2022/01/27 更新

写真a

ナツメダ マナブ
棗田 学
NATSUMEDA Manabu
所属
脳研究所 助教
職名
助教
外部リンク

学位

  • 博士(分子細胞医学) ( 2012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

経歴(researchmap)

  • Johns Hopkins大学神経病理学分野   Postdoctoral fellow

    2013年9月 - 2016年3月

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  • 新潟大学 脳研究所 脳神経外科   Brain Research Institute   助教

    2013年4月 - 現在

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経歴

  • 新潟大学   脳研究所 基礎神経科学部門   助教

    2020年4月 - 現在

  • 新潟大学   脳研究所 生命科学リソース研究センター   助教

    2013年4月 - 2020年3月

学歴

  • 新潟大学医歯学総合研究科(神経病理学)

    2007年4月 - 2011年3月

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  • 新潟大学医学部医学科

    1997年4月 - 2003年3月

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所属学協会

▶ 全件表示

委員歴

  • 日本臨床腫瘍研究グループ   JCOG PRC医学審査委員  

    2019年4月 - 現在   

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    団体区分:学協会

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留学歴

  • ジョンズ=ホプキンス大学   リサーチ=フェロー

    2013年10月 - 現在

取得資格

  • 医師

  • 日本癌治療認定医

  • 英語検定1級

  • TOEFL

 

論文

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

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

    Brain tumor pathology   38 ( 3 )   228 - 233   2021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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  • [The Present and Future of Less-invasive Liquid Biopsy for the Diagnosis of Gliomas and Brain Tumors].

    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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  • Low Detection Rate of H3K27M Mutations in Cerebrospinal Fluid Obtained from Lumbar Puncture in Newly Diagnosed Diffuse Midline Gliomas. 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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  • Topoisomerase IIβ immunoreactivity (IR) co-localizes with neuronal marker-IR but not glial fibrillary acidic protein-IR in GLI3-positive medulloblastomas: an immunohistochemical analysis of 124 medulloblastomas from the Japan Children's Cancer Group.

    Hiroaki Miyahara, Manabu Natsumeda, Yonehiro Kanemura, Kai Yamasaki, Yuichi Riku, Akio Akagi, Wataru Oohashi, Tomoko Shofuda, Ema Yoshioka, Yuya Sato, Takashi Taga, Yuki Naruke, Ryo Ando, Daiichiro Hasegawa, Makiko Yoshida, Tsukasa Sakaida, Naoki Okada, Hiroyoshi Watanabe, Michio Ozeki, Yoshiki Arakawa, Junichi Yoshimura, Yukihiko Fujii, Souichi Suenobu, Kenji Ihara, Junichi Hara, Akiyoshi Kakita, Mari Yoshida, Yasushi Iwasaki

    Brain tumor pathology   38 ( 2 )   109 - 121   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)  

    We previously reported observing GLI3 in medulloblastomas expressing neuronal markers (NM) and/or glial fibrillary acidic protein (GFAP). Furthermore, patients with medulloblastomas expressing NM or GFAP tended to show favorable or poor prognosis, respectively. In the present study, we focused on the role of topoisomerase IIβ (TOP2β) as a possible regulator for neuronal differentiation in medulloblastomas and examined the pathological roles of GLI3, NM, GFAP, and TOP2β expressions in a larger population. We divided 124 medulloblastomas into three groups (NM-/GFAP-, NM +/GFAP-, and GFAP +) based on their immunoreactivity (IR) against NM and GFAP. The relationship among GLI3, NM, GFAP, and TOP2β was evaluated using fluorescent immunostaining and a publicly available single-cell RNA sequencing dataset. In total, 87, 30, and 7 medulloblastomas were classified as NM-/GFAP-, NM + /GFAP-, and GFAP +, and showed intermediate, good, and poor prognoses, respectively. GLI3-IR was frequently observed in NM +/GFAP-  and GFAP + , and TOP2β-IR was frequently observed only in NM +/GFAP-  medulloblastomas. In fluorescent immunostaining, TOP2β-IR was mostly co-localized with NeuN-IR but not with GFAP-IR. In single-cell RNA sequencing, TOP2β expression was elevated in CMAS/DCX-positive, but not in GFAP-positive, cells. NM-IR and GFAP-IR are important for estimating the prognosis of patients with medulloblastoma; hence they should be assessed in clinical practice.

    DOI: 10.1007/s10014-021-00396-0

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

    Kouichirou Okamoto, Manabu Natsumeda, Makoto Oishi, Yukihiko Fujii

    No shinkei geka. Neurological surgery   49 ( 2 )   383 - 387   2021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)  

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

    DOI: 10.11477/mf.1436204402

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  • [Melanocytic Tumors].

    Kouichirou Okamoto, Manabu Natsumeda, Makoto Oishi, Yukihiko Fujii

    No shinkei geka. Neurological surgery   49 ( 2 )   389 - 394   2021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)  

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

    DOI: 10.11477/mf.1436204403

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

    Kouichirou Okamoto, Manabu Natsumeda, Makoto Oishi, Yukihiko Fujii

    No shinkei geka. Neurological surgery   49 ( 2 )   395 - 399   2021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)  

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

    DOI: 10.11477/mf.1436204404

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  • [Proton magnetic resonance spectroscopy (1H-MRS)].

    Hironaka Igarashi, Motohide Takeda, Manabu Natsumeda, Yukihiko Fujii

    No shinkei geka. Neurological surgery   49 ( 2 )   438 - 444   2021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)  

    Proton magnetic resonance spectroscopy(1H-MRS)is a non-invasive method for evaluating brain function and metabolism. 1H-MRS can quantify low-molecular-weight metabolites in a living brain; it shows their spectra without tracer administration. In this paper, we introduce 1H-MRS and MRS for imaging the distribution of metabolites. The applications of 1H-MRS imaging for several neurological disorders will be outlined.

    DOI: 10.11477/mf.1436204411

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  • GLI3 Is Associated With Neuronal Differentiation in SHH-Activated and WNT-Activated Medulloblastoma. 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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  • Necessity for craniospinal irradiation of germinoma with positive cytology without spinal lesion on MR imaging—A controversy

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

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

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

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


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


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


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


    </sec>

    DOI: 10.1093/noajnl/vdab086

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

  • Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1. 国際誌

    Daniel J Klionsky, Amal Kamal Abdel-Aziz, Sara Abdelfatah, Mahmoud Abdellatif, Asghar Abdoli, Steffen Abel, Hagai Abeliovich, Marie H Abildgaard, Yakubu Princely Abudu, Abraham Acevedo-Arozena, Iannis E Adamopoulos, Khosrow Adeli, Timon E Adolph, Annagrazia Adornetto, Elma Aflaki, Galila Agam, Anupam Agarwal, Bharat B Aggarwal, Maria Agnello, Patrizia Agostinis, Javed N Agrewala, Alexander Agrotis, Patricia V Aguilar, S Tariq Ahmad, Zubair M Ahmed, Ulises Ahumada-Castro, Sonja Aits, Shu Aizawa, Yunus Akkoc, Tonia Akoumianaki, Hafize Aysin Akpinar, Ahmed M Al-Abd, Lina Al-Akra, Abeer Al-Gharaibeh, Moulay A Alaoui-Jamali, Simon Alberti, Elísabet Alcocer-Gómez, Cristiano Alessandri, Muhammad Ali, M Abdul Alim Al-Bari, Saeb Aliwaini, Javad Alizadeh, Eugènia Almacellas, Alexandru Almasan, Alicia Alonso, Guillermo D Alonso, Nihal Altan-Bonnet, Dario C Altieri, Élida M C Álvarez, Sara Alves, Cristine Alves da Costa, Mazen M Alzaharna, Marialaura Amadio, Consuelo Amantini, Cristina Amaral, Susanna Ambrosio, Amal O Amer, Veena Ammanathan, Zhenyi An, Stig U Andersen, Shaida A Andrabi, Magaiver Andrade-Silva, Allen M Andres, Sabrina Angelini, David Ann, Uche C Anozie, Mohammad Y Ansari, Pedro Antas, Adam Antebi, Zuriñe Antón, Tahira Anwar, Lionel Apetoh, Nadezda Apostolova, Toshiyuki Araki, Yasuhiro Araki, Kohei Arasaki, Wagner L Araújo, Jun Araya, Catherine Arden, Maria-Angeles Arévalo, Sandro Arguelles, Esperanza Arias, Jyothi Arikkath, Hirokazu Arimoto, Aileen R Ariosa, Darius Armstrong-James, Laetitia Arnauné-Pelloquin, Angeles Aroca, Daniela S Arroyo, Ivica Arsov, Rubén Artero, Dalia Maria Lucia Asaro, Michael Aschner, Milad Ashrafizadeh, Osnat Ashur-Fabian, Atanas G Atanasov, Alicia K Au, Patrick Auberger, Holger W Auner, Laure Aurelian, Riccardo Autelli, Laura Avagliano, Yenniffer Ávalos, Sanja Aveic, Célia Alexandra Aveleira, Tamar Avin-Wittenberg, Yucel Aydin, Scott Ayton, Srinivas Ayyadevara, Maria Azzopardi, Misuzu Baba, Jonathan M Backer, Steven K Backues, Dong-Hun Bae, Ok-Nam Bae, Soo Han Bae, Eric H Baehrecke, Ahruem Baek, Seung-Hoon Baek, Sung Hee Baek, Giacinto Bagetta, Agnieszka Bagniewska-Zadworna, Hua Bai, Jie Bai, Xiyuan Bai, Yidong Bai, Nandadulal Bairagi, Shounak Baksi, Teresa Balbi, Cosima T Baldari, Walter Balduini, Andrea Ballabio, Maria Ballester, Salma Balazadeh, Rena Balzan, Rina Bandopadhyay, Sreeparna Banerjee, Sulagna Banerjee, Ágnes Bánréti, Yan Bao, Mauricio S Baptista, Alessandra Baracca, Cristiana Barbati, Ariadna Bargiela, Daniela Barilà, Peter G Barlow, Sami J Barmada, Esther Barreiro, George E Barreto, Jiri Bartek, Bonnie Bartel, Alberto Bartolome, Gaurav R Barve, Suresh H Basagoudanavar, Diane C Bassham, Robert C Bast Jr, Alakananda Basu, Henri Batoko, Isabella Batten, Etienne E Baulieu, Bradley L Baumgarner, Jagadeesh Bayry, Rupert Beale, Isabelle Beau, Florian Beaumatin, Luiz R G Bechara, George R Beck Jr, Michael F Beers, Jakob Begun, Christian Behrends, Georg M N Behrens, Roberto Bei, Eloy Bejarano, Shai Bel, Christian Behl, Amine Belaid, Naïma Belgareh-Touzé, Cristina Bellarosa, Francesca Belleudi, Melissa Belló Pérez, Raquel Bello-Morales, Jackeline Soares de Oliveira Beltran, Sebastián Beltran, Doris Mangiaracina Benbrook, Mykolas Bendorius, Bruno A Benitez, Irene Benito-Cuesta, Julien Bensalem, Martin W Berchtold, Sabina Berezowska, Daniele Bergamaschi, Matteo Bergami, Andreas Bergmann, Laura Berliocchi, Clarisse Berlioz-Torrent, Amélie Bernard, Lionel Berthoux, Cagri G Besirli, Sebastien Besteiro, Virginie M Betin, Rudi Beyaert, Jelena S Bezbradica, Kiran Bhaskar, Ingrid Bhatia-Kissova, Resham Bhattacharya, Sujoy Bhattacharya, Shalmoli Bhattacharyya, Md Shenuarin Bhuiyan, Sujit Kumar Bhutia, Lanrong Bi, Xiaolin Bi, Trevor J Biden, Krikor Bijian, Viktor A Billes, Nadine Binart, Claudia Bincoletto, Asa B Birgisdottir, Geir Bjorkoy, Gonzalo Blanco, Ana Blas-Garcia, Janusz Blasiak, Robert Blomgran, Klas Blomgren, Janice S Blum, Emilio Boada-Romero, Mirta Boban, Kathleen Boesze-Battaglia, Philippe Boeuf, Barry Boland, Pascale Bomont, Paolo Bonaldo, Srinivasa Reddy Bonam, Laura Bonfili, Juan S Bonifacino, Brian A Boone, Martin D Bootman, Matteo Bordi, Christoph Borner, Beat C Bornhauser, Gautam Borthakur, Jürgen Bosch, Santanu Bose, Luis M Botana, Juan Botas, Chantal M Boulanger, Michael E Boulton, Mathieu Bourdenx, Benjamin Bourgeois, Nollaig M Bourke, Guilhem Bousquet, Patricia Boya, Peter V Bozhkov, Luiz H M Bozi, Tolga O Bozkurt, Doug E Brackney, Christian H Brandts, Ralf J Braun, Gerhard H Braus, Roberto Bravo-Sagua, José M Bravo-San Pedro, Patrick Brest, Marie-Agnès Bringer, Alfredo Briones-Herrera, V Courtney Broaddus, Peter Brodersen, Jeffrey L Brodsky, Steven L Brody, Paola G Bronson, Jeff M Bronstein, Carolyn N Brown, Rhoderick E Brown, Patricia C Brum, John H Brumell, Nicola Brunetti-Pierri, Daniele Bruno, Robert J Bryson-Richardson, Cecilia Bucci, Carmen Buchrieser, Marta Bueno, Laura Elisa Buitrago-Molina, Simone Buraschi, Shilpa Buch, J Ross Buchan, Erin M Buckingham, Hikmet Budak, Mauricio Budini, Geert Bultynck, Florin Burada, Joseph R Burgoyne, M Isabel Burón, Victor Bustos, Sabrina Büttner, Elena Butturini, Aaron Byrd, Isabel Cabas, Sandra Cabrera-Benitez, Ken Cadwell, Jingjing Cai, Lu Cai, Qian Cai, Montserrat Cairó, Jose A Calbet, Guy A Caldwell, Kim A Caldwell, Jarrod A Call, Riccardo Calvani, Ana C Calvo, Miguel Calvo-Rubio Barrera, Niels Os Camara, Jacques H Camonis, Nadine Camougrand, Michelangelo Campanella, Edward M Campbell, François-Xavier Campbell-Valois, Silvia Campello, Ilaria Campesi, Juliane C Campos, Olivier Camuzard, Jorge Cancino, Danilo Candido de Almeida, Laura Canesi, Isabella Caniggia, Barbara Canonico, Carles Cantí, Bin Cao, Michele Caraglia, Beatriz Caramés, Evie H Carchman, Elena Cardenal-Muñoz, Cesar Cardenas, Luis Cardenas, Sandra M Cardoso, Jennifer S Carew, Georges F Carle, Gillian Carleton, Silvia Carloni, Didac Carmona-Gutierrez, Leticia A Carneiro, Oliana Carnevali, Julian M Carosi, 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Wang, Yanchang Wang, Yanzhuang Wang, Yen-Yun Wang, Yihua Wang, Yipeng Wang, Yu Wang, Yuqi Wang, Zhe Wang, Zhenyu Wang, Zhouguang Wang, Gary Warnes, Verena Warnsmann, Hirotaka Watada, Eizo Watanabe, Maxinne Watchon, Anna Wawrzyńska, Timothy E Weaver, Grzegorz Wegrzyn, Ann M Wehman, Huafeng Wei, Lei Wei, Taotao Wei, Yongjie Wei, Oliver H Weiergräber, Conrad C Weihl, Günther Weindl, Ralf Weiskirchen, Alan Wells, Runxia H Wen, Xin Wen, Antonia Werner, Beatrice Weykopf, Sally P Wheatley, J Lindsay Whitton, Alexander J Whitworth, Katarzyna Wiktorska, Manon E Wildenberg, Tom Wileman, Simon Wilkinson, Dieter Willbold, Brett Williams, Robin S B Williams, Roger L Williams, Peter R Williamson, Richard A Wilson, Beate Winner, Nathaniel J Winsor, Steven S Witkin, Harald Wodrich, Ute Woehlbier, Thomas Wollert, Esther Wong, Jack Ho Wong, Richard W Wong, Vincent Kam Wai Wong, W Wei-Lynn Wong, An-Guo Wu, Chengbiao Wu, Jian Wu, Junfang Wu, Kenneth K Wu, Min Wu, Shan-Ying Wu, Shengzhou Wu, Shu-Yan Wu, Shufang Wu, William K K Wu, Xiaohong Wu, Xiaoqing Wu, Yao-Wen Wu, Yihua Wu, Ramnik J Xavier, Hongguang Xia, Lixin Xia, Zhengyuan Xia, Ge Xiang, Jin Xiang, Mingliang Xiang, Wei Xiang, Bin Xiao, Guozhi Xiao, Hengyi Xiao, Hong-Tao Xiao, Jian Xiao, Lan Xiao, Shi Xiao, Yin Xiao, Baoming Xie, Chuan-Ming Xie, Min Xie, Yuxiang Xie, Zhiping Xie, Zhonglin Xie, Maria Xilouri, Congfeng Xu, En Xu, Haoxing Xu, Jing Xu, JinRong Xu, Liang Xu, Wen Wen Xu, Xiulong Xu, Yu Xue, Sokhna M S Yakhine-Diop, Masamitsu Yamaguchi, Osamu Yamaguchi, Ai Yamamoto, Shunhei Yamashina, Shengmin Yan, Shian-Jang Yan, Zhen Yan, Yasuo Yanagi, Chuanbin Yang, Dun-Sheng Yang, Huan Yang, Huang-Tian Yang, Hui Yang, Jin-Ming Yang, Jing Yang, Jingyu Yang, Ling Yang, Liu Yang, Ming Yang, Pei-Ming Yang, Qian Yang, Seungwon Yang, Shu Yang, Shun-Fa Yang, Wannian Yang, Wei Yuan Yang, Xiaoyong Yang, Xuesong Yang, Yi Yang, Ying Yang, Honghong Yao, Shenggen Yao, Xiaoqiang Yao, Yong-Gang Yao, Yong-Ming Yao, Takahiro Yasui, Meysam Yazdankhah, Paul M Yen, Cong Yi, Xiao-Ming Yin, Yanhai Yin, Zhangyuan Yin, Ziyi Yin, Meidan Ying, Zheng Ying, Calvin K Yip, Stephanie Pei Tung Yiu, Young H Yoo, Kiyotsugu Yoshida, Saori R Yoshii, Tamotsu Yoshimori, Bahman Yousefi, Boxuan Yu, Haiyang Yu, Jun Yu, Jun Yu, Li Yu, Ming-Lung Yu, Seong-Woon Yu, Victor C Yu, W Haung Yu, Zhengping Yu, Zhou Yu, Junying Yuan, Ling-Qing Yuan, Shilin Yuan, Shyng-Shiou F Yuan, Yanggang Yuan, Zengqiang Yuan, Jianbo Yue, Zhenyu Yue, Jeanho Yun, Raymond L Yung, David N Zacks, Gabriele Zaffagnini, Vanessa O Zambelli, Isabella Zanella, Qun S Zang, Sara Zanivan, Silvia Zappavigna, Pilar Zaragoza, Konstantinos S Zarbalis, Amir Zarebkohan, Amira Zarrouk, Scott O Zeitlin, Jialiu Zeng, Ju-Deng Zeng, Eva Žerovnik, Lixuan Zhan, Bin Zhang, Donna D Zhang, Hanlin Zhang, Hong Zhang, Hong Zhang, Honghe Zhang, Huafeng Zhang, Huaye Zhang, Hui Zhang, Hui-Ling Zhang, Jianbin Zhang, Jianhua Zhang, Jing-Pu Zhang, Kalin Y B Zhang, Leshuai W Zhang, Lin Zhang, Lisheng Zhang, Lu Zhang, Luoying Zhang, Menghuan Zhang, Peng Zhang, Sheng Zhang, Wei Zhang, Xiangnan Zhang, Xiao-Wei Zhang, Xiaolei Zhang, Xiaoyan Zhang, Xin Zhang, Xinxin Zhang, Xu Dong Zhang, Yang Zhang, Yanjin Zhang, Yi Zhang, Ying-Dong Zhang, Yingmei Zhang, Yuan-Yuan Zhang, Yuchen Zhang, Zhe Zhang, Zhengguang Zhang, Zhibing Zhang, Zhihai Zhang, Zhiyong Zhang, Zili Zhang, Haobin Zhao, Lei Zhao, Shuang Zhao, Tongbiao Zhao, Xiao-Fan Zhao, Ying Zhao, Yongchao Zhao, Yongliang Zhao, Yuting Zhao, Guoping Zheng, Kai Zheng, Ling Zheng, Shizhong Zheng, Xi-Long Zheng, Yi Zheng, Zu-Guo Zheng, Boris Zhivotovsky, Qing Zhong, Ao Zhou, Ben Zhou, Cefan Zhou, Gang Zhou, Hao Zhou, Hong Zhou, Hongbo Zhou, Jie Zhou, Jing Zhou, Jing Zhou, Jiyong Zhou, Kailiang Zhou, Rongjia Zhou, Xu-Jie Zhou, Yanshuang Zhou, Yinghong Zhou, Yubin Zhou, Zheng-Yu Zhou, Zhou Zhou, Binglin Zhu, Changlian Zhu, Guo-Qing Zhu, Haining Zhu, Hongxin Zhu, Hua Zhu, Wei-Guo Zhu, Yanping Zhu, Yushan Zhu, Haixia Zhuang, Xiaohong Zhuang, Katarzyna Zientara-Rytter, Christine M Zimmermann, Elena Ziviani, Teresa Zoladek, Wei-Xing Zong, Dmitry B Zorov, Antonio Zorzano, Weiping Zou, Zhen Zou, Zhengzhi Zou, Steven Zuryn, Werner Zwerschke, Beate Brand-Saberi, X Charlie Dong, Chandra Shekar Kenchappa, Zuguo Li, Yong Lin, Shigeru Oshima, Yueguang Rong, Judith C Sluimer, Christina L Stallings, Chun-Kit Tong

