2024/03/27 更新

写真a

オカダ マサヤス
岡田 正康
OKADA Masayasu
所属
脳研究所 助教
職名
助教
外部リンク

代表的な業績

学位

  • 博士(医学) ( 2016年3月   新潟大学 )

研究分野

  • ライフサイエンス / 脳神経外科学

  • ライフサイエンス / 医化学  / 神経生化学

  • ライフサイエンス / 実験病理学

  • ライフサイエンス / 神経形態学

経歴(researchmap)

  • 新潟大学脳研究所   腫瘍病態学分野   助教

    2023年4月 - 現在

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    国名:日本国

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経歴

  • 新潟大学   脳研究所   助教

    2023年4月 - 現在

  • 新潟大学   医歯学総合病院 脳神経外科   助教

    2019年4月 - 2023年3月

  • 新潟大学   医歯学総合病院 脳神経外科   特任助教

    2017年4月 - 2019年3月

  • 新潟大学   研究推進機構 超域学術院   特別研究員

    2016年4月 - 2017年3月

所属学協会

▶ 全件表示

 

論文

  • JNK1-Dependent Phosphorylation of GAP-43 Serine 142 is a Novel Molecular Marker for Axonal Growth. 査読 国際誌

    Masayasu Okada, Yosuke Kawagoe, Toshiyuki Takasugi, Motohiro Nozumi, Yasuyuki Ito, Hayato Fukusumi, Yonehiro Kanemura, Yukihiko Fujii, Michihiro Igarashi

    Neurochemical research   47 ( 9 )   2668 - 2682   2022年3月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Mammalian axon growth has mechanistic similarities with axon regeneration. The growth cone is an important structure that is involved in both processes, and GAP-43 (growth associated protein-43 kDa) is believed to be the classical molecular marker. Previously, we used growth cone phosphoproteomics to demonstrate that S96 and T172 of GAP-43 in rodents are highly phosphorylated sites that are phosphorylated by c-jun N-terminal protein kinase (JNK). We also revealed that phosphorylated (p)S96 and pT172 antibodies recognize growing axons in the developing brain and regenerating axons in adult peripheral nerves. In rodents, S142 is another putative JNK-dependent phosphorylation site that is modified at a lower frequency than S96 and T172. Here, we characterized this site using a pS142-specific antibody. We confirmed that pS142 was detected by co-expressing mouse GAP-43 and JNK1. pS142 antibody labeled growth cones and growing axons in developing mouse neurons. pS142 was sustained until at least nine weeks after birth in mouse brains. The pS142 antibody could detect regenerating axons following sciatic nerve injury in adult mice. Comparison of amino acid sequences indicated that rodent S142 corresponds to human T151, which is predicted to be a substrate of the MAPK family, which includes JNK. Thus, we confirmed that the pS142 antibody recognized human phospho-GAP-43 using activated JNK1, and also that its immunostaining pattern in neurons differentiated from human induced pluripotent cells was similar to those observed in mice. These results indicate that the S142 residue is phosphorylated by JNK1 and that the pS142 antibody is a new candidate molecular marker for axonal growth in both rodents and human.

    DOI: 10.1007/s11064-022-03580-6

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

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

    Cancers   14 ( 3 )   2022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)  

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

    DOI: 10.3390/cancers14030770

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  • Phosphorylation of GAP-43 T172 is a molecular marker of growing axons in a wide range of mammals including primates 査読 国際誌

    Masayasu Okada, Yosuke Kawagoe, Yuta Sato, Motohiro Nozumi, Yuya Ishikawa, Atsushi Tamada, Hiroyuki Yamazaki, Yuko Sekino, Yonehiro Kanemura, Yohei Shinmyo, Hiroshi Kawasaki, Naoko Kaneko, Kazunobu Sawamoto, Yukihiko Fujii, Michihiro Igarashi

    Molecular Brain   14 ( 1 )   66 - 66   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)   出版者・発行元:Springer Science and Business Media LLC  

    <title>Abstract</title>GAP-43 is a vertebrate neuron-specific protein and that is strongly related to axon growth and regeneration; thus, this protein has been utilized as a classical molecular marker of these events and growth cones. Although GAP-43 was biochemically characterized more than a quarter century ago, how this protein is related to these events is still not clear. Recently, we identified many phosphorylation sites in the growth cone membrane proteins of rodent brains. Two phosphorylation sites of GAP-43, S96 and T172, were found within the top 10 hit sites among all proteins. S96 has already been characterized (Kawasaki et al., 2018), and here, phosphorylation of T172 was characterized. In vitro (cultured neurons) and in vivo, an antibody specific to phosphorylated T172 (pT172 antibody) specifically recognized cultured growth cones and growing axons in developing mouse neurons, respectively. Immunoblotting showed that pT172 antigens were more rapidly downregulated throughout development than those of pS96 antibody. From the primary structure, this phosphorylation site was predicted to be conserved in a wide range of animals including primates. In the developing marmoset brainstem and in differentiated neurons derived from human induced pluripotent stem cells, immunoreactivity with pT172 antibody revealed patterns similar to those in mice. pT172 antibody also labeled regenerating axons following sciatic nerve injury. Taken together, the T172 residue is widely conserved in a wide range of mammals including primates, and pT172 is a new candidate molecular marker for growing axons.

    DOI: 10.1186/s13041-021-00755-0

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    その他リンク: http://link.springer.com/article/10.1186/s13041-021-00755-0/fulltext.html

  • Phosphoproteomic and bioinformatic methods for analyzing signaling in vertebrate axon growth and regeneration. 査読 国際誌

    Michihiro Igarashi, Asami Kawasaki, Yuya Ishikawa, Atsuko Honda, Masayasu Okada, Shujiro Okuda

    Journal of neuroscience methods   339   108723 - 108723   2020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)  

    Phosphorylation is the most important post-translational modification of proteins in many cells, including neurons. Phosphoproteomics is a relatively new technique for comprehensively identifying phosphorylation sites in the whole proteome of a given system. We applied this method to developmental neurobiology research to understand the signaling pathways that regulate the mammalian growth cone, which is formed at the tips of developing neurites to ensure accurate neuronal network formation. Using this powerful technique, we identified at least four phosphorylation sites tightly associated with axon growth. Because phosphoproteomic results include relatively large numbers of phosphopeptides, the data are typically analyzed using bioinformatics. We utilized three bioinformatics tools to identify the responsible protein kinases, the putative functions of the phosphorylated protein groups, and the evolutional aspects of the phosphorylated proteins. Collectively, these data indicate phosphoproteomics is a cutting-edge tool for neuroscience research.

    DOI: 10.1016/j.jneumeth.2020.108723

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  • The JNK pathway represents a novel target in the treatment of rheumatoid arthritis through the suppression of MMP-3. 査読 国際誌

    Tomotake Kanai, Naoki Kondo, Masayasu Okada, Hiroshige Sano, Go Okumura, Yasufumi Kijima, Akira Ogose, Hiroyuki Kawashima, Naoto Endo

    Journal of orthopaedic surgery and research   15 ( 1 )   87 - 87   2020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)  

    BACKGROUND AND AIM: The pathophysiology of rheumatoid arthritis (RA) is characterized by excess production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) by neutrophils and macrophages in synovium. Additionally, these cytokines promote the production of reactive oxygen species (ROS), and increased production of matrix metalloproteinases (MMPs), including MMP-3, in synoviocytes that result in joint destruction. There is limited information on how proteolytic enzymes such as MMP-3 can be regulated. We evaluated the effect of the antioxidant N-acetylcysteine (NAC) on RA and identified the relationship between the c-Jun N terminal kinase (JNK) pathway and MMP-3. We hypothesized that elucidating this relationship would lead to novel therapeutic approaches to RA treatment and management. METHODS: We investigated the effect of administering a low dose (1000 μM or less) of an antioxidant (NAC) to human rheumatoid fibroblast-like synoviocytes (MH7A cells). We also investigated the response of antioxidant genes such as nuclear factor erythroid -derived 2-related factor 2 (Nrf2) and Sequestosome 1 (p62). The influence of MMP-3 expression on the JNK pathway leading to joint destruction and the mechanisms underlying this relationship were investigated through primary dispersion culture cells collected from the synovial membranes of RA patients, consisting of rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLS). RESULTS: Low-dose NAC (1000 μM) increased the expression of Nrf2 and phospho-p62 in MH7A cells, activating antioxidant genes, suppressing the expression of MMP-3, and inhibiting the phosphorylation of JNK. ROS, MMP-3 expression, and IL-6 was suppressed by administering 30 μM of SP600125 (a JNK inhibitor) in MH7A cells. Furthermore, the administration of SP600125 (30 μM) to RA-FLS suppressed MMP-3. CONCLUSIONS: We demonstrated the existence of an MMP-3 suppression mechanism that utilizes the JNK pathway in RA-FLS. We consider that the JNK pathway could be a target for future RA therapies.

