine segment of the IMA in 45 sides (60%) and from the pterygoid segment in 30 sides (40%). It arose independently (77%), sharing the common trunk with the Vidian artery (15%) or with other branches. It ran posteromedially through the pterygovaginal canal to supply the mucosa over the nasopharyngeal roof, the choanae, and the pharyngeal ostium of the eustachian tube. It anastomosed with the ascending pharyngeal artery (n=37), the accessory meningeal artery (n=7), and the mandibular artery from the petrous internal carotid artery (n=2). It served as a feeder of osseous AVFs and skull base tumors. Conclusion: PtVA was often identified by CBCT even in normal anatomy. Its detailed angio-anatomy could be evaluated in the presence of parasellar or paraclival hypervascular lesions.

  • Recent progress in the research of suicide gene therapy for malignant glioma

    Tamura R., Miyoshi H., Yoshida K., Okano H., Toda M.

    Neurosurgical Review （Neurosurgical Review)  44 （ 1 ） 29 - 49 2021.02

    ISSN  03445607

    　View Summary

    Malignant glioma, which is characterized by diffuse infiltration into the normal brain parenchyma, is the most aggressive primary brain tumor with dismal prognosis. Over the past 40 years, the median survival has only slightly improved. Therefore, new therapeutic modalities must be developed. In the 1990s, suicide gene therapy began attracting attention for the treatment of malignant glioma. Some clinical trials used a viral vector for suicide gene transduction; however, it was found that viral vectors cannot cover the large invaded area of glioma cells. Interest in this therapy was recently revived because some types of stem cells possess a tumor-tropic migratory capacity, which can be used as cellular delivery vehicles. Immortalized, clonal neural stem cell (NSC) line has been used for patients with recurrent high-grade glioma, which showed safety and efficacy. Embryonic and induced pluripotent stem cells may be considered as sources of NSC because NSC is difficult to harvest, and ethical issues have been raised. Mesenchymal stem cells are alternative candidates for cellular vehicle and are easily harvested from the bone marrow. In addition, a new type of nonlytic, amphotropic retroviral replicating vector encoding suicide gene has shown efficacy in patients with recurrent high-grade glioma in a clinical trial. This replicating viral capacity is another possible candidate as delivery vehicle to tackle gliomas. Herein, we review the concept of suicide gene therapy, as well as recent progress in preclinical and clinical studies in this field.

  • Effect of Gravity on Brain Structure as Indicated on Upright Computed Tomography

    Yokoyama Y, Yamada Y, Kosugi K, Yamda M, Narita K, Nakahara T, Fujiwara H, Toda M, Jinzaki M

    Scientific Reports （Scientific Reports)  11 （ 1 ） 392 2021.01

    Research paper (scientific journal), Joint Work, Accepted

    　View Summary

    We aimed to use upright computed tomography (CT) to depict posture-related changes in the brain tissue under normal gravity. Thirty-two asymptomatic volunteers underwent upright CT in the sitting position and conventional CT in the supine position on the same day. We compared the shift of the pineal body, cerebellar tonsil, the length of pituitary stalk, optic nerve sheath area and perimeter (ONSA and ONSP, respectively), and lateral ventricular volume between the supine and sitting positions. We also compared shape changes of the cerebrospinal fluid (CSF) spaces at different sites between both positions. In the sitting position, the pineal body shifted 0.68 ± 0.27 mm in the ventral direction and 0.76 ± 0.24 mm in the caudal direction, the length of pituitary stalk decreased by 1.23 ± 0.71 mm, the cerebellar tonsil descended by 2.10 ± 0.86 mm, the right ONSA decreased by 15.21 ± 6.54%, the left ONSA decreased by 15.30 ± 7.37%, the right ONSP decreased by 8.52 ± 3.91%, the left ONSP decreased by 8.20 ± 4.38%, and the lateral ventricular volume decreased by 5.07 ± 3.24% (all P < 0.001). We also observed changes in the shape of CSF spaces with changes in posture. We concluded that the intracranial structure of healthy subjects and volume of ventricles changed according to posture on Earth.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

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Presentations 【 Display / hide 】

  • NF2に対するVEGFRワクチン療法の開発

    戸田正博

    第41回日本脳神経外科コングレス総会 (横浜) , 2021.05, Public discourse, seminar, tutorial, course, lecture and others

  • 頭蓋底腫瘍（経鼻内視鏡手術）

    戸田正博

    第1回Neurosurgery Web Academy 2021 (東京) , 2021.04, Oral Presentation(guest/special)

  • ゲノム編集iPS細胞を用いた悪性神経膠腫に対する遺伝子細胞療法の開発

    戸田正博

    第20回日本再生医療学会総会 (神戸) , 2021.03, Symposium, Workshop, Panelist (public offering)

