Faculty Profiles - OOISHI Makoto

Papers - OOISHI Makoto

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Novel Repositioning Therapy for Drug-Resistant Glioblastoma: In Vivo Validation Study of Clindamycin Treatment Targeting the mTOR Pathway and Combination Therapy with Temozolomide. International journal

Takeyoshi Eda, Masayasu Okada, Ryosuke Ogura, Yoshihiro Tsukamoto, Yu Kanemaru, Jun Watanabe, Jotaro On, Hiroshi Aoki, Makoto Oishi, Nobuyuki Takei, Yukihiko Fujii, Manabu Natsumeda

Cancers 14 ( 3 ) 2022.2

Language：English Publishing type：Research paper (scientific journal)

Multimodal therapy including surgery, radiation treatment, and temozolomide (TMZ) is performed on glioblastoma (GBM). However, the prognosis is still poor and there is an urgent need to develop effective treatments to improve survival. Molecular biological analysis was conducted to examine the signal activation patterns in GBM specimens and remains an open problem. Advanced macrolides, such as azithromycin, reduce the phosphorylation of p70 ribosomal protein S6 kinase (p70S6K), a downstream mammalian target of rapamycin (mTOR) effector, and suppress the proliferation of T-cells. We focused on its unique profile and screened for the antitumor activity of approved macrolide antibiotics. Clindamycin (CLD) reduced the viability of GBM cells in vitro. We assessed the effects of the candidate macrolide on the mTOR pathway through Western blotting. CLD attenuated p70S6K phosphorylation in a dose-dependent manner. These effects on GBM cells were enhanced by co-treatment with TMZ. Furthermore, CLD inhibited the expression of the O6-methylguanine-DNA methyltransferase (MGMT) protein in cultured cells. In the mouse xenograft model, CLD and TMZ co-administration significantly suppressed the tumor growth and markedly decreased the number of Ki-67 (clone MIB-1)-positive cells within the tumor. These results suggest that CLD suppressed GBM cell growth by inhibiting mTOR signaling. Moreover, CLD and TMZ showed promising synergistic antitumor activity.

DOI： 10.3390/cancers14030770

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Meningoencephalocele in the Lateral Sphenoid Sinus Showing Malformation of Cortical Development: A Case Report.

Taro Sato, Tetsuya Hiraishi, Mari Tada, Manabu Natsumeda, Jotaro On, Haruhiko Takahashi, Taiki Saito, Noritaka Okubo, Makoto Oishi, Akiyoshi Kakita, Yukihiko Fujii

NMC case report journal 9 281 - 287 2022

Language：English

Meningoencephalocele in the lateral sphenoid sinus (SS) has been determined to be a rare entity often detected by cerebrospinal fluid (CSF) rhinorrhea. To date, the pathology of meningoencephalocele in the lateral SS has remained to be unclear in many cases. In this study, we report on a case of a 72-year-old woman with an arteriovenous malformation who presented with CSF rhinorrhea. Radiologic investigations revealed a left temporal meningoencephalocele in the lateral SS. We removed the meningoencephalocele and performed skull base repair, after which the CSF rhinorrhea resolved. Pathological examination showed congenital cortical abnormalities with dysmorphic neurons in various shapes and acquired chronic tissue alterations including fibrillary gliosis and scattered Rosenthal fibers. These findings may further aid in understanding the etiopathogenesis of meningoencephalocele in the lateral SS.