    DOI: 10.1186/s13018-020-01595-9

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  • MGMT Expression Contributes to Temozolomide Resistance in H3K27M-Mutant Diffuse Midline Gliomas 査読 国際誌

    Hideaki Abe, Manabu Natsumeda, Masayasu Okada, Jun Watanabe, Yoshihiro Tsukamoto, Yu Kanemaru, Junichi Yoshimura, Makoto Oishi, Rintaro Hashizume, Akiyoshi Kakita, Yukihiko Fujii

    Frontiers in Oncology   9   1568 - 1568   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)  

    © Copyright © 2020 Abe, Natsumeda, Okada, Watanabe, Tsukamoto, Kanemaru, Yoshimura, Oishi, Hashizume, Kakita and Fujii. Diffuse midline gliomas (DMGs) show resistance to many chemotherapeutic agents including temozolomide (TMZ). Histone gene mutations in DMGs trigger epigenetic changes including DNA hypomethylation, one of which is a frequent lack of O6-methyl-guanine-DNA methyltransferase (MGMT) promoter methylation, resulting in increased MGMT expression. We established the NGT16 cell line with HIST1H3B K27M and ACVR1 G328E gene mutations from a DMG patient and used this cell line and other DMG cell lines with H3F3A gene mutation (SF7761, SF8628, JHH-DIPG1) to analyze MGMT promoter methylation, MGMT protein expression, and response to TMZ. Three out of 4 DMG cell lines (NGT16, SF8628, and JHH-DIPG1) had unmethylated MGMT promoter, increased MGMT expression, and showed resistance to TMZ treatment. SF7761 cells with H3F3A gene mutation showed MGMT promoter methylation, lacked MGMT expression, and sensitivity to TMZ treatment. NGT16 line showed response to ALK2 inhibitor K02288 treatment in vitro. We confirmed in vitro that MGMT expression contributes to TMZ resistance in DMG cell lines. There is an urgent need to develop new strategies to treat TMZ-resistant DMGs.

    DOI: 10.3389/fonc.2019.01568

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  • Phosphorylation sites of microtubule-associated protein 1B (MAP 1B) are involved in axon growth and regeneration. 査読 国際誌

    Ishikawa Y, Okada M, Honda A, Ito Y, Tamada A, Endo N, Igarashi M

    Molecular brain   12 ( 1 )   93 - 93   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)  

    DOI: 10.1186/s13041-019-0510-z

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  • Dramatic response of BRAF V600E-mutant epithelioid glioblastoma to combination therapy with BRAF and MEK inhibitor: establishment and xenograft of a cell line to predict clinical efficacy. 査読 国際誌

    Kanemaru Y, Natsumeda M, Okada M, Saito R, Kobayashi D, Eda T, Watanabe J, Saito S, Tsukamoto Y, Oishi M, Saito H, Nagahashi M, Sasaki T, Hashizume R, Aoyama H, Wakai T, Kakita A, Fujii Y

    Acta neuropathologica communications   7 ( 1 )   119 - 119   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)  

    DOI: 10.1186/s40478-019-0774-7

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  • Growth Cone Phosphoproteomics Reveals that GAP-43 Phosphorylated by JNK Is a Marker of Axon Growth and Regeneration. 査読 国際誌

    Asami Kawasaki, Masayasu Okada, Atsushi Tamada, Shujiro Okuda, Motohiro Nozumi, Yasuyuki Ito, Daiki Kobayashi, Tokiwa Yamasaki, Ryo Yokoyama, Takeshi Shibata, Hiroshi Nishina, Yutaka Yoshida, Yukihiko Fujii, Kosei Takeuchi, Michihiro Igarashi

    iScience   4   190 - 203   2018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)  

    Neuronal growth cones are essential for nerve growth and regeneration, as well as for the formation and rearrangement of the neural network. To elucidate phosphorylation-dependent signaling pathways and establish useful molecular markers for axon growth and regeneration, we performed a phosphoproteomics study of mammalian growth cones, which identified >30,000 phosphopeptides of ∼1,200 proteins. The phosphorylation sites were highly proline directed and primarily MAPK dependent, owing to the activation of JNK, suggesting that proteins that undergo proline-directed phosphorylation mediate nerve growth in the mammalian brain. Bioinformatics analysis revealed that phosphoproteins were enriched in microtubules and the cortical cytoskeleton. The most frequently phosphorylated site was S96 of GAP-43 (growth-associated protein 43-kDa), a vertebrate-specific protein involved in axon growth. This previously uncharacterized phosphorylation site was JNK dependent. S96 phosphorylation was specifically detected in growing and regenerating axons as the most frequent target of JNK signaling; thus it represents a promising new molecular marker for mammalian axonal growth and regeneration.

    DOI: 10.1016/j.isci.2018.05.019

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  • Missense mutation of NRAS is associated with malignant progression in neurocutaneous melanosis. 国際誌

    Haruhiko Takahashi, Manabu Natsumeda, Norikazu Hara, Akihide Koyama, Hiroshi Shimizu, Akinori Miyashita, Daiken Satake, Yoshihiro Mouri, Jun Tsukano, Keita Kawabe, Yoshihiro Tsukamoto, Masayasu Okada, Ryosuke Ogura, Akihiko Yuki, Hajime Umezu, Akiyoshi Kakita, Takeshi Ikeuchi, Makoto Oishi

    Acta neuropathologica communications   12 ( 1 )   14 - 14   2024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)  

    Neurocutaneous melanosis (NCM) is a rare congenital neurocutaneous syndrome characterized by congenital melanocytic nevus of skin and abnormal proliferation of leptomeningeal melanocytes. Early acquisition of post-zygotic somatic mutations has been postulated to underlie the pathogenesis of NCM. The pathogenesis of NCM remains to be fully elucidated, and treatment options have not been established. Here, we report for the first time, multiregional genomic analyses in a 3-year-old autopsied girl with leptomeningeal melanomatosis associated with NCM, in which a ventriculo-peritoneal (VP) shunt was inserted for the treatment of hydrocephalus. The patient expired six months after the onset due to respiratory failure caused by abdominal dissemination via VP shunt. We performed multiregional exome sequencing to identify genomic differences among brain and abdominal tumors, nevus, and normal tissues. A total of 87 somatic mutations were found in 71 genes, with a significantly large number of gene mutations found in the tumor site. The genetic alterations detected in the nevus were only few and not shared with other sites. Three mutations, namely GNAQ R183Q, S1PR3 G89S and NRAS G12V, considered pathogenic, were found, although S1PR3 mutations have not been previously reported in melanocytic tumors. GNAQ and S1PR3 mutations were shared in both tumor and normal sites. Moreover, the mutant allele frequencies of the two mutations were markedly higher in tumor sites than in normal sites, with copy-neutral loss-of-heterozygosity (CN-LOH) occurring in tumor. NRAS mutation was found only in the abdominal tumor and was thought to be responsible for malignant progression in the present case. Multiregional comprehensive genetic analysis may lead to discovering novel driver mutations associated with tumorigenesis and targeted therapy.

    DOI: 10.1186/s40478-024-01723-0

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  • Reliable detection of genetic alterations in cyst fluid DNA for the diagnosis of brain tumors. 国際誌

    Jotaro On, Manabu Natsumeda, Haruhiko Takahashi, Akihide Koyama, Satoshi Shibuma, Nao Shibata, Jun Watanabe, Shoji Saito, Yu Kanemaru, Yoshihiro Tsukamoto, Masayasu Okada, Ryosuke Ogura, Takeyoshi Eda, Mari Tada, Hiroshi Shimizu, Jun-Ichi Adachi, Kazuhiko Mishima, Ryo Nishikawa, Akiyoshi Kakita, Makoto Oishi

    Journal of neuro-oncology   166 ( 2 )   273 - 282   2024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)  

    PURPOSE: Liquid biopsy of cyst fluid in brain tumors has not been extensively studied to date. The present study was performed to see whether diagnostic genetic alterations found in brain tumor tissue DNA could also be detected in cell-free DNA (cfDNA) of cyst fluid in cystic brain tumors. METHODS: Cyst fluid was obtained from 22 patients undergoing surgery for a cystic brain tumor with confirmed genetic alterations in tumor DNA. Pathological diagnoses based on WHO 2021 classification and diagnostic alterations in the tumor DNA, such as IDH1 R132H and TERT promoter mutation for oligodendrogliomas, were detected by Sanger sequencing. The same alterations were analyzed by both droplet digital PCR (ddPCR) and Sanger sequencing in cyst fluid cfDNA. Additionally, multiplex ligation-dependent probe amplification (MLPA) assays were performed to assess 1p/19q status, presence of CDKN2A loss, PTEN loss and EGFR amplification, to assess whether differentiating between astrocytomas and oligodendrogliomas and grading is possible from cyst fluid cfDNA. RESULTS: Twenty-five genetic alterations were found in 22 tumor samples. All (100%) alterations were detected in cyst fluid cfDNA by ddPCR. Twenty of the 25 (80%) alterations were also detected by Sanger sequencing of cyst fluid cfDNA. Variant allele frequency (VAF) in cyst fluid cfDNA was comparable to that of tumor DNA (R = 0.62, Pearson's correlation). MLPA was feasible in 11 out of 17 (65%) diffuse gliomas, with close correlation of results between tumor DNA and cyst fluid cfDNA. CONCLUSION: Cell-free DNA obtained from cyst fluid in cystic brain tumors is a reliable alternative to tumor DNA when diagnosing brain tumors.

