2024/10/01 更新

お知らせ

 

写真a

ハタエ　リユウスケ
波多江 龍亮
HATAE RYUSUKE
所属
医学研究院 附属脳神経病研究施設 助教
医学部 医学科（併任）
職名
助教
電話番号
0926425524
外部リンク

経歴

  • 京都大学 (研究員)

研究テーマ・研究キーワード

  • 研究テーマ：腫瘍免疫治療

    研究キーワード：免疫治療

    研究期間： 2016年4月 - 2020年7月

  • 研究テーマ：神経膠腫の遺伝子診断

    研究キーワード：神経膠腫

    研究期間： 2012年4月 - 2020年7月

論文

  • AB029. Mitochondrial dysfunction and impaired growth of glioblastoma cell lines caused by antimicrobial agents inducing ferroptosis.

    Yoshimoto K, Miki K, Hatae R, Kuga D, Yagi M, Kunisaki Y, Uchiumi T

    Chinese clinical oncology   13 ( Suppl 1 )   AB029   2024年8月   （ ISSN:2304-3865 ）

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    記述言語：英語  

    DOI： 10.21037/cco-24-ab029

    PubMed

  • Hemizygous deletion of cyclin-dependent kinase inhibitor 2A/B with p16 immuno-negative and methylthioadenosine phosphorylase retention predicts poor prognosis in IDH-mutant adult glioma

    Otsuji, R; Hata, N; Yamamoto, H; Kuga, D; Hatae, R; Sangatsuda, Y; Fujioka, Y; Noguchi, N; Sako, A; Togao, O; Yoshitake, T; Nakamizo, A; Mizoguchi, M; Yoshimoto, K

    NEURO-ONCOLOGY ADVANCES   6 ( 1 )   vdae069   2024年7月   （ eISSN:2632-2498 ）

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    記述言語：英語   出版者・発行元：Neuro-Oncology Advances  

    Background. Homozygous deletion of the tumor suppression genes cyclin‑dependent kinase inhibitor 2A/B (CDKN2A/B) is a strong adverse prognostic factor in IDH‑mutant gliomas, particularly astrocytoma. However, the impact of hemizygous deletion of CDKN2A/B is unknown. Furthermore, the influence of CDKN2A/B status in IDH‑ mutant and 1p/19q‑codeleted oligodendroglioma remains controversial. We examined the impact of CDKN2A/B status classification, including hemizygous deletions, on the prognosis of IDH‑mutant gliomas. Methods. We enrolled 101 adults with IDH‑mutant glioma between December 2002 and November 2021. CDKN2A/B deletion was evaluated with multiplex ligation‑dependent probe amplification (MLPA). Immunohistochemical anal‑ ysis of p16/MTAP and promoter methylation analysis with methylation‑specific MLPA was performed for cases with CDKN2A/B deletion. Kaplan − Meier plots and Cox proportion hazards model analyses were performed to evaluate the impact on overall (OS) and progression‑free survival. Results. Of 101 cases, 12 and 4 were classified as hemizygous and homozygous deletion, respectively. Immunohistochemistry revealed p16‑negative and MTAP retention in cases with hemizygous deletion, whereas homozygous deletions had p16‑negative and MTAP loss. In astrocytoma, OS was shorter in the order of homozy‑ gous deletion, hemizygous deletion, and copy‑neutral groups (median OS: 38.5, 59.5, and 93.1 months, respec‑ tively). Multivariate analysis revealed hazard ratios of 9.30 (P = .0191) and 2.44 (P = .0943) for homozygous and hemizygous deletions, respectively. Conclusions. CDKN2A/B hemizygous deletions exerted a negative impact on OS in astrocytoma. Immunohistochemistry of p16/MTAP can be utilized to validate hemizygous or homozygous deletions in combina‑ tion with conventional molecular diagnosis.

    DOI： 10.1093/noajnl/vdae069

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  • In-house molecular diagnosis of diffuse glioma updating the revised WHO classification by a platform of the advanced medical care system, Senshin-Iryo

    Hata, N; Fujioka, Y; Otsuji, R; Kuga, D; Hatae, R; Sangatsuda, Y; Amemiya, T; Noguchi, N; Sako, A; Fujiki, M; Mizoguchi, M; Yoshimoto, K

    NEUROPATHOLOGY   2024年3月   （ ISSN:0919-6544 eISSN:1440-1789 ）

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    記述言語：英語   出版者・発行元：Neuropathology  

    Since the World Health Organization (WHO) 2016 revision, the number of molecular markers required for diffuse gliomas has increased, placing a burden on clinical practice. We have established an in-house, molecular diagnostic platform using Senshin-Iryo, a feature of Japan's unique healthcare system, and partially modified the analysis method in accordance with the WHO 2021 revision. Herein, we review over a total 5 years of achievements using this platform. Analyses of IDH, BRAF, and H3 point mutations, loss of heterozygosity (LOH) on 1p/19q and chromosomes 10 and 17, and MGMT methylation were combined into a set that was submitted to Senshin-Iryo as “Drug resistance gene testing for anticancer chemotherapy” and was approved in August 2018. Subsequently, in October 2021, Sanger sequencing for the TERT promoter mutation was added to the set, and LOH analysis was replaced with multiplex ligation-dependent probe amplification (MLPA) to analyze 1p/19q codeletion and newly required genetic markers, such as EGFR, PTEN, and CDKN2A from WHO 2021. Among the over 200 cases included, 54 were analyzed after the WHO 2021 revision. The laboratory has maintained a diagnostic platform where molecular diagnoses are confirmed within 2 weeks. Initial expenditures exceeded the income from patient copayments; however, it has gradually been reduced to running costs alone and is approaching profitability. After the WHO 2021 revision, diagnoses were confirmed using molecular markers obtained from Senshin-Iryo in 38 of 54 cases (70.1%). Among the remaining 16 patients, only four (7.4%) were diagnosed with diffuse glioma, not elsewhere classified, which was excluded in 12 cases where glioblastoma was confirmed by histopathological diagnosis. Our Senshin-Iryo trial functioned as a salvage system to overcome the transition period between continued revisions of WHO classification that has caused a clinical dilemma in the Japanese healthcare system.