    Autophagy   17 ( 1 )   1 - 382   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)  

    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

    DOI: 10.1080/15548627.2020.1797280

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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

    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

    サイトメトリーリサーチ   31 ( 1 )   7 - 13   2021年

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    記述言語:日本語   出版者・発行元:日本サイトメトリー学会  

    <p>For post-translational protein modifications such as phosphorylation, the involved residues have been recently identified by mass spectrometers. However, it is not easy to efficiently detect the therapeutic target from the vast amount of proteomic data. Neuronal growth cones are specialized, highly motile structures formed at the tip of axons, that are indispensable for synaptogenesis in the developing brain and for neuronal plasticity in the adult brain. However, there is lack of information on the molecular basis of growth cones in the mammalian brain. We performed a phosphoproteomic analysis of growth cone membrane fractions (2 mg) isolated from the rat forebrain on postnatal day 1. We chose the more abundant peptides as research-targets, based on the hypothesis that abundant phosphorylated sites are involved in important biological functions. The phosphopeptides detected with high frequency at the 1st (Serine [S] 96) and 9th (Threonine [T] 172) positions were the phosphorylation sites of neuronal growth-associated protein - 43 kDa (GAP 43). C-jun N-terminal kinase (JNK) was responsible for phosphorylation at these sites, which increased during neuronal development and axonal regeneration. T172 phosphorylation was also confi rmed in rodents and primates. This review introduces our methodology for fi nding novel phospho-proteins as therapeutic molecular targets for specifi c diseases, along with their regulatory kinases. We believe that our serial approach, as illustrated here, can be applied to various research fi elds. In future research, we propose to demonstrate that pT172 antibody can be utilized as an axonal growth and regeneration marker in humans.</p>

    DOI: 10.18947/cytometryresearch.31.1_7

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  • A Hyperactive RelA/p65-Hexokinase 2 Signaling Axis Drives Primary Central Nervous System Lymphoma. 国際誌

    Kensuke Tateishi, Yohei Miyake, Masahito Kawazu, Nobuyoshi Sasaki, Taishi Nakamura, Jo Sasame, Yukie Yoshii, Toshihide Ueno, Akio Miyake, Jun Watanabe, Yuko Matsushita, Norio Shiba, Naoko Udaka, Kentaro Ohki, Alexandria L Fink, Shilpa S Tummala, Manabu Natsumeda, Naoki Ikegaya, Mayuko Nishi, Makoto Ohtake, Ryohei Miyazaki, Jun Suenaga, Hidetoshi Murata, Ichio Aoki, Julie J Miller, Yukihiko Fujii, Akihide Ryo, Shoji Yamanaka, Hiroyuki Mano, Daniel P Cahill, Hiroaki Wakimoto, Andrew S Chi, Tracy T Batchelor, Motoo Nagane, Koichi Ichimura, Tetsuya Yamamoto

    Cancer research   80 ( 23 )   5330 - 5343   2020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)  

    Primary central nervous system lymphoma (PCNSL) is an isolated type of lymphoma of the central nervous system and has a dismal prognosis despite intensive chemotherapy. Recent genomic analyses have identified highly recurrent mutations of MYD88 and CD79B in immunocompetent PCNSL, whereas LMP1 activation is commonly observed in Epstein-Barr virus (EBV)-positive PCNSL. However, a lack of clinically representative preclinical models has hampered our understanding of the pathogenic mechanisms by which genetic aberrations drive PCNSL disease phenotypes. Here, we establish a panel of 12 orthotopic, patient-derived xenograft (PDX) models from both immunocompetent and EBV-positive PCNSL and secondary CNSL biopsy specimens. PDXs faithfully retained their phenotypic, metabolic, and genetic features, with 100% concordance of MYD88 and CD79B mutations present in PCNSL in immunocompetent patients. These models revealed a convergent functional dependency upon a deregulated RelA/p65-hexokinase 2 signaling axis, codriven by either mutated MYD88/CD79B or LMP1 with Pin1 overactivation in immunocompetent PCNSL and EBV-positive PCNSL, respectively. Notably, distinct molecular alterations used by immunocompetent and EBV-positive PCNSL converged to deregulate RelA/p65 expression and to drive glycolysis, which is critical for intracerebral tumor progression and FDG-PET imaging characteristics. Genetic and pharmacologic inhibition of this key signaling axis potently suppressed PCNSL growth in vitro and in vivo. These patient-derived models offer a platform for predicting clinical chemotherapeutics efficacy and provide critical insights into PCNSL pathogenic mechanisms, accelerating therapeutic discovery for this aggressive disease. SIGNIFICANCE: A set of clinically relevant CNSL xenografts identifies a hyperactive RelA/p65-hexokinase 2 signaling axis as a driver of progression and potential therapeutic target for treatment and provides a foundational preclinical platform. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/23/5330/F1.large.jpg.

    DOI: 10.1158/0008-5472.CAN-20-2425

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  • Molecular Features and Prognostic Factors of Pleomorphic Xanthoastrocytoma: A Collaborative Investigation of the Tohoku Brain Tumor Study Group.

    Takahiro Ono, Toshio Sasajima, Hiroaki Shimizu, Manabu Natsumeda, Masayuki Kanamori, Kenichiro Asano, Takaaki Beppu, Kenichiro Matsuda, Masahiro Ichikawa, Yukihiko Fujii, Hiroki Ohkuma, Kuniaki Ogasawara, Yukihiko Sonoda, Kiyoshi Saito, Sumihito Nobusawa, Yoichi Nakazato, Chifumi Kitanaka, Takamasa Kayama, Teiji Tominaga

    Neurologia medico-chirurgica   60 ( 11 )   543 - 552   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Pleomorphic xanthoastrocytoma (PXA) is a rare glial tumor, however, its histological differentiation from high-grade gliomas is often difficult. Molecular characteristics may contribute to a better diagnostic discrimination. Prognostic factors of PXA are also important but few relevant reports have been published. This study investigated the molecular features and prognostic factors of PXAs. Seven university hospitals participated in this study by providing retrospective clinical data and tumor samples of PXA cases between 1993 and 2014. Tumor samples were analyzed for immunohistochemical (IHC) neuronal and glial markers along with Ki67. The status of the BRAF and TERT promoter (TERTp) mutation was also evaluated using the same samples, followed by feature extraction of PXA and survival analyses. In all, 19 primary cases (17 PXA and 2 anaplastic PXA) were included. IHC examination revealed the stable staining of nestin and the close association of synaptophysin to NFP. Of the PXA cases, 57% had the BRAF mutation and only 7% had the TERTp mutation. On univariate analysis, age (≥60 years), preoperative Karnofsky performance status (KPS) (≤80%), and marked peritumoral edema were significantly associated with progression-free survival (PFS). No independent factor was indicated by the multivariate analysis. In conclusion, PXA was characterized by positive nestin staining and a few TERTp mutations. The neuronal differential marker and BRAF status may help in diagnosis. Patient age, preoperative KPS, and marked perifocal edema were associated with PFS. The present study is limited because of small number of cases and its retrospective nature. Further clinical study is needed.

    DOI: 10.2176/nmc.oa.2020-0155

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

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

    Neuro-oncology   23 ( 2 )   295 - 303   2020年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The Delphi consensus statements on the management of germ cell tumors (GCTs) failed to reach agreements on the statement that the cases with 1) pineal and neurohypophyseal bifocal lesion, 2) with diabetes insipidus, and 3) with negative tumor markers can be diagnosed as germinoma without histological verification. To answer this, multicenter retrospective analysis was performed. METHODS: A questionnaire on clinical findings, histological diagnosis, and details of surgical procedures was sent to 86 neurosurgical and 35 pediatrics departments in Japan. RESULTS: Fifty-one institutes reported 132 cases that fulfilled the three criteria. Tissue sampling was performed in 91 cases from pineal (n = 44), neurohypophyseal (n = 32), both (n = 6) and distant (n = 9) lesions. Histological diagnosis was established in 89 cases: pure germinoma or germinoma with syncytiotrophoblastic giant cells in 82 (92.1%) cases, germinoma and mature teratoma in two cases, and granulomatous inflammation in two cases. Histological diagnosis was not established in two cases. Although no tumors other than GCTs were identified, three (3.4%) patients had non-germinomatous GCTs (NGGCTs). None of the patients developed permanent complications after endoscopic or stereotactic biopsy. Thirty-nine patients underwent simultaneous procedure for acute hydrocephalus without permanent complications, and hydrocephalus was controlled in 94.9% of them. CONCLUSION: All patients who fulfilled the three criteria had GCTs or granulomatous inflammation, but not other types of tumors. However, no less than 3.4% of the patients had NGGCTs. Considering the safety and the effects of simultaneous procedures for acute hydrocephalus, biopsy was recommended in such patients.

    DOI: 10.1093/neuonc/noaa199

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  • [Endovascular Revascularization for Acute Ischemic Stroke Related to Blunt Carotid Injury:A Case Report].

    Shoji Saito, Hitoshi Hasegawa, Daisuke Sato, Kazuhiro Ando, Kunio Motohashi, Manabu Natsumeda, Bumpei Kikuchi, Makoto Oishi, Yukihiko Fujii

    No shinkei geka. Neurological surgery   48 ( 6 )   527 - 532   2020年6月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Although blunt carotid artery injury is known as an important cause of ischemic stroke, the role of the endovascular treatment for acute ischemic stroke related to blunt carotid injuries remains unclear. We report the case of a patient with acute ischemic stroke secondary to blunt carotid artery injury who was treated with endovascular revascularization. A 46-year-old man suffered from sudden left-sided hemiparesis a day after a strike from a Japanese fencing staff on his right neck. 3D-CT angiography revealed tandem internal carotid artery occlusions of the cervical and C1 portions. We performed endovascular revascularization with carotid artery stenting and direct aspiration of the thrombus and achieved complete recanalization. The patient recovered almost completely. We conclude that endovascular revascularization should not be withheld from patients with acute ischemic stroke related to blunt carotid injury.

    DOI: 10.11477/mf.1436204223

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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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  • 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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  • 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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  • Malignant Hyperthermia and Cerebral Venous Sinus Thrombosis After Ventriculoperitoneal Shunt in Infant with Schizencephaly and COL4A1 Mutation. 査読 国際誌

    Jun Watanabe, Kouichirou Okamoto, Tsukasa Ohashi, Manabu Natsumeda, Hitoshi Hasegawa, Makoto Oishi, Satoko Miyatake, Naomichi Matsumoto, Yukihiko Fujii

    World neurosurgery   127   446 - 450   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)  

    BACKGROUND: Schizencephaly is a rare congenital central nervous system malformation characterized by linear, thickened clefts of the cerebral mantle. Recently, germline mutations in collagen type IV alpha 1 (COL4A1) have been reported to be a genetic cause of schizencephaly as a result of prenatal stroke. Patients with COL4A1 mutation demonstrate a variety of disease phenotypes. However, little is known about the potential complications of patients with COL4A1 mutations before and after neurologic surgery. CASE DESCRIPTION: A 9-month-old boy with schizencephaly and a congenital cataract underwent a ventriculoperitoneal shunt for progressive hydrocephalus. Postoperatively, he developed malignant hyperthermia and cerebral venous thrombosis. Early treatment with dantrolene sodium and hydration was effective. Genetic testing revealed a germline COL4A1 mutation. CONCLUSIONS: To our knowledge, malignant hyperthermia and cerebral venous thrombosis have not been reported in the literature in patients with COL4A1 mutations after surgery. Schizencephaly arising from COL4A1 mutations might be a disease prone to these adverse effects because this mutation is known to be associated with venous tortuosity, venous vulnerability, and muscle spasms due to basement membrane protein abnormalities. We need to better understand the wide spectrum of clinical phenotypes of COL4A1 mutations and potential complications in order to better manage surgery of patients with schizencephaly.

    DOI: 10.1016/j.wneu.2019.04.156

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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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  • Inhibition of enhancer of zest homologue 2 is a potential therapeutic target for high-MYC medulloblastoma. 査読 国際誌

    Natsumeda M, Liu Y, Nakata S, Miyahara H, Hanaford A, Ahsan S, Stearns D, Skuli N, Kahlert UD, Raabe EH, Rodriguez FJ, Eberhart CG

    Neuropathology : official journal of the Japanese Society of Neuropathology   39 ( 2 )   71 - 77   2019年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/neup.12534

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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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  • Advances and Challenges in Assessing 2-Hydroxyglutarate in Gliomas by Magnetic Resonance Spectroscopy: A Short Review 査読

    Neuropsychiatry (London)   8 ( 6 )   1831 - 1838   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)  

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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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  • High Incidence of Deep Vein Thrombosis in the Perioperative Period of Neurosurgical Patients 査読

    Manabu Natsumeda, Takeo Uzuka, Jun Watanabe, Masafumi Fukuda, Yasuhisa Akaiwa, Kazuhiko Hanzawa, Masahiko Okada, Makoto Oishi, Yukihiko Fujii

    World Neurosurgery   112   e103 - e112   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)   出版者・発行元:Elsevier Inc.  

    Introduction: A prospective study was designed to elucidate incidence and predictors of deep venous thrombosis (DVT) in patients undergoing craniotomies. Materials and Methods: Ninety-two patients who underwent craniotomies received pre- and postoperative venous ultrasonography and/or contrast-enhanced spiral computed tomography for diagnosis of DVT. The primary endpoint was DVT occurrence. Serial levels of serum D-dimer, soluble fibrin, and thrombin–antithrombin complex (TAT) were analyzed. Results: Twenty-four of 92 patients (26.1%) had DVT, of whom 10 (41.7%) were diagnosed preoperatively. In patients with preoperative DVT, age, incidence of decreased performance status and leg paresis, levels of D-dimer, soluble fibrin, and TAT were significantly greater. In patients with postoperative DVT, length of surgery, incidence of decreased postoperative performance status, levels of D-dimer on postoperative days (POD) 3, 7, and 14, and TAT on POD7 were significantly greater. Patients with postoperative DVT had elevated D-dimer levels on POD 7 compared with POD 3. The D-dimer cutoff of 2.65 μg/mL at POD 7 could be used to identify DVT with 85.7% sensitivity and 72.3% specificity. A cutoff of 5.25 μg/mL at POD 7 yielded a specificity of 96.9%. Decreased performance status and elevated D-dimer were independent predictors for preoperative DVT, prolonged operation time, and elevated D-dimer on POD 7 for postoperative DVT. Conclusions: DVT frequently was observed in patients before and after undergoing craniotomies. Patients with decreased performance status should be preoperatively screened for DVT by checking D-dimer levels. Elevated D-dimer levels on POD 7 compared with POD 3 and D-dimer levels greater than 2.65 μg/mL at POD7 suggest the presence of DVT.