    DOI: 10.1007/s11060-023-04555-5

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  • Multi-omics analyses of choroid plexus carcinoma cell lines reveal potential targetable pathways and alterations. 国際誌

    Dina Hesham, Jotaro On, Nouran Alshahaby, Nada Amer, Sameh Magdeldin, Masayasu Okada, Yoshihiro Tsukamoto, Tetsuya Hiraishi, Chihaya Imai, Shujiro Okuda, Toshifumi Wakai, Akiyoshi Kakita, Makoto Oishi, Shahenda El-Naggar, Manabu Natsumeda

    Journal of neuro-oncology   166 ( 1 )   27 - 38   2024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)  

    PURPOSE: Choroid plexus carcinomas (CPCs) are extremely rare brain tumors and carry a dismal prognosis. Treatment options are limited and there is an urgent need to develop models to further research. In the present study, we established two CPC cell lines and performed multi-omics analyses. These cell lines serve as valuable models to propose new treatments in these rare but deadly brain tumors. METHODS: Multi-omic profiling including, (i) methylation array (EPIC 850 K), (ii) whole genome sequencing (WGS), (iii) CANCERPLEX cancer genome panel testing, (iv) RNA sequencing (RNA-seq), and (v) proteomics analyses were performed in CCHE-45 and NGT131 cell lines. RESULTS: Both cell lines were classified as methylation class B. Both harbored pathogenic TP53 point mutations; CCHE-45 additionally displayed TP53 loss. Furthermore, alterations of the NOTCH and WNT pathways were also detected in both cell lines. Two protein-coding gene fusions, BZW2-URGCP, and CTTNBP2-ERBB4, mutations of two oncodrivers, GBP-4 and KRTAP-12-2, and several copy number alterations were observed in CCHE-45, but not NGT131. Transcriptome and proteome analysis identified shared and unique signatures, suggesting that variability in choroid plexus carcinoma tumors may exist. The discovered difference's importance and implications highlight the possible diversity of choroid plexus carcinoma and call for additional research to fully understand disease pathogenesis. CONCLUSION: Multi-omics analyses revealed that the two choroid plexus carcinoma cell lines shared TP53 mutations and other common pathway alterations and activation of NOTCH and WNT pathways. Noticeable differences were also observed. These cell lines can serve as valuable models to propose new treatments in these rare but deadly brain tumors.

    DOI: 10.1007/s11060-023-04484-3

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  • 最先端医療の今 ヒト神経軸索伸長機構におけるGAP-43のリン酸化解析

    岡田 正康, 大石 誠, 五十嵐 道弘

    Medical Science Digest   49 ( 13 )   726 - 727   2023年12月

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    記述言語:日本語   出版者・発行元:(株)ニュー・サイエンス社  

    我々は,新生仔ラット(齧歯類)脳細胞の成長円錐をリン酸化プロテオミクス解析し,高頻度リン酸化タンパク質として成長関連タンパク質-43kDa(GAP-43)とそのキナーゼとしてJNKを同定した。齧歯類で検証を積み重ねた上,データベースを利用した齧歯類と霊長類のアミノ酸配列の相同性解析を元に,霊長類脳をリン酸化プロテオミクス解析するなどし,GAP-43のリン酸化について臨床応用を検証したプロセスを概説する。現在齧歯類の研究で発見したタンパク質のリン酸化シグナル伝達経路に関してヒト中枢神経疾患解析や治療へ応用を試みているが,一連の研究方法は他の疾患を解明においても一考の価値があるものと考える。(著者抄録)

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  • Clinical, imaging, and molecular features of radiation-induced glioblastomas developing more than 20 years after radiation therapy for intracranial germinomatous germ cell tumor: illustrative cases. 国際誌

    Yoshihiro Tsukamoto, Manabu Natsumeda, Haruhiko Takahashi, Asuka Ueno, Kiichi Sakai, Kazuki Shida, Hiroki Seto, Taiki Saito, Satoshi Shibuma, Yoko Nakayama, Yuki Tanaka, Toshimichi Nakano, Atsushi Ohta, Katsuya Maruyama, Masayasu Okada, Takeyoshi Eda, Yasuhiro Seki, Yuichirou Yoneoka, Hiroshi Shimizu, Kouichirou Okamoto, Akiyoshi Kakita, Makoto Oishi

    Journal of neurosurgery. Case lessons   6 ( 16 )   2023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)  

    BACKGROUND: Germinomatous germ cell tumor is highly sensitive to chemoradiotherapy; patients are expected to survive for decades. Many radiation-induced malignant gliomas (RIMGs) occur >10 years after radiotherapy. Standard therapy for RIMGs has not been established because of the lesion's rarity, the patient's shorter survival period, and the risk of radiation necrosis by repeat radiation. OBSERVATIONS: Two patients, a 32-year-old man and a 50-year-old man, developed glioblastomas more than 20 years after radiation monotherapy for germinoma with or without mature teratoma. The first patient showed a tumor in the left frontotemporal region with disseminated lesions and died 2 months after partial resection of the tumor without responding to the chemotherapy with temozolomide and bevacizumab. Methylation classifier analysis classified the pathology as closest to diffuse pediatric-type high-grade glioma, Rtk1 subtype. The second patient showed a tumor mass in the brainstem and left cerebellar peduncle, which worsened progressively during chemotherapy with temozolomide and bevacizumab. The tumor transiently responded to stereotactic radiotherapy with the CyberKnife. However, the patient died of RIMG recurrence-related aspiration pneumonia 11 months after the biopsy. Methylation classifier analysis classified the pathology as closest to infratentorial pilocytic astrocytoma. LESSONS: Chemoradiotherapy may improve the survival of patients with RIMGs. Furthermore, molecular features may influence the clinical, locoregional, and pathological features of RIMG.

    DOI: 10.3171/CASE23361

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  • プロラクチン産生下垂体腺腫が頸部に転移したPit-1陽性下垂体がんの一例

    岡田 正康, 植木 雄志, 棗田 学, 大石 誠, 近藤 修平, 梅津 哉, 柿田 明美, 藤井 幸彦

    Brain Tumor Pathology   40 ( Suppl. )   144 - 144   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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  • Administration of glucocorticoids prior to liquid biopsy dramatically reduces the detection rate of <i>MYD88 L265P</i> mutation in cerebrospinal fluid of primary CNS lymphoma patients 国際誌

    Haruhiko Takahashi, Manabu Natsumeda, Jotaro On, Jun Watanabe, Mari Tada, Hiroshi Shimizu, Yoshihiro Tsukamoto, Masayasu Okada, Makoto Oishi, Jun Takizawa, Yasuhiko Hayashi, Yasufumi Masaki, Akiyoshi Kakita, Yukihiko Fujii

    Leukemia &amp; Lymphoma   64 ( 6 )   1219 - 1222   2023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:Informa UK Limited  

    DOI: 10.1080/10428194.2023.2199895

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  • Rheumatoid Arthritis and Reactive Oxygen Species: A Review. 国際誌

    Naoki Kondo, Tomotake Kanai, Masayasu Okada

    Current issues in molecular biology   45 ( 4 )   3000 - 3015   2023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)  

    Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease that causes progressive joint damage and can lead to lifelong disability. Numerous studies support the hypothesis that reactive oxygen species (ROS) are associated with RA pathogenesis. Recent advances have clarified the anti-inflammatory effect of antioxidants and their roles in RA alleviation. In addition, several important signaling pathway components, such as nuclear factor kappa B, activator-protein-1, nuclear factor (erythroid-derived 2)-like 2/kelch-like associated protein, signal transducer and activator of transcription 3, and mitogen-activated protein kinases, including c-Jun N-terminal kinase, have been identified to be associated with RA. In this paper, we outline the ROS generation process and relevant oxidative markers, thereby providing evidence of the association between oxidative stress and RA pathogenesis. Furthermore, we describe various therapeutic targets in several prominent signaling pathways for improving RA disease activity and its hyper oxidative state. Finally, we reviewed natural foods, phytochemicals, chemical compounds with antioxidant properties and the association of microbiota with RA pathogenesis.

