2025/03/10 更新

写真a

オオタニ ヨシヒロ
大谷 理浩
Otani Yoshihiro
所属
医歯薬学域 助教
職名
助教
プロフィール

 

 

学位

  • 博士(医学) ( 2018年3月   岡山大学 )

研究キーワード

  • 遺伝子治療

  • 脳脊髄腫瘍

  • 腫瘍免疫

  • ウイルス療法

  • 脳神経外科

  • 頭蓋底腫瘍

  • 免疫療法

研究分野

  • ライフサイエンス / 脳神経外科学

学歴

  • 岡山大学大学院 医歯薬学総合研究科   脳神経外科  

    2014年3月 - 2018年3月

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経歴

  • 岡山大学学術研究院 医歯薬学域 脳神経外科   研究准教授

    2024年5月 - 現在

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  • 岡山大学学術研究院 医歯薬学域 脳神経外科   助教

    2024年4月 - 現在

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  • 岡山大学病院 がんゲノム医療総合推進センター 人材育成部門   副部門長

    2023年10月 - 現在

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  • 岡山大学病院   脳神経外科   研究助教

    2022年4月 - 2024年3月

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  • 岡山大学病院   脳神経外科   医員

    2020年12月 - 2022年3月

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  • University of Texas Health Science Center at Houston   Department of Neurosurgery

    2017年6月 - 2020年11月

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  • 岡山大学大学院 医歯薬学総合研究科   脳神経外科

    2014年4月 - 2017年5月

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  • 岡山市立市民病院   脳神経外科

    2012年4月 - 2014年3月

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  • 岡山大学病院   脳神経外科

    2011年3月 - 2012年3月

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  • 岡山市立市民病院

    2009年4月 - 2011年3月

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▼全件表示

所属学協会

  • 日本小児血液・がん学会

    2025年 - 現在

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  • 日本頭蓋底外科学会

    2024年 - 現在

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  • 日本癌学会

    2022年 - 現在

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  • 日本遺伝子細胞治療学会

    2022年 - 現在

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  • 日本脳神経外科コングレス

    2021年 - 現在

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  • 日本神経内視鏡学会

    2020年 - 現在

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  • 日本内分泌学会

    2020年 - 現在

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  • 日本間脳下垂体腫瘍学会

    2020年 - 現在

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  • Society for Neuro Oncology

    2017年 - 現在

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  • 日本脳卒中の外科学会

    2016年 - 現在

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  • 日本脳腫瘍の外科学会

    2016年 - 現在

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  • 日本脳腫瘍病理学会

    2014年 - 現在

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  • 日本分子脳神経外科学会

    2014年 - 現在

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  • 日本脳腫瘍学会

    2011年 - 現在

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  • 日本脳神経血管内治療学会

    2011年 - 現在

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  • 日本脳神経外科学会

    2010年 - 現在

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▼全件表示

委員歴

  • 日本脳腫瘍学会   脳腫瘍診療ガイドラインSR委員  

    2024年 - 現在   

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  • 日本脳腫瘍学会   U40委員会コアメンバー  

    2023年 - 現在   

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論文

  • Identification of factors related to functional prognoses in craniopharyngiomas. 査読 国際誌

    Tsuyoshi Umeda, Yoshihiro Otani, Kentaro Fujii, Joji Ishida, Shuichiro Hirano, Yasuki Suruga, Naoya Kemmotsu, Ryoji Imoto, Yasuhito Kegoya, Ryo Mizuta, Yohei Inoue, Madoka Hokama, Seiichiro Makihara, Kosei Hasegawa, Kenichi Inagaki, Fumio Otsuka, Takao Yasuhara, Shota Tanaka

    Journal of neuro-oncology   2025年1月

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    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: Craniopharyngiomas are histologically benign tumors, but their proximity to vital neurovascular structures can significantly deteriorate functional prognoses and severely restrict patients' social interaction and activity. We retrospectively identified risk factors related to the functional prognoses in patients with craniopharyngioma treated at our center. METHODS: A retrospective analysis was conducted on 40 patients who underwent surgery for craniopharyngioma and follow-up at our institution between 2003 and 2022. Functional prognoses were evaluated in terms of obesity (body mass index [BMI] ≥ 25 for adults, BMI-Z ≥ 1.65 for children), visual function, endocrine function, and social participation. We investigated whether patient characteristics, tumor size, tumor location, hypothalamic involvement, surgical hypothalamic damage, extent of resection, and recurrence rate correlated with these functional prognostic factors. RESULTS: The median age at diagnosis was 28.0 years, with a median follow-up of 80.5 months. Postoperative obesity was present in 22 patients, and those with postoperative obesity had a significantly higher preoperative BMI or BMI-Z (preoperative BMI for adults: p = 0.074; preoperative BMI-Z for children: p = 0.020) and were significantly correlated with preoperative hypothalamic involvement grade 2 (p = 0.012) and surgical hypothalamic damage grade II (p = 0.0001). Deterioration in social participation was significantly associated with a larger tumor size (p = 0.023) and tumor recurrence (p = 0.0047). CONCLUSIONS: Patients with higher preoperative BMI or BMI-Z and hypothalamic involvement have a greater risk of postoperative obesity, and larger tumor size and recurrence can significantly deteriorate the rate of patients' social participation.

    DOI: 10.1007/s11060-024-04925-7

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  • Myeloid Cells Induce Infiltration and Activation of B Cells and CD4+ T Follicular Helper Cells to Sensitize Brain Metastases to Combination Immunotherapy. 国際誌

    Toshifumi Ninomiya, Naoya Kemmotsu, Fumiaki Mukohara, Masaki Magari, Ai Miyamoto, Youki Ueda, Takamasa Ishino, Joji Nagasaki, Tomohiro Fujiwara, Hidetaka Yamamoto, Hidetoshi Hayashi, Kota Tachibana, Joji Ishida, Yoshihiro Otani, Shota Tanaka, Shinichi Toyooka, Isamu Okamoto, Yosuke Togashi

    Cancer research   2025年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Brain metastasis (BM) is a poor prognostic factor in cancer patients. Despite showing efficacy in many extracranial tumors, immunotherapy with anti-PD-1 monoclonal antibody (mAb) or anti-CTLA-4 mAb appears to be less effective against intracranial tumors. Promisingly, recent clinical studies have reported that combination therapy with anti-PD-1 and anti-CTLA-4 mAbs has a potent antitumor effect on BM, highlighting the need to elucidate the detailed mechanisms controlling the intracranial tumor microenvironment (TME) to develop effective immunotherapeutic strategies. Here, we analyzed the tumor-infiltrating lymphocytes in murine models of BM that responded to anti-CTLA-4 mAb to anti-PD-1 mAb. Activated CD4+ T follicular helper (TFH) cells with high CTLA-4 expression characteristically infiltrated the intracranial TME, which were activated by the combination anti-CTLA-4 and anti-PD-1 treatment. Loss of TFH cells suppressed the additive effect of CTLA-4 blockade on anti-PD-1 mAb. B cell-activating factor belonging to the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) produced by abundant myeloid cells, particularly CD80hiCD206lo pro-inflammatory M1-like macrophages, in the intracranial TME, induced B cell and TFH cell infiltration and activation. Furthermore, the intracranial TME of patients with non-small cell lung cancer featured TFH and B cell infiltration as tertiary lymphoid structures. Together, these findings provide insights into the immune cell crosstalk in the intracranial TME that facilitates an additive anti-tumor effect of CTLA-4 blockade with anti-PD-1 treatment, supporting the potential of a combination immunotherapeutic strategy for BM.