    DOI： 10.1111/neup.12970

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  • Liquid Biopsy for Glioma Using Cell-Free DNA in Cerebrospinal Fluid

    Otsuji, R; Fujioka, Y; Hata, N; Kuga, D; Hatae, R; Sangatsuda, Y; Nakamizo, A; Mizoguchi, M; Yoshimoto, K

    CANCERS   16 ( 5 )   2024年3月   （ ISSN:2072-6694 eISSN:2072-6694 ）

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    記述言語：英語   出版者・発行元：Cancers  

    Glioma is one of the most common primary central nervous system (CNS) tumors, and its molecular diagnosis is crucial. However, surgical resection or biopsy is risky when the tumor is located deep in the brain or brainstem. In such cases, a minimally invasive approach to liquid biopsy is beneficial. Cell-free DNA (cfDNA), which directly reflects tumor-specific genetic changes, has attracted attention as a target for liquid biopsy, and blood-based cfDNA monitoring has been demonstrated for other extra-cranial cancers. However, it is still challenging to fully detect CNS tumors derived from cfDNA in the blood, including gliomas, because of the unique structure of the blood–brain barrier. Alternatively, cerebrospinal fluid (CSF) is an ideal source of cfDNA and is expected to contribute significantly to the liquid biopsy of gliomas. Several successful studies have been conducted to detect tumor-specific genetic alterations in cfDNA from CSF using digital PCR and/or next-generation sequencing. This review summarizes the current status of CSF-based cfDNA-targeted liquid biopsy for gliomas. It highlights how the approaches differ from liquid biopsies of other extra-cranial cancers and discusses the current issues and prospects.

    DOI： 10.3390/cancers16051009

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  • OUTCOME IMPACT OF THE CDKN2A/B HEMI-ZYGOUS DELETION IN IDH-MUTANT ASTROCYTOMA

    Otsuji, R; Hata, N; Yamamoto, H; Kuga, D; Hatae, R; Sangatsuda, Y; Fujioka, Y; Noguchi, N; Nakamizo, A; Mizoguchi, M; Yoshimoto, K

    NEURO-ONCOLOGY   25   2023年11月   （ ISSN:1522-8517 eISSN:1523-5866 ）

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  • Supramaximal Resection Can Prolong the Survival of Patients with Cortical Glioblastoma: A Volumetric Study

    Otsuji, R; Hata, N; Funakoshi, Y; Kuga, D; Togao, O; Hatae, R; Sangatsuda, Y; Fujioka, Y; Takigawa, K; Sako, A; Kikuchi, K; Yoshitake, T; Yamamoto, H; Mizoguchi, M; Yoshimoto, K

    NEUROLOGIA MEDICO-CHIRURGICA   63 ( 8 )   364 - 374   2023年8月   （ ISSN:04708105 eISSN:13498029 ）

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    記述言語：英語   出版者・発行元：一般社団法人 日本脳神経外科学会  

    We aimed to retrospectively determine the resection rate of fluid-attenuated inversion recovery (FLAIR) lesions to evaluate the clinical effects of supramaximal resection (SMR) on the survival of patients with glioblastoma (GBM). Thirty-three adults with newly diagnosed GBM who underwent gross total tumor resection were enrolled. The tumors were classified into cortical and deep-seated groups according to their contact with the cortical gray matter. Pre-and postoperative FLAIR and gadolinium-enhanced T1-weighted imaging tumor volumes were measured using a three-dimensional imaging volume analyzer, and the resection rate was calculated. To evaluate the association between SMR rate and outcome, we subdivided patients whose tumors were totally resected into the SMR and non-SMR groups by moving the threshold value of SMR in 10% increments from 0% and compared their overall survival (OS) change. An improvement in OS was observed when the threshold value of SMR was 30% or more. In the cortical group (n = 23), SMR (n = 8) tended to prolong OS compared with gross total resection (GTR) (n = 15), with the median OS of 69.6 and 22.1 months, respectively (p = 0.0945). Contrastingly, in the deep-seated group (n = 10), SMR (n = 4) significantly shortened OS compared with GTR (n = 6), with median OS of 10.2 and 27.9 months, respectively (p = 0.0221). SMR could help prolong OS in patients with cortical GBM when 30% or more volume reduction is achieved in FLAIR lesions, although the impact of SMR for deep-seated GBM must be validated in larger co-horts.