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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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  • 髄膜播種をきたしたEpithelioid glioblastomaの1例

    金丸 優, 棗田 学, 齋藤 理恵, 野澤 孝徳, 阿部 英明, 岡本 浩一郎, 大石 誠, 藤井 幸彦, 柿田 明美, 信澤 純人

    信州医学雑誌   66 ( 1 )   104 - 105   2018年2月

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    記述言語:日本語   出版者・発行元:信州医学会  

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  • The dual mTOR kinase inhibitor TAK228 inhibits tumorigenicity and enhances radiosensitization in diffuse intrinsic pontine glioma 査読

    Hiroaki Miyahara, Sridevi Yadavilli, Manabu Natsumeda, Jeffrey A. Rubens, Louis Rodgers, Madhuri Kambhampati, Isabella C. Taylor, Harpreet Kaur, Laura Asnaghi, Charles G. Eberhart, Katherine E. Warren, Javad Nazarian, Eric H. Raabe

    CANCER LETTERS   400   110 - 116   2017年8月

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

    Diffuse intrinsic pontine glioma (DIPG) is an invasive and treatment-refractory pediatric brain tumor. Primary DIPG tumors harbor a number of mutations including alterations in PTEN, AKT, and PI3K and exhibit activation of mammalian Target of Rapamycin Complex 1 and 2 (mTORC1/2). mTORC1/2 regulate protein translation, cell growth, survival, invasion, and metabolism. Pharmacological inhibition of mTORC1 is minimally effective in DIPG. However, the activity of dual TORC kinase inhibitors has not been examined in this tumor type.
    Nanomolar levels of the mTORC1/2 inhibitor TAK228 reduced expression of p-AKT(S473) and p-S6(S240/244) and suppressed the growth of DIPG lines JHH-DIPG1, SF7761, and SU-DIPG-XIII. TAK228 induced apoptosis in DIPG cells and cooperated with radiation to further block proliferation and enhance apoptosis.
    TAK228 monotherapy inhibited the tumorigenicity of a murine orthotopic model of DIPG, more than doubling median survival (p = 0.0017) versus vehicle. We conclude that dual mTOR inhibition is a promising potential candidate for DIPG treatment. (C) 2017 Elsevier B.V. All rights reserved.

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  • Long-term survivors of primary central nervous system lymphoma 査読

    Ryuya Yamanaka, Ken Morii, Masakazu Sano, Jumpei Homma, Naoki Yajima, Yoshihiro Tsukamoto, Ryouske Ogura, Manabu Natsumeda, Hiroshi Aoki, Katsuhiko Akiyama, Takafumi Saitoh, Hiroaki Hondoh, Atsushi Kawaguchi, Hitoshi Takahashi, Yukihiko Fujii

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   47 ( 2 )   101 - 107   2017年2月

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

    Objective: In this study, we provide long-term outcome data of patients with primary central nervous system lymphoma
    Methods: The long-term outcomes of PCNSL patients diagnosed between 1982 and 2006 were reviewed. Neurological late neurotoxicity symptoms, neuroradiological brain atrophy and leukoen-cephalopathy were evaluated. Surviving patients completed the Quality of Life Questionnaire-30 and Brain Cancer Module-20. The differences in overall survival were assessed using the Kaplan-Meier method and log-rank test. The differences between groups in terms of each investigated parameter were analyzed using the Wilcoxon signed-rank test
    Results: Among 112 PCNSL patients, there were 33 (29.4%) long-term (&gt; 5 years) survivors. The median survival of all long-term survivors was 105.7 months; of these, 8 (7.1%) were alive at the latest follow-up, with a mean survival time of 170.2 months (range, 121.8-286.4). Clinical assessment revealed severe neurotoxicity in 14 patients (42.4%), moderate neurotoxicity in 5 (15.1%), and normal status in 14 (42.4%). Correlations were seen between the neuroradiological imaging score changes and neurocognitive condition (P= 0.0001), neurocognitive condition and the whole brain irradiation dose (P= 0.0004), and atrophy and the whole brain irradiation dose (P= 0.0035).
    Conclusions: A more severe clinical condition was found to be associated with increasing age and whole brain irradiation dose in long-term survivors with PCNSL.

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  • Late relapse of primary central nervous system lymphoma 査読

    Ryuya Yamanaka, Ken Morii, Yoshikatsu Shinbo, Masakazu Sano, Jumpei Homma, Naoto Tsuchiya, Naoki Yajima, Yoshihiro Tsukamoto, Ryouske Ogura, Manabu Natsumeda, Hiroshi Aoki, Katsuhiko Akiyama, Takafumi Saitoh, Tetsuro Tamura, Hiroaki Hondoh, Atsushi Kawaguchi, Hitoshi Takahashi, Yukihiko Fujii

    LEUKEMIA & LYMPHOMA   58 ( 2 )   475 - 477   2017年2月

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    記述言語:英語   出版者・発行元:TAYLOR & FRANCIS LTD  

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  • Targeting Notch Signaling and Autophagy Increases Cytotoxicity in Glioblastoma Neurospheres 査読

    Manabu Natsumeda, Kosuke Maitani, Yang Liu, Hiroaki Miyahara, Harpreet Kaur, Qian Chu, Hongyan Zhang, Ulf D. Kahlert, Charles G. Eberhart

    BRAIN PATHOLOGY   26 ( 6 )   713 - 723   2016年11月

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

    Glioblastomas are highly aggressive tumors that contain treatment resistant stem-like cells. Therapies targeting developmental pathways such as Notch eliminate many neoplastic glioma cells, including those with stem cell features, but their efficacy can be limited by various mechanisms. One potential avenue for chemotherapeutic resistance is the induction of autophagy, but little is known how it might modulate the response to Notch inhibitors. We used the -secretase inhibitor MRK003 to block Notch pathway activity in glioblastoma neurospheres and assessed its effects on autophagy. A dramatic, several fold increase of LC3B-II/LC3B-I autophagy marker was noted on western blots, along with the emergence of punctate LC3B immunostaining in cultured cells. By combining the late stage autophagy inhibitor chloroquine (CQ) with MRK003, a significant induction in apoptosis and reduction in growth was noted as compared to Notch inhibition alone. A similar beneficial effect on inhibition of cloogenicity in soft agar was seen using the combination treatment. These results demonstrated that pharmacological Notch blockade can induce protective autophagy in glioma neurospheres, resulting in chemoresistance, which can be abrogated by combination treatment with autophagy inhibitors.

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  • [Gli3: a favorable prognostic factor for patients with medulloblastoma]. 査読

    Yoshimura J, Miyahara H, Natsumeda M, Kakita A, Fujii Y

    Nihon rinsho. Japanese journal of clinical medicine   74 Suppl 7   292 - 297   2016年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Chemical Screening Identifies EUrd as a Novel Inhibitor Against Temozolomide-Resistant Glioblastoma-Initiating Cells 査読

    Yoshihiro Tsukamoto, Naoki Ohtsu, Smile Echizenya, Satoko Otsuguro, Ryosuke Ogura, Manabu Natsumeda, Mizuho Isogawa, Hiroshi Aoki, Satoshi Ichikawa, Masahiro Sakaitani, Akira Matsuda, Katsumi Maenaka, Yukihiko Fujii, Toru Kondo

    STEM CELLS   34 ( 8 )   2016 - 2025   2016年8月

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

    Glioblastoma (GBM), one of the most malignant human cancers, frequently recurs despite multi-modal treatment with surgery and chemo/radiotherapies. GBM-initiating cells (GICs) are the likely cell-of-origin in recurrences, as they proliferate indefinitely, form tumors in vivo, and are resistant to chemo/radiotherapies. It is therefore crucial to find chemicals that specifically kill GICs. We established temozolomide (the standard medicine for GBM)-resistant GICs (GICRs) and used the cells for chemical screening. Here, we identified 1-(3-C-ethynyl-beta-D-ribopentofuranosyl) uracil (EUrd) as a selective drug for targeting GICRs. EUrd induced the death in GICRs more effectively than their parental GICs, while it was less toxic to normal neural stem cells. We demonstrate that the cytotoxic effect of EUrd on GICRs partly depended on the increased expression of uridine-cytidine kinase-like 1 (UCKL1) and the decreased one of 5'-nucleotidase cytosolic III (NT5C3), which regulate uridine-monophosphate synthesis positively and negatively respectively. Together, these findings suggest that EUrd can be used as a new therapeutic drug for GBM with the expression of surrogate markers UCKL1 and NT5C3.

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  • Pharmacologic Wnt Inhibition Reduces Proliferation, Survival, and Clonogenicity of Glioblastoma Cells 査読

    Ulf D. Kahlert, Abigail K. Suwala, Katharina Koch, Manabu Natsumeda, Brent A. Orr, Masanori Hayashi, Jarek Maciaczyk, Charles G. Eberhart

    JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY   74 ( 9 )   889 - 900   2015年9月

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

    Wingless (Wnt) signaling is an important pathway in gliomagenesis and in the growth of stem-like glioma cells. Using immunohistochemistry to assess the translocation of beta-catenin protein, we identified intranuclear staining suggesting Wnt pathway activation in 8 of 43 surgical samples (19%) from adult patients with glioblastoma and in 9 of 30 surgical samples (30%) from pediatric patients with glioblastoma. Wnt activity, evidenced by nuclear beta-catenin in our cohort and high expression of its target AXIN2 (axis inhibitor protein 2) in published glioma datasets, was associated with shorter patient survival, although this was not statistically significant. We determined the effects of the porcupine inhibitor LGK974 on 3 glioblastoma cell lines with elevated AXIN2 and found that it reduced Wnt pathway activity by 50% or more, as assessed by T-cell factor luciferase reporters. Wnt inhibition led to suppression of growth, proliferation in cultures, and modest induction of cell death. LGK974 reduced NANOG messenger RNA levels and the fraction of cells expressing the stem cell marker CD133 in neurosphere cultures, induced glial differentiation, and suppressed clonogenicity. These data indicate that LGK974 is a promising new agent that can inhibit the canonical Wnt pathway in vitro, slow tumor growth, and deplete stem-like clonogenic cells, thereby providing further support for targeting Wnt in patients with glioblastoma.

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  • Immunohistochemical profiles of IDH1, MGMT and P53: Practical significance for prognostication of patients with diffuse gliomas 査読

    Ryosuke Ogura, Yoshihiro Tsukamoto, Manabu Natsumeda, Mizuho Isogawa, Hiroshi Aoki, Tsutomu Kobayashi, Seiichi Yoshida, Kouichiro Okamoto, Hitoshi Takahashi, Yukihiko Fujii, Akiyoshi Kakita

    NEUROPATHOLOGY   35 ( 4 )   324 - 335   2015年8月

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

    Genetic and epigenetic status, including mutations of isocitrate dehydrogenase (IDH) and TP53 and methylation of O-6-methylguanine-DNA methyltransferase (MGMT), are associated with the development of various types of glioma and are useful for prognostication. Here, using routinely available histology sections from 312 patients with diffuse gliomas, we performed immunohistochemistry using antibodies specific for IDH1 mutation, MGMT methylation status, and aberrant p53 expression to evaluate the possible prognostic significance of these features. With regard to overall survival (OS), univariate analysis indicated that an IDH1-positive profile in patients with glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligoastrocytoma and oligodendroglioma, or a MGMT-negative profile in patients with GBM and AA were significantly associated with a favorable outcome. Multivariate analysis revealed that both profiles were independent factors influencing prognosis. The OS of patients with IDH1-positive/MGMT-negative profiles was significantly longer than that of patients with negative/negative and negative/positive profiles. A p53 profile was not an independent prognostic factor. However, for GBM/AA patients with IDH1-negative/MGMT-negative profiles, p53 overexpression was significantly associated with an unfavorable outcome. Thus, the immunohistochemical profiles of IDH1 and MGMT are of considerable significance in gliomas, and a combination of IDH1, MGMT and p53 profiles may be useful for prognostication of GBM/AA.

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  • Neuronal differentiation associated with Gli3 expression predicts favorable outcome for patients with medulloblastoma 査読

    Hiroaki Miyahara, Manabu Natsumeda, Junichi Yoshimura, Ryosuke Ogura, Kenichi Okazaki, Yasuko Toyoshima, Yukihiko Fujii, Hitoshi Takahashi, Akiyoshi Kakita

    NEUROPATHOLOGY   34 ( 1 )   1 - 10   2014年2月

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

    Medulloblastoma (MB) is a malignant cerebellar tumor arising in children, and its ontogenesis is regulated by Sonic Hedgehog (Shh) signaling. No data are available regarding the correlation between expression of Gli3, a protein lying downstream of Shh, and neuronal differentiation of MB cells, or the prognostic significance of these features. We re-evaluated the histopathological features of surgical specimens of MB taken from 32 patients, and defined 15 of them as MB with neuronal differentiation (ND), three as MB with both glial and neuronal differentiation (GD), and 14 as differentiation-free (DF) MB. Gli3-immunoreactivity (IR) was evident as a clear circular stain outlining the nuclei of the tumor cells. The difference in the frequency of IR between the ND+GD (94.4%) and DF (0%) groups was significant (P&lt;0.001). The tumor cells with ND showed IR for both Gli3 and neuronal nuclei. Ultrastructurally, Gli3-IR was observed at the nuclear membrane. The overall survival and event-free survival rates of the patients in the ND group were significantly higher than those in the other groups. The expression profile of Gli3 is of considerable significance, and the association of ND with this feature may be prognostically favorable in patients with MB.

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  • Accumulation of 2-hydroxyglutarate in gliomas correlates with survival: a study by 3.0-tesla magnetic resonance spectroscopy 査読

    Manabu Natsumeda, Hironaka Igarashi, Toshiharu Nomura, Ryosuke Ogura, Yoshihiro Tsukamoto, Tsutomu Kobayashi, Hiroshi Aoki, Kouichirou Okamoto, Akiyoshi Kakita, Hitoshi Takahashi, Tsutomu Nakada, Yukihiko Fujii

    ACTA NEUROPATHOLOGICA COMMUNICATIONS   2   158   2014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:BIOMED CENTRAL LTD  

    Introduction: Previous magnetic resonance spectroscopy (MRS) and mass spectroscopy studies have shown accumulation of 2-hydroxyglutarate (2HG) in mutant isocitrate dehydrogenase (IDH) gliomas. IDH mutation is known to be a powerful positive prognostic marker in malignant gliomas. Hence, 2HG accumulation in gliomas was assumed to be a positive prognostic factor in gliomas, but this has not yet been proven. Here, we analyzed 52 patients harboring World Health Organization (WHO) grade II and III gliomas utilizing 3.0-tesla MRS.
    Results: Mutant IDH gliomas showed significantly higher accumulation of 2HG (median 5.077 vs. 0.000, p = 0.0002, Mann-Whitney test). 2HG was detectable in all mutant IDH gliomas, whereas in 10 out of 27 (37.0%) wild-type IDH gliomas, 2HG was below the detectable range (2HG = 0) (p = 0.0003, chi-squared test). Screening for IDH mutation by 2HG analysis was highly sensitive (cutoff 2HG = 1.489 mM, sensitivity 100.0%, specificity 72.2%). Gliomas with high 2HG accumulation had better overall survival than gliomas with low 2HG accumulation (p = 0.0401, Kaplan-Meier analysis).
    Discussion: 2HG accumulation detected by 3.0-tesla MRS not only correlates well with IDH status, but also positively correlates with survival in WHO grade II and III gliomas.

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  • Gene expression signature-based prognostic risk score in patients with glioblastoma 査読

    Atsushi Kawaguchi, Naoki Yajima, Naoto Tsuchiya, Jumpei Homma, Masakazu Sano, Manabu Natsumeda, Hitoshi Takahashi, Yukihiko Fujii, Tatsuyuki Kakuma, Ryuya Yamanaka

    Cancer Science   104 ( 9 )   1205 - 1210   2013年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The present study aimed to identify genes associated with patient survival to improve our understanding of the underlying biology of gliomas. We investigated whether the expression of genes selected using random survival forests models could be used to define glioma subgroups more objectively than standard pathology. The RNA from 32 non-treated grade 4 gliomas were analyzed using the GeneChip Human Genome U133 Plus 2.0 Expression array (which contains approximately 47 000 genes). Twenty-five genes whose expressions were strongly and consistently related to patient survival were identified. The prognosis prediction score of these genes was most significant among several variables and survival analyses. The prognosis prediction score of three genes and age classifiers also revealed a strong prognostic value among grade 4 gliomas. These results were validated in an independent samples set (n = 488). Our method was effective for objectively classifying grade 4 gliomas and was a more accurate prognosis predictor than histological grading. © 2013 Japanese Cancer Association.

    DOI: 10.1111/cas.12214

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  • Gene expression signature-based prognostic risk score in patients with glioblastoma 査読

    Atsushi Kawaguchi, Naoki Yajima, Naoto Tsuchiya, Jumpei Homma, Masakazu Sano, Manabu Natsumeda, Hitoshi Takahashi, Yukihiko Fujii, Tatsuyuki Kakuma, Ryuya Yamanaka

    CANCER SCIENCE   104 ( 9 )   1205 - 1210   2013年9月

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

    The present study aimed to identify genes associated with patient survival to improve our understanding of the underlying biology of gliomas. We investigated whether the expression of genes selected using random survival forests models could be used to define glioma subgroups more objectively than standard pathology. The RNA from 32 non-treated grade 4 gliomas were analyzed using the GeneChip Human Genome U133 Plus 2.0 Expression array (which contains approximately 47000 genes). Twenty-five genes whose expressions were strongly and consistently related to patient survival were identified. The prognosis prediction score of these genes was most significant among several variables and survival analyses. The prognosis prediction score of three genes and age classifiers also revealed a strong prognostic value among grade 4 gliomas. These results were validated in an independent samples set (n=488). Our method was effective for objectively classifying grade 4 gliomas and was a more accurate prognosis predictor than histological grading.

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  • Epstein-Barr virus-associated primary central nervous system cytotoxic T-cell lymphoma 査読

    Ryosuke Ogura, Hiroshi Aoki, Manabu Natsumeda, Hiroshi Shimizu, Tsutomu Kobayashi, Tomohisa Saito, Jun Takizawa, Kouichirou Okamoto, Go Hasegawa, Hajime Umezu, Kouichi Ohshima, Hitoshi Takahashi, Yukihiko Fujii, Akiyoshi Kakita

    NEUROPATHOLOGY   33 ( 4 )   436 - 441   2013年8月

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

    Primary central nervous system lymphoma (PCNSL) expressing T-cell markers is rare, among which nasal-type extranodal NK/T-cell lymphoma is an extremely rare subtype associated with Epstein-Barr virus (EBV) infection. Here we report the clinicopathologic features of a case of EBV-associated PCNSL showing a cytotoxic T-cell phenotype. The patient, a 73-year-old woman, presented with rapidly progressive mental deterioration. Brain MRI revealed multiple lesions with swelling in the bilateral cerebral hemispheres, which were hypointense on T1-weighted images, hyperintense on T2-weighted and fluid-attenuated inversion recovery images, and slightly hyperintense on diffusion-weighted images. Biopsy specimens from the temporal region showed many medium-sized anaplastic lymphocytic cells with perivascular and angio-invasive patterns in the cortex. Immunohistochemically, the cells were positive for CD3, CD8, T-cell-restricted intracellular antigen-1 (TIA-1), granzyme B and perforin, but negative for CD56 and CD20. In situ hybridization revealed EBV-encoded RNAs in the tumor cell nuclei. A rearrangement study showed T-cell receptor g-chain gene rearrangement with a clonal appearance. The patient died 6 months after surgery, and a general autopsy revealed no lymphoma cells outside the brain. These cellular profiles are inconsistent with those of extranodal NK/T-cell lymphoma, and have not been previously described. This case appears to represent an unusual CNS manifestation of EBV-associated T-cell lymphoma.

