2024/05/18 更新

写真a

タナカ ショウタ
田中 將太
Tanaka Shota
所属
医歯薬学域 教授
職名
教授
外部リンク

学位

  • 医学博士 ( 東京大学 )

研究分野

  • ライフサイエンス / 脳神経外科学

学歴

  • 東京大学   Faculty of Medicine   School of Medicine

    1995年4月 - 2001年3月

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経歴

  • 岡山大学   大学院医歯薬学総合研究科   教授

    2024年1月 - 現在

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  • 東京大学   大学院医学系研究科   講師

    2021年4月 - 2023年12月

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論文

  • Transcriptomic and epigenetic dissection of spinal ependymoma (SP-EPN) identifies clinically relevant subtypes enriched for tumors with and without NF2 mutation

    Sina Neyazi, Erika Yamazawa, Karoline Hack, Shota Tanaka, Genta Nagae, Catena Kresbach, Takayoshi Umeda, Alicia Eckhardt, Kenji Tatsuno, Lara Pohl, Taijun Hana, Michael Bockmayr, Phyo Kim, Mario M. Dorostkar, Toshihiro Takami, Denise Obrecht, Keisuke Takai, Abigail K. Suwala, Takashi Komori, Shweta Godbole, Annika K. Wefers, Ryohei Otani, Julia E. Neumann, Fumi Higuchi, Leonille Schweizer, Yuta Nakanishi, Camelia Maria Monoranu, Hirokazu Takami, Lara Engertsberger, Keisuke Yamada, Viktoria Ruf, Masashi Nomura, Theresa Mohme, Akitake Mukasa, Jochen Herms, Shunsaku Takayanagi, Martin Mynarek, Reiko Matsuura, Katrin Lamszus, Kazuhiko Ishii, Lan Kluwe, Hideaki Imai, Andreas von Deimling, Tsukasa Koike, Martin Benesch, Yoshihiro Kushihara, Matija Snuderl, Shohei Nambu, Stephan Frank, Takaki Omura, Christian Hagel, Kazuha Kugasawa, Viktor F. Mautner, Koichi Ichimura, Stefan Rutkowski, Hiroyuki Aburatani, Nobuhito Saito, Ulrich Schüller

    Acta Neuropathologica   147 ( 1 )   2024年6月

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    掲載種別:研究論文(学術雑誌)  

    Ependymomas encompass multiple clinically relevant tumor types based on localization and molecular profiles. Tumors of the methylation class “spinal ependymoma” (SP-EPN) represent the most common intramedullary neoplasms in children and adults. However, their developmental origin is ill-defined, molecular data are scarce, and the potential heterogeneity within SP-EPN remains unexplored. The only known recurrent genetic events in SP-EPN are loss of chromosome 22q and NF2 mutations, but neither types and frequency of these alterations nor their clinical relevance have been described in a large, epigenetically defined series. Transcriptomic (n = 72), epigenetic (n = 225), genetic (n = 134), and clinical data (n = 112) were integrated for a detailed molecular overview on SP-EPN. Additionally, we mapped SP-EPN transcriptomes to developmental atlases of the developing and adult spinal cord to uncover potential developmental origins of these tumors. The integration of transcriptomic ependymoma data with single-cell atlases of the spinal cord revealed that SP-EPN display the highest similarities to mature adult ependymal cells. Unsupervised hierarchical clustering of transcriptomic data together with integrated analysis of methylation profiles identified two molecular SP-EPN subtypes. Subtype A tumors primarily carried previously known germline or sporadic NF2 mutations together with 22q loss (bi-allelic NF2 loss), resulting in decreased NF2 expression. Furthermore, they more often presented as multilocular disease and demonstrated a significantly reduced progression-free survival as compared to SP-EP subtype B. In contrast, subtype B predominantly contained samples without NF2 mutation detected in sequencing together with 22q loss (monoallelic NF2 loss). These tumors showed regular NF2 expression but more extensive global copy number alterations. Based on integrated molecular profiling of a large multi-center cohort, we identified two distinct SP-EPN subtypes with important implications for genetic counseling, patient surveillance, and drug development priorities.

    DOI: 10.1007/s00401-023-02668-9

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  • Molecular biology and novel therapeutics for IDH mutant gliomas: The new era of IDH inhibitors. 国際誌

    Yosuke Kitagawa, Ami Kobayashi, Daniel P Cahill, Hiroaki Wakimoto, Shota Tanaka

    Biochimica et biophysica acta. Reviews on cancer   1879 ( 3 )   189102 - 189102   2024年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Gliomas with Isocitrate dehydrogenase (IDH) mutation represent a discrete category of primary brain tumors with distinct and unique characteristics, behaviors, and clinical disease outcomes. IDH mutations lead to aberrant high-level production of the oncometabolite D-2-hydroxyglutarate (D-2HG), which act as a competitive inhibitor of enzymes regulating epigenetics, signaling pathways, metabolism, and various other processes. This review summarizes the significance of IDH mutations, resulting upregulation of D-2HG and the associated molecular pathways in gliomagenesis. With the recent finding of clinically effective IDH inhibitors in these gliomas, this article offers a comprehensive overview of the new era of innovative therapeutic approaches based on mechanistic rationales, encompassing both completed and ongoing clinical trials targeting gliomas with IDH mutations.

    DOI: 10.1016/j.bbcan.2024.189102

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  • Glioblastoma with high O6-methyl-guanine DNA methyltransferase expression are more immunologically active than tumors with low MGMT expression. 国際誌

    Yoshihiro Kushihara, Shota Tanaka, Yukari Kobayashi, Koji Nagaoka, Miyu Kikuchi, Takahide Nejo, Erika Yamazawa, Shohei Nambu, Kazuha Kugasawa, Hirokazu Takami, Shunsaku Takayanagi, Nobuhito Saito, Kazuhiro Kakimi

    Frontiers in immunology   15   1328375 - 1328375   2024年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Glioblastoma (GBM) is a highly lethal brain tumor. The effectiveness of temozolomide (TMZ) treatment in GBM is linked to the methylation status of O6-methyl-guanine DNA methyltransferase (MGMT) promoter. Patients with unmethylated MGMT promoter have limited treatment options available. Consequently, there is a pressing need for alternative therapeutic strategies for such patients. METHODS: Data, including transcriptomic and clinical information, as well as information on MGMT promoter methylation status in primary GBM, were obtained from The Cancer Genome Atlas (TCGA) (n=121) and Chinese Glioma Genome Atlas (CGGA) (n=83) datasets. Samples were categorized into high and low MGMT expression groups, MGMT-high (MGMT-H) and MGMT-low (MGMT-L) tumors. A comprehensive transcriptome analysis was conducted to explore the tumor-immune microenvironment. Furthermore, we integrated transcriptome data from 13 GBM patients operated at our institution with findings from tumor-infiltrating lymphocyte (TIL) cultures, specifically investigating their response to autologous tumors. RESULTS: Gene signatures associated with various immune cells, including CD8 T cells, helper T cells, B cells, and macrophages, were noted in MGMT-H tumors. Pathway analysis confirmed the enrichment of immune cell-related pathways. Additionally, biological processes involved in the activation of monocytes and lymphocytes were observed in MGMT-H tumors. Furthermore, TIL culture experiments showed a greater presence of tumor-reactive T cells in MGMT-H tumors compared to MGMT-L tumors. These findings suggest that MGMT-H tumors has a potential for enhanced immune response against tumors mediated by CD8 T cells. CONCLUSION: Our study provides novel insights into the immune cell composition of MGMT-H tumors, which is characterized by the infiltration of type 1 helper T cells and activated B cells, and also the presence of tumor-reactive T cells evidenced by TIL culture. These findings contribute to a better understanding of the immune response in MGMT-H tumors, emphasizing their potential for immunotherapy. Further studies are warranted to investigate on the mechanisms of MGMT expression and antitumor immunity.

    DOI: 10.3389/fimmu.2024.1328375

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  • Region-specific DNA hydroxymethylation along the malignant progression of IDH-mutant gliomas

    Taijun Hana, Akitake Mukasa, Masashi Nomura, Genta Nagae, Shogo Yamamoto, Kenji Tatsuno, Hiroki Ueda, Shiro Fukuda, Takayoshi Umeda, Shota Tanaka, Takahide Nejo, Yosuke Kitagawa, Erika Yamazawa, Satoshi Takahashi, Tsukasa Koike, Yoshihiro Kushihara, Hirokazu Takami, Shunsaku Takayanagi, Hiroyuki Aburatani, Nobuhito Saito

    Cancer Science   2024年

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    掲載種別:研究論文(学術雑誌)  

    The majority of low-grade isocitrate dehydrogenase-mutant (IDHmt) gliomas undergo malignant progression (MP), but their underlying mechanism remains unclear. IDHmt gliomas exhibit global DNA methylation, and our previous report suggested that MP could be partly attributed to passive demethylation caused by accelerated cell cycles. However, during MP, there is also active demethylation mediated by ten-eleven translocation, such as DNA hydroxymethylation. Hydroxymethylation is reported to potentially contribute to gene expression regulation, but its role in MP remains under investigation. Therefore, we conducted a comprehensive analysis of hydroxymethylation during MP of IDHmt astrocytoma. Five primary/malignantly progressed IDHmt astrocytoma pairs were analyzed with oxidative bisulfite and the Infinium EPIC methylation array, detecting 5-hydroxymethyl cytosine at over 850,000 locations for region-specific hydroxymethylation assessment. Notably, we observed significant sharing of hydroxymethylated genomic regions during MP across the samples. Hydroxymethylated CpGs were enriched in open sea and intergenic regions (p < 0.001), and genes undergoing hydroxymethylation were significantly associated with cancer-related signaling pathways. RNA sequencing data integration identified 91 genes with significant positive/negative hydroxymethylation-expression correlations. Functional analysis suggested that positively correlated genes are involved in cell-cycle promotion, while negatively correlated ones are associated with antineoplastic functions. Analyses of The Cancer Genome Atlas clinical data on glioma were in line with these findings. Motif-enrichment analysis suggested the potential involvement of the transcription factor KLF4 in hydroxymethylation-based gene regulation. Our findings shed light on the significance of region-specific DNA hydroxymethylation in glioma MP and suggest its potential role in cancer-related gene expression and IDHmt glioma malignancy.

    DOI: 10.1111/cas.16127

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  • Distinct patterns of copy number alterations may predict poor outcome in central nervous system germ cell tumors

    Hirokazu Takami, Kaishi Satomi, Kohei Fukuoka, Taishi Nakamura, Shota Tanaka, Akitake Mukasa, Nobuhito Saito, Tomonari Suzuki, Takaaki Yanagisawa, Kazuhiko Sugiyama, Masayuki Kanamori, Toshihiro Kumabe, Teiji Tominaga, Kaoru Tamura, Taketoshi Maehara, Masahiro Nonaka, Akio Asai, Kiyotaka Yokogami, Hideo Takeshima, Toshihiko Iuchi, Keiichi Kobayashi, Koji Yoshimoto, Keiichi Sakai, Yoichi Nakazato, Masao Matsutani, Motoo Nagane, Ryo Nishikawa, Koichi Ichimura

    Scientific Reports   13 ( 1 )   2023年9月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    Abstract

    We have previously reported that 12p gain may predict the presence of malignant components and poor prognosis for CNS germ cell tumor (GCT). Recently, 3p25.3 gain was identified as an independent predictor of poor prognosis for testicular GCT. Eighty-one CNS GCTs were analyzed. Copy number was calculated using methylation arrays. Five cases (6.2%) showed 3p25.3 gain, but only among the 40 non-germinomatous GCTs (NGGCTs) (5/40, 12.5%; p = 0.03). Among NGGCTs, those with a yolk sac tumor component showed a significantly higher frequency of 3p25.3 gain (18.2%) than those without (1.5%; p = 0.048). NGGCTs with gain showed significantly shorter progression-free survival (PFS) than those without (p = 0.047). The 3p25.3 gain and 12p gain were independent from each other. The combination of 3p25.3 gain and/or 12p gain was more frequent among NGGCTs with malignant components (69%) than among those without (29%; p = 0.02). Germinomas containing a higher number of copy number alterations showed shorter PFS than those with fewer (p = 0.03). Taken together, a finding of 3p25.3 gain may be a copy number alteration specific to NGGCTs and in combination with 12p gain could serve as a marker of negative prognosis or treatment resistance. Germinoma with frequent chromosomal instability may constitute an unfavorable subgroup.

    DOI: 10.1038/s41598-023-42842-3

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    その他リンク: https://www.nature.com/articles/s41598-023-42842-3

  • Intraventricular central neurocytoma molecularly defined as extraventricular neurocytoma: a case representing the discrepancy between clinicopathological and molecular classifications.

    Daisuke Sato, Hirokazu Takami, Shunsaku Takayanagi, Masako Ikemura, Reiko Matsuura, Shota Tanaka, Nobuhito Saito

    Brain tumor pathology   40 ( 4 )   230 - 234   2023年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Central neurocytoma (CN) is classically defined by its intraventricular location, neuronal/neurocytic differentiation, and histological resemblance to oligodendroglioma. Extraventricular neurocytoma (EVN) shares similar histological features with CN, while it distributes any site without contact with the ventricular system. CN and EVN have distinct methylation landscapes, and EVN has a signature fusion gene, FGFR1-TACC1. These characteristics distinguish between CN and EVN. A 30-year-old female underwent craniotomy and resection of a left intraventricular tumor at our institution. The histopathology demonstrated the classical findings of CN. Adjuvant irradiation with 60 Gy followed. No recurrence has been recorded for 25 years postoperatively. RNA sequencing revealed FGFR1-TACC1 fusion and methylation profile was discrepant with CN but compatible with EVN. We experienced a case of anatomically and histologically proven CN in the lateral ventricle. However, the FGFR1-TACC1 fusion gene and methylation profiling suggested the molecular diagnosis of EVN. The representative case was an "intraventricular" neurocytoma displaying molecular features of an "extraventricular" neurocytoma. Clinicopathological and molecular definitions have collided in our case and raised questions about the current definition of CN and EVN.

    DOI: 10.1007/s10014-023-00469-2

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  • PTPN11 variant may be a prognostic indicator of IDH-wildtype glioblastoma in a comprehensive genomic profiling cohort. 国際誌

    Ryohei Otani, Masachika Ikegami, Ryoji Yamada, Hirohisa Yajima, Shinji Kawamura, Sakura Shimizu, Shota Tanaka, Shunsaku Takayanagi, Hirokazu Takami, Tatsuro Yamaguchi

    Journal of neuro-oncology   164 ( 1 )   221 - 229   2023年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: Glioblastoma (GBM) is the most common type of primary malignant brain tumor and has a poor prognosis. Identifying novel targets and stratification strategies is urgently needed to improve patient survival. The present study aimed to identify clinically relevant genomic alterations in IDH-wildtype GBM using data from comprehensive genomic profiling (CGP) assays performed nationwide in Japan. METHODS: The CGP assay results of 392 IDH-wildtype GBM cases performed between October 2019 and February 2023 obtained from the Center for Cancer Genomics and Advanced Therapeutics were retrospectively analyzed. RESULTS: The median patient age was 52.5 years, and 207 patients (53%) were male. In the 286 patients for whom survival information was available, a protein-tyrosine phosphatase non-receptor type 11 (PTPN11) variant detected in 20 patients (6.8%) was extracted as the gene associated with significantly shorter overall survival (p = 0.002). Multivariate analysis demonstrated that the PTPN11 variant and poor performance status were independent prognostic indicators. In contrast, no prognostic impact was observed in the cohort in The Cancer Genome Atlas data. The discrepancy in the prognostic impact of the PTPN11 variant from these two pools might have resulted from differences in the biases affecting the survival of patients who underwent a CGP assay, including left-truncation and right-censored bias. However, survival simulation done to adjust for these biases showed that the prognostic impact of the PTPN11 variant was also significant. CONCLUSIONS: The PTPN11 variant was a negative prognostic indicator of IDH-wildtype GBM in the patient cohort with the CGP assay.

    DOI: 10.1007/s11060-023-04411-6

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  • CHD5 gene variant predicts leptomeningeal metastasis after surgical resection of brain metastases of breast cancer. 国際誌

    Ryohei Otani, Daichi Sadato, Ryoji Yamada, Hirohisa Yajima, Shinji Kawamura, Sakura Shimizu, Shota Tanaka, Shunsaku Takayanagi, Hirokazu Takami, Tatsuro Yamaguchi

    Journal of neuro-oncology   163 ( 3 )   657 - 662   2023年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: Leptomeningeal metastasis (LM) is a complication of surgery for brain metastasis and is a risk factor of poor prognosis. The risk of LM is particularly high after surgery for a breast cancer metastasis to the brain. If the risk of LM after surgical resection for a brain metastasis were predictable, appropriate adjuvant therapy could be administered to individual patients to improve their prognosis. The present study aimed to reveal the genetic characteristics of brain metastases as means of predicting LM in breast cancer patients. METHODS: Ten patients with brain metastases of breast cancer presented LM after surgical resection were analyzed by whole-exome sequencing. RESULTS: A chromodomain-helicase-DNA-binding protein 5 (CHD5) gene alteration was detected in nine cases (90%), including a nonsynonymous variant in four cases and copy number deletion in five cases. CHD5 protein expression was lost in nine cases and had decreased in one case. The frequency of CHD5 gene alteration in brain metastases with LM was significantly higher than in primary breast cancer (2.3%) or in brain metastases of breast cancer (0%) (p < 0.0001). CONCLUSIONS: These results suggested that the CHD5 gene alteration was associated with LM after surgical resection of breast cancer brain metastases. Searching for the gene alteration might predict the LM risk after surgical resection.

    DOI: 10.1007/s11060-023-04381-9

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  • Lymphoproliferative disorder during temozolomide therapy; a representative case of a formidable complication and management challenges. 国際誌

    Daisuke Sato, Hirokazu Takami, Shunsaku Takayanagi, Kazuki Taoka, Mariko Tanaka, Reiko Matsuura, Shota Tanaka, Nobuhito Saito

    BMC neurology   23 ( 1 )   224 - 224   2023年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Lymphoproliferative disorder represents a heterogeneous clinicopathological spectrum characterized by uncontrolled proliferation of lymphocytes. Immunodeficiency is a major trigger of its development. While induction of immunodeficiency is a well-known adverse effect of temozolomide therapy, development of lymphoproliferative disorder following temozolomide therapy has not previously been described. CASE PRESENTATION: A patient with brainstem glioma developed constitutional symptoms, pancytopenia, splenomegaly and generalized lymphadenopathy during the 2nd cycle of maintenance therapy following induction therapy with temozolomide. Epstein-Barr virus-infected lymphocytes were observed histopathologically and "other iatrogenic immunodeficiency-associated lymphoproliferative disorder" (OIIA-LPD) was diagnosed. Although discontinuation of temozolomide led to rapid remission, relapse was observed 4 months later. CHOP chemotherapy was induced, resulting in secondary remission. Vigilant follow-up for another 14 months showed radiologically stable brainstem glioma and no further recurrence of OIIA-LPD. CONCLUSIONS: This is the first report documenting OIIA-LPD during temozolomide administration. Timely diagnosis of the disease and discontinuation of the causative agent were considered to be the management of choice. Close monitoring for relapse should be continued. Finding a balance between glioma management and controlling the remission of OIIA-LPD remains to be clarified.

    DOI: 10.1186/s12883-023-03274-8

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  • 脳腫瘍のメチル化診断 中枢神経胚細胞腫におけるコピー数異常と予後との相関

    高見 浩数, 里見 介史, 福岡 講平, 中村 大志, 田中 將太, 武笠 晃丈, 齊藤 延人, 鈴木 智成, 柳澤 隆昭, 杉山 一彦, 金森 政之, 隈部 俊宏, 冨永 悌二, 田村 郁, 前原 健寿, 埜中 正博, 淺井 昭雄, 横上 聖貴, 竹島 秀雄, 井内 俊彦, 小林 啓一, 吉本 幸司, 酒井 圭一, 中里 洋一, 松谷 雅生, 永根 基雄, 西川 亮, 市村 幸一

    Brain Tumor Pathology   40 ( Suppl. )   063 - 063   2023年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • IDH野生型低悪性度星細胞腫の臨床・病理学的特徴と治療の変遷 46症例の解析

    高柳 俊作, 田中 將太, 高見 浩数, 池村 雅子, 齊藤 延人

    Brain Tumor Pathology   40 ( Suppl. )   099 - 099   2023年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • Isolated relapse of plasma cell leukemia in the central nervous systems: a case report and literature review.

    Takafumi Obo, Ken Morita, Yutaro Sumida, Kumi Nakazaki-Watadani, Masako Ikemura, Koichiro Yasaka, Osamu Abe, Hirokazu Takami, Shunsaku Takayanagi, Shota Tanaka, Hiroaki Maki, Yosuke Masamoto, Akiyoshi Miwa, Mineo Kurokawa

    International journal of hematology   118 ( 1 )   135 - 140   2023年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Plasma cell leukemia is a rare yet aggressive form of multiple myeloma characterized by high levels of plasma cells circulating in the peripheral blood. We recently experienced a case of plasma cell leukemia that had been in stringent complete remission for nine years after autologous stem cell transplantations with subsequent courses of lenalidomide maintenance therapy, and then relapsed as an extramedullary plasmacytoma in the central nervous system. Assessment of the bone marrow did not prove proliferation of plasma cells at relapse, but imbalanced elevation of serum levels of free light chains was observed without changes in other clinical biomarkers including immunoglobulin levels. Salvage chemotherapy with isatuximab, pomalidomide, and dexamethasone (IsaPD) was promptly initiated. After two courses of IsaPD, significant remission was achieved and the neuronal symptoms completely resolved. When excessive serum levels of clonotypic free light chains are noted, their significance should be carefully assessed even when plasma cell propagation in the bone marrow is not observed. In such cases, hematologists should search for extramedullary proliferation of plasma cells, including in the immune-privileged central nervous system.

    DOI: 10.1007/s12185-023-03545-7

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  • Correction: Morphologically, genetically and spatially mixed astrocytoma and oligodendroglioma; chronological acquisition of 1p/19q codeletion and CDKN2A deletion: a case report.

    Hirokazu Takami, Akitake Mukasa, Shunsaku Takayanagi, Tsukasa Koike, Reiko Matsuura, Masako Ikemura, Tetsuo Ushiku, Gakushi Yoshikawa, Junji Shibahara, Shota Tanaka, Nobuhito Saito

    Brain tumor pathology   40 ( 2 )   142 - 142   2023年1月

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  • Safety and efficacy of tumour-treating fields (TTFields) therapy for newly diagnosed glioblastoma in Japanese patients using the Novo-TTF System: a prospective post-approval study. 国際誌

    Ryo Nishikawa, Fumiyuki Yamasaki, Yoshiki Arakawa, Yoshihiro Muragaki, Yoshitaka Narita, Shota Tanaka, Shigeru Yamaguchi, Akitake Mukasa, Masayuki Kanamori

    Japanese journal of clinical oncology   53 ( 5 )   371 - 377   2023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)  

    BACKGROUND: Tumour-treating fields therapy is a locoregional, anti-cancer treatment. Efficacy and safety of tumour-treating fields therapy in adults with newly diagnosed glioblastoma were demonstrated in the pivotal phase 3 EF-14 study (NCT00916409). Here, we report post-approval data of tumour-treating fields therapy in Japanese patients with newly diagnosed glioblastoma. METHODS: Unsolicited post-marketing surveillance data from Japanese patients with newly diagnosed glioblastoma treated with tumour-treating fields therapy (December 2016-June 2020) were retrospectively analysed. The primary endpoints were skin, neurological and psychiatric adverse events. The secondary endpoints were 1- and 2-year overall survival rates, and the 6-month progression-free survival. adverse events were analysed using MedDRA v24.0. The overall survival and progression-free survival were assessed using the Kaplan-Meier survival analysis (log-rank testing). The Cox proportional hazard regression analyses were also performed. RESULTS: Forty patients with newly diagnosed glioblastoma were enrolled (62.5% male; median age 59 years; median baseline Karnofsky Performance Scale score 90). The most common tumour-treating-fields-therapy-related adverse event was beneath-array local skin reaction (60% of patients). The adverse events were mostly mild to moderate in severity. Neurological disorders were observed in 2.5% patients (one patient reported dysesthesia). No psychiatric disorders were reported. The 1- and 2-year overall survival rates were 77.9% (95% CI 60.6-88.3) and 53.6% (35.5-68.7%), respectively. The 6-month progression-free survival was 77.5% (61.2-87.6%). These survival rates compare favourably with those in the EF-14 trial (1- and 2-year overall survival rates: 73% [69-77%] and 43% [39-48%], respectively; 6-month progression-free survival rate: 56% (51-61%). CONCLUSION: This post-approval, real-world evidence study revealed no new safety signals and suggests the safety and efficacy of tumour-treating fields therapy in Japanese patients with newly diagnosed glioblastoma.

    DOI: 10.1093/jjco/hyad001

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  • Clinical utility of Todai OncoPanel in the setting of approved comprehensive cancer genomic profiling tests in Japan. 国際誌

    Hidenori Kage, Aya Shinozaki-Ushiku, Kazunaga Ishigaki, Yusuke Sato, Masahiko Tanabe, Shota Tanaka, Michihiro Tanikawa, Kousuke Watanabe, Shingo Kato, Kiwamu Akagi, Keita Uchino, Kinuko Mitani, Shunji Takahashi, Yuji Miura, Sadakatsu Ikeda, Yasushi Kojima, Kiyotaka Watanabe, Hitoshi Mochizuki, Hironori Yamaguchi, Yoshimasa Kawazoe, Kosuke Kashiwabara, Shinji Kohsaka, Kenji Tatsuno, Tetsuo Ushiku, Kazuhiko Ohe, Yutaka Yatomi, Yasuyuki Seto, Hiroyuki Aburatani, Hiroyuki Mano, Kiyoshi Miyagawa, Katsutoshi Oda

    Cancer science   114 ( 4 )   1710 - 1717   2023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)  

    Comprehensive cancer genome profiling (CGP) has been nationally reimbursed in Japan since June 2019. Less than 10% of the patients have been reported to undergo recommended treatment. Todai OncoPanel (TOP) is a dual DNA-RNA panel as well as a paired tumor-normal matched test. Two hundred patients underwent Todai OncoPanel as part of Advanced Medical Care B with approval by the Ministry of Health, Labour and Welfare between September 2018 and December 2019. Tests were performed in patients with cancers without standard treatment or when patients had already undergone standard treatment. Data from DNA and RNA panels were analyzed in 198 and 191 patients, respectively. The percentage of patients who were given therapeutic or diagnostic recommendations was 61% (120/198). One hundred and four samples (53%) harbored gene alterations that were detected with the DNA panel and had potential treatment implications, and 14 samples (7%) had a high tumor mutational burden. Twenty-two samples (11.1%) harbored 30 fusion transcripts or MET exon 14 skipping that were detected by the RNA panel. Of those thirty transcripts, six had treatment implications and four had diagnostic implications. Thirteen patients (7%) were found to have pathogenic or likely pathogenic germline variants and genetic counseling was recommended. Overall, 12 patients (6%) received recommended treatment. In summary, patients benefited from both TOP DNA and RNA panels while following the same indication as the approved CGP tests. (UMIN000033647).

    DOI: 10.1111/cas.15717

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  • Morphologically, genetically and spatially mixed astrocytoma and oligodendroglioma; chronological acquisition of 1p/19q codeletion and CDKN2A deletion: a case report.

    Hirokazu Takami, Akitake Mukasa, Shunsaku Takayanagi, Tsukasa Koike, Reiko Matsuura, Masako Ikemura, Tetsuo Ushiku, Gakushi Yoshikawa, Junji Shibahara, Shota Tanaka, Nobuhito Saito

    Brain tumor pathology   40 ( 1 )   26 - 34   2023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)  

    "Oligoastrocytoma" disappeared as of the revised fourth edition of the World Health Organization Classification of Tumours of the Central Nervous System, except where appended with "not otherwise specified (NOS)". However, histopathological and genetic backgrounds of cases with dual features of astrocytoma/oligodendroglioma have been sparsely reported. We encountered a 54-year-old man with right frontal glioma comprising two distinct parts on imaging and histopathological examination: grade 4 astrocytoma with IDH1-R132H, ATRX loss, p53-positivity and intact 1p/19q; and oligodendroglioma with IDH1-R132H, intact ATRX, p53-negativity and partially deleted 1p/19q. At recurrence, histopathology showed low-grade mixed astrocytic and oligodendroglial features: the former with IDH1-R132H, ATRX loss, p53-positivity and intact 1p/19q and the latter showing IDH1-R132H, intact ATRX, p53-negativity and 1p/19q codeletion. At second recurrence, histopathology was astrocytoma grade 4 with IDH1-R132H, ATRX loss, p53-positivity and intact 1p/19q. Notably, 1p/19q codeletion was acquired at recurrence and CDKN2A was deleted at second recurrence. These findings suggest insights into tumorigenesis: (1) gliomas with two distinct lineages might mix to produce "oligoastrocytoma"; and (2) 1p/19q codeletion and CDKN2A deletion might be acquired during chemo-radiotherapy. Ultimately, astrocytic and oligodendroglial clones might co-exist developmentally or these two lineages might share a common cell-of-origin, with IDH1-R132H as the shared molecular feature.

    DOI: 10.1007/s10014-022-00448-z

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  • Recurrent glioblastoma metastatic to the lumbar vertebra: A case report and literature review: Surgical oncology. 国際誌

    Ako Matsuhashi, Shota Tanaka, Hirokazu Takami, Masashi Nomura, Masako Ikemura, Yoshitaka Matsubayashi, Yusuke Shinoda, Keisuke Yamada, Yu Sakai, Yasuaki Karasawa, Shunsaku Takayanagi, Nobuhito Saito

    Frontiers in oncology   13   1101552 - 1101552   2023年

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    記述言語:英語  

    BACKGROUND: Glioblastoma is a malignant tumor, and its prognosis is as poor as 1.5 to 2 years. Most cases recur within one year even under the standard treatment. The majority of recurrences are local, and in rare cases, metastasize mostly within the centra nervous system. Extradural metastasis of glioma is exceedingly rare. Here, we present a case of vertebral metastasis of glioblastoma. CASE PRESENTATION: We present a 21-year-old man post total resection of the right parietal glioblastoma, diagnosed with lumbar metastasis. He originally presented with impaired consciousness and left hemiplegia and underwent gross total resection of the tumor. Given the diagnosis of glioblastoma, he was treated with radiotherapy combined with concurrent and adjuvant temozolomide. Six months after tumor resection, the patient presented with severe back pain, and was diagnosed as metastatic glioblastoma on the first lumbar vertebrae. Posterior decompression with fixation and postoperative radiotherapy were conducted. He went on to receive temozolomide and bevacizumab. However, at 3 months after the diagnosis of lumbar metastasis, further disease progression was noted, and his care was transitioned to best supportive care. Comparison on copy number status between primary and metastatic lesions on methylation array analysis revealed more enhanced chromosomal instability including 7p loss, 7q gain and 8 gain in the metastatic lesion. CONCLUSION: Based upon the literature review and our case, younger age of initial presentation, multiple surgical interventions, and long overall survival seem to be the risk factors of vertebral metastasis. As the prognosis of glioblastoma improves over time, its vertebral metastasis is seemingly more common. Therefore, extradural metastasis should be kept in mind in the treatment of glioblastoma. Further, detailed genomic analysis on multiple paired specimens is mandated to elucidate the molecular mechanisms of vertebral metastasis.

    DOI: 10.3389/fonc.2023.1101552

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  • Case report and literature review: exploration of molecular therapeutic targets in recurrent malignant meningioma through comprehensive genetic analysis with Todai OncoPanel. 国際誌

    Kenta Ohara, Satoru Miyawaki, Hirofumi Nakatomi, Atsushi Okano, Yu Teranishi, Yuki Shinya, Daiichiro Ishigami, Hiroki Hongo, Shunsaku Takayanagi, Shota Tanaka, Aya Shinozaki-Ushiku, Shinji Kohsaka, Hidenori Kage, Katsutoshi Oda, Kiyoshi Miyagawa, Hiroyuki Aburatani, Hiroyuki Mano, Kenji Tatsuno, Nobuhito Saito

    Frontiers in neurology   14   1270046 - 1270046   2023年

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    記述言語:英語  

    BACKGROUND: Despite accumulating research on the molecular characteristics of meningiomas, no definitive molecularly targeted therapy for these tumors has been established to date. Molecular mechanisms underlying meningioma progression also remain unclear. Comprehensive genetic testing approaches can reveal actionable gene aberrations in meningiomas. However, there is still limited information on whether profiling the molecular status of subsequent recurrent meningiomas could influence the choice of molecular-targeted therapies. CASE PRESENTATION: We report a case of meningioma with malignant progression and multiple recurrences. We performed matched tumor pair analysis using the Todai OncoPanel to investigate the possibility of additional standard treatments. The loss of several chromosomal regions, including NF2 and CDKN2A, which is associated with aggressive meningiomas, was considered a significant driver event for malignant progression. Using additional matched tumor pair analysis, mutations in TRAF7, ARID1A, and ERBB3 were identified as subclonal driver events at the time of recurrence. No genetic aberrations were found for which evidence-based targeted therapy was applicable. We also reviewed previous reports of molecular therapies in meningioma to discuss issues with the current molecular testing approach. CONCLUSION: Gene panel testing platforms such as the Todai OncoPanel represent a powerful approach to elucidate actionable genetic alterations in various types of tumors, although their use is still limited to the diagnosis and prediction of prognosis in meningiomas. To enable targeted molecular therapy informed by gene-panel testing, further studies including matched tumor pair analyses are required to understand the molecular characteristics of meningiomas and develop treatments based on genetic abnormalities.

    DOI: 10.3389/fneur.2023.1270046

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  • Bevacizumab beyond Progression for Newly Diagnosed Glioblastoma (BIOMARK): Phase II Safety, Efficacy and Biomarker Study. 国際誌

    Motoo Nagane, Koichi Ichimura, Ritsuko Onuki, Daichi Narushima, Mai Honda-Kitahara, Kaishi Satomi, Arata Tomiyama, Yasuhito Arai, Tatsuhiro Shibata, Yoshitaka Narita, Takeo Uzuka, Hideo Nakamura, Mitsutoshi Nakada, Yoshiki Arakawa, Takanori Ohnishi, Akitake Mukasa, Shota Tanaka, Toshihiko Wakabayashi, Tomokazu Aoki, Shigeki Aoki, Soichiro Shibui, Masao Matsutani, Keisuke Ishizawa, Hideaki Yokoo, Hiroyoshi Suzuki, Satoshi Morita, Mamoru Kato, Ryo Nishikawa

    Cancers   14 ( 22 )   2022年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We evaluated the efficacy and safety of bevacizumab beyond progression (BBP) in Japanese patients with newly diagnosed glioblastoma and explored predictors of response to bevacizumab. This phase II study evaluated a protocol-defined primary therapy by radiotherapy with concurrent and adjuvant temozolomide plus bevacizumab, followed by bevacizumab monotherapy, and secondary therapy (BBP: bevacizumab upon progression). Ninety patients received the protocol-defined primary therapy (BBP group, n = 25). Median overall survival (mOS) and median progression-free survival (mPFS) were 25.0 and 14.9 months, respectively. In the BBP group, in which O6-methylguanine-DNA methyltransferase (MGMT)-unmethylated tumors predominated, mOS and mPFS were 5.8 and 1.9 months from BBP initiation and 16.8 and 11.4 months from the initial diagnosis, respectively. The primary endpoint, the 2-year survival rate of the BBP group, was 27.0% and was unmet. No unexpected adverse events occurred. Expression profiling using RNA sequencing identified that Cluster 2, which was enriched with the genes involved in macrophage or microglia activation, was associated with longer OS and PFS independent of the MGMT methylation status. Cluster 2 was identified as a significantly favorable independent predictor for PFS, along with younger age and methylated MGMT. The novel expression classifier may predict the prognosis of glioblastoma patients treated with bevacizumab.