    DOI： 10.2176/jns-nmc.2022-0351

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    CiNii Research

  • Predicting <i>TERT</i> promoter mutation status using <SUP>1</SUP>H-MR spectroscopy and stretched-exponential model of diffusion-weighted imaging in <i>IDH</i>-wildtype diffuse astrocytic glioma without intense enhancement

    Yamashita, K; Hatae, R; Kikuchi, K; Kuga, D; Hata, N; Yamamoto, H; Obara, M; Yoshimoto, K; Ishigami, K; Togao, O

    NEURORADIOLOGY   65 ( 8 )   1205 - 1213   2023年8月   （ ISSN:0028-3940 eISSN:1432-1920 ）

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    記述言語：英語   出版者・発行元：Neuroradiology  

    Purpose: Isocitrate dehydrogenase (IDH)-wildtype diffuse astrocytic glioma with telomerase reverse transcriptase (TERT) promoter mutation is defined as glioblastoma by the WHO 2021 criteria, revealing that TERT promotor mutation is highly associated with tumor aggressiveness. The aim of this study was to identify features from MR spectroscopy (MRS) and multi-exponential models of DWI distinguishing wild-type TERT (TERTw) from TERT promoter mutation (TERTm) in IDH-wildtype diffuse astrocytic glioma. Methods: Participants comprised 25 adult patients with IDH-wildtype diffuse astrocytic glioma. Participants were classified into TERTw and TERTm groups. Point-resolved spectroscopy sequences were used for MRS data acquisition. DWI was performed with 13 different b-factors. Peak height ratios of NAA/Cr and Cho/Cr were calculated from MRS data. Mean apparent diffusion coefficient (ADC), perfusion fraction (f), diffusion coefficient (D), pseudo-diffusion coefficient (D*), distributed diffusion coefficient (DDC), and heterogeneity index (α) were obtained using multi-exponential models from DWI data. Each parameter was compared between TERTw and TERTm using the Mann–Whitney U test. Correlations between parameters derived from MRS and DWI were also evaluated. Results: NAA/Cr and Cho/Cr were both higher for TERTw than for TERTm. The α of TERTw was smaller than that of TERTm, while the f of TERTw was higher than that of TERTm. NAA/Cr correlated negatively with α, but not with other DWI parameters. Cho/Cr did not show significant correlations with any DWI parameters. Conclusion: The combination of NAA/Cr and α may have merit in clinical situation to predict the TERT mutation status of IDH-wildtype diffuse astrocytic glioma without intense enhancement.

    DOI： 10.1007/s00234-023-03177-y

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  • Supramaximal resectionは皮質神経膠腫患者の生存期間を延長させる　容積測定による研究(Supramaximal Resection Can Prolong the Survival of Patients with Cortical Glioblastoma: A Volumetric Study)

    Otsuji Ryosuke, Hata Nobuhiro, Funakoshi Yusuke, Kuga Daisuke, Togao Osamu, Hatae Ryusuke, Sangatsuda Yuhei, Fujioka Yutaka, Takigawa Kosuke, Sako Aki, Kikuchi Kazufumi, Yoshitake Tadamasa, Yamamoto Hidetaka, Mizoguchi Masahiro, Yoshimoto Koji

    Neurologia medico-chirurgica   63 ( 8 )   364 - 374   2023年8月   （ ISSN:0470-8105 ）

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    記述言語：英語   出版者・発行元：(一社)日本脳神経外科学会  

    膠芽腫患者を対象とした後ろ向き研究を実施し、FLAIR病変切除率を評価することで、supramaximal resection(SMR)の臨床効果について検討した。2006年12月～2018年8月に神経膠腫と診断された成人患者のうち、肉眼的全切除(GTR)が施行された成人33例(年齢中央値64歳、男性19例)を対象とした。評価項目は腫瘍切除率(手術前後のFLAIRおよびガドリニウム強調T1強調画像の腫瘍体積を3D画像体積分析装置により測定)、SMR率(0%から10%刻み)などとした。腫瘍を皮質灰白質との接触により、皮質群23例(SMR 8例、GTR 15例)、深在性群10例(SMR 4例、全切除6例)に分けて検討した。その結果、SMR閾値が30%以上の場合に全生存期間の改善が観察された。皮質群ではGTRと比較してSMRで全生存期間が延長する傾向が認められた(69.6ヵ月対22.1ヵ月)。一方、深在群ではGTRと比較してSMRで全生存期間が有意に短縮していた(10.2ヵ月対27.9ヵ月、p=0.0221)。以上から、FLAIR病変のsupramaximal resectionは神経膠腫患者の生存期間を延長可能であることが示された。

  • Combination bezafibrate and nivolumab treatment of patients with advanced non-small cell lung cancer

    Tanaka, K; Chamoto, K; Saeki, S; Hatae, R; Ikematsu, Y; Sakai, K; Ando, N; Sonomura, K; Kojima, S; Taketsuna, M; Kim, YH; Yoshida, H; Ozasa, H; Sakamori, Y; Hirano, T; Matsuda, F; Hirai, T; Nishio, K; Sakagami, T; Fukushima, M; Nakanishi, Y; Honjo, T; Okamoto, I

    SCIENCE TRANSLATIONAL MEDICINE   14 ( 675 )   eabq0021   2022年12月   （ ISSN:1946-6234 eISSN:1946-6242 ）

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    記述言語：英語   出版者・発行元：Science Translational Medicine  

    Despite the success of cancer immunotherapies such as programmed cell death-1 (PD-1) and PD-1 ligand 1 (PDL1) inhibitors, patients often develop resistance. New combination therapies with PD-1/PD-L1 inhibitors are needed to overcome this issue. Bezafibrate, a ligand of peroxisome proliferator-activated receptor-γ coactivator 1α/peroxisome proliferator-activated receptor complexes, has shown a synergistic antitumor effect with PD-1 blockade in mice that is mediated by activation of mitochondria in T cells. We have therefore now performed a phase 1 trial (UMIN000017854) of bezafibrate with nivolumab in previously treated patients with advanced non-small cell lung cancer. The primary end point was the percentage of patients who experience dose-limiting toxicity, and this combination regimen was found to be well tolerated. Preplanned comprehensive analysis of plasma metabolites and gene expression in peripheral cytotoxic T cells indicated that bezafibrate promoted T cell function through up-regulation of mitochondrial metabolism including fatty acid oxidation and may thereby have prolonged the duration of response. This combination strategy targeting T cell metabolism thus has the potential to maintain antitumor activity of immune checkpoint inhibitors and warrants further validation.