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  • Radiation-induced intracranial osteosarcoma after radiation for acute lymphocytic leukemia associated with Li-Fraumeni syndrome 査読

    Junichi Yoshimura, Manabu Natsumeda, Yasushi Nishihira, Kenichi Nishiyama, Akihiko Saito, Kouichirou Okamoto, Hitoshi Takahashi, Yukihiko Fujii

    Neurological Surgery   41 ( 6 )   499 - 505   2013年6月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 28-year-old man presented with osteosarcoma of the occipital bone 16 years after 24 Gy of craniospinal irradiation for acute lymphocytic leukemia. The tumor had both intra- and extracranial components. However, the affected skull appeared to be normal on imaging because of permeative infiltration by the tumor. Subtotal resection was achieved and the tumor was verified histologically as an osteosarcoma. The residual tumor soon showed remarkable enlargement and disseminated to the spinal cord. Both of the enlarged and disseminated tumor masses were treated by surgical intervention and chemotherapy. However, the patient deteriorated due to the tumor regrowth and died 11 months after the initial diagnosis. This patient had previously developed a leukemia, a colon cancer, a rectal cancer and a hepatocellular carcinoma. His brother also died of leukemia. The patient had a heterozygous TP53 germ-line mutation of codon 248 in the exon 7. In conclusion, we consider the present tumor to be a rare example of radiation-induced skull osteosarcoma in a member of the cancer-prone family with TP53 germline mutation which is associated with Li-Fraumeni syndrome.

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  • Suppressed expression of autophagosomal protein LC3 in cortical tubers of tuberous sclerosis complex 査読

    Hiroaki Miyahara, Manabu Natsumeda, Atsushi Shiga, Hiroshi Aoki, Yasuko Toyoshima, Yingjun Zheng, Ryoko Takeuchi, Hiroatsu Murakami, Hiroshi Masuda, Shigeki Kameyama, Tatsuro Izumi, Yukihiko Fujii, Hitoshi Takahashi, Akiyoshi Kakita

    Brain Pathology   23 ( 3 )   254 - 262   2013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)  

    Tuberous sclerosis complex (TSC) is characterized by benign tumors and hamartomas, including cortical tubers. Hamartin and tuberin, encoded by the TSC 1 and 2 genes, respectively, constitute a functional complex that negatively regulates the mammalian target of rapamycin (mTOR) signaling pathway, eventually promoting the induction of autophagy. In the present study, we assessed the induction of autophagy in cortical tubers surgically removed from seven patients with TSC in comparison with five controls of cortical tissue taken from non-TSC patients with epilepsy. Immunoblotting demonstrated a marked reduction of LC3B-I and LC3B-II in tubers relative to the controls. In tubers, strong, diffuse and dot-like immunoreactivity (IR) for LC3B was observed in dysmorphic neurons and balloon cells, but LC3B-IR in other neurons with normal morphology was significantly weaker than that in neurons in the controls. Immunoelectron microscopy revealed diffuse distribution of LC3B-IR within the cytoplasm of balloon cells. The dot-like pattern may correspond to abnormal aggregation bodies involving LC3. In an autopsy patient with TSC, we observed that LC3B-IR in neurons located outside of the tubers was preserved. Thus, autophagy is suppressed in tubers presumably through the mTOR pathway, and possibly a pathological autophagy reaction occurs in the dysmorphic neurons and balloon cells. © 2012 The Authors
    Brain Pathology © 2012 International Society of Neuropathology.

    DOI: 10.1111/j.1750-3639.2012.00634.x

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  • Factors affecting functional outcomes in long-term survivors of intracranial germinomas: A 20-year experience in a single institution: Clinical article 査読

    Shinya Jinguji, Junichi Yoshimura, Kenichi Nishiyama, Hiroshi Aoki, Keisuke Nagasaki, Manabu Natsumeda, Yuichiro Yoneoka, Masafumi Fukuda, Yukihiko Fujii

    Journal of Neurosurgery: Pediatrics   11 ( 4 )   454 - 463   2013年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Object. Radiation monotherapy-prophylactic craniospinal or whole-brain irradiation paired with a radiation boost to the primary tumor-is the standard treatment for intracranial germinomas at the authors' institution. The authors assessed long-term outcomes of patients with germinoma who underwent therapy and identified factors affecting them. Methods. The authors retrospectively analyzed data obtained in 46 patients (35 males and 11 females, age 5-43 years at diagnosis) who had been treated for intracranial germinomas between 1990 and 2009 at the authors' institution. Thirty patients had germinomas in localized regions and 16 in multiple regions. Thirty-eight patients (83%) underwent radiotherapy alone (craniospinal irradiation in 32 and whole-brain irradiation in 6). Seven patients underwent radiochemotherapy and 1 underwent chemotherapy alone. The mean radiation doses for the whole brain, spine, and primary tumor site were 26.9, 26.6, and 49.8 Gy, respectively. The median follow-up period was 125 months. Results. The 10-year overall and recurrence-free survival rates were 93.3% and 89.3%, respectively. None of the 38 patients who received radiation monotherapy developed a recurrent lesion, whereas 1 of 7 who underwent radiochemotherapy and the 1 patient who underwent chemotherapy had a recurrent lesion. Of the entire population, 26 patients required hormone replacement therapy, 2 had short stature, and 1 developed a radiation-induced meningioma. Seventeen of the 25 childhood- or adolescent-onset patients were 19 years or older at the latest follow-up visit, 15 of whom graduated from senior high school, and only 2 of whom graduated from college. Of 34 patients who were 19 years or older at the latest visit, 4 were students, 18 worked independently, 4 worked in sheltered workplaces, and 8 were unemployed. Of the 34 patients, 4 got married after the initial treatment, 3 of whom had children. There were 8 patients (17%) with low postoperative Karnofsky Performance Scale (KPS) scores that were significantly associated with impaired neurocognitive functions, severe surgical complications, and neurological impairments. In 10 of the 46 patients, KPS scores at the latest visit were lower than their postoperative KPS scores. These decreases in KPS scores were significantly correlated with a delayed decline in neurocognitive functions in childhood-onset patients and a postoperative impairment of neurocognitive functions in patients with adolescent- or adult-onset germinoma. Conclusions. No tumor recurrence occurred in germinoma patients treated with the authors' radiation monotherapy, which appears to be effective enough to cure the tumor. Brain damage caused by tumors themselves and surgical complications were found to adversely affect functional outcomes in patients regardless of their age. Although radiotherapy rarely caused late adverse effects in patients with adolescent- or adult-onset, in some childhood-onset lesions, the radiation seems to carry the risk of neurocognitive dysfunctions, which are attributable to late adverse effects. Accordingly, treatments for germinoma patients should be selected according to a patient's age and the extent of the tumor and with particular care to avoid surgical complications. Copyright © AANS, 2013.

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  • Radiation-Induced Glioblastoma Following Radiotherapy for Pituitary Adenomas: Marked Response to Chemotherapy. 査読

    Kon T, Natsumeda M, Takahashi H, Taki T, Fujii Y, Yamanaka R

    J Neurol Neurophysiol   4   155   2013年

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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 Natsumeda, 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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  • Effectiveness of Maximal Safe Resection for Glioblastoma Including Elderly and Low Karnofsky Performance Status Patients: Retrospective Review at a Single Institute 査読

    Takeo Uzuka, Hiroshi Aoki, Manabu Natsumeda, Hideaki Takahashi, Yukihiko Fujii

    NEUROLOGIA MEDICO-CHIRURGICA   52 ( 8 )   570 - 576   2012年8月

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

    Elderly and low Karnofsky performance status (KPS) patients have been excluded from most prospective trials. This retrospective study investigated glioblastoma treatment outcomes, including those of elderly and low KPS patients, and analyzed the prognostic factors using the medical records of 107 consecutive patients, 59 men and 48 women aged from 21 to 85 years (median 65 years), with newly diagnosed glioblastoma treated at our institute. There were 71 high-risk patients with age &gt;70 years and/or KPS &lt;70%. Based on the extent of resection, the patients were classified into 3 groups: more than subtotal resection (subtotal, n = 44), partial resection (partial, n = 29), and biopsy only (biopsy, n = 34). Median overall survival (OS) of all 107 patients was 13.5 months. Median OS was 13.2 months in the high-risk group. Median OSs were 15.8, 12.8, and 12.1 months in the subtotal, partial, and biopsy groups, respectively. Multivariate analysis of 73 patients in the subtotal and partial groups found age &lt;= 65 years (p = 0.047), 60 Gy irradiation (p = 0.009), O-6-methylguanine-deoxyribonucleic acid methyltransferase-negative (p = 0.027), and more than subtotal removal (p = 0.003) were significant prognostic factors. The median postoperative KPS score tended to be better than the preoperative score, even in the high-risk group. We recommend maximal safe resection for glioblastoma patients, even those with advanced age and/or with low KPS scores.

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  • Short course radiotherapy in elderly patients with high-grade glioma 査読

    Hiroshi Aoki, Manabu Natsumeda, Eisuke Abe, Takeo Uzuka, Tsutomu Kobayashi, Hidefumi Aoyama, Yukihiko Fujii

    Neurological Surgery   40 ( 7 )   593 - 598   2012年7月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Purpose: There is no standard therapy for elderly patients with high-grade glioma. We have adopted short course radiotherapy for such patients since 2005. The efficacy of this therapy was assessed retrospectively. Methods: This study reviewed 16 newly diagnosed high-grade glioma patients aged 75 years or older who were treated with short course radiotherapy (focal radiation in daily fraction of 3 Gy given 5 days per week, for a total dose of 39 Gy). Results: All patients received 100% of the planed radiation dose. No patients received prior or concomitant chemotherapy. Thirteen patients had died and median follow-up period was 9 months at the time of analysis. The median age at surgery was 79 years (range 75-86). The estimated median overall survival was 9.6 months. The median Karnofsky Performance Status on admission was 60% (range 40-90) and at discharge was 60% (range 40-80). The median length of hospital stay was 38 days (range19-61 ). There is no severe adverse events related to radiation therapy. The rate of discharge to home was 69%. Conclusion: Short course radiotherapy can reduce the treatment time and adverse events of conventional radiotherapy without decrement in survival. This therapy seems to be a considerable treatment option for elderly patients with high-grade glioma.

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  • Identification and validation of a gene expression signature that predicts outcome in malignant glioma patients 査読

    Atsushi Kawaguchi, Naoki Yajima, Yoshihiro Komohara, Hiroshi Aoki, Naoto Tsuchiya, Jumpei Homma, Masakazu Sano, Manabu Natsumeda, Takeo Uzuka, Akihiko Saitoh, Hideaki Takahashi, Yuko Sakai, Hitoshi Takahashi, Yukihiko Fujii, Tatsuyuki Kakuma, Ryuya Yamanaka

    INTERNATIONAL JOURNAL OF ONCOLOGY   40 ( 3 )   721 - 730   2012年3月

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

    Better understanding of the underlying biology of malignant gliomas is critical for the development of early detection strategies and new therapeutics. This study aimed to define genes associated with survival. We investigated whether genes selected using random survival forests model could be used to define subgroups of gliomas objectively. RNAs from 50 non-treated gliomas were analyzed using the GeneChip Human Genome U133 Plus 2.0 Expression array. We identified 82 genes whose expression was strongly and consistently related to patient survival. For practical purposes, a 15-gene set was also selected. Both the complete 82 gene signature and the 15 gene set subgroup indicated their significant predictivity in the 3 out of 4 independent external dataset. Our method was effective for objectively classifying gliomas, and provided a more accurate predictor of prognosis. We assessed the relationship between gene expressions and survival time by using the random survival forests model and this performance was a better classifier compared to significance analysis of microarrays.

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  • Thyroid-stimulating hormone (thyrotropin)-secretion pituitary adenoma in an 8-year-old boy: case report 査読

    Yoko Nakayama, Shinya Jinguji, Shin-ichi Kumakura, Keisuke Nagasaki, Manabu Natsumeda, Yuichiro Yoneoka, Takafumi Saito, Yukihiko Fujii

    PITUITARY   15 ( 1 )   110 - 115   2012年3月

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

    In this report, an extremely rare case of pediatric thyrotropin-secreting pituitary macroadenoma (TSHoma) is described. An 8-year-old boy, complaining of unsteady gait, was suspected of endocrinopathy because of emaciation and muscle weakness of the legs. Endocrinological work-up established a diagnosis of hyperthyroidism due to syndrome of inappropriate secretion of TSH. Magnetic resonance imaging showed a pituitary macroadenoma with suprasellar and sphenoidal extension without cavernous sinus invasion. He underwent an endoscopic endonasal transsphenoidal adenomectory due to the diagnosis of TSHoma. The adenoma was soft and it was totally removed. Histopathological staining confirmed diagnosis of TSHoma. Postoperative evaluation revealed a subnormal level of TSH (from 13-21 to 0.03 micro U/ml), normalization of alpha-subunit (from 10.0 to 0.09 ng/ml), and as a result, hypothyroidism. The boy left the hospital with oral levothyroxine that continued until 12 months of discharge. The present 8-year-old case is the youngest case to the best of our knowledge based on a bibliographical search. Reasons for endocrinological remission following adenomectomy are (1) correct diagnosis without delay: lack of cavernous sinus invasion, (2) soft and non-fibrous adenoma tissue, and (3) endoscopic technique with wide vision and illumination: safe even for a 8-year-old child. Early recognition/detection and pituitary-conserving adenomectomy can cure TSHoma and avoid long-term medical therapy and/or irradiation, which contribute to the best interests of patients with TSHoma.

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  • Near-infrared spectroscopic study and the Wada test for presurgical evaluation of expressive and receptive language functions in glioma patients: With a case report of dissociated language functions 査読

    Yosuke Sato, Takeo Uzuka, Hiroshi Aoki, Manabu Natsumeda, Makoto Oishi, Masafumi Fukuda, Yukihiko Fujii

    NEUROSCIENCE LETTERS   510 ( 2 )   104 - 109   2012年2月

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

    Near-infrared spectroscopy (NIRS) has proven to be useful for the evaluation of language lateralization in healthy subjects, infants, and epileptic patients. This study for the first time investigated the expressive and receptive language functions separately, using NIRS in presurgical glioma patients. We also describe a special case with dissociated pattern of language functions. Ten glioma patients were examined. Using NIRS, the hemodynamic changes during a verb generation task or story listening task were measured in the cerebral hemisphere on either side covering the language areas. Following the NIRS study, the Wada test was performed in all the patients. The NIRS study revealed increases of oxyhemoglobin and decreases of deoxyhemoglobin in the language areas elicited by both tasks. In 9 patients, who were all right-handed, the expressive and receptive language functions were lateralized to the left hemisphere. The results of the NIRS study were completely consistent with those of the Wada test. In the remaining 1 patient with a right sided insular glioma, who was right-handed, the NIRS study revealed stronger activation of the right inferior frontal region during the verb generation task, and stronger activation of the left superior temporal region during the story listening task. This dissociated language function was validated by the Wada test and the postoperative neurological course. These results demonstrate that a NIRS study using our technique is extremely valuable for preoperative assessment of the language functions and exemplifies how a preoperative NIRS study can allow detection of unforeseen language lateralization. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

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  • Identification of a gene expression signature that predicts outcome in primary central nervous system lymphoma patients 査読

    18 ( 20 )   2012年

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  • Induction of autophagy in temozolomide treated malignant gliomas 査読

    Manabu Natsumeda, Hiroshi Aoki, Hiroaki Miyahara, Naoki Yajima, Takeo Uzuka, Yasuko Toyoshima, Akiyoshi Kakita, Hitoshi Takahashi, Yukihiko Fujii

    NEUROPATHOLOGY   31 ( 5 )   486 - 493   2011年10月

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

    Autophagy is a dynamic process of protein degradation. Induction of autophagy by temozolomide (TMZ) has been noted in glioma cell lines. Twenty-eight specimens, obtained from 14 patients before and after TMZ treatment, were analyzed to investigate whether induction of autophagy could be detected in surgical specimens by immunohistochemical analysis. Macroautophagy was monitored by immunohistochemical analysis employing anti-light chain 3 isoform B (LC3B) and anti-lysosome-associated membrane protein 1 (LAMP1) antibodies; chaperone-mediated autophagy was monitored by anti-LAMP2A antibody immunostaining. Furthermore, detection of LC3B protein by Western blotting was performed on six specimens obtained from the preserved frozen tissues of three patients. All specimens showed dot-like staining for each immunostain in the cytoplasm of glioma cells, indicating induction of autophagy. LC3B, LAMP1 and LAMP2A immunostains were semiquantitatively scored from 1 to 3 points. Combination of the three scores after TMZ treatment (6.4 +/- 1.2) showed a significant increase (P = 0.020) compared to pre-treatment scores (5.2 +/- 1.5). Western blotting for LC3B showed increased LC3B-I and LC3B-II expression after TMZ treatment. The present study proved that autophagy monitoring by immunohistochemical staining of surgical specimens was feasible. These results suggest that autophagy is induced by TMZ.

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  • Indication of intraoperative immunohistochemistry for accurate pathological diagnosis of brain tumors 査読

    Takeo Uzuka, Hiroshi Aoki, Manabu Natsumeda, Akiyoshi Kakita, Hitoshi Takahashi, Yukihiko Fujii

    BRAIN TUMOR PATHOLOGY   28 ( 3 )   239 - 246   2011年7月

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

    Immunohistochemical staining is important for histological diagnosis of brain tumors; however, its intraoperative application has rarely been reported. Herein, we describe our methods and four successfully diagnosed cases. Between January 2008 and April 2010, intraoperative immunohistochemical analysis was performed in 43 patients undergoing brain tumor surgery at our institute. The time for rapid histological diagnosis was 70 min. MIB-1 immunostaining was performed; staining index (SI) was 0.8-76.2% (median, 2.5%) in rapid diagnoses and 0.6-83.9% (median, 7.7%) in permanent diagnoses. There was no discrepancy in low- or high-grade tumors between intraoperative and final pathological diagnosis. The antibodies used for staining were MIB-1 in all cases, L26 in 8 cases, UCHL-1 in 6 cases, GFAP in 4 cases, AFP in 3 cases, and PLAP in 5 cases. The staining patterns were similar between rapid and permanent diagnoses. We think that immunohistochemical examination is indicated under the following conditions: (1) preoperative radiologic differential diagnosis includes both high- and low-grade tumors, (2) intraoperative assessment is necessary to determine the extent of excision, and (3) quick and accurate pathological diagnosis is necessary for early initiation of treatment after surgery.

