2025/08/21 更新

所属以外の情報はresearchmapへの登録情報を転載しています。

写真a

タテイシ ケンスケ
立石 健祐
Kensuke Tateishi
所属
生命医科学研究科 生命医科学専攻 准教授
医学部 医学科 脳神経外科学 准教授
職名
准教授
プロフィール

脳神経外科学と生命医科学研究科を兼任し、脳神経外科医と基礎研究者の「二刀流」として活動している。主たるテーマは難治性中枢神経系腫瘍であり、治療成績の向上を目指して、独創的かつ実用性の高い治療法の開発に取り組んでいる。特に、トランスレーショナルリサーチを基盤とし、主任研究者(PI)として多領域にわたる研究を主導している。臨床面では、脳神経外科医として神経機能の温存を前提に、分子情報や画像情報を駆使し、従来の視覚的限界を超えて腫瘍の可視化を図ることで、最大限の切除を目指す臨床研究を展開している。また、腫瘍治療医としては、基礎研究で得られた知見をもとに新たな治療法を提案し、実際の臨床現場へ還元することで、個別化医療の実現に貢献する臨床研究を推進している。

 

外部リンク

学位

  • 博士(医学) ( 2013年3月   横浜市立大学 )

研究キーワード

  • 腫瘍学

  • 分子イメージング

  • 脳神経外科学

  • 分子遺伝学

  • 癌代謝

  • 脳腫瘍学

研究分野

  • ライフサイエンス / 腫瘍生物学

  • ライフサイエンス / 脳神経外科学  / Neurosurgery

  • ライフサイエンス / 腫瘍診断、治療学

論文

  • Digital FDG-PET detects MYD88 mutation-driven glycolysis in primary central nervous system lymphoma. 査読 国際誌

    Mayu Sasaki, Yuri Teraoka, Ayumi Kato, Tadaaki Nakajima, Yoshinobu Ishiwata, Yohei Miyake, Hirokuni Honma, Taishi Nakamura, Naoki Ikegaya, Yutaro Takayama, Osamu Yazawa, Shungo Sawamura, Akito Oshima, Hiroaki Hayashi, Wei Kai Ye, Kanoko Sasaoka, Yukie Yoshii, Satoshi Fujii, Ukihide Tateishi, Tetsuya Yamamoto, Daisuke Utsunomiya, Shingo Kato, Kensuke Tateishi

    AJNR. American journal of neuroradiology   2025年7月

     詳細を見る

    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND AND PURPOSE: The relationship between digital 18F-fluorodeoxyglucose positron emission tomography (dFDG-PET) findings and glucose metabolism-related genetic alterations remains unclear in primary central nervous system lymphoma (PCNSL). This study aimed to evaluate whether dFDG-PET can serve as a noninvasive tool to detect MYD88 mutation-driven glycolytic activity in PCNSL. MATERIALS AND METHODS: We retrospectively analyzed the imaging and molecular data of 54 patients with PCNSL (55 lesions). MRI and FDG-PET parameters, including the maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR), were assessed. Tumor specimens were subjected to histopathological and genomic evaluations, including the MYD88 mutation status. RESULTS: Among 55 tumors, 34 (61.8%) were examined with dFDG-PET and 21 (38.2%) with analog 18F-FDG-PET (aFDG-PET). In the dFDG-PET group, MYD88-mutant tumors showed significantly higher SUVmax (30.2 ± 9.9) and TBR (6.1 ± 1.5) compared to wild-type tumors (SUVmax: 19.3 ± 7.2, P = 0.006; TBR: 3.5 ± 1.3, P < 0.001). In the aFDG-PET group, the SUVmax was significantly higher in MYD88-mutant tumors (P = 0.01), whereas the TBR differences were not statistically significant (P = 0.38). Receiver operating characteristic analysis of TBR in dFDG-PET yielded an area under the curve of 0.913 (95% CI: 0.954-1.000) with a cutoff value of 4.49, achieving 88% sensitivity and 88% specificity for MYD88 mutation detection. Multivariate logistic regression identified SUVmax and TBR from dFDG-PET as independent predictors of MYD88 mutation status. The transcriptomic analysis confirmed the significant upregulation of glycolysis-related genes, including hexokinase 2, in MYD88-mutant tumors, supporting increased glycolytic activity. CONCLUSIONS: dFDG-PET may serve as a valuable noninvasive imaging modality to detect MYD88 mutation-driven enhanced glycolysis in patients with PCNSL. ABBREVIATIONS: dPET= Digital positron emission tomography; PCNSL= Primary central nervous system lymphoma; SUVmax=maximum standardized uptake value; TBR= tumor-to background ratio.

    DOI: 10.3174/ajnr.A8935

    PubMed

    researchmap

  • HR eye & MMR eye: one-day assessment of DNA repair-defective tumors eligible for targeted therapy 査読

    Shinta Saito, Shingo Kato, Usaki Arai, Atsuki En, Jun Tsunezumi, Taichi Mizushima, Kensuke Tateishi, Noritaka Adachi

    Nature Communications   2025年5月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41467-025-59462-2

    researchmap

  • Primary intracranial sarcoma associated with DICER1 mutant: a case report and preclinical investigation 査読

    Hirokuni Honma, Kensuke Tateishi, Hiromichi Iwashita, Yohei Miyake, Shinichi Tsujimoto, Hiroaki Hayashi, Fukutaro Ohgaki, Yoshiko Nakano, Koichi Ichimura, Shoji Yamanaka, Motohiro Kato, Satoshi Fujii, Shuichi Ito, Hideaki Yokoo, Tetsuya Yamamoto

    Brain Tumor Pathology   2025年1月

     詳細を見る

    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s10014-024-00495-8

    researchmap

  • The impact of initial vascular morphology on outcomes in patients with intracranial vertebral artery dissection presenting with isolated headache. 査読 国際誌

    Akito Oshima, Masakazu Higurashi, Hajime Takase, Kyosuke Asada, Sachiko Yamada, Kensuke Tateishi, Tetsuya Yamamoto

    Journal of neurosurgery   1 - 9   2024年11月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: The prognosis of isolated headache intracranial vertebral artery dissection (iVAD) without subarachnoid hemorrhage (SAH) or stroke is unknown. The authors of this study aimed to evaluate isolated headache iVAD prognosis. METHODS: This is a single-center retrospective study of consecutive patients who presented with headache as their main complaint and underwent MRI between November 2016 and August 2022; those with acute isolated headache iVAD who were followed up for vascular morphological stability were eligible for study inclusion. The patients were divided into three groups based on the vascular morphology at initial diagnosis: aneurysm dilatation without stenosis (group 1), aneurysm dilatation with stenosis (group 2), and no aneurysm dilatation (group 3). Prognosis, time to radiological stability, and final vascular morphology were compared among the groups. RESULTS: One hundred five patients with isolated headache iVAD were included in the study. During a median follow-up of 478 (IQR 143-1094) days, none of the patients developed SAH or stroke, but 3/41 (7%) patients in group 1 underwent endovascular intervention for aneurysm enlargement. Patients in group 1 required significantly more long-term follow-up for morphological stability (p = 0.013), primarily due to aneurysm enlargement (p < 0.001), and were more likely to require surgical intervention (p = 0.043) than those in the other two groups. Residual aneurysm risk was significantly associated with initial vascular morphology in group 1 (OR 7.28, 95% CI 2.30-23.1, p < 0.001). CONCLUSIONS: Most patients with isolated headache iVAD had a favorable prognosis. However, patients with aneurysm dilatation without stenosis required the most careful follow-up, as this group had the highest aneurysm enlargement risk from early disease onset through the chronic phase. In such cases, patients may require surgical intervention to prevent critical conditions.

    DOI: 10.3171/2024.7.JNS24575

    PubMed

    researchmap

  • Translational Research Platform for Malignant Central Nervous System Tumors. 査読

    Kensuke Tateishi

    Neurologia medico-chirurgica   2024年8月

     詳細を見る

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

    Some central nervous system (CNS) malignancies are highly aggressive and urgently need innovative treatment strategies to improve prognosis. A significant concern for therapeutic development is the time-consuming nature of developing treatments for CNS tumors. Therefore, a rapid and efficient translational approach is needed to address this problem. Translational and reverse translational research aims to bridge the gap between laboratory data and clinical applications and has been developed in the field of neuro-oncology. This study presents our translational platform systems for malignant CNS tumors, which combine an intraoperative integrated diagnostic system and comprehensive in vitro and in vivo assay systems. These laboratory systems may contribute to a better understanding of tumor biology and the development of novel therapeutic strategies for the poor prognosis of CNS tumors.

    DOI: 10.2176/jns-nmc.2024-0078

    PubMed

    researchmap

  • Rapid Tumor DNA Analysis of Cerebrospinal Fluid Accelerates Treatment of Central Nervous System Lymphoma. 査読 国際誌

    Mihir Gupta, Joseph Bradley, Elie Massaad, Evan Burns, N Zeke Georgantas, Garrett Maron, Julie Batten, Aidan Gallagher, Julia Thierauf, Naema Nayyar, Amanda Gordon, SooAe Jones, Michelle Pisapia, Ying Sun, Pamela Stuart Jones, Fred G Barker 2nd, William Curry, Rajiv Gupta, Javier Romero, Nancy Wang, Priscilla Brastianos, Maria Martinez-Lage, Kensuke Tateishi, Deborah Anne Forst, Brian Vala Nahed, Tracy T Batchelor, Lauren L Ritterhouse, Florian Iser, Tobias Kessler, Justin T Jordan, Jorg Dietrich, Matthew L Meyerson, Daniel P Cahill, Jochen K Lennerz, Bob Carter, Ganesh M Shankar

    Blood   2024年5月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Delays and risks associated with neurosurgical biopsies preclude timely diagnosis and treatment of central nervous system (CNS) lymphoma and other CNS neoplasms. We prospectively integrated targeted rapid genotyping of cerebrospinal fluid (CSF) into the evaluation of 70 patients with CNS lesions of unknown etiology. Participants underwent genotyping of CSF-derived DNA using a qPCR-based approach for parallel detection of single-nucleotide variants in the MYD88, TERT promoter, IDH1, IDH2, BRAF and H3F3A genes within 80 minutes of sample acquisition. Canonical mutations were detected in 42% of patients with neoplasms, including cases of primary and secondary CNS lymphoma, glioblastoma, IDH-mutant brainstem glioma and H3K27M-mutant diffuse midline glioma. Genotyping results eliminated the need for surgical biopsies in 7/33 (21.2%) cases of newly diagnosed neoplasms, resulting in significantly accelerated initiation of disease-directed treatment (median 3 vs 12 days; p = 0.027). This assay was then implemented in a Clinical Laboratory Improvement Amendments (CLIA) environment, with 2-day median turnaround for diagnosis of central nervous system lymphoma from 66 patients across 4 clinical sites. Our study prospectively demonstrates that targeted rapid CSF genotyping influences oncologic management for suspected CNS tumors.

    DOI: 10.1182/blood.2024023832

    PubMed

    researchmap

  • Anti-epileptic drug use and subsequent degenerative dementia occurrence. 査読 国際誌

    Naoki Ikegaya, Honoka Nakamura, Yutaro Takayama, Yohei Miyake, Takahiro Hayashi, Masaki Sonoda, Mitsuru Sato, Kensuke Tateishi, Jun Suenaga, Masao Takaishi, Yu Kitazawa, Misako Kunii, Hiroki Abe, Tomoyuki Miyazaki, Tetsuaki Arai, Manabu Iwasaki, Takayuki Abe, Tetsuya Yamamoto

    Alzheimer's & dementia (New York, N. Y.)   10 ( 3 )   e70001   2024年

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    INTRODUCTION: The use of anti-epileptic drugs (AEDs) in degenerative dementia (DD) remains uncertain. We aimed to evaluate the association of early AED administration with subsequent DD occurrence. METHODS: Using a large nationwide database, we enrolled patients newly diagnosed with epilepsy from 2014 to 2019 (n = 104,225), and using propensity score matching, we divided them into treatment (those prescribed AEDs in 2014) and control groups. The primary outcome was subsequent DD occurrence in 2019. RESULTS: Overall, 4489 pairs of patients (2156 women) were matched. The odds ratio (treatment/control) for DD occurrence was 0.533 (95% confidence interval: 0.459-0.617). The DD proportions significantly differed between the treatment (340/4489 = 0.076) and control (577/4489 = 0.129) groups. DISCUSSION: Among patients newly diagnosed with epilepsy, compared to non-use, early AED use was associated with a lower occurrence of subsequent DD. Further investigations into and optimization of early intervention for epilepsy in DD are warranted. HIGHLIGHTS: Anti-epileptic drug (AED) use before epilepsy diagnosis was linked with a lower subsequent degenerative dementia (DD) occurrence.Identifying the epileptic phenotype was crucial for justifying early AED use in DD.AED use with an epilepsy diagnosis did not pose an additional risk of DD.The potential contribution of combination drug therapy to the strategy was noted.

    DOI: 10.1002/trc2.70001

    PubMed

    researchmap

  • Arteries Around the Superior Limiting Sulcus: Motor Complication Avoidance in Insular and Insulo-Opercular Surgery. 査読 国際誌

    Naoki Ikegaya, Takahiro Hayashi, Takefumi Higashijima, Yutaro Takayama, Masaki Sonoda, Masaki Iwasaki, Yohei Miyake, Mitsuru Sato, Kensuke Tateishi, Jun Suenaga, Tetsuya Yamamoto

    Operative neurosurgery (Hagerstown, Md.)   25 ( 6 )   e308-e314   2023年12月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND AND OBJECTIVES: Insulo-opercular surgery can cause ischemic motor complications. A source of this is the arteries around the superior limiting sulcus (SLS), which reach the corona radiata, but the detailed anatomy remains unclear. To characterize arteries around the SLS including the long insular arteries (LIAs) and long medullary arteries, we classified them and examined their distribution in relation to the SLS, which helps reduce the risk of ischemia. METHODS: Twenty adult cadaveric hemispheres were studied. Coronal brain slices were created perpendicular to the SLS representing insular gyri (anterior short, middle short, posterior short, anterior long, and posterior long). The arteries within 10-mm proximity of the SLS that reached the corona radiata were excavated and classified by the entry point. RESULTS: A total of 122 arteries were identified. Sixty-three (52%), 20 (16%), and 39 (32%) arteries penetrated the insula (LIAs), peak of the SLS, and operculum (long medullary arteries), respectively. 100 and six (87%) arteries penetrated within 5 mm of the peak of the SLS. The arteries were distributed in the anterior short gyrus (19%), middle short gyrus (17%), posterior short gyrus (20%), anterior long gyrus (19%), and posterior long gyrus (25%). Seven arteries (5.7%) had anastomoses after they penetrated the parenchyma. CONCLUSION: Approximately 90% of the arteries that entered the parenchyma and reached the corona radiata were within a 5-mm radius of the SLS in both the insula and operculum side. This suggests that using the SLS as a landmark during insulo-opercular surgery can decrease the chance of ischemia.

