Updated on 2021/06/15

写真a

 
TANAHASHI Kuniaki
 
Organization
Nagoya University Hospital Neurosurgery Assistant Professor
Graduate School
Graduate School of Medicine
Title
Assistant Professor

Degree 1

  1. 博士(医学) ( 2014.10   名古屋大学 ) 

 

Papers 37

  1. Neurod4 converts endogenous neural stem cells to neurons with synaptic formation after spinal cord injury

    Fukuoka Toshiki, Kato Akira, Hirano Masaki, Ohka Fumiharu, Aoki Kosuke, Awaya Takayuki, Adilijiang Alimu, Sachi Maeda, Tanahashi Kuniaki, Yamaguchi Junya, Motomura Kazuya, Shimizu Hiroyuki, Nagashima Yoshitaka, Ando Ryo, Wakabayashi Toshihiko, Lee-Liu Dasfne, Larrain Juan, Nishimura Yusuke, Natsume Atsushi

    ISCIENCE   Vol. 24 ( 2 ) page: 102074   2021.2

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    DOI: 10.1016/j.isci.2021.102074

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  2. Intraoperative seizure outcome of levetiracetam combined with perampanel therapy in patients with glioma undergoing awake brain surgery.

    Motomura K, Chalise L, Shimizu H, Yamaguchi J, Nishikawa T, Ohka F, Aoki K, Tanahashi K, Hirano M, Wakabayashi T, Natsume A

    Journal of neurosurgery     page: 1 - 10   2021.1

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    DOI: 10.3171/2020.8.JNS201400

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  3. Surgical outcome and graded prognostic assessment of patients with brain metastasis from adult sarcoma: multi-institutional retrospective study in Japan

    Deguchi Shoichi, Nakasu Yoko, Sakaida Tsukasa, Akimoto Jiro, Tanahashi Kuniaki, Natsume Atsushi, Takahashi Masamichi, Okuda Takeshi, Asakura Hirofumi, Mitsuya Koichi, Hayashi Nakamasa, Narita Yoshitaka

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   Vol. 25 ( 11 ) page: 1995 - 2005   2020.11

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    Publishing type:Research paper (scientific journal)   Publisher:International Journal of Clinical Oncology  

    DOI: 10.1007/s10147-020-01740-8

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  4. Long-term survival in patients with primary intracranial germ cell tumors treated with surgery, platinum-based chemotherapy, and radiotherapy: a single-institution study.

    Shimizu H, Motomura K, Ohka F, Aoki K, Tanahashi K, Hirano M, Chalise L, Nishikawa T, Yamaguchi J, Yoshida J, Natsume A, Wakabayashi T

    Journal of neurosurgery     page: 1 - 9   2020.10

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    DOI: 10.3171/2020.6.JNS20638

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  5. STA-enhanced vascularized galeal flap for revascularization of moyamoya disease: technical report

    Tanahashi Kuniaki, Zomorodi Ali R., Fukushima Takanori

    ACTA NEUROCHIRURGICA   Vol. 162 ( 8 ) page: 1841 - 1845   2020.8

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    Publishing type:Research paper (scientific journal)   Publisher:Acta Neurochirurgica  

    DOI: 10.1007/s00701-020-04441-3

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  6. Surgical Designs of Revascularization for Moyamoya Disease: 15 Years of Experience in a Single Center

    Araki Yoshio, Uda Kenji, Yokoyama Kinya, Kanamori Fumiaki, Mamiya Takashi, Nishihori Masahiro, Izumi Takashi, Tanahashi Kuniaki, Masaki Sumitomo, Sho Okamoto, Wakabayashi Toshihiko, Natsume Atsushi

    WORLD NEUROSURGERY   Vol. 139   page: E325 - E334   2020.7

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    Publishing type:Research paper (scientific journal)   Publisher:World Neurosurgery  

    DOI: 10.1016/j.wneu.2020.03.217

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  7. Neurocognitive and functional outcomes in patients with diffuse frontal lower-grade gliomas undergoing intraoperative awake brain mapping

    Motomura Kazuya, Chalise Lushun, Ohka Fumiharu, Aoki Kosuke, Tanahashi Kuniaki, Hirano Masaki, Nishikawa Tomohide, Yamaguchi Junya, Shimizu Hiroyuki, Wakabayashi Toshihiko, Natsume Atsushi

    JOURNAL OF NEUROSURGERY   Vol. 132 ( 6 ) page: 1683 - 1691   2020.6

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    Publishing type:Research paper (scientific journal)   Publisher:Journal of Neurosurgery  

    DOI: 10.3171/2019.3.JNS19211

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  8. Trautmann-focused mastoidectomy for a simple, safe presigmoid approach: technical note.