    DOI： 10.1126/scitranslmed.abq0021

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  • A case of ganglioglioma grade 3 with H3 K27M mutation arising in the medial temporal lobe in an elderly patient

    Fujii, Y; Hatae, R; Hata, N; Suzuki, SO; Sangatsuda, Y; Takigawa, K; Funakoshi, Y; Fujioka, Y; Kuga, D; Mizoguchi, M; Iwaki, T; Yoshimoto, K

    NEUROPATHOLOGY   42 ( 3 )   197 - 203   2022年6月   （ ISSN:0919-6544 eISSN:1440-1789 ）

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    記述言語：英語   出版者・発行元：Neuropathology  

    The mutation p.K27M in H3F3A (H3 K27M mutation) is mainly detected in diffuse midline glioma. However, recent studies have demonstrated that H3 K27M mutation could also be observed in a subset of gangliogliomas. Importantly, most H3 K27-mutated ganglioglioma cases also harbor BRAF V600E mutation. Herein, we report a rare case of H3 K27M-mutated ganglioglioma grade 3 without BRAF mutation arising in the medial temporal lobe in an elderly man. A small biopsy specimen was sampled. The pathological diagnosis was diffuse astrocytoma. The tumor progressed gradually during an 18-month follow-up period. Gadolinium enhancement on magnetic resonance imaging was noted 36 months after the biopsy. The patient was referred to a hospital for tumor resection. Histological analysis of resected specimens led to a diagnosis of ganglioglioma grade 3 with H3 K27M mutation. The patient underwent concurrent temozolomide chemotherapy with radiotherapy. Although the patient's condition deteriorated after chemotherapy due to disease progression, he survived for more than 23 months after tumor resection. We present this rare case and discuss the involvement of H3 K27M mutation in ganglioglioma grade 3.

    DOI： 10.1111/neup.12793

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  • 高齢患者の内側側頭葉に発症した、H3 K27M変異を伴うグレード3の神経節膠腫症例(A case of ganglioglioma grade 3 with H3 K27M mutation arising in the medial temporal lobe in an elderly patient)

    Fujii Yutaro, Hatae Ryusuke, Hata Nobuhiro, Suzuki Satoshi O., Sangatsuda Yuhei, Takigawa Kosuke, Funakoshi Yusuke, Fujioka Yutaka, Kuga Daisuke, Mizoguchi Masahiro, Iwaki Toru, Yoshimoto Koji

    NEUROPATHOLOGY   42 ( 3 )   197 - 203   2022年6月   （ ISSN:0919-6544 ）

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    記述言語：英語   出版者・発行元：John Wiley & Sons Australia, Ltd  

    高齢患者の内側側頭葉に発症した、BRAF変異を伴わずH3 K27M変異を伴った、グレード3神経節膠腫の稀少例を報告した。症例は56歳男性で、一過性の視野欠損を主訴に、他院に来院した。MRI所見では左側頭葉に腫瘍を認め、生検により、びまん性星細胞腫と病理診断されたが、18ヵ月の経過観察の間に病変が徐々に増大し、生検から36ヵ月後に施行したT1強調画像でガドリウム増強が認められたため、九州大学病院脳神経外科に紹介された。治療では腫瘍切除術が行われ、切除試料の組織学的検査から、グレード3の神経節膠腫と診断され、テモゾロミドによる同時化学放射線治療が施行された。治療サイクル2サイクル後に病状進行による悪化はみられたが、腫瘍切除術後23ヵ月以上の生存転帰が得られた。なお、Sanger法によるシーケンス解析と高感度融解曲線解析をIDH1遺伝子、IDH2遺伝子、BRAF遺伝子、H3F3A遺伝子の各遺伝子について行ったところ、IDH1/2やBRAF V600E遺伝子変異は検出されなかったが、H3 K27M遺伝子変異が検出された。

  • Changes in the Relapse Pattern and Prognosis of Glioblastoma After Approval of First-Line Bevacizumab: A Single-Center Retrospective Study

    Funakoshi, Y; Takigawa, K; Hata, N; Kuga, D; Hatae, R; Sangatsuda, Y; Fujioka, Y; Otsuji, R; Sako, A; Yoshitake, T; Togao, O; Hiwatashi, A; Iwaki, T; Mizoguchi, M; Yoshimoto, K

    WORLD NEUROSURGERY   159   E479 - E487   2022年3月   （ ISSN:1878-8750 eISSN:1878-8769 ）

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    記述言語：英語   出版者・発行元：World Neurosurgery  

    Background: Controversies exist regarding the aggressive recurrence of glioblastoma after bevacizumab treatment. We analyzed the clinical impact of bevacizumab approval in Japan by evaluating the clinical course and relapse pattern in patients with glioblastoma. Methods: We included 100 patients with IDH-wild-type glioblastoma from September 2006 to February 2018 in our institution. The patients were classified into the pre-bevacizumab (n = 51) and post-bevacizumab (n = 49) groups. Overall, progression-free, deterioration-free, and postprogression survivals were compared. We analyzed the relapse pattern of 72 patients, whose radiographic progressions were evaluated. Results: Significant improvement in progression-free (pre-bevacizumab, 7.5 months; post-bevacizumab, 9.9 months; P = 0.0153) and deterioration-free (pre-bevacizumab, 8.5 months; post-bevacizumab, 13.8 months; P = 0.0046) survivals was seen. These survival prolongations were strongly correlated (r: 0.91, P < 0.0001). The nonenhancing tumor pattern was novel in the post-bevacizumab era (5 of 33). The presence of a nonenhancing tumor did not indicate poor postprogression survival (hazard ratio: 0.82 [0.26–2.62], P = 0.7377). The rate of early focal recurrence was significantly lower (P = 0.0155) in the post-bevacizumab (4 of 33) than in the pre-bevacizumab (18 of 39) era. There was a significant decrease in early focal recurrence after approval of bevacizumab in patients with unresectable tumors (P = 0.0110). The treatment era was significantly correlated with a decreased rate of early focal recurrence (P = 0.0021, univariate analysis; P = 0.0144, multivariate analysis). Conclusions: Approval of first-line bevacizumab in Japan for unresectable tumors may prevent early progression and clinical deterioration of glioblastoma without worsening the clinical course after relapse.