    DOI: 10.1227/ons.0000000000000879

    PubMed

    researchmap

  • Genetic alterations that deregulate RB and PDGFRA signaling pathways drive tumor progression in IDH2-mutant astrocytoma. 査読 国際誌

    Kensuke Tateishi, Yohei Miyake, Taishi Nakamura, Hiromichi Iwashita, Takahiro Hayashi, Akito Oshima, Hirokuni Honma, Hiroaki Hayashi, Kyoka Sugino, Miyui Kato, Kaishi Satomi, Satoshi Fujii, Takashi Komori, Tetsuya Yamamoto, Daniel P Cahill, Hiroaki Wakimoto

    Acta neuropathologica communications   11 ( 1 )   186 - 186   2023年11月

     詳細を見る

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

    In IDH-mutant astrocytoma, IDH2 mutation is quite rare and biological mechanisms underlying tumor progression in IDH2-mutant astrocytoma remain elusive. Here, we report a unique case of IDH2 mutant astrocytoma, CNS WHO grade 3 that developed tumor progression. We performed a comprehensive genomic and epigenomic analysis for primary and recurrent tumors and found that both tumors harbored recurrent IDH2R172K and TP53R248W mutation with CDKN2A/B hemizygous deletion. We also found amplifications of CDK4 and MDM2 with PDGFRA gain in the recurrent tumor and upregulated protein expressions of these genes. We further developed, for the first time, a xenograft mouse model of IDH2R172K and TP53R248W mutant astrocytoma from the recurrent tumor, but not from the primary tumor. Consistent with parent recurrent tumor cells, amplifications of CDK4 and MDM2 and PDGFRA gain were found, while CDKN2A/B was identified as homozygous deletion in the xenografts, qualifying for integrated diagnosis of astrocytoma, IDH2-mutant, CNS WHO grade 4. Cell viability assay found that CDK4/6 inhibitor and PDGFR inhibitor potently decreased cell viability in recurrent tumor cells, as compared to primary tumor cells. These findings suggest that gene alterations that activate retinoblastoma (RB) signaling pathways and PDGFR may drive tumor progression and xenograft formation in IDH2-mutant astrocytoma, which is equivalent to progressive IDH1-mutant astrocytoma. Also, our findings suggest that these genomic alterations may represent therapeutic targets in IDH2-mutant astrocytoma.

    DOI: 10.1186/s40478-023-01683-x

    PubMed

    researchmap

  • Transvenous embolization for an intraosseous clival arteriovenous fistula via a proper access route guiding a three-dimensional fusion image: illustrative case. 査読 国際誌

    Yu Iida, Jun Suenaga, Nobuyuki Shimizu, Kaoru Shizawa, Ryosuke Suzuki, Shigeta Miyake, Taisuke Akimoto, Satoshi Hori, Kensuke Tateishi, Yasunobu Nakai, Tetsuya Yamamoto

    Journal of neurosurgery. Case lessons   6 ( 18 )   2023年10月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Intraosseous clival arteriovenous fistulas (AVFs), in which the shunt drains extracranially from the posterior and anterior condylar veins rather than from the cavernous sinus (CS), are rare. Targeting embolization of an intraosseous clival AVF is challenging because of its complex venous and skull base anatomy; therefore, a therapeutic strategy based on detailed preoperative radiological findings is required to achieve a favorable outcome. Here, the authors report the successful targeted embolization of an intraosseous clival AVF using an ingenious access route. OBSERVATIONS: A 74-year-old woman presented with left-sided visual impairment, oculomotor nerve palsy, and right facial pain. A fusion image of three-dimensional rotational angiography and cone-beam computed tomography revealed a left CS dural AVF and a right intraosseous clival AVF. The shunt flow of the clival AVF drained extracranially from the posterior and anterior condylar veins via the intraosseous venous route. Transvenous embolization was performed by devising suboccipital, posterior condylar, and intraosseous access routes. The symptoms resolved after the bilateral AVFs were treated. LESSONS: Accurate diagnosis and proper transvenous access based on detailed intraosseous and craniocervical venous information obtained from advanced imaging modalities are key to resolving intraosseous clival AVF.

    DOI: 10.3171/CASE23492

    PubMed

    researchmap

  • Intraoperative integrated diagnostic system for malignant central nervous system tumors. 査読 国際誌

    Takahiro Hayashi, Kensuke Tateishi, Shinichiro Matsuyama, Hiromichi Iwashita, Yohei Miyake, Akito Oshima, Hirokuni Homma, Jo Sasame, Katsuhiro Takabayashi, Kyoka Sugino, Emi Hirata, Naoko Udaka, Yuko Matsushita, Ikuma Kato, Hiroaki Hayashi, Taishi Nakamura, Naoki Ikegaya, Yutaro Takayama, Masaki Sonoda, Chihiro Oka, Mitsuru Sato, Masataka Isoda, Miyui Kato, Kaho Uchiyama, Tamon Tanaka, Toshiki Muramatsu, Shigeta Miyake, Ryosuke Suzuki, Mutsumi Takadera, Junya Tatezuki, Junichi Ayabe, Jun Suenaga, Shigeo Matsunaga, Kosuke Miyahara, Hiroshi Manaka, Hidetoshi Murata, Takaakira Yokoyama, Yoshihide Tanaka, Takashi Shuto, Koichi Ichimura, Shingo Kato, Shoji Yamanaka, Daniel P Cahill, Satoshi Fujii, Ganesh M Shankar, Tetsuya Yamamoto

    Clinical cancer research : an official journal of the American Association for Cancer Research   2023年10月

     詳細を見る

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

    PURPOSE: The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors uses an integrated approach involving histopathology and molecular profiling. Since majority of adult malignant brain tumors are gliomas and primary central nervous system lymphomas (PCNSL), rapid differentiation of these diseases is required for therapeutic decisions. Additionally, diffuse gliomas require molecular information on single nucleotide variants (SNV), such as IDH1/2. Here, we report an intraoperative integrated diagnostic (i-ID) system to classify CNS malignant tumors, which updates legacy frozen section (FS) diagnosis through incorporation of a quantitative polymerase chain reaction (qPCR)-based genotyping assay. EXPERIMENTAL DESIGN: FS evaluation, including GFAP and CD20 rapid immunohistochemistry, was performed on adult malignant CNS tumors. PCNSL was diagnosed through positive CD20 and negative GFAP immunostaining. For suspected glioma, genotyping for IDH1/2, TERT SNV, and CDKN2A copy number alteration was routinely performed, whereas H3F3A and BRAF SNV were assessed for selected cases. i-ID was determined based on the 2021 WHO classification and compared with the permanent integrated diagnosis (p-ID) to assess its reliability. RESULTS: After retrospectively analyzing 153 cases, 101 cases were prospectively examined using the i-ID system. Assessment of IDH1/2, TERT, H3F3AK27M, BRAFV600E, and CDKN2A alterations with i-ID and permanent genomic analysis was concordant in 100%, 100%, 100%, 100%, and 96.4%, respectively. Combination with FS and intraoperative genotyping assay improved diagnostic accuracy in gliomas. Overall, i-ID matched with p-ID in 80/82 (97.6%) patientswith glioma and 18/19 (94.7%) with PCNSL. CONCLUSIONS: The i-ID system provides reliable integrated diagnosis of adult malignant CNS tumors.

    DOI: 10.1158/1078-0432.CCR-23-1660

    PubMed

    researchmap

  • Extranodal lymphoma: pathogenesis, diagnosis and treatment. 査読 国際誌

    Hua Yang, Yang Xun, Chao Ke, Kensuke Tateishi, Hua You

    Molecular biomedicine   4 ( 1 )   29 - 29   2023年9月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Approximately 30% of lymphomas occur outside the lymph nodes, spleen, or bone marrow, and the incidence of extranodal lymphoma has been rising in the past decade. While traditional chemotherapy and radiation therapy can improve survival outcomes for certain patients, the prognosis for extranodal lymphoma patients remains unsatisfactory. Extranodal lymphomas in different anatomical sites often have distinct cellular origins, pathogenic mechanisms, and clinical manifestations, significantly influencing their diagnosis and treatment. Therefore, it is necessary to provide a comprehensive summary of the pathogenesis, diagnosis, and treatment progress of extranodal lymphoma overall and specifically for different anatomical sites. This review summarizes the current progress in the common key signaling pathways in the development of extranodal lymphomas and intervention therapy. Furthermore, it provides insights into the pathogenesis, diagnosis, and treatment strategies of common extranodal lymphomas, including gastric mucosa-associated lymphoid tissue (MALT) lymphoma, mycosis fungoides (MF), natural killer/T-cell lymphoma (nasal type, NKTCL-NT), and primary central nervous system lymphoma (PCNSL). Additionally, as PCNSL is one of the extranodal lymphomas with the worst prognosis, this review specifically summarizes prognostic indicators and discusses the challenges and opportunities related to its clinical applications. The aim of this review is to assist clinical physicians and researchers in understanding the current status of extranodal lymphomas, enabling them to make informed clinical decisions that contribute to improving patient prognosis.

    DOI: 10.1186/s43556-023-00141-3

    PubMed

    researchmap

  • Arteries Around the Superior Limiting Sulcus: Motor Complication Avoidance in Insular and Insulo-Opercular Surgery. 査読 国際誌

    Naoki Ikegaya, Takahiro Hayashi, Takefumi Higashijima, Yutaro Takayama, Masaki Sonoda, Masaki Iwasaki, Yohei Miyake, Mitsuru Sato, Kensuke Tateishi, Jun Suenaga, Tetsuya Yamamoto

    Operative neurosurgery (Hagerstown, Md.)   2023年9月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND AND OBJECTIVES: Insulo-opercular surgery can cause ischemic motor complications. A source of this is the arteries around the superior limiting sulcus (SLS), which reach the corona radiata, but the detailed anatomy remains unclear. To characterize arteries around the SLS including the long insular arteries (LIAs) and long medullary arteries, we classified them and examined their distribution in relation to the SLS, which helps reduce the risk of ischemia. METHODS: Twenty adult cadaveric hemispheres were studied. Coronal brain slices were created perpendicular to the SLS representing insular gyri (anterior short, middle short, posterior short, anterior long, and posterior long). The arteries within 10-mm proximity of the SLS that reached the corona radiata were excavated and classified by the entry point. RESULTS: A total of 122 arteries were identified. Sixty-three (52%), 20 (16%), and 39 (32%) arteries penetrated the insula (LIAs), peak of the SLS, and operculum (long medullary arteries), respectively. 100 and six (87%) arteries penetrated within 5 mm of the peak of the SLS. The arteries were distributed in the anterior short gyrus (19%), middle short gyrus (17%), posterior short gyrus (20%), anterior long gyrus (19%), and posterior long gyrus (25%). Seven arteries (5.7%) had anastomoses after they penetrated the parenchyma. CONCLUSION: Approximately 90% of the arteries that entered the parenchyma and reached the corona radiata were within a 5-mm radius of the SLS in both the insula and operculum side. This suggests that using the SLS as a landmark during insulo-opercular surgery can decrease the chance of ischemia.

    DOI: 10.1227/ons.0000000000000879

    PubMed

    researchmap

  • Understanding the molecular pathogenesis of primary central nervous system lymphoma by experimental animal models. 査読 国際誌

    Di Wu, Dahai Liu, Kensuke Tateishi, Fei Qi, Fang Yang, Chao Ke, Hua You

    Journal of cellular physiology   238 ( 10 )   2191 - 2205   2023年8月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Primary central nervous system lymphoma (PCNSL) is a rare and invasive diffuse large B cell lymphoma confined in central nervous system (CNS). The effort to press forward the translational progress has been frustrated by the insufficient understanding of immunophenotype of CNS and tumor genetic alterations of PCNSL, and the lack of validated diagnostic biomarkers. Researchers now have a variety of PCNSL animal models at their disposal that resemble the morphology and immunophenotype of PCNSL, however, a careful and detailed re-examination of these animal models is needed to clarify the differences in genetic alterations, migration capability, and immune status. In this review, we present the knowledge about the phenotypic and genotypic features of PCNSL tumor cells, and compile the preclinical animal models of PCNSL with regard to various injection sites, cell origins, recipient animals, and immune status, and elaborate on the tropism and migration of tumor cells and novel therapeutic strategies for PCNSL. We envisage that the selection of suitable animal models will serve as a well-defined preclinical system to understand the molecular pathogenesis of PCNSL, thereby galvanizing the development of novel and potent therapeutic approaches.

    DOI: 10.1002/jcp.31107

    PubMed

    researchmap

  • A case of midbrain germinoma: A literature review for radiographic and clinical features 査読 国際誌

    Yohei Miyake, Kensuke Tateishi, Akito Oshima, Takeshi Hongo, Kaishi Satomi, Koichi Ichimura, Ayumi Kato, Hiromichi Iwashita, Daisuke Utsunomiya, Tetsuya Yamamoto

    Neuro-Oncology Advances   5 ( 1 )   vdad043   2023年4月

     詳細を見る

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

    DOI: 10.1093/noajnl/vdad043

    PubMed

    researchmap

  • Development of a contacting transwell co-culture system for the in vitro propagation of primary central nervous system lymphoma. 査読 国際誌

    Mayuko Nishi, Kensuke Tateishi, Jeremiah Stanleyraj Sundararaj, Yoko Ino, Yusuke Nakai, Yasuyoshi Hatayama, Yutaro Yamaoka, Yusaku Mihana, Kei Miyakawa, Hirokazu Kimura, Yayoi Kimura, Tetsuya Yamamoto, Akihide Ryo

    Frontiers in cell and developmental biology   11   1275519 - 1275519   2023年

     詳細を見る

    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 a malignant neoplasm of the central nervous system that is refractory to treatment and has extremely poor prognosis. One factor hindering the development of therapeutic options for PCNSL is its molecular heterogeneity and the extreme difficulty in establishing in vitro cell lines that permit intensive research on this disease. In the present study, we developed a method to propagate PCNSL cells in vitro using a contacting transwell cell culture system involving brain vascular pericytes. The co-culture system was found to recapitulate the tumor microenvironment that is influenced by the biological activity of adjacent pericytes, and to sustain the survival and proliferation of PCNSL cells in vitro. We further delineated the underlying molecular mechanisms and found that the HGF-c-Met axis may be involved in the long-term in vitro culture of PCNSL cells. Moreover, the peptidylprolyl isomerase Pin1 was found to play a key role in PCNSL cell survival and it sustained proliferation through interactions with key transcription factors related to B-cell lymphomagenesis. These results suggest that our in vitro co-culture system is well suited to analyzing the biological and molecular characteristics of PCNSL, and may contribute to the discovery of new therapeutic interventions.