    Tanahashi K, Uda K, Araki Y, Takeuchi K, Choo J, Chalise L, Motomura K, Ohka F, Wakabayashi T, Natsume A

    Journal of neurosurgery   Vol. 134 ( 3 ) page: 1 - 5   2020.3

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    Publishing type:Research paper (scientific journal)   Publisher:Journal of Neurosurgery  

    DOI: 10.3171/2020.1.JNS193179

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  9. H3F3A mutant allele specific imbalance in an aggressive subtype of diffuse midline glioma, H3 K27M-mutant

    Maeda Sachi, Ohka Fumiharu, Okuno Yusuke, Aoki Kosuke, Motomura Kazuya, Takeuchi Kazuhito, Kusakari Hironao, Yanagisawa Nobuyuki, Sato Shinya, Yamaguchi Junya, Tanahashi Kuniaki, Hirano Masaki, Kato Akira, Shimizu Hiroyuki, Kitano Yotaro, Yamazaki Shintaro, Yamashita Shinji, Takeshima Hideo, Shinjo Keiko, Kondo Yutaka, Wakabayashi Toshihiko, Natsume Atsushi

    ACTA NEUROPATHOLOGICA COMMUNICATIONS   Vol. 8 ( 1 ) page: 8   2020.2

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    Publishing type:Research paper (scientific journal)   Publisher:Acta neuropathologica communications  

    DOI: 10.1186/s40478-020-0882-4

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  10. Multiple metastases to the bone and bone marrow from a 1p/19q-codeleted and <i>IDH2</i>-mutant anaplastic oligodendroglioma: a case report and literature review.

    Shimizu H, Motomura K, Ohka F, Aoki K, Tanahashi K, Hirano M, Chalise L, Nishikawa T, Yamaguchi J, Wakabayashi T, Natsume A

    Neuro-oncology advances   Vol. 2 ( 1 ) page: vdaa101   2020.1

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    DOI: 10.1093/noajnl/vdaa101

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  11. MACHINE LEARNING TO DETECT GLIOMAS IN URINE-BASED LIQUID BIOPSY

    Kitano Yotaro, Aoki Kosuke, Yasui Takao, Motomura Kazuya, Ohka Fumiharu, Tanahashi Kuniaki, Hirano Masaki, Nishikawa Tomohide, Shimizu Hiroyuki, Yamaguchi Junya, Maeda Sachi, Yamazaki Shintaro, Wakabayashi Toshihiko, Natsume Atsushi

    NEURO-ONCOLOGY   Vol. 21   page: 151 - 151   2019.11

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  12. Spontaneous Tumor Regression of Intracranial Solitary Fibrous Tumor Originating From the Medulla Oblongata: A Case Report and Literature Review

    Yamaguchi Junya, Motomura Kazuya, Ohka Fumiharu, Aoki Kosuke, Tanahashi Kuniaki, Hirano Masaki, Nishikawa Tomohide, Shimizu Hiroyuki, Wakabayashi Toshihiko, Natsume Atsushi

    WORLD NEUROSURGERY   Vol. 130   page: 400 - 404   2019.10

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    Publishing type:Research paper (scientific journal)   Publisher:World Neurosurgery  

    DOI: 10.1016/j.wneu.2019.07.052

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  13. Next Generation Sequencing-Based Transcriptome Predicts Bevacizumab Efficacy in Combination with Temozolomide in Glioblastoma

    Adilijiang Alimu, Hirano Masaki, Okuno Yusuke, Aoki Kosuke, Ohka Fumiharu, Maeda Sachi, Tanahashi Kuniaki, Motomura Kazuya, Shimizu Hiroyuki, Yamaguchi Junya, Wakabayashi Toshihiko, Natsume Atsushi

    MOLECULES   Vol. 24 ( 17 )   2019.9

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    Publishing type:Research paper (scientific journal)   Publisher:Molecules  

    DOI: 10.3390/molecules24173046

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  14. Posterior Cerebral Artery Reconstruction by In-Situ Bypass with Superior Cerebellar Artery via Occipital Transtentorial Approach

    Tanahashi Kuniaki, Araki Yoshio, Uda Kenji, Muraoka Shinsuke, Motomura Kazuya, Lushun Chalise, Wakabayashi Toshihiko, Natsume Atsushi

    WORLD NEUROSURGERY   Vol. 126   page: 24 - 29   2019.6

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    DOI: 10.1016/j.wneu.2019.02.127

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  15. Characterization of Intraoperative Motor Evoked Potential Monitoring for Surgery of the Pediatric Population with Brain Tumors. Reviewed

    Motomura K, Sumita K, Chalise L, Nishikawa T, Tanahashi K, Ohka F, Aoki K, Hirano M, Nakamura T, Matsushita T, Wakabayashi T, Natsume A

    World neurosurgery   Vol. 119   page: E1052 - E1059   2018.11

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    DOI: 10.1016/j.wneu.2018.08.039

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  16. Supratotal Resection of Diffuse Frontal Lower Grade Gliomas with Awake Brain Mapping, Preserving Motor, Language, and Neurocognitive Functions. Reviewed

    Motomura K, Chalise L, Ohka F, Aoki K, Tanahashi K, Hirano M, Nishikawa T, Wakabayashi T, Natsume A

    World neurosurgery   Vol. 119   page: 30 - 39   2018.11

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    DOI: 10.1016/j.wneu.2018.07.193