    DOI: 10.3390/cancers14225522

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  • 再発膠芽腫に対するエリブリンの第2相多施設単群医師主導治験

    高橋 雅道, 川嶋 聡, 口羽 文, 佐立 崚, 米盛 勧, 永根 基雄, 荒川 芳輝, 武笠 晃丈, 田中 將太, 西川 亮, 村垣 善浩, 増富 健吉, 市村 幸一, 中村 健一, 成田 善孝

    日本癌治療学会学術集会抄録集   60回   EN6 - 3   2022年10月

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    記述言語:英語   出版者・発行元:(一社)日本癌治療学会  

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  • 【神経疾患とゲノム医療】個別病態・疾患のゲノム医療 脳腫瘍

    高柳 俊作, 田中 將太, 齊藤 延人

    Clinical Neuroscience   40 ( 9 )   1100 - 1103   2022年9月

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    記述言語:日本語   出版者・発行元:(株)中外医学社  

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  • Revisitation of imaging features of skull base chondrosarcoma in comparison to chordoma. 国際誌

    Hirotaka Hasegawa, Masahiro Shin, Ryoko Niwa, Satoshi Koizumi, Shoko Yoshimoto, Naoyuki Shono, Yuki Shinya, Hirokazu Takami, Shota Tanaka, Motoyuki Umekawa, Shiori Amemiya, Taichi Kin, Nobuhito Saito

    Journal of neuro-oncology   159 ( 3 )   581 - 590   2022年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: Pre-surgical diagnosis of skull base chondrosarcoma (SBC) is often challenging due to the resemblance to chordoma. The goal of this study was to develop an optimal method for predicting SBC diagnosis. METHODS: This retrospective study included patients with histologically diagnosed SBC and skull base chordoma. Their clinical and radiologic features were compared, and the predictive factors of SBC were examined. RESULTS: Forty-one patients with SBC and 41 with chordoma were included. Most SBCs exhibited hypointensity (25, 64.1%) or isointensity (12, 30.8%) on T1-weighted images, and hyperintensity (34, 87.1%) or mixed intensity (5, 12.8%) on T2-weighted images. MRI contrast enhancement was usually avid or fair (89.7%) with "arabesque"-like pattern (41.0%). The lateral/paramidline location was more common in SBC than in chordoma (85.4% vs. 9.8%; P < 0.01), while midline SBCs (14.6%) were also possible. Multivariate analysis demonstrated that higher apparent diffusion coefficient (ADC) value (unit odds ratio 1.01; 95% confidence interval 1.00-1.02; P < 0.01) was associated with an SBC diagnosis. An ADC value of ≥ 1750 × 10-6 mm2/s demonstrated a strong association with an SBC diagnosis (odds ratio 5.89 × 102; 95% confidence interval 51.0-6.80 × 103; P < 0.01) and yielded a sensitivity of 93.9%, specificity of 97.4%, positive predictive value of 96.9%, and negative predictive value of 95.0%. CONCLUSION: The ADC-based method is helpful in distinguishing SBC from chordoma and readily applicable in clinical practice. The prediction accuracy increases when other characteristics of SBC, such as non-midline location and arabesque-like enhancement, are considered together.

    DOI: 10.1007/s11060-022-04097-2

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  • 東大オンコパネル(TOP)を用いたプレシジョンメディシン(先進医療B)(Precision Medicine with Todai OncoPanel(TOP) in Advanced Medicine Care B)

    鹿毛 秀宣, 牛久 綾, 石垣 和祥, 佐藤 悠佑, 田辺 真彦, 田中 將太, 谷川 道洋, 渡邊 広祐, 高阪 真路, 辰野 健二, 牛久 哲男, 油谷 浩幸, 間野 博行, 宮川 清, 織田 克利

    日本癌学会総会記事   81回   P - 1070   2022年9月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • ゲノムおよびトランスクリプトーム解析による膠芽腫の分子的多様性の解明(Dissecting the molecular complexity underlying glioblastoma by genomic and transcriptome profiling)

    中島 拓真, 舟越 勇介, 南部 翔平, 畝田 篤仁, 片山 琴絵, 花谷 亮典, 井元 清哉, 田中 將太, 齋藤 竜太, 吉本 幸司, 成田 善孝, 鈴木 啓道

    日本癌学会総会記事   81回   E - 1040   2022年9月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • 星細胞腫IDH変異型の全ゲノムシークエンスと包括的な分子学的解析(Whole-genome sequencing and comprehensive molecular profiling of Astrocytoma, IDH-mutant)

    舟越 勇介, 中島 拓真, 南部 翔平, 畝田 篤仁, 片山 琴絵, 井元 清哉, 花谷 亮典, 田中 將太, 齋藤 竜太, 吉本 幸司, 成田 善孝, 鈴木 啓道

    日本癌学会総会記事   81回   E - 1038   2022年9月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • ゲノムおよびトランスクリプトーム解析による膠芽腫の分子的多様性の解明(Dissecting the molecular complexity underlying glioblastoma by genomic and transcriptome profiling)

    中島 拓真, 舟越 勇介, 南部 翔平, 畝田 篤仁, 片山 琴絵, 花谷 亮典, 井元 清哉, 田中 將太, 齋藤 竜太, 吉本 幸司, 成田 善孝, 鈴木 啓道

    日本癌学会総会記事   81回   E - 1040   2022年9月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • Oligodendroglioma,IDH-mutant and 1p/19q-codeletedのマルチオミクス解析による全ゲノム解析の全貌(Whole genome multi-omics landscape of Oligodenderoglioma, IDH-mutant and 1p/19q-codeleted)

    舟越 勇介, 南部 翔平, 中島 拓真, 畝田 篤仁, 片山 琴絵, 井元 清哉, 花谷 亮典, 田中 將太, 齋藤 竜太, 吉本 幸司, 成田 善孝, 鈴木 啓道

    日本癌学会総会記事   81回   E - 1041   2022年9月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • Metformin with Temozolomide for Newly Diagnosed Glioblastoma: Results of Phase I Study and a Brief Review of Relevant Studies. 国際誌

    Makoto Ohno, Chifumi Kitanaka, Yasuji Miyakita, Shota Tanaka, Yukihiko Sonoda, Kazuhiko Mishima, Eiichi Ishikawa, Masamichi Takahashi, Shunsuke Yanagisawa, Ken Ohashi, Motoo Nagane, Yoshitaka Narita

    Cancers   14 ( 17 )   2022年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Glioblastoma (GBM) inevitably recurs due to a resistance to current standard therapy. We showed that the antidiabetic drug metformin (MF) can induce the differentiation of stem-like glioma-initiating cells and suppress tumor formation through AMPK-FOXO3 activation. In this study, we design a phase I/II study to examine the clinical effect of MF. We aim to determine a recommended phase II MF dose with maintenance temozolomide (TMZ) in patients with newly diagnosed GBM who completed standard concomitant radiotherapy and TMZ. MF dose-escalation was planned using a 3 + 3 design. Dose-limiting toxicities (DLTs) were assessed during the first six weeks after MF initiation. Three patients were treated with 1500 mg/day MF and four patients were treated with 2250 mg/day MF between February 2021 and January 2022. No DLTs were observed. The most common adverse effects were appetite loss, nausea, and diarrhea, all of which were manageable. Two patients experienced tumor progression at 6.0 and 6.1 months, and one died 12.2 months after initial surgery. The other five patients remained stable at the last follow-up session. The MF dose of up to 2250 mg/day combined with maintenance TMZ appeared to be well tolerated, and we proceeded to a phase II study with 2250 mg/day MF.

    DOI: 10.3390/cancers14174222

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  • Chronological Progression and Management of Syringobulbia Caused by Spinal Hemangioblastoma: A Case Series and Review of the Literature. 国際誌

    Takahiro Tsuchiya, Hirokazu Takami, Shoko Yoshimoto, Shohei Nambu, Shunsaku Takayanagi, Shota Tanaka, Nobuhito Saito

    World neurosurgery   167   e127-e136   2022年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Syringomyelia often accompanies spinal hemangioblastoma (SHB). It often shows progression to the medulla oblongata, dubbed as "syringobulbia", which presents critical symptoms such as dysphagia and respiratory compromise. Appropriate management of chronological syringomyelia progression toward syringobulbia is not set in stone. This study aims to unravel the clinical and chronological behavior of syringobulbia and its management. METHODS: A single-institution case series study of 5 patients operated for SHB with syringobulbia was conducted. Serial preoperative magnetic resonance imaging scans were analyzed in further details, especially focusing on the chronological progression of syringomyelia. A literature review was performed to describe clinical/imaging characteristics. RESULTS: Chronological imaging analyses revealed that despite the relatively steady progression of syringomyelia over years, it accelerated when developing syringobulbia. Intramedullary signal change ("presyringomyelia") was observed in the area where syringomyelia subsequently occurred. Literature review yielded another 15 cases of SHB with syringobulbia, totaling 20 cases. Bulbar dysfunction was seen in 4 cases (20%). Gross total resection was performed in all cases except 1, which underwent just syringotomy. Rapid postoperative symptom improvement was observed in all cases, as well as immediate imaging resolution of syringomyelia. CONCLUSIONS: The symptoms associated with syringobulbia often become life-threatening. Notably, its resolution may be near-synchronous to surgical resection of the spinal lesion. The speed of progression of syringomyelia is usually steady, but it may accelerate when extending to syringobulbia. Regular imaging follow-up is thus highly recommended to determine the best timing of intervention when presyringomyelia and syringomyelia are ascending toward the medulla oblongata.

    DOI: 10.1016/j.wneu.2022.07.118

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  • Accurate Preoperative Identification of Motor Speech Area as Termination of Arcuate Fasciculus Depicted by Q-Ball Imaging Tractography. 国際誌

    Tsukasa Koike, Shota Tanaka, Taichi Kin, Yuichi Suzuki, Shunsaku Takayanagi, Hirokazu Takami, Kazuha Kugasawa, Shohei Nambu, Takaki Omura, Erika Yamazawa, Yoshihiro Kushihara, Yasuyuki Furuta, Ryoko Niwa, Katsuya Sato, Tatsuya Uchida, Yasuhiro Takeda, Satoshi Kiyofuji, Toki Saito, Hiroshi Oyama, Nobuhito Saito

    World neurosurgery   164   e764-e771   2022年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Tractography is one way to predict the distribution of cortical functional domains preoperatively. Diffusion tensor tractography (DTT) is commonly used in clinical practice, but is known to have limitations in delineating crossed fibers, which can be overcome by Q-ball imaging tractography (QBT). We aimed to compare the reliability of these 2 methods based on the spatial correlation between the arcuate fasciculus depicted by tractography and direct cortical stimulation during awake surgery. METHODS: In this study, 15 patients with glioma underwent awake surgery with direct cortical stimulation. Tractography was depicted in a three-dimensional computer graphic model preoperatively, which was integrated with a photograph of the actual brain cortex using our novel mixed-reality technology. The termination of the arcuate fasciculus depicted by either DTT or QBT and the results of direct cortical stimulation were compared, and sensitivity and specificity were calculated in speech-associated brain gyri: pars triangularis, pars opercularis, ventral precentral gyrus, and middle frontal gyrus. RESULTS: QBT had significantly better sensitivity and lower false-positive rate than DTT in the pars opercularis. The same trend was noted for the other gyri. CONCLUSIONS: QBT is more reliable than DTT in identification of the motor speech area and may be clinically useful in brain tumor surgery.

    DOI: 10.1016/j.wneu.2022.05.041

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  • Prognostic Factors and Histopathological Features of Pediatric Intracranial Ependymomas: Nationwide Brain Tumor Registry-based Study of Japan.

    Takahiro Sasaki, Yuji Uematsu, Junya Fukai, Shota Tanaka, Akitake Mukasa, Nobuhito Saito, Yoshitaka Narita, Naoyuki Nakao

    Neurologia medico-chirurgica   62 ( 7 )   322 - 327   2022年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    To assess the clinicopathological features and prognostic factors of pediatric intracranial ependymomas and to explore the current diagnostic practice, we analyzed clinical data from the Brain Tumor Registry of Japan (BTRJ). Data of fifty children under 18 years of age diagnosed with intracranial ependymoma were extracted from the BTRJ database. Cases were reviewed for overall survival (OS) and progression-free survival (PFS), with attention to gender, preoperative Karnofsky performance status score, location of the tumor, the extent of resection, World Health Organization (WHO) histopathological grading, and adjuvant therapy. The median age at diagnosis was 6.1 years, ranging from 7 months to 17.6 years. Based on the WHO histopathological grading, 27 patients were classified under grade 2 (54%) and 23 patients were classified under grade 3 (46%). Gross total resection (GTR) was achieved in 30 patients (60%). The median follow-up time was 65 months. Five-year PFS and OS were 47.2 ± 7.3% and 73.3 ± 6.7%, respectively. GTR was associated with longer OS (P = 0.02). The histopathological grading was not an independent prognostic factor for the OS. Mitosis and microvascular proliferation were higher among patients with grade 3 than in those with grade 2, which aided in deciding the WHO grade. This nationwide study revealed the characteristics and outcomes of patients with childhood ependymomas. GTR was the factor most consistently associated with improved survival. In contrast, the histopathological grading in this cohort was not a significant prognostic factor. More reproducible and practical criteria for the diagnosis of intracranial ependymomas should be further pursued in future studies.

    DOI: 10.2176/jns-nmc.2022-0027

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  • MRI-Based Radiomics Differentiates Skull Base Chordoma and Chondrosarcoma: A Preliminary Study

    Erika Yamazawa, Satoshi Takahashi, Masahiro Shin, Shota Tanaka, Wataru Takahashi, Takahiro Nakamoto, Yuichi Suzuki, Hirokazu Takami, Nobuhito Saito

    Cancers   14 ( 13 )   3264 - 3264   2022年7月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Chordoma and chondrosarcoma share common radiographic characteristics yet are distinct clinically. A radiomic machine learning model differentiating these tumors preoperatively would help plan surgery. MR images were acquired from 57 consecutive patients with chordoma (N = 32) or chondrosarcoma (N = 25) treated at the University of Tokyo Hospital between September 2012 and February 2020. Preoperative T1-weighted images with gadolinium enhancement (GdT1) and T2-weighted images were analyzed. Datasets from the first 47 cases were used for model creation, and those from the subsequent 10 cases were used for validation. Feature extraction was performed semi-automatically, and 2438 features were obtained per image sequence. Machine learning models with logistic regression and a support vector machine were created. The model with the highest accuracy incorporated seven features extracted from GdT1 in the logistic regression. The average area under the curve was 0.93 ± 0.06, and accuracy was 0.90 (9/10) in the validation dataset. The same validation dataset was assessed by 20 board-certified neurosurgeons. Diagnostic accuracy ranged from 0.50 to 0.80 (median 0.60, 95% confidence interval 0.60 ± 0.06%), which was inferior to that of the machine learning model (p = 0.03), although there are some limitations, such as the risk of overfitting and the lack of an extramural cohort for truly independent final validation. In summary, we created a novel MRI-based machine learning model to differentiate skull base chordoma and chondrosarcoma from multiparametric signatures.

    DOI: 10.3390/cancers14133264

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  • The Role of Stereotactic Frame-Based Biopsy for Brainstem Tumors in the Era of Molecular-Based Diagnosis and Treatment Decisions. 国際誌

    Yudai Hirano, Yuki Shinya, Toshiya Aono, Hirotaka Hasegawa, Mariko Kawashima, Masahiro Shin, Hirokazu Takami, Shunsaku Takayanagi, Motoyuki Umekawa, Masako Ikemura, Tetsuo Ushiku, Kazuki Taoka, Shota Tanaka, Nobuhito Saito

    Current oncology (Toronto, Ont.)   29 ( 7 )   4558 - 4565   2022年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Stereotactic frame-based brain tumor biopsy (SFB) is a potent diagnostic tool considering its minimal invasiveness, though its diagnostic power and safety for brainstem lesions remain to be discussed. Here, we aimed to examine the usefulness of SFB for brainstem tumors. Twenty-two patients with brainstem tumors underwent 23 SFBs at our institution during 2002-2021. We retrospectively analyzed patient characteristics, tumor pathology, surgical procedures, and outcomes, including surgery-related complications and the diagnostic value. Seven (32%) tumors were located from the midbrain to the pons, eleven (50%) in the pons only, and four (18%) from the pons to the medulla oblongata. The target lesions were in the middle cerebellar peduncles in sixteen procedures (70%), the cerebellum in four (17%), the inferior cerebellar peduncles in two (9%), and the superior cerebellar peduncles in one (4%). A definitive diagnosis was made in 21 patients (95%) at the first SFB. The diagnoses were glioma in seventeen (77%) cases, primary central nervous system lymphoma in four (18%), and a metastatic brain tumor in one (5%). The postoperative complications (cranial nerve palsy in three [13%] cases, ataxia in one [4%]) were all transient. SFB for brainstem tumors yields a high diagnostic rate with a low risk of morbidity.

    DOI: 10.3390/curroncol29070360

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  • A phase II, multicenter, single-arm trial of eribulin in patients with bevacizumab-resistant recurrent glioblastoma.

    Masamichi Takahashi, Satoshi Kawashima, Yohei Otake, Natsuko Satomi-Tsushita, Aya Kuchiba, Ryo Sadachi, Keiko Ohata, Hitoshi Ozawa, Kan Yonemori, Motoo Nagane, Yoshiki Arakawa, Akitake Mukasa, Shota Tanaka, Ryo Nishikawa, Yoshihiro Muragaki, Kenkichi Masutomi, Koichi Ichimura, Kenichi Nakamura, Yoshitaka Narita

    Journal of Clinical Oncology   40 ( 16_suppl )   2036 - 2036   2022年6月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:American Society of Clinical Oncology (ASCO)  

    2036

    Background: Glioblastoma (GBM) is one of the worst prognostic cancers and there is no effective treatment after failure of bevacizumab. Eribulin is a microtubule inhibitor used for the treatment of patients with metastatic breast cancer and liposarcoma. We previously reported that eribulin strongly inhibits the RNA-dependent RNA polymerase (RdRP) activity of TERT protein in cancer cells, and has a strong anti-tumor effect against GBM cells with TERT promoter mutation. In this study we aim to investigate the efficacy and safety of eribulin in patients with bevacizumab-resistant recurrent GBM. Methods: This is an open-label, multicenter, single-arm phase II trial. Eligible patients aged 20-75 years with bevacizumab-resistant recurrent GBM were enrolled from 2018-2020. Patients received eribulin 1.4 mg/m2 on days 1 and 8 of 21-day cycle until disease progression or intolerable toxicity was observed. The primary endpoint was one-year overall survival rate (1yOS%). The 35 patients are needed to achieve an 80% power at a one-sided alpha of 10%, under threshold 1yOS% of 10% and expected 1yOS% of 25%. Results: Thirty-seven patients aged 26-73 (median: 54) years were treated. Twenty-six of 37 (70.3%) patients were diagnosed as IDH-wildtype GBM, 4 (10.8%) were with IDH-mutant GBM and 7 (18.9%) were GBM, NOS. Thirty-four (91.9%) patients had a Karnofsky performance status of 70 or 80 at the registration. Thirty-one (83.8%) patients received additional treatments, including 28 (75.7%) bevacizumab, 11 (29.7%) re-irradiation and 3 (8.1%) resection after failure of eribulin. Among 37 subjects, 32 surgical specimens were analyzed for TERT promoter mutation and 15 for RdRP activity. 1yOS% was 29.7% [80% CI: 20.5 to 39.5 (p &lt; 0.0001), 95% CI: 16.1 to 44.6]. Median OS was 9.0 months [95% CI: 6.2 to 11.0] and median progression-free survival was 1.5 months [95% CI: 1.4 to 1.7]. Neither TERT nor RdRP statuses was associated with prolonged OS. Among all the target lesions evaluated, two lesions decreased more than 50% in size and the patients survived more than one year, however no obvious PR was confirmed at the final evaluation. The disease control rate was 25.7% [95% CI: 12.5 to 43.3]. Common ≥ grade 2 AEs were neutropenia (70.3%), leukopenia (56.8%), lymphopenia (27.0%), elevation of γ-GTP (13.5%), elevation of ALT (10.8%), elevation of AST (8.1%), alopecia (8.1%). Treatment-related grade 3 or 4 AEs occurred in 59.5% of subjects. There were no AEs leading to death. Conclusions: Eribulin was safely applied for the patients with recurrent GBM. This phase II study met its primary endpoint of 1yOS%, although no obvious response was observed. Further investigation to reveal the biomarkers related to longer survival is underway. Clinical trial information: UMIN000030359.

    DOI: 10.1200/jco.2022.40.16_suppl.2036

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  • Performance of an artificial intelligence-based annotation algorithm for reporting cancer genomic profiling tests.

    Hidenori Kage, Takashi Aoki, Aya Shinozaki-Ushiku, Kousuke Watanabe, Nana Akiyama, Hideaki Isago, Kazunaga Ishigaki, Nariaki Odawara, Yusuke Sato, Kazuhito Sasaki, Shota Tanaka, Michihiro Tanikawa, Motohiro Kato, Masahiko Tanabe, Kenji Tatsuno, Tetsuo Ushiku, Kiyoshi Miyagawa, Kunihiro Nishimura, Hiroyuki Aburatani, Katsutoshi Oda

    Journal of Clinical Oncology   40 ( 16_suppl )   1551 - 1551   2022年6月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:American Society of Clinical Oncology (ASCO)  

    1551

    Background: Cancer genomic profiling (CGP) tests have been approved in Japan since June 2019, with the requisite that all test results be discussed by molecular tumor boards (MTBs). More than 20,000 patients in over 200 designated hospitals have taken CGP tests by December 2021. As CGP tests have entered clinical practice, streamlining decision making by MTBs and standardizing interpretation of test results and treatment recommendations have become urgent issues. Here, we evaluated the utility of Chrovis, an annotation algorithm for reporting CGP tests to support MTBs make their recommendations. Methods: We retrospectively reviewed the reporting process of all approved CGP tests done at The University of Tokyo Hospital between December 2019 and November 2021. Chrovis provided annotation for each genetic variant by incorporating biologic, clinical, and therapeutic information by referencing several public knowledge databases and using natural language processing, and generated reports using the automated program. The MTB reviewed and made any necessary changes before finalizing the report. Changes in disclosure of germline findings were made according to the recommendations of a national guideline with consideration of past and family history. Results: Of the 243 tests, 91 changes in 81 Chrovis reports (33% of all reports) were made by the MTB. The most common type of change was germline disclosure with 26 changes (29%), followed by clinical trial information in Japan (18 changes, 20%) and recommendation of the patient-proposed national basket trial with multiple targeted agents (17 changes, 19%). Changes in germline disclosure increased from June 2021, when an update to a national guideline was released, while the proportion of changes in the latter two types remained unchanged. Gene alterations that led to the highest number of changes was TP53, with 13 changes. Changes in therapeutic recommendations were frequently observed in the RAS/MAPK pathway ( BRAF, KRAS, NF1, NRAS) with 12 changes. More changes were required with a tumor-only tissue CGP panel (57 of 149) compared with a matched tumor/normal tissue CGP panel (24 of 94, p = 0.04), mostly due to germline disclosure (24 vs. 2 changes). Conclusions: We observed that automated algorithm-based reporting was sufficient in 67% of reports. Recommendation for germline disclosure still requires manual supervision, particularly with tumor-only tissue CGP panels if algorithms do not incorporate medical history. The process of recommending clinical trials needs improvement, e.g., standardizing database formats for inclusion and exclusion criteria.

    DOI: 10.1200/jco.2022.40.16_suppl.1551

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  • 12p gain is predominantly observed in non-germinomatous germ cell tumors and identifies an unfavorable subgroup of central nervous system germ cell tumors

    Kaishi Satomi, Hirokazu Takami, Shintaro Fukushima, Satoshi Yamashita, Yuko Matsushita, Yoichi Nakazato, Tomonari Suzuki, Shota Tanaka, Akitake Mukasa, Nobuhito Saito, Masayuki Kanamori, Toshihiro Kumabe, Teiji Tominaga, Keiichi Kobayashi, Motoo Nagane, Toshihiko Iuchi, Koji Yoshimoto, Kaoru Tamura, Taketoshi Maehara, Keiichi Sakai, Kazuhiko Sugiyama, Kiyotaka Yokogami, Hideo Takeshima, Masahiro Nonaka, Akio Asai, Toshikazu Ushijima, Masao Matsutani, Ryo Nishikawa, Koichi Ichimura

    Neuro-Oncology   24 ( 5 )   834 - 846   2022年5月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

    Abstract

    Background

    Central nervous system (CNS) germ cell tumors (GCTs) are neoplasms predominantly arising in pediatric and young adult populations. While germinomas generally respond to chemotherapy and radiation, non-germinomatous GCTs (NGGCTs) require more intensive treatment. This study aimed to determine whether 12p gain could predict the prognosis of CNS GCTs.

    Methods

    Eighty-two CNS GCTs were included in this study. The 12p gain was defined by an additional 12p in the background of potential polyploidy or polysomy. Cases were analyzed using an Illumina methylation 450K array for copy number investigations and validated by fluorescence in situ hybridization (FISH).

    Results

    A 12p gain was found in 25-out-of-82 cases (30%) and was more frequent in NGGCTs (12% of germinoma cases and 50% of NGGCT cases), particularly in cases with malignant components, such as immature teratoma, yolk sac tumor, choriocarcinoma, and embryonal carcinoma. 12p gain and KIT mutation were mutually exclusive events. The presence of 12p gain correlated with shorter progression-free (PFS) and overall survival (OS) (10-year OS: 59% vs. 94%, with and without 12p gain, respectively, P = 0.0002), even with histology and tumor markers incorporated in the multivariate analysis. Among NGGCTs, 12p gain still had prognostic significance for PFS and OS (10-year OS: 47% vs. 90%, respectively, P = 0.02). The 12p copy number status was shared among histological components in mixed GCTs.

    Conclusions

    12p gain may predict the presence of malignant components of NGGCTs, and poor prognosis of the patients. It may be associated with early tumorigenesis of CNS GCT.

    DOI: 10.1093/neuonc/noab246

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    その他リンク: https://academic.oup.com/neuro-oncology/article-pdf/24/5/834/43548783/noab246.pdf

  • 網羅的メチル化解析を施行した成人脳室内pilocytic astrocytomaの一例

    高柳 俊作, 矢島 寛久, 高見 浩数, 田中 將太, 池村 雅子, 齊藤 延人

    Brain Tumor Pathology   39 ( Suppl. )   081 - 081   2022年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 脳腫瘍研究のcutting edge-先端画像、実験/分子病理、デジタル病理- 脳腫瘍分子診断時代における網羅的メチル化解析の有用性と課題

    矢島 寛久, 田中 將太, 高見 浩数, 高柳 俊作, 池村 雅子, 齊藤 延人

    Brain Tumor Pathology   39 ( Suppl. )   072 - 072   2022年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 脳神経外科学 がん遺伝子パネル検査による脳腫瘍治療

    高柳 俊作, 田中 將太, 齊藤 延人

    医学のあゆみ   281 ( 2 )   193 - 195   2022年4月

  • 12p gainは中枢神経系胚細胞腫瘍の予後不良群を同定する

    里見 介史, 高見 浩数, 福島 慎太郎, 山下 聡, 松下 裕子, 中里 洋一, 鈴木 智成, 田中 將太, 武笠 晃丈, 齊藤 延人, 金森 政之, 隈部 俊宏, 冨永 悌二, 小林 啓一, 永根 基雄, 井内 俊彦, 吉本 幸司, 田村 郁, 前原 健寿, 酒井 圭一, 杉山 一彦, 横上 聖貴, 竹島 秀雄, 埜中 正博, 淺井 昭雄, 牛島 俊和, 松谷 雅生, 西川 亮, 市村 幸一, 頭蓋内胚細胞腫コンソーシアム

    日本病理学会会誌   111 ( 1 )   220 - 220   2022年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • Transcriptome and Methylome Analysis of CNS Germ Cell Tumor Finds its Cell-of-Origin in Embryogenesis and Reveals Shared Similarities with Testicular Counterparts. 国際誌

    Hirokazu Takami, Asmaa Elzawahry, Yasin Mamatjan, Shintaro Fukushima, Kohei Fukuoka, Tomonari Suzuki, Takaaki Yanagisawa, Yuko Matsushita, Taishi Nakamura, Kaishi Satomi, Shota Tanaka, Akitake Mukasa, Nobuhito Saito, Masayuki Kanamori, Toshihiro Kumabe, Teiji Tominaga, Keiichi Kobayashi, Motoo Nagane, Toshihiko Iuchi, Kaoru Tamura, Taketoshi Maehara, Kazuhiko Sugiyama, Koji Yoshimoto, Keiichi Sakai, Masahiro Nonaka, Akio Asai, Kiyotaka Yokogami, Hideo Takeshima, Yoshitaka Narita, Soichiro Shibui, Yoichi Nakazato, Natsuko Hama, Yasushi Totoki, Mamoru Kato, Tatsuhiro Shibata, Ryo Nishikawa, Masao Matsutani, Koichi Ichimura

    Neuro-oncology   24 ( 8 )   1246 - 1258   2022年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: CNS germ cell tumors (GCTs) predominantly develop in pediatric and young adult patients with variable responses to surgery, radiation, and chemotherapy. This study aimed to examine the complex and largely unknown pathogenesis of CNS GCTs. METHODS: We used a combined transcriptomic and methylomic approach in 84 cases and conducted an integrative analysis of the normal cells undergoing embryogenesis and testicular GCTs. RESULTS: Genome-wide transcriptome analysis in CNS GCTs indicated that germinoma had a transcriptomic profile representative of primitive cells during early embryogenesis with high meiosis/mitosis potentials, while non-germinomatous GCTs (NGGCTs) had differentiated phenotypes oriented toward tissue formation and organogenesis. Co-analysis with the transcriptome of human embryonic cells revealed that germinomas had expression profiles similar to those of primordial germ cells, while the expression profiles of NGGCTs were similar to those of embryonic stem cells. Some germinoma cases were characterized by extensive immune-cell infiltration and high expression of cancer-testis antigens. NGGCTs had significantly higher immune-cell infiltration, characterized by immune-suppression phenotype. CNS and testicular GCTs (TGCTs) had similar mutational profiles; TGCTs showed enhanced copy number alterations. Methylation analysis clustered germinoma/seminoma and non-germinoma/non-seminoma separately. Germinoma and seminoma were co-categorized based on the degree of the tumor microenvironment balance. CONCLUSIONS: These results suggested that the pathophysiology of GCTs was less dependent on their site of origin and more dependent on the state of differentiation as well as on the tumor microenvironment balance. This study revealed distinct biological properties of GCTs, which will hopefully lead to future treatment development.

    DOI: 10.1093/neuonc/noac021

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  • [Molecularly Targeted Therapy for Craniopharyngioma].

    Shota Tanaka, Shunsaku Takayanagi, Hirokazu Takami, Nobuhito Saito

    No shinkei geka. Neurological surgery   50 ( 1 )   171 - 178   2022年1月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Craniopharyngioma is a pathologically benign but clinically malignant brain tumor typically located in the parasellar region. It is treated by surgical resection, but in most cases, total removal is not amenable due to its adhesion to the adjacent vital structures, such as the optic nerve, hypothalamus, and pituitary stalk. Often, tumor regrowth or recurrence occursand it is usually treated with either re-resection or radiotherapy, including stereotactic radiosurgery. Either treatment carries some important risks, including blindness, hypopituitarism, and cognitive impairment. A recent comprehensive genomic analysis revealed that the majority of papillary craniopharyngioma cases harbor a hotspot BRAF-V600E mutation. Several case reports have illustrated dramatic response of the residual or recurrent papillary craniopharyngioma to molecularly targeted therapy with a BRAF inhibitor(vemurafenib or dabrafenib)and a MEK inhibitor(trametinib), which are currently approved for melanoma and non-small cell lung carcinoma. This medical treatment can potentially be a wonderful treatment option for papillary craniopharyngioma, given its freedom from the aforementioned serious risks associated with surgery and radiotherapy.

    DOI: 10.11477/mf.1436204542

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  • [Evolving Exploration of the Pathogenesis of CNS Germ Cell Tumors with Regard to Precision Medicine].

    Hirokazu Takami, Shunsaku Takayanagi, Shota Tanaka, Nobuhito Saito

    No shinkei geka. Neurological surgery   50 ( 1 )   39 - 50   2022年1月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Genomic and epigenomic analyses have progressed the exploration of the pathogenesis of CNS germ cell tumors(GCTs)in the past decade. GCTs are characterized by mutations in MAPK or PI3K pathways(55%)and unstable chromosomes, especially 12p gain(45%), as well as global hypomethylation in germinoma. Highly specific microRNA, miR-371a-3p, can be a diagnostic marker in serum and cerebrospinal fluid. Tumor cell content examined in H-E specimens has a prognostic value in germinoma: cases with higher tumor cell content show a worse prognosis. 12p gain in non-germinomatous GCTs(NGGCTs)has an unfavorable prognostic significance. PD-L1 and PD-1 are highly expressed in germinomas and the tumor cell microenvironment, respectively, highlighting the potential effectiveness of immune checkpoint inhibitors. Clinical trials from the Children's Oncology Group(COG)in the US and the Society for Paediatric Oncology(SIOP)in Europe and Japan have shown that whole ventricular irradiation is the most appropriate for germinomas, and that radiation fields can be reduced to the whole ventricle or a local area for localized NGGCTs. Toward personalized medicine, investigations into the structural abnormalities and variants in non-coding regions are needed to develop targeted therapy. A stratified treatment regimen is expected by incorporating newly-found biomarkers to reduce the treatment burden for generally young patients and circumvent late toxicity and sequelae. Establishing effective treatments is crucial for relapsed GCT that has a dismal prognosis.

    DOI: 10.11477/mf.1436204530

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  • [Hemangioblastoma and von Hippel-Lindau Disease].

    Shunsaku Takayanagi, Hirokazu Takami, Shota Tanaka, Nobuhito Saito

    No shinkei geka. Neurological surgery   50 ( 1 )   101 - 110   2022年1月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Hemangioblastoma(HB)is a tumor that frequently occurs in von Hippel-Lindau(VHL)disease, a hereditary tumor disease. It is a benign tumor and excision is the first choice of treatment, but in VHL disease, where HB occurs frequently, the emergence of more promising molecularly-targeted therapeutic agents has been desired. In this paper, we first explain HB and VHL disease and then outline the function of the VHL gene and the mechanism of onset of VHL disease. After that, we explain the analysis technology and frequency of VHL gene abnormalities and finally describe HIF2α inhibitors, which are promising as molecularly-targeted therapeutic agents for VHL disease. As the medical system for personalized medicine/precision medicine is being developed in Japan, it is expected that HB and VHL diseases will attract attention as target diseases in the future.

    DOI: 10.11477/mf.1436204535

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  • Primary Intracranial Spindle Cell Sarcoma, DICER1-Mutant, with MDM2 Amplification Diagnosed on the Basis of Extensive Molecular Profiling. 国際誌

    Takahide Nejo, Shunsaku Takayanagi, Shota Tanaka, Aya Shinozaki-Ushiku, Shinji Kohsaka, Keisuke Nagata, Munehiro Yokoyama, Shigeo Sora, Tetsuo Ushiku, Akitake Mukasa, Hiroyuki Aburatani, Hiroyuki Mano, Nobuhito Saito

    Clinical medicine insights. Case reports   15   11795476221131189 - 11795476221131189   2022年

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    記述言語:英語  

    Primary intracranial spindle cell sarcoma is an extremely rare mesenchymal tumor, the molecular pathogenesis of which is poorly understood. Because of the lack of specific markers, diagnosis sometimes relies on ruling out all possible differential diagnoses, often making it difficult to reach a definitive diagnosis. In this case study, we report a 69 year-old female patient for whom the integration of multi-layered molecular analyses contributed to making the diagnosis. The disease exhibited aggressive clinical behavior, requiring two sequential surgeries because of rapid regrowth within a short period. Primary and recurrent tumors exhibited similar histological features, in which spindle-shaped cells arranged in interlacing fascicles without any specific architectures, implicating sarcomatous tumors. In immunohistochemistry testing, tumor cells were immunopositive for vimentin but lacked any specific findings that contribute to narrowing down the differential diagnoses. Seeking further diagnostic clues, we performed DNA methylation-based analysis. The copy number analysis revealed MDM2 gene amplification and loss of heterozygosity of 22q. Moreover, dimension reduction clustering analysis implicated a methylation pattern comparable to aggressive types of sarcomas. In addition, an in-house next-generation sequencing panel ("Todai-OncoPanel") analysis identified somatic mutations in DICER1, NF2, and ATRX genes. Taken all together, we finally made the diagnosis of primary intracranial spindle cell sarcoma, DICER1-mutant, with MDM2 gene amplification. This case report suggests that even for the tumors with insufficient morphological and immuno-histological diagnostic clues, integration of multi-layered molecular analyses can contribute to making the diagnoses as well as to understanding the rare tumors by elucidating unexpected genetic and epigenetic features.

    DOI: 10.1177/11795476221131189

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  • Novel case of primary intracranial solitary plasmacytoma presenting with significant intratumoral hemorrhage. 国際誌

    Daisuke Sato, Shunsaku Takayanagi, Hirokazu Takami, Tetsuaki Iwamoto, Masashi Nomura, Shohei Nambu, Masako Ikemura, Shota Tanaka, Nobuhito Saito

    Surgical neurology international   13   157 - 157   2022年

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    記述言語:英語  

    Background: Solitary plasmacytoma is a localized lesion comprising monoclonal neoplastic proliferation of plasma cells. This disease is rarely encountered and few reports have described primary intracranial solitary plasmacytoma (PISP). Case Description: We report a case of PISP that presented initially as status epilepticus and exhibited massive intratumoral hemorrhage at the subcortical area. To the best of our knowledge, this is the first recorded presentation of this pathology in this manner. Following evacuation of the hematoma and decompressive craniectomy, the patient underwent radiation therapy and showed no sign of tumor recurrence at 3 years after diagnosis. Conclusion: This case reveals that PISP can present as subcortical intraparenchymal hemorrhage. It should be emphasized that the precise diagnosis of this disease is of utmost importance, because solitary plasmacytoma without a background of multiple myeloma responds well to radiation therapy.