DOI： 10.2176/jns-nmc.2022-0152

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Endovascular treatment of an infectious aneurysm using the selective provocative test and transcranial motor evoked potential monitoring under general anesthesia: a case report. International journal

Kazuhiro Ando, Tetsuya Hiraishi, Makoto Oishi, Hitoshi Hasegawa, Bumpei Kikuchi, Manabu Natsumeda, Tomoaki Suzuki, Shoji Saito, Tomoyoshi Ota, Yuichi Yoshida, Yukihiko Fujii

Acta neurochirurgica 164 ( 5 ) 1265 - 1269 2021.9

Language：English Publishing type：Research paper (scientific journal)

The selective provocative test (SPT) under local anesthesia aids in protecting against ischemic complications during endovascular treatment. However, the use of this test under general anesthesia is not well described. Herein, we present a case of a 51-year-old man with a ruptured fusiform aneurysm in the middle cerebral artery M4 segment, which was thought to possibly supply the motor cortex. Internal trapping of the affected vessel and aneurysm by endovascular intervention was successfully performed after SPT using transcranial motor evoked potential (MEP) monitoring under general anesthesia. Transcranial MEP is suitable for neurological assessment during SPT under general anesthesia.

DOI： 10.1007/s00701-021-05001-z

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脳神経外科領域におけるPDTの現状と問題点当科における光線力学療法の経験および次世代への挑戦

棗田学, 塚本佳広, 温城太郎, 渡邉潤, 江田岳誉, 平石哲也, 佐野正和, 大石誠, 藤井幸彦

日本レーザー医学会誌 42 ( 3 ) 161 - 161 2021.9

Reactive astrocytes contribute to epileptogenesis in patients with cavernous angioma. International journal

Hiroki Kitaura, Tetsuya Hiraishi, Yosuke Itoh, Makoto Oishi, Yukihiko Fujii, Masafumi Fukuda, Akiyoshi Kakita

Epilepsy research 176 106732 - 106732 2021.7

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Patients with cavernous angioma (CA) often suffer from severe epilepsy, and surgical resection is often performed to attenuate these epileptic seizures. Several studies have suggested that surgical removal of the surrounding hemosiderin-pigmented tissues adjacent to CA achieves better seizure control than restricted lesionectomy. Pathological examination of the resected foci reveals not only hemosiderin pigmentation but also various degrees of inflammatory change, such as hemosiderin-laden macrophages, gliosis and fibrosis. However, there is some controversy regarding the epileptogenic potential of these regions due to the uncertain nature of the mechanisms contributing to these histopathological changes. METHODS: To investigate the correlations between neuron hyperexcitability and evident pathological changes, we performed ex vivo flavoprotein fluorescence imaging using surgically resected epileptogenic foci surrounding CA. The mirror surfaces of the tissues used for the physiological experiment were also subjected to morphological examination. RESULTS: Hemosiderin-laden macrophages and many gemistocytic astrocytes were observed in the area adjacent to CA, where horizontal spreading excitations were detected significantly more frequently. Outside these areas, we found fine granular iron deposits and only a few fibrillary astrocytes, and weakly propagating excitations were detected. Furthermore, areas of enhanced activation were more clearly correlated with the glial proliferation index than with iron deposition. CONCLUSION: These results suggest that the epileptogenesis in patients with CA may be based on a biological process, such as alteration of glial function, rather than direct chemical reactions involving iron deposition.

DOI： 10.1016/j.eplepsyres.2021.106732

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Predicting BRAF V600E mutation in glioblastoma: utility of radiographic features.

Manabu Natsumeda, Michael Chang, Ramil Gabdulkhaev, Haruhiko Takahashi, Yoshihiro Tsukamoto, Yu Kanemaru, Masayasu Okada, Makoto Oishi, Kouichirou Okamoto, Fausto J Rodriguez, Akiyoshi Kakita, Yukihiko Fujii, Karisa C Schreck

Brain tumor pathology 38 ( 3 ) 228 - 233 2021.7

Language：English Publishing type：Research paper (scientific journal)

Detection of BRAF V600E mutation in glioblastomas (GBMs) is important because of potential therapeutic implications. Still, the relative paucity of these mutations makes molecular detection in all GBMs controversial. In the present study, we analyzed clinical, radiographic and pathologic features of 12 BRAF V600E-mutant GBMs and 12 matched controls from 2 institutions. We found that a majority of BRAF V600E-mutant GBMs displayed a combination of well-circumscribed lesions, large cystic components with thin walls and solid cortical component on MRI, but with some overlap with matched BRAF wildtype controls (p = 0.069). BRAF V600E-mutant GBMs were also apt to gross total resection (83% vs 17%, p = 0.016) and morphologically displayed epithelioid features (83% vs 0%, p < 0.0001). Identification of these clinical, radiographic, and pathologic characteristics should prompt testing for BRAF V600E in IDH-wildtype GBM.