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  17. A novel high-sensitivity assay to detect a small fraction of mutant IDH1 using droplet digital PCR. Reviewed

    Hirano M, Ohka F, Maeda S, Chalise L, Yamamichi A, Aoki K, Kato A, Tanahashi K, Motomura K, Nishimura Y, Hara M, Shinjo K, Kondo Y, Wakabayashi T, Natsume A

    Brain tumor pathology   Vol. 35 ( 2 ) page: 97 - 105   2018.4

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    DOI: 10.1007/s10014-018-0310-7

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  18. Immunohistochemical ATRX expression is not a surrogate for 1p19q codeletion. Reviewed

    Yamamichi A, Ohka F, Aoki K, Suzuki H, Kato A, Hirano M, Motomura K, Tanahashi K, Chalise L, Maeda S, Wakabayashi T, Kato Y, Natsume A

    Brain tumor pathology   Vol. 35 ( 2 ) page: 106 - 113   2018.4

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    DOI: 10.1007/s10014-018-0312-5

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  19. Treatment of Primary CNS Lymphoma with RMPV (Rituximab, Methotrexate, Procarbazine, Vincristine) Therapy : Challenges and Prospects

    Chalise Lushun, Ohka Fumiharu, Hirano Masaki, Tanahashi Kuniaki, Wakabayashi Toshihiko

    Japanese Journal of Neurosurgery   Vol. 27 ( 1 ) page: 29 - 36   2018

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    Publishing type:Research paper (scientific journal)   Publisher:The Japanese Congress of Neurological Surgeons  

    <p>  Combination of systemic administration of high dose methotrexate (HD-MTX) and whole brain radiation therapy (WBRT) has widely been used as the standard treatment modality for primary CNS lymphoma (PCNSL). In this study, we retrospectively analyzed newly diagnosed PCNSL cases treated with different regimens at our institute. First, by comparing the results of our historical data of DeVIC (dexamethasone, etoposide, ifosfamide, carboplatin)/WBRT and HD-MTX/WBRT, we evaluated their strengths and limitations. We then compared the results of RMPV (rituximab, methotrexate, procarbazine, vincristine)/reduce dose WBRT (rd-WBRT) therapy to the historical regimens to examine if RMPV therapy could overcome the drawbacks of the past regimens. We report here our experience with RMPV therapy from Nagoya University where our Department of Neurosurgery carries out all neuro-oncologic duties including systemic chemotherapy.</p><p>  DeVIC group had a higher response rate compared to HD-MTX group (DeVIC 95%, HD-MTX 50%). One year overall and progression free survival was also longer in DeVIC group. These results highlighted the need to improve the initial response as a major issue to be resolved in HD-MTX therapy. On the other hand, RMPV therapy achieved a much better response (complete remission 86%) with induction chemotherapy alone. One year and two year overall survival after RMPV therapy was 100% and 75% respectively. Moreover, incidence of leukoencephalopathy was lower in RMPV patients, where rd-WBRT of 23.4 Gy was administered, compared to HD-MTX group with WBRT of 40 Gy. There was one case of treatment limiting toxicity in the RMPV group where treatment was discontinued after severe gastro-intestinal hemorrhage. Although RMPV therapy caused more adverse events than HD-MTX in general, there was no significant difference between grade 4 neutropenia requiring G-CSF administration (RMPV 28%, HD-MTX 7.1%, p=0.186).</p><p>  Our results show that RMPV could overcome the drawbacks of HD-MTX monotherapy. These results are one of the first reports of newly diagnosed PCNSL treated with RMPV/rd-WBRT in a Japanese population. These promising results require further investigation preferably with a prospective trial carried out in an institution with the capacity to properly manage the possible adverse events.</p>

    DOI: 10.7887/jcns.27.29

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  20. A novel all-in-one intraoperative genotyping system for IDH1-mutant glioma Reviewed

    Fumiharu Ohka, Akane Yamamichi, Michihiro Kurimoto, Kazuya Motomura, Kuniaki Tanahashi, Hiromichi Suzuki, Kosuke Aoki, Shoichi Deguchi, Lushun Chalise, Masaki Hirano, Akira Kato, Yusuke Nishimura, Masahito Hara, Yukinari Kato, Toshihiko Wakabayashi, Atsushi Natsume

    BRAIN TUMOR PATHOLOGY   Vol. 34 ( 2 ) page: 91 - 97   2017.4

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    IDH1 gene mutation has been demonstrated to be an oncogenic driver in a majority of lower-grade gliomas (LGGs). In contrast to other central nervous neoplasms and normal brain tissue without IDH1 mutation, almost 80% of LGGs exhibit IDH1 mutation. Therefore, expeditious detection of IDH1 mutation is useful, not only for intraoperative diagnosis of these gliomas but also for determination of the border between the tumor and normal brain tissue. In this study, we established a rapid genotyping assay with a simple DNA extraction method, involving only incubation of the tumor specimen with Tris-EDTA buffer, which can be easily performed in an operating room. In all 11 tested cases, we could identify the IDH1 status within 90-100 min intraoperatively. In a case of anaplastic astrocytoma, IDH-mutant, we could detect the tumor border by IDH1 profiling. In addition, with this assay, we could detect IDH1 mutation using cell-free tumor DNA derived from cerebrospinal fluid in a case of glioblastoma, IDH-mutant. Considering that clinical trials of mutated IDH1 inhibitors are ongoing, less-invasive intraoperative IDH1 gene profiling might be useful for decision making of the overall treatment strategy of LGGs. Our assay might be a useful tool for precision medicine and surgery of IDH1-mutant gliomas.