    DOI： 10.1016/j.wneu.2021.12.075

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  • Gamma distribution model of diffusion MRI for evaluating the isocitrate dehydrogenase mutation status of glioblastomas

    Takase, H; Togao, O; Kikuchi, K; Hata, N; Hatae, R; Chikui, T; Tokumori, K; Kami, Y; Kuga, D; Sangatsuda, Y; Mizoguchi, M; Hiwatashi, A; Ishigami, K

    BRITISH JOURNAL OF RADIOLOGY   95 ( 1133 )   20210392   2022年   （ ISSN:0007-1285 eISSN:1748-880X ）

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    記述言語：英語   出版者・発行元：British Journal of Radiology  

    Objective: To determine whether the γ distribution (GD) model of diffusion MRI is useful in the evaluation of the isocitrate dehydrogenase (IDH) mutation status of glioblastomas. Methods: 12 patients with IDH-mutant glioblastomas and 54 patients with IDH-wildtype glioblastomas were imaged with diffusion-weighted imaging using 13 b-values from 0 to 1000 s/mm2. The shape parameter (κ) and scale parameter (θ) were obtained with the GD model. Fractions of three different areas under the probability density function curve (f1, f2, f3) were defined as follows: f1, diffusion coefficient (D) < 1.0×10−3 mm2/s; f2, D > 1.0×10−3 and <3.0×10−3 mm2/s; f3, D > 3.0 × 10−3 mm2/s. The GD model-derived parameters measured in gadolinium-enhancing lesions were compared between the IDH-mutant and IDH-wildtype groups. Receiver operating curve analyses were performed to assess the parameters' diagnostic performances. Results: The IDH-mutant group’s f1 (0.474 ± 0.143) was significantly larger than the IDH-wildtype group’s (0.347 ± 0.122, p = 0.0024). The IDH-mutant group’s f2 (0.417 ± 0.131) was significantly smaller than the IDH-wildtype group’s (0.504 ± 0.126, p = 0.036). The IDH-mutant group’s f3 (0.109 ± 0.060) was significantly smaller than the IDH-wildtype group’s (0.149 ± 0.063, p = 0.0466). The f1 showed the best diagnostic performance among the GD model-derived parameters with the area under the curve value of 0.753. Conclusion: The GD model could well describe the pathological features of IDH-mutant and IDH-wildtype glioblastomas, and was useful in the differentiation of these tumors. Advances in knowledge: Diffusion MRI based on the γ distribution model could well describe the pathological features of IDH-mutant and IDH-wildtype glioblastomas, and its use enabled the significant differentiation of these tumors. The γ distribution model may contribute to the non-invasive identification of the IDH mutation status based on histological viewpoint.

    DOI： 10.1259/bjr.20210392

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  • Giant cranial angiolipoma with arteriovenous fistula: A case report

    Hatae R., Mizoguchi M., Arimura K., Kiyozawa D., Shimogawa T., Sangatsuda Y., Nishimura A., Ono K., Oda Y., Yoshimoto K.

    Surgical Neurology International   13   314   2022年   （ ISSN:2229-5097 ）

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    記述言語：英語   出版者・発行元：Surgical Neurology International  

    Background: Angiolipomas are benign mesenchymal tumors comprising mature adipocytes and abnormal blood vessels, commonly found in the subcutaneous tissue of the trunk and rarely in the skull. Furthermore, sporadic cases of angiolipoma with arteriovenous fistula (AVF) have been reported. Case Description: We reported the case of a 72-year-old woman who presented with head swelling, seizures, and cognitive dysfunction. Computed tomography and magnetic resonance imaging revealed a right frontal bone tumor exceeding a sagittal suture of up to 10.7 cm. Angiography revealed AVF and varices formation. Endovascular embolization was performed to treat the AVF and reduce blood loss during surgical resection. Two days after the embolization, a craniotomy was performed; however, uncontrollable bleeding was observed at the time of tumor resection. Postoperatively, the patient was symptom-free and has been stable for 2 years without recurrence. Conclusion: Despite careful preoperative evaluation and treatment planning, the patient in this case report was difficult to treat. Such cases require adequate preparation.