    DOI: 10.3390/cimb45040197

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  • Elevated ratio of C-type lectin-like receptor 2 level and platelet count (C2PAC) aids in the diagnosis of post-operative venous thromboembolism in IDH-wildtype gliomas. 国際誌

    Kazuhiro Ando, Manabu Natsumeda, Masahide Kawamura, Kamon Shirakawa, Masayasu Okada, Yoshihiro Tsukamoto, Takeyoshi Eda, Jun Watanabe, Shoji Saito, Haruhiko Takahashi, Akiyoshi Kakita, Makoto Oishi, Yukihiko Fujii

    Thrombosis research   223   36 - 43   2023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)  

    INTRODUCTION: Podoplanin (PDPN) is known to induce platelet aggregation via interacting with the C-type lectin-like receptor-2 on platelets and is involved in postoperative venous thromboembolism (VTE) formation. In this study, we investigate the correlation between soluble C-type lectin-like receptor (sCLEC-2) levels and PDPN expression in patients with high grade gliomas and the relationship between sCLEC-2 levels and the occurrence of VTE. MATERIALS AND METHODS: Forty-four patients harboring high grade gliomas, treated surgically at the Department of Neurosurgery, Niigata University from April 2018 to August 2020, were included. Patients with high grade gliomas were divided into isocitrate dehydrogenase (IDH)- wildtype and mutant groups, and the presence or absence of VTE and the intensity of PDPN by immunohistochemistry were confirmed. Platelet counts, as well as plasma sCLEC-2 and PDPN were measured in these patients. Furthermore, the levels of sCLEC-2 concentration were divided by the platelet count (C2PAC index) for comparison. RESULTS: IDH-wildtype glioma patients highly expressed PDPN (P < 0.001) compared to IDH-mutant glioma patients. In total, 9 (20.5 %) patients were diagnosed with VTE during the follow-up period, of which 8 patients harbored IDH-wildtype gliomas, and one patient an IDH-mutant glioma. Mean sCLEC-2 levels and C2PAC index in patients with IDH-wildtype gliomas were significantly higher than that of low or no PDPN expression group, which included patients with IDH-mutant gliomas (P = 0.0004, P = 0.0002). In patients with IDH-wildtype gliomas, the C2PAC index in patients with VTE was significantly higher than in patients without VTE (P = 0.0492). The optimal cutoff point of C2PAC for predicting VTE in IDH-wildtype glioma patients was 3.7 with a sensitivity of 87.5 % and specificity of 51.9 %. CONCLUSION: Platelet activation is strongly involved in the development of VTE in patients with IDH-wildtype high grade gliomas, and C2PAC index is a potential marker to detect VTE formation after surgery.

    DOI: 10.1016/j.thromres.2023.01.018

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  • A Collision Tumor of Pit-1/SF-1-positive Double Pituitary Adenoma and a Craniopharyngioma Coexisting with Graves' Disease.

    Haruhiko Kikuta, Shinya Jinguji, Taku Sato, Mudathir Bakhit, Ryo Hiruta, Yusuke Sato, Rei Sekine, Hayato Tanabe, Masayasu Okada, Kiyoshi Saito, Masazumi Fujii

    NMC case report journal   10   169 - 175   2023年

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    記述言語:英語  

    Double or multiple pituitary adenomas expressing different types of transcription factors and collision tumors of pituitary adenomas and craniopharyngiomas are rare. In this report, we present a case of pituitary adenoma of two different cell populations, Pit-1 and SF-1, and an adenoma and craniopharyngioma collision tumor with coexisting Graves' disease. The patient had a 16-mm pituitary tumor with pituitary stalk calcification and optic chiasm compression but no visual dysfunction. Based on hormonal profile results, the tumor in the sella was considered a nonfunctioning pituitary adenoma; nevertheless, the pituitary stalk was invaded by a different lesion, which was later confirmed to be a craniopharyngioma. Using an endoscopic endonasal approach, the pituitary adenoma was removed; however, a small remnant remained medial to the right cavernous sinus. Because the pituitary stalk lesion was isolated from the pituitary adenoma, it was preserved to maintain pituitary function. Three years after the initial surgery, the patient suffered from Graves' disease and was treated with antithyroid medications. However, the intrasellar residual and pituitary stalk lesions gradually increased in size. A second surgery was performed, and the residual intrasellar and stalk lesions were completely removed. As per the initial and second histopathologies, the pituitary adenoma comprised different cell groups positive for thyroid-(TSH) and follicle-stimulating hormones, and each cell group was positive for Pit-1 and SF-1. The pituitary stalk lesion was an adamantinomatous craniopharyngioma. We believe that TSH-producing adenoma was involved in the development of Graves' disease or that treatment for Graves' disease increased TSH-producing adenoma.

    DOI: 10.2176/jns-nmc.2022-0396

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  • リン酸化プロテオミクスによる神経軸索成長のメカニズム解明

    岡田 正康

    神経化学   61 ( 2 )   90 - 95   2022年12月

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    記述言語:日本語   出版者・発行元:(一社)日本神経化学会  

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  • 髄液よりH3K27M変異が検出可能なdiffuse midline gliomaの検討

    棗田 学, 温 城太郎, 渡邉 潤, 高橋 陽彦, 塚本 佳広, 岡田 正康, 平石 哲也, 吉村 淳一, 大石 誠, 藤井 幸彦

    小児の脳神経   47 ( 4 )   358 - 364   2022年11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  

    Diffuse midline glioma(DMG)の80%以上がヒストンH3K27M変異を有する.橋に局在する病変は摘出術の適応はなく,針生検でも重篤な合併症が生じ得るためDMGに対してliquid biopsyの確立が切望される.我々は初発時に腰椎穿刺で採取した脳脊髄液よりH3K27Mを同定するのは困難と報告した.本稿では,多発病変および播種病変を有しliquid biopsyによりH3K27M変異と同定された2症例を紹介し,liquid biopsyの恩恵を受ける症例の特徴について迫る.(著者抄録)

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    その他リンク: https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00650&link_issn=&doc_id=20230215270002&doc_link_id=10.34544%2Fjspn.47.4_358&url=https%3A%2F%2Fdoi.org%2F10.34544%2Fjspn.47.4_358&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

  • Epigenetic upregulation of Schlafen11 renders WNT- and SHH- activated medulloblastomas sensitive to cisplatin. 国際誌

    Satoshi Nakata, Junko Murai, Masayasu Okada, Haruhiko Takahashi, Tyler H Findlay, Kristen Malebranche, Akhila Parthasarathy, Satoshi Miyashita, Ramil Gabdulkhaev, Ilan Benkimoun, Sabine Druillennec, Sara Chabi, Eleanor Hawkins, Hiroaki Miyahara, Kensuke Tateishi, Shinji Yamashita, Shiori Yamada, Taiki Saito, Jotaro On, Jun Watanabe, Yoshihiro Tsukamoto, Junichi Yoshimura, Makoto Oishi, Toshimichi Nakano, Masaru Imamura, Chihaya Imai, Tetsuya Yamamoto, Hideo Takeshima, Atsuo T Sasaki, Fausto J Rodriguez, Sumihito Nobusawa, Pascale Varlet, Celio Pouponnot, Satoru Osuka, Yves Pommier, Akiyoshi Kakita, Yukihiko Fujii, Eric H Raabe, Charles G Eberhart, Manabu Natsumeda

    Neuro-oncology   25 ( 5 )   899 - 912   2022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)  

    BACKGROUND: Intensive chemotherapeutic regimens with craniospinal irradiation have greatly improved survival in medulloblastoma patients. However, survival markedly differs among molecular subgroups and their biomarkers are unknown. Through unbiased screening, we found Schlafen family member 11 (SLFN11), which is known to improve response to DNA damaging agents in various cancers, to be one of the top prognostic markers in medulloblastomas. Hence, we explored the expression and functions of SLFN11 in medulloblastoma. METHODS: SLFN11 expression for each subgroup was assessed by immunohistochemistry in 98 medulloblastoma patient samples and by analyzing transcriptomic databases. We genetically or epigenetically modulated SLFN11 expression in medulloblastoma cell lines and determined cytotoxic response to the DNA damaging agents cisplatin and topoisomerase I inhibitor SN-38 in vitro and in vivo. RESULTS: High SLFN11 expressing cases exhibited significantly longer survival than low expressing cases. SLFN11 was highly expressed in the WNT-activated subgroup and in a proportion of the SHH-activated subgroup. While WNT activation was not a direct cause of the high expression of SLFN11, a specific hypomethylation locus on the SLFN11 promoter was significantly correlated with high SLFN11 expression. Overexpression or deletion of SLFN11 made medulloblastoma cells sensitive and resistant to cisplatin and SN-38, respectively. Pharmacological upregulation of SLFN11 by the brain-penetrant histone deacetylase-inhibitor RG2833 markedly increased sensitivity to cisplatin and SN-38 in SLFN11-negative medulloblastoma cells. Intracranial xenograft studies also showed marked sensitivity to cisplatin by SLFN11-overexpression in medulloblastoma cells. CONCLUSIONS: High SLFN11 expression is one factor which renders favorable outcomes in WNT-activated and a subset of SHH-activated medulloblastoma possibly through enhancing response to cisplatin.