DOI： 10.1007/s10014-021-00407-0

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Four-dimensional multifusion imaging for assessment of meningioma hemodynamics

Ryosuke Ogura, Makoto Oishi, Tetsuya Hiraishi, Haruhiko Takahashi, Kohei Shibuya, Tomoaki Suzuki, Manabu Natsumeda, Kouichirou Okamoto, Yukihiko Fujii

Interdisciplinary Neurosurgery 24 101118 - 101118 2021.6

Delayed Bleeding of Unruptured Intracranial Aneurysms After Coil Embolization: A Retrospective Case Series. International journal

Kazuhiro Ando, Hitoshi Hasegawa, Tomoaki Suzuki, Shoji Saito, Kohei Shibuya, Haruhiko Takahashi, Makoto Oishi, Yukihiko Fujii

World neurosurgery 149 e135-e145 2021.5

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Delayed bleeding of unruptured intracranial aneurysms (UIAs) after coil embolization is rare; this study aimed to analyze the occurrence of delayed bleeding of UIAs after coil embolization. METHODS: We retrospectively analyzed patients with UIAs after coil embolization between January 2002 and December 2018 and assessed the features of UIAs with delayed bleeding after coil embolization. RESULTS: Analysis included 307 patients with 335 UIAs. Mean follow-up was 7.1 ± 4.9 years, and total follow-up was 2365 aneurysm-years. There were 271 (80.9%) aneurysms located in the anterior circulation and 64 (19.1%) aneurysms located in the posterior circulation. Significant differences were observed between the 2 groups in terms of maximum size of the aneurysm (P < 0.01), width of the aneurysm neck (P < 0.01), and number of retreatment cases (P < 0.01). During the follow-up period, delayed bleeding occurred in 4 aneurysms (annual bleeding rate of 0.17%); all were located in the posterior circulation. The original size was not relatively large (mean 8.6 ± 2.4 mm). All aneurysms bled within 5 years (mean 35 ± 9.6 months) after the initial treatment. Two were de novo aneurysms that developed adjacent to the coiled aneurysms and were not detected on follow-up magnetic resonance angiography. CONCLUSIONS: Cautious follow-up of UIAs with digital subtraction angiography is important, articularly within the first 5 years after the procedure. If there are changes in the anatomic outcomes, short-term reassessment or additional treatment should be actively considered, particularly for aneurysms in the posterior circulation.

DOI： 10.1016/j.wneu.2021.02.061

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脳腫瘍遺伝子異常の画像診断 IDH変異型神経膠腫における3T-MRSを用いた2HGの検出

棗田学, 五十嵐博中, 本橋邦夫, 塚本佳広, 小倉良介, 岡本浩一郎, 大石誠, 柿田明美, 藤井幸彦

Brain Tumor Pathology 38 ( Suppl. ) 059 - 059 2021.5

小児脳腫瘍の新展開髄芽腫におけるGLI3発現および役割の解明完結編

棗田学, 宮原弘明, 吉村淳一, 塚本佳広, 大石誠, エバーハート・チャールズ, 柿田明美, 藤井幸彦

Brain Tumor Pathology 38 ( Suppl. ) 058 - 058 2021.5

High grade astrocytomaに準じて治療したprimary anaplastic pleomorphic xanthoastrocytomaの4症例の検討