    DOI： 10.25259/SNI_422_2022

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    PubMed

  • First-line bevacizumab contributes to survival improvement in glioblastoma patients complementary to temozolomide 査読

    Nobuhiro Hata, Masahiro Mizoguchi, Daisuke Kuga, Ryusuke Hatae, Yojiro Akagi, Yuhei Sangatsuda, Takeo Amemiya, Yuhei Michiwaki, Yutaka Fujioka, Kosuke Takigawa, Satoshi O. Suzuki, Tadamasa Yoshitake, Osamu Togao, Akio Hiwatashi, Koji Yoshimoto, Koji Iihara

    Journal of Neuro-Oncology   146 ( 3 )   451 - 458   2020年2月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1007/s11060-019-03339-0

  • Combination of host immune metabolic biomarkers for the PD-1 blockade cancer immunotherapy 査読

    Ryusuke Hatae, Kenji Chamoto, Young Hak Kim, Kazuhiro Sonomura, Kei Taneishi, Shuji Kawaguchi, Hironori Yoshida, Hiroaki Ozasa, Yuichi Sakamori, Maryam Akrami, Sidonia Fagarasan, Izuru Masuda, Yasushi Okuno, Fumihiko Matsuda, Toyohiro Hirai, Tasuku Honjo

    JCI Insight   5 ( 2 )   2020年1月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1172/jci.insight.133501

  • Analytical performance of a new automated chemiluminescent magnetic immunoassays for soluble PD-1, PD-L1, and CTLA-4 in human plasma 査読

    Megumi Goto, Kenji Chamoto, Keiko Higuchi, Saya Yamashita, Kenta Noda, Takuya Iino, Masahiro Miura, Toshinari Yamasaki, Osamu Ogawa, Makoto Sonobe, Hiroshi Date, Junzo Hamanishi, Masaki Mandai, Yoshimasa Tanaka, Shunsuke Chikuma, Ryusuke Hatae, Manabu Muto, Sachiko Minamiguchi, Nagahiro Minato, Tasuku Honjo

    Scientific reports   9 ( 1 )   2019年12月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1038/s41598-019-46548-3

  • Relevance of calcification and contrast enhancement pattern for molecular diagnosis and survival prediction of gliomas based on the 2016 World Health Organization Classification 査読

    Yuhei Michiwaki, Nobuhiro Hata, Masahiro Mizoguchi, Akio Hiwatashi, Daisuke Kuga, Ryusuke Hatae, Yojiro Akagi, Takeo Amemiya, Yutaka Fujioka, Osamu Togao, Satoshi O. Suzuki, Koji Yoshimoto, Toru Iwaki, Koji Iihara

    Clinical Neurology and Neurosurgery   187   2019年12月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.clineuro.2019.105556

  • Correlation between prognosis of glioblastoma and choline/N-acetyl aspartate ratio in MR spectroscopy 査読

    Yojiro Akagi, Naoki Noguchi, Nobuhiro Hata, Ryusuke Hatae, Yuhei Michiwaki, Yuhei Sangatsuda, Takeo Amemiya, Daisuke Kuga, Koji Yamashita, Osamu Togao, Akio Hiwatashi, Koji Yoshimoto, Masahiro Mizoguchi, Koji Iihara

    Interdisciplinary Neurosurgery: Advanced Techniques and Case Management   18   2019年12月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.inat.2019.100498

  • Predicting TERT promoter mutation using MR images in patients with wild-type IDH1 glioblastoma 査読

    K. Yamashita, R. Hatae, A. Hiwatashi, O. Togao, K. Kikuchi, D. Momosaka, Y. Yamashita, D. Kuga, N. Hata, K. Yoshimoto, S. O. Suzuki, T. Iwaki, K. Iihara, H. Honda

    Diagnostic and Interventional Imaging   100 ( 7-8 )   411 - 419   2019年7月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.diii.2019.02.010

  • The Effectiveness of Salvage Treatments for Recurrent Lesions of Oligodendrogliomas Previously Treated with Upfront Chemotherapy 査読

    Daisuke Kuga, Nobuhiro Hata, Yojiro Akagi, Takeo Amemiya, Yuhei Sangatsuda, Ryusuke Hatae, Koji Yoshimoto, Masahiro Mizoguchi, Koji Iihara

    World Neurosurgery   114   e735 - e742   2018年6月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.wneu.2018.03.069

  • Reclassification of 400 consecutive glioma cases based on the revised 2016WHO classification 査読

    Yojiro Akagi, Koji Yoshimoto, Nobuhiro Hata, Daisuke Kuga, Ryusuke Hatae, Takeo Amemiya, Yuhei Sangatsuda, Satoshi O. Suzuki, Toru Iwaki, Masahiro Mizoguchi, Koji Iihara

    Brain tumor pathology   35 ( 2 )   81 - 89   2018年4月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1007/s10014-018-0313-4

  • High-resolution melting and immunohistochemical analysis efficiently detects mutually exclusive genetic alterations of adamantinomatous and papillary craniopharyngiomas 査読

    Koji Yoshimoto, Ryusuke Hatae, Satoshi O. Suzuki, Nobuhiro Hata, Daisuke Kuga, Yojiro Akagi, Takeo Amemiya, Yuhei Sangatsuda, Nobutaka Mukae, Masahiro Mizoguchi, Toru Iwaki, Koji Iihara

    Neuropathology   38 ( 1 )   3 - 10   2018年2月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1111/neup.12408

  • Prevalence and clinicopathological features of H3.3 G34-mutant high-grade gliomas a retrospective study of 411 consecutive glioma cases in a single institution 査読

    Koji Yoshimoto, Ryusuke Hatae, Yuhei Sangatsuda, Satoshi O. Suzuki, Nobuhiro Hata, Yojiro Akagi, Daisuke Kuga, Murata Hideki, Koji Yamashita, Osamu Togao, Akio Hiwatashi, Toru Iwaki, Masahiro Mizoguchi, Koji Iihara

    Brain tumor pathology   34 ( 3 )   103 - 112   2017年7月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1007/s10014-017-0287-7

  • Insular primary glioblastomas with IDH mutations Clinical and biological specificities 査読

    Nobuhiro Hata, Ryusuke Hatae, Koji Yoshimoto, Hideki Murata, Daisuke Kuga, Yojiro Akagi, Yuhei Sangatsuda, Satoshi O. Suzuki, Toru Iwaki, Masahiro Mizoguchi, Koji Iihara