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  • Anaplastic astrocytoma with angiocentric ependymal differentiation 査読

    Hiroaki Miyahara, Yasuko Toyoshima, Manabu Natsumeda, Takeo Uzuka, Hiroshi Aoki, Yoko Nakayama, Kouichiou Okamoto, Yukihiko Fujii, Akiyoshi Kakita, Hitoshi Takahashi

    NEUROPATHOLOGY   31 ( 3 )   292 - 298   2011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:WILEY-BLACKWELL  

    Angiocentric glioma (AG) is an epileptogenic benign cerebral tumor primarily affecting children and young adults, and characterized histopathologically by an angiocentric pattern of growth of monomorphous bipolar cells with features of ependymal differentiation (WHO grade I). We report an unusual cerebral glial tumor in a 66-year-old woman with generalized tonic-clonic seizure; the patient also had a 6-year history of headache. On MRI, the tumor appeared as a large T2-hyperintense lesion involving the right insular gyri-anterior temporal lobe, with post-contrast enhancement in the insula region. Histopathologically, the tumor involving the insular cortex-subcortical white matter was composed of GFAP-positive glial cells showing two different morphologies: one type had monomorphous bipolar cytoplasm and was angiocentric with circumferential alignment to the blood vessels, with dot-like structures positive for epithelial membrane antigen and a Ki-67 labeling index of &lt; 1%, and the other was apparently astrocytic, being diffusely and more widely distributed in the parenchyma, showing mitoses and a Ki-67 labeling index of &gt; 5%. In the anterior temporal lobe, a diffuse increase in the number of astrocytic cells was evident in part of the cortex and subcortical white matter. On the basis of these findings, we considered whether the present tumor may represent an unusual example of AG with infiltrating astrocytic cells showing primary anaplastic features (AG with anaplastic features), or anaplastic astrocytoma showing primary vascular-associated ependymal differentiation (anaplastic astrocytoma with angiocentric ependymal differentiation). At present, the latter appears to be the more appropriate interpretation.

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  • Clinicopathological factors related to regrowth of vestibular schwannoma after incomplete resection 査読

    Masafumi Fukuda, Makoto Oishi, Tetsuya Hiraishi, Manabu Natsumeda, Yukihiko Fujii

    JOURNAL OF NEUROSURGERY   114 ( 5 )   1224 - 1231   2011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)   出版者・発行元:AMER ASSOC NEUROLOGICAL SURGEONS  

    Object. The authors retrospectively analyzed various clinicopatholouical factors to determine which are related to regrowth during a long-term follow-up period in patients who underwent incomplete vestibular schwannoma (VS) resection.
    Methods. This study involved 74 patients (25 men and 49 women) in whom a VS was treated surgically via the lateral suboccipital approach, and who had postoperative follow-up periods exceeding 5 years. The mean follow-up was 104.1 months (range 60-241 months), and the mean patient age at surgery was 48.1 years (range 19-75 years). The tumors ranged in size from 0 mm (localized within the internal auditory canal) to 56 mm (28.3 +/- 12.2 mm [mean S 13]).
    Results. Gross-total resection (GTR) was performed in 41 (55%) of the 74 patients; subtotal resection GSTR]; 90-99%) in 25 (34%); and partial resection ([PR]; &lt; 90%) in 8 (11%). Regrowth rates in the GTR, STR, and PR groups were 2.4% (1 of 41 cases), 52% (13 of 25), and 62.5% (5 of 8), respectively, and the times to regrowth ranged from 6 to 76 months (median 31.9 months). The regrowth-free survival curves differed significantly between the complete (GTR) and incomplete (STR and PR) resection groups. Eighteen (54.5%) of the 33 patients who underwent incomplete resection showed evidence of regrowth during follow-up. Univariate and multivariate analyses of various factors revealed that both the thickness of the residual tumor, based on MR imaging after surgery, and the MIB-1 index were positively related to residual tumor regrowth. The receiver operating characteristic curves, plotted for both the thickness of the residual tumor and the MIB-1 index, identified the optimal cutoff points for these values as 7.4 mm (sensitivity 83.3%, specificity 86.7%) and 1.6 (sensitivity 83.3%, specificity 66.7%), respectively.
    Conclusions. Greater residual tumor thickness, based on MR imaging after the initial surgery, and a higher MIB-1 index are both important factors related to postoperative tumor regrowth in patients who have undergone incomplete VS resection. These patients require frequent neuroimaging investigation during follow-up to assure early detection of tumor regrowth. (DO!: 10.3171/2010.11.JNS101041)

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  • Synchronized multiple regression of diagnostic radiation-induced rather than spontaneous: Disseminated primary intracranial germinoma in a woman: A case report 査読

    Yuichiro Yoneoka, Itaru Tsumanuma, Shinya Jinguji, Manabu Natsumeda, Yukihiko Fujii

    Journal of Medical Case Reports   5   39   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Introduction. Examples of the spontaneous regression of primary intracranial germinomas can be found in the literature. We present the case of a patient with disseminated lesions of primary intracranial germinoma which synchronously shrunk following diagnostic irradiation. We will discuss whether this regression was spontaneous or radiation-induced. Case presentation. A 43-year-old Japanese woman presented to our hospital complaining of memory problems over a period of one year and blurred vision over a period of three months. Following magnetic resonance imaging, she was found to have a massive lesion in the third ventricle and small lesions in the pineal region, fourth ventricle, and in the anterior horn of the left lateral ventricle. Prior to an open biopsy to confirm the pathology of the lesions, she underwent a single cranial computed tomography scan and a single cranial digital subtraction angiography for a transcranial biopsy. Fourteen days after the first magnetic resonance image - 12 and eight days after the computed tomography scan and digital subtraction angiography, respectively - a pre-operative magnetic resonance image was taken, which showed a notable synchronous shrinkage of the third ventricle tumor, as well as shrinkage of the lesions in the pineal region and in the fourth ventricle. She did not undergo steroid administration until after a biopsy that confirmed the pathological diagnosis of pure germinoma. She then underwent whole craniospinal irradiation and went into a complete remission. Conclusions. In our case report, we state that diagnostic radiation can induce the regression of germinomas
    this is the most reasonable explanation for the synchronous multiple regression observed in this case of germinoma. Clinicians should keep this non-spontaneous regression in mind and monitor germinoma lesions with minimal exposure to diagnostic radiation before diagnostic confirmation, and also before radiation treatment with or without chemotherapy begins. © 2011 Yoneoka et al
    licensee BioMed Central Ltd.

    DOI: 10.1186/1752-1947-5-39

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  • Intraventricular pleomorphic xanthoastrocytoma with anaplastic features 査読

    Yong-Juan Fu, Hiroaki Miyahara, Takeo Uzuka, Manabu Natsumeda, Kouichirou Okamoto, Takanori Hirose, Yukihiko Fujii, Hitoshi Takahashi

    NEUROPATHOLOGY   30 ( 4 )   443 - 448   2010年8月

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

    Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic tumor that usually occurs in the superficial cerebral hemispheres of children and young adults and has a relatively favorable prognosis. We report an unusual case of supratentorial, intraventricular tumor in a 52-year-old man. The tumor was composed of pleomorphic cells, including giant cells, most of which were multinucleated, and small cells. In addition, frequent xanthic changes in the cytoplasm of the tumor cells, and widespread reticulin deposits and lymphocytic infiltrates in the stroma were characteristic features. Large areas of necrosis were also evident. However, mitotic figures were rare (1-2 mitoses per 10 high-power fields). Many tumor cells were positive for GFAP, and a number were positive for neurofilament protein and synaptophysin, indicating their neuronal differentiation. In addition, occasional tumor cells were positive for CD34. p53 protein was entirely negative in the tumor cells. In diagnosing this tumor histopathologically, differentiation between PXA and giant cell glioblastoma (GCG), a rare variant of glioblastoma, was problematic. However, considering the overall histopathological picture, a final diagnosis of PXA with anaplastic features was made. The present case indicates that PXA can occur as an intraventricular tumor, and suggests that in some instances, it would be very difficult to differentiate PXA and GCG histopathologically.

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  • Examination of the hypothalamic artery during clipping operations of anterior communicating artery aneurysms 査読

    Takafumi Saito, Akihiko Kurashima, Shinya Yamashita, Junpei Honma, Tarou Nishikawa, Manabu Natsumeda

    NEUROLOGICAL SURGERY   35 ( 9 )   881 - 885   2007年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:IGAKU-SHOIN LTD  

    Relationships between hypothalamic arteries and anterior communicating artery aneurysms were examined in 34 cases treated by clipping operations, using the anterior interhemispheric approach. The directions of the aneurysmal domes and hypothalamic arteries were analyzed and divided into 2 groups. The different direction(D.D.) group involved cases in which a hypothalamic artery ran in a different direction to that of the dome of the aneurysm. The same direction (S.D.) group involved cases in which a hypothalamic artery ran parallel to the dome of the aneurysm. The D.D. group consisted of 15 cases, and the S.D. group consisted of 13 cases. In the remaining 6 cases, the hypothalamic artery was not found during the operation. In many cases of the D.D. group, the aneurysm was located anterior to the A2 portions of the bilateral anterior cerebral arteries, whereas, in all cases of the S,D. group, the aneurysm was located between or posterior to the bilateral A2 portions. We also investigated the flow direction of the anterior communicating artery in the S.D. group, The dominant At was defined as the side of internal carotid angiography in which the aneurysm was depicted on preoperative angiography. The flow direction of the anterior communicating artery was assumed to flow from the dominant A1 side to the recessive A1 side. Considering the flow direction of the anterior communicating artery, the hypothalamic artery was located downstream from the aneurysm in 9 cases and upstream in 3 cases. These results suggested that it is important to pay more attention to the downstream of the aneurysm to avoid injury of the hypothalamic artery in the S.D. group. For cases in which the hypothalamic artery was located upstream to the aneurysm, these aneurysms seemed to arise from the bifurcation of the anterior communicating artery and hypothalamic artery, and might be named hypothalamic artery aneurisms.

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MISC

  • 放射線療法併用下でのニボルマブ投与により一定の進行抑制効果を得た小児meningeal malanomatosisの1例

    武居 慎吾, 結城 明彦, 阿部 理一郎, 太田 智慶, 棗田 学, 大石 誠, 柿田 明美

    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集   36回   139 - 139   2020年12月

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    記述言語:日本語   出版者・発行元:(一社)日本皮膚悪性腫瘍学会  

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  • 栄養動脈塞栓術を行い摘出したhypervascular cerebellopontine angle pilocytic astrocytomaの一例

    吉村 淳一, 棗田 学, 長谷川 仁, 大石 誠, 藤井 幸彦

    小児の脳神経   45 ( 3 )   256 - 256   2020年10月

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

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  • 脈絡叢乳頭癌の臨床像と治療経験

    大石 誠, 棗田 学, 吉村 淳一, 塚本 佳広, 今井 千速, 藤井 幸彦

    小児の脳神経   45 ( 3 )   257 - 257   2020年10月

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

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  • 小児悪性神経膠腫におけるBevacizumabの治療効果に関しての後方視的検討

    塚本 佳広, 棗田 学, 岡田 正康, 吉村 淳一, 岡本 浩一郎, 大石 誠, 藤井 幸彦

    小児の脳神経   45 ( 3 )   257 - 257   2020年10月

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

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  • 小児神経外科領域における画像診断の進歩と工夫 V-Pシャント後に上矢状静脈洞の流速は改善する脊髄髄膜瘤に対するPhase contrast法とエコーを用いた解析

    渡邉 潤, 佐野 正和, 中村 公彦, 斎藤 祥二, 棗田 学, 大石 誠, 藤井 幸彦

    小児の脳神経   45 ( 3 )   219 - 219   2020年10月

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

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  • 側頭葉に主座を持つH3K27M変異陽性の退形成性星細胞腫の一例

    塚本 佳広, 棗田 学, 大倉 良太, 太田 智慶, 温 城太郎, 齋藤 祥二, 岡本 浩一郎, 大石 誠, 柿田 明美, 藤井 幸彦

    Brain Tumor Pathology   37 ( Suppl. )   134 - 134   2020年8月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • GHホルモンは頭蓋咽頭腫の増大に寄与したか? GH産生下垂体腺腫と頭蓋咽頭腫が併存した一例から

    岡田 正康, 米岡 有一郎, 棗田 学, 大石 誠, 柿田 明美, 藤井 幸彦

    Brain Tumor Pathology   37 ( Suppl. )   094 - 094   2020年8月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • Topoisomerase IIβは髄芽腫細胞の神経分化を誘導する

    宮原 弘明, 棗田 学, 吉村 淳一, 藤井 幸彦, 柿田 明美, 岩崎 靖, 吉田 眞理

    Brain Tumor Pathology   37 ( Suppl. )   104 - 104   2020年8月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 脳腫瘍の遺伝子診断とゲノム医療2 ゲノム医療を想定したBRAF V600E変異を有する脳腫瘍の臨床病理像

    棗田 学, 金丸 優, 齋藤 祥二, 塚本 佳広, 岡田 正康, 大石 誠, 柿田 明美, 藤井 幸彦

    Brain Tumor Pathology   37 ( Suppl. )   076 - 076   2020年8月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • MYD88 mutationの検出が診断に有用であったlymphomatosis cerebriの1例

    渡邉 潤, 菊池 文平, 山下 慎也, 田村 哲郎, 棗田 学, 大石 誠, 藤井 幸彦, 酒井 剛

    Brain Tumor Pathology   37 ( Suppl. )   126 - 126   2020年8月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 血管内再開通療法が奏効した鈍的頸動脈損傷による急性期脳梗塞の1例

    齋藤 祥二, 長谷川 仁, 佐藤 大輔, 安藤 和弘, 本橋 邦夫, 棗田 学, 菊池 文平, 大石 誠, 藤井 幸彦

    Neurological Surgery   48 ( 6 )   527 - 532   2020年6月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

    46歳男。主訴は左片麻痺で、発症から63分後に救急搬送され、CTでは右中大脳動脈近位部にhyperdense signを認めた。3D-CT angiographyでは右頸部内頸動脈起始部の高度狭窄と頭蓋内内頸動脈以遠の閉塞を認めた。前日に剣道で右前頸部へ直接突きを受けており、鈍的外傷による右頸部内頸動脈解離と同部由来の塞栓による頭蓋内内頸動脈閉塞、急性期脳梗塞と診断した。到着から109分後に血管内再開通療法を開始し、内頸動脈起始部の狭窄部にステント留置を先行させ、その後総頸動脈遮断下に閉塞した内頸動脈終末部を直接吸引して血栓を回収した。再開通までは発症から245分であった。術後頭部MRIでは、右被殻、尾状核頭、島皮質、前頭葉弁蓋部、側頭葉内側に梗塞巣を認めたが、症状は劇的に改善し、23病日には軽度の注意障害を残し、modified Rankin Scale 1で退院した。

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01228&link_issn=&doc_id=20200626070011&doc_link_id=10.11477%2Fmf.1436204223&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1436204223&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

  • Current Topics MRSの臨床応用に向けて 脳腫瘍におけるMRSの利用

    棗田 学, 藤井 幸彦, 五十嵐 博中

    臨床画像   36 ( 5 )   557 - 562   2020年5月

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    記述言語:日本語   出版者・発行元:(株)メジカルビュー社  

    <文献概要>成人の代表的な脳実質内腫瘍は神経膠腫,転移性脳腫瘍,中枢神経原発性リンパ腫(PCNSL)である。それぞれ治療方針が異なるため,術前画像診断はきわめて重要である。頭部CT,MRIなどでの鑑別が難しい場合は,MRSが診断の一助となる。本稿では脳実質内腫瘍におけるプロトンMRSの特徴および診断のピットフォールについてまとめた。

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  • Precision Medicine 固形癌における包括的ゲノム解析に基づくPrecision Medicine(Precision Medicine)

    若井 俊文, 島田 能史, 永橋 昌幸, 市川 寛, 油座 築, 根本 万里子, 中野 麻恵, 廣瀬 雄己, 滝沢 一泰, 坂田 純, 亀山 仁史, 小林 隆, 棗田 学, 吉原 弘祐, 奥田 修二郎

    日本癌治療学会学術集会抄録集   57回   JSY1 - 4   2019年10月

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    記述言語:英語   出版者・発行元:(一社)日本癌治療学会  

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  • 診断 悪性神経膠腫における術後静脈血栓塞栓症危険因子の検討 ポドプラニンとIDH変異の関係

    棗田 学, 渡邉 潤, 岡田 正康, 金丸 優, 塚本 佳広, 大石 誠, 柿田 明美, 藤井 幸彦

    Brain Tumor Pathology   36 ( Suppl. )   070 - 070   2019年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • びまん性正中グリオーマの細胞株を用いた薬剤治療研究

    宮原弘明, 宮原弘明, 棗田学, 棗田学, 藤井幸彦, 吉田眞理

    小児の脳神経   44 ( 2 )   140   2019年4月

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    記述言語:日本語  

    J-GLOBAL

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  • 初発髄芽腫に対する術後2週間以内の全脳脊髄照射及びSJMB‐96式自家末梢血幹細胞救援併用反復大量化学療法:単一施設での治療経験

    今村勝, 石井孝規, 久保暢大, 笠原靖史, 岩渕晴子, 棗田学, 大石誠, 今井千速, 吉村淳一, 青山英史, 藤井幸彦

    小児の脳神経   44 ( 2 )   125   2019年4月

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    記述言語:日本語  

    J-GLOBAL

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  • 悪性高熱と静脈洞血栓症を併発したCOL4A1 mutationを伴う裂脳症の1例

    渡邉潤, 大橋伯, 棗田学, 岡本浩一郎, 大石誠, 藤井幸彦

    小児の脳神経   44 ( 2 )   150   2019年4月

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    記述言語:日本語  

    J-GLOBAL

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  • プレシジョン=メディシンを念頭に入れた小児脳腫瘍のモデル確立の試み

    棗田学, 金丸優, 阿部英明, 渡邉潤, 塚本佳広, 岡田正康, 吉村淳一, 大石誠, 藤井幸彦

    小児の脳神経   44 ( 2 )   143   2019年4月

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    記述言語:日本語  

    J-GLOBAL

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  • MYC高発現髄芽腫に対してEZH2阻害剤を用いた新規治療戦略

    棗田学, 棗田学, 中田聡, 宮原弘明, 宮原弘明, 吉村淳一, 大石誠, 藤井幸彦

    小児の脳神経   44 ( 2 )   139   2019年4月

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    記述言語:日本語  

    J-GLOBAL

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  • Temozolomide and Notch inhibitor MRK-003 induce cell protective autophagy in malignant gliomas 査読

    Natsumeda Manabu, Aoki Hiroshi, Miyahara Hiroaki, Kakita Akiyoshi, Takahashi Hitoshi, Eberhart Charles G, Fujii Yukihiko