    DOI: 10.1007/s10014-017-0281-0

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  21. CAR T Cells Targeting Podoplanin Reduce Orthotopic Glioblastomas in Mouse Brains Reviewed

    Satoshi Shiina, Masasuke Ohno, Fumiharu Ohka, Shunichiro Kuramitsu, Akane Yamamichi, Akira Kato, Kazuya Motomura, Kuniaki Tanahashi, Takashi Yamamoto, Reiko Watanabe, Ichiro Ito, Takeshi Senga, Michinari Hamaguchi, Toshihiko Wakabayashi, Mika K. Kaneko, Yukinari Kato, Vidyalakshmi Chandramohan, Darell D. Bigner, Atsushi Natsume

    CANCER IMMUNOLOGY RESEARCH   Vol. 4 ( 3 ) page: 259 - 268   2016.3

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    Glioblastoma (GBM) is the most common and lethal primary malignant brain tumor in adults with a 5-year overall survival rate of less than 10%. Podoplanin (PDPN) is a type I transmembrane mucin-like glycoprotein, expressed in the lymphatic endothelium. Several solid tumors overexpress PDPN, including the mesenchymal type of GBM, which has been reported to present the worst prognosis among GBM subtypes. Chimeric antigen receptor (CAR)-transduced T cells can recognize predefined tumor surface antigens independent of MHC restriction, which is often downregulated in gliomas. We constructed a lentiviral vector expressing a third-generation CAR comprising a PDPN-specific antibody (NZ-1-based single-chain variable fragment) with CD28, 4-1BB, and CD3 zeta intracellular domains. CAR-transduced peripheral blood monocytes were immunologically evaluated by calcein-mediated cytotoxic assay, ELISA, tumor size, and overall survival. The generated CAR T cells were specific and effective against PDPN-positive GBM cells in vitro. Systemic injection of the CAR T cells into an immunodeficient mouse model inhibited the growth of intracranial glioma xenografts in vivo. CAR T-cell therapy that targets PDPN would be a promising adoptive immunotherapy to treat mesenchymal GBM. (C) 2016 AACR.

    DOI: 10.1158/2326-6066.CIR-15-0060

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  22. Efficacy of early carotid endarterectomy for vulnerable plaque in the common carotid artery Reviewed

    Kuniaki Tanahashi, Yoshio Araki, Mikio Maruwaka, Atsushi Natsume

    ACTA NEUROCHIRURGICA   Vol. 158 ( 3 ) page: 561 - 563   2016.3

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    DOI: 10.1007/s00701-016-2706-7

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  23. Lenalidomide enhances the function of chimeric antigen receptor T cells against the epidermal growth factor receptor variant III by enhancing immune synapses

    Kuramitsu S., Ohno M., Ohka F., Shiina S., Yamamichi A., Kato A., Tanahashi K., Motomura K., Kondo G., Kurimoto M., Senga T., Wakabayashi T., Natsume A.

    CANCER GENE THERAPY   Vol. 22 ( 10 ) page: 487 - 495   2015.10

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    DOI: 10.1038/cgt.2015.47

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  24. Activation of Yes-Associated Protein in Low-Grade Meningiomas Is Regulated by Merlin, Cell Density, and Extracellular Matrix Stiffness Reviewed

    Kuniaki Tanahashi, Atsushi Natsume, Fumiharu Ohka, Kazuya Motomura, Adiljan Alim, Ichidai Tanaka, Takeshi Senga, Ichiro Harada, Ryuichi Fukuyama, Naoyuki Sumiyoshi, Yoshitaka Sekido, Toshihiko Wakabayashi

    JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY   Vol. 74 ( 7 ) page: 704 - 709   2015.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    The NF2 gene product Merlin is a protein containing ezrin, radixin, and moesin domains; it is a member of the 4.1 protein superfamily associated with the membrane cytoskeleton and also interacts with cell surface molecules. The mammalian Hippo cascade, a downstream signaling cascade of merlin, inactivates the Yes-associated protein (YAP). Yes-associated protein is activated by loss of the NF2 gene and functions as an oncogene in meningioma cells; however, the factors controlling YAP expression, phosphorylation, and subcellular localization in meningiomas have not been fully elucidated. Here, we demonstrate that merlin expression is heterogeneous in 1 NF2 gene-negative and 3 NF2 gene-positive World Health Organization grade I meningiomas. In the NF2 gene-positive meningiomas, regions with low levels of merlin (tumor rims) had greater numbers of cells with nuclear YAP versus regions with high merlin levels (tumor cores). Merlin expression and YAP phosphorylation were also affected by cell density in the IOMM-Lee and HKBMM human meningioma cell lines; nuclear localization of YAP was regulated by cell density and extracellular matrix (ECM) stiffness in IOMM-Lee cells. These results suggest that cell density and ECM stiffness may contribute to the heterogeneous loss of merlin and increased nuclear YAP expression in human meningiomas.