    DOI: 10.1158/0008-5472.CAN-24-2274

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  • Comparative analysis of intraoperative MRI and early postoperative MRI findings in glioma surgery patients. 査読 国際誌

    Yoshihiro Otani, Fumiyo Higaki, Kentaro Fujii, Joji Ishida, Yosuke Shimazu, Shuichiro Hirano, Naoya Kemmotsu, Yasuki Suruga, Ryoji Imoto, Ryo Mizuta, Yasuhito Kegoya, Yohei Inoue, Tsuyoshi Umeda, Madoka Hokama, Takao Yasuhara, Takao Hiraki, Kazuhiko Kurozumi, Tomotsugu Ichikawa, Shota Tanaka, Isao Date

    Journal of neurosurgery   1 - 9   2024年12月

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    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)  

    OBJECTIVE: The extent of resection (EOR) is an important prognostic factor for both low- and high-grade gliomas. Intraoperative MRI (iMRI) has been used to increase the EOR in glioma surgery. While a recent study reported differences between iMRI and early postoperative MRI (epMRI), their specific relationship to postoperative clinical symptoms remains unclear. This study aims to compare the differences between iMRI and epMRI in glioma surgery. METHODS: A retrospective assessment was conducted on 43 patients with glioma who underwent surgery with iMRI and for whom no additional resection was performed after iMRI. The study evaluated the discrepancies in EOR, surgically induced contrast enhancement (SICE), and diffusion-weighted imaging (DWI) abnormality between iMRI and epMRI. EOR was defined as gross-total resection (GTR), near-total resection, subtotal resection (STR), or partial resection (PR) for enhancing lesions, and GTR, STR, or PR for nonenhancing lesions. In addition, the relationship between postoperative neurological findings and iMRI findings was evaluated. RESULTS: Discrepancies in EOR were observed in 2 (11.1%) of 18 cases with nonenhanced lesions and 1 (4.0%) of 25 cases with enhanced lesions. The positive rate of SICE was 25.0% on iMRI and 67.9% on epMRI. Enhancement at the resection cavity was the most frequent pattern in both iMRI and epMRI. The positive rate of enhancement of the resection cavity was strongly increased on epMRI compared with iMRI, potentially mimicking residual tumor. The positive rate of DWI abnormality was 73% on iMRI and 89.2% on epMRI. Among the 10 patients who showed no DWI abnormality on iMRI, 6 exhibited DWI abnormality on epMRI (the late-developing group). Two patients developed new neurological deficits postoperatively, and both showed DWI abnormality on both iMRI and epMRI. No patient in the late-developing group developed postoperative neurological deficits. CONCLUSIONS: Overall, iMRI demonstrated more accurate EOR and less SICE compared with epMRI. Although the positive rate of DWI abnormality was lower on iMRI than on epMRI, the late-developing group showed no postoperative neurological deficits. Therefore, iMRI is more useful in assessing accurate EOR and detecting postoperative neurological deficits than epMRI.

    DOI: 10.3171/2024.7.JNS24784

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  • Machine Learning-based Prognostic Subgrouping of Glioblastoma: A Multi-center Study. 査読 国際誌

    Hamed Akbari, Spyridon Bakas, Chiharu Sako, Anahita Fathi Kazerooni, Javier Villanueva-Meyer, Jose A Garcia, Elizabeth Mamourian, Fang Liu, Quy Cao, Russell T Shinohara, Ujjwal Baid, Alexander Getka, Sarthak Pati, Ashish Singh, Evan Calabrese, Susan Chang, Jeffrey Rudie, Aristeidis Sotiras, Pamela LaMontagne, Daniel S Marcus, Mikhail Milchenko, Arash Nazeri, Carmen Balana, Jaume Capellades, Josep Puig, Chaitra Badve, Jill S Barnholtz-Sloan, Andrew E Sloan, Vachan Vadmal, Kristin Waite, Murat Ak, Rivka R Colen, Yae Won Park, Sung Soo Ahn, Jong Hee Chang, Yoon Seong Choi, Seung-Koo Lee, Gregory S Alexander, Ayesha S Ali, Adam P Dicker, Adam E Flanders, Spencer Liem, Joseph Lombardo, Wenyin Shi, Gaurav Shukla, Brent Griffith, Laila M Poisson, Lisa R Rogers, Aikaterini Kotrotsou, Thomas C Booth, Rajan Jain, Matthew Lee, Abhishek Mahajan, Arnab Chakravarti, Joshua D Palmer, Dominic DiCostanzo, Hassan Fathallah-Shaykh, Santiago Cepeda, Orazio Santo Santonocito, Anna Luisa Di Stefano, Benedikt Wiestler, Elias R Melhem, Graeme F Woodworth, Pallavi Tiwari, Pablo Valdes, Yuji Matsumoto, Yoshihiro Otani, Ryoji Imoto, Mariam Aboian, Shinichiro Koizumi, Kazuhiko Kurozumi, Toru Kawakatsu, Kimberley Alexander, Laveniya Satgunaseelan, Aaron M Rulseh, Stephen J Bagley, Michel Bilello, Zev A Binder, Steven Brem, Arati S Desai, Robert A Lustig, Eileen Maloney, Timothy Prior, Nduka Amankulor, Mac Lean P Nasrallah, Donald M O'Rourke, Suyash Mohan, Christos Davatzikos

    Neuro-oncology   2024年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Glioblastoma is the most aggressive adult primary brain cancer, characterized by significant heterogeneity, posing challenges for patient management, treatment planning, and clinical trial stratification. METHODS: We developed a highly reproducible, personalized prognostication and clinical subgrouping system using machine learning (ML) on routine clinical data, MRI, and molecular measures from 2,838 demographically diverse patients across 22 institutions and 3 continents. Patients were stratified into favorable, intermediate, and poor prognostic subgroups (I, II, III) using Kaplan-Meier analysis (Cox proportional model and hazard ratios [HR]). RESULTS: The ML model stratified patients into distinct prognostic subgroups with HRs between subgroups I-II and I-III of 1.62 (95%CI: 1.43-1.84, p<0.001) and 3.48 (95%CI: 2.94-4.11, p<0.001), respectively. Analysis of imaging features revealed several tumor properties contributing unique prognostic value, supporting the feasibility of a generalizable prognostic classification system in a diverse cohort. CONCLUSIONS: Our ML model demonstrates extensive reproducibility and online accessibility, utilizing routine imaging data rather than complex imaging protocols. This platform offers a unique approach for personalized patient management and clinical trial stratification in glioblastoma.