    DOI: 10.25259/SNI_66_2022

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  • Development of a New Image-Guided Neuronavigation System: Mixed-Reality Projection Mapping Is Accurate and Feasible

    Tsukasa Koike, Taichi Kin, Shota Tanaka, Katsuya Sato, Tatsuya Uchida, Yasuhiro Takeda, Hiroki Uchikawa, Satoshi Kiyofuji, Toki Saito, Hirokazu Takami, Shunsaku Takayanagi, Akitake Mukasa, Hiroshi Oyama, Nobuhito Saito

    Operative Neurosurgery   21 ( 6 )   549 - 557   2021年12月

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    掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Image-guided systems improve the safety, functional outcome, and overall survival of neurosurgery but require extensive equipment. OBJECTIVE: To develop an image-guided surgery system that combines the brain surface photographic texture (BSP-T) captured during surgery with 3-dimensional computer graphics (3DCG) using projection mapping. METHODS: Patients who underwent initial surgery with brain tumors were prospectively enrolled. The texture of the 3DCG (3DCG-T) was obtained from 3DCG under similar conditions as those when capturing the brain surface photographs. The position and orientation at the time of 3DCG-T acquisition were used as the reference. The correct position and orientation of the BSP-T were obtained by aligning the BSP-T with the 3DCG-T using normalized mutual information. The BSP-T was combined with and displayed on the 3DCG using projection mapping. This mixed-reality projection mapping (MRPM) was used prospectively in 15 patients (mean age 46.6 yr, 6 males). The difference between the centerlines of surface blood vessels on the BSP-T and 3DCG constituted the target registration error (TRE) and was measured in 16 fields of the craniotomy area. We also measured the time required for image processing. RESULTS: The TRE was measured at 158 locations in the 15 patients, with an average of 1.19 ± 0.14 mm (mean ± standard error). The average image processing time was 16.58 min. CONCLUSION: Our MRPM method does not require extensive equipment while presenting information of patients' anatomy together with medical images in the same coordinate system. It has the potential to improve patient safety.

    DOI: 10.1093/ons/opab353

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  • 透明中隔に生じたmyxoid glioneuronal tumor、PDGFRA p.K385-mutantの1例

    藤井 源太, 田中 將太, 辛 正廣, 菊池 美佑, 高見 浩数, 高柳 俊作, 齊藤 延人

    脳神経外科ジャーナル   30 ( 12 )   871 - 875   2021年12月

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    記述言語:日本語   出版者・発行元:(一社)日本脳神経外科コングレス  

    Myxoid glioneuronal tumor、PDGFRA p.K385-mutantは近年新たに提唱された中枢神経系腫瘍の概念である。その発生母地としては透明中隔や側脳室が考えられている。提唱後間もないため症例報告は少なく、その治療法や予後については一定の見解が得られていない。今回われわれは、透明中隔に生じたmyxoid glioneuronal tumor、PDGFRA p.K385-mutantに対し全摘出を行い、その後再発なく良好な経過を辿った1例を経験したので報告する。(著者抄録)

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    その他リンク: https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J02632&link_issn=&doc_id=20211202230007&doc_link_id=1390572012410134912&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390572012410134912&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

  • Efficacy and safety of nivolumab in Japanese patients with first recurrence of glioblastoma: an open-label, non-comparative study.

    Tomokazu Aoki, Naoki Kagawa, Kazuhiko Sugiyama, Toshihiko Wakabayashi, Yoshiki Arakawa, Shigeru Yamaguchi, Shota Tanaka, Eiichi Ishikawa, Yoshihiro Muragaki, Motoo Nagane, Mitsutoshi Nakada, Satoshi Suehiro, Nobuhiro Hata, Junichiro Kuroda, Yoshitaka Narita, Yukihiko Sonoda, Yasuo Iwadate, Manabu Natsumeda, Yoichi Nakazato, Hironobu Minami, Yuki Hirata, Shunsuke Hagihara, Ryo Nishikawa

    International journal of clinical oncology   26 ( 12 )   2205 - 2215   2021年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: An open-label, non-comparative study assessed the efficacy and safety of nivolumab in Japanese patients with first recurrence glioblastoma. METHODS: Patients with first recurrence of histologically confirmed World Health Organization Grade IV glioma, after treatment with temozolomide and radiotherapy, received nivolumab 3 mg/kg every 2 weeks until confirmed disease progression (Response Assessment in Neuro-Oncology criteria) or toxicity. Primary endpoint was 1-year overall survival rate assessed by Bayesian approach. The prespecified efficacy criterion was that the Bayesian posterior probability threshold for exceeding the 1-year overall survival of bevacizumab (34.5%) from the Japanese phase 2 study (JO22506) would be 93%. RESULTS: Of the 50 enrolled patients, 44 (88.0%) had recurrent malignant glioma (glioblastoma, gliosarcoma), and of these, 26 (59.1%) had at least one measurable lesion at baseline. The Bayesian posterior mean 1-year overall survival (90% Bayesian credible intervals) with nivolumab was 54.4% (42.27-66.21), and the Bayesian posterior probability of exceeding the threshold of the 1-year overall survival rate of bevacizumab (34.5%) was 99.7%. Median (90% confidence interval) overall and progression-free survival was 13.1 (10.4-17.7) and 1.5 (1.4-1.5) months, respectively. One partial response was observed (objective response rate 1/26 evaluable patients [3.8%]). Treatment-related adverse event rates were 14.0% for Grade 3-4 and 2.0% for Grade 5; most adverse events resolved and were manageable. CONCLUSIONS: The 1-year overall survival with nivolumab monotherapy in Japanese patients with glioblastoma met the prespecified efficacy criterion. The safety profile of nivolumab was consistent with that observed in other tumor types. CLINICAL TRIAL REGISTRATION: JapicCTI-152967.

    DOI: 10.1007/s10147-021-02028-1

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  • Development of a New Image-Guided Neuronavigation System: Mixed-Reality Projection Mapping Is Accurate and Feasible. 国際誌

    Tsukasa Koike, Taichi Kin, Shota Tanaka, Katsuya Sato, Tatsuya Uchida, Yasuhiro Takeda, Hiroki Uchikawa, Satoshi Kiyofuji, Toki Saito, Hirokazu Takami, Shunsaku Takayanagi, Akitake Mukasa, Hiroshi Oyama, Nobuhito Saito

    Operative neurosurgery (Hagerstown, Md.)   21 ( 6 )   549 - 557   2021年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Image-guided systems improve the safety, functional outcome, and overall survival of neurosurgery but require extensive equipment. OBJECTIVE: To develop an image-guided surgery system that combines the brain surface photographic texture (BSP-T) captured during surgery with 3-dimensional computer graphics (3DCG) using projection mapping. METHODS: Patients who underwent initial surgery with brain tumors were prospectively enrolled. The texture of the 3DCG (3DCG-T) was obtained from 3DCG under similar conditions as those when capturing the brain surface photographs. The position and orientation at the time of 3DCG-T acquisition were used as the reference. The correct position and orientation of the BSP-T were obtained by aligning the BSP-T with the 3DCG-T using normalized mutual information. The BSP-T was combined with and displayed on the 3DCG using projection mapping. This mixed-reality projection mapping (MRPM) was used prospectively in 15 patients (mean age 46.6 yr, 6 males). The difference between the centerlines of surface blood vessels on the BSP-T and 3DCG constituted the target registration error (TRE) and was measured in 16 fields of the craniotomy area. We also measured the time required for image processing. RESULTS: The TRE was measured at 158 locations in the 15 patients, with an average of 1.19 ± 0.14 mm (mean ± standard error). The average image processing time was 16.58 min. CONCLUSION: Our MRPM method does not require extensive equipment while presenting information of patients' anatomy together with medical images in the same coordinate system. It has the potential to improve patient safety.

    DOI: 10.1093/ons/opab353

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  • Gene expression profiling of 19q-loss astrocytomas suggest a specific pattern associated with the better prognosis. 国際誌

    Ryohei Otani, Akitake Mukasa, Takeo Uzuka, Fumi Higuchi, Hadzki Matsuda, Masashi Nomura, Shota Tanaka, Phyo Kim, Keisuke Ueki

    Journal of neuro-oncology   154 ( 2 )   221 - 228   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: We previously reported that there was a subgroup of IDH-mutated astrocytomas harboring only 19q-loss showing oligodendroglioma-like morphology and significantly longer overall survival (OS) compared with 19q-intact astrocytomas. The aim of this study was to further explore the biological characteristics of this possible subgroup and obtain insight into the mechanism of their relatively benign clinical behavior. METHODS: We compared gene expression pattern between five 19q-loss and five 19q-intact IDH-mutated astrocytomas by microarray analysis. RESULTS: By comparing expression levels of genes of 19q-loss astrocytomas to those of 19q-intact astrocytomas, 102 up-regulated genes and 162 down-regulated genes were extracted. The down-regulated genes clustered heavily to 19q and 4p while the up-regulated genes clustered to 4q. It was noteworthy that fibroblast growth factor 1 associated with stem cell maintenance and multiple genes associated with glioma progression were down-regulated in 19q-loss astrocytomas, and these results were validated with the independent TCGA data set. On t-SNE analysis of the 19q-loss astrocytomas with other IDH-mutant glioma subgroups from the TCGA datasets, the expression pattern of the 19q-loss astrocytomas showed no shift toward oligodendrogliomas with 1p/19q codeletion but rather constituted a subgroup of astrocytoma. CONCLUSIONS: These findings suggested that 19q-loss in astrocytomas is more likely acquired event rather than an early event in oncogenesis like the 1p/19q-codeletion in oligodendrogliomas, and that the biological features of 19q-loss astrocytomas are possibly related to differentially expressed genes associated with stem cell maintenance and glioma progression.

    DOI: 10.1007/s11060-021-03816-5

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  • Clinical Features and Prognostic Factors for Primary Anaplastic Large Cell Lymphoma of the Central Nervous System: A Systematic Review. 国際誌

    Yudai Hirano, Satoru Miyawaki, Shota Tanaka, Kazuki Taoka, Hiroki Hongo, Yu Teranishi, Hirokazu Takami, Shunsaku Takayanagi, Mineo Kurokawa, Nobuhito Saito

    Cancers   13 ( 17 )   2021年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Primary anaplastic large cell lymphoma (ALCL) of the central nervous system (CNS) is a subtype of primary CNS lymphoma (PCNSL). There are very few comprehensive reports on this extremely rare tumor. Therefore, it is necessary to investigate the clinical features and prognostic factors for primary ALCL of the CNS. We performed a systematic review of the published literature. Past cases were comprehensively searched using PubMed, Cochrane Library, and Web of Science. Clinical information, such as age, sex, anaplastic lymphoma kinase (ALK) status, lesion sites, treatment methods, and survivorship were extracted. Thirty-nine cases with information on ALK status and treatment course were identified. The average observation period was 13 months, and the overall 2-year survival rate was 58%. Univariate analyses showed a statistically significantly better prognosis among patients < 40 years of age (p = 0.039, HR 0.32 (0.11-0.95)) and in relation to ALK positivity (p = 0.010, HR 0.24 (0.08-0.71) and methotrexate treatment (p = 0.003, HR 0.17 (0.05-0.56)). Because of the sparsity of cases, it is necessary to accumulate cases in order to perform more detailed analyses.

    DOI: 10.3390/cancers13174358

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  • TERT promoter mutation status is necessary and sufficient to diagnose IDH-wildtype diffuse astrocytic glioma with molecular features of glioblastoma. 国際誌

    Kenji Fujimoto, Hideyuki Arita, Kaishi Satomi, Kai Yamasaki, Yuko Matsushita, Taishi Nakamura, Yasuji Miyakita, Toru Umehara, Keiichi Kobayashi, Kaoru Tamura, Shota Tanaka, Fumi Higuchi, Yoshiko Okita, Yonehiro Kanemura, Junya Fukai, Daisuke Sakamoto, Takehiro Uda, Ryunosuke Machida, Aya Kuchiba, Taketoshi Maehara, Motoo Nagane, Ryo Nishikawa, Hiroyoshi Suzuki, Makoto Shibuya, Takashi Komori, Yoshitaka Narita, Koichi Ichimura

    Acta neuropathologica   142 ( 2 )   323 - 338   2021年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) update 3 recommends that histologic grade II and III IDH-wildtype diffuse astrocytic gliomas that harbor EGFR amplification, the combination of whole chromosome 7 gain and whole chromosome 10 loss (7 + /10 -), or TERT promoter (pTERT) mutations should be considered as glioblastomas (GBM), World Health Organization grade IV. In this retrospective study, we examined the utility of molecular classification based on pTERT status and copy-number alterations (CNAs) in IDH-wildtype lower grade gliomas (LGGs, grade II, and III). The impact on survival was evaluated for the pTERT mutation and CNAs, including EGFR gain/amplification, PTEN loss, CDKN2A homozygous deletion, and PDGFRA gain/amplification. We analyzed 46 patients with IDH-wildtype/pTERT-mutant (mut) LGGs and 85 with IDH-wildtype/pTERT-wildtype LGGs. EGFR amplification and a combination of EGFR gain and PTEN loss (EGFR + /PTEN -) were significantly more frequent in pTERT-mut patients (p < 0.0001). Cox regression analysis showed that the pTERT mutation was a significant predictor of poor prognosis (hazard ratio [HR] 2.79, 95% confidence interval [CI] 1.55-4.89, p = 0.0008), but neither EGFR amplification nor EGFR + /PTEN - was an independent prognostic factor in IDH-wildtype LGGs. PDGFRA gain/amplification was a significant poor prognostic factor in IDH-wildtype/pTERT-wildtype LGGs (HR 2.44, 95% CI 1.09-5.27, p = 0.03, Cox regression analysis). The IDH-wildtype LGGs with either pTERT-mut or PDGFRA amplification were mostly clustered with GBM by DNA methylation analysis. Thus, our study suggests that analysis of pTERT mutation status is necessary and sufficient to diagnose IDH-wildtype diffuse astrocytic gliomas with molecular features of glioblastoma. The PDGFRA status may help further delineate IDH-wildtype/pTERT-wildtype LGGs. Methylation profiling showed that IDH-wildtype LGGs without molecular features of GBM were a heterogeneous group of tumors. Some of them did not fall into existing categories and had significantly better prognoses than those clustered with GBM.

    DOI: 10.1007/s00401-021-02337-9

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  • polymorphous low-grade neuroepithelial tumor of the young(PLNTY)が考えられた側頭葉腫瘍の一例

    畑野 颯佑, 雨宮 史織, 鈴木 文夫, 中井 雄大, 池村 雅子, 田中 將太, 國井 尚人, 阿部 修

    日本医学放射線学会秋季臨床大会抄録集   57回   S389 - S389   2021年8月

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    記述言語:日本語   出版者・発行元:(公社)日本医学放射線学会  

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  • A Novel Topical Fluorescent Probe for Detection of Glioblastoma. 国際誌

    Yosuke Kitagawa, Shota Tanaka, Mako Kamiya, Yugo Kuriki, Kyoko Yamamoto, Takenori Shimizu, Takahide Nejo, Taijun Hana, Reiko Matsuura, Tsukasa Koike, Erika Yamazawa, Yoshihiro Kushihara, Satoshi Takahashi, Masashi Nomura, Hirokazu Takami, Shunsaku Takayanagi, Akitake Mukasa, Yasuteru Urano, Nobuhito Saito

    Clinical cancer research : an official journal of the American Association for Cancer Research   27 ( 14 )   3936 - 3947   2021年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: Five-aminolevulinic acid (5-ALA) is widely used as an intraoperative fluorescent probe for radical resection of high-grade glioma, and thus aids in extending progression-free survival of patients. However, there exist some cases where 5-ALA fails to fluoresce. In some other cases, it may undergo fluorescence quenching but cannot be orally readministered during surgery. This study aimed to develop a novel hydroxymethyl rhodamine green (HMRG)-based fluorescence labeling system that can be repeatedly administered as a topical spray during surgery for the detection of glioblastoma. EXPERIMENTAL DESIGN: We performed a three-stage probe screening using tumor lysates and fresh tumor tissues with our probe library consisting of a variety of HMRG probes with different dipeptides. We then performed proteome and transcript expression analyses to detect candidate enzymes responsible for cleaving the probe. Moreover, in vitro and ex vivo studies using U87 glioblastoma cell line were conducted to validate the findings. RESULTS: The probe screening identified proline-arginine-HMRG (PR-HMRG) as the optimal probe that distinguished tumors from peritumoral tissues. Proteome analysis identified calpain-1 (CAPN1) to be responsible for cleaving the probe. CAPN1 was highly expressed in tumor tissues which reacted to the PR-HMRG probe. Knockdown of this enzyme suppressed fluorescence intensity in U87 glioblastoma cells. In situ assay using a mouse U87 xenograft model demonstrated marked contrast of fluorescence with the probe between the tumor and peritumoral tissues. CONCLUSIONS: The novel fluorescent probe PR-HMRG is effective in detecting glioblastoma when applied topically. Further investigations are warranted to assess the efficacy and safety of its clinical use.

    DOI: 10.1158/1078-0432.CCR-20-4518

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  • Development of Innovative Neurosurgical Operation Support Method Using Mixed-Reality Computer Graphics. 国際誌

    Tsukasa Koike, Taichi Kin, Shota Tanaka, Yasuhiro Takeda, Hiroki Uchikawa, Taketo Shiode, Toki Saito, Hirokazu Takami, Shunsaku Takayanagi, Akitake Mukasa, Hiroshi Oyama, Nobuhito Saito

    World neurosurgery: X   11   100102 - 100102   2021年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: In neurosurgery, it is important to inspect the spatial correspondence between the preoperative medical image (virtual space), and the intraoperative findings (real space) to improve the safety of the surgery. Navigation systems and related modalities have been reported as methods for matching this correspondence. However, because of the influence of the brain shift accompanying craniotomy, registration accuracy is reduced. In the present study, to overcome these issues, we developed a spatially accurate registration method of medical fusion 3-dimensional computer graphics and the intraoperative brain surface photograph, and its registration accuracy was measured. Methods: The subjects included 16 patients with glioma. Nonrigid registration using the landmarks and thin-plate spline methods was performed for the fusion 3-dimensional computer graphics and the intraoperative brain surface photograph, termed mixed-reality computer graphics. Regarding the registration accuracy measurement, the target registration error was measured by two neurosurgeons, with 10 points for each case at the midpoint of the landmarks. Results: The number of target registration error measurement points was 160 in the 16 cases. The target registration error was 0.72 ± 0.04 mm. Aligning the intraoperative brain surface photograph and the fusion 3-dimensional computer graphics required ∼10 minutes on average. The average number of landmarks used for alignment was 24.6. Conclusions: Mixed-reality computer graphics enabled highly precise spatial alignment between the real space and virtual space. Mixed-reality computer graphics have the potential to improve the safety of the surgery by allowing complementary observation of brain surface photographs and fusion 3-dimensional computer graphics.

    DOI: 10.1016/j.wnsx.2021.100102

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  • Indocyanine green illuminates the way to cut the tentorium in occipital transtentorial approach: technical note. 国際誌

    Hirokazu Takami, Shota Tanaka, Shunsaku Takayanagi, Hirofumi Nakatomi, Nobuhito Saito

    British journal of neurosurgery   1 - 3   2021年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND AND IMPORTANCE: The occipital transtentorial approach is used to address lesions at the posterior incisural space or upper cerebellum. This approach is rarely used, making standardization of the surgical procedure challenging. Here we describe the effectiveness of indocyanine green (ICG) and dye markings before tentorial incision in charting a safe and bloodless surgical trajectory for improved manoeuvrability. CLINICAL PRESENTATION: The first case was a 40-year-old man with a residual pineal mass after chemoradiation therapy for pathologically-proven germinoma. Surgical resection was performed via left occipital craniotomy. Incision of the left cerebellar tentorium by a radiofrequency knife was preceded by visualization of the straight sinus and venous lake, which were marked with dye, enabling safe entry into the quadrigeminal cistern. Finally, total-resection of the mature teratoma was achieved. The second case was a 50-year-old man with an enhancing mass at the cerebellar vermis and left hemisphere. Left occipital craniotomy was followed by ICG administration, illuminating the straight sinus and a complex structure of dural venous channels, which were marked with dye. This visualization maximized the tentorial incision by carefully avoiding venous structures and widely exposed the upper cerebellum. Subtotal-resection of the tumor was achieved, with a diagnosis of glioblastoma. CONCLUSION: ICG administration and dye marking are feasible and useful methods for precise identification/visualization of venous structures. They enable maximization as well as safe and appropriate tentorial incision to provide a sufficient surgical corridor for the occipital transtentorial approach.

    DOI: 10.1080/02688697.2021.1927982

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  • [Glioblastoma].

    Shota Tanaka

    No shinkei geka. Neurological surgery   49 ( 3 )   623 - 631   2021年5月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Glioblastoma, the most malignant and most common form of glioma, is known to portend very poor prognosis with the median overall survival of approximately 1.5 years. Its treatment requires a multidisciplinary approach, which consists of maximal safe resection followed by radiotherapy and chemotherapy with temozolomide. Bevacizumab is approved for newly diagnosed as well as recurrent malignant glioma in Japan. NovoTTF is a novel medical device that emits alternating electric fields; it inhibits the proliferation and growth of the tumor by interfering with tumor cell mitosis at anaphase. A photodynamic therapy with talaporfin sodium has been approved for primary malignant brain tumor including glioblastoma in Japan. For epilepsy secondary to glioblastoma, a novel class of antiepileptics such as levetiracetam and lacosamide is preferred given the lack of drug-drug interactions. Perampanel is a selective antagonist of AMPA receptors, the major subtype of ionotropic glutamate receptors; it may be a preferred antiepileptics for glioblastoma, given the in vitro and in vivo analyses suggesting that it decreases the proliferation and invasion of tumor cells. In this chapter, I describe the overview of the multidisciplinary treatments of glioblastoma. I also describe the future perspectives.

    DOI: 10.11477/mf.1436204436

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  • 成人移行期に当院へ紹介された結節性硬化症症例の特徴

    佐藤 敦志, 高柳 俊作, 辛 正廣, 田中 將太, 國井 尚人, 嶋田 勢二郎, 佐藤 悠佑, 管 析, 坊木 ひかり, 澤村 裕正, 漆山 博和, 水口 雅

    脳と発達   53 ( Suppl. )   S303 - S303   2021年5月

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    記述言語:日本語   出版者・発行元:(一社)日本小児神経学会  

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  • 癌ゲノム医療 TodaiOncoPanelなどのがん遺伝子パネル検査と脳腫瘍病理の今後の展望

    高柳 俊作, 田中 將太, 高見 浩数, 宮脇 哲, 辛 正廣, 池村 雅子, 牛久 哲男, 牛久 綾, 織田 克利, 齊藤 延人

    Brain Tumor Pathology   38 ( Suppl. )   068 - 068   2021年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 癌ゲノム医療 TodaiOncoPanelなどのがん遺伝子パネル検査と脳腫瘍病理の今後の展望

    高柳 俊作, 田中 將太, 高見 浩数, 宮脇 哲, 辛 正廣, 池村 雅子, 牛久 哲男, 牛久 綾, 織田 克利, 齊藤 延人

    Brain Tumor Pathology   38 ( Suppl. )   068 - 068   2021年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • A New Era of Neuro-Oncology Research Pioneered by Multi-Omics Analysis and Machine Learning. 国際誌

    Satoshi Takahashi, Masamichi Takahashi, Shota Tanaka, Shunsaku Takayanagi, Hirokazu Takami, Erika Yamazawa, Shohei Nambu, Mototaka Miyake, Kaishi Satomi, Koichi Ichimura, Yoshitaka Narita, Ryuji Hamamoto

    Biomolecules   11 ( 4 )   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Although the incidence of central nervous system (CNS) cancers is not high, it significantly reduces a patient's quality of life and results in high mortality rates. A low incidence also means a low number of cases, which in turn means a low amount of information. To compensate, researchers have tried to increase the amount of information available from a single test using high-throughput technologies. This approach, referred to as single-omics analysis, has only been partially successful as one type of data may not be able to appropriately describe all the characteristics of a tumor. It is presently unclear what type of data can describe a particular clinical situation. One way to solve this problem is to use multi-omics data. When using many types of data, a selected data type or a combination of them may effectively resolve a clinical question. Hence, we conducted a comprehensive survey of papers in the field of neuro-oncology that used multi-omics data for analysis and found that most of the papers utilized machine learning techniques. This fact shows that it is useful to utilize machine learning techniques in multi-omics analysis. In this review, we discuss the current status of multi-omics analysis in the field of neuro-oncology and the importance of using machine learning techniques.

    DOI: 10.3390/biom11040565

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  • Fine-Tuning Approach for Segmentation of Gliomas in Brain Magnetic Resonance Images with a Machine Learning Method to Normalize Image Differences among Facilities. 国際誌

    Satoshi Takahashi, Masamichi Takahashi, Manabu Kinoshita, Mototaka Miyake, Risa Kawaguchi, Naoki Shinojima, Akitake Mukasa, Kuniaki Saito, Motoo Nagane, Ryohei Otani, Fumi Higuchi, Shota Tanaka, Nobuhiro Hata, Kaoru Tamura, Kensuke Tateishi, Ryo Nishikawa, Hideyuki Arita, Masahiro Nonaka, Takehiro Uda, Junya Fukai, Yoshiko Okita, Naohiro Tsuyuguchi, Yonehiro Kanemura, Kazuma Kobayashi, Jun Sese, Koichi Ichimura, Yoshitaka Narita, Ryuji Hamamoto

    Cancers   13 ( 6 )   2021年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Machine learning models for automated magnetic resonance image segmentation may be useful in aiding glioma detection. However, the image differences among facilities cause performance degradation and impede detection. This study proposes a method to solve this issue. We used the data from the Multimodal Brain Tumor Image Segmentation Benchmark (BraTS) and the Japanese cohort (JC) datasets. Three models for tumor segmentation are developed. In our methodology, the BraTS and JC models are trained on the BraTS and JC datasets, respectively, whereas the fine-tuning models are developed from the BraTS model and fine-tuned using the JC dataset. Our results show that the Dice coefficient score of the JC model for the test portion of the JC dataset was 0.779 ± 0.137, whereas that of the BraTS model was lower (0.717 ± 0.207). The mean Dice coefficient score of the fine-tuning model was 0.769 ± 0.138. There was a significant difference between the BraTS and JC models (p < 0.0001) and the BraTS and fine-tuning models (p = 0.002); however, no significant difference between the JC and fine-tuning models (p = 0.673). As our fine-tuning method requires fewer than 20 cases, this method is useful even in a facility where the number of glioma cases is small.

    DOI: 10.3390/cancers13061415

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  • So-called bifocal tumors with diabetes insipidus and negative tumor markers: are they all germinoma? 国際誌

    Masayuki Kanamori, Hirokazu Takami, Shigeru Yamaguchi, Takashi Sasayama, Koji Yoshimoto, Teiji Tominaga, Akihiro Inoue, Naokado Ikeda, Atsushi Kambe, Toshihiro Kumabe, Masahide Matsuda, Shota Tanaka, Manabu Natsumeda, Ken-Ichiro Matsuda, Masahiro Nonaka, Jun Kurihara, Masayoshi Yamaoka, Naoki Kagawa, Naoki Shinojima, Tetsuya Negoto, Yukiko Nakahara, Yoshiki Arakawa, Seiji Hatazaki, Hiroaki Shimizu, Atsuo Yoshino, Hiroshi Abe, Jiro Akimoto, Yu Kawanishi, Tomonari Suzuki, Atsushi Natsume, Motoo Nagane, Yukinori Akiyama, Dai Keino, Tadateru Fukami, Takahiro Tomita, Kohei Kanaya, Tsutomu Tokuyama, Shuichi Izumoto, Mitsutoshi Nakada, Daisuke Kuga, Shohei Yamamoto, Ryogo Anei, Takeo Uzuka, Junya Fukai, Noriyuki Kijima, Keita Terashima, Koichi Ichimura, Ryo Nishikawa

    Neuro-oncology   23 ( 2 )   295 - 303   2021年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The Delphi consensus statements on the management of germ cell tumors (GCTs) failed to reach agreements on the statement that the cases with (i) pineal and neurohypophyseal bifocal lesion, (ii) with diabetes insipidus, and (iii) with negative tumor markers can be diagnosed as germinoma without histological verification. To answer this, multicenter retrospective analysis was performed. METHODS: A questionnaire on clinical findings, histological diagnosis, and details of surgical procedures was sent to 86 neurosurgical and 35 pediatrics departments in Japan. RESULTS: Fifty-one institutes reported 132 cases that fulfilled the 3 criteria. Tissue sampling was performed in 91 cases from pineal (n = 44), neurohypophyseal (n = 32), both (n = 6), and distant (n = 9) lesions. Histological diagnosis was established in 89 cases: pure germinoma or germinoma with syncytiotrophoblastic giant cells in 82 (92.1%) cases, germinoma and mature teratoma in 2 cases, and granulomatous inflammation in 2 cases. Histological diagnosis was not established in 2 cases. Although no tumors other than GCTs were identified, 3 (3.4%) patients had non-germinomatous GCTs (NGGCTs). None of the patients developed permanent complications after endoscopic or stereotactic biopsy. Thirty-nine patients underwent simultaneous procedure for acute hydrocephalus without permanent complications, and hydrocephalus was controlled in 94.9% of them. CONCLUSION: All patients who fulfilled the 3 criteria had GCTs or granulomatous inflammation, but not other types of tumors. However, no fewer than 3.4% of the patients had NGGCTs. Considering the safety and the effects of simultaneous procedures for acute hydrocephalus, biopsy was recommended in such patients.

    DOI: 10.1093/neuonc/noaa199

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  • Necessity for craniospinal irradiation of germinoma with positive cytology without spinal lesion on MR imaging—A controversy

    Masayuki Kanamori, Hirokazu Takami, Tomonari Suzuki, Teiji Tominaga, Jun Kurihara, Shota Tanaka, Seiji Hatazaki, Motoo Nagane, Masahide Matsuda, Atsuo Yoshino, Manabu Natsumeda, Masayoshi Yamaoka, Naoki Kagawa, Yukinori Akiyama, Junya Fukai, Tetsuya Negoto, Ichiyo Shibahara, Kazuhiro Tanaka, Akihiro Inoue, Mitsuhiro Mase, Takahiro Tomita, Daisuke Kuga, Noriyuki Kijima, Tadateru Fukami, Yukiko Nakahara, Atsushi Natsume, Koji Yoshimoto, Dai Keino, Tsutomu Tokuyama, Kenichiro Asano, Kenta Ujifuku, Hiroshi Abe, Mitsutoshi Nakada, Ken-ichiro Matsuda, Yoshiki Arakawa, Naokado Ikeda, Yoshitaka Narita, Naoki Shinojima, Atsushi Kambe, Masahiko Nonaka, Shuichi Izumoto, Yu Kawanishi, Kohei Kanaya, Sadahiro Nomura, Kohei Nakajima, Shohei Yamamoto, Keita Terashima, Koichi Ichimura, Ryo Nishikawa

    Neuro-Oncology Advances   3 ( 1 )   2021年1月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

    <title>Abstract</title>
    <sec>
    <title>Background</title>
    Cerebrospinal fluid (CSF) cytology and spinal MR imaging are routinely performed for staging before treatment of intracranial germinoma. However, the interpretation of the results of CSF cytology poses 2 unresolved clinical questions: (1) Does positive CSF cytology correlate with the presence of spinal lesion before treatment? and (2) Is craniospinal irradiation (CSI) necessary for patients with positive CSF cytology in the absence of spinal lesion?


    </sec>
    <sec>
    <title>Methods</title>
    Multicenter retrospective analyses were performed based on a questionnaire on clinical features, spinal MR imaging finding, results of CSF cytology, treatments, and outcomes which was sent to 86 neurosurgical and 35 pediatrics departments in Japan. Pretreatment frequencies of spinal lesion on MR imaging were compared between the patients with positive and negative cytology. Progression-free survival (PFS) rates were compared between patients with positive CSF cytology without spinal lesion on MR imaging treated with CSI and with whole brain or whole ventricular irradiation (non-CSI).


    </sec>
    <sec>
    <title>Results</title>
    A total of 92 germinoma patients from 45 institutes were evaluated by both CSF cytology and spinal MR images, but 26 patients were excluded because of tumor markers, the timing of CSF sampling or incomplete estimation of spinal lesion. Of the remaining 66 germinoma patients, spinal lesions were equally identified in patients with negative CSF cytology and positive cytology (4.9% and 8.0%, respectively). Eleven patients treated with non-CSI had excellent PFS comparable to 11 patients treated with CSI.


    </sec>
    <sec>
    <title>Conclusion</title>
    CSI is unnecessary for germinoma patients with positive CSF cytology without spinal lesions on MR imaging.


    </sec>

    DOI: 10.1093/noajnl/vdab086

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    その他リンク: http://academic.oup.com/noa/article-pdf/3/1/vdab086/39555495/vdab086.pdf

  • Low tumor cell content predicts favorable prognosis in germinoma patients

    Hirokazu Takami, Kaishi Satomi, Kohei Fukuoka, Shintaro Fukushima, Yuko Matsushita, Kai Yamasaki, Taishi Nakamura, Shota Tanaka, Akitake Mukasa, Nobuhito Saito, Tomonari Suzuki, Takaaki Yanagisawa, Hideo Nakamura, Kazuhiko Sugiyama, Kaoru Tamura, Taketoshi Maehara, Mitsutoshi Nakada, Masahiro Nonaka, Akio Asai, Kiyotaka Yokogami, Hideo Takeshima, Toshihiko Iuchi, Yonehiro Kanemura, Keiichi Kobayashi, Motoo Nagane, Kazuhiko Kurozumi, Koji Yoshimoto, Masahide Matsuda, Akira Matsumura, Yuichi Hirose, Tsutomu Tokuyama, Toshihiro Kumabe, Yoshitaka Narita, Soichiro Shibui, Yoichi Nakazato, Ryo Nishikawa, Masao Matsutani, Koichi Ichimura

    Neuro-Oncology Advances   3 ( 1 )   2021年1月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

    <title>Abstract</title>
    <sec>
    <title>Background</title>
    Germinoma preferentially occurs in pediatric and young adult age groups. Although they are responsive to treatment with chemotherapy and radiation, the treatment may cause long-term sequelae in their later lives. Here, we searched for clinical and histopathological features to predict the prognosis of germinoma and affect treatment response.


    </sec>
    <sec>
    <title>Methods</title>
    A total of 114 germinoma cases were included in the analysis. We investigated the association between clinical factors, tumor cell content, and progression-free survival (PFS).


    </sec>
    <sec>
    <title>Results</title>
    The tumor cell content was widely distributed from &amp;lt;5% to 90% in the specimens, with a median value of 50%. Female patients showed higher tumor cell content in the specimens (P = .002). Cases with lesions at atypical sites showed shorter PFS than those with lesions at other sites (P = .03). Patients with a higher tumor cell content (≥50%) showed shorter PFS than those with a lower tumor cell content (&amp;lt;50%) (P = .03). In multivariate analysis, tumor cell content was the only statistically significant prognostic factor (P = .04). Among the 7 cases treated with local radiation and chemotherapy, all 3 cases that recurred (2 outside of the radiation field, 1 unknown) had tumor cell content of ≥50% in the original specimen, whereas all 4 cases without recurrence had tumor cell contents of &amp;lt;50%.


    </sec>
    <sec>
    <title>Conclusions</title>
    We found that tumor cell content significantly affected the prognosis of germinomas. Although validation of these results using an independent and larger cohort is necessary, this potentially opens the possibility of leveraging this pathological factor in future clinical trials when stratifying the treatment intensity.


    </sec>

    DOI: 10.1093/noajnl/vdab110

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    その他リンク: http://academic.oup.com/noa/article-pdf/3/1/vdab110/40404167/vdab110.pdf

  • 検査からみる神経疾患 オンコパネル検査と脳腫瘍

    高柳 俊作, 田中 將太, 齊藤 延人

    Clinical Neuroscience   39 ( 1 )   120 - 122   2021年1月

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    記述言語:日本語   出版者・発行元:(株)中外医学社  

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  • MPC-11 Comprehensive gene expression analysis of IDH-mutated astrocytomas with 19q-loss

    Ryohei Otani, Akitake Mukasa, Takeo Uzuka, Fumi Higuchi, Hadzki Matsuda, Shota Tanaka, Phyo Kim, Keisuke Ueki

    Neuro-Oncology Advances   2 ( Supplement_3 )   ii12 - ii12   2020年11月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

    Abstract

    We previously reported that there was a subgroup of IDH-mutated astrocytomas harboring only 19q-loss showing oligodendroglioma-like morphology and significantly longer overall survival (OS) compared with 19q-intact astrocytomas. To further explore the biological characteristics of this possible subgroup and obtain insight into the mechanism of their relatively benign clinical behavior, we compared gene expression pattern between five 19q-loss and five 19q-intact IDH-mutated astrocytomas by microarray analysis. By comparing expression levels of genes of 19q-loss astrocytomas to those of 19q-intact astrocytomas,136 up-regulated genes and 203 down-regulated genes were extracted. Down-regulated genes in the 19q-loss astrocytomas were heavily clustered to 19q and 4p, and up-regulated genes to 4q. It was noted that fibroblast growth factor 1 associated with stem cell maintenance was down-regulated in 19q-loss astrocytomas and genes associated with glioma progression were differentially expressed, these results were validated with the independent TCGA data set. On t-SNE analysis of the 19q-loss astrocytomas with other IDH-mutant glioma subgroups from the TCGA datasets, 19q-loss astrocytomas did not shift to oligodendrogliomas with 1p/19q codeletion but were a subgroup in astrocytomas. These results indicated that 19q-loss in astrocytomas is more likely to be an acquired event rather than early event in oncogenesis like 1p/19q codeletion in oligodendrogliomas, and the biological and morphological features of 19q-loss astrocytomas were possibly related to differentially expressed genes associated with stem cell maintenance and glioma progression.