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  25. Effectiveness of plasma treatment on gastric cancer cells Reviewed

    Koji Torii, Suguru Yamada, Kae Nakamura, Hiromasa Tanaka, Hiroaki Kajiyama, Kuniaki Tanahashi, Naoki Iwata, Mitsuro Kanda, Daisuke Kobayashi, Chie Tanaka, Tsutomu Fujii, Goro Nakayama, Masahiko Koike, Hiroyuki Sugimoto, Shuji Nomoto, Atsushi Natsume, Michitaka Fujiwara, Masaaki Mizuno, Masaru Hori, Hideyuki Saya, Yasuhiro Kodera

    GASTRIC CANCER   Vol. 18 ( 3 ) page: 635 - 643   2015.7

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    Treatment of peritoneal carcinomatosis arising from gastric cancer remains a considerable challenge. In recent years, the anticancer effect of nonequilibrium atmospheric pressure plasma (NEAPP) has been reported in several cancer cell lines. Use of NEAPP may develop into a new class of anticancer therapy that augments surgery, chemotherapy, and radiotherapy.
    Gastric cancer cells were assessed for changes in cell morphology and rate of proliferation after treatment with NEAPP-exposed medium (PAM). To explore the functional mechanism, caspase 3/7, annexin V, and uptake of reactive oxygen species (ROS) were evaluated, along with the effect of the ROS scavenger N-acetylcysteine (NAC).
    PAM treatment for 24 h affected cell morphology, suggestive of induction of apoptosis. PAM cytotoxicity was influenced by the time of exposure to PAM, the type of cell line, and the number of cells seeded. Cells treated with PAM for 2 h demonstrated activated caspase 3/7 and an increased proportion of annexin V-positive cells compared with untreated cells. Additionally, ROS uptake was observed in PAM-treated cells, whereas NAC reduced the cytotoxicity induced by PAM presumably through reduction of ROS uptake. Furthermore, CD44 variant 9, which reportedly leads to glutathione synthesis and suppresses stress signaling of ROS, was overexpressed in PAM-resistant cells.
    PAM treatment induced apoptosis of gastric cancer cells through generation and uptake of ROS. Local administration of PAM could develop into an option to treat peritoneal carcinomatosis.

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  26. Mutational landscape and clonal architecture in grade II and III gliomas Reviewed

    Hiromichi Suzuki, Kosuke Aoki, Kenichi Chiba, Yusuke Sato, Yusuke Shiozawa, Yuichi Shiraishi, Teppei Shimamura, Atsushi Niida, Kazuya Motomura, Fumiharu Ohka, Takashi Yamamoto, Kuniaki Tanahashi, Melissa Ranjit, Toshihiko Wakabayashi, Tetsuichi Yoshizato, Keisuke Kataoka, Kenichi Yoshida, Yasunobu Nagata, Aiko Sato-Otsubo, Hiroko Tanaka, Masashi Sanada, Yutaka Kondo, Hideo Nakamura, Masahiro Mizoguchi, Tatsuya Abe, Yoshihiro Muragaki, Reiko Watanabe, Ichiro Ito, Satoru Miyano, Atsushi Natsume, Seishi Ogawa

    NATURE GENETICS   Vol. 47 ( 5 ) page: 458 - U52   2015.5

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    Grade II and III gliomas are generally slowly progressing brain cancers, many of which eventually transform into more aggressive tumors. Despite recent findings of frequent mutations in IDH1 and other genes, knowledge about their pathogenesis is still incomplete. Here, combining two large sets of high-throughput sequencing data, we delineate the entire picture of genetic alterations and affected pathways in these glioma types, with sensitive detection of driver genes. Grade II and III gliomas comprise three distinct subtypes characterized by discrete sets of mutations and distinct clinical behaviors. Mutations showed significant positive and negative correlations and a chronological hierarchy, as inferred from different allelic burdens among coexisting mutations, suggesting that there is functional interplay between the mutations that drive clonal selection. Extensive serial and multi-regional sampling analyses further supported this finding and also identified a high degree of temporal and spatial heterogeneity generated during tumor expansion and relapse, which is likely shaped by the complex but ordered processes of multiple clonal selection and evolutionary events.