    DOI: 10.1093/neuonc/noae260

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  • Tectal glioma: clinical, radiological, and pathological features, and the importance of molecular analysis. 査読

    Ryoji Imoto, Yoshihiro Otani, Kentaro Fujii, Joji Ishida, Shuichiro Hirano, Naoya Kemmotsu, Yasuki Suruga, Ryo Mizuta, Yasuhito Kegoya, Yohei Inoue, Tsuyoshi Umeda, Madoka Hokama, Kana Washio, Hiroyuki Yanai, Shota Tanaka, Kaishi Satomi, Koichi Ichimura, Isao Date

    Brain tumor pathology   2024年10月

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    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)  

    Tectal glioma (TG) is a rare lower grade glioma (LrGG) that occurs in the tectum, mainly affecting children. TG shares pathological similarities with pilocytic astrocytoma (PA), but recent genetic analyses have revealed distinct features, such as alterations in KRAS and BRAF. We conducted a retrospective review of cases clinically diagnosed as TG and treated at our institute between January 2005 and March 2023. Six cases were identified and the median age was 30.5 years. Four patients underwent biopsy and two patients underwent tumor resection. Histological diagnoses included three cases of PA, one case of astrocytoma, and two cases of high-grade glioma. The integrated diagnosis, according to the fifth edition of the World Health Organization Classification of Tumours of the central nervous system, included two cases of PA and one case each of diffuse high-grade glioma; diffuse midline glioma H3 K27-altered; glioblastoma; and circumscribed astrocytic glioma. Among the three patients who underwent molecular evaluation, two had KRAS mutation and one had H3-3A K27M mutation. Our results demonstrate the diverse histological and molecular characteristics of TG distinct from other LrGGs. Given the heterogeneous pathological background and the risk of pathological progression in TG, we emphasize the importance of comprehensive diagnosis, including molecular evaluation.

    DOI: 10.1007/s10014-024-00494-9

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  • New Anti-Angiogenic Therapy for Glioblastoma With the Anti-Depressant Sertraline. 査読 国際誌

    Nobushige Tsuboi, Yoshihiro Otani, Atsuhito Uneda, Joji Ishida, Yasuki Suruga, Yuji Matsumoto, Atsushi Fujimura, Kentaro Fujii, Hideki Matsui, Kazuhiko Kurozumi, Isao Date, Hiroyuki Michiue

    Cancer medicine   13 ( 20 )   e70288   2024年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND AND AIMS: Anti-angiogenic therapies prolong patient survival in some malignancies but not glioblastoma. We focused on the relationship between the differentiation of glioma stem like cells (GSCs) into tumor derived endothelial cells (TDECs) and, anti-angiogenic therapy resistance. Especially we aimed to elucidate the mechanisms of drug resistance of TDECs to anti-angiogenic inhibitors and identify novel anti-angiogenic drugs with clinical applications. RESULTS: The mouse GSCs, 005, were differentiated into TDECs under hypoxic conditions, and TDECs had endothelial cell characteristics independent of the vascular endothelial growth factor (VEGF) pathway. In vivo, inhibition of the VEGF pathway had no anti-tumor effect and increased the percentage of TDECs in the 005 mouse model. Novel anti-angiogenic drugs for glioblastoma were evaluated using a tube formation assay and a drug repositioning strategy with existing blood-brain barrier permeable drugs. Drug screening revealed that the antidepressant sertraline inhibited tube formation of TDECs. Sertraline was administered to differentiated TDECs in vitro and 005 mouse models in vivo to evaluate genetic changes by RNA-Seq and tumor regression effects by immunohistochemistry and MRI. Sertraline reduced Lama4 and Ang2 expressions of TDEC, which play an important role in non-VEGF-mediated angiogenesis in tumors. The combination of a VEGF receptor inhibitor axitinib, and sertraline improved survival and reduced tumor growth in the 005 mouse model. CONCLUSION: Collectively, our findings showed the diversity of tumor vascular endothelial cells across VEGF and non-VEGF pathways led to anti-angiogenic resistance. The combination of axitinib and sertraline can represent an effective anti-angiogenic therapy for glioblastoma with safe, low cost, and fast availability.

    DOI: 10.1002/cam4.70288

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  • Cranial and spinal computed tomography (CT) angiography with photon-counting detector CT: comparison with angiographic and operative findings. 査読

    Fumiyo Higaki, Masafumi Hiramatsu, Takao Yasuhara, Susumu Sasada, Yoshihiro Otani, Jun Haruma, Tomohiro Inoue, Yusuke Morimitsu, Noriaki Akagi, Yusuke Matsui, Toshihiro Iguchi, Takao Hiraki

    Japanese journal of radiology   2024年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The clinical imaging features of photon-counting detector (PCD) computed tomography (CT) are mainly known as dose reduction, improvement of spatial resolution, and reduction of artifacts compared to energy-integrating detector CT (EID-CT). The utility of cranial and spinal PCD-CT and PCD-CT angiography (CTA) has been previously reported. CTA is a widely used technique for noninvasive evaluation. Cranial CTA is important in brain tumors, especially glioblastoma; it evaluates whether the tumor is highly vascularized prior to an operation and helps in the diagnosis and assessment of bleeding risk. Spinal CTA has an important role in the estimation of feeders and drainers prior to selective angiography in the cases of spinal epidural arteriovenous fistulas and spinal tumors, especially in hemangioblastoma. So far, EID-CTA is commonly performed in an adjunctive role prior to selective angiography; PCD-CTA with high spatial resolution can be an alternative to selective angiography. In the cases of cerebral aneurysms, flow diverters are important tools for the treatment of intracranial aneurysms, and postoperative evaluation with cone beam CT with angiography using diluted contrast media is performed to evaluate stent adhesion and in-stent thrombosis. If CTA can replace selective angiography, it will be less invasive for the patient. In this review, we present representative cases with PCD-CT. We also show how well the cranial and spinal PCD-CTA approaches the accuracy of angiographic and intraoperative findings.