    DOI: 10.3389/fcell.2023.1275519

    PubMed

    researchmap

  • Thigh leiomyosarcoma-derived brain metastasis with intracerebral hematoma: A case report and literature review. 査読 国際誌

    Chihiro Oka, Yohei Miyake, Kensuke Tateishi, Yusuke Kawabata, Hiromichi Iwashita, Tetsuya Yamamoto

    Surgical neurology international   14   80 - 80   2023年

     詳細を見る

    記述言語:英語  

    BACKGROUND: Brain metastases with hematoma are clinically important as they indicate the potential for rapid neurological deterioration. Non-uterine leiomyosarcoma-derived brain metastases are particularly rare, and their clinical features, including the bleeding rate, are unclear. Herein, we present a rare case of thigh leiomyosarcoma-derived brain metastasis with intratumoral hematoma and review previous case reports. CASE DESCRIPTION: A 68-year-old man with a right thigh leiomyosarcoma presented with multiple brain metastases. The patient received stereotactic radiotherapy; however, he reported sudden right-sided hemiparesis. We found a right frontal irradiated lesion with intratumoral hemorrhage and performed gross total tumor resection. Histopathological examination showed highly atypical cells with prominent necrosis and hemorrhage. Abnormal thin-walled vessels were prominent within the brain tumor, and vascular endothelial growth factor was diffusely expressed immunohistopathologically. To date, 11 cases of brain metastasis from non-uterine leiomyosarcoma, including the present case, have been reported. Of note, six patients had hemorrhage. Three out of six patients presented with hemorrhage before therapeutic intervention, three cases were from residual sites after surgery or radiation. CONCLUSION: More than half the patients with non-uterine leiomyosarcoma-derived brain metastases presented with intracerebral hemorrhage. Furthermore, these patients are at risk of developing rapid neurological deterioration due to intracerebral hemorrhage.

    DOI: 10.25259/SNI_113_2023

    PubMed

    researchmap

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

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

    Neuro-oncology   25 ( 5 )   899 - 912   2022年10月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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

    DOI: 10.1093/neuonc/noac243

    PubMed

    researchmap

  • Availability of tracheal shift in the chest X-ray image as pre-treatment evaluation of mechanical thrombectomy. 査読 国際誌

    Fukutaro Ohgaki, Nobuyuki Shimizu, Jun Suenaga, Kensuke Tateishi, Naoki Ikegaya, Ryosuke Suzuki, Koji Yamamura, Tetsuya Yamamoto

    The neuroradiology journal   35 ( 5 )   19714009221084237 - 19714009221084237   2022年5月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The use of mechanical thrombectomy (MT) for treatment of acute large vessel occlusion has recently increased. Prompt and timely guiding catheter (GC) induction is necessary to improve prognosis of MT and reduce the time for recanalization. However, difficulties in GC induction are encountered in some patients. This GC induction depends mainly on the aortic arch structure. Therefore, this study focused on assessing presence of tracheal shift on chest X-ray images as pre-treatment evaluation method for GC induction due to its wide availability as an indicator for status of the mediastinum. METHODS: We retrospectively examined 33 patients who underwent MT at our facilities between April 2017 and March 2021. The patients were divided into two groups according to presence or absence of tracheal shift on chest X-ray images. Background characteristics and treatment courses in these two groups were compared. RESULTS: Among 33 patients, tracheal shift was observed on the chest X-ray images of 14 patients. Furthermore, tracheal shift was positively correlated with the time of GC induction (32.9 min vs. 11.6 min, [p < 0.05]) and the female sex (p = 0.03). Additionally, tracheal shift exhibited correlations with multiple risk factors of atherosclerosis (p = 0.04). CONCLUSIONS: In patients with tracheal shift, GC induction could be expectedly difficult. Therefore, advanced disinfection of the right upper arm and affected side of the neck during MT in preparation for changing an approach route is required.

    DOI: 10.1177/19714009221084237

    PubMed

    researchmap

  • HSP90 inhibition overcomes resistance to molecular targeted therapy in BRAFV600E mutant high-grade glioma. 査読 国際誌

    Jo Sasame, Naoki Ikegaya, Masahito Kawazu, Manabu Natsumeda, Takahiro Hayashi, Masataka Isoda, Kaishi Satomi, Arata Tomiyama, Akito Oshima, Hirokuni Honma, Yohei Miyake, Katsuhiro Takabayashi, Taishi Nakamura, Toshihide Ueno, Yuko Matsushita, Hiromichi Iwashita, Yu Kanemaru, Hidetoshi Murata, Akihide Ryo, Keita Terashima, Shoji Yamanaka, Yukihiko Fujii, Hiroyuki Mano, Takashi Komori, Koichi Ichimura, Daniel P Cahill, Hiroaki Wakimoto, Tetsuya Yamamoto, Kensuke Tateishi

    Clinical cancer research : an official journal of the American Association for Cancer Research   28 ( 11 )   2425 - 2439   2022年3月

     詳細を見る

    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: Molecular targeted therapy using BRAF and/or MEK inhibitors has been applied to BRAFV600E mutant high-grade gliomas (HGGs); however, the therapeutic effect is limited by the emergence of drug resistance. EXPERIMENTAL DESIGN: We established multiple paired BRAFV600E mutant HGG patient-derived xenograft (PDX) models based on tissues collected prior to and at relapse after molecular targeted therapy. Using these models, we dissected treatment resistant mechanisms for molecular targeted therapy and explored therapeutic targets to overcome resistance in BRAFV600E HGG models in vitro and in vivo. RESULTS: We found that, despite causing no major genetic and epigenetic changes, BRAF and/or MEK inhibitor treatment deregulated multiple negative feedback mechanisms, which led to the re-activation of the MAPK pathway through c-Raf and AKT signaling. This altered oncogenic signaling primarily mediated resistance to molecular targeted therapy in BRAFV600E mutant HGG. To overcome this resistance mechanism, we performed a high-throughput drug screening to identify therapeutic agents that potently induce additive cytotoxicity with BRAF and MEK inhibitors. We discovered that HSP90 inhibition combined with BRAF/MEK inhibition coordinately deactivated the MAPK and AKT/mTOR pathways, and subsequently induced apoptosis via dephosphorylation of GSK3β (Ser9) and inhibition of Bcl-2 family proteins. This mediated potent cytotoxicity in vitro and in vivo in refractory models with acquired resistance to molecular-targeted therapy. CONCLUSIONS: The combination of an HSP90 inhibitor with BRAF or MEK inhibitors can overcome the limitations of the current therapeutic strategies for BRAFV600E mutant HGG.

    DOI: 10.1158/1078-0432.CCR-21-3622

    PubMed

    researchmap

  • Primary central nervous system lymphoma: clinicopathological and genomic insights for therapeutic development. 査読

    Kensuke Tateishi, Yohei Miyake, Taishi Nakamura, Tetsuya Yamamoto

    Brain tumor pathology   38 ( 3 )   173 - 182   2021年7月

     詳細を見る

    担当区分:筆頭著者, 責任著者   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 a highly aggressive, extra-nodal non-Hodgkin lymphoma that is confined to the central nervous system (CNS) and the eyes. Most PCNSLs arise in immunocompetent older patients and less frequently in immunocompromised patients with Epstein-Barr virus infection. Although a patient's initial response to chemotherapy and radiation therapy is favorable, the clinical outcome of PCNSL remains poor compared to that of systemic lymphoma. Radiation-induced neurotoxicity is also a critical problem for patients with PCNSL. Therefore, a novel therapeutic strategy is required to overcome these challenges. Recent studies have largely uncovered the genomic landscape and associated histopathological features of PCNSL. Based on this background, novel therapeutic agents, such as Bruton's tyrosine kinase inhibitors and immune checkpoint inhibitors, have been introduced for patients with PCNSL. Here, we provide an overview of the updated histopathological and genomic characterization of PCNSL and summarize the current therapeutic strategies. We also review current preclinical PCNSL models for translational research.

    DOI: 10.1007/s10014-021-00408-z

    PubMed

    researchmap

  • Practical Arachnoid Anatomy for the Technical Consideration of Galen Complex Dissection: Cadaveric and Clinical Evaluation. 査読 国際誌

    Shigeta Miyake, Jun Suenaga, Taishi Nakamura, Taisuke Akimoto, Ryosuke Suzuki, Makoto Ohtake, Hajime Takase, Kensuke Tateishi, Nobuyuki Shimizu, Hidetoshi Murata, Kengo Funakoshi, Yutaka Sawamura, Tetsuya Yamamoto

    World neurosurgery   151   e372-e378   2021年4月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The occipital transtentorial approach (OTA) is a very useful but challenging approach to expose the pineal region because the deep-seated arachnoid membranes usually fold and extend over the great vein of Galen (GVG), leading to dense and poor visibility. In addition, the practical aspects of arachnoid anatomy are not well understood. We aimed to develop a safe surgical procedure for the OTA according to the practical aspects of arachnoid anatomy. METHODS: The procedure is shown through an illustrative video of surgery and cadaver. Five cadavers were analyzed for their arachnoid structures and the surgical procedures via the OTA, in strict compliance with legal and ethical requirements. RESULTS: All cadavers showed a 2-layered arachnoid structure-one belonging to the occipital lobe, and the other to the cerebellum. According to our cadaveric analysis, the arachnoid attachment of the tentorial apex can be peeled bluntly, with an average distance of 10.2 mm. For our clinical presentation, a pineal tumor with hydrocephalus was detected in a 14-year-old boy. While using the OTA and expanding the deep surgical field, we detached the membrane from the tentorial apex and bluntly peeled it to reveal the deep veins. Finally, gross total removal of the tumor was achieved. CONCLUSIONS: A 2-layered arachnoid structure interposes the GVG from above and below the tentorium. The arachnoid membrane below the tentorium can be peeled off bluntly from the GVG to the attachment bundle limited by the penetrating veins. This detachment technique is useful for safe enlargement of the surgical field for the OTA.

    DOI: 10.1016/j.wneu.2021.04.041

    PubMed

    researchmap

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

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

    Cancers   13 ( 6 )   2021年3月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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

    DOI: 10.3390/cancers13061415

    PubMed

    researchmap

  • A Rapid Genotyping Panel for Detection of Primary Central Nervous System Lymphoma. 査読 国際誌

    Mihir Gupta, Evan Burns, Nicholas Zeke Georgantas, Julia Thierauf, Naema Nayyar, Amanda Gordon, SooAe Jones, Michelle Pisapia, Ying Sun, Ryan Patrick Burns, Jose Kaleb Velarde, Justin T Jordan, Matthew J Frigault, Brian Vala Nahed, Pamela Stuart Jones, Fred G Barker, William Curry, Rajiv Gupta, Tracy T Batchelor, Javier Romero, Priscilla Brastianos, Hetal Marble, Maria Martinez-Lage, Kensuke Tateishi, Jochen K Lennerz, Jorg Dietrich, Daniel Cahill, Bob Carter, Ganesh M Shankar

    Blood   138 ( 5 )   382 - 386   2021年3月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Diagnosing primary central nervous system lymphoma (PCNSL) frequently requires neurosurgical biopsy due to nonspecific radiologic features and the low yield of cerebrospinal fluid (CSF) studies. We characterized the clinical evaluation of suspected PCNSL (N=1007 patients) and designed a rapid multiplexed genotyping assay for MYD88, TERT promoter, IDH1/2, H3F3A, and BRAF mutations to facilitate the diagnosis of PCNSL from CSF and detect other neoplasms in the differential diagnosis. Among 159 patients with confirmed PCNSL, the median time to secure a diagnosis of PCNSL was 10 days, with a range of 0-617 days. Permanent histopathology confirmed PCNSL in 142/152 biopsies (93.4%), whereas CSF analyses were diagnostic in only 15/113 samplings (13.3%). Among 86 archived clinical specimens, our targeted genotyping assay accurately detected hematologic malignancies with 57.6% sensitivity and 100% specificity (95% CI: 44.1-70.4% and 87.2-100%, respectively). MYD88 and TERT promoter mutations were prospectively identified in DNA extracts of CSF obtained from patients with PCNSL and glioblastoma, respectively, within 80 minutes. Across 132 specimens, hallmark mutations indicating the presence of malignancy were detected with 65.8% sensitivity and 100% specificity (95% CI: 56.2-74.5% and 83.9-100%, respectively). This targeted genotyping approach offers a rapid, scalable adjunct to reduce diagnostic and treatment delays in PCNSL.

    DOI: 10.1182/blood.2020010137

    PubMed

    researchmap

  • IDH-Mutant Astrocytoma With Chromosome 19q13 Deletion Manifesting as an Oligodendroglioma-Like Morphology. 査読 国際誌

    Yohei Miyake, Keita Fujii, Taishi Nakamaura, Naoki Ikegaya, Yuko Matsushita, Yuko Gobayashi, Hiromichi Iwashita, Naoko Udaka, Jiro Kumagai, Hidetoshi Murata, Yasunori Takemoto, Shoji Yamanaka, Koichi Ichimura, Kensuke Tateishi, Tetsuya Yamamoto

    Journal of neuropathology and experimental neurology   80 ( 3 )   247 - 253   2021年2月

     詳細を見る

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

    Partial deletions in chromosomes 1p and 19q are found in a subset of astrocytic tumors; however, it remains unclear how these alterations affect their histological features and prognosis. Herein, we present 3 cases of isocitrate dehydrogenase (IDH)-mutant astrocytoma with chromosome 19q13 deletion. In the first case, the primary tumor harbored an IDH1 mutation with chromosome 1p/19q partial deletions, which covered 19q13 and exhibited a durable initial response to radiotherapy and temozolomide (TMZ) treatment. However, the tumor lost the chromosome 1p/19q partial deletions at recurrence and became resistant to TMZ. Histologically, an oligodendroglioma-like feature was found in the primary tumor but not in the recurrent tumor. Capicua transcriptional repressor (CIC), located on 19q13, was less expressed in the primary tumor but was highly expressed in the recurrent tumor. Similar histological findings were observed in 2 other astrocytic tumors with IDH1 or IDH2 mutations. These tumors also had chromosome 19q13 deletion, including the CIC gene, weakly expressed CIC, and oligodendroglioma-like morphology. These tumors recurred at 6 and 32 months, respectively. These findings suggest that IDH-mutant astrocytoma with chromosome 19q13 partial deletion, including the CIC gene, may induce an oligodendroglioma-like phenotype, but the clinical prognosis may not be similar to that of genetically defined oligodendroglioma.