    DOI: 10.1093/noajnl/vdaa143.053

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  • TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations. 国際誌

    Hideyuki Arita, Yuko Matsushita, Ryunosuke Machida, Kai Yamasaki, Nobuhiro Hata, Makoto Ohno, Shigeru Yamaguchi, Takashi Sasayama, Shota Tanaka, Fumi Higuchi, Toshihiko Iuchi, Kuniaki Saito, Masayuki Kanamori, Ken-Ichiro Matsuda, Yohei Miyake, Kaoru Tamura, Sho Tamai, Taishi Nakamura, Takehiro Uda, Yoshiko Okita, Junya Fukai, Daisuke Sakamoto, Yasuhiko Hattori, Eriel Sandika Pareira, Ryusuke Hatae, Yukitomo Ishi, Yasuji Miyakita, Kazuhiro Tanaka, Shunsaku Takayanagi, Ryohei Otani, Tsukasa Sakaida, Keiichi Kobayashi, Ryuta Saito, Kazuhiko Kurozumi, Tomoko Shofuda, Masahiro Nonaka, Hiroyoshi Suzuki, Makoto Shibuya, Takashi Komori, Hikaru Sasaki, Masahiro Mizoguchi, Haruhiko Kishima, Mitsutoshi Nakada, Yukihiko Sonoda, Teiji Tominaga, Motoo Nagane, Ryo Nishikawa, Yonehiro Kanemura, Aya Kuchiba, Yoshitaka Narita, Koichi Ichimura

    Acta neuropathologica communications   8 ( 1 )   201 - 201   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    TERT promoter mutations are commonly associated with 1p/19q codeletion in IDH-mutated gliomas. However, whether these mutations have an impact on patient survival independent of 1p/19q codeletion is unknown. In this study, we investigated the impact of TERT promoter mutations on survival in IDH-mutated glioma cases. Detailed clinical information and molecular status data were collected for a cohort of 560 adult patients with IDH-mutated gliomas. Among these patients, 279 had both TERT promoter mutation and 1p/19q codeletion, while 30 had either TERT promoter mutation (n = 24) or 1p/19q codeletion (n = 6) alone. A univariable Cox proportional hazard analysis for survival using clinical and genetic factors indicated that a Karnofsky performance status score (KPS) of 90 or 100, WHO grade II or III, TERT promoter mutation, 1p/19q codeletion, radiation therapy, and extent of resection (90-100%) were associated with favorable prognosis (p < 0.05). A multivariable Cox regression model revealed that TERT promoter mutation had a significantly favorable prognostic impact (hazard ratio = 0.421, p = 0.049), while 1p/19q codeletion did not have a significant impact (hazard ratio = 0.648, p = 0.349). Analyses incorporating patient clinical and genetic information were further conducted to identify subgroups showing the favorable prognostic impact of TERT promoter mutation. Among the grade II-III glioma patients with a KPS score of 90 or 100, those with IDH-TERT co-mutation and intact 1p/19q (n = 17) showed significantly longer survival than those with IDH mutation, wild-type TERT, and intact 1p/19q (n = 185) (5-year overall survival, 94% and 77%, respectively; p = 0.032). Our results demonstrate that TERT promoter mutation predicts favorable prognosis independent of 1p/19q codeletion in IDH-mutated gliomas. Combined with its adverse effect on survival among IDH-wild glioma cases, the bivalent prognostic impact of TERT promoter mutation may help further refine the molecular diagnosis and prognostication of diffuse gliomas.

    DOI: 10.1186/s40478-020-01078-2

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  • PATH-10. EFFECTS OF 19q-LOSS IN IDH-MUTATED ASTROCYTOMAS ON BETTER PROGNOSIS AND OLIGODENDROGLIOMA-LIKE MORPHOLOGY

    Ryohei Otani, Takeo Uzuka, Fumi Higuchi, Hadzki Matsuda, Shota Tanaka, Akitake Mukasa, Phyo Kim, Keisuke Ueki

    Neuro-Oncology   22 ( Supplement_2 )   ii165 - ii166   2020年11月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

    Abstract

    We previously reported that there was a subgroup of IDH-mutated astrocytomas harboring only 19q-loss showing oligodendroglioma-like morphology and significantly longer overall survival (OS) compared with 19q-intact astrocytomas. To further explore the biological characteristics of this possible subgroup and obtain insight into the mechanism of their clinical behavior, we compared gene expression pattern between five 19q-loss and five 19q-intact IDH-mutated astrocytomas by microarray analysis. Comparing expression level of each genes between 19q-loss and 19q-intact astrocytomas,136 up-regulated genes and 203 down-regulated genes were extracted. Gene expression patterns of 19q-loss astrocytomas were partially different from that of 19q-intact astrocytomas. More down-regulated genes distributed on 19q and 4p, and more up-regulated genes distributed on 4q. Multiple genes associated with stem cell maintenance were down-regulated in 19q-loss astrocytomas, and genes associated with glioma progression were differentially expressed. Comparing expression patterns among 19q-loss astrocytomas and other IDH-mutant glioma subgroups using TCGA datasets by t-SNE analysis revealed that expression pattern of 19q-loss astrocytomas did not shift to that of oligodendrogliomas with 1p/19q codeletion but were a subgroup in astrocytomas. These results indicated that 19q-loss in astrocytomas was an acquired event different from 1p/19q codeletion in oligodendrogliomas, and better prognosis morphological features in 19q-loss astrocytomas were derived from differentially expressed genes associated with stem cell maintenance and glioma progression.

    DOI: 10.1093/neuonc/noaa215.692

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  • グリオーマを術中標識する新規局所噴霧型蛍光プローブの開発

    田中 將太, 北川 陽介, 高柳 俊作, 武笠 晃丈, 浦野 泰照

    日本癌学会総会記事   79回   OE15 - 4   2020年10月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • 神経内視鏡手術:適応・手術手技・合併症回避、そして新たな展開 脳室拡大を伴わない小児脳室内腫瘍に対する神経内視鏡手術 適応、手術手技、合併症の回避と新たな展開

    辛 正廣, 田中 将太, 高柳 俊作, 斉藤 延人

    小児の脳神経   45 ( 3 )   214 - 214   2020年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児神経外科学会  

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  • 脊髄上衣腫のエピゲノム解析

    山澤 恵理香, 田中 將太, 永江 玄太, 目黒 裕子, 梅田 高呂, 花 大洵, 高見 俊宏, 中西 勇太, 谷口 真, 高井 敬介, 小森 隆司, 市村 幸一, 福岡 講平, 高柳 俊作, 油谷 浩幸, 齋藤 延人

    日本癌学会総会記事   79回   OE9 - 3   2020年10月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • グリオーマを術中標識する新規局所噴霧型蛍光プローブの開発

    田中 將太, 北川 陽介, 高柳 俊作, 武笠 晃丈, 浦野 泰照

    日本癌学会総会記事   79回   OE15 - 4   2020年10月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • 脊髄上衣腫のエピゲノム解析

    山澤 恵理香, 田中 將太, 永江 玄太, 目黒 裕子, 梅田 高呂, 花 大洵, 高見 俊宏, 中西 勇太, 谷口 真, 高井 敬介, 小森 隆司, 市村 幸一, 福岡 講平, 高柳 俊作, 油谷 浩幸, 齋藤 延人

    日本癌学会総会記事   79回   OE9 - 3   2020年10月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • Factors associated with health-related quality of life in patients with glioma: impact of symptoms and implications for rehabilitation. 査読 国際誌

    Shigeko Umezaki, Yusuke Shinoda, Akitake Mukasa, Shota Tanaka, Shunsaku Takayanagi, Hiroyuki Oka, Hisato Tagawa, Nobuhiko Haga, Mariko Yoshino

    Japanese journal of clinical oncology   50 ( 9 )   990 - 998   2020年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: The factors associated with health-related quality of life in patients with glioma remain unclear; particularly, the impact of symptoms on quality of life has not been studied comprehensively. This study aims to document the quality of life of patients with glioma and clarify the impact of symptoms. METHODS: In this cross-sectional study, participants were recruited from patients at The University of Tokyo Hospital and from patients who were registered at the Japan Brain Tumor Alliance. We included adult patients with World Health Organization grade II-IV glioma and excluded those with disturbances of consciousness or aphasia. We used the European Organization for Research and Treatment of Cancer QLQ-C30 and BN20 to evaluate quality of life and the symptoms. Multiple regression analyses were performed to investigate the impact of symptoms on European Organization for Research and Treatment of Cancer global health status and QLQ-C30 social functioning. In addition, we performed univariate subgroup analyses classified by World Health Organization grade and history of chemotherapy. RESULTS: This study included 76 patients. Seven symptoms occurred in more than 50% of the patients: fatigue, future uncertainty, drowsiness, communication deficit, financial difficulties, motor dysfunction and weakness of legs. Multiple regression analyses showed that insomnia affected their global health status, and appetite loss, financial difficulties and motor dysfunction were significantly related to their social functioning. In subgroup analysis, the number of symptom subscales that were significantly related to global health status and social functioning was larger in World Health Organization grade II patients compared with grade III/IV patients. CONCLUSIONS: In addition to neurological deficits, symptoms were associated with poor quality of life in patients with glioma. This study provided the basis on further investigation of usefulness of symptom evaluation on quality of life improvement.

    DOI: 10.1093/jjco/hyaa068

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  • 現場最前線 覚醒下腫瘍摘出術における言語聴覚士の役割 日英米の比較

    兼岡 麻子, 荻野 亜希子, 高柳 俊作, 國井 尚人, 田中 将太, 芳賀 信彦

    言語聴覚研究   17 ( 3 )   177 - 180   2020年9月

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    記述言語:日本語   出版者・発行元:(一社)日本言語聴覚士協会  

    <文献概要>1.はじめに 覚醒下腫瘍摘出手術は,脳腫瘍周辺の機能領域に対する損傷を避けつつ,腫瘍を最大限に切除することを目的とした術式で,通常の開頭腫瘍摘出術に比べて腫瘍摘出率,術後後遺症,生命予後の点で優位とされる.言語野近傍の腫瘍に対する覚醒下手術では,術中に患者を覚醒させ,言語タスクを実施する間に患者の脳表に電気刺激を与えてその機能を一時的に低下させ,電気刺激によって誘発または抑制される言語症状から患者の機能領域を同定する(図1).術者はこの皮質マッピングの結果を考慮して腫瘍の切除範囲を決定する.また,言語に関わる神経線維近傍の腫瘍切除術では,脳白質に電気刺激を与えて陽性反応を観察する皮質下マッピングも行われる.本邦では,2012年に日本Awake Surgery学会が世界初の英語版覚醒下手術ガイドラインを,また翌年には日本語版ガイドラインを発表した.さらに,2014年には覚醒下脳手術施設認定制度が始まり,2015年には脳腫瘍覚醒下マッピング加算の算定が可能となった.2016年には全国で105件,2017年には185件の覚醒下腫瘍摘出術が施行され,今後覚醒下手術を行う施設はさらに増えるものと予想される.覚醒下手術は多職種によるチーム医療であり,言語・高次脳機能の専門職として言語聴覚士もその一端を担う.当院においても,2016年より言語聴覚士が覚醒下手術に参加し,術前評価,術中マッピング,術後評価とリハビリテーションを行っている.覚醒下手術は世界的に広く行われているが,各国の覚醒下手術における言語聴覚士の役割を知る機会は少ない.今回,英米の2大学病院に勤務する言語聴覚士とともに,当院を含めた3大学病院の覚醒下手術における言語聴覚士の業務内容を比較し,課題や今後の展望について考察したので報告する.なお,本稿の要旨は,The American Speech-Language-Hearing Association Convention 2019において,各病院の言語聴覚士と共同で発表した.また,言語聴覚士の職名は各国で異なるが(英国:Speech Language Therapist,SLT/米国:Speech Language Pathologist,SLP/日本:Speech Therapist,ST),本稿では便宜上,一律に「言語聴覚士」と記載した.

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  • 初発膠芽腫におけるMGMTと腫瘍微小環境との関連

    串原 義啓, 齋藤 範之, 手島 太郎, 孫 長博, 小林 由香利, 長岡 孝治, 細井 亮宏, 唐崎 隆弘, 田中 將太, 齊藤 延人, 垣見 和宏

    日本がん免疫学会総会プログラム・抄録集   24回   91 - 91   2020年9月

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    記述言語:日本語   出版者・発行元:日本がん免疫学会  

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  • 専門医に求められる最新の知識 脳腫瘍 がん遺伝子パネル検査結果に基づく脳腫瘍治療の展望

    高柳 俊作, 田中 將太, 齊藤 延人

    脳神経外科速報   30 ( 9 )   970 - 977   2020年9月

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    記述言語:日本語   出版者・発行元:(株)メディカ出版  

    NCCオンコパネルやFoundationOneといった、多数のがん関連遺伝子の異常を一度に解析できるがん遺伝子パネル検査が日本でも保険診療で行えるようになり、わが国のがんゲノム医療体制は急速に整備されてきた。パネル検査により、脳腫瘍領域でも、治療に有用と思われる多数の遺伝子異常が同定できる。例えばEGFR、IDH、H3F3A、HIST1H3B、BRAF遺伝子、NTRK融合遺伝子などである。これらの遺伝子異常に対応した分子標的薬は、現状ではまだまだ少ない状況である。しかし、NTRK融合遺伝子陽性腫瘍に対するエヌトレクチニブは保険承認され、さらにIDH阻害薬やBRAF阻害薬などの臨床試験も行われており、少しずつではあるが、脳腫瘍領域においてもパネル検査結果に基づく個別化医療が推進されていくことが予想される。(著者抄録)

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    その他リンク: https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J03120&link_issn=&doc_id=20200826180004&doc_link_id=issn%3D0917-1495%26volume%3D30%26issue%3D9%26spage%3D970&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0917-1495%26volume%3D30%26issue%3D9%26spage%3D970&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

  • 膠芽腫を標識する噴霧式新規蛍光プローブの開発

    北川 陽介, 田中 將太, 神谷 真子, 栗木 優五, 高柳 俊作, 武笠 晃丈, 浦野 泰照, 齊藤 延人

    日本レーザー医学会誌   41 ( 3 )   277 - 277   2020年9月

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    記述言語:日本語   出版者・発行元:(NPO)日本レーザー医学会  

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  • 脳腫瘍の遺伝子診断とゲノム医療2 19q-lossを伴うastrocytomaが予後良好である機序の解明

    大谷 亮平, 宇塚 岳夫, 樋口 芙未, 松田 葉月, 田中 将太, 金 彪, 植木 敬介

    Brain Tumor Pathology   37 ( Suppl. )   075 - 075   2020年8月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 家族性腫瘍(遺伝性腫瘍)における脳腫瘍 遺伝性腫瘍疾患における脳腫瘍の病理と遺伝子解析

    高柳 俊作, 高見 浩数, 田中 将太, 寺西 裕, 宮脇 哲, 辛 正廣, 中冨 浩文, 池村 雅子, 織田 克利, 齊藤 延人

    Brain Tumor Pathology   37 ( Suppl. )   078 - 078   2020年8月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 脳腫瘍の遺伝子診断とゲノム医療1 IDH wildtype LGGにおける最も重要な予後不良因子はTERT promoter mutationである

    藤本 健二, 有田 英之, 金村 米博, 田中 將太, 永根 基雄, 植木 敬介, 西川 亮, 小森 隆司, 成田 善孝, 市村 幸一

    Brain Tumor Pathology   37 ( Suppl. )   065 - 065   2020年8月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 家族性腫瘍(遺伝性腫瘍)における脳腫瘍 遺伝性腫瘍疾患における脳腫瘍の病理と遺伝子解析

    高柳 俊作, 高見 浩数, 田中 将太, 寺西 裕, 宮脇 哲, 辛 正廣, 中冨 浩文, 池村 雅子, 織田 克利, 齊藤 延人

    Brain Tumor Pathology   37 ( Suppl. )   078 - 078   2020年8月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 脳腫瘍の遺伝子診断とゲノム医療2 19q-lossを伴うastrocytomaが予後良好である機序の解明

    大谷 亮平, 宇塚 岳夫, 樋口 芙未, 松田 葉月, 田中 将太, 金 彪, 植木 敬介

    Brain Tumor Pathology   37 ( Suppl. )   075 - 075   2020年8月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • Validation study of the Japanese version of MD Anderson Symptom Inventory for Brain Tumor module. 査読 国際誌

    Shota Tanaka, Iori Sato, Masamichi Takahashi, Terri S Armstrong, Charles S Cleeland, Tito R Mendoza, Akitake Mukasa, Shunsaku Takayanagi, Yoshitaka Narita, Kiyoko Kamibeppu, Nobuhito Saito

    Japanese journal of clinical oncology   50 ( 7 )   787 - 793   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: The MD Anderson Symptom Inventory for Brain Tumor (MDASI-BT) module is a widely used instrument for measuring symptom burden and interference of daily activities in brain tumor patients. This study aims to develop and validate its Japanese version (MDASI-BT-Japanese). METHODS: Following forward and backward translation of the original MDASI-BT into Japanese, understandability and feasibility were assessed by cognitive debriefing. Subsequently, patients with brain tumors were asked to fill out MDASI-BT-Japanese and European Quality of Life-5 Dimensions (EQ-5D). Feasibility, reliability and validity of MDASI-BT-Japanese were assessed. RESULTS: Cognitive debriefing confirmed overall ease of completion and good understandability. The study population composed of 140 patients with brain tumors (most commonly gliomas). The mean symptom severity score and mean interference score were 1.9 ± 1.7 and 2.8 ± 2.7, respectively. The top items included distress and drowsiness for symptom severity and general activity and work for interference. The median time required was 4 minutes (range, 0.5-30), and missing values were seen in 1%. Internal consistency was proven by excellent Cronbach's coefficient alpha (0.94 for symptom severity, 0.92 for interference). Test-retest reliability was assessed with acceptable intra-class correlation coefficient (mean, 0.76). Correlation efficient ranged between 0.7 and 0.9 for convergent validity. Known-group validity was confirmed by significantly different mean symptom severity score and mean interference score among patients with different performance status. As evidence of concurrent validity, MDASI-BT-Japanese correlated with EQ-5D in the hypothesized magnitude and direction. CONCLUSIONS: The newly developed MDASI-BT-Japanese has demonstrated feasibility, reliability and validity in evaluation of clinical benefit in Japanese-speaking brain tumor patients.

    DOI: 10.1093/jjco/hyaa036

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  • Small Cell Variant of Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma of the Dura Mimicking Tentorial Meningioma. 査読 国際誌

    Yudai Hirano, Satoru Miyawaki, Michiaki Satou, Kazuki Taoka, Kazuhiro Toyama, Masako Ikemura, Ryo Tanaka, Shunsaku Takayanagi, Shota Tanaka, Hirofumi Nakatomi, Mineo Kurokawa, Nobuhito Saito

    World neurosurgery   138   169 - 173   2020年6月

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    記述言語:英語  

    BACKGROUND: Primary central nervous system (CNS) anaplastic large cell lymphoma (ALCL) is an uncommon type of brain tumor, usually treated with a regimen that includes high-dose methotrexate (MTX). Only a few cases of primary CNS anaplastic lymphoma kinase (ALK)-positive ALCL have been reported so far, with no reported cases of a small cell variant. CASE DESCRIPTION: A 26-year-old man presenting with headache and visual field impairment was found to have a supratentorial mass mimicking meningioma. Craniotomy was performed for tumor resection, and postoperative histologic examination revealed atypical cells that were nonenlarged lymphocytes with irregularly shaped and enlarged nuclei; these cells were cluster of differentiation 30 and ALK-positive, leading to the diagnosis of a small cell variant of ALK-positive ALCL. In this case, the tumor exhibited an aggressive behavior with MTX resistance with metastases in the pelvis but responded well to cytarabine and etoposide (CYVE). CONCLUSIONS: In general, CNS ALK-positive ALCL responds well to MTX, but small cell variants show aggressive behavior and may be resistant to MTX. For small cell variants of ALCL that are resistant to MTX therapy, as in this case, CYVE therapy may be an effective treatment.

    DOI: 10.1016/j.wneu.2020.02.171

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  • Increased Vascular Adhesion Protein 1 (VAP-1) Levels are Associated with Alternative M2 Macrophage Activation and Poor Prognosis for Human Gliomas. 国際誌

    Shu-Jyuan Chang, Hung-Pin Tu, Yen-Chang Clark Lai, Chi-Wen Luo, Takahide Nejo, Shota Tanaka, Chee-Yin Chai, Aij-Lie Kwan

    Diagnostics (Basel, Switzerland)   10 ( 5 )   2020年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Glioma is characterized by a high heterogeneity in the brain tumor. Abundant tumor-associated macrophages (TAMs) exist as neoplastic tissues, implicating tumor plasticity and thus leading to therapeutic challenges. Vascular adhesion protein (VAP-1) potentially serves as a mediator for TAM immunity in tumor milieu. We previously demonstrated that VAP-1 could contribute to tumor malignancy, but its characteristics in TAM immunity of glioma progression are still unclear. This study explored the association of VAP-1 expression with TAM distribution as well as the resulting clinical significance and prognostic value in human gliomas. An in-depth analysis of AOC3 (VAP-1) gene expression was performed using 695 glioma samples derived from the cancer genome atlas (TCGA)-lower grade glioma and glioblastoma (GBMLGG) cohort. Bioinformatic analysis confirmed that VAP-1 expression is associated with poor prognosis of glioma patients (p = 0.0283). VAP-1 and TAM biomarkers (CD68, iNOS, and CD163) were evaluated by immunohistochemistry in 108 gliomas from Kaohsiung Medical University Hospital. VAP-1+ was expressed in 56 (51.85%) cases and this phenotype revealed a significant association with overall survival in Kaplan-Meier analysis (p < 0.0001). Immunohistochemical double staining showed that VAP-1 immunoreactivity was present around CD163+ M2 infiltration location, including aggressive lesions and neighboring neovasculature. We demonstrated that high VAP-1 expression levels positively correlated with CD163+ M2 activation and coexpression of these two proteins was associated with worse survival in gliomas (p < 0.0001). Multivariate analysis indicated that VAP-1 alone and co-expressed with CD163 were the significantly independent indicators (both p < 0.0001). Furthermore, VAP-1/CD163 coexpression exhibited excellent diagnostic accuracy in gliomas (AUC = 0.8008). In conclusion, VAP-1 and TAM CD163 M2 coexpression was found in glioma tissues belonging to a highly malignant subgroup that was associated with poor prognosis. These results implied VAP-1 abundance is closely linked to alternative M2 activation during glioma progression. From the aforementioned data, a reasonable inference is that VAP-1 combined with targeting M2 immunity might be an effective therapeutic target for human gliomas.

    DOI: 10.3390/diagnostics10050256

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  • Publisher Correction: Prediction of malignant glioma grades using contrast-enhanced T1-weighted and T2-weighted magnetic resonance images based on a radiomic analysis. 国際誌

    Takahiro Nakamoto, Wataru Takahashi, Akihiro Haga, Satoshi Takahashi, Shigeru Kiryu, Kanabu Nawa, Takeshi Ohta, Sho Ozaki, Yuki Nozawa, Shota Tanaka, Akitake Mukasa, Keiichi Nakagawa

    Scientific reports   10 ( 1 )   3073 - 3073   2020年2月

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    記述言語:英語  

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    DOI: 10.1038/s41598-020-60086-3

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  • Medical Care-Related Decisions among Patients Diagnosed with Early Stage Malignant Brain Tumor: A Qualitative Study 国際誌

    Hanako Numata, Maiko Noguchi-Watanabe, Akitake Mukasa, Shota Tanaka, Shunsaku Takayanagi, Nobuhito Saito, Noriko Yamamoto-Mitani

    Global Qualitative Nursing Research   7   233339362096005 - 233339362096005   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)   出版者・発行元:SAGE Publications  

    Medical care-related decision-making among patients with malignant brain tumors has not been sufficiently discussed. This study aimed to develop a framework for understanding patients’ experiences in the decision-making process. Semi-structured interviews with 14 patients were analyzed using a grounded theory approach, focusing on their 48 decision-making points. Additionally, interviews with two family members and seven healthcare providers, and participant observations were used to gain contextual insight into patients’ experiences. Patients faced decisions while they struggled in vulnerability under shock, fear, and anxiety while hoping. Under this context, they showed four decision-making patterns: (1) led by the situation, (2) controlled by others, (3) entrusted someone with the decision, and (4) myself as a decision-making agent. Across these patterns, the patients were generally satisfied with their decisions even when they did not actively participate in the process. Healthcare providers need to understand patients’ contexts and their attitudes toward yielding decision-making to others.

    DOI: 10.1177/2333393620960059

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    その他リンク: http://journals.sagepub.com/doi/full-xml/10.1177/2333393620960059

  • Exploring Predictors of Response to Dacomitinib in EGFR-Amplified Recurrent Glioblastoma. 国際誌

    Andrew S Chi, Daniel P Cahill, David A Reardon, Patrick Y Wen, Tom Mikkelsen, David M Peereboom, Eric T Wong, Elizabeth R Gerstner, Jorg Dietrich, Scott R Plotkin, Andrew D Norden, Eudocia Q Lee, Lakshmi Nayak, Shota Tanaka, Hiroaki Wakimoto, Nina Lelic, Mara V Koerner, Lindsay K Klofas, Mia S Bertalan, Isabel C Arrillaga-Romany, Rebecca A Betensky, William T Curry, Darrel R Borger, Leonora Balaj, Robert R Kitchen, Sudipto K Chakrabortty, Michael D Valentino, Johan Skog, Xandra O Breakefield, A John Iafrate, Tracy T Batchelor

    JCO precision oncology   4   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: Despite the high frequency of EGFR genetic alterations in glioblastoma (GBM), EGFR-targeted therapies have not had success in this disease. To improve the likelihood of efficacy, we targeted adult patients with recurrent GBM enriched for EGFR gene amplification, which occurs in approximately half of GBM, with dacomitinib, a second-generation, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that penetrates the blood-brain barrier, in a multicenter phase II trial. PATIENTS AND METHODS: We retrospectively explored whether previously described EGFR extracellular domain (ECD)-sensitizing mutations in the context of EGFR gene amplification could predict response to dacomitinib, and in a predefined subset of patients, we measured post-treatment intratumoral dacomitinib levels to verify tumor penetration. RESULTS: We found that dacomitinib effectively penetrates contrast-enhancing GBM tumors. Among all 56 treated patients, 8 (14.3%) had a clinical benefit as defined by a duration of treatment of at least 6 months, of whom 5 (8.9%) remained progression free for at least 1 year. Presence of EGFRvIII or EGFR ECD missense mutation was not associated with clinical benefit. We evaluated the pretreatment transcriptome in circulating extracellular vesicles (EVs) by RNA sequencing in a subset of patients and identified a signature that distinguished patients who had durable benefit versus those with rapid progression. CONCLUSION: While dacomitinib was not effective in most patients with EGFR-amplified GBM, a subset experienced a durable, clinically meaningful benefit. Moreover, EGFRvIII and EGFR ECD mutation status in archival tumors did not predict clinical benefit. RNA signatures in circulating EVs may warrant investigation as biomarkers of dacomitinib efficacy in GBM.

    DOI: 10.1200/PO.19.00295

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  • Prediction of malignant glioma grades using contrast-enhanced T1-weighted and T2-weighted magnetic resonance images based on a radiomic analysis. 査読 国際誌

    Takahiro Nakamoto, Wataru Takahashi, Akihiro Haga, Satoshi Takahashi, Shigeru Kiryu, Kanabu Nawa, Takeshi Ohta, Sho Ozaki, Yuki Nozawa, Shota Tanaka, Akitake Mukasa, Keiichi Nakagawa

    Scientific reports   9 ( 1 )   19411 - 19411   2019年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We conducted a feasibility study to predict malignant glioma grades via radiomic analysis using contrast-enhanced T1-weighted magnetic resonance images (CE-T1WIs) and T2-weighted magnetic resonance images (T2WIs). We proposed a framework and applied it to CE-T1WIs and T2WIs (with tumor region data) acquired preoperatively from 157 patients with malignant glioma (grade III: 55, grade IV: 102) as the primary dataset and 67 patients with malignant glioma (grade III: 22, grade IV: 45) as the validation dataset. Radiomic features such as size/shape, intensity, histogram, and texture features were extracted from the tumor regions on the CE-T1WIs and T2WIs. The Wilcoxon-Mann-Whitney (WMW) test and least absolute shrinkage and selection operator logistic regression (LASSO-LR) were employed to select the radiomic features. Various machine learning (ML) algorithms were used to construct prediction models for the malignant glioma grades using the selected radiomic features. Leave-one-out cross-validation (LOOCV) was implemented to evaluate the performance of the prediction models in the primary dataset. The selected radiomic features for all folds in the LOOCV of the primary dataset were used to perform an independent validation. As evaluation indices, accuracies, sensitivities, specificities, and values for the area under receiver operating characteristic curve (or simply the area under the curve (AUC)) for all prediction models were calculated. The mean AUC value for all prediction models constructed by the ML algorithms in the LOOCV of the primary dataset was 0.902 ± 0.024 (95% CI (confidence interval), 0.873-0.932). In the independent validation, the mean AUC value for all prediction models was 0.747 ± 0.034 (95% CI, 0.705-0.790). The results of this study suggest that the malignant glioma grades could be sufficiently and easily predicted by preparing the CE-T1WIs, T2WIs, and tumor delineations for each patient. Our proposed framework may be an effective tool for preoperatively grading malignant gliomas.

    DOI: 10.1038/s41598-019-55922-0

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  • Radiomics Analysis for Glioma Malignancy Evaluation Using Diffusion Kurtosis and Tensor Imaging. 査読 国際誌

    Satoshi Takahashi, Wataru Takahashi, Shota Tanaka, Akihiro Haga, Takahiro Nakamoto, Yuichi Suzuki, Akitake Mukasa, Shunsaku Takayanagi, Yosuke Kitagawa, Taijun Hana, Takahide Nejo, Masashi Nomura, Keiichi Nakagawa, Nobuhito Saito

    International journal of radiation oncology, biology, physics   105 ( 4 )   784 - 791   2019年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: A noninvasive diagnostic method to predict the degree of malignancy accurately would be of great help in glioma management. This study aimed to create a highly accurate machine learning model to perform glioma grading. METHODS AND MATERIALS: Preoperative magnetic resonance imaging acquired for cases of glioma operated on at our institution from October 2014 through January 2018 were obtained retrospectively. Six types of magnetic resonance imaging sequences (T2-weighted image, diffusion-weighted image, apparent diffusion coefficient [ADC], fractional anisotropy, and mean kurtosis [MK]) were chosen for analysis; 476 features were extracted semiautomatically for each sequence (2856 features in total). Recursive feature elimination was used to select significant features for a machine learning model that distinguishes glioblastoma from lower-grade glioma (grades 2 and 3). RESULTS: Fifty-five data sets from 54 cases were obtained (14 grade 2 gliomas, 12 grade 3 gliomas, and 29 glioblastomas), of which 44 and 11 data sets were used for machine learning and independent testing, respectively. We detected 504 features with significant differences (false discovery rate <0.05) between glioblastoma and lower-grade glioma. The most accurate machine learning model was created using 6 features extracted from the ADC and MK images. In the logistic regression, the area under the curve was 0.90 ± 0.05, and the accuracy of the test data set was 0.91 (10 out of 11); using a support vector machine, they were 0.93 ± 0.03 and 0.91 (10 out of 11), respectively (kernel, radial basis function; c = 1.0). CONCLUSIONS: Our machine learning model accurately predicted glioma tumor grade. The ADC and MK sequences produced particularly useful features.

    DOI: 10.1016/j.ijrobp.2019.07.011

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  • NIMG-49. THE ACCURACY EVALUATION OF ARCUATE FASCICULUS OF DIFFUSION TENSOR TRACTOGRAPHY BY FUSION OF REAL SPACE AND VIRTUAL SPACE

    Tsukasa Koike, Taichi Kin, Yasuhiro Takeda, Hiroki Uchikawa, Taketo Shiode, Shunsaku Takayanagi, Shota Tanaka, Nobuhito Saito

    Neuro-Oncology   21 ( Supplement_6 )   vi172 - vi172   2019年11月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

    Abstract

    PURPOSE

    Diffusion tensor-based tractography (DTT) is a method to estimate the direction of white matter fibers, but it is difficult to verify the relationship with brain function spatially with high accuracy. We developed a registration method to fuse the real space (brain surface photograph) and preoperative fused 3D image (virtual space) using the landmark method and thin plate spline method. In our previous study, this method was able to achieve highly accurate alignment registration error 0.7±0.1mm (mean±SE) even after brain shift due to craniotomy. In this study, we proposed a method to examine spatial errors of DTT and direct cortical stimulation (DCS) and verify its accuracy.

    METHODS

    We included 7 gliomas performed awake surgery. We created the fused three – dimensional image before surgery and acquired the brain surface photograph immediately after craniotomy, then we aligned them using the proposed method. Sites that showed speech arrest by DCS were plotted on the fused image. A circle with a radius of 15 mm centered on the same site was taken as the range over which the current spreads. The surface area of each of the circles was calculated to make it true if there was arcuate fasciculus drawn with DTT in the circle, and false if it did not exist. By using this method, the accuracy of the DTT was verified. RESULT: In 7 cases, speech arrest was shown at 21 DCS plots. The probability of the presence of DTT within the current spread of DCS was 64.4%.

    CONCLUSION

    The proposed method indicates that DTT does not necessarily match the DCS results by verification using real space and virtual space. We present some illustrative cases.

    DOI: 10.1093/neuonc/noz175.718

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  • Two cases of primary supratentorial intracranial rhabdomyosarcoma with DICER1 mutation which may belong to a "spindle cell sarcoma with rhabdomyosarcoma-like feature, DICER1 mutant". 査読

    Sakaguchi M, Nakano Y, Honda-Kitahara M, Kinoshita M, Tanaka S, Oishi M, Noguchi K, Fukuda M, Maeba H, Watanabe T, Hayashi Y, Ikeda H, Minato H, Ichimura K, Nojima T, Nakada M

    Brain tumor pathology   36 ( 4 )   174 - 182   2019年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s10014-019-00352-z

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  • 領域特異的な5-hydroxymethylcytosine(5hmC)の変動がGlioma悪性転化に関与する(Region-specific 5-hydroxymethylcytosine(5hmC) alteration affects the glioma malignant transformation) 査読

    花 大洵, 野村 昌志, 武笠 晃丈, 田中 將太, 永江 玄太, 油谷 浩幸

    日本癌学会総会記事   78回   P - 1369   2019年9月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 領域特異的な5-hydroxymethylcytosine(5hmC)の変動がGlioma悪性転化に関与する(Region-specific 5-hydroxymethylcytosine(5hmC) alteration affects the glioma malignant transformation)

    花 大洵, 野村 昌志, 武笠 晃丈, 田中 將太, 永江 玄太, 油谷 浩幸

    日本癌学会総会記事   78回   P - 1369   2019年9月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • Reduced Neoantigen Expression Revealed by Longitudinal Multiomics as a Possible Immune Evasion Mechanism in Glioma. 査読 国際誌

    Takahide Nejo, Hirokazu Matsushita, Takahiro Karasaki, Masashi Nomura, Kuniaki Saito, Shota Tanaka, Shunsaku Takayanagi, Taijun Hana, Satoshi Takahashi, Yosuke Kitagawa, Tsukasa Koike, Yukari Kobayashi, Genta Nagae, Shogo Yamamoto, Hiroki Ueda, Kenji Tatsuno, Yoshitaka Narita, Motoo Nagane, Keisuke Ueki, Ryo Nishikawa, Hiroyuki Aburatani, Akitake Mukasa, Nobuhito Saito, Kazuhiro Kakimi

    Cancer immunology research   7 ( 7 )   1148 - 1161   2019年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Immune-based therapies have shown limited efficacy in glioma thus far. This might be at least in part due to insufficient numbers of neoantigens, thought to be targets of immune attack. In addition, we hypothesized that dynamic genetic and epigenetic tumor evolution in gliomas might also affect the mutation/neoantigen landscape and contribute to treatment resistance through immune evasion. Here, we investigated changes in the neoantigen landscape and immunologic features during glioma progression using exome and RNA-seq of paired primary and recurrent tumor samples obtained from 25 WHO grade II-IV glioma patients (glioblastoma, IDH-wild-type, n = 8; grade II-III astrocytoma, IDH-mutant, n = 9; and grade II-III oligodendroglioma, IDH-mutant, 1p/19q-codeleted, n = 8). The number of missense mutations, predicted neoantigens, or expressed neoantigens was not significantly different between primary and recurrent tumors. However, we found that in individual patients the ratio of expressed neoantigens to predicted neoantigens, designated the "neoantigen expression ratio," decreased significantly at recurrence (P = 0.003). This phenomenon was particularly pronounced for "high-affinity," "clonal," and "passenger gene-derived" neoantigens. Gene expression and IHC analyses suggested that the decreased neoantigen expression ratio was associated with intact antigen presentation machinery, increased tumor-infiltrating immune cells, and ongoing immune responses. Our findings imply that decreased expression of highly immunogenic neoantigens, possibly due to persistent immune selection pressure, might be one of the immune evasion mechanisms along with tumor clonal evolution in some gliomas.