    DOI: 10.1007/s11604-024-01661-w

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  • Cost of medical care for malignant brain tumors at hospitals in the Japan Clinical Oncology Group brain-tumor study group. 査読 国際誌

    Kazuya Motomura, Keita Sasaki, Narushi Sugii, Shigeru Yamaguchi, Hirotaka Inoue, Akito Oshima, Kazuhiro Tanaka, Yoshihiro Otani, Mitsuaki Shirahata, Ichiyo Shibahara, Motoo Nagane, Shunsuke Tsuzuki, Tomoo Matsutani, Yoshihiro Tsukamoto, Noriyuki Kijima, Kenichiro Asano, Makoto Ohno, Akihiro Inoue, Yohei Mineharu, Keisuke Miyake, Yuta Mitobe, Mitsuto Hanihara, Yu Kawanishi, Shoichi Deguchi, Masato Saito, Ryosuke Matsuda, Kenta Ujifuku, Hideyuki Arita, Yuichi Sato, Shinji Yamashita, Ushio Yonezawa, Junya Yamaguchi, Yasutomo Momii, Takahiro Ogawa, Atsushi Kambe, Shigeo Ohba, Junya Fukai, Norihiko Saito, Masashi Kinoshita, Koichiro Sumi, Ryohei Otani, Takeo Uzuka, Noriyoshi Takebe, Shinichiro Koizumi, Ryuta Saito, Yoshiki Arakawa, Yoshitaka Narita

    Japanese journal of clinical oncology   2024年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: This study aimed to investigate what treatment are selected for malignant brain tumors, particularly glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL), in real-world Japan and the costs involved. METHODS: We conducted a questionnaire survey regarding treatment selections for newly diagnosed GBM and PCNSL treated between July 2021 and June 2022 among 47 institutions in the Japan Clinical Oncology Group-Brain Tumor Study Group. We calculated the total cost and cost per month of the initial therapy for newly diagnosed GBM or PCNSL. RESULTS: The most used regimen (46.8%) for GBM in patients aged ≤74 years was 'Surgery + radiotherapy concomitant with temozolomide'. This regimen's total cost was 7.50 million JPY (Japanese yen). Adding carmustine wafer implantation (used in 15.0%), TTFields (used in 14.1%), and bevacizumab (BEV) (used in 14.5%) to the standard treatment of GBM increased the cost by 1.24 million JPY for initial treatment, and 1.44 and 0.22 million JPY per month, respectively. Regarding PCNSL, 'Surgery (biopsy) + rituximab, methotrexate, procarbazine, and vincristine (R-MPV) therapy' was the most used regimen (42.5%) for patients of all ages. This regimen incurred 1.07 million JPY per month. The three PCNSL regimens based on R-MPV therapy were in ultra-high-cost medical care (exceeding 1 million JPY per month). CONCLUSIONS: Treatment of malignant brain tumors is generally expensive, and cost-ineffective treatments such as BEV are frequently used. We believe that the results of this study can be used to design future economic health studies examining the cost-effectiveness of malignant brain tumors.

    DOI: 10.1093/jjco/hyae116

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  • Overcoming immunotherapy resistance and inducing abscopal effects with boron neutron immunotherapy (B-NIT). 査読 国際誌

    Takuya Fujimoto, Osamu Yamasaki, Noriyuki Kanehira, Hirokazu Matsushita, Yoshinori Sakurai, Naoya Kenmotsu, Ryo Mizuta, Natsuko Kondo, Takushi Takata, Mizuki Kitamatsu, Kazuyo Igawa, Atsushi Fujimura, Yoshihiro Otani, Makoto Shirakawa, Kunitoshi Shigeyasu, Fuminori Teraishi, Yosuke Togashi, Minoru Suzuki, Toshiyoshi Fujiwara, Hiroyuki Michiue

    Cancer science   2024年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Immune checkpoint inhibitors (ICIs) are effective against many advanced malignancies. However, many patients are nonresponders to immunotherapy, and overcoming this resistance to treatment is important. Boron neutron capture therapy (BNCT) is a local chemoradiation therapy with the combination of boron drugs that accumulate selectively in cancer and the neutron irradiation of the cancer site. Here, we report the first boron neutron immunotherapy (B-NIT), combining BNCT and ICI immunotherapy, which was performed on a radioresistant and immunotherapy-resistant advanced-stage B16F10 melanoma mouse model. The BNCT group showed localized tumor suppression, but the anti-PD-1 antibody immunotherapy group did not show tumor suppression. Only the B-NIT group showed strong tumor growth inhibition at both BNCT-treated and shielded distant sites. Intratumoral CD8+ T-cell infiltration and serum high mobility group box 1 (HMGB1) levels were higher in the B-NIT group. Analysis of CD8+ T cells in tumor-infiltrating lymphocytes (TILs) showed that CD62L- CD44+ effector memory T cells and CD69+ early-activated T cells were predominantly increased in the B-NIT group. Administration of CD8-depleting mAb to the B-NIT group completely suppressed the augmented therapeutic effects. This indicated that B-NIT has a potent immune-induced abscopal effect, directly destroying tumors with BNCT, inducing antigen-spreading effects, and protecting normal tissue. B-NIT, immunotherapy combined with BNCT, is the first treatment to overcome immunotherapy resistance in malignant melanoma. In the future, as its therapeutic efficacy is demonstrated not only in melanoma but also in other immunotherapy-resistant malignancies, B-NIT can become a new treatment candidate for advanced-stage cancers.

    DOI: 10.1111/cas.16298

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  • Pneumocephalus with Inverted Papilloma in the Frontoethmoidal Sinus: Case Report and Literature Review. 査読

    Seiichiro Makihara, Yoshihiro Otani, Kensuke Uraguchi, Sawako Ono, Aiko Shimizu, Ryosuke Ikemachi, Yosuke Okazaki, Tomoyuki Ota, Hiroshi Matsumoto, Shotaro Miyamoto, Munechika Tsumura, Seiya Hayashi, Michiari Umakoshi, Koji Hirashita, Mizuo Ando

    Acta medica Okayama   78 ( 4 )   337 - 343   2024年8月

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

    Here, we describe the unique case of a pneumocephalus originating from an inverted papilloma (IP) in the frontoethmoidal sinus. A 71-year-old man with diabetes presented with headaches and altered consciousness. Imaging revealed the pneumocephalus together with bone destruction in the left frontal sinus. He underwent simultaneous endoscopic endonasal and transcranial surgery using an ORBEYE exoscope. Pathological diagnosis of the tumor confirmed IP. Post-surgery, the pneumocephalus was significantly resolved and the squamous cell carcinoma antigen level, which had been elevated, decreased. This case underscores the importance of a multidisciplinary approach and innovative surgical methods in treating complex sinonasal pathologies.

    DOI: 10.18926/AMO/67550

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  • Targeting IGF2-IGF1R Signaling to Reprogram the Tumor Microenvironment for Enhanced Viro-Immunotherapy. 査読 国際誌

    Min Hye Noh, Jin Muk Kang, Alexandra A Miller, Grace Nguyen, Minxin Huang, Ji Seon Shim, Alberto J Bueso-Perez, Sara A Murphy, Kimberly A Rivera-Caraballo, Yoshihiro Otani, Eunju Kim, Seung-Hee Yoo, Yuanqing Yan, Yeshavanth Banasavadi-Siddegowda, Hiroshi Nakashima, E Antonio Chiocca, Balveen Kaur, Zhongming Zhao, Tae Jin Lee, Ji Young Yoo