    BRAIN PATHOLOGY   29   142   2019年2月

  • H3K9 methyltransferase inhibitor BIX01294 inhibits tumorigenicity in diffuse intrinsic pontine glioma and glioblastoma 査読

    Miyahara Hiroaki, Natsumeda Manabu, Koldobsky Michael, Liu Yang, Kaur Harpreet, Asnaghi Laura, Yoshida Mari, Eberhart Charles G, Raabe Eric H

    BRAIN PATHOLOGY   29   156   2019年2月

  • 7-tesla MR susceptibility-weighted imaging can dipict astrocytic and oligodendroglial pathology 査読

    Natsumeda Manabu, Matsuzawa Hitoshi, Tsukamoto Yoshihiro, Motohashi Kunio, Kanemaru Yu, Okamoto Kouichirou, Kakita Akiyoshi, Igarashi Hironaka, Nakata Tsutomu, Fujii Yukihiko

    BRAIN PATHOLOGY   29   68 - 69   2019年2月

  • 悪性髄膜腫における個別化医療の可能性

    平石 哲也, 棗田 学, 岡田 正康, 大石 誠, 藤井 幸彦

    Precision Medicine   2 ( 1 )   54 - 58   2019年1月

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    記述言語:日本語   出版者・発行元:(株)北隆館  

    近年の遺伝子発現解析技術の飛躍的な進歩により髄膜腫の分子生物学的な背景の理解が深まった。基本的に良性腫瘍である髄膜腫にあって悪性髄膜腫は、手術や放射線治療に抵抗性の症例では、次の有効な治療手段が確立されていない。我々の施設では、がん医療で先行して利用され始めた遺伝子パネルを利用することで悪性髄膜腫固有のドライバー変異が同定可能であるという仮説を立て、現在研究を行っている。本研究について本コーナーで概説する。(著者抄録)

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  • HIGH DETECTION RATE OF MYD88MUTATIONS IN CEREBROSPINAL FLUID FROM PATIENTS WITH CENTRAL NERVOUS SYSTEM LYMPHOMAS 査読

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

    NEURO-ONCOLOGY   20   169   2018年11月

  • 3D‐Exoscope使用下における脳腫瘍手術の可能性

    平石哲也, 大石誠, 棗田学, 温城太郎, 安藤和弘, 太田智慶, 吉田雄一, 藤井幸彦

    日本神経内視鏡学会プログラム・抄録集   25th   119   2018年10月

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    記述言語:日本語  

    J-GLOBAL

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  • IDH変異型グリオーマの診断と術中治療―コラボレーションを通して実現を目指す―

    棗田学, 阿部英明, 岡田正康, 五十嵐博中, 中田力, 小山哲秀, 小野寺理, 柿田明美, 大石誠, 藤井幸彦

    日本蛋白質科学会年会プログラム・要旨集   18th   25   2018年5月

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    記述言語:日本語  

    J-GLOBAL

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  • Diffuse midline gliomaに対するテモゾロミド感受性はMGMT発現により規定される in vitroでの検証

    棗田 学, 阿部 英明, 岡田 正康, 吉村 淳一, 大石 誠, 藤井 幸彦

    小児の脳神経   43 ( 2 )   261 - 261   2018年4月

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

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  • びまん性橋グリオーマに対する外科治療の役割と成績 びまん性橋グリオーマ(DIPG)に対する摘出術の役割と成績

    吉村 淳一, 岡田 正康, 棗田 学, 大石 誠, 藤井 幸彦

    小児の脳神経   43 ( 2 )   169 - 169   2018年4月

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

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  • 10年以上経過して再発した髄芽腫の2症例

    岡田 正康, 吉村 淳一, 西山 健一, 棗田 学, 大石 誠, 藤井 幸彦

    小児の脳神経   43 ( 2 )   215 - 215   2018年4月

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

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  • Diffuse midline gliomaに対するテモゾロミド感受性はMGMT発現により規定される in vitroでの検証

    棗田 学, 阿部 英明, 岡田 正康, 吉村 淳一, 大石 誠, 藤井 幸彦

    小児の脳神経   43 ( 2 )   261 - 261   2018年4月

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

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  • びまん性橋グリオーマに対する外科治療の役割と成績 びまん性橋グリオーマ(DIPG)に対する摘出術の役割と成績

    吉村 淳一, 岡田 正康, 棗田 学, 大石 誠, 藤井 幸彦

    小児の脳神経   43 ( 2 )   169 - 169   2018年4月

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

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  • 10年以上経過して再発した髄芽腫の2症例

    岡田 正康, 吉村 淳一, 西山 健一, 棗田 学, 大石 誠, 藤井 幸彦

    小児の脳神経   43 ( 2 )   215 - 215   2018年4月

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

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  • 【日本一カンタン・わかりやすい 脳神経の解剖&疾患ノート】(2章)ゆる〜く、やさしく脳神経疾患 転移性脳腫瘍

    棗田 学

    Brain Nursing   別冊 ( 脳神経の解剖&疾患ノート-日本一カンタン・わかりやすい )   126 - 128   2018年2月

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    記述言語:日本語   出版者・発行元:(株)メディカ出版  

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  • 髄膜播種をきたしたEpithelioid glioblastomaの1例

    金丸 優, 棗田 学, 齋藤 理恵, 野澤 孝徳, 阿部 英明, 岡本 浩一郎, 大石 誠, 藤井 幸彦, 柿田 明美, 信澤 純人

    信州医学雑誌   66 ( 1 )   104 - 105   2018年2月

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    記述言語:日本語   出版者・発行元:信州医学会  

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  • 細胞突起形成抑制による膠芽腫治療戦略

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

    新潟県医師会報   ( 814 )   9 - 10   2018年1月

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    記述言語:日本語   出版者・発行元:新潟県医師会  

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  • Gli3 INDUCES NEURONAL DIFFERENTIATION IN WNT- AND SHH-ACTIVATED MEDULLOBLASTOMA 査読

    Manabu Natsumeda, Hiroaki Miyahara, Junichi Yoshimura, Takanori Nozawa, Yoshihiro Tsukamoto, Takafumi Wataya, Charles Eberhart, Hitoshi Takahashi, Akiyoshi Kakita, Yukihiko Fujii

    NEURO-ONCOLOGY   19   183 - 183   2017年11月

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

    Web of Science

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  • 分子病理と分子病態 Oncogenesis and Progression WNT群、SHH群におけるGli3高発現と神経細胞分化

    棗田 学, 吉村 淳一, 宮原 弘明, 野澤 孝徳, 塚本 佳広, 綿谷 崇史, Eberhart Charles, 高橋 均, 柿田 明美, 藤井 幸彦

    Brain Tumor Pathology   34 ( Suppl. )   073 - 073   2017年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • グリオーマにおけるhistone H3K9 methyltransferase阻害薬の有効性(その1)

    服部 修太, 富澤 元, 阿部 英明, 梨本 望, 野澤 孝徳, 塚本 佳広, 岡田 正康, 棗田 学, 藤井 幸彦

    Brain Tumor Pathology   34 ( Suppl. )   135 - 135   2017年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • グリオーマにおけるhistone H3K9 methyltransferase阻害薬の有効性(その2)

    富澤 元, 服部 修太, 阿部 英明, 梨本 望, 野澤 孝徳, 塚本 佳広, 岡田 正康, 棗田 学, 藤井 幸彦

    Brain Tumor Pathology   34 ( Suppl. )   136 - 136   2017年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 脳実質びまん性に認められた小型リンパ球増殖性疾患の一手術例

    塚本 佳広, 野澤 孝徳, 渡邉 潤, 佐藤 朋江, 棗田 学, 大石 誠, 高橋 均, 杉田 保雄, 柿田 明美, 藤井 幸彦

    Brain Tumor Pathology   34 ( Suppl. )   138 - 138   2017年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 4 H3F3A G34Rが認められたcerebral hemispheric glioblastomaの1例 (一般演題, 第42回上信越神経病理懇談会)

    塚本 佳広, 野澤 孝徳, 伊藤 絢子, 阿部 英明, 小倉 良介, 五十川 瑞穂, 棗田 学, 青木 洋, 岡本 浩一郎, 高橋 均, 藤井 幸彦, 柿田 明美

    新潟医学会雑誌 = 新潟医学会雑誌   131 ( 5 )   313 - 313   2017年5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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  • H3F3A G34Rが認められたcerebral hemispheric glioblastomaの1例

    塚本 佳広, 野澤 孝徳, 伊藤 絢子, 阿部 英明, 小倉 良介, 五十川 瑞穂, 棗田 学, 青木 洋, 岡本 浩一郎, 高橋 均, 藤井 幸彦, 柿田 明美

    新潟医学会雑誌   131 ( 5 )   313 - 313   2017年5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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  • 集学的治療を行ったH3.1 K27M mutationを有するDiffuse Intrinsic Pontine Gliomaの一例

    塚本 佳広, 吉村 淳一, 棗田 学, 大石 誠, 岡本 浩一郎, 藤井 幸彦

    小児の脳神経   42 ( 2 )   168 - 168   2017年4月

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

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  • 【新人ナース応援号 日本一カンタン・わかりやすい 脳神経外科疾患ノート】転移性脳腫瘍

    棗田 学

    Brain Nursing   33 ( 4 )   374 - 376   2017年4月

  • C-myc高発現髄芽腫に対してEZH2 inhibitorを用いた新規治療戦略

    棗田 学, 宮原 弘明, 吉村 淳一, 大石 誠, 藤井 幸彦, チャールズ・エバーハート

    小児の脳神経   42 ( 2 )   120 - 120   2017年4月

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

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  • 小児悪性脳腫瘍の集学的治療 各論 初発髄芽腫に対するmodified SJMB-96プロトコールの長期治療成績

    吉村 淳一, 棗田 学, 佐野 正和, 大石 誠, 藤井 幸彦

    小児の脳神経   42 ( 2 )   132 - 132   2017年4月

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

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  • Targeting cancer stem-like cells in glioblastoma and colorectal cancer through metabolic pathways

    U. D. Kahlert, S. M. Mooney, M. Natsumeda, H. J. Steiger, J. Maciaczyk

    International Journal of Cancer   140 ( 1 )   10 - 22   2017年1月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:Wiley-Liss Inc.  

    Cancer stem-like cells (CSCs) are thought to be the main cause of tumor occurrence, progression and therapeutic resistance. Strong research efforts in the last decade have led to the development of several tailored approaches to target CSCs with some very promising clinical trials underway
    however, until now no anti-CSC therapy has been approved for clinical use. Given the recent improvement in our understanding of how onco-proteins can manipulate cellular metabolic networks to promote tumorigenesis, cancer metabolism research may well lead to innovative strategies to identify novel regulators and downstream mediators of CSC maintenance. Interfering with distinct stages of CSC-associated metabolics may elucidate novel, more efficient strategies to target this highly malignant cell population. Here recent discoveries regarding the metabolic properties attributed to CSCs in glioblastoma (GBM) and malignant colorectal cancer (CRC) were summarized. The association between stem cell markers, the response to hypoxia and other environmental stresses including therapeutic insults as well as developmentally conserved signaling pathways with alterations in cellular bioenergetic networks were also discussed. The recent developments in metabolic imaging to identify CSCs were also summarized. This summary should comprehensively update basic and clinical scientists on the metabolic traits of CSCs in GBM and malignant CRC.

    DOI: 10.1002/ijc.30259

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  • 【脳腫瘍学-基礎研究と臨床研究の進歩-】脳腫瘍の予後因子 髄芽腫の予後因子Gli3

    吉村 淳一, 宮原 弘明, 棗田 学, 柿田 明美, 藤井 幸彦

    日本臨床   74 ( 増刊7 脳腫瘍学 )   292 - 297   2016年9月

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  • CELL CULTURE CONDITIONS AFFECT DIFFUSE INTRINSIC PONTINE GLIOMA EPIGENETICS AND RESPONSE TO THERAPEUTIC AGENTS 査読

    Sama Ahsan, Michael Haffner, Hiroaki Miyahara, Manabu Natsumeda, Yang Liu, Lauren Rocco, Charles Eberhart, Eric Raabe

    NEURO-ONCOLOGY   18   64 - 64   2016年6月

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

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  • 髄芽腫のmolecular分類 MAGIC分類とGli3免疫染色の対比

    吉村 淳一, 宮原 弘明, 綿谷 崇史, 清家 尚彦, 棗田 学, 柿田 明美, 藤井 幸彦

    Brain Tumor Pathology   33 ( Suppl. )   096 - 096   2016年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 3T-MRSを用いたグリオーマのIDH変異術前評価

    棗田 学, 五十嵐 博中, 野村 俊春, 小倉 良介, 塚本 佳広, 小林 勉, 青木 洋, 岡本 浩一郎, 中田 力, 藤井 幸彦

    CI研究   37 ( 3-4 )   105 - 110   2016年3月

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    記述言語:日本語   出版者・発行元:日本脳神経CI学会  

    2-ヒドロキシグルタル酸(2HG)は正常組織では殆ど検出されないが、IDH変異を有するグリオーマでは蓄積する。IDH変異を有するグリオーマ症例で、3T-single voxel Magnetic Resonance Spectroscopy(3T-SVMRS)を用いて、2HGを検出できることを報告した。その内容を、1)IDH変異と2HG、2)IDH変異を有するグリオーマの特異なbiology、3)3T-SVMRSの撮像条件、4)SVMRSによる2HGの検出、5)2HGの測定の臨床的意義、の5項目に分けて解説した。

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  • 悪性星細胞腫瘍におけるp53の発現意義

    小倉 良介, 塚本 佳広, 棗田 学, 五十川 瑞穂, 青木 洋, 小林 勉, 吉田 誠一, 高橋 均, 柿田 明美, 藤井 幸彦

    Brain Tumor Pathology   32 ( Suppl. )   105 - 105   2015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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  • グリオーマ幹細胞研究の取り組み

    塚本 佳広, 小倉 良介, 岡田 正康, 棗田 学, 五十川 瑞穂, 青木 洋, 吉田 誠一, 藤井 幸彦, 小林 勉

    新潟医学会雑誌   128 ( 11 )   610 - 610   2014年11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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  • 5 グリオーマ幹細胞研究の取り組み(Ⅰ.一般演題, 第62回新潟脳神経外科懇話会)

    塚本 佳広, 小倉 良介, 岡田 正康, 棗田 学, 五十川 瑞穂, 青木 洋, 吉田 誠一, 藤井 幸彦, 小林 勉

    新潟医学会雑誌 = 新潟医学会雑誌   128 ( 11 )   610 - 610   2014年11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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  • INDUCTION OF AUTOPHAGY MARKERS IN GLIOMAS FOLLOWING PHARMACOLOGICAL NOTCH BLOCKADE 査読

    Manabu Natsumeda, Hongyan Zhang, Harpreet Kaur, Laura Asnaghi, Charles G. Eberhart

    NEURO-ONCOLOGY   16   2014年11月

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

    DOI: 10.1093/neuonc/nou244.2

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  • 【マルチモダリティによるHead & Neck Imaging 2014 臨床編 最新技術が臨床にもたらす変革とベネフィット】MRIのストラテジー&アウトカム 臨床施設からの報告 脳腫瘍 神経膠腫の診断・鑑別診断、術前情報取得におけるMRIの有用性

    岡本 浩一郎, 野村 俊春, 倉部 聡, 塚本 佳広, 棗田 学, 小倉 良介, 五十川 瑞穂, 青木 洋, 金沢 勉, 淡路 正則, 稲川 正一, 五十嵐 博中, 藤井 幸彦

    INNERVISION   29 ( 5 )   21 - 24   2014年4月

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    記述言語:日本語   出版者・発行元:(株)インナービジョン  

    脳腫瘍の画像診断は、(1)存在・局在診断(腫瘍性病変の検出と部位・進展範囲の把握)、(2)質的(腫瘍の組織型と悪性度)診断推定と鑑別診断、(3)術前情報取得、(4)術後評価、(5)治療効果判定のいずれにも大きく関与する。CTは、(1)(2)における腫瘍の石灰化の検出、(3)での頭蓋骨描出などにおいて有用であるが、MRI情報はすべての過程において重要である。本稿では、神経膠腫の(2)(3)における当施設でのMRI撮像について、症例を提示して示す。なお、3T MRI装置を用いたMRスペクトロスコピー(MRS)、arterial spin labeling(ASL)法による灌流MRI、拡散テンソル画像(DTI)、three dimensional anisotropy contrast(3D-AC)法による神経線維描出は、本学脳研究所統合脳機能研究センターの協力を得て行っている。(著者抄録)

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  • 大きな転移性脳腫瘍に対するガンマナイフによる2分割定位照射の有用性と安全性

    五十川 瑞穂, 佐藤 光弥, 小倉 良介, 棗田 学, 青木 洋, 藤井 幸彦

    新潟医学会雑誌   128 ( 3 )   146 - 146   2014年3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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  • 9 大きな転移性脳腫瘍に対するガンマナイフによる2分割定位照射の有用性と安全性(Ⅰ.一般演題, 第73回新潟癌治療研究会)

    五十川 瑞穂, 佐藤 光弥, 小倉 良介, 棗田 学, 青木 洋, 藤井 幸彦

    新潟医学会雑誌 = 新潟医学会雑誌   128 ( 3 )   146 - 146   2014年3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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  • 出血性梗塞を疑うも診断に苦慮した1例

    棗田 学, 安藤 和弘, 岡田 正康, 渡邉 徹, 小倉 良介, 岡本 浩一郎, 牧野 邦比古

    新潟医学会雑誌   128 ( 1 )   37 - 38   2014年1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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  • 3 出血性梗塞を疑うも診断に苦慮した1例(Ⅰ.一般演題, 第61回新潟脳神経外科懇話会)

    棗田 学, 安藤 和広, 岡田 正康, 渡邉 徹, 小倉 良介, 岡本 浩一郎, 牧野 邦比古

    新潟医学会雑誌 = 新潟医学会雑誌   128 ( 1 )   37 - 38   2014年1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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  • マウス脳腫瘍モデルを用いた脳腫瘍幹細胞の分離培養法の確立

    五十川 瑞穂, 塚本 佳広, 小倉 良介, 岡田 正康, 棗田 学, 青木 洋, 吉田 誠一, 藤井 幸彦

    新潟県医師会報   ( 766 )   10 - 12   2014年1月

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    記述言語:日本語   出版者・発行元:新潟県医師会  

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  • 頭部MRI上Target signを示しToxoplasma脳症と鑑別を要した中枢悪性リンパ腫の1例