    DOI: 10.1158/2326-6066.CIR-18-0599

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  • Publisher Correction: DNA demethylation is associated with malignant progression of lower-grade gliomas. 査読 国際誌

    Masashi Nomura, Kuniaki Saito, Koki Aihara, Genta Nagae, Shogo Yamamoto, Kenji Tatsuno, Hiroki Ueda, Shiro Fukuda, Takayoshi Umeda, Shota Tanaka, Shunsaku Takayanagi, Ryohei Otani, Takahide Nejo, Taijun Hana, Satoshi Takahashi, Yosuke Kitagawa, Mayu Omata, Fumi Higuchi, Taishi Nakamura, Yoshihiro Muragaki, Yoshitaka Narita, Motoo Nagane, Ryo Nishikawa, Keisuke Ueki, Nobuhito Saito, Hiroyuki Aburatani, Akitake Mukasa

    Scientific reports   9 ( 1 )   7935 - 7935   2019年5月

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    記述言語:英語  

    A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

    DOI: 10.1038/s41598-019-43790-7

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  • 結節性硬化症診療連携チーム結成による患者受診状況の変化

    佐藤 敦志, 佐藤 悠佑, 高柳 俊作, 辛 正廣, 田中 將太, 國井 尚人, 宮垣 朝光, 澤村 裕正, 漆山 博和, 谷口 豪, 大瀬戸 久美子, 張 香里, 岡 明, 水口 雅

    脳と発達   51 ( Suppl. )   S313 - S313   2019年5月

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    記述言語:日本語   出版者・発行元:(一社)日本小児神経学会  

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  • 微小環境 神経膠腫(1) グリオーマ悪性転化に於ける5-hydroxymethylcytosine(5hmC)変動の網羅的解析

    花 大洵, 武笠 晃丈, 野村 昌志, 田中 將太, 池村 雅子, 北川 陽介, 根城 尭英, 高柳 俊作, 油谷 浩幸, 斉藤 延人

    Brain Tumor Pathology   36 ( Suppl. )   065 - 065   2019年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • PIK3CA activating mutations are associated with more disseminated disease at presentation and earlier recurrence in glioblastoma. 査読 国際誌

    Shota Tanaka, Tracy T Batchelor, A John Iafrate, Dora Dias-Santagata, Darrell R Borger, Leif W Ellisen, Daniel Yang, David N Louis, Daniel P Cahill, Andrew S Chi

    Acta neuropathologica communications   7 ( 1 )   66 - 66   2019年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Phosphatidylinositol 3-kinase signaling promotes cell growth and survival and is frequently activated in infiltrative gliomas. Activating mutations in PIK3CA gene are observed in 6-15% of glioblastomas, although their clinical significance is largely undescribed. The objective of this study was to examine whether PIK3CA mutations are associated with a specific clinical phenotype in glioblastoma. We retrospectively reviewed 157 consecutive newly diagnosed glioblastoma patients from December 2009 to June 2012 who underwent molecular profiling consisting of targeted hotspot genotyping, fluorescence in situ hybridization for gene amplification, and methylation-specific PCR for O6-methylguanine-DNA methyltransferase promoter methylation. Molecular alterations were correlated with clinical features, imaging and outcome. The Cancer Genome Atlas data was analyzed as a validation set. There were 91 males; median age was 58 years (range, 23-85). With a median follow-up of 20.9 months, median progression-free survival (PFS) and estimated overall survival (OS) were 11.9 and 24.0 months, respectively. Thirteen patients (8.3%) harbored PIK3CA mutation, which was associated with younger age (mean 49.4 vs. 58.1 years, p = 0.02). PIK3CA mutation correlated with shorter PFS (median 6.9 vs. 12.4 months, p = 0.01) and OS (median 21.2 vs. 24.2 months, p = 0.049) in multivariate analysis. A significant association between PIK3CA mutation and more disseminated disease at diagnosis, as defined by gliomatosis, multicentric lesions, or distant leptomeningeal lesions, was observed (46.2% vs. 11.1%, p = 0.004). In conclusion, despite the association with younger age, PIK3CA activating mutations are associated with earlier recurrence and shorter survival in adult glioblastoma. The aggressive course of these tumors may be related to their propensity for disseminated presentation.

    DOI: 10.1186/s40478-019-0720-8

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  • 脳転移巣で横紋筋肉腫様変化を示した胎児型消化管胃癌の遺伝子解析

    山澤 翔, 牛久 哲男, 山下 裕玄, 田中 將太, 鈴木 章浩, 油谷 浩幸, 深山 正久

    日本病理学会会誌   108 ( 1 )   365 - 365   2019年4月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • Pattern of FDG and MET Distribution in High- and Low-Grade Gliomas on PET Images. 査読 国際誌

    Miwako Takahashi, Tsutomu Soma, Akitake Mukasa, Shota Tanaka, Shunsuke Yanagisawa, Toshimitsu Momose

    Clinical nuclear medicine   44 ( 4 )   265 - 271   2019年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE OF THE REPORT: This study aimed to determine the most effective metabolic index of FDG-PET and MET-PET to differentiate high- and low-grade gliomas, and then to characterize tumor metabolism according to the 2016 WHO classification. We also developed a new calculation method of potential infiltrative tumor volume to overcome the current limitations of tumor evaluation according to metabolic index, which focuses solely on tumor core area. MATERIALS AND METHODS: Patients who underwent both FDG-PET and MET-PET, as well as surgical treatment, were retrospectively identified. All tumors were diagnosed histologically and included 44 high-grade and 19 low-grade gliomas. Metabolic indices of tumor-to-normal (T/N) ratio and maximum value within the tumor itself were compared between high- and low-grade tumors. A calculation method for potential infiltrative tumor volume was developed and compared between these 2 grades. RESULTS: T/N, calculated as tumor value divided by normal cortex value, was the most effective (area under the curve, 0.800 for FDG-PET; area under the curve, 0.773 for MET-PET) for differentiating high- and low-grade gliomas. Potential infiltrative volume effectively distinguished between high- and low-grade glioma (43.8 ± 30.2 mL vs 14.0 ± 12.6 mL; P = 0.005 [t test]). A combination of T/N, with a cutoff value of 0.9 or higher on FDG-PET and/or 3.0 or higher on MET-PET, and potential infiltrative volume, with a cutoff value of 20.0 mL or higher, provided a diagnostic accuracy of 89% in distinguishing high- from low-grade gliomas. CONCLUSIONS: Evaluation of potential infiltrative volume surrounding the tumor core area, in addition to the T/N ratio of the tumor core, may help distinguish between high- and low-grade gliomas.

    DOI: 10.1097/RLU.0000000000002460

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  • DNA demethylation is associated with malignant progression of lower-grade gliomas. 査読 国際誌

    Masashi Nomura, Kuniaki Saito, Koki Aihara, Genta Nagae, Shogo Yamamoto, Kenji Tatsuno, Hiroki Ueda, Shiro Fukuda, Takayoshi Umeda, Shota Tanaka, Shunsaku Takayanagi, Ryohei Otani, Takahide Nejo, Taijun Hana, Satoshi Takahashi, Yosuke Kitagawa, Mayu Omata, Fumi Higuchi, Taishi Nakamura, Yoshihiro Muragaki, Yoshitaka Narita, Motoo Nagane, Ryo Nishikawa, Keisuke Ueki, Nobuhito Saito, Hiroyuki Aburatani, Akitake Mukasa

    Scientific reports   9 ( 1 )   1903 - 1903   2019年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    To elucidate the mechanisms of malignant progression of lower-grade glioma, molecular profiling using methylation array, whole-exome sequencing, and RNA sequencing was performed for 122, 36 and 31 gliomas, respectively. This cohort included 24 matched pairs of initial lower-grade gliomas and recurrent tumors, most of which showed malignant progression. Nearly half of IDH-mutant glioblastomas that had progressed from lower-grade gliomas exhibited characteristic partial DNA demethylation in previously methylated genomic regions of their corresponding initial tumors, which had the glioma CpG island methylator phenotype (G-CIMP). In these glioblastomas, cell cycle-related genes, RB and PI3K-AKT pathway genes were frequently altered. Notably, late-replicating domain was significantly enriched in the demethylated regions that were mostly located in non-regulatory regions, suggesting that the loss of DNA methylation during malignant transformation may involve mainly passive demethylation due to a delay in maintenance of methylation during accelerated cell division. Nonetheless, a limited number of genes including IGF2BP3, which potentially drives cell proliferation, were presumed to be upregulated due to demethylation of their promoter. Our data indicated that demethylation of the G-CIMP profile found in a subset of recurrent gliomas reflects accelerated cell divisions accompanied by malignant transformation. Oncogenic genes activated by such epigenetic change represent potential therapeutic targets.

    DOI: 10.1038/s41598-019-38510-0

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  • Mining-Guided Machine Learning Analyses Revealed the Latest Trends in Neuro-Oncology. 査読 国際誌

    Taijun Hana, Shota Tanaka, Takahide Nejo, Satoshi Takahashi, Yosuke Kitagawa, Tsukasa Koike, Masashi Nomura, Shunsaku Takayanagi, Nobuhito Saito

    Cancers   11 ( 2 )   2019年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    In conducting medical research, a system which can objectively predict the future trends of the given research field is awaited. This study aims to establish a novel and versatile algorithm that predicts the latest trends in neuro-oncology. Seventy-nine neuro-oncological research fields were selected with computational sorting methods such as text-mining analyses. Thirty journals that represent the recent trends in neuro-oncology were also selected. As a novel concept, the annual impact (AI) of each year was calculated for each journal and field (number of articles published in the journal × impact factor of the journal). The AI index (AII) for the year was defined as the sum of the AIs of the 30 journals. The AII trends of the 79 fields from 2008 to 2017 were subjected to machine learning predicting analyses. The accuracy of the predictions was validated using actual past data. With this algorithm, the latest trends in neuro-oncology were predicted. As a result, the linear prediction model achieved relatively good accuracy. The predicted hottest fields in recent neuro-oncology included some interesting emerging fields such as microenvironment and anti-mitosis. This algorithm may be an effective and versatile tool for prediction of future trends in a particular medical field.

    DOI: 10.3390/cancers11020178

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  • Genetically distinct glioma stem-like cell xenografts established from paired glioblastoma samples harvested before and after molecularly targeted therapy. 査読 国際誌

    Shota Tanaka, Samantha Luk, Juri Kiyokawa, Maristela L Onozato, A John Iafrate, Khalid Shah, Robert L Martuza, Samuel D Rabkin, Tracy T Batchelor, Daniel P Cahill, Andrew S Chi, Hiroaki Wakimoto

    Scientific reports   9 ( 1 )   139 - 139   2019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)  

    Intratumoural heterogeneity underlies tumour escape from molecularly targeted therapy in glioblastoma. A cell-based model preserving the evolving molecular profiles of a tumour during treatment is key to understanding the recurrence mechanisms and development of strategies to overcome resistance. In this study, we established a matched pair of glioblastoma stem-like cell (GSC) cultures from patient glioblastoma samples before and after epidermal growth factor receptor (EGFR)-targeted therapy. A patient with recurrent glioblastoma (MGG70R) harboring focal, high-level EGFR amplification received the irreversible EGFR tyrosine kinase inhibitor dacomitinib. The tumour that subsequently recurred (MGG70RR) showed diploid EGFR, suggesting inhibitor-mediated elimination of EGFR-amplified tumour cells and propagation of EGFR non-amplified cell subpopulations. The MGG70R-GSC line established from MGG70R formed xenografts retaining EGFR amplification and EGFR overexpression, while MGG70RR-GSC established from MGG70RR generated tumours that lacked EGFR amplification and EGFR overexpression. MGG70R-GSC-derived intracranial xenografts were more proliferative than MGG70RR-GSC xenografts, which had upregulated mesenchymal markers, mirroring the pathological observation in the corresponding patient tumours. In vitro MGG70R-GSC was more sensitive to EGFR inhibitors than MGG70RR-GSC. Thus, these molecularly distinct GSC lines recapitulated the subpopulation alteration that occurred during glioblastoma evasion of targeted therapy, and offer a valuable model facilitating therapeutic development for recurrent glioblastoma.

    DOI: 10.1038/s41598-018-37437-2

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  • Brain Metastasis Mimicking Brain Abscess in ALK-Positive Non-Small-Cell Lung Cancer. 査読 国際誌

    Toshio Sakatani, Hidenori Kage, Shunsaku Takayanagi, Kaoru Watanabe, Yoshihisa Hiraishi, Aya Shinozaki-Ushiku, Shota Tanaka, Tetsuo Ushiku, Nobuhito Saito, Takahide Nagase

    Case reports in oncological medicine   2019   9141870 - 9141870   2019年

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    記述言語:英語  

    Brain metastasis frequently develops in non-small-cell lung cancer (NSCLC). Here, we report a patient who developed brain metastasis from ALK-positive NSCLC which mimicked brain abscess. He was admitted for suspected obstructive pneumonia nine months after curative lung resection. Head magnetic resonance imaging revealed a cavitary lesion, which was compatible with brain abscess but rare in brain metastasis. However, after treatment with antibiotics, the brain lesion increased in size. Aspiration of the liquid content of the brain lesion revealed cancer cells. When a brain lesion suggestive of abscess develops in a patient with ALK-positive NSCLC, aspiration may be necessary to differentiate metastasis from abscess.

    DOI: 10.1155/2019/9141870

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  • Spray Fluorescent Probes for Fluorescence-Guided Neurosurgery. 国際誌

    Yosuke Kitagawa, Shota Tanaka, Yugo Kuriki, Kyoko Yamamoto, Akira Ogasawara, Takahide Nejo, Reiko Matsuura, Tsukasa Koike, Taijun Hana, Satoshi Takahashi, Masashi Nomura, Shunsaku Takayanagi, Akitake Mukasa, Mako Kamiya, Yasuteru Urano, Nobuhito Saito

    Frontiers in oncology   9 ( AUG )   727 - 727   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3389/fonc.2019.00727

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  • Maffucci syndrome complicated by three different central nervous system tumors sharing an IDH1 R132C mutation: case report. 査読 国際誌

    Takahide Nejo, Shota Tanaka, Masako Ikemura, Masashi Nomura, Shunsaku Takayanagi, Masahiro Shin, Tetsuo Ushiku, Junji Shibahara, Nobuhito Saito, Akitake Mukasa

    Journal of neurosurgery   131 ( 6 )   1829 - 1834   2018年12月

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    記述言語:英語  

    Maffucci syndrome (MS) and Ollier disease (OD) are nonhereditary congenital diseases characterized by multiple enchondromas and/or chondrosarcomas. Recent studies have implicated somatic mosaic mutations of isocitrate dehydrogenase 1 or 2 (IDH1/2) as contributing to the pathogenesis of MS and OD. Occasionally, patients with these disorders may also present with central nervous system (CNS) tumors; however, detailed genetic analyses are limited. In this article, the authors report on a male patient with MS, harboring three CNS tumors that share a common genetic alteration. Over a 9-year period, three separate tumor resections were conducted for sellar, intraparenchymal brainstem, and osseous clival tumors. The histopathological diagnoses were pituitary adenoma, diffuse astrocytoma, and chondrosarcoma, respectively. Sanger sequencing revealed a common IDH1 R132C mutation among all three CNS tumors but not in blood DNA. Administering chemotherapy (nimustine) and subsequent radiation therapy to the brainstem glioma and the residual lesion in the clivus have kept the patient progression free for 18 months. This is the first report demonstrating an IDH1 mutation shared among three different CNS tumors in a single patient with MS. The findings support the hypothesis that in MS and OD, a single common IDH1 mutation triggers tumorigenesis in cells of different origins and locations in a somatic mosaic fashion.

    DOI: 10.3171/2018.6.JNS18729

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  • IDH変異型腫瘍におけるTERT変異と1p/19q共欠失の予後因子としての意義の比較

    有田 英之, 大野 誠, 中村 大志, 田村 郁, 三宅 勇平, 齊藤 邦昭, 田中 將太, 樋口 芙未, 金村 米博, 市村 幸一

    Brain Tumor Pathology   35 ( Suppl. )   141 - 141   2018年9月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 拡散画像のRadiomics解析と機械学習モデルによるIDH1遺伝子変異の同定 査読

    高橋 慧, 高橋 渉, 田中 将太, 芳賀 昭弘, 仲本 宗泰, 鈴木 雄一, 武笠 晃丈, 高柳 俊作

    Brain Tumor Pathology   35 ( Suppl. )   142 - 142   2018年9月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • IDH変異グリオーマに於けるシトシンメチル化状態の変化と腫瘍発生メカニズムの解明(Analyses of the cytosine methylation status among IDH mutated gliomas and the mechanism of gliomagenesis) 査読

    花 大洵, 野村 昌志, 武笠 晃丈, 田中 將太, 永江 玄太, 油谷 浩幸

    日本癌学会総会記事   77回   2307 - 2307   2018年9月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 右モンロー孔近傍diffuse midline gliomaの一剖検例

    池村 雅子, 近藤 篤史, 阿部 浩幸, 牛久 哲男, 高柳 俊作, 辛 正廣, 田中 將太, 深山 正久

    Brain Tumor Pathology   35 ( Suppl. )   157 - 157   2018年9月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • がん遺伝子パネル検査を施行した成人の左側頭後頭部gliofibromaの1例

    高柳 俊作, 野村 昌志, 田中 將太, 池村 雅子, 牛久 綾, 高阪 真路, 油谷 浩幸, 間野 博行

    Brain Tumor Pathology   35 ( Suppl. )   189 - 189   2018年9月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • クリニカルシークエンスによりNF2変異とATRXの遺伝子変異を認めた頭蓋内線維肉腫症例

    根城 尭英, 高柳 俊作, 田中 將太, 牛久 綾, 高阪 真路, 楚良 繁雄, 油谷 浩幸, 間野 博行, 武笠 晃丈, 斉藤 延人

    Brain Tumor Pathology   35 ( Suppl. )   173 - 173   2018年9月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 神経膠腫におけるネオアンチゲンと免疫微小環境の経時変化に関するマルチオミクス解析 査読

    根城 尭英, 松下 博和, 唐崎 隆弘, 野村 昌志, 永江 玄太, 高柳 俊作, 田中 將太, 成田 善孝, 永根 基雄, 西川 亮, 植木 敬介, 油谷 浩幸, 武笠 晃丈, 垣見 和宏, 齊藤 延人

    日本がん免疫学会総会プログラム・抄録集   22回   84 - 84   2018年7月

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    記述言語:日本語   出版者・発行元:日本がん免疫学会  

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  • Response 招待

    Ryohei Otani, Akitake Mukasa, Masahiro Shin, Mayu Omata, Shunsaku Takayanagi, Shota Tanaka, Keisuke Ueki, Nobuhito Saito

    Journal of Neurosurgery   129 ( 1 )   274 - 275   2018年7月

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  • IDH-mutated astrocytomas with 19q-loss constitute a subgroup that confers better prognosis. 査読 国際誌

    Ryohei Otani, Takeo Uzuka, Fumi Higuchi, Hadzki Matsuda, Masashi Nomura, Shota Tanaka, Akitake Mukasa, Koichi Ichimura, Phyo Kim, Keisuke Ueki

    Cancer science   109 ( 7 )   2327 - 2335   2018年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    IDH-mutant gliomas are classified into astrocytic or oligodendroglial tumors by 1p/19q status in the WHO 2016 classification, with the latter presenting with characteristic morphology and better prognosis in general. However, the morphological and genetic features within each category are varied, and there might be distinguishable subtypes. We analyzed 170 WHO grade II-IV gliomas resected in our institution. 1p/19q status was analyzed by microsatellite analysis, and genetic mutations were analyzed by next-generation sequencing and Sanger sequencing. For validation, the Brain Lower Grade Glioma dataset of The Cancer Genome Atlas was analyzed. Of the 42 grade III IDH-mutated gliomas, 12 were 1p-intact/19q-intact (anaplastic astrocytomas [AA]), 7 were 1p-intact/19q-loss (AA), and 23 showed 1p/19q-codeletion (anaplastic oligodendrogliomas). Of the 88 IDH-wild type glioblastomas (GBMs), 14 showed 1p-intact/19q-loss status. All of the seven 1p-intact/19q-loss AAs harbored TP53 mutation, but no TERT promotor mutation. All 19q-loss AAs had regions presenting oligodendroglioma-like morphology, and were associated with significantly longer overall survival compared to 19q-intact AAs (P = .001). This tendency was observed in The Cancer Genome Atlas Lower Grade Glioma dataset. In contrast, there was no difference in overall survival between the 19q-loss GBM and 19q-intact GBM (P = .4). In a case of 19q-loss AA, both oligodendroglial morphology and 19q-loss disappeared after recurrence, possibly indicating correlation between 19q-loss and oligodendroglial morphology. We showed that there was a subgroup, although small, of IDH-mutated astrocytomas harboring 19q-loss that present oligodendroglial morphology, and also were associated with significantly better prognosis compared to other 19q-intact astrocytomas.

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  • Brachyury gene copy number gain and activation of the PI3K/Akt pathway: association with upregulation of oncogenic Brachyury expression in skull base chordoma. 査読 国際誌

    Ryohei Otani, Akitake Mukasa, Masahiro Shin, Mayu Omata, Shunsaku Takayanagi, Shota Tanaka, Keisuke Ueki, Nobuhito Saito

    Journal of neurosurgery   128 ( 5 )   1428 - 1437   2018年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE Chordoma is a slow-growing but clinically malignant tumor, and the prognosis remains poor in many cases. There is a strong impetus to develop more effective targeted molecular therapies. On this basis, the authors investigated the potential of Brachyury, a transcription factor involved in notochord development, as a candidate molecular target for the treatment of chordoma. METHODS Brachyury gene copy number and expression levels were evaluated by quantitative polymerase chain reaction in 27 chordoma samples, and the transcriptomes of Brachyury high-expression tumors (n = 4) and Brachyury low-expression tumors (n = 4) were analyzed. A chordoma cell line (U-CH2) was used to investigate the signaling pathways that regulate Brachyury expression. RESULTS All chordoma specimens expressed Brachyury, and expression levels varied widely. Patients with higher Brachyury expression had significantly shorter progression-free survival (5 months, n = 11) than those with lower expression (13 months, n = 16) (p = 0.03). Somatic copy number gain was confirmed in 12 of 27 (44%) cases, and copy number was positively correlated with Brachyury expression (R = 0.61, p < 0.001). Expression of PI3K/Akt pathway genes was upregulated in Brachyury high-expression tumors, and suppression of PI3K signaling led to reduced Brachyury expression and inhibition of cell growth in the U-CH2 chordoma cell line. CONCLUSIONS Activation of the PI3K/Akt pathway and Brachyury copy number gain are strongly associated with Brachyury overexpression, which appears to be a key event in chordoma growth regulation. These findings suggest that targeting Brachyury and PI3K/Akt signaling may be an effective new approach for treating chordoma.

    DOI: 10.3171/2016.12.JNS161444

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  • Spinal Cord Astrocytoma with Isocitrate Dehydrogenase 1 Gene Mutation. 査読 国際誌

    Keisuke Takai, Shota Tanaka, Takashi Sota, Akitake Mukasa, Takashi Komori, Makoto Taniguchi

    World neurosurgery   108   991.e13-991.e16 - 991.e16   2017年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    BACKGROUND: In 2016, the World Health Organization updated its classification of tumors, adding genetic profiles to the conventional histopathologic typing. CASE DESCRIPTION: The authors present herein the first case of a 44-year-old female with isocitrate dehydrogenase-mutant World Health Organization grade II diffuse spinal astrocytoma diagnosed on the basis of both histopathologic and genetic findings. CONCLUSIONS: The present case underscores the significant role of a molecular genetic analysis in the differential diagnosis of intramedullary spinal gliomas.

    DOI: 10.1016/j.wneu.2017.08.142

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  • Distinct molecular profile of diffuse cerebellar gliomas. 査読 国際誌

    Masashi Nomura, Akitake Mukasa, Genta Nagae, Shogo Yamamoto, Kenji Tatsuno, Hiroki Ueda, Shiro Fukuda, Takayoshi Umeda, Tomonari Suzuki, Ryohei Otani, Keiichi Kobayashi, Takashi Maruyama, Shota Tanaka, Shunsaku Takayanagi, Takahide Nejo, Satoshi Takahashi, Koichi Ichimura, Taishi Nakamura, Yoshihiro Muragaki, Yoshitaka Narita, Motoo Nagane, Keisuke Ueki, Ryo Nishikawa, Junji Shibahara, Hiroyuki Aburatani, Nobuhito Saito

    Acta neuropathologica   134 ( 6 )   941 - 956   2017年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Recent studies have demonstrated that tumor-driving alterations are often different among gliomas that originated from different brain regions and have underscored the importance of analyzing molecular characteristics of gliomas stratified by brain region. Therefore, to elucidate molecular characteristics of diffuse cerebellar gliomas (DCGs), 27 adult, mostly glioblastoma cases were analyzed. Comprehensive analysis using whole-exome sequencing, RNA sequencing, and Infinium methylation array (n = 17) demonstrated their distinct molecular profile compared to gliomas in other brain regions. Frequent mutations in chromatin-modifier genes were identified including, noticeably, a truncating mutation in SETD2 (n = 4), which resulted in loss of H3K36 trimethylation and was mutually exclusive with H3F3A K27M mutation (n = 3), suggesting that epigenetic dysregulation may lead to DCG tumorigenesis. Alterations that cause loss of p53 function including TP53 mutation (n = 9), PPM1D mutation (n = 2), and a novel type of PPM1D fusion (n = 1), were also frequent. On the other hand, mutations and copy number changes commonly observed in cerebral gliomas were infrequent. DNA methylation profile analysis demonstrated that all DCGs except for those with H3F3A mutations were categorized in the "RTK I (PDGFRA)" group, and those DCGs had a gene expression signature that was highly associated with PDGFRA. Furthermore, compared with the data of 315 gliomas derived from different brain regions, promoter methylation of transcription factors genes associated with glial development showed a characteristic pattern presumably reflecting their tumor origin. Notably, SOX10, a key transcription factor associated with oligodendroglial differentiation and PDGFRA regulation, was up-regulated in both DCG and H3 K27M-mutant diffuse midline glioma, suggesting their developmental and biological commonality. In contrast, SOX10 was silenced by promoter methylation in most cerebral gliomas. These findings may suggest potential tailored targeted therapy for gliomas according to their brain region, in addition to providing molecular clues to identify the region-related cellular origin of DCGs.

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  • CHARACTERISTIC MOLECULAR PROFILE CHANGES IN PRIMARY AND RECURRENT GLIOMAS DEPENDING ON THEIR HISTOPATHOLOGY 査読

    Akitake Mukasa, Masashi Nomura, Kuniaki Saito, Koki Aihara, Genta Nagae, Takahide Nejo, Shota Tanaka, Shunsaku Takayanagi, Satoshi Takahashi, Mayu Omata, Taishi Nakamura, Yoshitaka Narita, Yoshihiro Muragaki, Motoo Nagane, Keisuke Ueki, Ryo Nishikawa, Hiroyuki Aburatani, Nobuhito Saito

    NEURO-ONCOLOGY   19   94 - 94   2017年11月

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    記述言語:英語   出版者・発行元:OXFORD UNIV PRESS INC  

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  • Definitive surgical treatment of osteomalacia induced by skull base tumor and determination of the half-life of serum fibroblast growth factor 23. 査読

    Taijun Hana, Shota Tanaka, Hirofumi Nakatomi, Masaaki Shojima, Seiji Fukumoto, Masako Ikemura, Nobuhito Saito

    Endocrine journal   64 ( 10 )   1033 - 1039   2017年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPAN ENDOCRINE SOC  

    Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome often associated with fibroblast growth factor 23 (FGF23)-producing tumors such as phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT) affecting the bone and soft tissue. We experienced a patient with progressive bone and muscle pain due to FGF23-related TIO. Venous sampling had strongly suggested the anterior skull base as a source of FGF23, which led to the discovery of a small tumor in the ethmoid sinus extending intracranially. Radical surgical resection confirmed the histological diagnosis of PMTMCT with FGF23 immunopositivity and achieved durable tumor control with complete resolution of symptoms. We serially measured serum FGF23 level before, during and after surgery and analyzed the data to determine the half-life of FGF23. Serum FGF23 level sharply declined as early as 20 minutes after en bloc tumor resection and completely normalized after surgery. The half-life of FGF23 was calculated to be approximately 18.5 minutes using single phase exponential decay model as well as semilog transformation formula. Serial measurements of serum FGF23 level can potentially declare "complete" resection of a FGF23-producing tumor and total cure of TIO; in this regard, development of its intraoperative measurement would be helpful in the management of this endocrine tumor.

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  • Differences in genetic and epigenetic alterations between von Hippel-Lindau disease-related and sporadic hemangioblastomas of the central nervous system. 査読 国際誌

    Shunsaku Takayanagi, Akitake Mukasa, Shota Tanaka, Masashi Nomura, Mayu Omata, Shunsuke Yanagisawa, Shogo Yamamoto, Koichi Ichimura, Hirofumi Nakatomi, Keisuke Ueki, Hiroyuki Aburatani, Nobuhito Saito

    Neuro-oncology   19 ( 9 )   1228 - 1236   2017年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS INC  

    Background: Although inactivation of the von Hippel-Lindau gene (VHL), located on chromosome 3p25, is considered to be a major cause of hemangioblastomas (HBs), the incidence of biallelic inactivation of VHL is reportedly low. The aim of this study was to determine the prevalence of VHL alterations in HBs, as well as to identify additional molecular aberrations. Methods: Genetic and epigenetic alterations were comprehensively and comparatively analyzed in 11 VHL-related and 21 sporadic HBs. Results: VHL alterations detected by sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis were more frequent in VHL-related HBs than in sporadic HBs (100% vs 62%; P = 0.029). VHL alterations were found only in 4 sporadic HBs by direct sequencing; however, targeted deep sequencing detected 9 additional alterations. Loss of heterozygosity (LOH) on chromosome 3 was found in 64% and 57% of VHL-related and sporadic HBs, respectively, by single nucleotide polymorphism (SNP) array analysis. Among 19 tumors with chromosome 3 LOH, 5 were classified as copy-neutral LOH. VHL promoter hypermethylation was detected only in sporadic HBs (33%), indicating that epigenetic suppression of VHL is a common mechanism in sporadic HBs. The rate of biallelic VHL inactivation among VHL-related and sporadic HBs was 64% and 52%, respectively. LOH on either chromosome 6 or 10 was detected only in sporadic HBs (43%). Conclusion: Although biallelic inactivation of VHL is a dominant mechanistic cause of the pathogenesis of HB, other unknown mechanisms may also be involved, and such mechanisms may be different between VHL-related and sporadic HB.

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  • The Alkylating Chemotherapeutic Temozolomide Induces Metabolic Stress in IDH1-Mutant Cancers and Potentiates NAD+ Depletion-Mediated Cytotoxicity. 査読 国際誌

    Kensuke Tateishi, Fumi Higuchi, Julie J Miller, Mara V A Koerner, Nina Lelic, Ganesh M Shankar, Shota Tanaka, David E Fisher, Tracy T Batchelor, A John Iafrate, Hiroaki Wakimoto, Andrew S Chi, Daniel P Cahill

    Cancer research   77 ( 15 )   4102 - 4115   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    IDH1-mutant gliomas are dependent upon the canonical coenzyme NAD+ for survival. It is known that PARP activation consumes NAD+ during base excision repair (BER) of chemotherapy-induced DNA damage. We therefore hypothesized that a strategy combining NAD+ biosynthesis inhibitors with the alkylating chemotherapeutic agent temozolomide could potentiate NAD+ depletion-mediated cytotoxicity in mutant IDH1 cancer cells. To investigate the impact of temozolomide on NAD+ metabolism, patient-derived xenografts and engineered mutant IDH1-expressing cell lines were exposed to temozolomide, in vitro and in vivo, both alone and in combination with nicotinamide phosphoribosyltransferase (NAMPT) inhibitors, which block NAD+ biosynthesis. The acute time period (<3 hours) after temozolomide treatment displayed a burst of NAD+ consumption driven by PARP activation. In IDH1-mutant-expressing cells, this consumption reduced further the abnormally lowered basal steady-state levels of NAD+, introducing a window of hypervulnerability to NAD+ biosynthesis inhibitors. This effect was selective for IDH1-mutant cells and independent of methylguanine methyltransferase or mismatch repair status, which are known rate-limiting mediators of adjuvant temozolomide genotoxic sensitivity. Combined temozolomide and NAMPT inhibition in an in vivo IDH1-mutant cancer model exhibited enhanced efficacy compared with each agent alone. Thus, we find IDH1-mutant cancers have distinct metabolic stress responses to chemotherapy-induced DNA damage and that combination regimens targeting nonredundant NAD+ pathways yield potent anticancer efficacy in vivo Such targeting of convergent metabolic pathways in genetically selected cancers could minimize treatment toxicity and improve durability of response to therapy. Cancer Res; 77(15); 4102-15. ©2017 AACR.

    DOI: 10.1158/0008-5472.CAN-16-2263

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  • グリオーマ複数回手術症例のオミクス解析によるネオアンチゲンと免疫微小環境の経時変化の検討

    根城 尭英, 松下 博和, 唐崎 隆弘, 相原 功輝, 野村 昌志, 高柳 俊作, 田中 將太, 永江 玄太, 山本 尚吾, 上田 宏生, 辰野 健二, 成田 善孝, 永根 基雄, 西川 亮, 植木 敬介, 油谷 浩幸, 武笠 晃丈, 垣見 和宏, 齊藤 延人

    日本がん免疫学会総会プログラム・抄録集   21回   84 - 84   2017年6月

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    記述言語:日本語   出版者・発行元:日本がん免疫学会  

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  • Long-term risk of recurrence and regrowth after gross-total and subtotal resection of sporadic vestibular schwannoma. 査読 国際誌

    Hirofumi Nakatomi, Jeffrey T Jacob, Matthew L Carlson, Shota Tanaka, Minoru Tanaka, Nobuhito Saito, Christine M Lohse, Colin L W Driscoll, Michael J Link

    Journal of neurosurgery   1 - 7   2017年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE The management of vestibular schwannoma (VS) remains controversial. One commonly cited advantage of microsurgery over other treatment modalities is that tumor removal provides the greatest chance of long-term cure. However, there are very few publications with long-term follow-up to support this assertion. The purpose of the current study is to report the very long-term risk of recurrence among a large historical cohort of patients who underwent microsurgical resection. METHODS The authors retrospectively reviewed the medical records of patients who had undergone primary microsurgical resection of unilateral VS via a retrosigmoid approach performed by a single neurosurgeon-neurotologist team between January 1980 and December 1999. Complete tumor removal was designated gross-total resection (GTR), and anything less than complete removal was designated subtotal resection (STR). The primary end point was radiological recurrence-free survival. Time-to-event analyses were performed to identify factors associated with recurrence. RESULTS Four hundred fourteen patients met the study inclusion criteria and were analyzed. Overall, 67 patients experienced recurrence at a median of 6.9 years following resection (IQR 3.9-12.1, range 1.2-22.5 years). Estimated recurrence-free survival rates at 5, 10, 15, and 20 years following resection were 93% (95% CI 91-96, 248 patients still at risk), 78% (72-85, 88), 68% (60-77, 47), and 51% (41-64, 22), respectively. The strongest predictor of recurrence was extent of resection, with patients who underwent STR having a nearly 11-fold greater risk of recurrence than the patients treated with GTR (HR 10.55, p < 0.001). Among the 18 patients treated with STR, 15 experienced recurrence at a median of 2.7 years following resection (IQR 1.9-8.9, range 1.2-18.7). Estimated recurrence-free survival rates at 5, 10, 15, and 20 years following GTR were 96% (95% CI 93-98, 241 patients still at risk), 82% (77-89, 86), 73% (65-81, 46), and 56% (45-70, 22), respectively. Estimated recurrence-free survival rates at 5, 10, and 15 years following STR were 47% (95% CI 28-78, 7 patients still at risk), 17% (5-55, 2), and 8% (1-52, 1), respectively. CONCLUSIONS Long-term surveillance is required following microsurgical resection of VS even after GTR. Subtotal resection alone should not be considered a definitive long-term cure. These data emphasize the importance of long-term follow-up when reporting tumor control outcomes for VS.