    DOI: 10.1093/neuonc/noac243

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  • SWI by 7T MR Imaging for the Microscopic Imaging Diagnosis of Astrocytic and Oligodendroglial Tumors 査読

    M. Natsumeda, H. Matsuzawa, M. Watanabe, K. Motohashi, R. Gabdulkhaev, Y. Tsukamoto, Y. Kanemaru, J. Watanabe, R. Ogura, M. Okada, S. Kurabe, K. Okamoto, A. Kakita, H. Igarashi, Y. Fujii

    American Journal of Neuroradiology   2022年10月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.3174/ajnr.A7666

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  • Elucidating the multiple genetic alterations involved in the malignant transformation of a KRAS mutant neurenteric cyst. A case report. 国際誌

    Shoji Saito, Manabu Natsumeda, Makoto Sainouchi, Toru Takino, Kohei Shibuya, Jotaro On, Yu Kanemaru, Ryosuke Ogura, Masayasu Okada, Makoto Oishi, Yoshifumi Shimada, Toshifumi Wakai, Shujiro Okuda, Yoichi Ajioka, Akiyoshi Kakita, Yukihiko Fujii

    Neuropathology : official journal of the Japanese Society of Neuropathology   42 ( 6 )   519 - 525   2022年9月

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    記述言語:英語  

    Neurenteric cyst (NC) shows benign histopathology and rarely demonstrate malignant transformation. We herein describe a case of NC that exhibited malignant transformation. A 65-year-old female presented with gait disturbance due to compression by a cystic mass on the dorsal surface of the medulla oblongata. Partial resection was performed twice, leading to improvement of her symptoms. Two years after the second surgery, gadolinium-perfused T1-weighted magnetic resonance imaging revealed an invasive lesion with contrast enhancement at the trigone of the left lateral ventricle for which partial resection followed by radiotherapy was performed. However, mass regrowth was observed, with the patient eventually succumbing to her disease 11 months after her third surgery. Histopathological analyses of the first and second surgical specimens identified pseudostratified cuboidal epithelial cells, with no nuclear or cellular atypia resembling gastrointestinal mucosa, lining the inner surface of the cystic wall. Based on these findings the lesion was diagnosed as NC. The third surgical specimen exhibited apparent malignant features of the epithelial cells with elongated and hyperchromatic nuclei, several mitotic figures, small necrotic foci, and a patternless or sheet-like arrangement. Based on these findings, the lesion was diagnosed as NC with malignant transformation. Next-generation sequencing revealed KRAS p.G12D mutation in all specimens. Additionally, the third surgical specimen harbored the following 12 de novo gene alterations: ARID1A loss, BAP1 p.F170L, CDKN1B loss, CDKN2A loss, CDKN2B loss, FLCN loss, PTCH1 loss, PTEN loss, PTPRD loss, SUFU loss, TP53 loss, and TSC1 loss. The aforementioned results suggest that KRAS mutation is associated with the development of the NC, and that the additional gene alterations contribute to malignant transformation of the NC.

    DOI: 10.1111/neup.12822

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  • Successful Treatment of Acute Uric Acid Nephropathy with Rasburicase in a Primary Central Nervous System Lymphoma Patient Showing a Dramatic Response to Methotrexate-Case Report. 国際誌

    Yoshihiro Mouri, Manabu Natsumeda, Noritaka Okubo, Taro Sato, Taiki Saito, Kohei Shibuya, Shiori Yamada, Jotaro On, Yoshihiro Tsukamoto, Masayasu Okada, Makoto Oishi, Takeyoshi Eda, Junko Murai, Hiroshi Shimizu, Akiyoshi Kakita, Yukihiko Fujii

    Journal of clinical medicine   11 ( 19 )   2022年9月

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    記述言語:英語  

    BACKGROUND: Primary central nervous system lymphomas (PCNSLs) are sensitive to chemotherapy. The standard treatment is high-dose methotrexate (MTX)-based chemotherapy. There are no reports of successful treatment of acute uric acid nephropathy with rasburicase after MTX administration in PCNSLs. CASE PRESENTATION: A 54-year-old man with a history of gout presented with a change in character and cognitive dysfunction. MRI showed a large enhancing mass spanning the bilateral frontal lobes and the right temporal lobe. After endoscopic biopsy, an MTX, procarbazine, and vincristine (MPV) regimen was initiated for the treatment of the PCNSL. After the initiation of chemotherapy, the patient experienced a gout attack, and blood examination revealed acute renal failure (ARF) and hyperuricemia. The considered causes of ARF included MTX toxicity and acute uric acid nephropathy. As the dramatic effect of MTX was observed, treatment was continued despite ARF, most probably due to acute hyperuricemia due to tumor lysis, which was treated in parallel. After an improvement in renal function, MTX was resumed, and rasburicase was initiated to control hyperuricemia. A complete response was obtained after induction chemotherapy. Hyperuricemia was controlled with rasburicase, and renal function was preserved. CONCLUSIONS: Acute uric acid nephropathy should be considered when ARF occurs after the initiation of MTX in PCNSLs, especially in newly diagnosed PCNSL patients with large tumors or hyperuricemia.

    DOI: 10.3390/jcm11195548

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  • Correction to: JNK1‑Dependent Phosphorylation of GAP‑43 Serine 142 is a Novel Molecular Marker for Axonal Growth. 国際誌

    Masayasu Okada, Yosuke Kawagoe, Toshiyuki Takasugi, Motohiro Nozumi, Yasuyuki Ito, Hayato Fukusumi, Yonehiro Kanemura, Yukihiko Fujii, Michihiro Igarashi

    Neurochemical research   47 ( 9 )   2683 - 2683   2022年9月

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  • 統合失調症様の症状経過を呈し精神科に医療保護入院した脳動脈瘤破裂によるくも膜下出血の一症例

    坂上 仁, 湯川 尊行, 米岡 有一郎, 岡田 正康, 坪谷 隆介, 恩田 啓伍, 秋山 克彦, 関 泰弘

    新潟医学会雑誌   136 ( 6 )   206 - 207   2022年6月

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    記述言語:日本語   出版者・発行元:新潟医学会  

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  • Peripheral precocious puberty in a girl with an intracranial hCG-producing tumor: case report and literature review. 査読

    Nao Shibata, Hiromi Nyuzuki, Sunao Sasaki, Yohei Ogawa, Masayasu Okada, Keisuke Nagasaki

    Endocrine journal   68 ( 12 )   1463 - 1467   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)  

    Human chorionic gonadotropin (hCG)-producing tumors cause peripheral precocious puberty (PP) in boys, but generally not in girls. Homology between LH and hCG activates the LH receptor in testicular Leydig cells, increases testosterone production, and causes virilization. However, since FSH action is required for follicle development, hCG action alone does not increase estradiol (E2) production and does not cause feminization. Only a few cases of peripheral PP with hCG tumors in girls have been reported. We describe the case of a 7-year-old Japanese girl with peripheral PP associated with an hCG-producing tumor. She had prolonged vomiting, loss of appetite, and Tanner stage III breast development. Although no apparent increase in growth rate, bone age was advanced at 9.8 years. Serum E2 was slightly elevated and LH and FSH were below the measurement sensitivity, and abdominal ultrasonography and computed tomography images showed no abnormal findings in the uterus or ovaries. Subsequently, she developed visual field disturbance and loss of consciousness, and brain magnetic resonance imaging revealed an intracranial tumor. Based on pathological findings and abnormally high serum hCG-β level (48,800 IU/L), intracranial choriocarcinoma was diagnosed. 2.5 months after the start of chemotherapy, the hCG-β level became almost negative and the breast development disappeared synchronously. Tissue immunostaining of the tumor showed strong positivity for aromatase and hCG, indicating that the choriocarcinoma cells themselves may have produced estrogen via aromatase. This unique case highlights the possibility that hCG-producing tumors can cause peripheral PP in girls as well as boys.