塚本佳広, 棗田学, 温城太郎, 小倉良介, 清水宏, 岡本浩一郎, 大石誠, 藤井幸彦, 柿田明美

Brain Tumor Pathology 38 ( Suppl. ) 078 - 078 2021.5

悪性神経膠腫におけるテモゾロミド療法前後のミスマッチ修復蛋白発現の検討

山田史織, 棗田学, 高橋陽彦, 安藤和弘, 温城太郎, 塚本佳広, 岡田正康, 大石誠, 柿田明美, 藤井幸彦

Brain Tumor Pathology 38 ( Suppl. ) 076 - 076 2021.5

Development and natural course of lateral posterior choroidal artery aneurysms arising from fragile choroidal collaterals in moyamoya disease: illustrative cases. International journal

Tomoaki Suzuki, Hitoshi Hasegawa, Kouichirou Okamoto, Kazuhiro Ando, Kohei Shibuya, Haruhiko Takahashi, Shoji Saito, Makoto Oishi, Yukihiko Fujii

Journal of neurosurgery. Case lessons 1 ( 15 ) CASE2110 2021.4

Language：English

BACKGROUND: Choroidal collaterals are a risk factor for hemorrhagic stroke, even in the nonhemorrhagic hemisphere, among patients with moyamoya disease (MMD). Peripheral choroidal aneurysms rupture in fragile collaterals; however, the development and natural course of these aneurysms remain elusive. OBSERVATIONS: A 51-year-old woman, who had experienced a right cerebral hemorrhage 3 years earlier, presented with asymptomatic minor bleeding from a left lateral choroidal artery aneurysm in a predeveloped choroidal anastomosis. Although the aneurysm spontaneously thrombosed within 2 months, the choroidal collaterals persisted. After bypass surgery, the choroidal anastomosis regressed, and neither a de novo aneurysm nor a hemorrhagic stroke occurred. A 75-year-old woman with MMD, who had experienced a left frontal infarction 6 years earlier, experienced recurrent right intraventricular hemorrhage from a ruptured lateral choroidal artery aneurysm that developed in the choroidal anastomosis. The aneurysm spontaneously regressed 3 days after the rebleeding with no recurrence over the following 7 years. LESSONS: Choroidal artery aneurysms may develop in the choroidal anastomosis and rupture in the nonsurgical or contralateral hemispheres. Patients with MMD who have a history of hemorrhagic or ischemic stroke and impaired cerebral blood flow require careful observation. Although aneurysms may rapidly regress spontaneously, bypass surgery can stabilize hemodynamic stress and prevent further hemorrhage.

DOI： 10.3171/CASE2110

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Low Detection Rate of H3K27M Mutations in Cerebrospinal Fluid Obtained from Lumbar Puncture in Newly Diagnosed Diffuse Midline Gliomas. International journal

Jotaro On, Manabu Natsumeda, Jun Watanabe, Shoji Saito, Yu Kanemaru, Hideaki Abe, Yoshihiro Tsukamoto, Masayasu Okada, Makoto Oishi, Junichi Yoshimura, Akiyoshi Kakita, Yukihiko Fujii

Diagnostics (Basel, Switzerland) 11 ( 4 ) 2021.4

Language：English Publishing type：Research paper (scientific journal)

Recent studies have suggested the feasibility of detecting H3K27M mutations in the cerebrospinal fluid of diffuse midline glioma (DMG) patients. However, cerebrospinal fluid from patients in these studies were collected mainly during biopsy, ventriculo-peritoneal shunt procedures or postmortem. We assessed circulating tumor DNA (ctDNA) extracted from cerebrospinal fluid (CSF) and plasma in a series of 12 radiographically suspected and/or pathologically confirmed diffuse midline glioma patients and assessed for H3F3A K27M mutation using digital droplet PCR. In 10 patients, CSF was obtained by lumbar puncture at presentation. A definitive detection of H3F3A K27M mutation was achieved in only one case (10%); H3F3A K27M mutation was suspected in three other cases (30%). H3F3A K27M mutation was detected in two patients in CSF obtained by ventricular tap during a ventriculo-peritoneal shunt for obstructive hydrocephalus. Cases in which a definitive assessment was possible (definite H3F3A K27M or definite H3F3A wildtype) tended to be younger (median 7.5 years vs. 40.5 years; p = 0.07) and have a higher concentration of CSF protein (median 123 mg/dL vs. 27.5 mg/dL; p = 0.21) compared to nondefinite cases. Low proliferation and apoptotic rates seemed to be characteristics of DMG unfavorable for liquid biopsy. More advanced lesions with necrosis and evidence of dissemination were unlikely to be candidates for lumbar puncture due to the fear of exacerbating obstructive hydrocephalus. Methods to safely sample CSF and a more sensitive detection of ctDNA are necessary for reliable liquid biopsy of DMG at presentation.