    DOI: 10.1093/jnen/nlaa161

    PubMed

    researchmap

  • Sirtuin activation targets IDH-mutant tumors. 査読 国際誌

    Julie J Miller, Alexandria Fink, Jack A Banagis, Hiroaki Nagashima, Megha Subramanian, Christine K Lee, Lisa Melamed, Shilpa S Tummala, Kensuke Tateishi, Hiroaki Wakimoto, Daniel P Cahill

    Neuro-oncology   23 ( 1 )   53 - 62   2021年1月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Isocitrate dehydrogenase (IDH)-mutant tumors exhibit an altered metabolic state and are critically dependent upon nicotinamide adenine dinucleotide (NAD+) for cellular survival. NAD+ steady-state levels can be influenced by both biosynthetic and consumptive processes. Here, we investigated activation of sirtuin (SIRT) enzymes, which consume NAD+ as a coenzyme, as a potential mechanism to reduce cellular NAD+ levels in these tumors. METHODS: The effect of inhibition or activation of sirtuin activity, using (i) small molecules, (ii) clustered regularly interspaced short palindromic repeat/CRISPR associated protein 9 gene editing, and (iii) inducible overexpression, was investigated in IDH-mutant tumor lines, including patient-derived IDH-mutant glioma lines. RESULTS: We found that Sirt1 activation led to marked augmentation of NAD+ depletion and accentuation of cytotoxicity when combined with inhibition of nicotinamide phosphoribosyltransferase (NAMPT), consistent with the enzymatic activity of SIRT1 as a primary cellular NAD+ consumer in IDH-mutant cells. Activation of Sirt1 through either genetic overexpression or pharmacologic Sirt1-activating compounds (STACs), an existing class of well-tolerated drugs, led to inhibition of IDH1-mutant tumor cell growth. CONCLUSIONS: Activation of Sirt1 can selectively target IDH-mutant tumors. These findings indicate that relatively nontoxic STACs, administered either alone or in combination with NAMPT inhibition, could alter the growth trajectory of IDH-mutant gliomas while minimizing toxicity associated with cytotoxic chemotherapeutic regimens.

    DOI: 10.1093/neuonc/noaa180

    PubMed

    researchmap

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

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

    Journal of neuropathology and experimental neurology   80 ( 2 )   129 - 136   2021年1月

     詳細を見る

    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

    PubMed

    researchmap

  • Verbal and memory deficits caused by aphasic status epilepticus after resection of a left temporal lobe glioma. 査読 国際誌

    Misaki Kamogawa, Naoki Ikegaya, Yohei Miyake, Takahiro Hayashi, Hidetoshi Murata, Kensuke Tateishi, Tetsuya Yamamoto

    Surgical neurology international   12   614 - 614   2021年

     詳細を見る

    記述言語:英語  

    Background: Nonconvulsive status epilepticus (NCSE) is induced by common neurosurgical conditions, for example, trauma, stroke, tumors, and surgical interventions in the brain. The aggressiveness of the treatment for NCSE depends on its neurological prognosis. Aphasic status epilepticus (ASE) is a subtype of focal NCSE without consciousness impairment. The impact of ASE on neurological prognosis is poorly documented. We describe a case of postoperative ASE resulting in verbal and memory deficits. Case Description: A 54-year-old, right-handed man with focal impaired awareness seizures underwent partial resection for a left temporal lobe tumor. No neurological deficits were observed immediately after surgery. Three days later, however, a focal to bilateral tonic-clonic seizure (FBTCS) occurred, followed by aphasia. Electroencephalography revealed 1.5 Hz left-sided periodic discharges. He was diagnosed with ASE. Multiple anti-seizure drugs were ineffective for the resolution of the patient's verbal disturbance. Nine days after the FBTCS, deep sedation with intravenous anesthetics was performed and the ASE stopped. Thereafter, his symptoms gradually improved. However, the prolonged ASE resulted in verbal and memory deficits. Automated hippocampal volumetry revealed an approximate decrease of 20% on the diseased side on magnetic resonance imaging 3 months after surgery. Conclusion: Prolonged ASE can induce verbal and memory deficits. Early intervention with intravenous anesthetics is required to obtain a favorable neurological prognosis.

    DOI: 10.25259/SNI_1120_2021

    PubMed

    researchmap

  • Superficial siderosis and nonobstructive hydrocephalus due to subependymoma in the ventricle: An illustrative case report. 査読 国際誌

    Yuta Otomo, Naoki Ikegaya, Akito Oshima, Shutaro Matsumoto, Naoko Udaka, Chia-Cheng Chang, Kensuke Tateishi, Hidetoshi Murata, Tetsuya Yamamoto

    Surgical neurology international   12   631 - 631   2021年

     詳細を見る

    記述言語:英語  

    Background: Intraventricular tumors can generally result in obstructive hydrocephalus as they grow. Rarely, however, some intraventricular tumors develop superficial siderosis (SS) and trigger hydrocephalus, even though the tumor has hardly grown. Here, we present an illustrative case of SS and nonocclusive hydrocephalus caused by subependymoma of the lateral ventricles. Case Description: A 78-year-old man with an intraventricular tumor diagnosed 7 years ago had been suffering from gait disturbance for 2 years. He also developed cognitive impairment. Intraventricular tumors showed little growth on annual magnetic resonance imaging (MRI). MRI T2-star weighted images (T2*WI) captured small intratumoral hemorrhages from the beginning of the follow-up. Three years before, at the same time as the onset of ventricular enlargement, T2*WI revealed low intensity in the whole tumor and cerebral surface. Subsequent follow-up revealed that this hemosiderin deposition had spread to the brain stem and cerebellar surface, and the ventricles had expanded further. Cerebrospinal fluid (CSF) examination revealed xanthochromia. The tumor was completely removed en bloc. Histopathological findings were consistent with those of subependymoma. Although CSF findings improved, SS and hydrocephalus did not improve. Therefore, the patient underwent a lumboperitoneal shunt for CSF diversion after tumor resection. Conclusion: Some intraventricular tumors cause SS and nonobstructive hydrocephalus due to microbleeding, even in the absence of tumor growth. T2*WI and, if necessary, timely CSF examination can allow identification of presymptomatic SS. This follow-up strategy may provide a favorable course by facilitating early intervention in patients with intraventricular lesions, not just subependymomas.

    DOI: 10.25259/SNI_868_2021

    PubMed

    researchmap

  • Evaluation of Tumor Cell Infiltration to the Skull in Dermatofibrosarcoma Protuberans of the Scalp: Case Report and Literature Review. 査読

    Takeshi Hongo, Taishi Nakamura, Akio Miyake, Ikuma Kato, Kensuke Tateishi, Shoji Yamanaka, Tetsuya Yamamoto

    NMC case report journal   8 ( 1 )   287 - 293   2021年

     詳細を見る

    記述言語:英語  

    Dermatofibrosarcoma protuberans (DFSP) originates from the dermal layer of the skin; the optimum treatment is an extended marginal resection. We describe a case of DFSP of the scalp with a skull invasive defect that was thoroughly examined pathologically to determine the optimum length of surgical margins. The tumor cells infiltrated up to 26 mm into the dermal tissues, whereas no infiltrating tumor cells were present in the skull, indicating the combination of marginal resection of the dermal tissues and lower of the skull can be a clinically relevant strategy for treatment of DFSP cases with skull invasion.

    DOI: 10.2176/nmccrj.cr.2020-0297

    PubMed

    researchmap

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

     詳細を見る

    担当区分:筆頭著者, 責任著者   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

    PubMed

    researchmap

  • Poly(ADP-ribose) Glycohydrolase Inhibition Sequesters NAD+ to Potentiate the Metabolic Lethality of Alkylating Chemotherapy in IDH-Mutant Tumor Cells. 査読 国際誌

    Hiroaki Nagashima, Christine K Lee, Kensuke Tateishi, Fumi Higuchi, Megha Subramanian, Seamus Rafferty, Lisa Melamed, Julie J Miller, Hiroaki Wakimoto, Daniel P Cahill

    Cancer discovery   10 ( 11 )   1672 - 1689   2020年11月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    NAD+ is an essential cofactor metabolite and is the currency of metabolic transactions critical for cell survival. Depending on tissue context and genotype, cancer cells have unique dependencies on NAD+ metabolic pathways. PARPs catalyze oligomerization of NAD+ monomers into PAR chains during cellular response to alkylating chemotherapeutics, including procarbazine or temozolomide. Here we find that, in endogenous IDH1-mutant tumor models, alkylator-induced cytotoxicity is markedly augmented by pharmacologic inhibition or genetic knockout of the PAR breakdown enzyme PAR glycohydrolase (PARG). Both in vitro and in vivo, we observe that concurrent alkylator and PARG inhibition depletes freely available NAD+ by preventing PAR breakdown, resulting in NAD+ sequestration and collapse of metabolic homeostasis. This effect reversed with NAD+ rescue supplementation, confirming the mechanistic basis of cytotoxicity. Thus, alkylating chemotherapy exposes a genotype-specific metabolic weakness in tumor cells that can be exploited by PARG inactivation. SIGNIFICANCE: Oncogenic mutations in the isocitrate dehydrogenase genes IDH1 or IDH2 initiate diffuse gliomas of younger adulthood. Strategies to maximize the effectiveness of chemotherapy in these tumors are needed. We discover alkylating chemotherapy and concurrent PARG inhibition exploits an intrinsic metabolic weakness within these cancer cells to provide genotype-specific benefit.See related commentary by Pirozzi and Yan, p. 1629.This article is highlighted in the In This Issue feature, p. 1611.

    DOI: 10.1158/2159-8290.CD-20-0226

    PubMed

    researchmap

  • Thiel's embalming method with additional intra-cerebral ventricular formalin injection (TEIF) for cadaver training of head and brain surgery. 査読

    Shigeta Miyake, Jun Suenaga, Ryohei Miyazaki, Jo Sasame, Taisuke Akimoto, Takahiro Tanaka, Makoto Ohtake, Hajime Takase, Kensuke Tateishi, Nobuyuki Shimizu, Hidetoshi Murata, Kengo Funakoshi, Tetsuya Yamamoto

    Anatomical science international   95 ( 4 )   564 - 570   2020年9月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Thiel's embalming method provides natural coloration, flexibility, and tissue plasticity, and is used widely to prepare specimens for cadaver surgical training. However, this method causes brain softening, thereby restricting the cadaver surgical training of intra-cranial procedures. In this study, three cadavers were embalmed using formalin fixation, Thiel's embalming method, and Thiel's embalming method with additional intra-cerebral ventricular formalin injection, respectively. We also established rat models of the three embalming methods to develop and determine the best method for retaining adequate brain elasticity. The intra-ventricular formalin injection in the cadaver was performed through the Kocher's point, as in the classical external ventricular drain procedure. Both, the cadaver brains and rat models yielded consistent shear wave measurements and brain surface stiffness data. Notably, the Thiel's embalming method with additional intra-cerebral ventricular formalin injection yielded suitable elasticity for brain cadaver surgical training in terms of brain mobilization and surgical field deployment, and also discharged formaldehyde in undetectable quantities. To our knowledge, this is the first report in which a fixed quality, namely, brain elasticity for the performance of head and brain cadaver surgical training, has been evaluated in a cadaver subjected to the Thiel's embalming method with immersion fixation in the cerebrospinal fluid space. We conclude that the Thiel's embalming method with additional intra-cerebral ventricular formalin injection can maintain the brain elasticity, and may therefore improve the quality of head and brain cadaver surgical training safely and easily.

    DOI: 10.1007/s12565-020-00545-z

    PubMed

    researchmap

  • Incision Edge "Lifting Method" in Cerebral Bypass Surgery: A Novel Optional Technique for Narrow or Thin Recipient Arteries. 査読 国際誌

    Ryohei Miyazaki, Hidetoshi Murata, Mitsuru Sato, Ryu Ueno, Naoki Ikegaya, Shutaro Matsumoto, Hiroyuki Abe, Kagemichi Nagao, Nobuyuki Shimizu, Kensuke Tateishi, Jun Suenaga, Tetsuya Yamamoto

    World neurosurgery   141   196 - 202   2020年9月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Cerebral bypass surgery, such as the superficial temporal artery-middle cerebral artery bypass, is one of the essential procedures for cerebral revascularization. However, very narrow or thin blood vessels will increase the risk of anastomotic problems, such as occurs in Moyamoya disease. For such vessels, we have devised a "lifting method" in the recipient arteriotomy. In the present study, we have introduced this novel optional technique and evaluated its effects. METHODS: The lifting method is a procedure of lifting the incision edge of a linear incision on the recipient vessel to widen the ostium. We attempted the lifting method in 23 consecutive patients (41 arteries) and, as a historical control, compared the results with those from the conventional method in 25 consecutive patients (37 arteries) for the previous 3 years. We compared patient age, years of surgical experience, recipient vessel diameter, anastomotic events, and final patency. As a subanalysis, the same evaluations were performed separately for patients with Moyamoya disease. Furthermore, the time required for the lifting procedure was measured retrospectively. RESULTS: The incidence of anastomotic events with the conventional method was 13.5% overall and 19% in those with Moyamoya disease. No adverse events occurred with the lifting method (P < 0.05). No statistically significant differences were found for the other factors, including final patency between the 2 groups. The time required for the lifting procedure averaged 1 minute, 15 seconds. CONCLUSIONS: Use of the lifting method widens and secures the ostium in a recipient vessel and greatly facilitates operability. We have found it to be a foolproof method enabling safe and reliable anastomosis even with narrow or thin vessels.

    DOI: 10.1016/j.wneu.2020.06.077

    PubMed

    researchmap

  • BRAF V600E mutation mediates FDG-methionine uptake mismatch in polymorphous low-grade neuroepithelial tumor of the young. 査読 国際誌

    Kensuke Tateishi, Naoki Ikegaya, Naoko Udaka, Jo Sasame, Takahiro Hayashi, Yohei Miyake, Tetsuhiko Okabe, Ryogo Minamimoto, Hidetoshi Murata, Daisuke Utsunomiya, Shoji Yamanaka, Tetsuya Yamamoto

    Acta neuropathologica communications   8 ( 1 )   139 - 139   2020年8月

     詳細を見る

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

    We present a case of a 14-year old boy with tumor-associated refractory epilepsy. Positron emission tomography imaging demonstrated a region with heterogeneous high 11C-methionine uptake and a region with homogenous low 18F-fluorodeoxyglucose uptake within the tumor. Histopathological and genomic analyses confirmed the tumor as BRAF V600E-mutated polymorphous low-grade neuroepithelial tumor of the young (PLNTY). Within the high-methionine-uptake region, we observed increased protein levels of L-type amino acid transporter 1 (LAT1), a major transporter of methionine; c-Myc; and constituents of the mitogen-activated protein kinase (MAPK) pathway. We also found that LAT1 expression was linked to the BRAF V600E mutation and subsequent activation of MAPK signaling and c-Myc. Pharmacological and genetic inhibition of the MAPK pathway suppressed c-Myc and LAT1 expression in BRAF V600E-mutated PLNTY and glioblastoma cells. The BRAF inhibitor dabrafenib moderately suppressed cell viability in PLNTY. Collectively, our results indicate that BRAF V600E mutation-activated MAPK signaling and downstream c-Myc induces specific metabolic alterations in PLNTY, and may represent an attractive target in the treatment of the disease.