    小池 佑佳, 佐藤 朋江, 大内 東香, 新保 淳輔, 佐藤 晶, 五十嵐 修一, 橋立 英樹, 棗田 学, 佐々木 修, 岡本 浩一郎

    新潟医学会雑誌   127 ( 6 )   332 - 333   2013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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  • 3 頭部MRI上Target signを示しToxoplasma脳症と鑑別を要した中枢悪性リンパ腫の1例(Ⅰ.一般演題, 第67回新潟画像医学研究会)

    小池 佑佳, 佐藤 朋江, 大内 東香, 新保 淳輔, 佐藤 晶, 五十嵐 修一, 橋立 英樹, 棗田 学, 佐々木 修, 岡本 浩一郎

    新潟医学会雑誌 = 新潟医学会雑誌   127 ( 6 )   332 - 333   2013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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  • 白血病に対する全脳脊髄照射後に頭蓋内外に進展する骨肉腫を生じたLi-Fraumeni類縁症候群の1例

    吉村 淳一, 棗田 学, 西平 靖, 西山 健一, 斉藤 明彦, 岡本 浩一郎, 高橋 均, 藤井 幸彦

    Neurological Surgery   41 ( 6 )   499 - 505   2013年6月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

    28歳男。12歳時、急性リンパ性白血病にて化学療法と予防的全脳全脊髄照射で完解したが、化学療法により拡張型心筋症となり、27歳時に透析導入、直腸癌と肝細胞癌の治療、大腸癌の手術を施行された。今回、頭痛、嘔気、嘔吐から歩行困難となり、左小脳半球と後頭部の皮下腫瘍が認められた。頭部CTで左小脳に径5cm、左後頭部に皮下腫瘍を認めたが、間に介在する後頭骨破壊はなかった。MRIでは、CT同様の腫瘍病変を認め、間に介在する後頭骨に明らかな信号変化はなく腫瘍は独立しており、放射線誘発髄膜腫が疑われた。小脳腫瘍と皮下腫瘍を介在する後頭骨と共に摘出し、大孔部で椎骨動脈に癒着した部分を一部残存して亜摘出した。病理所見では、皮下・小脳腫瘍ともに類骨形成を伴う骨肉腫の腫瘍細胞が密に増生し、介在する後頭骨にも浸潤していた。術後1ヵ月で頭蓋内に局所再発を認めた。その後、胸髄への播種病変による対麻痺が出現したため胸髄腫瘍を摘出したが、頭蓋内・脊髄の残存病変は急速に進行し11ヵ月後に死亡した。白血球DNA検査でTP53遺伝子に点突然変異が認められた。剖検では、肺・腎など頭蓋外転移も認め、腫瘍細胞はp53免疫染色に強陽性を示し、Li-Fraumeni類縁症候群に発症した頭蓋内骨肉腫と診断した。

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  • 硬膜への播種性再発と腫瘍内出血を繰り返した膠肉腫の一例

    青木 洋, 小倉 良介, 塚本 佳広, 棗田 学, 小林 勉, 岡本 浩一郎, 吉田 誠一, 柿田 明美, 高橋 均, 藤井 幸彦

    Brain Tumor Pathology   30 ( Suppl. )   157 - 157   2013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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  • 再発・進行性びまん性内在性橋膠腫(DIPG)に対するベバシズマブの効果

    吉村 淳一, 棗田 学, 佐野 正和, 青木 洋, 西山 健一, 藤井 幸彦

    小児の脳神経   38 ( 1 )   92 - 92   2013年4月

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

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  • 神経膠腫摘出標本における免疫染色法を用いたIDH1 mutationの評価と予後解析

    小倉 良介, 棗田 学, 青木 洋, 小林 勉, 柿田 明美, 高橋 均, 藤井 幸彦

    新潟医学会雑誌   127 ( 3 )   172 - 172   2013年3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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  • 7 神経膠腫摘出標本における免疫染色法を用いたIDH1 mutationの評価と予後解析(Ⅰ.一般演題, 第60回新潟脳神経外科懇話会)

    小倉 良介, 棗田 学, 青木 洋, 小林 勉, 柿田 明美, 高橋 均, 藤井 幸彦

    新潟医学会雑誌 = 新潟医学会雑誌   127 ( 3 )   172 - 172   2013年3月

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  • 高齢悪性神経膠腫症例に対する少分割照射

    青木 洋, 棗田 学, 阿部 英輔, 宇塚 岳夫, 小林 勉, 青山 英史, 藤井 幸彦

    Neurological Surgery   40 ( 7 )   593 - 598   2012年7月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

    1995年1月〜2004年12月に標準的放射線療法を施行した75歳以上の初発膠芽腫10例、2005年1月〜2011年4月に少分割照射を施行した75歳以上の初発膠芽腫16例を対象に、2005年以降の患者の負担を軽減するために採用した少分割照射の有用性を標準的放射線療法と比較検討した。標準的放射線療法は10例中8例(80%)において放射線治療を完遂し得た。3例は温熱療法を併用し、1例でラニムスチンを用いた化学療法を併用した。フォローアップ期間は3〜20ヵ月、中央値10ヵ月で全例死亡した。入院期間は44〜96日、中央値68日、生存期間は3〜20ヵ月、中央値10ヵ月であった。少分割照射は16例中14例において総照射線量を39Gyに設定し、残り2例において30Gyに設定した。フォローアップ期間は2〜45ヵ月、中央値9.6ヵ月で2011年12月迄に13例(81%)が死亡した。入院期間は19〜61日、中央値38日、生存期間は2〜45ヵ月、中央値9.6ヵ月であった。入院時との比較では改善5例、悪化5例、不変6例であった。両群間において退院時のKarnofsky Performance Status(KPS)はほぼ同様の数値を示し、有意差を認めていない。少分割照射の治療効果として全生存期間が同等で、利点とし治療期間(入院期間)の短縮(30日間)、合併症の軽減(有害事象0%)、ステロイド減少、高い治療完遂率、自宅退院割合の増加、医療費削減、放射線部の負担軽減が挙げられる。欠点として白質脳症、認知機能低下、放射線壊死の増加、長期生存の割合の低下の潜在的可能性がある。

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  • 2 当院における特発性脊髄硬膜外血腫の治験例(I.一般演題,第59回新潟脳神経外科懇話会)

    中村 公彦, 佐々木 修, 西野 和彦, 棗田 学, 三橋 大樹, 吉井 雅美, 小池 哲雄

    新潟医学会雑誌 = 新潟医学会雑誌   126 ( 7 )   373 - 374   2012年7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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  • 当院における特発性脊髄硬膜外血腫の治験例

    中村 公彦, 佐々木 修, 西野 和彦, 棗田 学, 三橋 大樹, 吉井 雅美, 小池 哲雄

    新潟医学会雑誌   126 ( 7 )   373 - 374   2012年7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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  • 12 高流量ACNU動注を主体とした化学療法単独で治療している, 成人テント上 Low-grade glioma の3例(I.一般演題,第59回新潟脳神経外科懇話会)

    菅井 努, 武田 憲夫, 井上 明, 妻沼 到, 熊谷 孝, 野村 俊春, 温 城太郎, 田村 元, 棗田 学, 藤井 幸彦, 高橋 均

    新潟医学会雑誌 = 新潟医学会雑誌   126 ( 7 )   379 - 379   2012年7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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  • 19 頭蓋内胚腫の治療成績と新たな治療プロトコル(I.一般演題,第59回新潟脳神経外科懇話会)

    神宮字 伸哉, 吉村 淳一, 青木 洋, 棗田 学, 米岡 有一郎, 西山 健一, 藤井 幸彦

    新潟医学会雑誌 = 新潟医学会雑誌   126 ( 7 )   383 - 383   2012年7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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  • 小児期発症の頭蓋内胚腫患者の長期予後

    神宮字 伸哉, 吉村 淳一, 青木 洋, 長崎 啓祐, 棗田 学, 米岡 有一郎, 西山 健一, 藤井 幸彦

    小児の脳神経   37 ( 3 )   243 - 250   2012年6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  

    当施設における小児期発症の頭蓋内胚腫の治療成績と長期予後を検討した。対象は、1990年から2009年に初期治療を行った15歳以下の胚腫23名で、88%に照射単独治療(全脳脊髄照射15名、全脳照射5名)を、残り3名に化学療法単独もしくは併用治療を行った。照射単独治療群では、再発を認めなかった。10歳以下で同治療を行った3名で高次脳機能低下を認めた。胚腫における照射単独治療は、治癒が望める有効な治療法ではあるが、低年齢時の放射線治療は、高次脳機能低下を来す可能性があり、年齢や病変の広がりに応じた治療法の検討が必要である。(著者抄録)

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  • 神経膠腫におけるIDH1 mutationと予後との関連 摘出組織を用いた免疫組織化学的検討

    小倉 良介, 棗田 学, 青木 洋, 小林 勉, 高橋 均, 柿田 明美, 藤井 幸彦

    Brain Tumor Pathology   29 ( Suppl. )   190 - 190   2012年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 脳腫瘍病理学の新傾向 日常の病理組織診断への分子遺伝学の応用(パートII)(髄芽腫) Gli3は髄芽腫におけるニューロンおよびグリア分化に関連する(New Trends in Brain Tumor Pathology: Application of Molecular Genetics to Routine Histopathological Diagnosis(Part II)(Medulloblastoma) Gli3 is Associated with Neuronal and Glial Di

    棗田 学, 宮原 弘明, 吉村 淳一, 西山 健一, 豊島 靖子, 柿田 明美, 高橋 均, 藤井 幸彦

    Brain Tumor Pathology   29 ( Suppl. )   116 - 116   2012年5月

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    記述言語:英語   出版者・発行元:日本脳腫瘍病理学会  

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  • 脳腫瘍に対する治療戦略の新しい展望 分子解析に基づく臨床試験 神経膠腫の擬似進行ではIDH1変異ではなくnegative MGMT発現が高頻度に発生する(New Horizon of Treatment Strategy for Brain Tumor: Clinical Trial Based on Molecular Analyses High Incidence of Negative MGMT Expression but not IDH1 Mutation in Pseudoprogressio

    棗田 学, 小倉 良介, 青木 洋, 小林 勉, 宇塚 岳夫, 柿田 明美, 高橋 均, 藤井 幸彦

    Brain Tumor Pathology   29 ( Suppl. )   151 - 151   2012年5月

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    記述言語:英語   出版者・発行元:日本脳腫瘍病理学会  

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  • 急性硬膜外血腫を呈し術中大量出血を伴った外傷性内頸動脈損傷の1例

    三橋 大樹, 佐々木 修, 西野 和彦, 中村 公彦, 棗田 学, 吉井 雅美, 小池 哲雄

    日本脳神経外傷学会プログラム・抄録集   35回   111 - 111   2012年3月

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    記述言語:日本語   出版者・発行元:(一社)日本脳神経外傷学会  

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  • 17 PseudoprogressionにおけるMGMT発現の検討(I.一般演題,第58回新潟脳神経外科懇話会)

    棗田 学, 小倉 良介, 青木 洋, 小林 勉, 宇塚 岳夫, 藤井 幸彦

    新潟医学会雑誌 = 新潟医学会雑誌   126 ( 2 )   117 - 117   2012年2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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  • Merci retrieval systemを用いた血栓回収療法の初期治療成績

    西野 和彦, 佐々木 修, 中村 公彦, 棗田 学, 佐藤 洋輔, 三橋 大樹, 小池 哲雄

    JNET: Journal of Neuroendovascular Therapy   5 ( 4 )   282 - 282   2011年11月

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

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  • 21 脳腫瘍摘出手術おける術中CTの使用経験(一般演題,第57回新潟脳神経外科懇話会)

    青木 洋, 棗田 学, 宇塚 岳夫, 藤井 幸彦

    新潟医学会雑誌 = 新潟医学会雑誌   125 ( 8 )   461 - 461   2011年8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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  • 深部白質に境界明瞭な病変を呈したPXAの一例

    青木 洋, 棗田 学, 宇塚 岳夫, 柿田 明美, 高橋 均, 藤井 幸彦

    Brain Tumor Pathology   28 ( Suppl. )   126 - 126   2011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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  • 効果判定のための病理診断 Pseudoprogression症例におけるMGMT発現及びオートファジー誘導の検討

    棗田 学, 青木 洋, 宮原 弘明, 宇塚 岳夫, 柿田 明美, 高橋 均, 藤井 幸彦

    Brain Tumor Pathology   28 ( Suppl. )   052 - 052   2011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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  • 髄芽腫におけるGli3の発現 神経細胞への分化と良好な患者予後との関連

    宮原 弘明, 棗田 学, 吉村 淳一, 豊島 靖子, 藤井 幸彦, 高橋 均, 柿田 明美

    Brain Tumor Pathology   28 ( Suppl. )   081 - 081   2011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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  • ベバシズマブ治療を施行した小児脳幹グリオーマの一剖検例

    吉村 淳一, 棗田 学, 西山 健一, 藤井 幸彦, 高橋 均

    Brain Tumor Pathology   28 ( Suppl. )   115 - 115   2011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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  • LC3B抗体を用いた悪性グリオーマのオートファジーモニタリング(Monitoring autophagy in malignant glioma with antibody against LC3B)

    青木 洋, 棗田 学, 近藤 精二, 藤井 幸彦

    日本癌学会総会記事   69回   354 - 355   2010年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • TP53遺伝子の胚細胞変異を有する多発がん患者に発生し、特異な広がりを呈した頭蓋内骨肉腫の一例

    吉村 淳一, 棗田 学, 西平 靖, 西山 健一, 斉藤 明彦, 藤井 幸彦, 高橋 均

    Brain Tumor Pathology   27 ( Suppl. )   135 - 135   2010年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 脳腫瘍における術中迅速免疫組織化学的診断の有用性

    宇塚 岳夫, 棗田 学, 青木 洋, 宮原 弘明, 柿田 明美, 高橋 均, 藤井 幸彦

    Brain Tumor Pathology   27 ( Suppl. )   71 - 71   2010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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  • 悪性神経膠腫症例におけるオートファジーモニタリングと治療抵抗性獲得の検討

    棗田 学, 青木 洋, 宮原 弘明, 宇塚 岳夫, 豊島 靖子, 柿田 明美, 高橋 均, 藤井 幸彦

    Brain Tumor Pathology   27 ( Suppl. )   101 - 101   2010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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  • Sotos症候群の一例 特異な解剖異常と病態の考察

    原田 敦子, 西山 健一, 棗田 学, 斉藤 なか, 吉村 淳一, 山田 謙一, 森 宏, 岡本 浩一郎, 藤井 幸彦

    小児の脳神経   35 ( 2 )   280 - 280   2010年4月

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

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  • 水頭症治療に併発する'akinetic mutism and parkinsonism'の考察

    西山 健一, 吉村 淳一, 原田 敦子, 棗田 学, 永谷 哲也, 宮嶋 雅一, 藤井 幸彦

    小児の脳神経   35 ( 2 )   204 - 204   2010年4月

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

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  • 当科における小児期発症の頭蓋内胚腫の治療成績と長期予後

    神宮字 伸哉, 棗田 学, 青木 洋, 長崎 啓祐, 米岡 有一郎, 吉村 淳一, 西山 健一, 妻沼 到, 森井 研, 田村 哲郎, 藤井 幸彦

    小児の脳神経   35 ( 2 )   216 - 216   2010年4月

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

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  • 小児脳幹グリオーマに対するベバシズマブとイリノテカンの治療経験

    棗田 学, 原田 敦子, 吉村 淳一, 西山 健一, 岡本 浩一郎, 藤井 幸彦

    小児の脳神経   35 ( 2 )   224 - 224   2010年4月

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

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  • FUNCTIONAL RESULTS AFTER RESECTION OF GLIOMA INVOLVING THE SUPPLEMENTARY MOTOR AREA 査読

    Takeo Uzuka, Manabu Natsumeda, Hiroshi Aoki, Makoto Oishi, Masafumi Fukuda, Akihiko Saito, Yukihiko Fujii

    NEURO-ONCOLOGY   11 ( 6 )   918 - 918   2009年12月

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

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  • IMMUNOHISTOCHEMICAL ASSESSMENT OF O-6-METHYLGUANINE-DNA METHYLTRANSFERASE FOR GLIOBLASTOMAS: A REAPPRAISAL 査読

    Manabu Natsumeda, Akiyoshi Kakita, Takeo Uzuka, Yukihiko Fujii, Hitoshi Takahashi

    NEURO-ONCOLOGY   11 ( 6 )   945 - 945   2009年12月

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

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  • 長期予後を踏まえた頭蓋咽頭腫の治療戦略

    妻沼 到, 米岡 有一郎, 神宮字 伸哉, 棗田 学, 藤井 幸彦, 武田 憲夫

    日本内分泌学会雑誌   85 ( Suppl. )   8 - 9   2009年10月

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    記述言語:日本語   出版者・発行元:(一社)日本内分泌学会  

    頭蓋咽頭腫60例を対象に、治療経過の分析、治療方法と内分泌機能・視機能・ADL・高次脳機能・有害事象との関連を検討した。観察期間は平均100.9ヵ月であった。その結果、59例に初回手術が行われ、到達法はpterional/subfrontal approachが27例、anterior/basal interhemispheric approachが23例と多用されていた。手術後放射線治療群は、手術単独群に比べ無増悪生存期間が有意に長かったが、全生存期間に有意差はなかった。全摘・亜全摘群と部分摘出・生検群の間でも、全生存期間に有意差は認めなかった。視機能は治療後44例中32例が改善した。下垂体前葉機能は52例中2例が改善したが、14例で悪化し、41例にホルモン補充療法を要した。尿崩症は11例中1例が改善したが、治療後に25例が新たに尿崩症を呈し、35例でDDAVP投与を要した。腫瘍摘出度・到達法・照射療法の有無と下垂体前葉機能ならびに後葉機能・視機能・KPS・高次脳機能の転帰の間に関連性は認めなかった。

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  • 14 IC blister-like aneurysmに対するEC-IC bypassを併用したtrapping手術(一般演題,第48回新潟脳神経外科懇話会)

    斎藤 隆史, 倉島 昭彦, 山下 慎也, 西川 太郎, 棗田 学, 小池 哲雄

    新潟医学会雑誌 = 新潟医学会雑誌   121 ( 7 )   423 - 424   2009年7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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  • 神経膠芽腫におけるbiomarkerとしてのMGMT免疫染色法確立の試み

    棗田 学, 柿田 明美, 青木 洋, 宇塚 岳夫, 高橋 均, 藤井 幸彦

    Brain Tumor Pathology   26 ( Suppl. )   63 - 63   2009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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  • 画像上脳腫瘍が疑われた炎症性病変の4例

    宇塚 岳夫, 棗田 学, 藤井 幸彦, 高橋 均

    Brain Tumor Pathology   26 ( Suppl. )   56 - 56   2009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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  • 初期治療をせずに、テモゾロマイド単独投与で1年間生存した神経膠芽腫の1例