    DOI: 10.1507/endocrj.EJ21-0117

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

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

    Brain tumor pathology   38 ( 3 )   228 - 233   2021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)  

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

    DOI: 10.1007/s10014-021-00407-0

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  • リン酸化プロテオミクスで同定した新規霊長類神経成長・再生マーカー リン酸化GAP-43 T172 査読

    岡田 正康, 河嵜 麻実, 金子 奈穂子, 棗田 学, 大石 誠, 藤井 幸彦, 五十嵐 道弘

    Cytometry Research   31 ( 1 )   7 - 13   2021年7月

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    担当区分:筆頭著者   記述言語:日本語   出版者・発行元:(一社)日本サイトメトリー学会  

    筆者らは、神経の成長や再生に関わる因子を同定する目的で齧歯類のin vivoのサンプルからリン酸化GAP-43 T172を検出した。そのリン酸化蛋白質に対するリン酸化検出抗体を作製し、さらに責任キナーゼを同定した。次に齧歯類で検証したリン酸化配列がアミノ酸配列上、霊長類にも保存されていたことから、霊長類としてマーモセットの新生仔脳組織を用いたリン酸化プロテオミクスで局在性を検証した。これらのプロセスについて解説した。

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  • [The Present and Future of Less-invasive Liquid Biopsy for the Diagnosis of Gliomas and Brain Tumors]. 査読

    Manabu Natsumeda, Jotaro On, Jun Watanabe, Yoshihiro Tsukamoto, Masayasu Okada, Yukihiko Fujii, Junichi Adachi, Ryo Nishikawa

    No shinkei geka. Neurological surgery   49 ( 3 )   527 - 534   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)  

    There is growing interest in liquid biopsy, the less-invasive detection of circulating tumor DNA(ctDNA)or circulating tumor cells(CTCs)from cerebrospinal fluid(CSF)and/or serum of patients, for the diagnosis of brain tumors. We share our experience of detecting hot spot point mutations using droplet digital PCR(ddPCR)in ctDNA obtained from the CSF of patients with brain tumors. The detection of mutations such as IDH1 R132H, BRAF V600E, and TERT promoter mutations in gliomas can be diagnostic. For optimal detection of ctDNA, which is only seen at very low concentrations, proper handling and storage of CSF, high-yield extraction of ctDNA, and usage of sensitive PCR methods for detection are imperative. We discuss which mutations can be assessed when diagnosing brain tumors, with a specific focus on gliomas. Finally, we look at what the near future holds for liquid biopsy of brain tumor patients, including next-generation sequencing panel analysis and accurate assessment of fusion genes.

    DOI: 10.11477/mf.1436204425

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  • 【グリオーマ-現在の常識と近未来のスタンダード】グリオーマの疫学と診断 グリオーマの低侵襲的診断法 Liquid biopsyの現状および展望

    棗田 学, 温 城太郎, 渡邉 潤, 塚本 佳広, 岡田 正康, 藤井 幸彦, 安達 淳一, 西川 亮

    Neurological Surgery   49 ( 3 )   527 - 534   2021年5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 ・脳腫瘍の低侵襲診断法liquid biopsyには,ddPCRによるctDNAの解析が有用である.・ctDNAの検出精度を向上させるためには,脳脊髄液サンプル採取後に適正な処理が重要である.・将来的には次世代シーケンスゲノムパネル検索や融合遺伝子解析が可能となると期待される.

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  • Low Detection Rate of H3K27M Mutations in Cerebrospinal Fluid Obtained from Lumbar Puncture in Newly Diagnosed Diffuse Midline Gliomas. 査読 国際誌

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

    Diagnostics (Basel, Switzerland)   11 ( 4 )   2021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)  

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

    DOI: 10.3390/diagnostics11040681

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  • GLI3 Is Associated With Neuronal Differentiation in SHH-Activated and WNT-Activated Medulloblastoma. 査読 国際誌

    Manabu Natsumeda, Hiroaki Miyahara, Junichi Yoshimura, Satoshi Nakata, Takanori Nozawa, Junko Ito, Yu Kanemaru, Jun Watanabe, Yoshihiro Tsukamoto, Masayasu Okada, Makoto Oishi, Junko Hirato, Takafumi Wataya, Sama Ahsan, Kensuke Tateishi, Tetsuya Yamamoto, Fausto J Rodriguez, Hitoshi Takahashi, Volker Hovestadt, Mario L Suva, Michael D Taylor, Charles G Eberhart, Yukihiko Fujii, Akiyoshi Kakita

    Journal of neuropathology and experimental neurology   80 ( 2 )   129 - 136   2021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)  

    Glioma-associated oncogene homolog 3 (GLI3), whose main function is to inhibit GLI1, has been associated with neuronal differentiation in medulloblastoma. However, it is not clear what molecular subtype(s) show increased GLI3 expression. GLI3 levels were assessed by immunohistochemistry in 2 independent cohorts, including a total of 88 cases, and found to be high in both WNT- and SHH-activated medulloblastoma. Analysis of bulk mRNA expression data and single cell RNA sequencing studies confirmed that GLI1 and GLI3 are highly expressed in SHH-activated medulloblastoma, whereas GLI3 but not GLI1 is highly expressed in WNT-activated medulloblastoma. Immunohistochemical analysis has shown that GLI3 is expressed inside the neuronal differentiated nodules of SHH-activated medulloblastoma, whereas GLI1/2 are expressed in desmoplastic areas. In contrast, GLI3 is diffusely expressed in WNT-activated medulloblastoma, whereas GLI1 is suppressed. Our data suggest that GLI3 may be a master regulator of neuronal differentiation and morphology in these subgroups.

    DOI: 10.1093/jnen/nlaa141

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  • [Coexisting Symptomatic Adrenocorticotropic Hormone- and Growth Hormone-producing Double Pituitary Adenomas with Difficulty in Tumor Localization:A Case Report]. 査読

    Yuhei Ito, Shinya Jinguji, Yusuke Sato, Taku Sato, Yuta Murakami, Masazumi Fujii, Jun Sakuma, Mariko Iwasaki, Akihiro Kudo, Michio Shimabukuro, Yuichiro Kiko, Masayasu Okada, Kiyoshi Saito

    No shinkei geka. Neurological surgery   48 ( 3 )   253 - 260   2020年3月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Double functional pituitary adenomas are rare, and only a few cases of excessive clinical symptoms of both adrenocorticotropic hormone(ACTH)and growth hormone(GH)have been reported. We herein report a case of symptomatic ACTH-and GH-producing double pituitary adenomas, which were discretely located within the same pituitary gland. A 38-year-old woman presented with general malaise, facial and lower limb edema, unexplained weight gain, facial redness, acne, and nasal enlargement. Endocrinological findings matched with the diagnostic criteria for both acromegaly and Cushing's disease. Preoperative magnetic resonance imaging showed a 15-mm cyst-like lesion on the right side of the sellae surrounded by what was thought to be the normal contrast-enhancing pituitary gland. We assumed that the cyst-like lesion was an adenoma and performed endoscopic endonasal transsphenoidal surgery. However, the cyst-like lesion was a parenchymal tumor. Furthermore, the region we considered to be a normal pituitary gland was also found to be an adenoma. Both adenomas were completely resected. The postoperative blood analysis showed ACTH<1.0pg/dL, cortisol 1.8μg/dL, and insulin-like growth factor-1 60ng/mL, all of which were below reference levels. The histopathological examination confirmed the coexistence of two adenomas, a GH-producing adenoma and an ACTH-producing adenoma. We concluded that these adenomas were endocrinologically active within the pituitary gland. Thus, a diagnosis of double pituitary adenomas was made. When treating a patient with symptoms caused by hypersecretion of multiple anterior pituitary hormones, the possibility of coexisting multiple pituitary adenomas should be considered.

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  • High Detection Rate of MYD88 Mutations in Cerebrospinal Fluid From Patients With CNS Lymphomas. 査読 国際誌

    Jun Watanabe, Manabu Natsumeda, Masayasu Okada, Daiki Kobayashi, Yu Kanemaru, Yoshihiro Tsukamoto, Makoto Oishi, Akiyoshi Kakita, Yukihiko Fujii

    JCO precision oncology   3   1 - 13   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)  

    PURPOSE: Biopsy is the gold standard for the diagnosis of primary CNS lymphoma (PCNSL). However, surgical biopsy has problems of morbidity related to hemorrhagic complications and false-negative findings, so safer and more reliable diagnostic methods are required. The aim of this study is to detect the MYD88 mutation, an important driver mutation, in the cerebrospinal fluid (CSF) of patients with CNS lymphoma. PATIENTS AND METHODS: Twenty-six patients with CNS lymphoma (20 primary CNS lymphoma and six CNS relapse from systemic lymphoma) were studied. We extracted cell-free DNA (cfDNA) from CSF by lumbar puncture. cfDNA was extracted from 1 mL of CSF, and Sanger sequencing and droplet digital polymerase chain reaction (ddPCR) were performed. Furthermore, we performed DNA sequencing of MYD88 in 21 cases with available surgically obtained formalin-fixed paraffin-embedded (FFPE) tissue and compared the results. RESULTS: The median cfDNA amount extracted from 1 mL CSF was 219 ng/mL (25th to 75th percentile, 129 to 333 ng/mL). MYD88 mutations were detected from CSF in 76.9% (20 of 26 cases), and L265P in exon 5 was the most frequent mutation in 19 out of 20 (95.0%) cases. S219C in exon 3 was detected in one case. In four patients, MYD88 mutation was confirmed by ddPCR but not by Sanger sequencing. In all 21 cases with sufficient FFPE tissue for DNA analysis, the detection of MYD88 mutation from cfDNA was consistent with those of tumor-derived DNA from FFPE tissue. CONCLUSION: This pilot study provided evidence that the somatic driver mutation MYD88 can be reliably detected by combination of Sanger sequencing and ddPCR in the cfDNA taken from 1 mL of CSF in patients with CNS lymphomas.