    DOI: 10.1186/s40478-020-01023-3

    PubMed

    researchmap

  • Redox reaction and clinical outcome of primary diffuse large B-cell lymphoma of the central nervous system: Prognostic role of metabolic and textural parameters of 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) PET/computed tomography in a small patient cohort. 査読 国際誌

    Junichi Tsuchiya, Tomohiro Yoneyama, Makoto Ohtake, Kensuke Tateishi, Hyeyeol Bae, Mitsuhiro Kishino, Ukihide Tateishi

    Nuclear medicine communications   41 ( 6 )   567 - 574   2020年6月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: This study aimed to clarify the relationship between tumor redox reaction evaluated by Cu-diacetyl-bis (N4-methylthiosemicarbazone) (Cu-ATSM) PET/computed tomography (CT) and disease-free survival (DFS) in patients with primary diffuse large B-cell lymphoma of the central nervous system (DLBCL-CNS). METHODS: Fifteen consecutive patients with histologically confirmed DLBCL-CNS underwent preoperative Cu-ATSM PET/CT and F-fluorodeoxyglucose (FDG) PET/CT. Statistical features of seven first-order parameters, including the standardized uptake value (SUV); 12 second-order parameters, including gray-level co-occurrence matrices and gray-level zone size matrices; and 5 high-order parameters, including neighborhood gray-tone difference matrices, were calculated from the volume of interest. We compared DFS with parameters, including SUVmax and tumor-to-background (T/B) ratio of FDG, and SUVmax, T/B ratio, and other textural features of Cu-ATSM. RESULTS: The mean follow-up duration after PET/CT was 458 (range, 41-1071) days. The SUVmax of FDG was significantly higher than that of Cu-ATSM (P = 0.001), but the T/B ratio was not significantly different between the scans (3.49 ± 2.29 vs 2.48 ± 1.18; P = 0.244). A Mantel-Cox log-rank test revealed no significant association between SUVmax of FDG and DFS (P = 0.641). A high SUVmax of Cu-ATSM had a tendency of shorter DFS (P = 0.055). Total lesion reduction, reductive tumor volume, and T/B ratio of Cu-ATSM were significantly correlated with poor DFS by univariate analysis (P = 0.049, 0.031, and 0.007, respectively). Neighborhood gray-level co-occurrence matrix dissimilarity was significantly correlated with poor DFS (P = 0.015). CONCLUSIONS: Metabolic and textural features derived from pretreatment Cu-ATSM PET/CT could be used for predicting DFS and establishing a novel treatment strategy in DLBCL-CNS patients.

    DOI: 10.1097/MNM.0000000000001197

    PubMed

    researchmap

  • Autologous Transfusion of Blood Aspirated during Suction Decompression in Clipping of Large or Giant Cerebral Aneurysm. 査読

    Ryo Matsuzawa, Hidetoshi Murata, Mitsuru Sato, Ryohei Miyazaki, Takahiro Tanaka, Nobuyuki Shimizu, Kensuke Tateishi, Jun Suenaga, Tetsuya Yamamoto

    Neurologia medico-chirurgica   59 ( 9 )   351 - 356   2019年9月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The suction decompression (SD) method, which proactively aspirates the blood flowing into the aneurysm and reduces the internal pressure of the aneurysm, is useful for clipping surgery of large and giant cerebral aneurysm. However, there has been little discussion on re-utilization of blood aspirated during SD. This study aimed to examine the safety, convenience, and usefulness of autologous transfusion of aspirated blood using a transfusion bag. At the time of craniotomy, the cervical carotid artery is fully exposed. An angiocatheter sheath was inserted into the carotid artery and placed in the internal carotid artery. In SD, blood was aspirated from the sheath at a constant speed and quickly stored in a blood transfusion storage bag. Blood aspiration was repeated with a new syringe; once the transfusion bag was full, the blood was re-administered to the patient. Changes in vital sign and hemoglobin/hematocrit values before and after SD were examined in five cases performed in this procedure. The aspirated blood volumes of five cases ranged from 130 to 400 mL, and all aspirated blood was successfully re-transfused. There was no critical change in vital sign, and no significant decrease in the hemoglobin/hematocrit value. No findings suggestive of complications of thrombus formation, infection, and hemolysis were noted. Re-transfusion of aspirated blood during SD using a transfusion bag is a simple and safe method, which can minimize potential risk of re-utilizing aspirated blood, and enables the safe and easy execution of SD regardless of aspirated blood volume.

    DOI: 10.2176/nmc.tn.2018-0299

    PubMed

    researchmap

  • PI3K/AKT/mTOR Pathway Alterations Promote Malignant Progression and Xenograft Formation in Oligodendroglial Tumors. 査読 国際誌

    Kensuke Tateishi, Taishi Nakamura, Tareq A Juratli, Erik A Williams, Yuko Matsushita, Shigeta Miyake, Mayuko Nishi, Julie J Miller, Shilpa S Tummala, Alexandria L Fink, Nina Lelic, Mara V A Koerner, Yohei Miyake, Jo Sasame, Kenji Fujimoto, Takahiro Tanaka, Ryogo Minamimoto, Shigeo Matsunaga, Shigeo Mukaihara, Takashi Shuto, Hiroki Taguchi, Naoko Udaka, Hidetoshi Murata, Akihide Ryo, Shoji Yamanaka, William T Curry, Dora Dias-Santagata, Tetsuya Yamamoto, Koichi Ichimura, Tracy T Batchelor, Andrew S Chi, A John Iafrate, Hiroaki Wakimoto, Daniel P Cahill

    Clinical cancer research : an official journal of the American Association for Cancer Research   25 ( 14 )   4375 - 4387   2019年7月

     詳細を見る

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

    PURPOSE: Oligodendroglioma has a relatively favorable prognosis, however, often undergoes malignant progression. We hypothesized that preclinical models of oligodendroglioma could facilitate identification of therapeutic targets in progressive oligodendroglioma. We established multiple oligodendroglioma xenografts to determine if the PI3K/AKT/mTOR signaling pathway drives tumor progression. EXPERIMENTAL DESIGN: Two anatomically distinct tumor samples from a patient who developed progressive anaplastic oligodendroglioma (AOD) were collected for orthotopic transplantation in mice. We additionally implanted 13 tumors to investigate the relationship between PI3K/AKT/mTOR pathway alterations and oligodendroglioma xenograft formation. Pharmacologic vulnerabilities were tested in newly developed AOD models in vitro and in vivo. RESULTS: A specimen from the tumor site that subsequently manifested rapid clinical progression contained a PIK3CA mutation E542K, and yielded propagating xenografts that retained the OD/AOD-defining genomic alterations (IDH1R132H and 1p/19q codeletion) and PIK3CAE542K, and displayed characteristic sensitivity to alkylating chemotherapeutic agents. In contrast, a xenograft did not engraft from the region that was clinically stable and had wild-type PIK3CA. In our panel of OD/AOD xenografts, the presence of activating mutations in the PI3K/AKT/mTOR pathway was consistently associated with xenograft establishment (6/6, 100%). OD/AOD that failed to generate xenografts did not have activating PI3K/AKT/mTOR alterations (0/9, P < 0.0001). Importantly, mutant PIK3CA oligodendroglioma xenografts were vulnerable to PI3K/AKT/mTOR pathway inhibitors in vitro and in vivo-evidence that mutant PIK3CA is a tumorigenic driver in oligodendroglioma. CONCLUSIONS: Activation of the PI3K/AKT/mTOR pathway is an oncogenic driver and is associated with xenograft formation in oligodendrogliomas. These findings have implications for therapeutic targeting of PI3K/AKT/mTOR pathway activation in progressive oligodendrogliomas.

    DOI: 10.1158/1078-0432.CCR-18-4144

    PubMed

    researchmap

  • Molecular genetics and therapeutic targets of pediatric low-grade gliomas. 査読

    Kensuke Tateishi, Taishi Nakamura, Tetsuya Yamamoto

    Brain tumor pathology   36 ( 2 )   74 - 83   2019年4月

     詳細を見る

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

    Pediatric low-grade gliomas (PLGGs) have relatively favorable prognosis and some resectable PLGGs, such as cerebellar pilocytic astrocytoma, can be cured by surgery alone. However, many PLGG cases are unresectable and some of them undergo tumor progression. Therefore, a multidisciplinary approach is necessary to treat PLGG patients. Recent genomic analysis revealed a broad genomic landscape underlying PLGG. Notably, the majority of PLGGs present MAPK pathway-associated genomic alterations and MAPK signaling-dependent tumor progression. Following preclinical evidence, many clinical trials based on molecular target therapy have been conducted on PLGG patients, some of whom exhibited durable response to target therapy. Here, we provide an overview of PLGG genetics and the evidence supporting the application of molecular target therapy in these patients.

    DOI: 10.1007/s10014-019-00340-3

    PubMed

    researchmap

  • Genome-wide DNA methylation profiling shows molecular heterogeneity of anaplastic pleomorphic xanthoastrocytoma. 査読 国際誌

    Taishi Nakamura, Kohei Fukuoka, Yoshiko Nakano, Kai Yamasaki, Yuko Matsushita, Satoshi Yamashita, Junji Ikeda, Naoko Udaka, Reo Tanoshima, Norio Shiba, Kensuke Tateishi, Shoji Yamanaka, Tetsuya Yamamoto, Junko Hirato, Koichi Ichimura

    Cancer science   110 ( 2 )   828 - 832   2019年2月

     詳細を見る

    記述言語:英語  

    In the revised World Health Organization classification 2016, anaplastic pleomorphic xanthoastrocytoma (PXA) has been newly defined as a variant of the PXA entity. Furthermore, some anaplastic PXA were reported to have extremely poor prognosis which showed a type of pediatric glioblastoma (GBM) molecular profile. Recent integrated molecular classification for primary central nervous system tumors proposed some differences between histological and molecular features. Herein, in a genome-wide molecular analysis, we show an extreme aggressive anaplastic PXA that resulted in a pediatric GBM molecular profile. A full implementation of the molecular approach is the key to predict prognosis and decide the treatment strategy for anaplastic PXA.

    DOI: 10.1111/cas.13903

    PubMed

    researchmap

  • [Traumatic Subacute Pre-Pontine Hematoma in a Hemophilia Patient]. 査読

    Ryo Matsuzawa, Kensuke Tateishi, Junya Iwata, Yoshihiro Numagami, Yasunori Takemoto, Yasuhiko Mochimatsu, Tetsuya Yamamoto

    No shinkei geka. Neurological surgery   47 ( 2 )   225 - 229   2019年2月

     詳細を見る

    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.11477/mf.1436203922

    PubMed

    researchmap

  • The usefulness of straight chemotherapy for dermal exposed anaplastic lymphoma kinase fusion-positive anaplastic large-cell lymphoma with intracranial invasion 査読

    Taishi Nakamura, Hiroyuki Abe, Masahiro Yoshitomi, Makiko Enaka, Kensuke Tateishi, Norio Shiba, Shoji Yamanaka, Tetsuya Yamamoto

    Asian Journal of Neurosurgery   14 ( 4 )   1218 - 1218   2019年

     詳細を見る

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

    DOI: 10.4103/ajns.ajns_158_19

    researchmap

  • Human recombinant erythropoietin improves motor function in rats with spinal cord compression-induced cervical myelopathy. 査読 国際誌

    Takahiro Tanaka, Hidetoshi Murata, Ryohei Miyazaki, Tetsuya Yoshizumi, Mitsuru Sato, Makoto Ohtake, Kensuke Tateishi, Phyo Kim, Tetsuya Yamamoto

    PloS one   14 ( 12 )   e0214351   2019年

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: Erythropoietin (EPO) is a clinically available hematopoietic cytokine. EPO has shown beneficial effects in the context of spinal cord injury and other neurological conditions. The aim of this study was to evaluate the effect of EPO on a rat model of spinal cord compression-induced cervical myelopathy and to explore the possibility of its use as a pharmacological treatment. METHODS: To develop the compression-induced cervical myelopathy model, an expandable polymer was implanted under the C5-C6 laminae of rats. EPO administration was started 8 weeks after implantation of a polymer. Motor function of rotarod performance and grip strength was measured after surgery, and motor neurons were evaluated with H-E, NeuN and choline acetyltransferase staining. Apoptotic cell death was assessed with TUNEL and Caspase-3 staining. The 5HT, GAP-43 and synaptophysin were evaluated to investigate the protection and plasticity of axons. Amyloid beta precursor protein (APP) was assessed to evaluate axonal injury. To assess transfer of EPO into spinal cord tissue, the EPO levels in spinal cord tissue were measured with an ELISA for each group after subcutaneous injection of EPO. RESULTS: High-dose EPO maintained motor function in the compression groups. EPO significantly prevented the loss of motor neurons and significantly decreased neuronal apoptotic cells. Expression of 5HT and synaptophysin was significantly preserved in the EPO group. APP expression was partly reduced in the EPO group. The EPO levels in spinal cord tissue were significantly higher in the high-dose EPO group than other groups. CONCLUSION: EPO improved motor function in rats with compression-induced cervical myelopathy. EPO suppressed neuronal cell apoptosis, protected motor neurons, and induced axonal protection and plasticity. The neuroprotective effects were produced following transfer of EPO into the spinal cord tissue. These findings suggest that EPO has high potential as a treatment for degenerative cervical myelopathy.

    DOI: 10.1371/journal.pone.0214351

    PubMed

    researchmap

  • Delayed C5 Palsy After Anterior Cervical Decompression Surgery: Preoperative Foraminal Stenosis and Postoperative Spinal Cord Shift Increase the Risk of Palsy. 査読 国際誌

    Hajime Takase, Hidetoshi Murata, Mitsuru Sato, Takahiro Tanaka, Ryohei Miyazaki, Tetsuya Yoshizumi, Kensuke Tateishi, Nobutaka Kawahara, Tetsuya Yamamoto

    World neurosurgery   120   e1107-e1119 - e1119   2018年12月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: Postoperative C5 palsy is a well-known complication after cervical decompression with either a posterior or an anterior approach. Its cause has been discussed more regarding the posterior approach. The main hypothesis is that postoperative spinal cord shift causes root traction and palsy. However, the pathogenesis in anterior cases has not been fully described. Therefore, the purpose of this study was to clarify the risk factors for C5 palsy in the anterior approach through our C5 palsy cases. METHODS: A total of 149 surgical patients with an anterior cervical lesion were treated by a specific spinal surgeon under consistent same treatment strategy. Of these patients, 88 who satisfied the evaluation criteria were enrolled. Postoperative C5 palsy was defined as postoperative weakness of the deltoid with or without weakness of the biceps brachii. Risk factors of C5 palsy were extracted from clinical backgrounds, surgical approaches, and radiologic findings from patients with palsy. RESULTS: Four sides of 3 individuals (4.6%) who underwent multiple corpectomy developed C5 palsy. All paralyses became evident several days after the surgery and recovered. Older age, multiple corpectomy, postoperative spinal cord shift, and foraminal stenosis of C4-5 and C5-6 were statistically extracted as causative factor of C5 palsy. In the patients with palsy, distortion of the anterior nerve root as a result of a residual vertebral spur was observed with anterior spinal cord shift after anterior corpectomy. CONCLUSIONS: Multiple corpectomy for patients with longer anterior lesions and locally developed kyphosis is related to a larger postoperative cord shift, which can cause the occurrence of C5 palsy. Moreover, C4-5 or C5-6 foraminal stenosis can accelerate tethering of the C5 or C6 nerve root. Older patients undergoing multiple corpectomy are susceptible to these risks of palsy. Appropriate patient selection and sufficient additional foraminotomy should be considered for extensive anterior lesions and locally developed kyphosis to avoid postoperative C5 palsy.