    Neuro-oncology   2024年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The FDA approval of oncolytic herpes simplex-1 virus (oHSV) therapy underscores its therapeutic promise and safety as a cancer immunotherapy. Despite this promise, the current efficacy of oHSV is significantly limited to a small subset of patients largely due to the resistance in tumor and tumor microenvironment (TME). METHODS: RNA sequencing (RNA-Seq) was used to identify molecular targets of oHSV resistance. Intracranial human and murine glioma or breast cancer brain metastasis (BCBM) tumor-bearing mouse models were employed to elucidate the mechanism underlying oHSV therapy-induced resistance. RESULTS: Transcriptome analysis identified IGF2 as one of the top secreted proteins following oHSV treatment. Moreover, IGF2 expression was significantly upregulated in 10 out of 14 recurrent GBM patients after treatment with oHSV, rQNestin34.5v.2 (71.4%) (p=0.0020) (ClinicalTrials.gov, NCT03152318). Depletion of IGF2 substantially enhanced oHSV-mediated tumor cell killing in vitro and improved survival of mice bearing BCBM tumors in vivo. To mitigate the oHSV-induced IGF2 in the TME, we constructed a novel oHSV, oHSV-D11mt, secreting a modified IGF2R domain 11 (IGF2RD11mt) that acts as IGF2 decoy receptor. Selective blocking of IGF2 by IGF2RD11mt significantly increased cytotoxicity, reduced oHSV-induced neutrophils/PMN-MDSCs infiltration, and reduced secretion of immune suppressive/proangiogenic cytokines, while increased CD8+cytotoxic T lymphocytes (CTLs) infiltration, leading to enhanced survival in GBM or BCBM tumor-bearing mice. CONCLUSION: This is the first study reporting that oHSV-induced secreted IGF2 exerts a critical role in resistance to oHSV therapy, which can be overcome by oHSV-D11mt as a promising therapeutic advance for enhanced viro-immunotherapy.

    DOI: 10.1093/neuonc/noae105

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  • Organized Chronic Subdural Hematoma (OCSDH) Mimicking Meningioma. 査読

    Shuichiro Hirano, Yoshihiro Otani, Kentaro Fujii, Isao Date

    Acta medica Okayama   78 ( 3 )   285 - 290   2024年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Organized chronic subdural hematoma (OCSDH) is a relatively rare condition that forms over a longer period of time compared to chronic subdural hematoma and is sometimes difficult to diagnose with preoperative imaging. We resected an intracranial lesion in a 37-year-old Japanese man; the lesion had been increasing in size for >17 years. The preoperative diagnosis based on imaging findings was meningioma; however, pathological findings revealed OCSDH. Clinicians should be aware that OCSDH mimics other tumors and consider surgical strategies for this disease.

    DOI: 10.18926/AMO/67204

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  • Genomic landscape of glioblastoma without IDH somatic mutation in 42 cases: a comprehensive analysis using RNA sequencing data. 査読 国際誌

    Takanari Okamoto, Ryo Mizuta, Yoshinobu Takahashi, Yoshihiro Otani, Eiichi Sasaki, Yoshitsugu Horio, Hiroaki Kuroda, Hirokazu Matsushita, Isao Date, Naoya Hashimoto, Katsuhiro Masago

    Journal of neuro-oncology   167 ( 3 )   489 - 499   2024年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: Glioblastoma is a malignant brain tumor with a poor prognosis. Genetic mutations associated with this disease are complex are not fully understood and require further elucidation for the development of new treatments. The purpose of this study was to comprehensively analyze genetic mutations in glioblastomas and evaluate the usefulness of RNA sequencing. PATIENTS AND METHODS: We analyzed 42 glioblastoma specimens that were resected in routine clinical practice and found wild-type variants of the IDH1 and IDH2 genes. RNA was extracted from frozen specimens and sequenced, and genetic analyses were performed using the CLC Genomics Workbench. RESULTS: The most common genetic alterations in the 42 glioblastoma specimens were TP53 mutation (28.6%), EGFR splicing variant (16.7%), EGFR mutation (9.5%), and FGFR3 fusion (9.5%). Novel genetic mutations were detected in 8 patients (19%). In 12 cases (28.6%), driver gene mutations were not detected, suggesting an association with PPP1R14A overexpression. Our findings suggest the transcription factors SOX10 and NKX6-2 are potential markers in glioblastoma. CONCLUSION: RNA sequencing is a promising approach for genotyping glioblastomas because it provides comprehensive information on gene expression and is relatively cost-effective.

    DOI: 10.1007/s11060-024-04628-z

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  • Sex-Specific Differences in Patients withIDH1–Wild-Type Grade 4 Glioma in the ReSPOND Consortium 査読

    Sree Gongala, Jose A. Garcia, Nisha Korakavi, Nirav Patil, Hamed Akbari, Andrew Sloan, Jill S. Barnholtz-Sloan, Jessie Sun, Brent Griffith, Laila M. Poisson, Thomas C. Booth, Rajan Jain, Suyash Mohan, MacLean P. Nasralla, Spyridon Bakas, Charit Tippareddy, Josep Puig, Joshua D. Palmer, Wenyin Shi, Rivka R. Colen, Aristeidis Sotiras, Sung Soo Ahn, Yae Won Park, Christos Davatzikos, Chaitra Badve

    American Journal of Neuroradiology   45 ( 9 )   1299 - 1307   2024年4月

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

    DOI: 10.3174/ajnr.a8319

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  • Combined simultaneous endoscopic endonasal and transcranial surgery using high-definition three-dimensional exoscope for malignant tumors of the anterior skull base. 査読 国際誌

    Seiichiro Makihara, Yoshihiro Otani, Kensuke Uraguchi, Aiko Shimizu, Aya Murai, Takaya Higaki, Naoki Akisada, Shohei Fujimoto, Takuma Makino, Joji Ishida, Kentaro Fujii, Takao Yasuhara, Tomoyuki Ota, Hiroshi Matsumoto, Mizuo Ando

    Head & neck   2024年3月

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

    BACKGROUND: Advanced surgical interventions are required to treat malignancies in the anterior skull base (ASB). This study investigates the utility of endoscopic endonasal and transcranial surgery (EETS) using a high-definition three-dimensional exoscope as an alternative to traditional microscopy. METHODS: Six patients with carcinomas of varying histopathologies underwent surgery employing the EETS maneuver, which synchronized three distinct surgical modalities: harvesting of the anterolateral thigh flap, initiation of the transnasal technique, and initiation of the transcranial procedure. RESULTS: The innovative strategy enabled successful tumor resection and skull base reconstruction without postoperative local neoplastic recurrence, cerebrospinal fluid leakage, or neurological deficits. CONCLUSION: The integration of the exoscope and EETS is a novel therapeutic approach for ASB malignancies. This strategy demonstrates the potential of the exoscope in augmenting surgical visualization, enhancing ergonomics, and achieving seamless alignment of multiple surgical interventions. This technique represents a progressive shift in the management of these complex oncological challenges.