    Neuropathology   37 ( 3 )   200 - 206   2017年6月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1111/neup.12362

  • A comprehensive analysis identifies BRAF hotspot mutations associated with gliomas with peculiar epithelial morphology 査読

    Ryusuke Hatae, Nobuhiro Hata, Satoshi O. Suzuki, Koji Yoshimoto, Daisuke Kuga, Hideki Murata, Yojiro Akagi, Yuhei Sangatsuda, Toru Iwaki, Masahiro Mizoguchi, Koji Iihara

    Neuropathology   37 ( 3 )   191 - 199   2017年6月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1111/neup.12347

  • Add-on bevacizumab can prevent early clinical deterioration and prolong survival in newly diagnosed partially resected glioblastoma patients with a poor performance status 査読

    Nobuhiro Hata, Koji Yoshimoto, Ryusuke Hatae, Daisuke Kuga, Yojiro Akagi, Yuhei Sangatsuda, Satoshi O. Suzuki, Tadahisa Shono, Masahiro Mizoguchi, Koji Iihara

    OncoTargets and Therapy   10   429 - 437   2017年1月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.2147/OTT.S125587

  • Deferred radiotherapy and upfront procarbazine-ACNU-vincristine administration for 1p19q codeleted oligodendroglial tumors are associated with favorable outcome without compromising patient performance, regardless of WHO grade 査読

    Nobuhiro Hata, Koji Yoshimoto, Ryusuke Hatae, Daisuke Kuga, Yojiro Akagi, Satoshi O. Suzuki, Toru Iwaki, Tadahisa Shono, Masahiro Mizoguchi, Koji Iihara

    OncoTargets and Therapy   9   7123 - 7131   2016年11月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.2147/OTT.S115911

  • Precise detection of IDH1/2 and BRAF hotspot mutations in clinical glioma tissues by a differential calculus analysis of high-resolution melting data 査読

    Ryusuke Hatae, Nobuhiro Hata, Koji Yoshimoto, Daisuke Kuga, Yojiro Akagi, Hideki Murata, Satoshi O. Suzuki, Masahiro Mizoguchi, Koji Iihara

    PloS one   11 ( 8 )   2016年8月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1371/journal.pone.0160489

  • A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas 査読

    Hideyuki Arita, Kai Yamasaki, Yuko Matsushita, Taishi Nakamura, Asanao Shimokawa, Hirokazu Takami, Shota Tanaka, Akitake Mukasa, Mitsuaki Shirahata, Saki Shimizu, Kaori Suzuki, Kuniaki Saito, Keiichi Kobayashi, Fumi Higuchi, Takeo Uzuka, Ryohei Otani, Kaoru Tamura, Kazutaka Sumita, Makoto Ohno, Yasuji Miyakita, Naoki Kagawa, Naoya Hashimoto, Ryusuke Hatae, Koji Yoshimoto, Naoki Shinojima, Hideo Nakamura, Yonehiro Kanemura, Yoshiko Okita, Manabu Kinoshita, Kenichi Ishibashi, Tomoko Shofuda, Yoshinori Kodama, Kanji Mori, Yusuke Tomogane, Junya Fukai, Koji Fujita, Yuzo Terakawa, Naohiro Tsuyuguchi, Shusuke Moriuchi, Masahiro Nonaka, Hiroyoshi Suzuki, Makoto Shibuya, Taketoshi Maehara, Nobuhito Saito, Motoo Nagane, Nobutaka Kawahara, Keisuke Ueki, Toshiki Yoshimine, Etsuo Miyaoka, Ryo Nishikawa, Takashi Komori, Yoshitaka Narita, Koichi Ichimura

    Acta neuropathologica communications   4 ( 1 )   2016年8月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1186/s40478-016-0351-2

  • MR imaging-based analysis of glioblastoma multiforme Estimation of IDH1 mutation status 査読

    K. Yamashita, Akio Hiwatashi, O. Togao, K. Kikuchi, R. Hatae, K. Yoshimoto, M. Mizoguchi, S. O. Suzuki, T. Yoshiura, H. Honda

    American Journal of Neuroradiology   37 ( 1 )   58 - 65   2016年1月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.3174/ajnr.A4491

  • Current trends and healthcare resource usage in the hospital treatment of primary malignant brain tumor in Japan A national survey using the diagnostic procedure combination database (J-ASPECT study-brain tumor) 査読

    Koji Yoshimoto, Akiko Kada, Daisuke Kuga, Ryusuke Hatae, Hideki Murata, Yojiro Akagi, Kunihiro Nishimura, Ryota Kurogi, Ataru Nishimura, Nobuhiro Hata, Masahiro Mizoguchi, Tetsuro Sayama, Koji Iihara

    Neurologia medico-chirurgica   56 ( 11 )   664 - 673   2016年1月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.2176/nmc.oa.2016-0172

  • Visionary approach for the treatment of brain tumors 査読

    Koji Yoshimoto, Akiko Kada, Ryusuke Hatae, Hideki Murata, Yojiro Akagi, Kunihiro Nishimura, Masahiro Mizoguchi, Koji Iihara

    Japanese Journal of Neurosurgery   24 ( 10 )   693 - 698   2015年10月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.7887/jcns.24.693

  • Detection of proneural/mesenchymal marker expression in glioblastoma temporospatial dynamics and association with chromatin-modifying gene expression 査読

    Hideki Murata, Koji Yoshimoto, Ryusuke Hatae, Yojiro Akagi, Masahiro Mizoguchi, Nobuhiro Hata, Daisuke Kuga, Akira Nakamizo, Toshiyuki Amano, Tetsuro Sayama, Koji Iihara