    DOI: 10.1038/ng.3273

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  27. Assessment of Tumor Cells in a Mouse Model of Diffuse Infiltrative Glioma by Raman Spectroscopy Reviewed

    Kuniaki Tanahashi, Atsushi Natsume, Fumiharu Ohka, Hiroyuki Momota, Akira Kato, Kazuya Motomura, Naoki Watabe, Shuichi Muraishi, Hitoshi Nakahara, Yahachi Saito, Ichiro Takeuchi, Toshihiko Wakabayashi

    BIOMED RESEARCH INTERNATIONAL   Vol. 2014   page: 860241   2014

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    Glioma of infiltrative nature is challenging for surgeons to achieve tumor-specific and maximal resection. Raman spectroscopy provides structural information on the targeted materials as vibrational shifts. We utilized Raman spectroscopy to distinguish invasive tumors from normal tissues. Spectra obtained from replication-competent avian sarcoma-(RCAS-) based infiltrative glioma cells and glioma tissues (resembling low-grade human glioma) were compared with those obtained from normal mouse astrocytes and normal tissues. In cell analysis, the spectra at 950-1000, 1030, 1050-1100, 1120-1130, 1120-1200, 1200-1300, 1300-1350, and 1450 cm(-1) were significantly higher in infiltrative glioma cells than in normal astrocytes. In brain tissue analysis, the spectra at 1030, 1050-1100, and 1200-1300 cm(-1) were significantly higher in infiltrative glioma tissues than in normal brain tissues. These spectra reflect the structures of proteins, lipids, and DNA content. The sensitivity and specificity to predict glioma cells by distinguishing normal cells were 98.3% and 75.0%, respectively. Principal component analysis elucidated the significance of spectral difference between tumor tissues and normal tissues. It is possible to distinguish invasive tumors from normal tissues by using Raman spectroscopy.

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  28. Expression of miR-17-92 enhances anti-tumor activity of T-cells transduced with the anti-EGFRvIII chimeric antigen receptor in mice bearing human GBM xenografts Reviewed

    Masasuke Ohno, Takayuki Ohkuri, Akemi Kosaka, Kuniaki Tanahashi, Carl H. June, Atsushi Natsume, Hideho Okada

    Journal for ImmunoTherapy of Cancer   Vol. 1   page: 21   2013

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:BioMed Central Ltd.  

    Background: Expression of miR-17-92 enhances T-cell survival and interferon (IFN)-γ production. We previously reported that miR-17-92 is down-regulated in T-cells derived from glioblastoma (GBM) patients. We hypothesized that transgene-derived co-expression of miR17-92 and chimeric antigen receptor (CAR) in T-cells would improve the efficacy of adoptive transfer therapy against GBM. Methods: We constructed novel lentiviral vectors for miR-17-92 (FG12-EF1a-miR-17/92) and a CAR consisting of an epidermal growth factor receptor variant III (EGFRvIII)-specific, single-chain variable fragment (scFv) coupled to the T-cell receptor CD3ζ chain signaling module and co-stimulatory motifs of CD137 (4-1BB) and CD28 in tandem (pELNS-3C10-CAR). Human T-cells were transduced with these lentiviral vectors, and their anti-tumor effects were evaluated both in vitro and in vivo. Results: CAR-transduced T-cells (CAR-T-cells) exhibited potent, antigen-specific, cytotoxic activity against U87 GBM cells that stably express EGFRvIII (U87-EGFRvIII) and, when co-transduced with miR-17-92, exhibited improved survival in the presence of temozolomide (TMZ) compared with CAR-T-cells without miR-17-92 co-transduction. In mice bearing intracranial U87-EGFRvIII xenografts, CAR-T-cells with or without transgene-derived miR-17-92 expression demonstrated similar levels of therapeutic effect without demonstrating any uncontrolled growth of CAR-T-cells. However, when these mice were re-challenged with U87-EGFRvIII cells in their brains, mice receiving co-transduced CAR-T-cells exhibited improved protection compared with mice treated with CAR-T-cells without miR-17-92 co-transduction. Conclusion: These results warrant the development of novel CAR-T-cell strategies that incorporate miR-17-92 to improve therapeutic potency, especially in patients with GBM.

    DOI: 10.1186/2051-1426-1-21

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  29. Disseminated nocardiosis presenting as retroperitoneal abscess: A case report Reviewed

    Kimiaki Takagi, Yoshiteru Yamada, Naruyasu Masue, Masahiro Uno, Yoshinori Fujimoto, Hisao Komeda, Akira Shiraki, Kuniaki Tanahashi

    Acta Urologica Japonica   Vol. 56 ( 12 ) page: 691 - 695   2010.12

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    A 64-year-old man presented to our emergency room with right back pain on July 10, 2009. At the emergency room, abdominal enhanced computed tomography revealed a cystic lesion in the retroperitoneum. Then he was referred to our department. We performed percutaneous drainage of the retroperitoneal lesion and aspirated white pus. The retroperitoneal cystic lesion proved to be an abscess. Microscopic examination of a Gram stained specimen of the abscess revealed gram-positive bacillary fragments
    therefore, we suspected the pathogen to be Nocardia. He had a history of chronic glomerulonephritis and had received treatment consisting of 20 mg prednisolone, and 75 mg cyclosporine per day. He was regularly visiting the department of cardiovascular for follow-up of chronic heart failure. On the day before his visit to our emergency room, his chest X-ray medicine had revealed a nodular shadow. Then he was referred to the department of respiratory medicine and was scheduled to receive a bronchoscopy later. We suspected the nodule of the lung also to be an abscess of Nocardia. Later, head computed tomography (CT) revealed a brain abscess the pathogen of which was Nocardia. Nocardia is a filamentous, gram-positive, branched bacterium and classified as an aerobic actinobacteria. Nocardia species are difficult to diagnose due to non-specific clinical and histological manifestation. We report this case of disseminated nocardiosis presenting as retroperitoneal abscess. The disseminated nocardiosis was diagnosed without delay by percutaneous drainage and appropriate treatment was provided.