    DOI: 10.1016/j.wneu.2018.08.240

    PubMed

    researchmap

  • Cell surface Notch ligand DLL3 is a therapeutic target in isocitrate dehydrogenase mutant glioma. 査読

    Spino M, Kurz SC, Chiriboga L, Serrano J, Zeck B, Sen N, Patel S, Shen G, Vasudevaraja V, Tsirigos A, Suryadevara CM, Frenster JD, Tateishi K, Wakimoto H, Jain R, Riina HA, Nicolaides T, Sulman EP, Cahill DP, Golfinos JG, Isse K, Saunders LR, Zagzag D, Placantonakis DG, Snuderl M, Chi AS

    Clinical cancer research : an official journal of the American Association for Cancer Research   25 ( 4 )   1261 - 1271   2018年11月

  • Transaminase Inhibition by 2-Hydroxyglutarate Impairs Glutamate Biosynthesis and Redox Homeostasis in Glioma. 査読

    McBrayer SK, Mayers JR, DiNatale GJ, Shi DD, Khanal J, Chakraborty AA, Sarosiek KA, Briggs KJ, Robbins AK, Sewastianik T, Shareef SJ, Olenchock BA, Parker SJ, Tateishi K, Spinelli JB, Islam M, Haigis MC, Looper RE, Ligon KL, Bernstein BE, Carrasco RD, Cahill DP, Asara JM, Metallo CM, Yennawar NH, Vander Heiden MG, Kaelin WG Jr

    Cell   175 ( 1 )   101 - 116.e25   2018年9月

  • Genotype-targeted local therapy of glioma. 査読 国際誌

    Shankar GM, Kirtane AR, Miller JJ, Mazdiyasni H, Rogner J, Tai T, Williams EA, Higuchi F, Juratli TA, Tateishi K, Koerner MVA, Tummala SS, Fink AL, Penson T, Schmidt SP, Wojtkiewicz GR, Baig A, Francis JM, Rinne ML, Batten JM, Batchelor TT, Brastianos PK, Curry WT Jr, Barker FG, Jordan JT, Iafrate AJ, Chi AS, Lennerz JK, Meyerson M, Langer R, Wakimoto H, Traverso G, Cahill DP

    Proceedings of the National Academy of Sciences of the United States of America   115 ( 36 )   E8388 - E8394   2018年8月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1073/pnas.1805751115

    PubMed

    researchmap

  • [Efficacy and Safety of Salvage ESHAP Chemotherapy for Recurrent/Refractory PCNSLs]. 査読

    Nagao K, Nakamura T, Tateishi K, Sato H, Shimizu N, Suenaga J, Murata H, Kanno H, Yamamoto T

    No shinkei geka. Neurological surgery   46 ( 7 )   575 - 581   2018年7月

     詳細を見る

    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.11477/mf.1436203773

    PubMed

    researchmap

  • Three-dimensional multimodality fusion imaging as an educational and planning tool for deep-seated meningiomas. 査読 国際誌

    Sato M, Tateishi K, Murata H, Kin T, Suenaga J, Takase H, Yoneyama T, Nishii T, Tateishi U, Yamamoto T, Saito N, Inoue T, Kawahara N

    British journal of neurosurgery   32 ( 5 )   1 - 7   2018年6月

     詳細を見る

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

    DOI: 10.1080/02688697.2018.1485877

    PubMed

    researchmap

  • Succinate Dehydrogenase B Subunit-Negative Jugular Foramen Paraganglioma Manifesting Malignant Progression with Pseudohypoxia-Related Atypical Uptake of [18F]-Fluoro-2-Deoxy-d-Glucose: A Case Report. 査読 国際誌

    Makoto Ohtake, Kensuke Tateishi, Hidetoshi Murata, Yoji Nagashima, Shoji Yamanaka, Tetsuya Yamamoto

    World neurosurgery   114   47 - 52   2018年6月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Paragangliomas are generally benign, slow-growing tumors. However, approximately 10%-20% are malignant, characterized by distant metastasis. Recently, a germ line mutation in succinate dehydrogenase B subunit (SDHB) has been shown to be associated with malignant behavior in paraganglioma. Here we present a case of SDHB-negative malignant paraganglioma of the jugular foramen with a pseudohypoxic microenvironment and unique imaging features on [18F]-fluoro-2-deoxy-d-glucose positron emission tomography ([18F]-FDG PET), and discuss the significance of SDHB immunohistochemistry and the potential of [18F]-FDG PET for clinical management. CASE DESCRIPTION: A 55-year-old woman was diagnosed with jugular foramen paraganglioma. Initial surgical resection was performed; however, follow-up [18F]-FDG PET indicated multiple uptake regions throughout the body. Biopsies for multiple recurrent lesions revealed consistent pathological features, suggesting distant metastasis. Immunohistochemical analysis revealed a lack of SDHB immunostaining in all specimens. Pseudohypoxic markers, including hypoxia-inducible factor-1α and downstream glycolysis enzymes, were strongly expressed. [18F]-FDG PET demonstrated increased uptake in the lesions, and the patient died 3 years after initial metastasis. CONCLUSION: In patients with head and neck paraganglioma without SDHB expression, close follow-up should be considered because of the risk for metastasis. In such cases, [18F]-FDG PET might be useful for detecting metastasis due to atypical accumulation from pseudohypoxia-induced glycolysis.

    DOI: 10.1016/j.wneu.2018.02.147

    PubMed

    researchmap

  • Prognostic implications of 62Cu-diacetyl-bis (N 4-methylthiosemicarbazone) PET/CT in patients with glioma 査読

    Akira Toriihara, Makoto Ohtake, Kensuke Tateishi, Ayako Hino-Shishikura, Tomohiro Yoneyama, Yoshio Kitazume, Tomio Inoue, Nobutaka Kawahara, Ukihide Tateishi

    Annals of Nuclear Medicine   32 ( 4 )   264 - 271   2018年5月

     詳細を見る

    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  

    DOI: 10.1007/s12149-018-1241-4

    Scopus

    PubMed

    researchmap

  • Genotype based local targeted therapy for glioma 査読

    Shankar Ganesh Mani, Kirtane Ameya, Wakimoto Hiroaki, Tateishi Kensuke, Higuchi Fumi, Juratli Tareq, Meyerson Matthew, Barker Fred, Iafrate A. John, Langer Robert, Traverso Giovanni, Cahill Daniel

    JOURNAL OF NEUROSURGERY   128 ( 4 )   10 - 11   2018年4月

  • Bow Hunter's Syndrome by Nondominant Vertebral Artery Compression: A Case Report, Literature Review, and Significance of Downbeat Nystagmus as the Diagnostic Clue 査読

    Yu Iida, Hidetoshi Murata, Ken Johkura, Testuhiro Higashida, Takahiro Tanaka, Kensuke Tateishi

    World Neurosurgery   111   367 - 372   2018年3月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.wneu.2017.12.167

    Web of Science

    Scopus

    PubMed

    researchmap

  • Deregulated NAD plus metabolism as a therapeutic target in IDH1 mutant gliomas. 査読

    Tateishi Kensuke

    CANCER SCIENCE   109   814   2018年1月

     詳細を見る

    担当区分:筆頭著者  

    Web of Science

    researchmap

  • Initial Treatment Strategy for Intracranial Mycotic Aneurysms: 2 Case Reports and Literature Review 査読

    Makoto Ohtake, Kensuke Tateishi, Naoki Ikegaya, Junya Iwata, Shoji Yamanaka, Hidetoshi Murata

    WORLD NEUROSURGERY   106   2017年10月

     詳細を見る

  • Encouraging option of multi-staged gross total resection for a C11orf-RelA fusion-positive supratentorial anaplastic ependymoma 査読

    Taishi Nakamura, Kohei Fukuoka, Junji Ikeda, Masahiro Yoshitomi, Naoko Udaka, Reo Tanoshima, Kensuke Tateishi, Shoji Yamanaka, Koichi Ichimura, Tetsuya Yamamoto

    BRAIN TUMOR PATHOLOGY   34 ( 4 )   160 - 164   2017年10月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s10014-017-0297-5

    Web of Science

    PubMed

    researchmap

  • IDH1 Mutation and World Health Organization 2016 Diagnostic Criteria for Adult Diffuse Gliomas: Advances in Surgical Strategy 査読

    Kensuke Tateishi, Hiroaki Wakimoto, Daniel P. Cahill

    Clinical Neurosurgery   64 ( CN_suppl_1 )   134 - 138   2017年9月

     詳細を見る

    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)   出版者・発行元:Oxford University Press  

    DOI: 10.1093/neuros/nyx247

    Scopus

    PubMed

    researchmap

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

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

    CANCER RESEARCH   77 ( 15 )   4102 - 4115   2017年8月

     詳細を見る

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

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

    Web of Science

    PubMed

    researchmap

  • Genome-wide DNA methylation profiling identifies primary central nervous system lymphoma as a distinct entity different from systemic diffuse large B-cell lymphoma 査読

    Taishi Nakamura, Satoshi Yamashita, Kazutaka Fukumura, Jun Nakabayashi, Kazuhiro Tanaka, Kaoru Tamura, Kensuke Tateishi, Manabu Kinoshita, Shintaro Fukushima, Hirokazu Takami, Kohei Fukuoka, Kai Yamazaki, Yuko Matsushita, Makoto Ohno, Yasuji Miyakita, Soichiro Shibui, Atsuhiko Kubo, Takashi Shuto, Sylvia Kocialkowski, Shoji Yamanaka, Akitake Mukasa, Takashi Sasayama, Kazuhiko Mishima, Taketoshi Maehara, Nobutaka Kawahara, Motoo Nagane, Yoshitaka Narita, Hiroyuki Mano, Toshikazu Ushijima, Koichi Ichimura

    ACTA NEUROPATHOLOGICA   133 ( 2 )   321 - 324   2017年2月

     詳細を見る

  • Characteristics and surgical strategies for posterior clinoid process meningioma: two case reports and review of the literature 査読

    Hajime Takase, Takafumi Kawasaki, Kensuke Tateishi, Taka-akira Yokoyama, Hidetoshi Murata, Nobutaka Kawahara

    NEUROSURGICAL REVIEW   40 ( 1 )   163 - 169   2017年1月

     詳細を見る

  • CHEMOTHERAPY-INDUCED METABOLIC STRESS IN IDH1 MUTANT GLIOMAS 査読

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

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

  • Myc-Driven Glycolysis Is a Therapeutic Target in Glioblastoma 査読

    Kensuke Tateishi, A. John Iafrate, Quan Ho, William T. Curry, Tracy T. Batchelor, Keith T. Flaherty, Maristela L. Onozato, Nina Lelic, Sudhandra Sundaram, Daniel P. Cahill, Andrew S. Chi, Hiroaki Wakimoto

    CLINICAL CANCER RESEARCH   22 ( 17 )   4452 - 4465   2016年9月

     詳細を見る

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

    DOI: 10.1158/1078-0432.CCR-15-2274

    Web of Science

    PubMed

    J-GLOBAL

    researchmap

  • Recurrent mutations of CD79B and MYD88 are the hallmark of primary central nervous system lymphomas 査読

    T. Nakamura, K. Tateishi, T. Niwa, Y. Matsushita, K. Tamura, M. Kinoshita, K. Tanaka, S. Fukushima, H. Takami, H. Arita, A. Kubo, T. Shuto, M. Ohno, Y. Miyakita, S. Kocialkowski, T. Sasayama, N. Hashimoto, T. Maehara, S. Shibui, T. Ushijima, N. Kawahara, Y. Narita, K. Ichimura

    NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY   42 ( 3 )   279 - 290   2016年4月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/nan.12259

    Web of Science

    PubMed

    researchmap

  • Extreme Vulnerability of IDH1 Mutant Cancers to NAD plus Depletion 査読

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

    CANCER CELL   28 ( 6 )   773 - 784   2015年12月

     詳細を見る

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

    DOI: 10.1016/j.ccell.2015.11.006

    Web of Science

    PubMed

    J-GLOBAL

    researchmap

  • NAD plus SYNTHESIS INHIBITION AS A THERAPEUTIC STRATEGY FOR GLIOBLASTOMA WITH MYC AMPLIFICATION 査読

    Kensuke Tateishi, Nina Lelic, Quan H. Ho, Shinichi Esakl, John A. Iafrate, Daniel P. Cahill, Andrew S. Chi, Hiroaki Wakimoto

    NEURO-ONCOLOGY   16   2014年11月

     詳細を見る

    担当区分:筆頭著者   記述言語:英語  

    DOI: 10.1093/neuonc/nou265.31

    Web of Science

    researchmap

  • Multimodal Approach to Detect Osseous Involvement in Meningioma: Additional Value of F-18-Fluoride PET/CT for Conventional Imaging 査読

    Ukihide Tateishi, Kensuke Tateishi, Ayako Hino-Shishikura, Ikuo Torii, Tomio Inoue, Nobutaka Kawahara

    RADIOLOGY   273 ( 2 )   521 - 528   2014年11月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1148/radiol.14132118

    Web of Science

    PubMed

    researchmap

  • Tumor hypoxia and microscopic diffusion capacity in brain tumors: A comparison of Cu-62-Diacetyl-Bis (N4-Methylthiosemicarbazone) PET/CT and diffusion-weighted MR imaging 査読

    Ayako Hino-Shishikura, Ukihide Tateishi, Hirofumi Shibata, Tomohiro Yoneyama, Toshiaki Nishii, Ikuo Torii, Kensuke Tateishi, Makoto Ohtake, Nobutaka Kawahara, Tomio Inoue

    EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING   41 ( 7 )   1419 - 1427   2014年7月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s00259-014-2714-x

    Web of Science

    PubMed

    researchmap

  • Occipitocervical fusion with relief of odontoid invagination: atlantoaxial distraction method using cylindrical titanium cage for basilar invagination-case report 査読