DOI： 10.3390/diagnostics11040681

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Diffuse midline gliomaにおけるliquid biopsyの現状及び課題

棗田学, 温城太郎, 渡邉潤, 塚本佳広, 岡田正康, 大石誠, 藤井幸彦

小児の脳神経 46 ( 2 ) 183 - 183 2021.4

Unilateral oculomotor nerve palsy caused by arterial compression accompanying subarachnoid hemorrhage: a case report. International journal

Shoji Saito, Hitoshi Hasegawa, Toru Takino, Kazuhiro Ando, Kohei Shibuya, Haruhiko Takahashi, Jotaro On, Tomoaki Suzuki, Makoto Oishi, Yukihiko Fujii

Acta neurochirurgica 163 ( 3 ) 813 - 816 2021.3

Language：English Publishing type：Research paper (scientific journal)

Unilateral oculomotor nerve palsy, often caused by aneurysmal compression, is one of the decisive findings for confirming the site of a ruptured aneurysm. However, arterial compression can also cause unilateral oculomotor nerve palsy. Here, we present the case of a 59-year-old woman with a ruptured right internal carotid-posterior communicating artery aneurysm accompanied by contralateral oculomotor nerve palsy. The nerve was found to be compressed by the posterior cerebral artery and was isolated from the ruptured aneurysm. When confirming a ruptured aneurysm based on the evidence of unilateral oculomotor palsy, the arteries surrounding the nerve must be thoroughly assessed.

DOI： 10.1007/s00701-020-04633-x

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[Melanocytic Tumors].

Kouichirou Okamoto, Manabu Natsumeda, Makoto Oishi, Yukihiko Fujii

No shinkei geka. Neurological surgery 49 ( 2 ) 389 - 394 2021.3

Language：Japanese Publishing type：Research paper (scientific journal)

Primary melanocytic neoplasms of the central nervous system(CNS)presumably arise from leptomeningeal melanocytes that are derived from the neural crest. Melanocytic neoplasms associated with neurocutaneous melanosis likely derive from melanocyte precursor cells that reach the CNS after somatic mutations, mostly, of the NRAS. They should be distinguished from other melanotic tumors involving the CNS, including metastatic melanoma and other primary tumors that undergo melanization, such as melanocytic schwannomas, medulloblastomas, paragangliomas, and various gliomas, because these lesions require different patient workups and therapy. Primary melanocytic neoplasms of the CNS that are diffuse and do not form macroscopic masses are called melanocytoses, whereas malignant diffuse or multifocal lesions are collectively called melanomatoses. Benign and intermediate-grade tumoral lesions are called melanocytomas. Discrete malignant tumors are called melanomas. CT and MRI of melanocytosis and melanomatosis show diffuse thickening and enhancement of the leptomeninges, often with focal or multifocal nodularity. Depending on the melanin content, diffuse and circumscribed melanocytic tumors of the CNS may show some characteristics on CT and MRI: iso- to hyperattenuation on CT and paramagnetic properties of melanin on MRI resulting in an isointense signal on T1WIs and iso- to hypointensity on T2WIs.

DOI： 10.11477/mf.1436204403

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[Multinodular and Vacuolating Neuronal Tumor of the Cerebrum(MVNT)].