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  • Comparison of circulating tumor DNA between body fluids in patients with primary central nervous system lymphoma. 査読 国際誌

    Watanabe J, Natsumeda M, Kanemaru Y, Okada M, Oishi M, Kakita A, Fujii Y

    Leukemia & lymphoma   60 ( 14 )   1 - 3   2019年7月

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  • Podoplanin Expression and IDH-Wildtype Status Predict Venous Thromboembolism in Patients with High-Grade Gliomas in the Early Postoperative Period. 査読 国際誌

    Watanabe J, Natsumeda M, Okada M, Kanemaru Y, Tsukamoto Y, Oishi M, Kakita A, Fujii Y

    World neurosurgery   128   e982-e988   2019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)  

    DOI: 10.1016/j.wneu.2019.05.049

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  • EGFRvIII Is Expressed in Cellular Areas of Tumor in a Subset of Glioblastoma. 査読

    Nozawa T, Okada M, Natsumeda M, Eda T, Abe H, Tsukamoto Y, Okamoto K, Oishi M, Takahashi H, Fujii Y, Kakita A

    Neurologia medico-chirurgica   59 ( 3 )   89 - 97   2019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)  

    DOI: 10.2176/nmc.oa.2018-0078

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  • MGMT Expression Contributes to Temozolomide Resistance in H3K27M-Mutant Diffuse Midline Gliomas and MGMT Silencing to Temozolomide Sensitivity in IDH-Mutant Gliomas. 査読

    Abe H, Natsumeda M, Kanemaru Y, Watanabe J, Tsukamoto Y, Okada M, Yoshimura J, Oishi M, Fujii Y

    Neurologia medico-chirurgica   58 ( 7 )   290 - 295   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)  

    DOI: 10.2176/nmc.ra.2018-0044

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  • Reliable diagnosis of IDH-mutant glioblastoma by 2-hydroxyglutarate detection: a study by 3-T magnetic resonance spectroscopy. 査読 国際誌

    Manabu Natsumeda, Kunio Motohashi, Hironaka Igarashi, Takanori Nozawa, Hideaki Abe, Yoshihiro Tsukamoto, Ryosuke Ogura, Masayasu Okada, Tsutomu Kobayashi, Hiroshi Aoki, Hitoshi Takahashi, Akiyoshi Kakita, Kouichirou Okamoto, Tsutomu Nakada, Yukihiko Fujii

    Neurosurgical review   41 ( 2 )   641 - 647   2018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)  

    We have previously reported that reliable detection of 2-hydroxyglutarate (2HG) in isocitrate dehydrogenase (IDH)-mutant WHO grade 2 and 3 gliomas is possible utilizing 3.0-T single-voxel magnetic resonance spectroscopy (SVMRS). We set out to determine whether the same method could be applied to detect 2HG in IDH-mutant glioblastoma. Forty-four patients harboring glioblastoma underwent pre-operative MRS evaluation to detect 2HG and other metabolites. Presence of IDH-mutations was determined by IDH1 R132H immunohistochemical analysis and DNA sequencing of surgically obtained tissues. Six out of 44 (13.6%) glioblastomas were IDH-mutant. IDH-mutant glioblastoma exhibited significantly higher accumulation of 2HG (median 3.191 vs. 0.000 mM, p < 0.0001, Mann-Whitney test). A cutoff of 2HG = 0.897 mM achieved high sensitivity (100.0%) and specificity (92.59%) in determining IDH-mutation in glioblastoma. Glioblastoma with high 2HG accumulation did not have significantly longer overall survival than glioblastoma with low 2HG accumulation (p = 0.107, log-rank test). Non-invasive and reliable detection of 2HG in IDH-mutant glioblastoma was possible by 3.0-T SVMRS.

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  • Has acromegaly been diagnosed earlier? 査読

    Ohno H, Yoneoka Y, Jinguji S, Watanabe N, Okada M, Fujii Y

    Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia   48   138 - 142   2018年2月

  • Third Ventricle Germ Cell Tumor Originating from the Infundibulum with Rapidly Expansive Enlargement 査読

    Yuichiro Yoneoka, Junichi Yoshimura, Masakazu Sano, Masayasu Okada, Akiyoshi Kakita, Yukihiko Fujii

    Pediatric Neurosurgery   53 ( 1 )   49 - 54   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:S. Karger AG  

    We present a pediatric case of a rapidly expanding third ventricle germ cell tumor (GCT). A 14-year-old boy suffered from gradual-onset central diabetes insipidus (DI) and received desmopressin treatment. Magnetic resonance imaging (MRI) showed nonspecific findings of the pituitary-hypothalamic axis. Nine months after the initial DI diagnosis, he developed progressively worsening headache. MRI demonstrated a third ventricle tumor causing noncommunicating hydrocephalus, although an MRI 16 weeks before admission did not show the lesion. We performed gross total resection (GTR) of the tumor in 2 stages: a translamina terminalis approach and an extended transsphenoidal approach. The lesion was histologically diagnosed as immature teratoma with some germinoma. His noncommunicating hydrocephalus resolved after surgery. Through postoperative radiochemotherapy (whole ventricle: 23.4 Gy/13 fractions, tumor bed: 27.0 Gy/15 fractions, and 3 courses of carboplatin-etoposide), he has was in complete remission at the 3-year follow-up and has continued his high school program. This case suggests the following: (1) a mixed GCT originating from the neurohypophysis/infundibulum can show rapidly expansive growth in a child with central DI
    (2) GTR and adjuvant radiochemotherapy can result in a good therapeutic outcome in rapidly expanding GCT
    and (3) the extended transsphenoidal approach is a complementary approach to transcranial resection of anterior third ventricle GCTs.

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  • Ectopic pituitary null cell adenoma arising from the infundibulum in the third ventricle: A successful endonasal transsphenoidal resection after long-term follow-up MR imaging – A technical note 査読

    Yuichiro Yoneoka, Masayasu Okada, Naoto Watanabe, Satoru Aoki, Akiyoshi Kakita, Yukihiko Fujii

    Interdisciplinary Neurosurgery: Advanced Techniques and Case Management   10   122 - 125   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 B.V.  

    Background Since the origin and growth pattern of third ventricle ectopic pituitary adenoma (ectPA) remain unclear, its optimal surgical approach is debatable. Clinical presentation We present a rare case of null cell pituitary adenoma arising from the pituitary infundibulum with long-term preoperative follow-up images. The tumor was resected gross-totally via an extended transsphenoidal approach. Conclusion To our best knowledge, this is the first case with long-term preoperative follow-up images, which can bridge the knowledge gap in operations of third ventricle ectPA as following: (1) Truly third ventricle ectPA can exist, (2) the third ventricle ectPA extended into the sella turcica along the pituitary stalk, (3) this ectPA can arise from the suprasellar peri-infundibular ectopic pituitary cells or the pars tuberalis of the adenohypophysis, and therefore adhere to the optic chiasm, (4) thus neurosurgeons should take great care in resection of ectPA arising from the infundibulum, and (5) it can be resected through an endoscopic extended transsphenoidal approach.