    Tetsuya Yoshizumi, Hidetoshi Murata, Yuriko Ikenishi, Mitsuru Sato, Hajime Takase, Kensuke Tateishi, Satoshi Nakanowatari, Jun Suenaga, Nobutaka Kawahara

    NEUROSURGICAL REVIEW   37 ( 3 )   519 - 525   2014年7月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s10143-014-0531-0

    Web of Science

    PubMed

    researchmap

  • Targetable Signaling Pathway Mutations Are Associated with Malignant Phenotype in IDH-Mutant Gliomas 査読

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

    CLINICAL CANCER RESEARCH   20 ( 11 )   2898 - 2909   2014年6月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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

    Web of Science

    PubMed

    researchmap

  • Cu-62-Diacetyl-Bis (N-4-Methylthiosemicarbazone) PET in Human Gliomas: Comparative Study with [F-18]Fluorodeoxyglucose and L-Methyl-[C-11]Methionine PET 査読

    K. Tateishi, U. Tateishi, S. Nakanowatari, M. Ohtake, R. Minamimoto, J. Suenaga, H. Murata, K. Kubota, T. Inoue, N. Kawahara

    AMERICAN JOURNAL OF NEURORADIOLOGY   35 ( 2 )   278 - 284   2014年2月

     詳細を見る

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

    DOI: 10.3174/ajnr.A3679

    Web of Science

    PubMed

    researchmap

  • MUTATIONS IN THE TERT PROMOTER ARE HIGHLY RECURRENT AND UPREGULATE TERT EXPRESSION IN GLIOMAS 査読

    Hideyuki Arita, Yoshitaka Narita, Shintaro Fukushima, Kensuke Tateishi, Yuko Matsushita, Akihiko Yoshida, Yasuji Miyakita, Makoto Ohno, V. Peter Collins, Nobutaka Kawahara, Soichiro Shibui, Koichi Ichimura

    NEURO-ONCOLOGY   15   12 - 12   2013年11月

     詳細を見る

    記述言語:英語  

    Web of Science

    researchmap

  • MUTATIONS OF CD79B ARE COMMON EVENT IN PRIMARY CENTRAL NERVOUS SYSTEM B-CELL LYMPHOMA PATIENTS AND ARE ASSOCIATED WITH UNFAVORABLE PROGNOSIS 査読

    Kensuke Tateishi, Yoshitaka Narita, Taishi Nakamura, Daniel Cahill, Nobutaka Kawahara, Koichi Ichimura

    NEURO-ONCOLOGY   15   28 - 28   2013年11月

     詳細を見る

    担当区分:筆頭著者   記述言語:英語  

    Web of Science

    researchmap

  • Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss 査読

    Hideyuki Arita, Yoshitaka Narita, Shintaro Fukushima, Kensuke Tateishi, Yuko Matsushita, Akihiko Yoshida, Yasuji Miyakita, Makoto Ohno, V. Peter Collins, Nobutaka Kawahara, Soichiro Shibui, Koichi Ichimura

    ACTA NEUROPATHOLOGICA   126 ( 2 )   267 - 276   2013年8月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s00401-013-1141-6

    Web of Science

    PubMed

    researchmap

  • F-18-Fluoride PET/CT Allows Detection of Hyperostosis and Osseous Involvement in Meningioma Initial Experience 査読

    Ukihide Tateishi, Kensuke Tateishi, Kazuya Shizukuishi, Ayako Shishikura, Hidetoshi Murata, Tomio Inoue, Nobutaka Kawahara

    CLINICAL NUCLEAR MEDICINE   38 ( 3 )   E125 - E131   2013年3月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1097/RLU.0b013e318279fd79

    Web of Science

    PubMed

    J-GLOBAL

    researchmap

  • Application of 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) PET imaging to predict highly malignant tumor grades and hypoxia-inducible factor-1α expression in patients with glioma. 査読

    Tateishi K, Tateishi U, Sato M, Yamanaka S, Kanno H, Murata H, Inoue T, Kawahara N

    AJNR. American journal of neuroradiology   34 ( 1 )   92 - 99   2013年1月

     詳細を見る

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

    DOI: 10.3174/ajnr.A3159

    Web of Science

    PubMed

    researchmap

  • Combined pre- and retrosigmold approach for petroclival meningiomas with the aid of a rotatable head frame: Peri-auricular three-quarter twist-rotation approach: Technical note 査読

    K Fujitsu, Y Kitsuta, Y Takemoto, S Matsunaga, K Tateishi

    SKULL BASE-AN INTERDISCIPLINARY APPROACH   14 ( 4 )   209 - 215   2004年11月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1055/s-2004-860952

    Web of Science

    PubMed

    researchmap

▼全件表示

MISC

▼全件表示

受賞

  • 横浜脳神経外科研究会 第2回学術総会最優秀指導者賞(山本賞)

    2024年2月  

     詳細を見る

  • 第1回 (2022年度)日本脳腫瘍学会 一般研究助成

    2023年12月   特定非営利活動法人 日本脳腫瘍学会  

     詳細を見る

  • がん研究助成事業(一般課題A)

    2023年1月   公益財団法人がん研究振興財団研究助成金  

    立石健祐

     詳細を見る

  • 横浜脳神経外科研究会 第1回学術総会最優秀指導者賞(山本賞)

    2022年12月  

     詳細を見る

  • 2020年度 横浜市立大学医学会賞

    2021年3月  

    立石健祐

     詳細を見る

  • 公益財団法人上原記念生命科学財団研究助成金(第3部門)

    2019年12月  

    立石 健祐

     詳細を見る

  • 第37回日本脳腫瘍学会Top Scoring Abstract

    2019年12月  

    立石 健祐

     詳細を見る

  • 2019年度RFLJ プロジェクト未来研究助成

    2019年10月   リレー・フォー・ジャパン  

    立石 健祐

     詳細を見る

  • SGHがん研究助成

    2018年10月   公益財団法人 SGH財団  

    立石 健祐

     詳細を見る

  • 第33回基礎医学医療研究助成

    2018年10月   公益財団法人金原一郎記念医学医療振興財団  

    立石 健祐

     詳細を見る

  • 研究助成(腫瘍免疫)

    2018年9月   ブリストル・マイヤーズスクイブ  

    立石 健祐

     詳細を見る

  • 横浜市立大学 学長奨励賞

    2018年3月  

    立石 健祐

     詳細を見る

  • 一般研究助成

    2017年12月   公益財団法人 日本脳神経財団  

    立石 健祐

     詳細を見る

  • 癌研究助成金

    2017年12月   公益財団法人 高松宮妃癌研究基金  

    立石 健祐

     詳細を見る

  • 第38回一般研究助成

    2017年10月   公益財団法人 がん集学的治療研究財団  

    立石 健祐

     詳細を見る

  • 2017年度医学系研究奨励 (癌領域・臨床)

    2017年8月   公益財団法人 武田科学振興財団  

    立石 健祐

     詳細を見る

  • 優秀ポスター賞

    2017年7月   がんと代謝研究会  

    立石 健祐

     詳細を見る

  • 公益財団法人 安田記念医学財団 若手癌研究助成

    2016年12月  

    立石 健祐

     詳細を見る

  • 日本脳腫瘍学会星野賞

    2016年12月  

    立石 健祐

     詳細を見る

  • SNMMI Wagner-Torizuka Fellowship

    2014年4月  

    立石 健祐

     詳細を見る

  • かなえ医学振興財団海外留学助成

    2013年4月  

    立石 健祐

     詳細を見る

  • JNEF President award

    2012年7月  

    立石 健祐

     詳細を見る

▼全件表示

共同研究・競争的資金等の研究課題

  • 難治性中枢神経系腫瘍の病態解明と新規治療法の開発

    2024年8月 - 2027年3月

    横浜市立大学 第6期戦略的研究推進事業 

    立石健祐

      詳細を見る

  • 光制御性麻疹ウイルスを用いたPCNSLに対する治療戦略の創出と検証

    研究課題/領域番号:24K10300  2024年4月 - 2027年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    西 真由子, 田原 舞乃, 立石 健祐

      詳細を見る

    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    researchmap

  • 悪性リンパ腫における細胞内脂質輸送制御破綻の検証

    研究課題/領域番号:24015868  2024年4月 - 2026年3月

    AMED FORCE  革新的先端研究開発支援事業 

    中津史, 立石健祐, 岡田正康, 棗田学

      詳細を見る

  • 第1回(2022年度)特定非営利活動法人日本脳腫瘍学会 一般研究助成

    2023年9月 - 2025年3月

    特定非営利活動法人日本脳腫瘍学会 

    立石健祐

      詳細を見る

  • 悪性膠芽腫の非コード領域由来ネオ抗原探索とその応用

    研究課題/領域番号:23K08574  2023年4月 - 2026年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    木村 弥生, 立石 健祐

      詳細を見る

    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    researchmap

  • 再発・難治性悪性神経膠腫に対する治療用放射性薬剤64Cu-ATSMの有効性を検証する研究開発

    研究課題/領域番号:23809097  2023年 - 2026年

    国立研究開発法人日本医療研究開発機構  臨床研究・治験推進研究事業 

    成田善孝、栗原宏明、吉井幸恵、松本博樹、伊藤公輝、楠本昌彦、柳澤俊介、水澤純基、佐藤秀光、立石健祐

      詳細を見る

  • 悪性リンパ腫における遺伝子異常・免疫微小環境の全体像および臨床的意義の統合的解明

    研究課題/領域番号:23808675  2023年 - 2025年

    日本医療研究開発機構  革新的がん医療実用化研究事業 

    片岡圭亮、福原規子、竹内賢吾、立石健祐

      詳細を見る

  • 中枢神経系原発悪性リンパ腫の全体像の解明と革新的治療法の開発

    2023年 - 2024年

    公益財団法人がん研究振興財団 

    立石健祐

      詳細を見る

  • 64Cu-ATSM局所治療:切除困難な膠芽腫への革新的術中RI治療への挑戦

    研究課題/領域番号:22K07267  2022年4月 - 2027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)

    檜原 扶紀子, 立石 健祐, 松本 博樹, 五十嵐 千佳, 吉井 幸恵, 立花 知子

      詳細を見る

    配分額:3900000円 ( 直接経費:3000000円 、 間接経費:900000円 )

    researchmap

  • IDH変異神経膠腫の特異的DNA修復機構の解明と治療法の創出

    研究課題/領域番号:22K09210  2022年4月 - 2025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)

    立石 健祐

      詳細を見る

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

    researchmap

  • 神経膠芽腫の増殖ストレス緩和システムを標的とする新規がん治療戦略の確立

    研究課題/領域番号:22712833  2022年 - 2024年

    国立研究開発法人日本医療研究開発機構  次世代がん医療加速化研究事業 

    佐々木敦朗、竹内恒、千田俊哉、棗田学、立石健祐

      詳細を見る

  • BRAF変異膠芽腫に対する分子標的治療克服を目指したトランスレーション研究

    2021年9月 - 2022年8月

    横浜総合医学振興財団 令和3年度指定寄附研究助成 

      詳細を見る

  • 小細胞肺癌転移性脳腫瘍における患者由来細胞株樹立による特異的局所浸潤機序の解明

    研究課題/領域番号:21K09132  2021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)

    中村 大志, 立石 健祐, 市村 幸一, 山下 聡

      詳細を見る

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

    まず本研究に向けて自施設より肺小細胞がん(Small cell lung cancer; SCLC)だけでなく非小細胞肺がん(non-Small cell lung cancer, NSCLC)による転移性脳腫瘍症例の腫瘍組織を摘出術時に残余検体を保存した。また研究協力者が確立している脳腫瘍細胞株樹立実験を利用していく手配を進めた。研究分担者である市村幸一博士及び山下聡博士と相談しながら脳転移病変における発現解析・遺伝子解析について準備を行なっている。具体的にはRNA sequencingによって転移性脳腫瘍において中枢神経に近似するような発現変化するpathwayが存在するか検証する予定である。また遺伝子解析によってこれまでに報告されているc-kitの遺伝子異常だけでなく、前述の異常pathwayに関わる遺伝子異常が起こるか検証する予定である。また研究協力者である宇高直子氏と相談して乳がん転移性脳腫瘍で報告されたように脳転移病変においてグリア細胞様の形態変化が境界領域において起こるのか検証することを準備している。特に神経内分泌機能をもつSCLCではNotch pathwayがそれに関与することが報告されており、内分泌機能の局在と腫瘍・正常脳組織の浸潤に関連があるか病理学的に評価する予定である。

    researchmap

  • 難治性中枢神経系悪性腫瘍に対する標的治療法の開発

    2021年4月 - 2023年3月

    横浜市立大学 第5期戦略的研究推進事業 

    立石健祐

      詳細を見る

  • 膠芽腫の標準治療後病勢を診断する血液バイオマーカーの実用化

    2021年 - 2023年

    革新的がん医療実用化研究事業 

      詳細を見る

  • 分子標的アプローチによるグリオーマ関連てんかん制御

    2021年

    公益財団法人木原記念横浜生命科学振興財団LIP. 横浜トライアル助成金 

    立石健祐

      詳細を見る

  • 中枢神経系悪性リンパ腫の腫瘍内多様性と微小環境解析による病態発生の解明と治療開発

    研究課題/領域番号:20H03795  2020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(B)  基盤研究(B)

    永根 基雄, 片岡 圭亮, 市村 幸一, 立石 健祐, 富山 新太

      詳細を見る

    配分額:17810000円 ( 直接経費:13700000円 、 間接経費:4110000円 )

    我々はこれまでに中枢神経系悪性リンパ腫(PCNSL)の包括的遺伝子解析を施行し、全身性のびまん性大型B細胞リンパ腫(DLBCL)と異なる特徴的遺伝子異常パターンを報告した。しかし、PCNSLと全身性DLBCLの病態の類似性および相違性については未だに明らかでない点が多い。そこで、本研究では特にPCNSLにおける遺伝子異常を起点とした腫瘍内の多様性および免疫微小環境の多様性を解明することを目的とした。
    2020年度は、実際のPCNSL臨床検体を用いたシングルセル解析を行うための基盤、すなわち、新規患者での生検術後に細胞の生存率を保ったまま、解析施設に検体移送を行い、組織からDNA/RNAを抽出し、残検体から細胞浮遊液を作製するという標本処理を行うロジスティックスを確立した。条件検討を重ね、シングルセル解析に耐えうる細胞数および生存率が得られる最適条件が得られ、そのロジスティックスに従って収集した検体を用いてフローサイトメトリー解析を行ったところ、腫瘍細胞に加えて、多様な免疫細胞の浸潤を確認することができ、当初の研究計画が十分に遂行可能であることを確認した。本年度は13症例のPCNSL臨床検体を収集し、全症例について、腫瘍組織からのDNA/RNA、末梢血からのDNA抽出を完了している。このうちの9検体については、130種類の表面マーカー解析、mRNAトランスクリプトーム解析、TCR/BCRレパトア解析を同一のシングルセルから取得可能なマルチオミクスシングルセル解析技術を用いたライブラリー調整を行い、次世代シーケンサーを用いて、これらのデータを既に取得済みである。

    researchmap

  • 難治性悪性脳腫瘍に対する日本発放射線薬剤64Cu-ATSMによる新治療法開発―早期承認を目指す第I相拡大コホート試験の実施

    2020年4月

    日本医療研究開発機構 革新的がん医療実用化研究事業(AMED) 