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  30. Ruptured pseudoaneurysm of the petrous internal carotid artery caused by chronic otitis media. Reviewed

    Oyama H, Hattori K, Tanahashi S, Kito A, Maki H, Tanahashi K

    Neurologia medico-chirurgica   Vol. 50 ( 7 ) page: 578 - 80   2010

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    DOI: 10.2176/nmc.50.578

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  31. Glioblastoma Detected at the Initial Stage in its Developmental Process - Case Report Reviewed

    Hirofumi Oyama, Yusuke Ando, Shinichirou Aoki, Akira Kito, Hideki Maki, Kenichi Hattori, Kuniaki Tanahashi

    NEUROLOGIA MEDICO-CHIRURGICA   Vol. 50 ( 5 ) page: 414 - 7   2010

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:JAPAN NEUROSURGICAL SOC  

    A 73-year-old male presented with a glioblastoma that was detected at the initial stage in the developmental process. He suffered cerebral infarction. Follow-up magnetic resonance (MR) imaging showed no abnormality. Ten months later, he had transient right hemiparesis. Diffusion-weighted and fluid-attenuated inversion recovery (FLAIR) MR imaging showed a hyperintense area in the left frontal lobe. The diagnosis was cerebral infarction and antiplatelet drug treatment was begun. The patient's right hemiparesis subsided. Ten days later, right hemiparesis reappeared. Diffusion-weighted and FLAIR MR imaging showed an enlarged hyperintense area in the left frontal lobe. Three weeks after the onset of right hemiparesis, MR imaging revealed an irregular ring-enhanced mass lesion that had further increased in size. The diagnosis was brain abscess and antibiotic treatment was initiated. However, the lesion did not respond and had further enlarged 5 weeks after the onset of right hemiparesis. The lesion was partially removed and the histological diagnosis was glioblastoma with Ki-67 labeling index of 26%. After surgical treatment, the patient received irradiation of 60 Gy and chemotherapy with temozolomide. Follow-up MR imaging showed regrowth of the tumor and aggravation of edema. The rapid progression of the tumor ultimately resulted in the patient's death 12 months after the onset of right hemiparesis. Diffusion-weighted imaging is a good method for the early detection of glioblastoma.

    DOI: 10.2176/nmc.50.414

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  32. Consciousness Recovery Induced by Intrathecal Baclofen Administration After Subarachnoid Hemorrhage - Two Case Reports Reviewed

    Hirofumi Oyama, Akira Kito, Hideki Maki, Kenichi Hattori, Kuniaki Tanahashi

    NEUROLOGIA MEDICO-CHIRURGICA   Vol. 50 ( 5 ) page: 386 - 90   2010

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:JAPAN NEUROSURGICAL SOC  

    Two patients with subarachnoid hemorrhage recovered consciousness after intrathecal baclofen administration using an implanted intrathecal baclofen pump delivering 50 mu g per day using a simple infusion mode. Intrathecal baclofen resulted in significant reduction of spasticity 3 months after the implantation. Case 1 was reduced to a completely bedridden state with spasticity and could slightly move her fingers following commands. However, the patient could eat food and wash her face with minimal assistance at 3 months after the implantation, and could stand up in the parallel bars with assistance and speak several words at 8 months. Case 2 was in a completely bedridden state at 10 months after onset and could neither drink water nor follow instructions. However, the patient became oriented and could eat by herself within 3 to 4 weeks of implantation. She could walk with a cane and use the stairs with minimal assistance at 2 and 3 months after implantation. The patient could speak fluently within 6 months of implantation. Flatulence and dysuria happened during the screening test, but these symptoms were not repeated after implantation of a pump-catheter-system and continuous intrathecal baclofen infusion. Continuous intrathecal baclofen infusion caused both improvement in muscle tone and spasms and consciousness recovery from the vegetative state. This therapy is a strong candidate treatment for patients with spasticity and consciousness disturbance.

    DOI: 10.2176/nmc.50.386

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  33. Compression of the medulla oblongata and acute respiratory failure caused by rupture of a thrombosed large aneurysm of the anterior inferior cerebellar artery. Reviewed

    Oyama H, Kito A, Maki H, Hattori K, Tanahashi K

    Neurologia medico-chirurgica   Vol. 50 ( 7 ) page: 571 - 3   2010

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    DOI: 10.2176/nmc.50.571

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  34. GM1 expression in H-ras-transformed NIH3T3 results in the suppression of cell proliferation inducing the partial transfer of activated H-ras from non-raft to raft fraction.

    Hamamura K.