Kouichirou Okamoto, Manabu Natsumeda, Makoto Oishi, Yukihiko Fujii

No shinkei geka. Neurological surgery 49 ( 2 ) 383 - 387 2021.3

Language：Japanese Publishing type：Research paper (scientific journal)

Multinodular and vacuolating neuronal tumors of the cerebrum(MVNTs)are rare brain tumors that were described first in 2013. MVNTs have been added to the World Health Organization Classification of Tumors of the Central Nervous System in 2016(2016WHO), although an MVNT is a clinical-pathological lesion with uncertain class assignment. It remains unclear whether MVNTs should be considered a true neoplasm or malformative lesion. Their prevalence and pathophysiology are unknown. MVNTs typically occur in adults, predominantly in the cerebral subcortical region, and are most frequently associated with seizures or seizure equivalents. MVMTs can also present incidentally without seizures. MVNTs have been reported to show highly suggestive imaging features, especially on MRI scans. MVNTs consist of small T2 and T2-FLAIR hyperintense nodules in subcortical and juxtacortical areas with rare or no post-contrast enhancement. Most MVNTs reported in the literature involve the supratentorial part of the brain. Recently, lesions exhibiting a remarkably similar pattern of imaging findings were described in the posterior fossa, which are referred to as multinodular and vacuolating posterior fossa of unknown significance(MV-PLUS). Both MVNT and MV-PLUS are considered "leave-me-alone" lesions because of the absence of malignancy criteria and the lack of evolutivity on follow-up MRI scans.

DOI： 10.11477/mf.1436204402

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[Dysplastic Cerebellar Gangliocytoma(Lhermitte-Duclos Disease)].

Kouichirou Okamoto, Manabu Natsumeda, Makoto Oishi, Yukihiko Fujii

No shinkei geka. Neurological surgery 49 ( 2 ) 395 - 399 2021.3

Language：Japanese Publishing type：Research paper (scientific journal)

Dysplastic cerebellar gangliocytoma or Lhermitte-Duclos disease(LDD)is a rare benign cerebellar lesion composed of dysplastic ganglion cells that conform to the existing cortical architecture. In this disease, the enlarged ganglion cells are predominantly located within the internal granular layer, and they thicken the cerebellar folia. The architecture of the affected cerebellar hemisphere with the enlarged cerebellar folia and the cystic changes, in some cases, present as "tiger-striped striations," a characteristic imaging finding that is not specific to LDD. This imaging feature may be observed in medulloblastoma and isolated cerebellar Rosai-Dorfman disease. This cerebellar lesion is a major central nervous system manifestation of Cowden syndrome, an autosomal dominant condition that causes various hamartomas and neoplasms. A molecular-based study estimated the prevalence of Cowden syndrome to be 1 case per 200,000. In a study involving 211 patients with Cowden syndrome, 32% developed LDD. LDD can be diagnosed in young children and older adults within the eighth decades of life. PTEN mutations have been identified in virtually all adult-onset LDDs, but not in childhood-onset cases.

DOI： 10.11477/mf.1436204404

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【脳神経画像Critical Findings-おさえておきたい症状とCT/MRI画像所見】特徴的な画像所見を示す新しい概念の脳腫瘍大脳多結節空胞状神経細胞腫瘍(MVNT)

岡本浩一郎, 棗田学, 大石誠, 藤井幸彦

Neurological Surgery 49 ( 2 ) 383 - 387 2021.3

Language：Japanese Publisher：(株)医学書院

＜文献概要＞Point ・大脳多結節空胞状神経細胞腫瘍(MVNT)は,痙攣,頭痛あるいは偶然発見される大脳半球の脳回に沿う皮質深部〜皮質下神経系腫瘍性病変(WHO 2016 gradeI相当)である.・MRIで1〜5mmの結節が3〜10個以上集合する7〜57mmの大きさで,mass effectは乏しくGd増強効果を示さない.・増大せず,痙攣を来す一部の例を除き生検や病変摘出などの外科的処置を必要としない"leave-me-alone" lesionと考えらえる.

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Papers - OOISHI Makoto