    立石健祐

      詳細を見る

    担当区分:研究分担者 

    researchmap

  • チラブルチニブの中枢神経系原発悪性リンパ腫(PCNSL)に対する効果に関する基礎研究

    2020年

    小野薬品工業共同研究 

    立石健祐

      詳細を見る

    担当区分:研究代表者 

    researchmap

  • IDH変異神経膠腫のDNA高変異に起因する悪性化回避を目指した治療法の開発

    研究課題/領域番号:19K09488  2019年4月 - 2022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)

    立石 健祐

      詳細を見る

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

    神経膠腫(グリオーマ)のアルキル化剤治療後に生じるDNA高変異状態と悪性転化の機序解明を図ること、またDNA高変異状態を呈したグリオーマに対する治療標的の探求を図ることを研究目的に掲げ、独自に樹立した内因性IDH1変異グリオーマ細胞を用いてmismatch repair遺伝子の一つであるMSH6のノックダウンを図った。この細胞とコントロール細胞に対しTMZを長期間にわたり連続投与した。Whole exome sequencing(WES)を用いて変異状態を検討したところ、コントロール細胞と比較してtumor mutational burden が著明に上昇しており、またアルキル化剤投与後に特有の塩基置換パターンが確認されたことからTMZ誘発性にDNA hypermutation phenotype (HM)が発生した可能性が強く示唆された。これらのペア腫瘍細胞モデルはいずれもin vitro培養下で安定して増殖可能となった。これによりDNA高変異状態の及ぼす生物学的特徴を検証可能なIDH1変異グリオーマ細胞株の樹立を世界に先駆けて成功した。その結果、DNA高変異状態への移行プロセスを研究レベルでモニタリング可能となった。これらの細胞に対してドラッグスクリーニングを行い、複数の化合物が候補薬剤として見出されており、現在さらなる解析を進めている。またコントロール細胞とTMZ長期投与後HMを呈した細胞をマウス脳内に定位的に移植し生存分析を行ったが、両群間で予後に有意な差は認められなかった。加えて内因性DNA高変異グリオーマモデル (YMG6R)から細胞株を作成した。経時的に得られた再発検体と細胞株をそれぞれ検討したところ、HMは可逆的な変化を示した。このことからもHM自体がグリオーマの悪性化促進に及ぼす影響は乏しいことが判明した。

    researchmap

  • マルチオミクスを活用した新規プロテオーム解析技術の創出と脳腫瘍バイオマーカー探索

    研究課題/領域番号:19H03774  2019年4月 - 2022年3月

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

    木村 弥生, 立石 健祐

      詳細を見る

    配分額:17550000円 ( 直接経費:13500000円 、 間接経費:4050000円 )

    本研究では、患者病変部より独自に樹立した病態再現性の高い、様々なヒト由来脳腫瘍細胞株(patient-derived cell, PDC)を活用して、血清中に分泌される脳腫瘍関連タンパク質を同定するための新技術の確立と、早期診断、腫瘍型の分類、治療効果予測などに有用な脳腫瘍ための血清バイオマーカーの開発を目指している。そのため、令和元年度は、以下の研究を行った。
    1.細胞のアイデンティティの決定に関与する遺伝子の発現制御にはたらくゲノム領域であるスーパーエンハンサー(SE)を探索するために、様々な遺伝的背景を有する4種類のPDCについて、ヒストンH3の27番目のリジン残基のアセチル化修飾(H3K27ac)抗体を用いたクロマチン免疫沈降(ChIP)と、大量並列シーケンステクノロジーを併用したChIP-seq解析を実施した。さらに、これらSEにより発現制御され、各PDCの表現型を決定する遺伝子座、およびそれらがコードする遺伝子群を選別し、薬剤抵抗性PDCに共通する遺伝子群を抽出した。
    2.質量分析装置を用いた細胞内プロテオーム定量解析を実施し、各PDCにおいて発現変動するタンパク質群を探索した。その結果、薬剤感受性PDC群に対して、薬剤抵抗性PDC群において2倍以上発現変動するタンパク質(p<0.001)を抽出した。この結果に基づき、パスウェイ解析ソフトウェアIPAを用いて関連する下流の生化学的機能を予測した。その結果、薬剤抵抗性PDCでは細胞の運動性が促進される一方で、細胞死が抑制される傾向にあることがわかった。
    3.上記2種類の解析結果から、薬剤抵抗性PDCに特徴的なタンパク質を16種類まで絞り込んだ。この中には癌の悪性化に関与することがわかっている転写因子やリン酸化酵素も含まれていた。

    researchmap

  • IDH1変異が誘導するDNA修復機構変化の解明と合成致死性治療法の開発

    2018年10月 - 2019年9月

    公益財団法人 SGH財団  SGHがん研究財団 

    立石 健祐

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • NF-kB経路を標的としたABCサブタイプ悪性リンパ腫治療法の開発

    2018年10月 - 2019年9月

    公益財団法人金原一郎記念医学医療振興財団  第33回基礎医学医療研究助成金 

    立石 健祐

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • 中枢神経原発悪性リンパ腫に対する遺伝子変異特異的治療法開発に向けたトランスレーショナル研究

    2018年9月 - 2019年8月

    香川大学医学部医学科同窓会讃樹会助成研究 

    立石 健祐

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • DNA高変異状態を呈する再発IDH1変異型神経膠腫に対する免疫制御機構の解明

    2018年9月 - 2019年8月

    ブリストル・マイヤーズスクイブ株式会社 研究助成 (腫瘍免疫) 

    立石 健祐

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • NF-kB経路を標的とした中枢神経原発悪性リンパ腫治療法開発に向けたトランスレーショナル研究

    2018年4月 - 2021年3月

    横浜市立大学学長裁量事業 (かもめプロジェクト) 

    立石 健祐

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • NF-kB活性化を標的とした中枢神経原発悪性リンパ腫治療法の開 発に向けた多施設共同研究

    2018年4月 - 2019年3月

    新潟大学脳研究所 共同研究 

    立石 健祐

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • IDH1変異が及ぼすDNA修復機構変化の解明と合成致死に基づく新規治療法の開発

    2018年3月 - 2019年3月

    公益財団法人 高松宮妃癌研究基金 

    立石 健祐

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • 中枢神経原発悪性リンパ腫に対する糖代謝異常を標的とした治療法の開発

    2018年1月 - 2018年12月

    公益財団法人 日本脳神経財団 

    立石 健祐

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • IDH1変異が及ぼすDNA修復機構変化の解明と合成致死に基づく新規治療法の開発

    2017年12月 - 2018年11月

    公益財団法人がん集学的治療研究財団  第38回一般研究助成 

    立石 健祐

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • IDH1変異が及ぼすDNA修復機構の解明と合成致死に基づく治療法の開発

    2017年8月 - 2018年7月

    一般財団法人横浜総合医学振興財団  推進研究助成 

    立石 健祐

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • IDH1変異の及ぼす代謝ストレス解明と特異的治療法の開発

    2017年8月

    公益財団法人 武田科学振興財団  2017年度医学系研究奨励 (癌領域・臨床) 

    立石 健祐

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • アルキル化剤が誘導する代謝ストレスの解明とIDH1変異神経膠芽腫に対する新規治療戦略

    2017年1月 - 2017年12月

    公益財団法人安田記念医学財団  若手癌研究助成金 

    立石 健祐

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • 代謝ストレスを応用したIDH1変異腫瘍制御法の確立

    2016年9月 - 2017年8月

    横浜市立大学  第1期学術的研究推進事業「若手女性研究者支援プロジェクト」 

    立石 健祐

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • 代謝ストレスを応用したIDH1変異腫瘍制御法の確立

    2016年8月 - 2017年7月

    公益財団法人横浜学術教育振興財団  研究助成 

    立石 健祐

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • IDH1変異神経膠腫に対するNAD+枯渇促進を目的とした修飾療法の開発.

    2016年6月 - 2018年3月

    科学研究費補助金  基盤研究 (C) 

    立石 健祐

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • 中枢神経系悪性リンパ腫に特異的な遺伝子異常の機能解析と新規分子標的治療の開発

    研究課題/領域番号:16H05442  2016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(B)  基盤研究(B)

    永根 基雄, 市村 幸一, 富山 新太, 中村 大志, 立石 健祐

      詳細を見る

    配分額:17290000円 ( 直接経費:13300000円 、 間接経費:3990000円 )

    我々のグループの先行研究で報告した、中枢神経系に原発する悪性リンパ腫(Primary Central Nervous System Lymphoma; PCNSL)において全身性悪性リンパ腫と比較して高頻度の変異が認められた遺伝子のうち、特にPCNSLで高頻度 (全身性悪性リンパ腫で10-30%の頻度であるのに対しPCNSLで100%)であった癌原遺伝子PIM1の変異がPCNSLの腫瘍原性においてどのような役割を果たしているのかを解明し、PCNSLに対する新規分子標的治療法を開発する事を目標として研究を開始した。2016年(初年度)は、まず臨床で特に繰り返し高頻度に認められたPIM1遺伝子変異の機能解析を開始し、それらのうち、一部については活性型変異である可能性が示唆された。2017年度、および2018年度はこれらの活性型変異が疑われたPIM1変異につき更なる機能解析ならびに発がんメカニズムへの関与についての検討を行い、今回検討を行った活性型変異体ではPim-1の局在変化を通じて細胞死抑制がもたらされる可能性が示唆された。
    さらに、中枢神経系に原発した悪性リンパ腫が全身へ転移した場合、逆に全身性のびまん性大細胞性B細胞リンパ腫(DLBCL)が中枢神経系に転移再発した場合、それぞれの病巣における遺伝子変異のプロファイルにどのような変異が生じているかを知ることにより、同じDLBCLである中枢神経系と全身他臓器の腫瘍の発生と進展に関する知見が得られる可能性があり、本研究のコンセプトの一部として当科における標本と、共同研究施設である横浜市立大学での症例の標本を収集し、パネル解析を行っている。

    researchmap

  • IDH1変異神経膠腫に対するNAD+枯渇促進を目的とした修飾療法の開発

    研究課題/領域番号:16K10765  2016年4月 - 2019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)

    立石 健祐, Cahill Daniel

      詳細を見る

    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    我々はこれまでにIDH1変異がNAD+合成代謝機構に影響を及ぼすことを見出してきた。本研究ではNAD+の消費経路に着目し、DNA修復機構の主要タンパク質であるPARPの活性の亢進を通じてNAD+を消費するテモゾロミドとNAD合成阻害剤の併用療法を試みた。その結果IDH1変異神経膠腫において遺伝子変異特異的に合成致死性が得られた。動物レベルにおいても薬剤併用による相乗効果的な抗腫瘍効果が認められた。これらの結果IDH1変異神経膠腫に対する遺伝子変異特異的な治療法の開発に成功した。

    researchmap

  • Wagner-Torizuka Fellowship

    2014年4月 - 2016年3月

    Society of Nuclear medicine and Molecular imaging 

      詳細を見る

    資金種別:競争的資金

    researchmap

  • 神経膠芽腫に対する治療抵抗性メカニズム解明のための遺伝子発現及び分子イメージングの研究.

    2013年4月 - 2014年3月

    第41回かなえ医薬振興財団  海外留学助成 (臨床医学) 

    立石 健祐

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • 内在性神経幹細胞の虚血後急性期応答

    2011年4月 - 2013年3月

    科学研究費補助金 若手研究(B) 

    立石 健祐

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • 内在性神経幹細胞の虚血後急性期応答解析

    研究課題/領域番号:23791612  2011年 - 2012年

    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)

    立石 健祐

      詳細を見る

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

    全脳虚血ラツトモデルの作成並びに内在性神経幹細胞の虚血後急性期応答解析を行った。本研究では海馬CA1領域に焦点を絞り解析を行ったが、有意な神経細胞増殖を示すには至らなかった。成長因子投与量、投与期間などの実験手法によるものか、強い虚血負荷侵襲によるものか、更には現実的治療オブションとしての意義に欠けるものなのか、研究期間内での結論づけは困難であった。 これらの疑問点解明のための研究継続が必要であると考えられた。

    researchmap

  • 大脳基底核、視床における虚血性脳障害後の神経再生誘導.

    2010年4月 - 2011年3月

    財団法人朝日生命成人病研究助成 

    立石 健祐

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • 大脳基底核、視床における虚血性脳障害後の神経再生誘導.

    2009年4月 - 2011年3月

    科学研究費補助金 若手研究(B) 

    立石 健祐

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • 大脳基底核、視床における虚血性脳障害後の神経再生誘導

    研究課題/領域番号:21791373  2009年 - 2010年

    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)

    立石 健祐

      詳細を見る

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

    海馬CA1領域における神経再生誘導を踏まえ、他領域にも同様の誘導が可能か検討を行った。今回線条体、視床をターゲットとし虚血モデル作成を行った。線条体、視床領域の安定的神経細胞死を観察するため海馬CA1と同様の方法で虚血モデル作成を開始した。しかしながら6分間全脳虚血ならびに低血圧負荷での遅発性神経細胞死は安定的な評価に至らなかった。このことから更なる虚血時間の延長および血圧コントロールを再設定し観察を行った。同領域は海馬神経細胞死よりも神経細胞死のための負荷が必要であり、選択的細胞死と個体生存の観点から課題が残った。

    researchmap

  • 大脳基底核・視床における虚血性脳障害後の神経再生誘導

    2008年4月 - 2009年3月

    横浜医学萌芽的研究助成 

    立石 健祐

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

▼全件表示

担当経験のある科目(授業)

  • 生命医科学研究科 生体制御科学IV

    2023年4月 機関名:横浜市立大学

     詳細を見る

  • 理学部 臨床概論・疾病病態学

    2022年9月 機関名:横浜市立大学

     詳細を見る

  • 生命医科学研究科 医科学特論

    2022年4月 機関名:横浜市立大学

     詳細を見る

  • 理学部 課題提案型演習Ac

    2022年4月 機関名:横浜市立大学

     詳細を見る

  • 生命医科学演算BC

    2022年4月 機関名:横浜市立大学

     詳細を見る

  • 理学部 人体の解剖生理学

    2022年4月 機関名:横浜市立大学

     詳細を見る

  • 臨床腫瘍学

    2016年10月 機関名:横浜市立大学

     詳細を見る

  • 脳神経外科学

    機関名:横浜市立大学

     詳細を見る

▼全件表示