    International journal of oncology   Vol. 26 ( 4 ) page: 897 - 904   2005.4

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    Publishing type:Research paper (scientific journal)   Publisher:International journal of oncology  

    DOI: 10.3892/ijo.26.4.897

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  35. GM1 expression in H-ras-transformed NIH3T3 results in the suppression of cell proliferation inducing the partial transfer of activated H-ras from non-raft to raft fraction Reviewed

    K Hamamura, K Tanahashi, K Furukawa, T Hattori, H Hattori, H Mizutani, M Ueda, T Urano, K Furukawa

    INTERNATIONAL JOURNAL OF ONCOLOGY   Vol. 26 ( 4 ) page: 897 - 904   2005.4

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:PROFESSOR D A SPANDIDOS  

    c-H-ras is located in lipid/rafts and undergoes cholesterol dependent regulation. To analyze the regulatory effects of ganglioside GM1 on the proliferation of fibroblasts transformed with mutated ras gene, GM1 synthase cDNA was transfected into NIH3T3/H-ras cells containing mutation. In the transient expression system with EGFP-fused GM1 synthase, the ratio of BrdU-positive cells among EGFP-positive cells was compared between GM1(+) transfectant cells and control cells, indicating that the transient GM1 expression suppresses cell proliferation. Then, established transfectant cells C21 and C34 expressed definite levels of GM1, and analyzed for the cell growth with the control cells D2 and D4 expressing no GM1. GM1(+) cells showed reduced proliferation compared with controls. Phosphorylation levels of ERK1/2 after FCS treatment were examined, showing that those on the GM1(+) transfectant cells increased slowly, while those in the controls rapidly reached the plateau. Fractionation of Triton X-100 extracts with sucrose density gradient ultracentrifugation revealed that activated H-ras proteins from controls as well as NIH3T3/H-ras were completely localized in non-GEM/raft fraction. On the other hand, some portions of activated H-ras were transferred to GEM/raft fraction, i.e., 32% in C21, and 8% in C34. Since the Ras effector Raf-1 was localized in non-GEM/raft, the growth suppression might be caused, at least partly, by the movement of activated H-ras to GEM/raft fraction.

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  36. GM1 expression in H-ras-transformed NIH3T3 results in the suppression of cell proliferation inducing the partial transfer of activated H-ras from non-raft to raft fraction.

    Hamamura K, Tanahashi K, Furukawa K, Hattori T, Hattori H, Mizutani H, Ueda M, Urano T, Furukawa K

    International journal of oncology   Vol. 26 ( 4 ) page: 897 - 904   2005.4

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    PubMed

  37. GM1 expression in H-ras-transformed NIH3T3 results in the suppression of cell proliferation inducing the partial transfer of activated H-ras from non-raft to raft fraction

    Hamamura K, Tanahashi K, Furukawa K, Hattori T, Hattori H, Mizutani H, Ueda M, Urano T, Furukawa K

    INTERNATIONAL JOURNAL OF ONCOLOGY   Vol. 26 ( 4 ) page: 897 - 904   2005.4

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KAKENHI (Grants-in-Aid for Scientific Research) 2

  1. 髄膜腫の局在と硬膜の発生学的背景に基づいた腫瘍進展機構と間葉系幹細胞の果たす役割

    Grant number:20K17928  2020.4 - 2022.3

    若手研究

    棚橋 邦明

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    Authorship:Principal investigator 

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    脳腫瘍の多くを占める髄膜腫の中には、脳底部に広がるように増大するものがあり、脳神経を巻き込んで障害するため外科的治療が難しい。髄膜腫がこのように増大する機序は未だ解明されていない。
    本研究では、髄膜腫が発生部位ごとに特徴的な遺伝子変異をもつことと、脳底部の正常髄膜が形作られる由来組織(中胚葉)に着目し、髄膜腫増大のメカニズムを解明することを目的とする。脳底部における髄膜組織に特徴的な幹細胞が、髄膜腫発育の足場環境を作り出しているという仮説を立て、髄膜腫摘出検体・培養髄膜腫細胞・髄膜腫マウスモデルを用いて解析することで、これを明らかにする。

  2. Mechano-sensor system of extracelluar matrix to control cancer-associated fibroblast differentiation regulating meningioma progression

    Grant number:17K16639  2017.4 - 2020.3

    Tanahashi Kuniaki

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    Authorship:Principal investigator 

    Grant amount:\4030000 ( Direct Cost: \3100000 、 Indirect Cost:\930000 )

    Meningiomas that arise from skull base regions show poor functional prognosis because they grow along dura mater and involve cranial nerves. They do not have NF2 gene mutations and mechanisms of the growth pattern should be clarified.
    Immunohistochemistry of meningiomas from skull base regions showed high expression of Meflin which is reported to be an undifferentiation marker of mesenchymal stem cells. The expression pattern of Hippo pathway-related proteins showed normal NF2 gene function in those meningiomas. Stiffness modulation of extracellular matrix of meningioma cell lines without NF2 mutation implied mechanosensor function for their growth pattern.
    The results implied Meningiomas without NF2 mutation has mechanosensor function which is related to mesenchymal stem cells for their growth pattern.