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  • Perifocal Inflammatory Reaction with Volume Fluctuation Caused by Diagnostic Radiation-Induced Regression in Germinoma Makes Histological Diagnosis Difficult despite Its Disappearance following Treatment: A Significant Pitfall and Countermeasures to It 査読

    Yuichiro Yoneoka, Junichi Yoshimura, Masayasu Okada, Yukihiko Fujii

    PEDIATRIC NEUROSURGERY   52 ( 2 )   87 - 92   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:KARGER  

    We present a pediatric case of neurohypophyseal germinoma with a perifocal inflammatory reaction (PIR) with volume fluctuation caused by diagnostic radiation-induced regression (DRIR). On-target biopsy failed to confirm the histology because PIR hardly contained any germinoma cells. DRIR-related fluctuation of the tumor volume disguised germinoma as inflammation. We analyzed the cerebrospinal fluid (CSF) and detected a high level of placental alkaline phosphatase (PLAP), which demonstrated the neurohypophyseal lesion to be germinoma and brought the patient from successful radiochemotherapy up to complete remission. PIR adjacent to the germinoma (PIRAG) disappeared completely following radiochemotherapy, although it contained almost no germinoma cells. Examination of the CSF-PLAP level can complement the diagnosis of germinoma and will decrease the risk of misdiagnosis. Neurosurgeons should keep in mind PIRAG, DRIR, and the diagnostic value of CSF-PLAP when germinoma is suspected. (C) 2016 S. Karger AG, Basel

    DOI: 10.1159/000450583

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  • Early morphological recovery of the optic chiasm is associated with excellent visual outcome in patients with compressive chiasmal syndrome caused by pituitary tumors 査読

    Yuichiro Yoneoka, Tetsuhisa Hatase, Naoto Watanabe, Shinya Jinguji, Masayasu Okada, Mineo Takagi, Yukihiko Fujii

    NEUROLOGICAL RESEARCH   37 ( 1 )   1 - 8   2015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:MANEY PUBLISHING  

    Objectives: The study objectives are (1) to identify factors predicting the excellent visual recovery after transsphenoidal removal of pituitary tumors and (2) to describe the association of excellent visual recovery and early restoration of symmetry of the decompressed optic chiasm.
    Methods: Thirty-five patients with visual symptoms due to pituitary tumors underwent endoscopic endonasal surgery. All patients received perioperative diagnostic magnetic resonance (MR) imaging and ophthalmological assessments within 2 weeks before surgery, within 2 weeks after surgery, and 3 months or later after surgery. Preoperative best-corrected visual acuity (BCVA &gt;= 20/20), degree of visual field deficit (VFD, less than half of VF), thickness of retinal nerve fiber layer (RNFL) measured by optical coherence tomography (OCT), and thickness of ganglion cell complex (GCC) measured by OCT were considered for statistical analysis as predictive factors of VF outcome. Multivariate logistic regression models were used in statistical evaluation of data.
    Results: In the multivariate analysis, RNFL (odds ratio = 62.137, P &lt; 0.001) and preoperative VFD (odds ratio = 8.244, P &lt; 0.02) proved to be effective as factors predicting sufficient VF recovery. Postoperative restoration of symmetry of the optic chiasm was related to sufficient VF recovery (P &lt; 0.0001, Fisher's exact test) and RNFL (P &lt; 0.0001, Fisher's exact test).
    Discussion: Early decompression is crucial for sufficient VF recovery, in particular, while RNFL preserves normal or borderline thickness and while VFD keeps within hemianopia. Morphological reversibility is associated with functional reversibility in the optic chiasm compressed by a pituitary tumor. In particular, early morphological recovery suggests functional recovery, which indicates neurocyte reserve in the compressed optic pathway with functional recovery.

    DOI: 10.1179/1743132814Y.0000000407

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  • Chondroitin sulphate N-acetylgalactosaminyl-transferase-1 inhibits recovery from neural injury 査読

    Kosei Takeuchi, Nozomu Yoshioka, Susumu Higa Onaga, Yumi Watanabe, Shinji Miyata, Yoshino Wada, Chika Kudo, Masayasu Okada, Kentaro Ohko, Kanako Oda, Toshiya Sato, Minesuke Yokoyama, Natsuki Matsushita, Masaya Nakamura, Hideyuki Okano, Kenji Sakimura, Hitoshi Kawano, Hiroshi Kitagawa, Michihiro Igarashi

    NATURE COMMUNICATIONS   4   2740   2013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:NATURE PUBLISHING GROUP  

    Extracellular factors that inhibit axon growth and intrinsic factors that promote it affect neural regeneration. Therapies targeting any single gene have not yet simultaneously optimized both types of factors. Chondroitin sulphate (CS), a glycosaminoglycan, is the most abundant extracellular inhibitor of axon growth. Here we show that mice carrying a gene knockout for CS N-acetylgalactosaminyltransferase-1 (T1), a key enzyme in CS biosynthesis, recover more completely from spinal cord injury than wild-type mice and even chondroitinase ABC-treated mice. Notably, synthesis of heparan sulphate (HS), a glycosaminoglycan promoting axonal growth, is also upregulated in TI knockout mice because HS-synthesis enzymes are induced in the mutant neurons. Moreover, chondroitinase ABC treatment never induces HS upregulation. Taken together, our results indicate that regulation of a single gene, T1, mediates excellent recovery from spinal cord injury by optimizing counteracting effectors of axon regeneration-an extracellular inhibitor of CS and intrinsic promoters, namely, HS-synthesis enzymes.

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  • Observation of the neurohypophysis, pituitary stalk, and adenohypophysis during endoscopic pituitary surgery: Demonstrative findings as clues to pituitary-conserving surgery 査読

    Yuichiro Yoneoka, Naoto Watanabe, Masayasu Okada, Yukihiko Fujii

    ACTA NEUROCHIRURGICA   155 ( 6 )   1049 - 1055   2013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:SPRINGER WIEN  

    High-definition imaging in endoscopic transsphenoidal pituitary surgery accounts for significantly better identification of anatomic structures. This report presents the clinical images of the adenohypophysis and neurohypophysis under high-definition endoscopic observation, and provides some clues for pituitary-sparing surgery.
    Ten demonstrative cases of pituitary lesions, including three cases of gonadotropin-producing pituitary adenoma, two cases of somatotropin-secreting pituitary adenoma, and five cases of Rathke's cleft cysts, were entered in this study. From these cases, we extracted helpful intraoperative findings that affected the surgeon's decision about surgical procedures and led to favorable results.
    The extracted findings contain the following lessons: (1) to find a boundary plane that separate a lesion from the pituitary; (2) to mark the difference of color between the adenohypophysis and the neurohypophysis; (3) to identify the location of the pituitary stalk connecting to the neurohypophysis; (4) to observe the color change of the pituitary induced by decompression; (5) to know pathological findings of the pituitary surface; (6) to distinguish the parenchyma of the neurohypophysis from pathological tissues; and (7) to recognize the intrasellar findings at the completion of removal. Recognition of these findings led to an excellent result in each case.
    Despite being shown in a limited number of cases, on the basis of HD endoscopic images, accurate identification of the neurohypophysis and the pituitary stalk as well as adenohypophysis during surgery contributes to pituitary-conserving operations.

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  • Advantages of dose-dense methotrexate protocol for primary central nervous system lymphoma: Comparison of two different protocols at a single institution 査読

    Hiroshi Aoki, Ryosuke Ogura, Yoshihiro Tsukamoto, Masayasu Okada, Manabu Nat Sumeda, Mizuho Isogawa, Seiichi Yoshida, Yukihiko Fujii

    Neurologia Medico-Chirurgica   53 ( 11 )   797 - 804   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The efficacy and toxicity of high-dose methotrexate (HD-MTX)-based chemotherapy were retrospectively reviewed in patients with primary central nervous system lymphoma (PCNSL). All immunocompetent patients with histologically or radiographically diagnosed PCNSL treated between 2006 and 2012 at Niigata University Hospital were enrolled. Thirty-eight patients with a diagnosis of PCNSL were treated with one of two regimens during different time periods. During the first period, from 2006 to 2009, three 3-week cycles of MPV (MTX + procarbazine + vincristine) were administered (MPV3 group). In the second period, from 2010 to 2012, five 2-week cycles of MTX were administered (MTX5 group). High-dose cytarabine was used in both groups following HD-MTX-based chemotherapy. Whole-brain radiotherapy was used for patients who did not attain a complete response (CR) based on magnetic resonance images. In the MPV3 group, 20 out of 23 patients (87%) completed the planned treatment. The CR rate after chemotherapy was 30%, and 57% after radiation therapy. Thirteen out of 15 patients (87%) in the MTX5 group completed the planned treatment. The CR rates after chemotherapy and radiation therapy were 53% and 93%, respectively. Renal dysfunction was assessed by measuring creatinine clearance rates, which were very similar in both groups. In terms of hematologic toxicity and other adverse reactions, there was no significant difference between the two groups. In conclusion, dose-dense MTX chemotherapy improved outcome with acceptable toxicity compared with the treatment schedule for three cycles of MPV treatment.

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担当経験のある授業科目(researchmap)

  • 脳神経外科

    機関名:新潟大学医学部医学科

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担当経験のある授業科目

  • 脳神経外科

    2016年4月
    機関名:新潟大学

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    科目区分:学部専門科目  国名:日本国