    DOI: 10.3171/2016.11.JNS16498

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  • 分子診断が有用であった脊髄Ewing sarcoma/peripheral PNETの1例 査読

    高橋 慧, 高柳 俊作, 池村 雅子, 根城 尭英, 野村 昌志, 柳澤 俊介, 田中 將太, 武笠 晃丈, 深山 正久, 斉藤 延人

    Brain Tumor Pathology   34 ( Suppl. )   150 - 150   2017年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 膠芽腫に近接して異なる遺伝子異常プロファイルを有する乏突起神経膠腫様の腫瘍が併存した一例

    小池 司, 武笠 晃武, 高柳 俊作, 田中 將太, 牛久 哲男, 吉河 学史, 堤 一生, 柴原 純二, 斉藤 延人

    Brain Tumor Pathology   34 ( Suppl. )   122 - 122   2017年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 分子病理と分子病態 治療による変化 再発oligodendrogliomaのゲノム・エピゲノムの安定性

    武笠 晃丈, 相原 功輝, 野村 昌志, 田中 將太, 高柳 俊作, 永根 基雄, 成田 喜孝, 植木 敬介, 油谷 浩幸, 斉藤 延人

    Brain Tumor Pathology   34 ( Suppl. )   076 - 076   2017年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 共通のIDH1 R132C変異を有する3つの異なる中枢神経系腫瘍を合併したMaffucci症候群の1例

    根城 尭英, 野村 昌志, 池村 雅子, 高橋 慧, 柳澤 俊介, 高柳 俊作, 田中 將太, 武笠 晃丈, 深山 正久, 斉藤 延人

    Brain Tumor Pathology   34 ( Suppl. )   152 - 152   2017年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 分子病理と分子病態 Oncogenesis and Progression 小脳に発生するびまん性神経膠腫のゲノム・エピゲノム解析 査読

    野村 昌志, 武笠 晃丈, 高橋 慧, 根城 尭英, 柳澤 俊介, 高柳 俊作, 田中 將太, 油谷 浩幸, 斉藤 延人

    Brain Tumor Pathology   34 ( Suppl. )   074 - 074   2017年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • Genetic and epigenetic stability of oligodendrogliomas at recurrence. 査読 国際誌

    Koki Aihara, Akitake Mukasa, Genta Nagae, Masashi Nomura, Shogo Yamamoto, Hiroki Ueda, Kenji Tatsuno, Junji Shibahara, Miwako Takahashi, Toshimitsu Momose, Shota Tanaka, Shunsaku Takayanagi, Shunsuke Yanagisawa, Takahide Nejo, Satoshi Takahashi, Mayu Omata, Ryohei Otani, Kuniaki Saito, Yoshitaka Narita, Motoo Nagane, Ryo Nishikawa, Keisuke Ueki, Hiroyuki Aburatani, Nobuhito Saito

    Acta neuropathologica communications   5 ( 1 )   18 - 18   2017年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Among diffuse gliomas, oligodendrogliomas show relatively better prognosis, respond well to radiotherapy and chemotherapy, and seldom progress to very aggressive tumors. To elucidate the genetic and epigenetic background for such behavior and tumor evolution during tumor relapse, we comparatively analyzed 12 pairs of primary and recurrent oligodendrogliomas with 1p/19q-codeletion. Initial treatment for these patients was mostly chemotherapy alone. Temozolomide was used for 3, and procarbazine, nimustine and vincristine (PAV chemotherapy) were used for 7 patients. World Health Organization histological grade at recurrence was mostly stable; it was increased in 2, the same in 9, and decreased in 1 cases. Whole-exome sequencing demonstrated that the rate of shared mutation between the primary and recurrent tumors was relatively low, ranging from 3.2-57.9% (average, 33.3%), indicating a branched evolutionary pattern. The trunk alterations that existed throughout the course were restricted to IDH1 mutation, 1p/19q-codeletion, and TERT promoter mutation, and mutation of the known candidate tumor suppressor genes CIC and FUBP1 were not consistently observed between primary and recurrent tumors. Multiple sampling from different regions within a tumor showed marked intratumoral heterogeneity. Notably, in general, the number of mutations was not significantly different after recurrence, remaining under 100, and no hypermutator phenotype was observed. FUBP1 mutation, loss of chr. 9p21, and TCF12 mutation were among a few recurrent de novo alterations that were found at recurrence, indicating that these events were clonally selected at recurrence but were not enough to enhance malignancy. Genome-wide methylation status, measured by Illumina 450 K arrays, was stable between recurrence and the primary tumor. In summary, although oligodendroglioma displays marked mutational heterogeneity, histological malignant transformation accompanying events such as considerable increase in mutation number and epigenetic profile change were not observed at recurrence, indicating that noticeable temporal and spatial genetic heterogeneity in oligodendrogliomas does not result in rapid tumor progression.

    DOI: 10.1186/s40478-017-0422-z

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  • Successful treatment of mixed yolk sac tumor and mature teratoma in the spinal cord: case report. 査読 国際誌

    Akitake Mukasa, Shunsuke Yanagisawa, Kuniaki Saito, Shota Tanaka, Keisuke Takai, Junji Shibahara, Masachika Ikegami, Yusuke Nakao, Katsushi Takeshita, Masao Matsutani, Nobuhito Saito

    Journal of neurosurgery. Spine   26 ( 3 )   319 - 324   2017年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC NEUROLOGICAL SURGEONS  

    Primary spinal germ cell tumors are rare, and spinal nongerminomatous germ cell tumors represent an even rarer subset for which no standard therapy has been established. The authors report the case of a 24-year-old woman with multifocal primary spinal germ cell tumors scattered from T-12 to L-5 that consisted of yolk sac tumor and mature teratoma. After diagnostic partial resection, the patient was treated with 30 Gy of craniospinal irradiation and 30 Gy of local spinal irradiation, followed by 8 courses of chemotherapy based on ifosfamide, cisplatin, and etoposide (ICE). Salvage surgery was also performed for residual mature teratoma components after the third course of ICE chemotherapy. Chemotherapy was continued after the operation, but ifosfamide was entirely eliminated from the ICE regimen because severe myelosuppression was observed after previous courses. The patient remains recurrence free as of more than 5 years after the completion of chemotherapy. This case suggests that this treatment strategy is an effective option for primary spinal yolk sac tumor.

    DOI: 10.3171/2016.8.SPINE16465

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  • Factors influencing mother-child communication about fathers with neurobehavioural sequelae after brain injury. 査読 国際誌

    Shiho Takanashi, Mariko Sakka, Iori Sato, Shu Watanabe, Shota Tanaka, Ayumi Ooshio, Nobuhito Saito, Kiyoko Kamibeppu

    Brain injury   31 ( 3 )   312 - 318   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS INC  

    OBJECTIVE: The present study clarified factors related to mother-child communication openness when fathers suffer neurobehavioural sequelae after stroke or traumatic brain injury. RESEARCH DESIGN: A cross-sectional study using self-report anonymous questionnaires was conducted. METHODS AND PROCEDURES: Forty-one mothers with 6-22-year-old children participated. The questionnaire examined personal factors (mother's psychological distress), social/family factors (family support functioning), illness-related factors (father's time at home and neurobehavioural sequelae severity) and mother's perceived level of open communication. Multiple regression was used to analyse factors related to mother-child communication openness. RESULTS: Mother-child open communication was explained by family support functioning (β = 0.449), father's time at home (β = -0.325) and mother's psychological distress (β = -0.303). Neurobehavioural sequelae severity was not associated with mother-child open communication. CONCLUSIONS: Personal, social/family and illness-related factors were related to mother-child communication about paternal illness. Professionals should promote optimal family support functioning, connect families with external resources and assess families' interaction processes.

    DOI: 10.1080/02699052.2016.1225986

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  • MOLECULAR PATHOLOGICAL ANALYSIS ON IDH-WILDTYPE ADULT LOW-GRADE GLIOMAS 査読

    Mukasa Akitake, Aihara Koki, Nagae Genta, Shibahara Junji, Tanaka Shota, Takayanagi Shunsaku, Nomura Masashi, Nagane Motoo, Narita Yoshitaka, Ueki Keisuke, Nishikawa Ryo, Aburatani Hiroyuki, Saito Nobuhito

    NEURO-ONCOLOGY   18   78 - 79   2016年11月

  • CHEMOTHERAPY-INDUCED METABOLIC STRESS IN IDH1 MUTANT GLIOMAS 査読

    Tateishi Kensuke, Wakimoto Hiroaki, Higuchi Fumi, Miller Julie, Koerner Mara V. A, Lelic Nina, Shankar Ganesh, Tanaka Shota, Curry William T, Fisher David E, Batchelor Tracy T, Iafrate A. John, Chi Andrew S, Cahill Daniel P

    NEURO-ONCOLOGY   18 ( 11 )   1559 - 1568   2016年11月

  • グリオーマのゲノム多様性とクローン進化に及ぼす抗がん治療の影響

    武笠 晃丈, 相原 功輝, 齊藤 邦昭, 野村 昌志, 永江 玄太, 高柳 俊作, 田中 將太, 成田 善孝, 植木 敬介, 永根 基雄, 西川 亮, 油谷 浩幸, 斉藤 延人

    日本癌学会総会記事   75回   IS11 - 1   2016年10月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • Intracranial Infantile Myofibromatosis Mimicking Malignant Brain Tumor: A Case Report and Literature Review. 査読 国際誌

    Mizuho Inoue, Shota Tanaka, Hirofumi Nakatomi, Shunsaku Takayanagi, Miwako Takahashi, Mariko Tanaka, Toshimitsu Momose, Akitake Mukasa, Nobuhito Saito

    World neurosurgery   93   487.e15-20 - 20   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    BACKGROUND: Myofibroma is a fibrous tumor of infancy that sometimes affects a single patient in a multiple fashion (infantile myofibromatosis). Its intracranial involvement is extremely rare, and its clinical picture has been poorly characterized. Here we report an interesting case of myofibromatosis with an intracranial lesion that behaved like an aggressive tumor and yet demonstrated very benign pathology. CASE DESCRIPTION: A 36-year-old man had never been diagnosed with infantile myofibromatosis despite his lifelong history of multiple tumors of various diagnoses. He presented with simple partial seizure and progressive right finger paresis. A series of brain magnetic resonance imaging scans revealed a rapidly growing lesion at his left frontal convexity, which corresponded to a high uptake area on a (18)F-fluorodeoxyglucose-positron emission tomography scan, highly suspicious of malignancy. He underwent complete tumor resection and his symptoms quickly resolved postoperatively. The pathological diagnosis was myofibroma with a MIB-1 labeling index of 1%-2%. A retrospective review of his previous tumors demonstrated the same pathology, which led to the diagnosis of myofibromatosis. Follow-up magnetic resonance imaging illustrated stabilization or regression of other preexisting lesions as well as formation of a new intracranial lesion. CONCLUSIONS: The discrepancy between rapid tumor growth associated with increased uptake on metabolic imaging and benign pathologic findings with a low proliferative index is noteworthy and should be recognized in the management of an intracranial lesion in a patient with infantile myofibromatosis. Given de novo formation of a lesion in this adult patient, long-term follow-up is essential in this disease.

    DOI: 10.1016/j.wneu.2016.06.105

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  • Intraneural ganglion cysts: a systematic review and reinterpretation of the world's literature. 査読 国際誌

    Nicholas M Desy, Huan Wang, Mohanad Ahmed Ibrahim Elshiekh, Shota Tanaka, Tae Woong Choi, B Matthew Howe, Robert J Spinner

    Journal of neurosurgery   125 ( 3 )   615 - 30   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC NEUROLOGICAL SURGEONS  

    OBJECTIVE The etiology of intraneural ganglion cysts has been controversial. In recent years, substantial evidence has been presented to support the articular (synovial) theory for their pathogenesis. The authors sought to 1) perform a systematic review of the world's literature on intraneural cysts, and 2) reinterpret available published MR images in articles by other authors to identify unrecognized joint connections. METHODS In Part 1, all cases were analyzed for demographic data, duration of symptoms, the presence of a history of trauma, whether electromyography or nerve conduction studies were performed, the type of imaging, surgical treatment, presence of a joint connection, intraneural cyst recurrence, and postoperative imaging. Two univariate analyses were completed: 1) to compare the proportion of intraneural ganglion cyst publications per decade and 2) to assess the number of recurrences from 1914 to 2003 compared with the years 2004-2015. Three multivariate regression models were used to identify risk factors for intraneural cyst recurrence. In Part 2, the authors analyzed all available published MR images and obtained MR images from selected cases in which joint connections were not identified by the original authors, specifically looking for unrecognized joint connections. Two univariate analyses were done: 1) to determine a possible association between the identification of a joint connection and obtaining an MRI and 2) to assess the number of joint connections reported from 1914 to 2003 compared with 2004 to 2015. RESULTS In Part 1, 417 articles (645 patients) were selected for analysis. Joint connections were identified in 313 intraneural cysts (48%). Both intraneural ganglion cyst cases and cyst recurrences were more frequently reported since 2004 (statistically significant difference for both). There was a statistically significant association between cyst recurrence and percutaneous aspiration as well as failure to disconnect the articular branch or address the joint. In Part 2, the authors identified 43 examples of joint connections that initially went unrecognized: 27 based on their retrospective MR image reinterpretation of published cases and 16 of 16 cases from their sampling of original MR images from published cases. Overall, joint connections were more commonly found in patients who received an MRI examination and were more frequently reported during the years 2004 to 2015 (statistically significant difference for both). CONCLUSIONS This comprehensive review of the world's literature and the MR images further supports the articular (synovial) theory and provides baseline data for future investigators.

    DOI: 10.3171/2015.9.JNS141368

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  • Impact of histopathological transformation and overall survival in patients with progressive anaplastic glioma. 査読 国際誌

    Allen L Ho, Matthew J Koch, Shota Tanaka, April F Eichler, Tracy T Batchelor, Jantima Tanboon, David N Louis, Daniel P Cahill, Andrew S Chi, William T Curry Jr

    Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia   31   99 - 105   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI LTD  

    Progression of anaplastic glioma (World Health Organization [WHO] grade III) is typically determined radiographically, and transformation to glioblastoma (GB) (WHO grade IV) is often presumed at that time. However, the frequency of actual histopathologic transformation of anaplastic glioma and the subsequent clinical impact is unclear. To determine these associations, we retrospectively reviewed all anaplastic glioma patients who underwent surgery at our center at first radiographic progression, and we examined the effects of histological diagnosis, clinical history, and molecular factors on transformation rate and survival. We identified 85 anaplastic glioma (39 astrocytoma, 24 oligodendroglioma, 22 oligoastrocytoma), of which 38.8% transformed to GB. Transformation was associated with shorter overall survival (OS) from the time of diagnosis (3.4 vs. 10.9years, p=0.0005) and second surgery (1.0 vs. 3.5years, p<0.0001). Original histologic subtype did not significantly impact the risk of transformation or OS. No other factors, including surgery, adjuvant therapy or molecular markers, significantly affected the risk of transformation. However, mutations in isocitrate dehydrogenase 1 (IDH1) was associated with longer time to progression (median 4.6 vs. 1.4years, p=0.008) and OS (median 10.0 vs. 4.2years, p=0.046). At radiographic progression, tissue diagnosis may be warranted as histologic grade may provide valuable prognostic information and affect therapeutic clinical trial selection criteria for this patient population.

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

    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 )   79 - 79   2016年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    The prognostic impact of TERT mutations has been controversial in IDH-wild tumors, particularly in glioblastomas (GBM). The controversy may be attributable to presence of potential confounding factors such as MGMT methylation status or patients' treatment. This study aimed to evaluate the impact of TERT status on patient outcome in association with various factors in a large series of adult diffuse gliomas. We analyzed a total of 951 adult diffuse gliomas from two cohorts (Cohort 1, n = 758; Cohort 2, n = 193) for IDH1/2, 1p/19q, and TERT promoter status. The combined IDH/TERT classification divided Cohort 1 into four molecular groups with distinct outcomes. The overall survival (OS) was the shortest in IDH wild-type/TERT mutated groups, which mostly consisted of GBMs (P < 0.0001). To investigate the association between TERT mutations and MGMT methylation on survival of patients with GBM, samples from a combined cohort of 453 IDH-wild-type GBM cases treated with radiation and temozolomide were analyzed. A multivariate Cox regression model revealed that the interaction between TERT and MGMT was significant for OS (P = 0.0064). Compared with TERT mutant-MGMT unmethylated GBMs, the hazard ratio (HR) for OS incorporating the interaction was the lowest in the TERT mutant-MGMT methylated GBM (HR, 0.266), followed by the TERT wild-type-MGMT methylated (HR, 0.317) and the TERT wild-type-MGMT unmethylated GBMs (HR, 0.542). Thus, patients with TERT mutant-MGMT unmethylated GBM have the poorest prognosis. Our findings suggest that a combination of IDH, TERT, and MGMT refines the classification of grade II-IV diffuse gliomas.

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  • The prognostic impact of TERT promoter mutations in adult diffuse gliomas depends on the IDH mutation and MGMT methylation status 査読

    Arita H, Yamasaki K, Matsushita Y, Nakamura T, Shimokawa A, Takami H, Tanaka S, Mukasa A, Shirahata M, Shimizu S, Suzuki K, Saito K, Kobayashi K, Higuchi F, Uzuka T, Otani R, Tamura K, Sumita K, Ohno M, Miyakita Y, Kagawa N, Hashimoto N, Hatae R, Yoshimoto K, Shinojima N, Nakamura H, Kanemura Y, Okita Y, Kinoshita M, Ishibashi K, Shofuda T, Kodama Y, Mori K, Tomogane Y, Fukai J, Fujita K, Terakawa Y, Tsuyuguchi N, Moriuchi S, Nonaka M, Suzuki H, Shibuya M, Maehara T, Saito N, Nagane M, Kawahara N, Ueki K, Yoshimine T, Miyaoka E, Nishikawa R, Komori T, Narita Y, Ichimura K

    Acta Neuropathologica Communications   4   2016年8月

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    記述言語:英語  

    DOI: 10.1186/s40478-016-0351-2

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  • 脊髄神経膠腫の病理学的特徴(Pathological feature of spinal cord gliomas) 査読

    小森 隆司, 田中 将太, 武笠 晃丈, 澁谷 誠, 谷口 真

    Brain Tumor Pathology   33 ( Suppl. )   087 - 087   2016年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 浸潤性midline gliomaにおけるヒストンH3K27M変異の免疫組織化学的検討 査読

    池村 雅子, 柴原 純二, 武笠 晃丈, 田中 将太, 相原 功輝, 野村 昌志, 深山 正久

    日本病理学会会誌   105 ( 1 )   357 - 357   2016年4月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • Extreme Vulnerability of IDH1 Mutant Cancers to NAD+ Depletion. 査読 国際誌

    Kensuke Tateishi, Hiroaki Wakimoto, A John Iafrate, Shota Tanaka, Franziska Loebel, Nina Lelic, Dmitri Wiederschain, Olivier Bedel, Gejing Deng, Bailin Zhang, Timothy He, Xu Shi, Robert E Gerszten, Yiyun Zhang, Jing-Ruey J Yeh, William T Curry, Dan Zhao, Sudhandra Sundaram, Fares Nigim, Mara V A Koerner, Quan Ho, David E Fisher, Elisabeth M Roider, Lajos V Kemeny, Yardena Samuels, Keith T Flaherty, Tracy T Batchelor, Andrew S Chi, Daniel P Cahill

    Cancer cell   28 ( 6 )   773 - 784   2015年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CELL PRESS  

    Heterozygous mutation of IDH1 in cancers modifies IDH1 enzymatic activity, reprogramming metabolite flux and markedly elevating 2-hydroxyglutarate (2-HG). Here, we found that 2-HG depletion did not inhibit growth of several IDH1 mutant solid cancer types. To identify other metabolic therapeutic targets, we systematically profiled metabolites in endogenous IDH1 mutant cancer cells after mutant IDH1 inhibition and discovered a profound vulnerability to depletion of the coenzyme NAD+. Mutant IDH1 lowered NAD+ levels by downregulating the NAD+ salvage pathway enzyme nicotinate phosphoribosyltransferase (Naprt1), sensitizing to NAD+ depletion via concomitant nicotinamide phosphoribosyltransferase (NAMPT) inhibition. NAD+ depletion activated the intracellular energy sensor AMPK, triggered autophagy, and resulted in cytotoxicity. Thus, we identify NAD+ depletion as a metabolic susceptibility of IDH1 mutant cancers.

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  • Neuroendoscopic Ventriculocisternostomy with Stent Placement for Trapped Temporal Horn After the Resection of Glioblastoma. 査読 国際誌

    Taijun Hana, Shota Tanaka, Masahiro Shin, Akitake Mukasa, Kazuha Kugasawa, Nobuhito Saito

    World neurosurgery   84 ( 6 )   2078.e5-8 - 8   2015年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    BACKGROUND: Endoscopic ventriculostomy is an attractive surgical alternative to ventriculoperitoneal shunt in the treatment of focal hydrocephalus, including trapped temporal horn (TTH). The major concern of this surgical approach is closure of a stoma, the risk of which may be minimized by placement of a stent after ventriculostomy. CASE DESCRIPTION: The authors report a case of a 60-year-old man with glioblastoma in the corpus callosum and the parietal lobe who developed TTH after partial tumor resection. After the failure of a ventriculoperitoneal shunt, endoscopic ventriculocisternostomy was chosen over the revision of the shunt. A stoma was placed at the medial wall of the dilated temporal horn. Endoscopic inspection confirmed communication with the interpeduncular cistern, but the collapsed lateral ventricle after fenestration suggested the risk of stoma closure. Therefore, a ventricular tube was placed through the stoma as a stent to secure its flow. No further surgical intervention was needed, and the patient was able to complete radiochemotherapy without cessation. CONCLUSIONS: The risk of recurrence of TTH after endoscopic ventriculocisternostomy may be minimized by combining ventriculostomy with stent placement. This surgical procedure would be beneficial, particularly in cases of TTH associated with malignant brain tumors, where the risk of delay or interruption of adjuvant oncologic treatments may negatively impact patient prognosis.

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  • Recurrent intraneural ganglion cysts: Pathoanatomic patterns and treatment implications. 査読 国際誌

    Nicholas M Desy, Lindsay J Lipinski, Shota Tanaka, Kimberly K Amrami, Michael G Rock, Robert J Spinner

    Clinical anatomy (New York, N.Y.)   28 ( 8 )   1058 - 69   2015年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    The etiology of intraneural ganglion cysts has been poorly understood. This has resulted in the development of multiple surgical treatment strategies and a high recurrence rate. We sought to analyze these recurrences in order to provide a pathoanatomic explanation and staging classification for intraneural cyst recurrence. An expanded literature search was performed to identify frequencies and patterns in cases of intraneural ganglion cyst recurrences following primary surgery. Two univariate analyses were completed to identify associations between the type of revision surgery and repeat cyst recurrences. The expanded literature search found an 11% recurrence rate following primary surgery, including 64 recurrences following isolated cyst decompression (Group 1); six after articular branch resection (Group 2); and none following surgical procedures that addressed the joint (Group 3). Eight cases did not specify the type of primary surgery. In group 1, forty-eight of the recurrences (75%) were in the parent nerve, three involved only the articular branch, and one travelled along the articular branch in a different distal direction without involving the main parent nerve. In group 2, only one case (17%) recurred/persisted within the parent nerve, one recurred within a persistent articular branch, and one formed within a persistent articular branch and travelled in a different distal direction. Intraneural recurrences most commonly occur following surgical procedures that only target the main parent nerve. We provide proven or theoretical explanations for all identified cases of intraneural recurrences for an occult or persistent articular branch pathway.

    DOI: 10.1002/ca.22615

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  • DNA methylation profile analysis of gliomas revealed a change in methylation status during malignant progression 査読

    Akitake Mukasa, Saito Kuniaki, Aihara Koki, Nagae Genta, Omata Mayu, Otani Ryohei, Takayangi Shunsaku, Tanaka Shota, Narita Yoshitaka, Ueki Keisuke, Nishikawa Ryo, Nagane Motoo, Aburatani Hiroyuki, Saito Nobuhito

    CANCER RESEARCH   75   2015年8月

  • GENOME-WIDE METHYLATION ANALYSIS IDENTIFIES GENOMIC DNA DEMETHYLATION DURING MALIGNANT PROGRESSION OF GLIOMAS 査読

    Saito Kuniaki, Mukasa Akitake, Nagae Genta, Aihara Koki, Otani Ryohei, Takayanagi Shunsaku, Omata Mayu, Tanaka Shota, Shibahara Junji, Takahashi Miwako, Momose Toshimitsu, Shimamura Teppei, Miyano Satoru, Narita Yoshitaka, Ueki Keisuke, Nishikawa Ryo, Nagane Motoo, Aburatani Hiroyuki, Saito Nobuhito

    NEURO-ONCOLOGY   16   2014年11月

  • Targetable signaling pathway mutations are associated with malignant phenotype in IDH-mutant gliomas. 査読 国際誌

    Hiroaki Wakimoto, Shota Tanaka, William T Curry, Franziska Loebel, Dan Zhao, Kensuke Tateishi, Juxiang Chen, Lindsay K Klofas, Nina Lelic, James C Kim, Dora Dias-Santagata, Leif W Ellisen, Darrell R Borger, Sarah-Maria Fendt, Matthew G Vander Heiden, Tracy T Batchelor, A John Iafrate, Daniel P Cahill, Andrew S Chi

    Clinical cancer research : an official journal of the American Association for Cancer Research   20 ( 11 )   2898 - 909   2014年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    PURPOSE: Isocitrate dehydrogenase (IDH) gene mutations occur in low-grade and high-grade gliomas. We sought to identify the genetic basis of malignant phenotype heterogeneity in IDH-mutant gliomas. METHODS: We prospectively implanted tumor specimens from 20 consecutive IDH1-mutant glioma resections into mouse brains and genotyped all resection specimens using a CLIA-certified molecular panel. Gliomas with cancer driver mutations were tested for sensitivity to targeted inhibitors in vitro. Associations between genomic alterations and outcomes were analyzed in patients. RESULTS: By 10 months, 8 of 20 IDH1-mutant gliomas developed intracerebral xenografts. All xenografts maintained mutant IDH1 and high levels of 2-hydroxyglutarate on serial transplantation. All xenograft-producing gliomas harbored "lineage-defining" mutations in CIC (oligodendroglioma) or TP53 (astrocytoma), and 6 of 8 additionally had activating mutations in PIK3CA or amplification of PDGFRA, MET, or N-MYC. Only IDH1 and CIC/TP53 mutations were detected in non-xenograft-forming gliomas (P = 0.0007). Targeted inhibition of the additional alterations decreased proliferation in vitro. Moreover, we detected alterations in known cancer driver genes in 13.4% of IDH-mutant glioma patients, including PIK3CA, KRAS, AKT, or PTEN mutation or PDGFRA, MET, or N-MYC amplification. IDH/CIC mutant tumors were associated with PIK3CA/KRAS mutations whereas IDH/TP53 tumors correlated with PDGFRA/MET amplification. Presence of driver alterations at progression was associated with shorter subsequent progression-free survival (median 9.0 vs. 36.1 months; P = 0.0011). CONCLUSION: A subset of IDH-mutant gliomas with mutations in driver oncogenes has a more malignant phenotype in patients. Identification of these alterations may provide an opportunity for use of targeted therapies in these patients. Clin Cancer Res; 20(11); 2898-909. ©2014 AACR.

    DOI: 10.1158/1078-0432.CCR-13-3052

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  • PDGFRBのgermline変異を認めたinfantile myofibromatosisの1例 査読

    高柳 俊作, 田中 将太, 井上 瑞穂, 武笠 晃丈, 中冨 浩文, 斉藤 延人

    家族性腫瘍   14 ( 2 )   A44 - A44   2014年5月

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    記述言語:日本語   出版者・発行元:日本家族性腫瘍学会  

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  • Effect of dural detachment on long-term tumor control for meningiomas treated using Simpson grade IV resection. 査読 国際誌

    Yuta Fukushima, Soichi Oya, Hirofumi Nakatomi, Junji Shibahara, Shunya Hanakita, Shota Tanaka, Masahiro Shin, Kensuke Kawai, Masashi Fukayama, Nobuhito Saito

    Journal of neurosurgery   119 ( 6 )   1373 - 9   2013年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC NEUROLOGICAL SURGEONS  

    OBJECT: Meningiomas treated by subtotal or partial resection are associated with significantly shorter recurrence-free survival than those treated by gross-total resection. The Simpson grading system classifies incomplete resections into a single category, namely Simpson Grade IV, with wide variations in the volume and location of residual tumors, making it complicated to evaluate the achievement of surgical goals and predict the prognosis of these tumors. Authors of the present study investigated the factors related to necessity of retreatment and tried to identify any surgical nuances achievable with the aid of modern neurosurgical techniques for meningiomas treated using Simpson Grade IV resection. METHODS: This retrospective analysis included patients with WHO Grade I meningiomas treated using Simpson Grade IV resection as the initial therapy at the University of Tokyo Hospital between January 1995 and April 2010. Retreatment was defined as reresection or stereotactic radiosurgery due to postoperative tumor growth. RESULTS: A total of 38 patients were included in this study. Regrowth of residual tumor was observed in 22 patients with a mean follow-up period of 6.1 years. Retreatment was performed for 20 of these 22 tumors with regrowth. Risk factors related to significantly shorter retreatment-free survival were age younger than 50 years (p = 0.006), postresection tumor volume of 4 cm(3) or more (p = 0.016), no dural detachment (p = 0.001), and skull base location (p = 0.016). Multivariate analysis revealed that no dural detachment (hazard ratio [HR] 6.42, 95% CI 1.41-45.0; p = 0.02) and skull base location (HR 11.6, 95% CI 2.18-218; p = 0.002) were independent risk factors for the necessity of early retreatment, whereas postresection tumor volume of 4 cm(3) or more was not a statistically significant risk factor. CONCLUSIONS: Compared with Simpson Grade I, II, and III resections, Simpson Grade IV resection includes highly heterogeneous tumors in terms of resection rate and location of the residual mass. Despite the difficulty in analyzing such diverse data, these results draw attention to the favorable effect of dural detachment (instead of maximizing the resection rate) on long-term tumor control. Surgical strategy with an emphasis on detaching the tumor from the affected dura might be another important option in resection of high-risk meningiomas not amenable to gross-total resection.

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  • IDENTIFICATION OF DISTINCT SUBGROUP OF GLIOMA AND NOVEL GENES RELATED TO MALIGNANT PROGRESSION BY GENOME-WIDE METHYLATION ANALYSIS 査読

    Saito Kuniaki, Mukasa Akitake, Nagae Genta, Nagane Motoo, Aihara Koki, Takayanagi Shunsaku, Tanaka Shota, Aburatani Hiroyuki, Saito Nobuhito

    NEURO-ONCOLOGY   15   150 - 151   2013年11月

  • 網羅的メチル化解析により同定された神経膠腫悪性転化に伴うメチル化プロファイルの変化(Identification of distinct subgroup of glioma related to malignant progression by genome-wide methylation analysis)

    齊藤 邦昭, 武笠 晃丈, 永江 玄太, 永根 基雄, 相原 功輝, 高柳 俊作, 田中 將太, 油谷 浩幸, 斉藤 延人

    日本癌学会総会記事   72回   125 - 125   2013年10月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • Stereotactic radiosurgery for intracranial gliomas. 査読 国際誌

    Shota Tanaka, Masahiro Shin, Akitake Mukasa, Shunya Hanakita, Kuniaki Saito, Tomoyuki Koga, Nobuhito Saito

    Neurosurgery clinics of North America   24 ( 4 )   605 - 12   2013年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

    This article presents an overview of stereotactic radiosurgery for intracranial glioma. It assists readers in reviewing up-to-date literature on this topic and determining indications of radiosurgery in the treatment of glioma. Discussion also includes its recent advances and future perspectives.

    DOI: 10.1016/j.nec.2013.05.010

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  • Stereotactic Radiosurgery for Trigeminal Pain Secondary to Benign Skull Base Tumors 査読

    Shota Tanaka, Bruce E. Pollock, Scott L. Stafford, Michael J. Link

    WORLD NEUROSURGERY   80 ( 3-4 )   371 - 377   2013年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    OBJECTIVE: To assess the outcome of stereotactic radiosurgery (SRS) for patients with benign skull base tumors and trigeminal-related facial pain.
    METHODS: We undertook a retrospective review of 31 consecutive patients (25 women, 6 men) with benign skull base tumors and trigeminal pain who underwent SRS between 1991 and 2008. The tumors included 17 posterior fossa meningiomas, 9 cavernous sinus meningiomas, and 5 trigeminal schwannomas. The median patient age was 62 years (range, 17-81 years). In all cases the tumor was the primary target for SRS. The median follow-up after SRS was 50 months (range, 12-184 months).
    RESULTS: The actuarial tumor control rate after SRS was 95% at both 3 years and 5 years. Eighteen patients (58%) initially achieved complete resolution of trigeminal pain. Higher maximum dose was associated with initial complete pain resolution on a multivariate analysis. However, 7 patients had recurrent pain during follow-up. At last follow-up, only 7 patients (23%) remained pain-free off medications. Further treatment in addition to medical therapy was required for 6 patients (19%).
    CONCLUSION: Although SRS offers excellent radiographic tumor control for benign skull base tumors, durable relief of tumor-related trigeminal pain without medication was noted in only one-fourth of patients at last follow-up.

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  • Update on glioma treatments in the United States 査読

    Shota Tanaka, Andrew S. Chi, Patrick Y. Wen, David N. Louis, A. John Iafrate, Tracy T. Batchelor

    Japanese Journal of Neurosurgery   22 ( 8 )   590 - 596   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Congress of Neurological Surgeons  

    Despite the use of maximal standard treatments, the prognosis of patients with glioblastoma remains poor
    hence novel therapies are desperately needed. Molecular targeted therapies have shown some promise in other malignancies, while they have not demonstrated remarkable tumor response or improved patient survival in glio-blastoma to date, due, in part, to the redundancy and crosstalk of multiple overactive molecular pathways and the lack of validated predictive biomarkers. At present, a comprehensive cancer genotyping platform that can reveal potentially targetable genes is being implemented into clinical practice at some cancer institutions in the United States. This may allow us to rationally tailor therapies to specific tumor genotypes that we predict may be susceptible. In this paper, an overview of current glioblastoma treatment strategies in the United States is presented.

    DOI: 10.7887/jcns.22.590

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  • Gliomatosis cerebri: clinical characteristics, management, and outcomes. 査読 国際誌

    Selby Chen, Shota Tanaka, Caterina Giannini, Jonathan Morris, Elizabeth S Yan, Jan Buckner, Daniel H Lachance, Ian F Parney

    Journal of neuro-oncology   112 ( 2 )   267 - 75   2013年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Gliomatosis cerebri is a rare diffusely infiltrating primary neoplastic glial process of the brain. Our objective is to review clinical presentation, management, and outcome in a large single institution series of gliomatosis cerebri patients. 54 consecutive gliomatosis cerebri cases presenting to Mayo Clinic Rochester between 1991 and 2008 were retrospectively reviewed. Inclusion criteria included involvement of at least three cerebral lobes, lack of a single discrete mass and pathological confirmation of diffuse glioma. Median overall survival (OS) was 18.5 months. Age, gender, presenting symptoms, and contrast enhancement did not correlate significantly with survival, though there was a trend toward decreased overall survival in patients above the median age of 46 years. Karnofsky performance score <70 was associated with poor OS (median 9.5 vs. 20.5 months, p = 0.02). Higher histologic grade was associated with poor progression-free survival (PFS; median for WHO grades II, III, and IV: 21.5, 6.5, and 4 months; p = 0.03) and OS (median 34, 15.5, and 8.5 months; p < 0.05). Radiation therapy was strongly associated with better prognosis (PFS 16.5 vs. 4.5 months, p < 0.01; OS 27.5 vs. 6.5, p < 0.01), but chemotherapy was not. Gliomatosis cerebri patients have a poor prognosis. Lower KPS upon presentation and higher histologic grade predict decreased survival. Surgery's role is limited beyond biopsy for diagnostic purposes. Radiotherapy appears beneficial, although selection bias could be present in this retrospective study. Chemotherapy's value is not as clear but this must be interpreted with caution given variable treatment regimens in this series.