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  • Midline invasion predicts poor prognosis in diffuse hemispheric glioma, H3 G34-mutant: an individual participant data review. 査読 国際誌

    Yasuhito Kegoya, Yoshihiro Otani, Yohei Inoue, Ryo Mizuta, Fumiyo Higaki, Kana Washio, Shinichiro Koizumi, Kazuhiko Kurozumi, Joji Ishida, Kentaro Fujii, Norio Yamamoto, Yoshihiro Tanaka, Isao Date

    Journal of neuro-oncology   2024年3月

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    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)  

    INTRODUCTION: Diffuse hemispheric glioma, H3 G34-mutant (DHGs), is a newly categorized tumor in pediatric-type diffuse high-grade gliomas, World Health Organization grade 4, with a poor prognosis. Although prognostic factors associated with genetic abnormalities have been reported, few reports have examined the clinical presentation of DHGs, especially from the viewpoint of imaging findings. In this study, we investigated the relationship between clinical factors, including imaging findings, and prognosis in patients with DHGs. METHODS: We searched Medline through the PubMed database using two search terms: "G34" and "glioma", between 1 April 2012 and 1 July 2023. We retrieved articles that described imaging findings and overall survival (OS), and added one DHG case from our institution. We defined midline invasion (MI) as invasion to the contralateral cerebrum, brainstem, corpus callosum, thalamus, and basal ganglia on magnetic resonance imaging. The primary outcome was 12-month survival, estimated using Kaplan-Meier curves and logistic regression. RESULTS: A total of 96 patients were included in this study. The median age was 22 years, and the proportion of male patients was 48.4%. Lesions were most frequently located in the frontal lobe (52.6%). MI was positive in 39.6% of all patients. The median OS was 14.4 months. Univariate logistic regression analysis revealed that OS was significantly worse in the MI-positive group compared with the MI-negative group. Multivariate logistic regression analysis revealed that MI was an independent prognostic factor in DHGs. CONCLUSIONS: In this study, MI-positive cases had a worse prognosis compared with MI-negative cases. PREVIOUS PRESENTATIONS: No portion of this study has been presented or published previously.

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  • Low frequency of intracranial progression in advanced NSCLC patients treated with cancer immunotherapies. 査読 国際誌

    Naoya Kemmotsu, Kiichiro Ninomiya, Kei Kunimasa, Takamasa Ishino, Joji Nagasaki, Yoshihiro Otani, Hiroyuki Michiue, Eiki Ichihara, Kadoaki Ohashi, Takako Inoue, Motohiro Tamiya, Kazuko Sakai, Youki Ueda, Hiromichi Dansako, Kazuto Nishio, Katsuyuki Kiura, Isao Date, Yosuke Togashi

    International journal of cancer   2023年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Intracranial metastases are common in nonsmall-cell lung cancer (NSCLC) patients, whose prognosis is very poor. In addition, intracranial progression is common during systemic treatments due to the inability to penetrate central nervous system (CNS) barriers, whereas the intracranial effects of cancer immunotherapies remain unclear. We analyzed clinical data to evaluate the frequency of intracranial progression in advanced NSCLC patients treated with PD-1 blockade therapies compared with those treated without PD-1 blockade therapies, and found that the frequency of intracranial progression in advanced NSCLC patients treated with PD-1 blockade therapies was significantly lower than that in patients treated with cytotoxic chemotherapies. In murine models, intracranial rechallenged tumors after initial rejection by PD-1 blockade were suppressed. Accordingly, long-lived memory precursor effector T cells and antigen-specific T cells were increased by PD-1 blockade in intracranial lesions. However, intracranial rechallenged different tumors are not suppressed. Our results indicate that cancer immunotherapies can prevent intracranial progression, maintaining long-term effects intracranially as well as systemically. If intracranial recurrence occurs during the treatment with PD-1 blockade therapies, aggressive local therapies could be worthwhile.

    DOI: 10.1002/ijc.34700

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  • Combination therapy with hydrogen peroxide and irradiation promotes an abscopal effect in mouse models. 査読 国際誌

    Naoya Kemmotsu, Li Zhu, Joji Nagasaki, Yoshihiro Otani, Youki Ueda, Hiromichi Dansako, Yue Fang, Isao Date, Yosuke Togashi

    Cancer science   114 ( 10 )   3848 - 3856   2023年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Hydrogen peroxide (H2 O2 ) induces oxidative stress and cytotoxicity, and can be used for treating cancers in combination with radiotherapy. A product comprising H2 O2 and sodium hyaluronate has been developed as a radiosensitizer. However, the effects of H2 O2 on antitumor immunity remain unclear. To investigate the effects of H2 O2 , especially the abscopal effect when combined with radiotherapy (RT), we implanted murine tumor cells simultaneously in two locations in mouse models: the hind limb and back. H2 O2 mixed with sodium hyaluronate was injected intratumorally, followed by irradiation only at the hind limb lesion. No treatment was administered to the back lesion. The H2 O2 /RT combination significantly reduced tumor growth at the noninjected/nonirradiated site in the back lesion, whereas H2 O2 or RT individually did not reduce tumor growth. Flow cytometric analyses of the tumor-draining lymph nodes in the injected/irradiated areas showed that the number of dendritic cells increased significantly with maturation in the H2 O2 /RT combination group. In addition, analyses of tumor-infiltrating lymphocytes showed that the number of CD8+ (cluster of differentiation 8) T cells and the frequency of IFN-γ+ (interferon gamma) CD8+ T cells were higher in the noninjected/nonirradiated tumors in the H2 O2 /RT group compared to those in the other groups. PD-1 (programmed death receptor 1) blockade further increased the antitumor effect against noninjected/nonirradiated tumors in the H2 O2 /RT group. Intratumoral injection of H2 O2 combined with RT therefore induces an abscopal effect by activating antitumor immunity, which can be further enhanced by PD-1 blockade. These findings promote the development of H2 O2 /RT therapy combined with cancer immunotherapies, even for advanced cancers.

    DOI: 10.1111/cas.15911

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  • 分子標的薬などの化学療法─その他の脊髄鞘腫の治療─ 招待

    大谷理浩、安原隆雄

    脊椎脊髄ジャーナル   36 ( 5 )   365 - 369   2023年6月

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

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  • 外視鏡─脊椎脊髄手術への応用─ 招待

    安原隆雄、佐々田晋、金 恭平、藪野 諭、大谷理浩

    脊椎脊髄ジャーナル   36 ( 4 )   275 - 280   2023年6月

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    担当区分:最終著者   記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Utility of Comprehensive Genomic Profiling for Precise Diagnosis of Pediatric-Type Diffuse High-Grade Glioma. 査読

    Keigo Makino, Yoshihiro Otani, Kentaro Fujii, Joji Ishida, Shuichiro Hirano, Yasuki Suruga, Kana Washio, Kenji Nishida, Hiroyuki Yanai, Shuta Tomida, Daisuke Ennishi, Isao Date

    Acta medica Okayama   77 ( 3 )   323 - 330   2023年6月

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    担当区分:責任著者   記述言語:英語  

    In the current World Health Organization classification of central nervous system tumors, comprehensive genetic and epigenetic analyses are considered essential for precise diagnosis. A 14-year-old male patient who presented with a cerebellar tumor was initially diagnosed with glioblastoma and treated with radiation and concomitant temozolomide chemotherapy after resection. During maintenance temozolomide therapy, a new contrast-enhanced lesion developed in the bottom of the cavity formed by the resection. A second surgery was performed, but the histological findings in specimens from the second surgery were different from those of the first surgery. Although genome-wide DNA methylation profiling was conducted using frozen tissue for a precise diagnosis, the proportion of tumor cells was insufficient and only normal cerebellum was observed. We then performed comprehensive genetic analysis using formalin-fixed paraffin-embedded sections, which revealed MYCN amplification without alteration of IDH1, IDH2, or Histone H3. Finally, the patient was diagnosed with pediatric-type diffuse high-grade glioma, H3-wildtype and IDH-wildtype. In conclusion, comprehensive genetic and epigenetic analysis should be considered in pediatric brain tumor cases.