    Journal of Neuro-Oncology   125 ( 1 )   33 - 41   2015年10月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1007/s11060-015-1886-y

▼全件表示

講演・口頭発表等

  • NSCLC患者の末梢血中PD-1high CD8+ T細胞はPD-1抗体の治療効果と関係する

    日本癌学会学術総会  2019年9月 

    　詳細を見る

    開催年月日： 2020年6月

    記述言語：日本語  

    国名：日本国  

    Current clinical biomarkers of PD-1 blockade cancer immunotherapy rely on properties of tumor. Less invasive biomarkers based on immune property is necessary to properly discriminate the responders and non-responders. Using the peripheral blood cells from the 64 patients with NSCLC before nivolumab injection, the expression of immune checkpoint molecules were investigated. We found that the frequency of PD-1high CD8+ T cells in the peripheral were lower in responders compared with that of non-responders. ROC analysis of this marker showed the AUC=0.72. The PD-1high population highly expressed Ki67 and EOMES, but less produced IFN-g and Granzyme B. On the other hand, PD-1intermediate population express less Ki67 and EOMES and produce high levels of IFN-g and Granzyme B. Thes e data suggest that PD-1high CD8+ T cells undergo exhausted state and PD-1intermediate CD8+ T cells are functional. The frequency of PD-1high CD8+ T cells in the peripheral blood might be useful as a predictive biomarker.

  • WHO新分類(WHO2021)の課題とその克服2:脳腫瘍病理形態診断と分子診断の融合の可能性　Astrocytoma,IDH-mutantにおけるCDKN2A/B hemizygous deletionの意義とp16/MTAP免疫染色の有用性

    尾辻 亮介, 秦 暢宏, 山元 英崇, 藤岡 寛, 三月田 祐平, 波多江 龍亮, 空閑 太亮, 溝口 昌弘, 吉本 幸司

    Brain Tumor Pathology  2024年5月  日本脳腫瘍病理学会

    　詳細を見る

    記述言語：日本語  

MISC

▼全件表示

所属学協会

  • 日本脳神経外科学会

  • 日本脳神経外科コングレス

  • 日本脳腫瘍学会

  • 日本脳腫瘍病理学会

  • 日本臨床腫瘍学会

  • 日本癌学会

  • 日本脳卒中学会

▼全件表示

学術貢献活動

  • 学術論文等の審査

    役割：査読

    2020年

    　詳細を見る

    種別：査読等 

    外国語雑誌　査読論文数：2

共同研究・競争的資金等の研究課題

  • liquid biopsyによる、神経膠腫の非侵襲的診断/病態把握システムの開発

    研究課題/領域番号：20K09392  2020年4月 - 2023年3月

    科学研究費助成事業  基盤研究(C)

    秦 暢宏, 溝口 昌弘, 空閑 太亮, 波多江 龍亮, 三月田 祐平, 樋渡 昭雄, 栂尾 理

    　 詳細を見る

    資金種別：科研費

    神経膠腫は、他の癌腫のような腫瘍マーカーが存在しないため、早期診断や病勢の把握が困難である。最近の遺伝子解析法の進歩：digital PCRシステムの開発により、髄液中のごく微量に存在する腫瘍由来の核酸を用いた分子診断：liquid biopsyが可能となった。この方法を応用して、髄液検査により分子マーカーを検出し、定量化する方法を確立し、MRI,PETなどの画像検査データと統合することで、腫瘍の経時的動態（治療反応性や再発・増勢）を正確にモニターするシステムを構築することが本研究の目的である。

    CiNii Research

  • リンパ球及び代謝産物解析による転移性脳腫瘍患者の免疫チェックポイント阻害剤に対する抵抗性の解明

    2020年

    稲盛研究助成

    　 詳細を見る

    担当区分：研究代表者  資金種別：受託研究

  • 免疫代謝と腸内細菌のクロストークに関連するPD-1抗体がん免疫治療制御因子の解析

    研究課題/領域番号：19K17673  2019年 - 2020年

    日本学術振興会  科学研究費助成事業  若手研究

    波多江 龍亮

    　 詳細を見る

    担当区分：研究代表者  資金種別：科研費

    PD-1抗体治療において治療効果を予測するバイオマーカーを確立すること、PD-1抗体に対する不応答性の機序を解明することが喫緊の課題である。我々が少数例のヒト肺がん末梢血検体を用いて予備検討を行ったところ、PD-1抗体の治療効果と、T細胞のエネルギー代謝状況および血中腸内細菌関連代謝産物に関連性が示唆された。
    本研究では、症例数を増やしてT細胞のエネルギー代謝と代謝産物に注目したPD-1抗体の治療効果予測バイオマーカーの確立を目指す。また、腸内細菌関連代謝産物や腸内細菌の状態がT細胞へ与える影響を調べることで、T細胞の免疫代謝と腸内細菌のクロストークのメカニズムを明らかにする。

    CiNii Research

担当授業科目

  • 保健学科臨床医学論Ⅱ　脳神経外科２

    2019年10月 - 2020年3月   後期

学内運営に関わる各種委員・役職等

  • 2019年7月 - 2020年6月   その他 小児がん部会

  • 2019年7月 - 2020年6月   その他 外来化学療法室運営委員会

  • 2019年7月 - 2020年6月   その他 がん薬物療法レジメン審査委員会

専門診療領域

  • 生物系／医歯薬学／外科系臨床医学／脳神経外科学

臨床医資格

  • 専門医

    日本脳神経外科学会

医師免許取得年

  • 2007年