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  • Presentation, management, and outcome of newly diagnosed glioblastoma in elderly patients. 査読 国際誌

    Shota Tanaka, Fredric B Meyer, Jan C Buckner, Joon H Uhm, Elizabeth S Yan, Ian F Parney

    Journal of neurosurgery   118 ( 4 )   786 - 98   2013年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECT: Optimum management for elderly patients with newly diagnosed glioblastoma (GBM) in the temozolomide (TMZ) era is not well defined. The object of this study was to clarify outcomes in this population. METHODS: The authors retrospectively reviewed 105 consecutive cases involving elderly patients (age ≥ 65 years) with newly diagnosed GBM who were treated at the Mayo Clinic between 2003 and 2008. RESULTS: The patients' median age was 74 years (range 66-87 years), and the median Karnofsky Performance Status (KPS) score was 80 (range 40-90). Half of the patients underwent biopsy and half underwent resection. Patients with deep-seated lesions (19 patients [18%]) or multifocal lesions (34 patients [32%]) were more likely to have biopsy than resection (p = 0.0001 and 0.0009, respectively). New persistent neurological deficits developed in 7 patients (6.7%). Postoperative hemorrhage occurred in 6 patients (5.7%), all of whom underwent biopsy. Complete follow-up data regarding adjuvant treatment was available in 84 patients. Forty-one (49%) were treated with chemotherapy (mostly TMZ) and radiation therapy (RT), and 23 (27%) with RT alone. Nineteen (23%) received only palliative care after surgery (more common with biopsy, p = 0.03). Chemotherapy complications occurred in 28.6% (Grade 3 or 4 hematological complications in 11.9%). The median values for progression-free survival (PFS) and overall survival (OS) were 3.5 and 5.5 months. In a multivariate analysis, younger age (p = 0.03, risk ratio [RR] 0.34, 95% CI 0.13-0.89), single lesion (p = 0.02, RR 0.51, 95% CI 0.30-0.89), resection (p = 0.04, RR 0.54, 95% CI 0.31-0.94), and adjuvant treatment (p = 0.0001, RR 0.24, 95% CI 0.11-0.49) were associated with better OS. Only adjuvant treatment was significantly associated with prolonged PFS (p = 0.0007, RR 0.27, 95% CI 0.13-0.57). With combined therapy with resection, RT, and chemotherapy, the median PFS and OS were 8 and 12.5 months, respectively. CONCLUSIONS: The prognosis for GBM worsens with increasing age in elderly patients. With important risks, resection and adjuvant treatment are associated with prolonged survival. Although selection bias cannot be excluded in this retrospective study, advanced age alone should not necessarily preclude optimal resection followed by adjuvant radiochemotherapy.

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  • Diagnostic and therapeutic avenues for glioblastoma: no longer a dead end? 査読 国際誌

    Shota Tanaka, David N Louis, William T Curry, Tracy T Batchelor, Jorg Dietrich

    Nature reviews. Clinical oncology   10 ( 1 )   14 - 26   2013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)   出版者・発行元:NATURE PUBLISHING GROUP  

    Glioblastomas are heterogeneous neoplasms that are driven by complex signalling pathways, and are among the most aggressive and challenging cancers to treat. Despite standard treatment with resection, radiation and chemotherapy, the prognosis of patients with glioblastomas remains poor. An increasing understanding of the molecular pathogenesis of glioblastomas has stimulated the development of novel therapies, including the use of molecular-targeted agents. Identification and validation of diagnostic, prognostic and predictive biomarkers has led to the advancement of clinical trial design, and identification of glioblastoma subgroups with a more-favourable prognosis and response to therapy. In this Review, we discuss common molecular alterations relevant to the biology of glioblastomas, targeted, antiangiogenic and immunotherapies that have impacted on the treatment of this disease, and the challenges and pitfalls associated with these therapies. In addition, we emphasize current biomarkers relevant to the management of patients with glioblastoma.

    DOI: 10.1038/nrclinonc.2012.204

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  • Increased Frameless Stereotactic Accuracy With High-Field Intraoperative Magnetic Resonance Imaging 査読

    Shota Tanaka, Ross C. Puffer, Jason M. Hoover, Stephan J. Goerss, Laura M. Haugen, Kiaran McGee, Ian F. Parney

    Operative Neurosurgery   71   ons321 - ons328   2012年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

    BACKGROUND: Frameless stereotaxy commonly registers preoperative magnetic resonance imaging (MRI) to patients by using surface scalp anatomy or adhesive fiducial scalp markers. Patients' scalps may shift slightly between preoperative imaging and final surgical positioning with pinion placement, introducing error. This might be reduced when frameless stereotaxy is performed in a high-field intraoperative MRI (iMRI), as patients are positioned before imaging. This could potentially improve accuracy.
    OBJECTIVE: To compare frameless stereotactic accuracy using a high-field iMRI with that using standard preoperative MRI.
    METHODS: Data were obtained in 32 adult patients undergoing frameless stereotactic-guided brain tumor surgery. Stereotactic images were obtained with 1.5T MRI scanner either preoperatively (14 patients) or intraoperative (18 patients). System-generated accuracy measurements and distances from the actual center of each fiducial marker to that represented by neuronavigation were recorded. Finally, accuracy at multiple deep targets was assessed by using a life-sized human head stereotactic phantom in which fiducials were placed on deformable foam to mimic scalp.
    RESULTS: System-generated accuracy measurements were significantly better for the iMRI group (mean +/- SEM = 1.04 +/- 0.05 mm) than for the standard group (1.82 +/- 0.09 mm; P &lt; .001). Measured distances from the actual center of scalp fiducial markers to that represented by neuronavigation were also significantly smaller for iMRI (1.72 +/- 0.10 mm) in comparison with the standard group (3.17 +/- 0.22 mm; P &lt; .001). Deep accuracy in the phantom model was significantly better with iMRI (1.67 +/- 0.12 mm) than standard imaging (2.28 +/- 0.14 mm; P = .003).
    CONCLUSION: Frameless stereotactic accuracy is increased by using high-field iMRI compared with standard preoperative imaging.

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  • Increased frameless stereotactic accuracy with high-field intraoperative magnetic resonance imaging. 査読 国際誌

    Shota Tanaka, Ross C Puffer, Jason M Hoover, Stephan J Goerss, Laura M Haugen, Kiaran McGee, Ian F Parney

    Neurosurgery   71 ( 2 Suppl Operative )   ons321-7; discussion ons327-8 - 328   2012年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    BACKGROUND: Frameless stereotaxy commonly registers preoperative magnetic resonance imaging (MRI) to patients by using surface scalp anatomy or adhesive fiducial scalp markers. Patients' scalps may shift slightly between preoperative imaging and final surgical positioning with pinion placement, introducing error. This might be reduced when frameless stereotaxy is performed in a high-field intraoperative MRI (iMRI), as patients are positioned before imaging. This could potentially improve accuracy. OBJECTIVE: To compare frameless stereotactic accuracy using a high-field iMRI with that using standard preoperative MRI. METHODS: Data were obtained in 32 adult patients undergoing frameless stereotactic-guided brain tumor surgery. Stereotactic images were obtained with 1.5T MRI scanner either preoperatively (14 patients) or intraoperative (18 patients). System-generated accuracy measurements and distances from the actual center of each fiducial marker to that represented by neuronavigation were recorded. Finally, accuracy at multiple deep targets was assessed by using a life-sized human head stereotactic phantom in which fiducials were placed on deformable foam to mimic scalp. RESULTS: : System-generated accuracy measurements were significantly better for the iMRI group (mean ± SEM = 1.04 ± 0.05 mm) than for the standard group (1.82 ± 0.09 mm; P < .001). Measured distances from the actual center of scalp fiducial markers to that represented by neuronavigation were also significantly smaller for iMRI (1.72 ± 0.10 mm) in comparison with the standard group (3.17 ± 0.22 mm; P < .001). Deep accuracy in the phantom model was significantly better with iMRI (1.67 ± 0.12 mm) than standard imaging (2.28 ± 0.14 mm; P = .003). CONCLUSION: Frameless stereotactic accuracy is increased by using high-field iMRI compared with standard preoperative imaging.

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  • Presentation, management, and outcome of elderly patients with newly-diagnosed anaplastic astrocytoma. 査読 国際誌

    Shota Tanaka, Fredric B Meyer, Jan C Buckner, Joon H Uhm, Elizabeth S Yan, Ian F Parney

    Journal of neuro-oncology   110 ( 2 )   227 - 35   2012年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Few studies have assessed the presentation, management, and outcome of anaplastic astrocytoma (AA) in elderly patients in the temozolomide era. We retrospectively reviewed 42 consecutive patients aged >65 years with newly-diagnosed AA who underwent surgical resection or biopsy between 2003 and 2008. Median age and KPS score were 73 years (range, 66-88) and 80 (range, 50-90), respectively. Thirty-two patients (76 %) presented with focal deficits. Twenty patients (48 %) experienced seizures before surgery. Tumor enhanced diffusely in 24 patients (57 %) and sparsely in 18 patients (43 %). Biopsy (79 %) was more common than resection. Post-operatively, new persistent neurological deficits and hemorrhage were seen in two (4.8 %) and three (7.1 %) patients, respectively. Complete follow-up data regarding adjuvant treatment was available in 31 patients. Sixteen patients (52 %) received temozolomide and radiation therapy (RT), while nine patients (29 %) received RT alone. Chemotherapy-related grade 3/4 hematologic complication rate was 17.6 %. Median overall survival (OS) was 6.5 months (12 months with resection; 3.5 months with biopsy). Resection (P = 0.007, risk ratio = 0.21) and sparse enhancement (P = 0.007, risk ratio = 0.13) were associated with longer OS in multivariate analysis. Similarly, chemoradiation was associated with longer survival compared to RT alone (OS: P = 0.01, progression-free survival (PFS): P = 0.02) after adjusting for age, KPS, enhancement, and surgery. Resection was associated with longer survival among elderly patients with AA, although this could reflect selection bias. Similarly, adding chemotherapy to RT was associated with prolonged survival but carried important complication risks. In appropriately selected AA patients, aggressive treatments with radical resection and chemoradiation may be appropriate even in this age group.

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  • Gamma Knife surgery for the management of glomus tumors: a multicenter study. 査読 国際誌

    Jason P Sheehan, Shota Tanaka, Michael J Link, Bruce E Pollock, Douglas Kondziolka, David Mathieu, Christopher Duma, A Byron Young, Anthony M Kaufmann, Heyoung McBride, Peter A Weisskopf, Zhiyuan Xu, Hideyuki Kano, Huai-che Yang, L Dade Lunsford

    Journal of neurosurgery   117 ( 2 )   246 - 54   2012年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC NEUROLOGICAL SURGEONS  

    OBJECT: Glomus tumors are rare skull base neoplasms that frequently involve critical cerebrovascular structures and lower cranial nerves. Complete resection is often difficult and may increase cranial nerve deficits. Stereotactic radiosurgery has gained an increasing role in the management of glomus tumors. The authors of this study examine the outcomes after radiosurgery in a large, multicenter patient population. METHODS: Under the auspices of the North American Gamma Knife Consortium, 8 Gamma Knife surgery centers that treat glomus tumors combined their outcome data retrospectively. One hundred thirty-four patient procedures were included in the study (134 procedures in 132 patients, with each procedure being analyzed separately). Prior resection was performed in 51 patients, and prior fractionated external beam radiotherapy was performed in 6 patients. The patients' median age at the time of radiosurgery was 59 years. Forty percent had pulsatile tinnitus at the time of radiosurgery. The median dose to the tumor margin was 15 Gy. The median duration of follow-up was 50.5 months (range 5-220 months). RESULTS: Overall tumor control was achieved in 93% of patients at last follow-up; actuarial tumor control was 88% at 5 years postradiosurgery. Absence of trigeminal nerve dysfunction at the time of radiosurgery (p = 0.001) and higher number of isocenters (p = 0.005) were statistically associated with tumor progression-free tumor survival. Patients demonstrating new or progressive cranial nerve deficits were also likely to demonstrate tumor progression (p = 0.002). Pulsatile tinnitus improved in 49% of patients who reported it at presentation. New or progressive cranial nerve deficits were noted in 15% of patients; improvement in preexisting cranial nerve deficits was observed in 11% of patients. No patient died as a result of tumor progression. CONCLUSIONS: Gamma Knife surgery was a well-tolerated management strategy that provided a high rate of long-term glomus tumor control. Symptomatic tinnitus improved in almost one-half of the patients. Overall neurological status and cranial nerve function were preserved or improved in the vast majority of patients after radiosurgery.

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  • Acute epidural spinal hemorrhage from vasculitis: resolution with immunosuppression. 査読 国際誌

    Jeffrey T Jacob, Shota Tanaka, Christopher P Wood, Eelco F Wijdicks, Giuseppe Lanzino

    Neurocritical care   16 ( 2 )   311 - 5   2012年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:HUMANA PRESS INC  

    BACKGROUND: Angiographic vasculitis affecting the spine has been rarely described. The use of immunosuppression as a primary treatment and a review of the literature is presented. METHODS: Case report. RESULTS: A 61-year-old female presented with sudden onset back pain and headache. The patient was found to have acute spinal epidural hemorrhage and subsequent work-up demonstrated angiographic spinal vasculitis. Immunosuppression with cyclophosphamide resulted in clinical and radiographic improvement. CONCLUSIONS: Immunomodulating therapy should be considered in the management of select patients with spinal vasculitis which may lead to improved clinical outcome and potentially disease resolution.

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  • Safety of concurrent bevacizumab therapy and anticoagulation in glioma patients. 査読 国際誌

    Andrew D Norden, Julia Bartolomeo, Shota Tanaka, Jan Drappatz, Abigail S Ciampa, Lisa M Doherty, Debra C Lafrankie, Sandra Ruland, Eudocia C Quant, Rameen Beroukhim, Patrick Y Wen

    Journal of neuro-oncology   106 ( 1 )   121 - 5   2012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)   出版者・発行元:SPRINGER  

    Venous thromboembolic events (VTE) are common in glioma patients and are typically treated with anticoagulant medications. The anti-angiogenic agent bevacizumab (BVZ) increases the risks of both VTE and hemorrhagic complications. Little is known about the hemorrhagic risk of anticoagulation in glioma patients receiving BVZ. We reviewed medical records from 282 BVZ-treated patients at our center and identified 64 who received concurrent anticoagulant therapy. The risk and severity of hemorrhagic complications were assessed. Fisher's exact test was used to compare the risk of hemorrhage between subjects who received and did not receive anticoagulants. Forty-seven patients (73%) had glioblastoma, 15 (23%) anaplastic glioma, and 2 (3%) other tumors. Thirteen (20%) and 51 (80%) patients received warfarin and low-molecular-weight heparin, respectively. The indication for anticoagulation was deep venous thrombosis in 37 patients (58%), pulmonary embolism in 22 (34%), and both in 5 (8%). Thirteen patients (20%) experienced hemorrhage, of which four hemorrhages (6%) were serious (grade ≥ 3): one patient had grade 5 intracerebral hemorrhage (ICH), one grade 4 ICH, one grade 3 epistaxis, and one grade 3 gastrointestinal hemorrhage. ICH was seen in seven patients (11%), of which five (8%) were grade 1. Among 218 patients who did not receive anticoagulants, there were two (1%) serious hemorrhages (both grade 4 ICH). Both the serious hemorrhage rate and overall ICH rate were higher in patients who received anticoagulants (P = 0.03 and 0.02, respectively). Anticoagulant use during BVZ therapy may increase the risk of hemorrhage in glioma patients, although it is generally well tolerated.

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  • Letter to the Editor. 査読 国際誌

    Robert J Spinner, Marie-Noëlle Hébert-Blouin, Shota Tanaka, Kimberly K Amrami, Karin R Swartz, Dominic B Fee, Makoto Sugita

    Journal of neurosurgery   2011年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3171/jns.0.0.0.jns10189

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  • Gamma knife radiosurgery for patients with prolactin-secreting pituitary adenomas. 査読 国際誌

    Shota Tanaka, Michael J Link, Paul D Brown, Scott L Stafford, William F Young Jr, Bruce E Pollock

    World neurosurgery   74 ( 1 )   147 - 52   2010年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    OBJECTIVE: To evaluate the efficacy of stereotactic radiosurgery (SRS) for patients with prolactin (PRL)-secreting pituitary adenomas that were refractory to medical management. METHODS: Retrospective review of 22 patients treated with SRS from 1994 until 2006. All patients were either intolerant or their tumors were unresponsive to dopamine agonist therapy. Nine patients (41%) had undergone prior transsphenoidal surgery. The median serum PRL concentration before SRS was 88.4 ng/mL (range, 25-943). The median treatment volume was 2.2 cm(3) (range, 0.4-29.0); the median margin radiation dose was 25 Gy (range, 16-30). The median endocrinologic follow-up was 60 months (range, 16-129). RESULTS: Tumor control after SRS was 100%. Serum PRL concentration was significantly lower (median, 28.4 ng/mL) (P = 0.006) at last follow-up, but the 4-year actuarial rate of biochemical remission off medications was only 17%. No tested variable was associated with biochemical remission off medications. Overall, four patients (18%) had biochemical remission off medications and clinical improvement, three patients (14%) had normal serum PRL concentrations and clinical improvement on dopamine agonist therapy, seven patients (32%) had improved symptoms off medications but continued to have elevated serum PRL levels, and eight patients (36%) continued to be symptomatic with elevated PRL levels either on (n = 3) or off (n = 5) dopamine agonist therapy. The incidence of new anterior pituitary deficits was 42% at 4 years. CONCLUSIONS: SRS was effective in controlling tumor growth for patients with PRL-secreting pituitary adenomas, and the majority of patients were clinically improved.

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  • Factors associated with endocrine deficits after stereotactic radiosurgery of pituitary adenomas. 査読 国際誌

    James L Leenstra, Shota Tanaka, Robert W Kline, Paul D Brown, Michael J Link, Todd B Nippoldt, William F Young Jr, Bruce E Pollock

    Neurosurgery   67 ( 1 )   27 - 32   2010年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    OBJECTIVE: To analyze the factors associated with anterior pituitary deficits after pituitary adenoma stereotactic radiosurgery (SRS). METHODS: The tumor, pituitary stalk, and pituitary gland were segmented on the dose plans of 82 patients (secreting tumors, n = 53; nonsecreting tumors, n=29) for dose-volume analysis. No patient had undergone prior radiation therapy and all patients had at least 12 months of endocrinological follow-up (median, 63 months; mean, 69 months; range, 13-134). RESULTS: Thirty-four patients (41%) developed new anterior pituitary deficits at a median of 32 months (range, 2-118) after SRS. The risk of developing new anterior pituitary deficits was 16% and 45% at 2 and 5 years, respectively. Multivariate analysis of the entire group showed that poor visualization of the pituitary gland (hazard ratio [HR]=2.63, 95% confidence interval [CI]=1.10-6.25, P=.03) was associated with a higher rate of new anterior pituitary deficits. Dosimetric analysis of 60 patients whose pituitary gland could be clearly identified showed that increasing mean pituitary gland radiation dose correlated with new anterior pituitary deficits (HR=1.11, 95% CI=1.02-1.20, P=.02). New anterior pituitary deficits stratified by mean pituitary gland radiation dose: <or=7.5 Gy, 0% (0/7); 7.6 to 13.2 Gy, 29% (7/24); 13.3 to 19.1 Gy, 39% (9/23); >19.1 Gy, 83% (5/6). CONCLUSION: New endocrine deficits after pituitary adenoma radiosurgery were correlated with increasing radiation dose to the pituitary gland. Methods that limit the radiation dose to the pituitary gland during SRS may increase the probability of preserving pituitary function.

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  • Hip- and pelvic-related intraneural ganglia. 査読 国際誌

    Robert J Spinner, Marie-Noëlle Hébert-Blouin, Shota Tanaka, Kimberly K Amrami, Karin R Swartz, Dominic B Fee, Makoto Sugita

    Journal of neurosurgery   112 ( 6 )   1353 - 6   2010年6月

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    記述言語:英語   出版者・発行元:AMER ASSOC NEUROLOGICAL SURGEONS  

    DOI: 10.3171/2010.3.JNS10189

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  • Adherence of intraneural ganglia of the upper extremity to the principles of the unifying articular (synovial) theory. 査読 国際誌

    Huan Wang, Robert Q Terrill, Shota Tanaka, Kimberly K Amrami, Robert J Spinner

    Neurosurgical focus   26 ( 2 )   E10   2009年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC NEUROLOGICAL SURGEONS  

    OBJECT: Intraneural ganglia are nonneoplastic mucinous cysts contained within the epineurium of peripheral nerves. Their pathogenesis has been controversial. Historically, the majority of authors have favored de novo formation (degenerative theory). Because of their rarity, intraneural ganglia affecting the upper limb have been misunderstood. This study was designed to critically analyze the literature and to test the hypothesis that intraneural ganglia of the upper limb act analogously to those in the lower limb, being derived from an articular source (synovial theory). METHODS: Two patients with digital intraneural cysts were included in the study. An extensive literature review of intraneural ganglia of the upper limb was undertaken to provide the historical basis for the study. RESULTS: In both cases, the digital intraneural ganglia were demonstrated to have joint connections; the one patient in whom an articular branch was not appreciated initially had evidence on postoperative MR images of persistence of intraneural cyst after simple decompression was performed. Eighty-six cases of intraneural lesions were identified in varied locations of the upper limb: the most common sites were the ulnar nerve at the elbow and wrist, occurring 38 and 22 times, respectively. Joint connections were present in only 20% of the cases published by other groups. CONCLUSIONS: The authors believe that the fundamental principles of the unifying articular (synovial) theory (that is, articular branch connections, cyst fluid following a path of least resistance, and the role of pressure fluxes) previously described to explain intraneural ganglia in the lower limb apply to those cases in the upper limb. In their opinion, the joint connection is often not identified because of the cysts' rarity, radiologists' and surgeons' inexperience, and the difficulty visualizing and demonstrating it because of the small size of the cysts. Furthermore, they believe that recurrence (subclinical or clinical) is not only underreported but also predictable after simple decompression that fails to address the articular branch. In contrast, intraneural recurrence can be eliminated with disconnection of the articular branch.

    DOI: 10.3171/FOC.2009.26.2.E10

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  • Direct and primary carotid endarterectomy for common carotid artery occlusion. Report of 2 cases. 査読 国際誌

    Tomohiro Inoue, Kazuo Tsutsumi, Shinobu Adachi, Shota Tanaka, Naoto Kunii, Masahiro Indo

    Surgical neurology   69 ( 6 )   620 - 6   2008年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    BACKGROUND: Cerebral ischemia associated with chronic CCA occlusion is a rare condition and raises strategic dilemma when the revascularization is needed. METHODS: Two patients with CCA occlusion presented with ischemic symptom associated with the affected side. Both patients underwent vascular reconstruction by direct carotid endarterectomy to achieve primary restoration of CCA to ICA flow. RESULTS: Successful reopening of the vessels was obtained in both patients without the evidence of postsurgical ischemic event. Follow-up MRA was obtained at later than 6 months after surgery, which demonstrated patent CCA-ICA in both patients. CONCLUSIONS: Direct carotid endarterectomy of the occluded CCA can be safely performed if the preoperative angiography suggest still patent vessels distal to carotid bifurcation and the substantial "back flow" is obtained from ICA during arteriotomy.

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  • Clipping and superficial temporal artery-M2 bypass for unruptured anterior communicating artery aneurysm associated with atherosclerotic internal carotid artery occlusion: report of 2 cases. 査読 国際誌

    Tomohiro Inoue, Kazuo Tsutsumi, Shinobu Adachi, Shota Tanaka, Kuniaki Saito, Naoto Kunii

    Surgical neurology   68 ( 2 )   226 - 31   2007年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    BACKGROUND: The management of the unruptured AcomA aneurysm associated with atherosclerotic occlusion of the unilateral internal carotid artery (ICA) raises several strategic dilemmas. METHODS: Two such patients with unruptured aneurysm on the AcomA, which supply cross-flow toward the hemisphere with ICA occlusion, are presented. RESULTS: Both patients were treated with STA-M2 bypass followed by clipping of the unruptured AcomA aneurysm in 1 stage through the transsylvian route. Both patients were doing well without neurological deficit nor cognitive impairment at 1 year follow-up. CONCLUSIONS: In the surgical treatment of unruptured AcomA aneurysm with atherosclerotic ICA occlusion, preceding bypass would be ideal in case of intraoperative rupture as well as to reduce perioperative ischemia if the bypass procedure itself could be performed with minimal risk. Enough and atraumatic exposure of the sylvian fissure contributed to reduce brain retraction during the clipping of AcomA aneurysm and, in addition, to ease the STA-M2 bypass.

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  • Recurrent subarachnoid hemorrhage after complete occlusion of a ruptured small-necked, small vertebral artery-posterior inferior cerebellar artery aneurysm. Case illustration. 査読 国際誌

    Tomohiro Inoue, Kazuo Tsutsumi, Kyoko Yako, Shota Tanaka

    Journal of neurosurgery   106 ( 3 )   514 - 514   2007年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC NEUROLOGICAL SURGEONS  

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  • Training of A3-A3 side-to-side anastomosis in a deep corridor using a box with 6.5-cm depth: technical note. 査読 国際誌

    Tomohiro Inoue, Kazuo Tsutsumi, Kuniaki Saito, Shinobu Adachi, Shota Tanaka, Naoto Kunii

    Surgical neurology   66 ( 6 )   638 - 41   2006年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    BACKGROUND: Cerebral revascularization in the deep surgical field is technically challenging. Especially, side-to-side anastomosis like A3-A3 could be technically more difficult compared with end-to-side anastomosis. To improve surgeon's dexterity and maneuverability in the deep surgical field, the authors developed an easily accessible and well-simulating training system using prosthetic tubes and a box. METHODS: Two prosthetic tubes (silicon tube, 1.2 mm in diameter) are mounted in parallel on the bottom of 6.5-cm-deep emptied 'tissue paper box.' The orifice of the box is restricted to 2 x 2 cm to simulate a deep and narrow surgical corridor. Using bayonet-shaped micro needle holder and forceps, the side-to-side anastomosis of the tubes is performed with 10-0 nylon under operative microscope. RESULTS: Prosthetic tubes well simulated real A3-A3 anastomosis. From the standpoint of technical difficulty, this training system needed slightly higher level of dexterity compared with real A3-A3 anastomosis because of narrower and deeper surgical corridor, and the wall of prosthetic tube was slightly thicker and more inflexible. After this training, the surgical technique in real A3-A3 anastomosis was improved. CONCLUSIONS: This training system worked well to ease the transition from anastomosis in shallow surgical field to deep and narrow surgical field. The prosthetic tube we used approximates real A3 relatively well, and the ease in setting up this system enabled repeated practice, which resulted in steep learning curve of the technique.

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  • Incidence of ischemic lesions by diffusion-weighted imaging after carotid endarterectomy with routine shunt usage. 査読

    Tomohiro Inoue, Kazuo Tsutsumi, Keiitirou Maeda, Shinobu Adachi, Shota Tanaka, Kyoko Yako, Kuniaki Saito, Naoto Kunii

    Neurologia medico-chirurgica   46 ( 11 )   529 - 33   2006年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPAN NEUROSURGICAL SOC  

    Temporary intraluminal shunt was used during 72 consecutive carotid endarterectomies (CEAs) in 61 patients (bilateral CEA in 11 patients) during October 2001 and September 2005. The medical records of these patients were retrospectively reviewed. All procedures were performed with routine shunt insertion without monitoring such as electroencephalography. Pre- and postoperative diffusion-weighted magnetic resonance (MR) imaging was used to detect ischemic complications. Postoperative angiography was performed in 70 cases to detect abnormalities such as major stenosis or dissection of the distal end. Symptomatic ischemic complication occurred in one patient at 1 month. Postoperative diffusion-weighted MR imaging detected new hyperintense lesions in three patients including the symptomatic patient. Postoperative angiography confirmed that the distal end was satisfactory in all cases. The incidence of ischemic lesions of embolic origin after CEA with routine shunt usage is acceptably low if the procedure of shunt device insertion and removal is meticulously conducted.

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  • Effectiveness of suturing training with 10-0 nylon under fixed and maximum magnification (x 20) using desk type microscope. 査読 国際誌

    Tomohiro Inoue, Kazuo Tsutsumi, Shinobu Adachi, Shota Tanaka, Kuniaki Saito, Naoto Kunii

    Surgical neurology   66 ( 2 )   183 - 7   2006年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    BACKGROUND: Microvascular anastomosis using 10-0 nylon needs a higher level of technical dexterity compared with routine neurosurgical maneuvers. Although this technique remains an important part of treating complex intracranial aneurysms or cerebrovascular disease, the surgeon's clinical experience in using this technique is not so common. METHODS: To improve dexterity and maneuverability in the limited clinical case volume, we developed an easily accessible training system, using commercially available desk type microscope and simply suturing neighboring fibers of the gauze with 10-0 nylon under fixed and highest (x 20) magnification. RESULT: This training system is somewhat of a drawback compared to the simulation of a real clinical setting. However, because of the extremely easy availability and accessibility of the dark type microscope repeated training and the accumulation of more than 10000 stitches, on average, was accomplished. This resulted in a steep learning curve of the technique. CONCLUSION: For residency and post-residency year young neurosurgeons, who need to brush up their skills due to lower surgical case volume compared with what senior neurosurgeons have experienced this easily available training would contribute to establishing daily and long-lasting microsurgical practice.

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  • 当院におけるnear occlusion例に対するCEA

    國井 尚人, 堤 一生, 井上 智弘, 安達 忍, 田中 将太, 齊藤 邦昭, Naoto KUNII, Kazuo TSUTSUMI, Tomohiro INOUE, Shinobu ADACHI, Shota TANAKA, Kuniaki SAITO, 公立昭和病院脳神経外科, 公立昭和病院脳神経外科, 公立昭和病院脳神経外科, 公立昭和病院脳神経外科, 公立昭和病院脳神経外科, 公立昭和病院脳神経外科, Department of Neurosurgery Showa General Hospital, Department of Neurosurgery Showa General Hospital, Department of Neurosurgery Showa General Hospital, Department of Neurosurgery Showa General Hospital, Department of Neurosurgery Showa General Hospital, Department of Neurosurgery Showa General Hospital

    脳卒中の外科 = Surgery for cerebral stroke   34 ( 1 )   27 - 31   2006年1月

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    記述言語:日本語   出版者・発行元:The Japanese Society on Surgery for Cerebral Stroke  

    The effectiveness of CEA in preventing further stroke of the patient with high grade carotid stenosis is well known. However, controversy still exists as for the choice of CEA or low flow bypass in the cases of near occlusion because of the uncertainty of the patency of distal ICA as well as the risk for postoperative hyperperfusion. We experienced 7 consecutive cases of near occlusion between May and November 2004 and performed CEA. In all cases, the flexible shunt (Furui shunt) was employed to reduce the risk of hemodynamic ischemia during clamping. To prevent distal embolism during distal shunt tube insertion, great care was taken to secure the "true distal lumen" high enough above the stenotic site. If necessary, arteriotomy was added on the distal wall and then connected toward the proximal. The use of a shunt tube was helpful in gaining a fine view of the distal end during endarterectomy because it held the collapsed lumen round open. There were no ischemic complications. Good patencies were demonstrated by postoperative DSAs in all cases. In our experiences, CEA could be safely performed as long as the angiography shows patent ICA distal to stenotic site even in delayed fashion.

    DOI: 10.2335/scs.34.27

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    その他リンク: https://jlc.jst.go.jp/DN/JALC/00273987947?from=CiNii

  • Endoscopic evacuation of hypertensive intracerebral hemorrhage: The importance of hemostasis in ultra-early surgery 査読

    Tetsuhiro Nishihara, Kazuya Nagata, Junichi Takeda, Shota Tanaka, Yasutaka Suzuki, Masafumi Izumi, Yubuhito Mochizuki, Atsuya Akabane, Chikayuki Ochiai

    Japanese Journal of Neurosurgery   14 ( 6 )   401 - 406   2005年

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    記述言語:日本語   掲載種別:研究論文(国際会議プロシーディングス)   出版者・発行元:Japanese Congress of Neurological Surgeons  

    Ultra-early surgical treatments are expected to be established, in which the associated brain injury is minimized and a maximal volume of hematoma is removed shortly after onset with secure hemostasis. We developed a transparent guiding sheath and other surgical instruments for endoscopic surgery, and we established a novel surgical procedure in the ultra-early stage using those instruments. This procedure has the following characteristics: (1) the capability of burr hole opening under local anesthesia, (2) a transparent sheath improves the surgical field visualization of the parenchyma and the hematoma, (3) free-hand surgery without fixing an endoscope and a sheath to a frame facilitates three-dimensional operation, (4) the capability of secure hemostasis by electric coagulation (When bleeding from a perforating artery occurs, a suction tube is placed at the bleeding point and hemostasis is achieved by electric coagulation), (5) easy preparation of relatively simple surgical instruments. We have performed this procedure on 85 patients with intracerebral or intraventricular hemorrhage. Among these 85 patients, 24 patients received our treatment in the ultra-early stage, or within 3 hours after onset. The mean duration of surgery was 63 minutes, the mean hematoma reduction rate was 96%, and no perioperative hemorrhage with deterioration of symptoms and/or signs occurred. Thus, we believe that endoscopic hematoma evacuation with our surgical procedure is a promising ultra-early-stage treatment for intracerebral hemorrhage, and that it may improve the long-term prognosis of patents with intracerebral hemorrhage.

    DOI: 10.7887/jcns.14.401

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  • Newly developed endoscopic instruments for the removal of intracerebral hematoma. 査読 国際誌

    Tetsuhiro Nishihara, Kazuya Nagata, Shota Tanaka, Yasutaka Suzuki, Masafumi Izumi, Yubuhito Mochizuki, Atsuya Akabane, Chikayuki Ochiai

    Neurocritical care   2 ( 1 )   67 - 74   2005年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:HUMANA PRESS INC  

    Ultra-early surgical treatment in which associated brain injury is minimized and maximal volume of hematoma is removed shortly after onset with secure hemostasis is expected to be established. We developed a transparent guiding sheath and other surgical instruments for endoscopic surgery and established a novel, ultra-early stage surgical procedure using those instruments. This procedure has the following characteristics: (a) burr hole opening under local anesthesia is possible; (b) a transparent sheath improves the visualization of the surgical field in the parenchyma and the hematoma; (c) free-hand surgery without fixing an endoscope and a sheath to a frame facilitates three-dimensional operation; (d) secure hemostasis by electric coagulation is possible; (e) relatively simple surgical instruments are easy to prepare. We have performed this procedure in 82 patients with intracerebral or intraventricular hemorrhage (44 with putaminal hemorrhage, 12 with thalamic hemorrhage, 8 with subcortical hemorrhage, 8 with cerebellar hemorrhage, 10 with intraventricular hemorrhage). Twenty-four of those patients received our treatment in the ultra-early stage (within 3 hours after onset). The mean duration of surgery was 63 minutes, the mean hematoma reduction rate was 96%, and no peri-operative hemorrhage with deterioration of symptoms and/or signs occurred. Therefore, we believe that endoscopic hematoma evacuation with our surgical procedure is a promising ultra-early stage treatment for intracerebral hemorrhage and that it may improve the long-term prognosis in patents with intracerebral hemorrhage.

    DOI: 10.1385/NCC:2:1:067

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  • がんゲノム診断とバイオインフォマティクス 大規模全ゲノムおよびトランスクリプトーム解析によるGlioblastoma,IDH-wild typeの多様性の解明

    中島 拓真, 舟越 勇介, 畝田 篤仁, 田中 將太, 石田 穣治, 齋藤 竜太, 花谷 亮典, 吉本 幸司, 成田 善孝, 鈴木 啓道

    Brain Tumor Pathology   40 ( Suppl. )   066 - 066   2023年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 頭蓋底発生の脱分化型脊索腫にはH3K27トリメチル化消失を伴う特異な一群がある

    牧瀬 尚大, 下井 辰徳, 角南 久仁子, 青柳 康子, 小林 寛, 田中 將太, 川井 章, 米盛 勧, 牛久 哲男, 吉田 朗彦

    日本病理学会会誌   112 ( 1 )   276 - 276   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 頭蓋底発生の脱分化型脊索腫にはH3K27トリメチル化消失を伴う特異な一群がある

    牧瀬 尚大, 下井 辰徳, 角南 久仁子, 青柳 康子, 小林 寛, 田中 將太, 川井 章, 米盛 勧, 牛久 哲男, 吉田 朗彦

    日本病理学会会誌   112 ( 1 )   276 - 276   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 再発膠芽腫に対するエリブリンの第2相多施設単群医師主導治験

    高橋 雅道, 川嶋 聡, 口羽 文, 佐立 崚, 米盛 勧, 永根 基雄, 荒川 芳輝, 武笠 晃丈, 田中 將太, 西川 亮, 村垣 善浩, 増富 健吉, 市村 幸一, 中村 健一, 成田 善孝

    日本癌治療学会学術集会抄録集   60回   EN6 - 3   2022年10月

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    記述言語:英語   出版者・発行元:(一社)日本癌治療学会  

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  • 【脊椎・脊髄外科の最先端】腫瘍 上衣腫と星細胞腫

    高見 浩数, 高柳 俊作, 田中 將太, 齊藤 延人

    Clinical Neuroscience   40 ( 10 )   1264 - 1269   2022年10月

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    記述言語:日本語   出版者・発行元:(株)中外医学社  

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  • Oligodendroglioma,IDH-mutant and 1p/19q-codeletedのマルチオミクス解析による全ゲノム解析の全貌(Whole genome multi-omics landscape of Oligodenderoglioma, IDH-mutant and 1p/19q-codeleted)

    舟越 勇介, 南部 翔平, 中島 拓真, 畝田 篤仁, 片山 琴絵, 井元 清哉, 花谷 亮典, 田中 將太, 齋藤 竜太, 吉本 幸司, 成田 善孝, 鈴木 啓道

    日本癌学会総会記事   81回   E - 1041   2022年9月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • 星細胞腫IDH変異型の全ゲノムシークエンスと包括的な分子学的解析(Whole-genome sequencing and comprehensive molecular profiling of Astrocytoma, IDH-mutant)

    舟越 勇介, 中島 拓真, 南部 翔平, 畝田 篤仁, 片山 琴絵, 井元 清哉, 花谷 亮典, 田中 將太, 齋藤 竜太, 吉本 幸司, 成田 善孝, 鈴木 啓道

    日本癌学会総会記事   81回   E - 1038   2022年9月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • 【Precision Medicine-個別化医療を目指した遺伝子診断と新治療の知見】良性脳腫瘍 頭蓋咽頭腫 分子標的治療の知見

    田中 將太, 高柳 俊作, 高見 浩数, 齊藤 延人

    Neurological Surgery   50 ( 1 )   171 - 178   2022年1月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

    <文献概要>Point ・網羅的遺伝子解析により,乳頭上皮型頭蓋咽頭腫の大半にBRAF-V600E変異がみられることが判明した.・他癌腫で承認済のBRAF阻害薬,MEK阻害薬が,BRAF変異陽性乳頭上皮型頭蓋咽頭腫に著効するという症例報告がなされた.・頭蓋咽頭腫は難治な脳腫瘍であり,乳頭上皮型においては従来の手術・放射線治療に分子標的治療を加えた集学的治療が重要となろう.