    DOI: 10.18926/AMO/65502

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  • Utility of genome-wide DNA methylation profiling for pediatric-type diffuse gliomas. 招待 査読

    Yoshihiro Otani, Kaishi Satomi, Yasuki Suruga, Joji Ishida, Kentaro Fujii, Koichi Ichimura, Isao Date

    Brain tumor pathology   40 ( 2 )   56 - 65   2023年4月

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    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)  

    Despite the current progress of treatment, pediatric-type diffuse glioma is one of the most lethal primary malignant tumors in the central nervous system (CNS). Since pediatric-type CNS tumors are rare disease entities and highly heterogeneous, the diagnosis is challenging. An accurate diagnosis is essential for the choice of optimal treatment, which leads to precision oncology and improvement of the patient's outcome. Genome-wide DNA methylation profiling recently emerged as one of the most important tools for the diagnosis of CNS tumors, and the utility of this novel assay has been reported in both pediatric and adult patients. In the current World Health Organization classification published in 2021, several new entities are recognized in pediatric-type diffuse gliomas, some of which require methylation profiling. In this review, we investigated the utility of genome-wide DNA methylation profiling in pediatric-type diffuse glioma, as well as issues in the clinical application of this assay. Furthermore, the combination of genome-wide DNA methylation profiling and other comprehensive genomic assays, which may improve diagnostic accuracy and detection of the actionable target, will be discussed.

    DOI: 10.1007/s10014-023-00457-6

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  • PKR induces TGF-β and limits oncolytic immune therapy. 国際誌

    Bangxing Hong, Upasana Sahu, Matthew P Mullarkey, Evan Hong, Guangsheng Pei, Yuanqing Yan, Yoshihiro Otani, Yeshavanth Banasavadi-Siddegowda, Huihui Fan, Zhongming Zhao, Jianhua Yu, Michael A Caligiuri, Balveen Kaur

    Journal for immunotherapy of cancer   11 ( 2 )   2023年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Mammalian cells have developed multiple intracellular mechanisms to defend against viral infections. These include RNA-activated protein kinase (PKR), cyclic GMP-AMP synthase and stimulation of interferon genes (cGAS-STING) and toll-like receptor-myeloid differentiation primary response 88 (TLR-MyD88). Among these, we identified that PKR presents the most formidable barrier to oncolytic herpes simplex virus (oHSV) replication in vitro. METHODS: To elucidate the impact of PKR on host responses to oncolytic therapy, we generated a novel oncolytic virus (oHSV-shPKR) which disables tumor intrinsic PKR signaling in infected tumor cells. RESULTS: As anticipated, oHSV-shPKR resulted in suppression of innate antiviral immunity and improves virus spread and tumor cell lysis both in vitro and in vivo. Single cell RNA sequencing combined with cell-cell communication analysis uncovered a strong correlation between PKR activation and transforming growth factor beta (TGF-ß) immune suppressive signaling in both human and preclinical models. Using a murine PKR targeting oHSV, we found that in immune-competent mice this virus could rewire the tumor immune microenvironment to increase the activation of antigen presentation and enhance tumor antigen-specific CD8 T cell expansion and activity. Further, a single intratumoral injection of oHSV-shPKR significantly improved the survival of mice bearing orthotopic glioblastoma. To our knowledge, this is the first report to identify dual and opposing roles of PKR wherein PKR activates antivirus innate immunity and induces TGF-ß signaling to inhibit antitumor adaptive immune responses. CONCLUSIONS: Thus, PKR represents the Achilles heel of oHSV therapy, restricting both viral replication and antitumor immunity, and an oncolytic virus that can target this pathway significantly improves response to virotherapy.

    DOI: 10.1136/jitc-2022-006164

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  • A Case of Radiation-Induced Osteosarcoma with RB1 Gene Alteration Treated by Skull Base Surgery and Craniofacial Reconstruction.

    Yuki Matsuda, Yoshihiro Otani, Takao Yasuhara, Mizuo Ando, Takaya Higaki, Takuma Makino, Hiroshi Matsumoto, Tadashi Oyama, Hisakazu Nishimori, Isao Date

    Acta medica Okayama   77 ( 1 )   85 - 90   2023年2月

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    担当区分:責任著者   記述言語:英語  

    A 35-year-old female presented with headache, photophobia and developed sudden loss of vision after having undergone right-side ophthalmectomy and radiochemotherapy for retinoblastoma in infancy. A neoplastic lesion was found in the left middle cranial fossa and was surgically removed. The diagnosis was radiation-induced osteosarcoma with RB1 gene alteration. Although she received chemotherapy for the residual tumor, it progressed 17 months later. Maximal surgical resection with craniofacial reconstruction was required. We utilized two three-dimensional models for surgical planning. She was discharged without neurological deficits other than loss of light perception subsequent to left ophthalmectomy. In cases where retinoblastoma is treated with radiotherapy, long-term follow-up is necessary to monitor for radiation-induced tumor development.

    DOI: 10.18926/AMO/64367

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  • IDH-mutant Astrocytoma Arising in the Brainstem with Symptom Improvement by Foramen Magnum Decompression: A Case Report.

    Takayuki Nagase, Joji Ishida, Susumu Sasada, Tatsuya Sasaki, Yoshihiro Otani, Satoru Yabuno, Kentaro Fujii, Atsuhito Uneda, Takao Yasuhara, Isao Date

    NMC case report journal   10   75 - 80   2023年

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    記述言語:英語  

    Diffusely infiltrative midline gliomas are known to have a poor prognosis. The standard treatment for typical diffuse midline glioma in the pons is local radiotherapy as surgical resection is inappropriate. This case reports a brainstem glioma in which stereotactic biopsy and foramen magnum decompression were concomitantly performed to confirm the diagnosis and improve symptoms. A 23-year-old woman was referred to our department with a chief complaint of headache for six months. Magnetic resonance imaging (MRI) showed diffuse T2 hyperintense swelling of the brainstem with the pons as the main locus. Enlargement of the lateral ventricles was observed because of cerebrospinal fluid obstruction out of the posterior fossa. This was atypical for a diffuse midline glioma in terms of the longstanding slow progression of symptoms and patient age. Stereotactic biopsy was performed for diagnosis, and foramen magnum decompression (FMD) was concomitantly performed to treat the obstructive hydrocephalus. The histological diagnosis was astrocytoma, IDH-mutant. Post-surgery, the patient's symptoms were relieved, and she was discharged on the fifth day after surgery. The hydrocephalus was resolved, and the patient returned to normal life without any symptoms. The tumor size follow-up with MRI demonstrated no marked change for 12 months. Even though diffuse midline glioma is considered to have a poor prognosis, clinicians should contemplate if it is atypical. In atypical cases like the one described herein, surgical treatment may contribute to pathological diagnosis and symptom improvement.