    棗田 学, 小阪 崇幸, 宇塚 岳夫, 藤井 幸彦, 高橋 均

    信州医学雑誌   57 ( 1 )   28 - 28   2009年2月

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    記述言語:日本語   出版者・発行元:信州医学会  

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  • グリオーマに対するクルクミンの抗腫瘍効果とオートファジー

    青木 洋, 棗田 学, 宇塚 岳夫, 神沢 孝夫, 近藤 精二, 藤井 幸彦

    日本脳神経外科学会総会CD-ROM抄録集   67回   2G - O16   2008年10月

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    記述言語:日本語   出版者・発行元:(一社)日本脳神経外科学会  

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  • 悪性グリオーマに対するクルクミンの抗腫瘍効果とその機序(Curcumin suppresses the growth of malignant gliomas in vitro and in vivo)

    青木 洋, 棗田 学, 宇塚 岳夫, 神澤 孝夫, 近藤 精二, 藤井 幸彦

    日本癌学会総会記事   67回   348 - 348   2008年9月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 脳出血を合併したHELLP症候群の1例

    倉島 昭彦, 斎藤 隆史, 山下 慎也, 西川 太郎, 棗田 学

    信州医学雑誌   56 ( 3 )   159 - 159   2008年6月

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    記述言語:日本語   出版者・発行元:信州医学会  

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  • The outcome for medulloblastoma treated with craniospinal irradiation in the ultra-early postoperative phase-our institutional experience 査読

    Junichi Yoshimura, Manabu Natsumeda, Kenichi Nishiyama, Takayuki Takachi, Chihaya Imai, Yukihiko Fujii

    NEURO-ONCOLOGY   10 ( 3 )   499 - 500   2008年6月

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

    Web of Science

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  • The management of fetal brain tumors: Challenges and controversies 査読

    Manabu Natsumeda, Junichi Yoshimura, Kenichi Nishiyama, Takayuki Takachi, Chihaya Imai, Yukihiko Fujii

    NEURO-ONCOLOGY   10 ( 3 )   437 - 437   2008年6月

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

    Web of Science

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  • Stereobiopsyにおけるfluorescein Naの使用経験

    棗田 学, 宇塚 岳夫, 高橋 均, 藤井 幸彦

    Brain Tumor Pathology   25 ( Suppl. )   95 - 95   2008年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 脳出血による環境適応障害に対してタオルによる接触刺激が有効であった症例

    金子 義弘, 渡邉 真帆, 平山 則子, 棗田 学, 小田 温, 小出 章, 富樫 由美

    新潟県厚生連医誌   17 ( 1 )   58 - 60   2008年3月

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    記述言語:日本語   出版者・発行元:新潟県厚生農業協同組合連合会  

    背景:中枢神経系障害でみられる環境適応障害とは、柏木によれば「空間に対して自己の位置関係を認知できないため、体の安定を喪失している状態である」と定義され、その特徴的な症状として「外部環境との接触抵抗に固執して、なるべく強く変化しない抵抗を求めようと体の一部を強く支持面に押し付ける。」「体の各部位を強く連結しておこうとする」の2点をあげている。これらの症状に対して、タオルによる接触刺激を加えることにより改善が得られたとする報告がみられる。症例内容:今回の症例は、脳出血再発により昭和60年の脳出血後遺症による右片麻痺と失語に新たに環境適応障害が加わったものである。これに対してタオルによる接触刺激を加えたところ環境適応障害の改善がみられ、予想以上に早期の運動機能の再獲得が得られた。結論:タオルによる接触刺激を加えることは、環境適応障害の症状を改善するのに有効である。(著者抄録)

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  • 脳出血にて環境適応障害を呈した1症例 排泄動作から学んだコーディネートの重要性

    渡辺 真帆, 今井 美保子, 立石 敦子, 小田 和也, 貝沼 美智子, 小林 紀枝, 金子 義弘, 梅田 貴, 平山 則子, 品川 良勝, 大宗 桂志, 棗田 学, 小田 温, 小出 章, 富樫 由美, 早見 栄治

    日本農村医学会雑誌   56 ( 4 )   653 - 654   2007年11月

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    記述言語:日本語   出版者・発行元:(一社)日本農村医学会  

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  • 脳出血にて環境適応障害を呈した1症例 触覚刺激が有効であった例

    金子 義弘, 小田 和也, 貝沼 美智子, 小林 紀枝, 品川 良勝, 大宗 桂志, 渡辺 真帆, 今井 美保子, 立石 敦子, 梅田 貴, 平山 則子, 棗田 学, 小田 温, 小出 章, 富樫 由美, 早見 栄治

    日本農村医学会雑誌   56 ( 4 )   653 - 653   2007年11月

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    記述言語:日本語   出版者・発行元:(一社)日本農村医学会  

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  • 前交通動脈瘤手術におけるhypothalamic artery温存のための検討

    斎藤 隆史, 倉島 昭彦, 山下 慎也, 本間 順平, 西川 太郎, 棗田 学

    日本脳神経外科学会総会CD-ROM抄録集   66回   2K - P29   2007年10月

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    記述言語:日本語   出版者・発行元:(一社)日本脳神経外科学会  

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  • 脳外科医の立場からみた重症誤嚥性肺炎の治療戦略 早めの人工呼吸器下管理およびシベレスタットナトリウム使用の有用性

    棗田 学, 小田 温, 小出 章

    医学と薬学   58 ( 4 )   607 - 614   2007年10月

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    記述言語:日本語   出版者・発行元:(株)自然科学社  

    重症肺炎のうちで、急性呼吸窮迫症候群(ARDS)の定義に当てはまるものは4例存在した。4例とも、ARDSの確定診断を待たずに気管内挿管、人工呼吸器管理を開始し、ARDSと診断後は速やかにシベレスタットナトリウムを使用したことが奏効し、早期に呼吸器から離脱し、抜管できた。4例中3例では気管内挿管、SIMV管理下でARDSの条件を満たし、ただちにシベレスタットナトリウムの使用を開始した。1例は気管内挿管後数時間は人工呼吸器管理が不要であったが、呼吸障害が進行するにつれ、ただちに人工呼吸器管理とし、ARDSの基準を満たしたためシベレスタットナトリウムの使用を開始した。躊躇することなく挿管し、シベレスタットナトリウムの適応を速やかに評価し、可及的早期に使用することが好成績につながったと思われた。

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  • 前交通動脈瘤手術におけるhypothalamic artery温存のための検討

    斎藤 隆史, 倉島 昭彦, 山下 慎也, 本間 順平, 西川 太郎, 棗田 学

    Neurological Surgery   35 ( 9 )   881 - 885   2007年9月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

    前交通動脈瘤に対しanterior interhemispheric approachによるクリッピング手術を行った34例(男性15例、女性19例、35〜84歳)を対象として視床下部動脈と脳動脈瘤との位置関係を検索した。術中、視床下部動脈と脳動脈瘤が別の方向を向いていたD.D.群は15例、両者が同方向を向いていたS.D.群は13例、残りの6例は視床下部動脈が不明であった。D.D群では安井らの分類におけるtype 1が13例、type 2が2例であり、S.D.群ではtype 2が6例、type 3が7例であった。S.D.群のうち前交通動脈の血流が右から左に向いている4症例のち視床下部動脈が脳動脈瘤の左に認めたのは3例であり、前交通動脈の血流が左から右に向いている8症例のうち視床下部動脈が右に認めたのは6例であったことから、視床下部動脈は脳動脈瘤の下流に存在する可能性が高いことが示唆された。

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  • 降圧療法中に両上肢痛・脱力を来たした1例

    小田 温, 棗田 学, 小出 章

    新潟医学会雑誌   121 ( 7 )   424 - 424   2007年7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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  • 15 降圧療法中に両上肢痛・脱力を来たした1例(一般演題,第48回新潟脳神経外科懇話会)

    小田 温, 棗田 学, 小出 章

    新潟医学会雑誌 = 新潟医学会雑誌   121 ( 7 )   424 - 424   2007年7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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  • 14 IC blister-like aneurysmに対するEC-IC bypassを併用したtrapping手術(一般演題,第48回新潟脳神経外科懇話会)

    斎藤 隆史, 倉島 昭彦, 山下 慎也, 西川 太郎, 棗田 学, 小池 哲雄

    新潟医学会雑誌   121 ( 7 )   423 - 424   2007年7月

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    記述言語:日本語   出版者・発行元:新潟大学  

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  • IC blister-like aneurysmに対するEC-IC bypassを併用したtrapping手術

    斎藤 隆史, 倉島 昭彦, 山下 慎也, 西川 太郎, 棗田 学, 小池 哲雄

    新潟医学会雑誌   121 ( 7 )   423 - 424   2007年7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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  • 15 Jugular foramen neurinomaの1例(一般演題,第47回新潟脳神経外科懇話会)

    斎藤 隆史, 倉島 昭彦, 山下 慎也, 西川 太郎, 棗田 学, 佐々木 修

    新潟医学会雑誌 = 新潟医学会雑誌   121 ( 3 )   182 - 182   2007年3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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  • Jugular foramen neurinomaの1例

    斎藤 隆史, 倉島 昭彦, 山下 慎也, 西川 太郎, 棗田 学, 佐々木 修

    新潟医学会雑誌   121 ( 3 )   182 - 182   2007年3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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  • 脳死期間418日を記録した13歳小児例

    斎藤 隆史, 倉島 昭彦, 山下 慎也, 西川 太郎, 棗田 学

    脳死・脳蘇生   18 ( 1 )   73 - 73   2006年5月

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    記述言語:日本語   出版者・発行元:日本脳死・脳蘇生学会  

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  • 正中付近にneckを有する破裂VA-PICA脳動脈瘤の1例

    山下 慎也, 斎藤 隆史, 倉島 昭彦, 西川 太郎, 棗田 学

    信州医学雑誌   54 ( 2 )   92 - 92   2006年4月

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    記述言語:日本語   出版者・発行元:信州医学会  

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  • 脳出血後のリハビリテーション中に急な経過をたどった敗血症の一例

    羽田 悟, 棗田 学, 岡嵜 洋一

    長野赤十字病院医誌   19   88 - 91   2006年3月

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    記述言語:日本語   出版者・発行元:長野赤十字病院  

    69歳男.呂律不良,右半身麻痺で発症し,頭部CTで2.0×1.5×2.5cmの左視床血腫を認めた.グリセオール200ml×2/dayで保存的に治療し,呼吸苦を訴えたため心エコーを施行したところびまん性の心筋肥厚を認め,高血圧性心筋症と診断した.体重80kg(推定)であったため摂食制限で体重減少を図り,リハビリテーションを開始し下肢麻痺はMMT4/5レベルとなり,上肢も動くようになった.頻尿のため自ら飲水を控えていたところ,上肢の軽度脱力,構音障害を来たし,MRIで右頭頂葉および左脳室周囲にlacunar infarctを認めた.飲水の徹底のみで症状は改善したが,40℃の熱発,嘔吐,背腹部痛が出現し,腎機能異常より腎盂腎炎と診断した.その後血圧が低下し,尿・血液培養でE.coli陽性,エンドトキシン陽性を認め,吸着療法,持続透析を開始した.呼吸性,代謝性アシドーシスが改善せず,DIC傾向,四肢不全麻痺,pAfなどを認め,頭部CTを行なったが脳出血や塞栓症の所見はなかった.CT施行後心肺停止となり,心臓マッサージ,気管内挿管,投薬にも反応がなく,発症2日後に死亡した

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  • 短期間に再発を繰り返した難治性慢性硬膜下血腫の1症例

    倉島 昭彦, 斎藤 隆史, 山下 慎也, 中村 公彦, 西川 太郎, 棗田 学

    信州医学雑誌   54 ( 1 )   45 - 45   2006年2月

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    記述言語:日本語   出版者・発行元:信州医学会  

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  • 14 Petroclival meningiomaに対するorbitozygomatic anterior temporal approach(第45回新潟脳神経外科懇話会)

    斎藤 隆史, 倉島 昭彦, 山下 慎也, 中村 公彦, 棗田 学

    新潟医学会雑誌 = 新潟医学会雑誌   119 ( 8 )   510 - 511   2005年8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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  • 臨床症状及び画像所見が遷延した産褥子癇の一例(A case of delayed postpartum preeclampsia with prolonged abnormalities on head scans)

    棗田 学, 斎藤 隆史, 横山 幸代, 倉島 昭彦, 山下 慎也, 中村 公彦

    長野赤十字病院医誌   18   58 - 63   2005年3月

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    記述言語:英語   出版者・発行元:長野赤十字病院  

    29歳妊婦.患者は分娩直後より,頭痛および軽度血圧上昇を認め,産褥第3日目に痙攣発作が生じ,産褥子癇と診断された.頭部MRI T2強調画像,ならびにFLAIRでは特徴的な高信号域を呈し,MRAでは主幹動脈の血管攣縮を認めた.そこで,抗痙攣剤,オザグレルナトリウムで加療を開始したところ,痙攣発作は消失したものの,意識障害と頭痛は遷延し,発症から10日目のMRI上,血管攣縮と浮腫の悪化が認められた.以上の経過より,プレドニンの経口投与を開始した結果,意識障害,頭痛は改善となり,画像所見も26日目には改善,51日目には消失が確認された

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  • 6 臨床的脳死判定後418日間生存した13才小児例(第44回新潟脳神経外科懇話会)

    斎藤 隆史, 倉島 昭彦, 山下 慎也, 中村 公彦, 棗田 学

    新潟医学会雑誌 = 新潟医学会雑誌   119 ( 2 )   133 - 134   2005年2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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  • 瞬目反射(blink reflex)の臨床応用

    山下 慎也, 斉藤 隆史, 倉島 昭彦, 中村 公彦, 棗田 学

    信州医学雑誌   52 ( 6 )   505 - 505   2004年12月

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    記述言語:日本語   出版者・発行元:信州医学会  

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  • 当科におけるSCU利用の現状と課題

    中村 公彦, 斎藤 隆史, 倉島 昭彦, 山下 慎也, 棗田 学

    日赤医学   56 ( 1 )   230 - 230   2004年9月

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    記述言語:日本語   出版者・発行元:日本赤十字社医学会  

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▶ 全件表示

受賞

  • 若手研究奨励賞

    2015年3月   Johns Hopkins大学病理学部門Young Investigator Day  

    棗田 学

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  • 最優秀発表賞

    2012年7月   第27回日本脳神経外科国際学会フォーラム  

    棗田 学

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  • 中田瑞穂若手研究奨励賞

    2010年8月   第40回新潟神経学夏期セミナー  

    棗田 学

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  • 若手医学研究賞

    2009年9月   新潟大学「みかんの会」  

    棗田 学

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共同研究・競争的資金等の研究

  • 膠芽腫に対する代謝リプログラミングおよびmTORを標的とした効果的薬物療法の確立

    研究課題/領域番号:20K07194  2020年4月 - 2023年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    江田 岳誉, 棗田 学

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

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  • 髄芽腫:3T-MRSでのglutamine, 2HG検出による遺伝子型・予後予測

    研究課題/領域番号:19K09522  2019年4月 - 2024年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    岡本 浩一郎, 棗田 学

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

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  • 悪性神経膠腫に対して腫瘍特異的ポドプラニンを標的とした術中療法の開発

    2019年4月 - 2022年3月

    文部科学省  科学研究助成事業(基盤研究C) 

    棗田 学

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    担当区分:研究代表者  資金種別:競争的資金

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  • 悪性髄膜腫における標的可能遺伝子変異の同定と新規治療確立

    研究課題/領域番号:18K08990  2018年4月 - 2021年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    平石 哲也, 大石 誠, 棗田 学, 永橋 昌幸, 藤井 幸彦

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    近年の遺伝子発現解析技術により、髄膜腫の腫瘍発生機序に関わる背景が徐々に解明されてきた。しかし、その疾患概念の基盤は脆弱でまだ不明な点が多く、がん医療で先行して利用され始めた「遺伝子パネルを利用することで悪性髄膜腫固有のドライバー変異同定可能である」という仮説を立て、本研究を計画している。
    本研究の目的は、悪性髄膜腫の標的可能遺伝子変異を同定することで悪性髄膜腫症例の個々に応じた最適治療薬を同定して新規治療を確立することである。そのため、H30年度は、実験基盤の確立と症例の蓄積が目標であった。実際、悪性髄膜腫症例から患者固有の腫瘍細胞の培養にも成功し、遺伝子パネルによる 標的可能遺伝子の検索を行った。培養細胞も樹立されているが、継代していくと増殖能が減退しており、H31年度以降の研究計画での治療実験へ対応できるように現在、培養細胞にTERT遺伝子を導入を試みている。また、頭蓋内希少固形腫瘍に関しても順次検索を進められる体制が整ってきた。

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  • mTORシグナルを標的とした悪性グリオーマに対する新規化学療法の基盤構築

    研究課題/領域番号:17K08304  2017年4月 - 2020年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    江田 岳誉, 棗田 学

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

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  • IDH変異型グリオーマにおける表面抗原を標的とした術注療法の開発

    2017年4月 - 2019年3月

    文部科学省  科学研究助成事業(若手研究B) 

    棗田 学

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    担当区分:研究代表者  資金種別:競争的資金

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  • IDH変異型神経膠腫における2HGによるミトコンドリア機能異常と新規治療展開

    研究課題/領域番号:17K16631  2017年4月 - 2019年3月

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    阿部 英明, 棗田 学, 岡田 正康

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    配分額:4030000円 ( 直接経費:3100000円 、 間接経費:930000円 )

    悪性神経膠腫には、高率にイソクエン酸デヒドロゲナーゼ(IDH)遺伝子変異を有し、同変異は2-ヒドロキシグルタル酸(2-HG)という代謝物を産生する事が腫瘍化の原因にと考えられている。しかし、IDH変異を有する悪性神経膠腫は予後良好である。2-HGの産生を抑制するIDH変異阻害剤が盛んに研究されているが、我々は2-HG は腫瘍細胞内ミトコンドリアにシャトルされ蓄積する事で、腫瘍細胞のミトコンドリア機能異常を来すと想定しており、2-HGを抑制することは腫瘍細胞に取ってはプラスに働く可能性がある。期間中には確信には迫れなかったが、新しい治療バラダイムをもたらす重要な研究と位置づけられる。

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  • 中枢神経原発リンパ腫の髄液診断と運動機能予後の予測

    2016年10月 - 2017年3月

    新潟大学  異分野融合研究助成(U-go grant) 

    棗田 学

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    担当区分:研究代表者  資金種別:競争的資金

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  • ヒト脳腫瘍サンプルにおけるオートファジーモニタリングと組織学的検討

    2009年4月 - 2012年3月

    文部科学省  科学研究助成事業(若手研究B) 

    棗田 学

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    担当区分:研究代表者  資金種別:競争的資金

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