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    その他リンク: https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J01228&link_issn=&doc_id=20220216220019&doc_link_id=10.11477%2Fmf.1436204542&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1436204542&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

  • 【Precision Medicine-個別化医療を目指した遺伝子診断と新治療の知見】悪性脳腫瘍 中枢神経胚細胞腫 個別化医療に向けた病態解明の最前線

    高見 浩数, 高柳 俊作, 田中 將太, 齊藤 延人

    Neurological Surgery   50 ( 1 )   39 - 50   2022年1月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

    <文献概要>Point ・遺伝子変異解析により,中枢神経胚細胞腫症例の55%においてMAPKとPI3K経路に変異がみつかり,両者は相互排他的であった.ターゲット治療はまだ開発されていない.・欧米・日本の臨床試験により,ジャーミノーマでは全脳室照射,非ジャーミノーマでは全脳室または局所照射の方向になりつつある.・腫瘍含有率の高いジャーミノーマ,12p gainのある非ジャーミノーマの予後が不良であることが報告され,今後の層別化治療につながる可能性がある.

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    その他リンク: https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J01228&link_issn=&doc_id=20220216220007&doc_link_id=10.11477%2Fmf.1436204530&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1436204530&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

  • MOLECULAR PROFILING OF SPINAL CORD EPENDYMOMA

    Erika Yamazawa, Shota Tanaka, Genta Nagae, Takayoshi Umeda, Taijun Hana, Phyo Kim, Fumi Higuchi, Toshihiro Takami, Yuta Nakanishi, Keisuke Takai, Takashi Komori, Hirokazu Takami, Masashi Nomura, Akitake Mukasa, Shunsaku Takayanagi, Kazuhiko Ishii, Hideaki Imai, Reiko Matsuura, Tsukasa Koike, Yoshihiro Kushihara, Shohei Nambu, Kazuha Kugasawa, Hiroyuki Aburatani, Nobuhito Saito

    NEURO-ONCOLOGY   23   1 - 1   2021年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

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  • 中枢神経系血管芽腫における腫瘍栄養血管塞栓術の役割 傾向スコアを用いた比較と3次元融合画像の有用性

    南部 翔平, 小泉 聡, 高柳 俊作, 石神 大一郎, 小池 司, 高見 浩数, 田中 將太, 金 太一, 齊藤 延人

    脳血管内治療   6 ( Suppl. )   S140 - S140   2021年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本脳神経血管内治療学会  

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  • DEVELOPMENT OF NOVEL TOPICAL FLUORESCENT PROBE FOR INTRAOPERATIVE RAPID DETECTION OF GLIOMA

    Shota Tanaka, Yosuke Kitagawa, Mako Kamiya, Yugo Kuriki, Kyoko Yamamoto, Takenori Shimizu, Takahide Nejo, Taijun Hana, Tsukasa Koike, Erika Yamazawa, Yoshihiro Kushihara, Satoshi Takahashi, Masashi Nomura, Hirokazu Takami, Shunsaku Takayanagi, Akitake Mukasa, Yasuteru Urano, Nobuhito Saito

    NEURO-ONCOLOGY   23   197 - 197   2021年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

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  • 成人脊髄H3K27M mutant gliomaの5例

    糸岐 一茂, 松田 葉月, 黒川 龍, 新郷 哲郎, 田中 將太, 山澤 恵梨香, 宇塚 岳夫, 樋口 芙未, 植木 敬介, 金 彪

    Brain Tumor Pathology   38 ( Suppl. )   079 - 079   2021年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 成人脊髄diffuse midline gliomaはしばしばsubclonalなH3K27M変異を有する 5症例の検討

    松田 葉月, 糸岐 一茂, 黒川 龍, 新郷 哲郎, 田中 將太, 山澤 恵梨香, 宇塚 岳夫, 樋口 芙未, 植木 敬介, 金 彪

    Brain Tumor Pathology   38 ( Suppl. )   111 - 111   2021年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • Development of novel topical fluorescent probes for intraoperative rapid detection of glioma

    Shota Tanaka, Yosuke Kitagawa, Shunsaku Takayanagi, Akitake Mukasa, Yasuteru Urano

    CANCER SCIENCE   112   526 - 526   2021年2月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY  

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  • Von Hippel-Lindau病専門外来10年間の取り組みと今後の課題

    高柳俊作, 南部翔平, 高見浩数, 田中将太, 宮脇哲, 辛正廣, 佐藤悠佑, 久米春喜, 久米春喜, 秋山奈々, 織田克利, 齊藤延人

    日本遺伝性腫瘍学会学術集会プログラム・抄録集   27th   2021年

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  • HEALTH-RELATED QUALITY OF LIFE AND SYMPTOM BURDEN IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA TREATED WITH BEVACIZUMAB BEYOND PROGRESSION: A PROSPECTIVE TRIAL

    Shota Tanaka, Yoshitaka Narita, Akitake Mukasa, Motoo Nagane, Tomokazu Aoki, Toshihiko Wakabayashi, Takeo Uzuka, Hideo Nakamura, Yoshiki Arakawa, Satoshi Suehiro, Mitsutoshi Nakada, Satoshi Morita, Mamoru Kato, Kouichi Ichimura, Ryo Nishikawa

    NEURO-ONCOLOGY   22   176 - 176   2020年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

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  • 多施設での利用を目指した深層学習を用いた脳腫瘍領域測定法の開発

    高橋雅道, 高橋雅道, 高橋慧, 高橋慧, 木下学, 三宅基隆, 河口理紗, 篠島直樹, 武笠晃丈, 齊藤邦昭, 永根基雄, 大谷亮平, 大谷亮平, 植木敬介, 田中將太, 秦暢宏, 田村郁, 立石健祐, 西川亮, 有田英之, 埜中正博, 埜中正博, 深井順也, 沖田典子, 沖田典子, 露口尚弘, 露口尚弘, 金村米博, 金村米博, 小林和馬, 小林和馬, 瀬々潤, 瀬々潤, 市村幸一, 成田善孝, 浜本隆二, 浜本隆二

    日本脳腫瘍学会プログラム・抄録集   38th   2020年

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  • EFFICACY AND SAFETY OF NIVOLUMAB IN PATIENTS WITH FIRST RECURRENCE OF GLIOBLASTOMA: A MULTICENTER, OPEN-LABEL, NON-COMPARATIVE STUDY (ONO-4538-19)

    Naoki Kagawa, Tomokazu Aoki, Kazuhiko Sugiyama, Toshihiko Wakabayashi, Yoshiki Arakawa, Shigeru Yamaguchi, Shota Tanaka, Ryo Nishikawa

    NEURO-ONCOLOGY   21   2 - 3   2019年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

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  • BIOMARK: A PHASE II STUDY OF BEVACIZUMAB BEYOND PROGRESSION FOR NEWLY DIAGNOSED GLIOBLASTOMA: SAFETY, EFFICACY AND PROSPECTIVE BIOMARKER ANALYSIS

    Koichi Ichimura, Motoo Nagane, Mamoru Kato, Yoshitaka Narita, Tomokazu Aoki, Shota Tanaka, Akitake Mukasa, Toshihiko Wakabayashi, Takeo Uzuka, Hideo Nakamura, Yoshiki Arakawa, Satoshi Suehiro, Mitsutoshi Nakada, Mai Kitahara, Yuko Hibiya, Daichi Narushima, Ritsuko Onuki, Satoshi Morita, Ryo Nishikawa

    NEURO-ONCOLOGY   21   12 - 13   2019年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

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  • 結節性硬化症診療連携チーム結成による患者受診状況の変化

    佐藤 敦志, 佐藤 悠佑, 高柳 俊作, 辛 正廣, 田中 將太, 國井 尚人, 宮垣 朝光, 澤村 裕正, 漆山 博和, 谷口 豪, 大瀬戸 久美子, 張 香里, 岡 明, 水口 雅

    脳と発達   51 ( Suppl. )   S313 - S313   2019年5月

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    記述言語:日本語   出版者・発行元:(一社)日本小児神経学会  

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  • Radiomics analysis for detection of IDH mutation of glioma using diffusion weighted sequence images

    Satoshi Takahashi, Wataru Takahashi, Shota Tanaka, Akihiro Haga, Takahiro Nakamoto, Yuuichi Suzuki, Akitake Mukasa, Shunsaku Takayanagi

    BRAIN PATHOLOGY   29   194 - 194   2019年2月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY  

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  • TERT promoter mutationはIDH wildtype LGGにおいて最も重要な予後予測因子である

    藤本健二, 藤本健二, 藤本健二, 有田英之, 有田英之, 有田英之, 山崎夏維, 山崎夏維, 松下裕子, 松下裕子, 中村大志, 中村大志, 梅原徹, 小林啓一, 田村郁, 田中將太, 白畑充章, 大谷亮平, 沖田典子, 木下学, 木下学, 金村米博, 武笠晃丈, 永根基雄, 植木敬介, 西川亮, 小森隆司, 成田善孝, 市村幸一

    日本脳腫瘍学会プログラム・抄録集   37th   2019年

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  • 様々な脳腫瘍疾患に対するがん遺伝子パネル検査(Todai Onco‐Panel)の活用について

    高柳俊作, 田中將太, 宮脇哲, 辛正廣, 中冨浩文, 牛久綾, 大瀬戸久美子, 織田克利, 高阪真路, 油谷浩幸, 間野博行, 齊藤延人

    日本家族性腫瘍学会学術集会プログラム・抄録集   25th   170   2019年

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  • TERT promoter mutationはIDH wildtype LGGにおいて最も重要な予後予測因子である

    藤本健二, 藤本健二, 藤本健二, 有田英之, 有田英之, 有田英之, 山崎夏維, 山崎夏維, 松下裕子, 松下裕子, 中村大志, 中村大志, 梅原徹, 小林啓一, 田村郁, 田中將太, 白畑充章, 大谷亮平, 沖田典子, 木下学, 木下学, 金村米博, 武笠晃丈, 永根基雄, 植木敬介, 西川亮, 小森隆司, 成田善孝, 市村幸一

    日本脳腫瘍学会プログラム・抄録集   37th   2019年

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  • 神経膠腫おける複合現実技術を用いた術中脳表電気刺激とトラクトグラフィーとの相関

    小池司, 金太一, 武田康寛, 内川裕貴, 塩出健人, 斎藤季, 高柳俊作, 田中將太, 小山博史, 齊藤延人

    日本脳腫瘍学会学術集会プログラム・抄録集   37th   2019年

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  • RADIOMICS ANALYSIS FOR DETECTION OF IDH MUTATION OF GLIOMA USING DIFFUSION TENSOR AND KURTOSIS IMAGES

    Satoshi Takahashi, Wataru Takahashi, Shota Tanaka, Akihiro Haga, Takahiro Nakamoto, Akitake Mukasa, Shunsaku Takayanagi, Yuichi Suzuki, Tsukasa Koike, Yosuke Kitagawa, Taijyun Hana, Takahide Nejo, Masashi Nomura, Nobuhito Saito

    NEURO-ONCOLOGY   20   188 - 188   2018年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

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  • 神経膠腫におけるネオアンチゲンと免疫微小環境の経時変化に関するマルチオミクス解析(Integrated Omics Analysis on Temporal Changes of Neoantigen and Tumor Microenvironment in Primary and Recurrent Gliomas)

    根城 尭英, 松下 博和, 野村 昌志, 田中 將太, 永江 玄太, 成田 善孝, 永根 基雄, 西川 亮, 植木 敬介, 油谷 浩幸, 武笠 晃丈, 垣見 和宏, 齊藤 延人

    日本癌学会総会記事   77回   1778 - 1778   2018年9月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • CLINICAL AND GENETIC CHARACTERISTICS OF DIFFUSE MIDLINE GLIOMA IN THE SPINAL CORD

    Shota Tanaka, Ryohei Otani, Hirotaka Hongo, Hazuki Matsuda, Masako Ikemura, Masashi Nomura, Shunsaku Takayanagi, Takahide Nejo, Satoshi Takahashi, Yosuke Kitagawa, Taijun Hana, Akitake Mukasa, Keisuke Ueki, Takashi Komori, Makoto Taniguchi, Nobuhito Saito, Pyo Kin

    NEURO-ONCOLOGY   19   176 - 176   2017年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

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  • IDH-MUTATED, 19q DELETED, TP53 MUTATED ANAPLASTIC GLIOMAS CONSTITUTE A SUBGROUP THAT LOOK LIKE AND BEHAVE LIKE ANAPLASTIC OLIGODENDROGLIOMAS

    Ryohei Otani, Takeo Uzuka, Fumi Higuchi, Hazuki Matsuda, Shota Tanaka, Akitake Mukasa, Kohichi Ichimura, Phyo Kim, Keisuke Ueki

    NEURO-ONCOLOGY   19   175 - 175   2017年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

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  • INTEGRATED GENOMIC AND EPIGENOMIC ANALYSIS FOR HEMANGIOBLASTOMAS OF THE CENTRAL NERVOUS SYSTEM

    Shunsaku Takayanagi, Akitake Mukasa, Masashi Nomura, Shota Tanaka, Hirofumi Nakatomi, Keisuke Ueki, Kohichi Ichimura, Hiroyuki Aburatani, Nobuhito Saito

    NEURO-ONCOLOGY   19   106 - 106   2017年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

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  • PRIMARY SPINAL CORD EWING'S SARCOMA IN 50-YEAR-OLD WOMAN: A CASE REPORT

    Satoshi Takahashi, Shunsaku Takayanagi, Masako Ikemura, Takahide Nejo, Masashi Nomura, Shunsuke Yanagisawa, Shota Tanaka, Akitake Mukasa, Nobuhito Saito

    NEURO-ONCOLOGY   19   212 - 212   2017年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

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  • THE EXPERIENCE OF MEDICAL CARE-RELATED DECISIONS AMONG MALIGNANT BRAIN TUMOR PATIENTS IN JAPAN: QUALITATIVE INTERVIEWS

    Hanako Numata, Maiko Noguchi-Watanabe, Shota Tanaka, Shunsaku Takayanagi, Akitake Mukasa, Nobuhito Saito, Noriko Yamamoto-Mitani

    NEURO-ONCOLOGY   19   211 - 211   2017年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

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  • 左頭頂葉腫瘍に対し覚醒下手術にて皮質マッピングを行った一症例

    荻野 亜希子, 兼岡 麻子, 田中 將太, 武笠 晃丈, 高柳 俊作, 井口 はるひ, 中原 康雄, 芳賀 信彦

    言語聴覚研究   14 ( 3 )   248 - 248   2017年9月

  • 初発神経膠腫におけるC-11 methionine PETと分子診断との関係および予後に関する検討

    柳澤 俊介, 高橋 美和子, 武笠 晃丈, 田中 將太, 高柳 俊作, 野村 昌志, 池村 雅子, 百瀬 敏光, 斉藤 延人

    Brain Tumor Pathology   34 ( Suppl. )   116 - 116   2017年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • Infantile myofibromatosisのoncogenesis 新規原因遺伝子PDGFRBの解析

    高柳 俊作, 武笠 晃丈, 田中 將太, 野村 昌志, 辛 正廣, 中冨 浩文, 樋渡 光輝, 滝田 順子, 牛久 哲男, 斉藤 延人

    Brain Tumor Pathology   34 ( Suppl. )   114 - 114   2017年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 分子病理と分子病態 Oncogenesis and Progression IDH1変異神経膠腫における悪性表現型と相関した標的可能シグナル伝達経路の変異(Targetable Signaling Pathway Mutations correlated with Malignant Phenotype in IDH1 Mutant Gliomas)

    立石 健祐, Chi Andrew, Cahill Daniel, 田中 将太, 脇本 浩明

    Brain Tumor Pathology   34 ( Suppl. )   075 - 075   2017年5月

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    記述言語:英語   出版者・発行元:日本脳腫瘍病理学会  

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  • THE CHARACTERISTICS OF MOLECULAR PROFILE CHANGES IN RECURRENT LOWER GRADE GLIOMAS AND THEIR IMPLICATION FOR THERAPEUTIC STRATEGY

    A. Mukasa, K. Saito, S. Tanaka, S. Takayanagi, Y. Narita, M. Nagane, K. Ueki, R. Nishikawa, H. Aburatani, N. Saito

    NEURO-ONCOLOGY   19   27 - 28   2017年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

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  • 左側頭頭頂葉腫瘍に対し硬膜下電極を用いた皮質電気刺激マッピングと覚醒下手術が機能温存に有効だった一例

    吉田 瑞, 齊藤 邦昭, 林 俊宏, 武笠 晃丈, 田中 將太, 高柳 俊作, 斉藤 延人, 辻 省次

    高次脳機能研究   37 ( 1 )   52 - 52   2017年3月

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    記述言語:日本語   出版者・発行元:(一社)日本高次脳機能障害学会  

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  • GENETICALLY-GUIDED TREATMENTS OF GLIOBLASTOMA IN THE ELDERLY POPULATION

    Shota Tanaka, Akitake Mukasa, Shunsaku Takayanagi, Shunsuke Yanagisawa, Masashi Nomura, Nobuhito Saito

    NEURO-ONCOLOGY   18   108 - 108   2016年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

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  • BRACHYURY AND ITS UPSTREAM, PI3K/AKT PATHWAY, ARE INVOLVED IN GROWTH OF SKULL BASE CHORDOMA

    Ryohei Otani, Akitake Mukasa, Masahiro Shin, Mayu Omata, Shunsaku Takayanagi, Shota Tanaka, Keisuke Ueki, Nobuhito Saito

    NEURO-ONCOLOGY   18   41 - 41   2016年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

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  • INTEGRATED GENOMIC ANALYSIS FOR VON HIPPEL-LINDAU DISEASE-RELATED AND SPORADIC HEMANGIOBLASTOMAS OF THE CENTRAL NERVOUS SYSTEM

    Shunsaku Takayanagi, Akitake Mukasai, Masashi Nomura, Shota Tanaka, Hirofumi Nakatomi, Hiroyuki Aburatani, Koichi Ichimura, Nobuhito Saito

    NEURO-ONCOLOGY   18   80 - 80   2016年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

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  • 【脳腫瘍学-基礎研究と臨床研究の進歩-】脳腫瘍の疫学と危険因子 脳腫瘍の部位別発症頻度と問題点

    武笠 晃丈, 田中 將太, 齊藤 延人

    日本臨床   74 ( 増刊7 脳腫瘍学 )   95 - 99   2016年9月

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    記述言語:日本語   出版者・発行元:(株)日本臨床社  

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  • [Incidence of brain tumors by location and related issues].

    Akitake Mukasa, Shota Tanaka, Nobuhito Saito

    Nihon rinsho. Japanese journal of clinical medicine   74 Suppl 7   95 - 99   2016年9月

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    記述言語:日本語  

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  • 診断に苦慮している小脳橋角部高悪性度腫瘍の1例

    北川 陽介, 高柳 俊作, 宮脇 哲, 田中 將太, 武笠 晃丈, 中冨 浩文, 柴原 純二, 斉藤 延人

    Brain Tumor Pathology   33 ( Suppl. )   082 - 082   2016年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 小脳腫瘍 (第1土曜特集 小脳の最新知見 : 基礎研究と臨床の最前線) -- (小脳の病態 : 小脳疾患の診療の最前線)

    田中 將太, 斉藤 延人

    医学のあゆみ   255 ( 10 )   993 - 998   2015年12月

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    記述言語:日本語   出版者・発行元:医歯薬出版  

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    その他リンク: http://search.jamas.or.jp/link/ui/2016058733

  • Validation study of the Japanese version of MD Anderson Symptom Inventory Brain Tumor Module.

    Shota Tanaka, Iori Sato, Terri S. Armstrong, Charles S. Cleeland, Tito R. Mendoza, Akitake Mukasa, Yoshitaka Narita, Kiyoko Kamibeppu, Nobuhito Saito

    JOURNAL OF CLINICAL ONCOLOGY   33 ( 15 )   2015年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

    DOI: 10.1200/jco.2015.33.15_suppl.e17658

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  • MULTI-CENTER RETROSPECTIVE COHORT STUDY OF ADULT INTRACRANIAL EPENDYMOMA: BRAIN TUMOR REGISTRY OF JAPAN 2001-2004

    Shota Tanaka, Akitake Mukasa, Yuji Uematsu, Junya Fukai, Nobuhito Saito

    NEURO-ONCOLOGY   16   2014年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

    DOI: 10.1093/neuonc/nou253.30

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  • Targetable signaling pathway mutations and progression of IDH-mutant glioma

    Hiroaki Wakimota, Shota Tanaka, William T. Curry, Franziska Loebel, Dan Zhao, Kensuke Tatelshi, Juxiang Chen, Lindsay K. Klofas, Nina Lellc, James C. Kim, Dora Dias-Santagata, Leif W. Ellison, Darrell R. Borger, Sarah-Maria Fendt, Matthew Vander Heiden, Tracy Batchelor, A. John Latrate, Daniel P. Cahill, Andrew S. Chi

    JOURNAL OF CLINICAL ONCOLOGY   32 ( 15 )   2014年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

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  • ESTABLISHMENT OF GENETICALLY DISTINCT BRAIN TUMOR STEM CELLS FROM GLIOBLASTOMA BEFORE AND AFTER MOLECULAR TARGETED THERAPY

    Shota Tanaka, Samantha Luk, Clarice Chang, John Iafrate, Daniel Cahill, Robert Martuza, Samuel Rabkin, Andrew Chi, Hiroaki Wakimoto

    NEURO-ONCOLOGY   15   216 - 216   2013年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

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  • EXPRESSION OF BRACHYURY IN CHORDOMAS: ASSOCIATION WITH MALIGNANCY

    Ryohei Otani, Akitake Mukasa, Shunsaku Takayanagi, Kuniaki Saito, Shota Tanaka, Masahiro Shin, Nobuhito Saito

    NEURO-ONCOLOGY   15   149 - 149   2013年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

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  • Association of PIK3CA-activating mutations with more disseminated disease at presentation and earlier recurrence in glioblastoma

    Shota Tanaka, Tracy Batchelor, Anthony John Iafrate, Dora Dias-Santagata, Darrell R. Borger, Leif William Ellisen, Daniel Yang, David N. Louis, Daniel P. Cahill, Andrew S. Chi

    JOURNAL OF CLINICAL ONCOLOGY   31 ( 15 )   2013年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

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  • Glioblastoma in the elderly Response

    Shota Tanaka, Ian F. Parney

    JOURNAL OF NEUROSURGERY   118 ( 4 )   784 - 785   2013年4月

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    記述言語:英語   出版者・発行元:AMER ASSOC NEUROLOGICAL SURGEONS  

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  • ANTI-TUMOR ACTIVITY OF DUAL PI3K/MTOR INHIBITORS PF-04691502 AND PF-05212384 IN GLIOBLASTOMA STEM-LIKE CELLS WITH DIFFERENTIAL PI3K PATHWAY ACTIVATION

    Shota Tanaka, Lindsay K. Klofas, Hiroaki Wakimoto, Darrell R. Borger, A. J. Iafrate, Tracy T. Batchelor, Andrew S. Chi

    NEURO-ONCOLOGY   14   26 - 26   2012年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

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  • 2. グリオーマの治療 : 海外からの最新情報(PS3-1 グリオーマ 新しい時代の到来(診断と基礎),プレナリーセッション,脳神経外科学の課題,第32回日本脳神経外科コングレス総会)

    Tanaka Shota, Chi Andrew S., Wen Patrick Y., Louis David N., Iafrate A. John, Batchelor Tracy T.

    脳神経外科ジャーナル   21   82 - 82   2012年4月

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    記述言語:英語   出版者・発行元:日本脳神経外科コングレス  

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  • Gliomatosis Cerebri: Clinical Characteristics, Management, and Outcome

    Selby G. Chen, Shota Tanaka, Ian F. Parney

    NEUROSURGERY   67 ( 2 )   561 - 561   2010年8月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    DOI: 10.1227/01.NEU.0000387049.61328.AD

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  • OUTCOMES OF STEREOTACTIC RADIOSURGERY FOR PROLACTIN-SECRETING PITUITARY ADENOMA: TUMOR CONTROL AND BIOCHEMICAL REMISSION

    Shota Tanaka, Michael J. Link, Bruce E. Pollock

    NEURO-ONCOLOGY   11 ( 5 )   661 - 661   2009年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:DUKE UNIV PRESS  

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  • FACTORS ASSOCIATED WITH PITUITARY INSUFFICIENCY AFTER STEREOTACTIC RADIOSURGERY OF PATIENTS WITH HORMONE-SECRETING PITUITARY ADENOMAS

    Shota Tanaka, Jarnes Leenstra, Robert Kline, Michael Link, Paul Brown, Bruce E. Pollock

    NEURO-ONCOLOGY   10 ( 5 )   891 - 892   2008年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

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  • 切迫脳ヘルニアを伴う破裂脳動脈瘤・脳動静脈奇形の手術―脳血管撮影なしでいかに対処するか―

    田中将太, 堤一生, 井上智弘, 安達忍, 齊藤邦昭, 國井尚人

    脳卒中の外科   35 ( 3 )   204 - 209   2007年5月

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    記述言語:日本語   出版者・発行元:The Japanese Society on Surgery for Cerebral Stroke  

    Preoperative angiography is basically essential for a patient of intracerebral hematoma, so as to check any underlying vascular anomaly such as a ruptured aneurysm or an arteriovenous malformation (AVM). When the hematoma causes impending herniation, however, we omit preoperative angiography to save time and perform emergency surgery even if a ruptured aneurysm or an AVM is highly suspected. We experienced 8 such cases during 2.5 years: 6 cases of ruptured aneurysm and 2 of AVM. Three of them achieved good recovery and none died.<br> Some special considerations and tactics are required before and during surgery to ensure safety. When a ruptured aneurysm is suspected, a microscope, a self-retractor and clips should be ready prior to surgery. The superficial temporal artery should be preserved just in case. After the craniotomy, the hematoma is evacuated partially for decompression away from the suspected aneurysm. Then, in case of premature rupture, the dissection is performed directly toward the bleeding site; otherwise sylvian fissure is dissected for aneurysm exploration. When an AVM is suspected, care must be taken not to injure the draining veins. It is safer to finish the emergency surgery after evacuating the hematoma and to go on to cerebral angiography. The resection of an AVM should then be performed in the chronic period.<br> In our experiences, we were able to perform emergency surgery safely for a ruptured aneurysm or an AVM, even when we had to omit preoperative angiography because of impending herniation.<br>

    DOI: 10.2335/scs.35.204

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▼全件表示

共同研究・競争的資金等の研究

  • HIF系経路以外の腫瘍血管新生機序解明と新規抗血管新生薬探索

    研究課題/領域番号:23K08559  2023年04月 - 2026年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    高柳 俊作, 高見 浩数, 田中 將太

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

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  • 脳腫瘍の新規術中蛍光診断システムの構築と治療への応用

    研究課題/領域番号:23H03017  2023年04月 - 2026年03月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    田中 將太, 高柳 俊作, 高見 浩数

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    配分額:18850000円 ( 直接経費:14500000円 、 間接経費:4350000円 )

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  • マルチオミクス統合解析を基にしたグリオーマ再発・悪性化機構解明と新規治療戦略創出

    研究課題/領域番号:20H03792  2020年04月 - 2023年03月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    武笠 晃丈, 永江 玄太, 菰原 義弘, 篠島 直樹, 田中 將太

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    配分額:17680000円 ( 直接経費:13600000円 、 間接経費:4080000円 )

    本研究は、グリオーマの腫瘍内多様性に着目し、その再発・悪性転化に関連して生じる変化を、主に分子プロファイルのマルチオミクス解析を基盤として解析することを目的としている。より具体的には、A)再発・悪性転化に伴うエピゲノム変化の網羅的解析を基にした腫瘍進展機構解明と治療標的創出、及び、B)再発・悪性転化に伴うグリオーマ微小環境の経時的変化解析による免疫逃避機構解明を行うための研究に注力した。
    A)の再発・悪性転化に伴うエピゲノム変化の解析においては、再発悪性化検体でのエピゲノム変化の解析を行うにあたり、2021年に改訂される脳腫瘍のWHO分類にてCDKN2A/Bのホモ欠失が、IDH変異を有する星細胞腫の悪性度(グレード)診断に必要となったため、これまで保存した検体のIDH遺伝子変異、染色体1p/19qヘテロ接合性喪失、CDKN2A/Bの欠失を、シークエンス、MLPA(multiplex ligation-dependent probe amplification)法、定量的リアルタイムPCR法にて解析した。CDKN2A/Bの欠失判定において、MLPA法と定量的リアルタイムPCR法において結果に相違があったため、適切な検査条件の検討を行うことで、真の悪性転化症例を抽出した。この他、そのプロモーターの能動的DNA脱メチル化が悪性化に関連することを先に報告したIGF2BP3遺伝子について機能解析を継続的に行った。
    B)のグリオーマ微小環境変化の免疫関連解析においては、微小環境に存在する腫瘍随伴マクロファージ(tumor-associated macrophage: TAM)の機能解析を行った。特に腫瘍やTAMより分泌されるサイトカインIL-1βにより、グリオーマ細胞の細胞増殖が3次元培養下にて引き起こされることを確認し、その詳細な機序解明のための解析を継続して施行した。

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  • 悪性脳腫瘍手術における術中判断を支援する局所噴霧式新規蛍光プローブの開発

    研究課題/領域番号:20K09365  2020年04月 - 2023年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    田中 將太

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

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  • 脊髄グリオーマの遺伝子解析と新規治療標的の探索

    研究課題/領域番号:17K10857  2017年04月 - 2021年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    田中 將太

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    脊髄グリオーマ・上衣腫の臨床像を明らかにし、予後に関連する分子マーカーを探索する目的で、獨協医科大学・都立神経病院・大阪市立大学・東京大学にて治療された脊髄グリオーマ30症例・上衣腫58症例を対象に、遺伝子解析を行った。Diffuse midline glioma, H3K27M-mutantは9例(30%)で、全例悪性、臨床像は多彩であった。IDH1-R132S変異を1例に認めた。WHOグレードは全生存期間の予後因子だが、H3K27M変異は有意でなかった。上衣腫のDNAメチル化解析では、グレード2は階層化クラスタリングにて比較的均質であったが、HOX遺伝子群により発生部位を明確に区別できた。

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  • エピゲノム制御機構の破綻によるグリオーマ発生・進展機構の解明と治療標的の探索

    研究課題/領域番号:17H04300  2017年04月 - 2020年03月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    武笠 晃丈, 永江 玄太, 篠島 直樹, 田中 將太

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    配分額:17030000円 ( 直接経費:13100000円 、 間接経費:3930000円 )

    神経膠腫(グリオーマ)発生機構のうちエピゲノム制御の異常に起因するものに焦点をあて、DNAメチル化制御異常に伴うハイドロキシメチルシトシン(5-hmc)の変化をOxidative Bisulfite(OxBS)法にて測定した。特にIDH遺伝子変異をもつグリオーマの悪性転化時の変化を解析したところ、悪性転化と関連した能動的脱メチル化領域が同定された。また、さらなる解析により、この能動的脱メチル化が共通の転写因子と関連しており、これに伴って、がん関連遺伝子の転写が制御されていることが示唆された。

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  • 脳腫瘍を特異的に標識する新規蛍光プローブの開発

    研究課題/領域番号:15K19952  2015年04月 - 2018年03月

    日本学術振興会  科学研究費助成事業  若手研究(B)

    田中 將太, 北川 陽介, 浦野 泰照, 武笠 晃丈

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    配分額:4030000円 ( 直接経費:3100000円 、 間接経費:930000円 )

    神経膠腫の安全かつ最大限の摘出には、術中蛍光プローブが有効で、5-アミノレブリン酸が保険収載され汎用されている。しかし偽陽性・偽陰性、再投与不可等の限界があるため、5-ALAを補完する局所噴霧にて診断可能な、脳腫瘍を特異的に標識する新規蛍光プローブの開発を行った。
    当科の神経膠腫の手術症例を用い、Hydroxymethyl rhodamine greenを蛍光母核に種々のアミノ酸を付加した約320種の蛍光プローブライブラリーから、凍結検体のホモジェナイズサンプルでスクリーニングを行い、さらに新鮮腫瘍検体に直接噴霧して蛍光強度の経時的変化を解析し、膠芽腫において有望な蛍光プローブを7種類選定した。

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  • 悪性神経膠腫のゲノム・エピゲノム変化による腫瘍進化機構の解明と新規標的療法の開発

    研究課題/領域番号:26293321  2014年04月 - 2018年03月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    武笠 晃丈, 田中 將太, 齋藤 邦昭

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    配分額:15990000円 ( 直接経費:12300000円 、 間接経費:3690000円 )

    神経膠腫の悪性化機序を理解し、これに対応した治療戦略を構築するため、次世代シークエンサーなどを用いたオミクス解析技術を駆使し、再発・悪性転化を遂げた神経膠腫の初発・再発時の計122腫瘍検体の比較解析を行った。悪性転化に伴うメチル化の変化では、G-CIMPの特定のゲノムDAN領域の脱メチルが特徴的であった。これら脱メチル化領域は遺伝子の転写調整には無関係である部位に多かった。悪性化に伴い発現変化している遺伝子は、細胞周期に関連したもの多かった。Temozolomide治療後の hypermutator phenotype が観察されるほか、PI3K-AKT経路関連分子の遺伝子異常を高率に認めた。

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  • 腫瘍血管新生の機序解明と新規治療開発を目的とした血管芽腫原因遺伝子の探索

    研究課題/領域番号:26670636  2014年04月 - 2017年03月

    日本学術振興会  科学研究費助成事業  挑戦的萌芽研究

    武笠 晃丈, 齊藤 邦昭, 中村 英二郎, 丹羽 明, 田中 將太

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    配分額:3640000円 ( 直接経費:2800000円 、 間接経費:840000円 )

    本研究は、著明な腫瘍血管新生を認める血管芽腫のゲノム解析を通して、その血管新生に関わる原因遺伝子同定などを目標とした。我々が収集した全32例の血管芽腫のVHL遺伝子を中心とした遺伝子変異、メチル化解析の結果、VHL病患者、孤発性患者のいずれの検体においても、VHLの2-hitによる不活化が多い事が判明した。但し、孤発例では、メチル化によるVHL不活化や染色体6番、10番の欠失が多いことが特徴的であった。VHL病の好発腫瘍である腎癌においては、VHLだけでなく、PBRM1やBAP1などの遺伝子異常が多い事が知られているが、我々のHB症例には、これらの遺伝子変異は認められなかった。

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  • 乏突起膠腫のエピジェネティックな腫瘍制御因子解析と新規分子診断マーカーの確立

    研究課題/領域番号:25861257  2013年04月 - 2016年03月

    日本学術振興会  科学研究費助成事業  若手研究(B)

    田中 將太

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    配分額:4030000円 ( 直接経費:3100000円 、 間接経費:930000円 )

    乏突起膠腫において染色体1p,19qのヘテロ接合性の消失は治療反応性や予後を予測する重要なバイオマーカーだが、統一された検査法はなく、サロゲートマーカーとしてmyelin transcription factor 1-like (MYT1L)に着目し、免疫染色で判定可能な抗体の開発研究を企画した。作成済の複数のポリクローナル抗体および市販抗MYT1L抗体はMYT1L強制発現細胞をウェスタンブロット・免疫染色で認識したが、ヒト腫瘍検体を用いた検証でqRT-PCRによるMYT1L発現量との相関はなかった。WHO脳腫瘍分類の2016年改訂で必須となった1p/19q共欠失の判定法の標準化が急務である。

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