  • 下垂体および頭蓋底疾患に対する治療法の変遷と今後の展望

    戸田正博

    第6回内分泌アゴラ (オンライン) , 2021.02, Oral Presentation(guest/special)

  • 頭蓋底疾患に対する内視鏡手術と新たな治療法の開発

    戸田正博

    Neuro Surgery Seminar 2020 (オンライン) , 2020.09, Oral Presentation(guest/special)

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • 複製制御型ウイルスを搭載した神経幹細胞による脳腫瘍治療法

    2020.04
    -
    2021.03

    AMED, 橋渡し研究戦略的推進プログラム, 戸田正博, 田村亮太, Research grant, Principal Investigator

    　View Summary

    本年度は、抗腫瘍効果と安全性をさらに高める新retroviral replicating vector (RRV)の開発に努めた。
    まず、自殺遺伝子yeast cytosine deaminase (yCD)の抗腫瘍効果を高めるuracil phosphoribosyl transferase (UPRT)（5-Fluorouracil [5-FU] を5-fluorouridine monophosphate [5-FUMP] へ変換することにより、yCD単独と比べ 100倍以上の細胞死誘導効率が得られる）に着目した。実際にグリオーマに対する抗腫瘍効果もyCD単独よりyCD/UPRTが優れていることを、あらかじめ予備実験で明らかにしており、RRVにyCDとUPRTを組み込むことを試みた。一方、UPRTは長配列であり、RRVが約1.5kb程度の配列長しか搭載できないため、この検討にやや時間を要した。最終的には、Envの下流にIRES-yCDを繋げるのではなく、2A-yCD/UPRTに変更することでyCD/UPRTの安定発現が可能となった。比較対象として、CAG-yCDも安定発現を確認できたため、これらRRVの抗腫瘍効果をin vitroで比較検討した。U87に各RRVをmoi-0.1で感染させ2週間培養後に5-FCを投与し、その1週間後にCCK-8 assayでLD50値を測定したところ、RRV-2A-yCD/UPRTの抗腫瘍効果が最も高いことが明らかになった。同様にGSC細胞株hG008に対しても、顕著な優位性を示すことに成功した。さらに、RRV-2A-yCD/UPRTがiPS-NSCに感染し複製可能であることを確認した。

  • ゲノム編集iPS細胞による遊走性を利用した悪性神経膠腫に対する遺伝子細胞療法の研究開発

    2019.04
    -
    2024.03

    AMED, 先端的バイオ創薬等基盤技術開発事業, 戸田正博, 田村亮太, Research grant, Principal Investigator

  • 遺伝性疾患・神経線維腫症２型に対する革新的治療法（新規免疫療法）の開発

    2019.04
    -
    2021.03

    橋渡し研究戦略的推進プログラム・シーズB

  • 自殺遺伝子CD-UPRTゲノム編集iPS細胞を用いた遺伝子治療

    2018.06
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 戸田　正博, Grant-in-Aid for Challenging Research (Exploratory) , Principal Investigator

  • 脳腫瘍に対するゲノム編集iPS細胞を用いた遺伝子治療

    2018.04
    -
    2019.03

    AMED橋渡し研究戦略的推進プログラム, 戸田正博, No Setting, Principal Investigator

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Intellectual Property Rights, etc. 【 Display / hide 】

  • 脳腫瘍幹細胞を用いた治療薬スクリーニング法

    Application No.： 特願2019-052704  2019.03 

    Patent, Joint, National application

  • 多能性幹細胞を用いた自殺遺伝子脳腫瘍治療薬

    Application No.： 特願２０１７－２２３２０２  2017.11 

    Patent, Joint, PCT international application

  • 脳神経疾患に対するペプチドワクチン及びペプチドワクチン組成物

    Application No.： 特願２０１７－１００３６１  2017.05 

    Patent, Single, PCT international application

  • 神経幹細胞の分離方法及び増殖促進方法

    Application No.： 特願2008-014243  2008.01 

    Patent, Joint, National application

  • 神経損傷の治療薬

    Application No.： 特願2003-128508  2003.05 

    Registration No.： 特許第3607271号  2004.10

    Patent, Joint, PCT international application

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Courses Taught 【 Display / hide 】

  • SURGERY

    2021

  • NEUROSURGERY: SEMINAR

    2021

  • NEUROSURGERY: PRACTICE

    2021

  • NEUROSURGERY

    2021

  • LECTURE SERIES, NEUROSURGERY

    2021

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Courses Previously Taught 【 Display / hide 】

  • Surgical simulation in Neurosurgery

    Keio University, 2015

  • pituitary tumor

    Keio University, 2015, Lecture

  • Topics in Neurosurgery

    Keio University, 2015, Full academic year, Lecture

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