    DOI: 10.2176/jns-nmc.2022-0159

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  • The utility of DNA methylation analysis in elderly patients with pilocytic astrocytoma morphology. 査読 国際誌

    Yasuki Suruga, Kaishi Satomi, Yoshihiro Otani, Kentaro Fujii, Joji Ishida, Atsuhito Uneda, Nobushige Tsuboi, Keigo Makino, Shuichiro Hirano, Naoya Kemmotsu, Ryoji Imoto, Ryo Mizuta, Yusuke Tomita, Takao Yasuhara, Kana Washio, Hiroyuki Yanai, Yuko Matsushita, Yuko Hibiya, Akihiko Yoshida, David Capper, Koichi Ichimura, Isao Date

    Journal of neuro-oncology   160 ( 1 )   179 - 189   2022年9月

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    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: Pilocytic astrocytoma (PA) is a circumscribed low-grade astrocytic glioma, generally considered to be associated with a good prognosis. However, a subset of PA patients shows unfavorable outcomes. In this study, we retrospectively reviewed PA patients and performed further molecular analysis, such as DNA methylation profiling, to identify prognostic factors. METHODS: We analyzed 29 histologically-confirmed PA patients from a single center from 2002 to 2021 and conducted integrated molecular analyses among elderly PA patients since age was an independent prognostic factor for poor outcomes. RESULTS: The median age at diagnosis was 14 years (range 3-82 years) and 4 patients (14%) were elderly (patients ≥ 60 years old). Age over 60 was associated with poor progression-free survival and overall survival. We performed DNA methylation analysis on 2 of the 4 elderly patients. Both cases were histologically diagnosed as PA, but DNA methylation profiling revealed one as high-grade astrocytoma with piloid features (all methylation class scores were below 0.3 in both v11b4 and v12.5) and the other as glioblastoma, IDH-wildtype (score was over 0.5 in both v11b4 and v12.5), using the German Cancer Research Center methylation profiling classifiers and t-SNE analysis. CONCLUSIONS: Elderly patients with PA morphology showed unfavorable outcomes in this cohort. In those patients, further molecular analysis and DNA methylation profiling revealed the possibility of high-grade astrocytic tumors, including newly defined entities.

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  • Potent bystander effect and tumor tropism in suicide gene therapy using stem cells from human exfoliated deciduous teeth. 国際誌

    Makoto Horikawa, Shinichiro Koizumi, Tomoya Oishi, Taisuke Yamamoto, Masashi Ikeno, Masahiko Ito, Tomohiro Yamasaki, Shinji Amano, Tetsuro Sameshima, Yasuyuki Mitani, Yoshihiro Otani, Yuanqing Yan, Tetsuro Suzuki, Hiroki Namba, Kazuhiko Kurozumi

    Cancer gene therapy   30 ( 1 )   85 - 95   2022年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Herpes simplex virus thymidine kinase (HSVTK)/ganciclovir (GCV) suicide gene therapy has a long history of treating malignant gliomas. Recently, stem cells from human exfoliated deciduous teeth (SHED), which are collected from deciduous teeth and have excellent harvestability, ethical aspects, and self-renewal, have been attracting attention mainly in the field of gene therapy. In the present study, we assessed SHED as a novel cellular vehicle for suicide gene therapy in malignant gliomas, as we have previously demonstrated with various cell types. SHED was transduced with the HSVTK gene (SHEDTK). In vitro experiments showed a significant bystander effect between SHEDTK and glioma cell lines in coculture. Furthermore, apoptotic changes caused by caspase 3/7 activation were simultaneously observed in SHEDTK and glioma cells. Mice implanted with a mixture of U87 and SHEDTK and treated with intraperitoneal GCV survived for longer than 100 days. Additionally, tumors in treatment model mice were significantly reduced in size during the treatment period. SHEDTK implanted at the contralateral hemisphere migrated toward the tumor crossing the corpus callosum. These results suggested that SHEDTK-based suicide gene therapy has potent tumor tropism and a bystander-killing effect, potentially offering a new promising therapeutic modality for malignant gliomas.

    DOI: 10.1038/s41417-022-00527-5

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  • Age is a major determinant for poor prognosis in patients with pilocytic astrocytoma: a SEER population study. 査読 国際誌

    Yusuke Tomita, Elizabeth A Hibler, Yasuki Suruga, Joji Ishida, Kentaro Fujii, Kaishi Satomi, Koichi Ichimura, Nobuyuki Hirotsune, Isao Date, Yoshihiro Tanaka, Yoshihiro Otani

    Clinical and experimental medicine   2022年9月

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    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 Pilocytic astrocytomas (PAs) are central nervous system tumors with variable prognosis and poorly understood risk factors. Little evidence exists regarding the effect of age on mortality in PA. Therefore, we conducted a thorough characterization of PA in the US. Methods We queried the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2018 to extract age-adjusted incidence rate (AAIR), age-adjusted mortality rate (AAMR), and survival data on PA. The age group comparisons for each measure varied depending on available SEER data. We compared trends in AAIR and AAMR by two age groups (children, 0-19 years; adults, 20 + years) and by sex. The cumulative incidence function and the Fine-Gray competing risk model were applied by 0-19, 20-39, 40-59, and 60 + years of age groups. Results This study included 5211 incident PA and 462 PA-specific deaths between 2000 and 2018. Trends in AAIRs and AAMRs were almost constant between 2000 and 2018. Average AAIRs had a sharp peak in 1-4 years of age groups, whereas AAMRs had a gradual peak in 80-84 years of age groups. Age groups, tumor location, and race/ethnicity were significantly associated with PA-specific death, whereas only age was associated with other cause of deaths. Conclusions Trends in AAIRs and AAMRs were constant regardless of age. PAs in older populations, especially over 60 years old, have higher incidence of death than those in younger populations.

    DOI: 10.1007/s10238-022-00882-5

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  • Genomic Profiling of a Case of Glioneuronal Tumor with Neuropil-like Islands. 査読

    Nobushige Tsuboi, Joji Ishida, Yosuke Shimazu, Hisanori Edaki, Atsuhito Uneda, Yoshihiro Otani, Kentaro Fujii, Kazuhiko Kurozumi, Daisuke Ennishi, Hiroyuki Yanai, Isao Date

    Acta medica Okayama   76 ( 4 )   473 - 477   2022年8月

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    記述言語:英語  

    Glioneuronal tumor with neuropil-like islands (GNTNI) is a very rare subtype of glioneuronal tumor. We present a case of a 62-year-old man with GNTNI. Two adjacent lesions in the left parietal lobe were removed by left parietal craniotomy. The histological findings were glial cell proliferation and scattered rosettes consisting of synaptophysin-positive and NeuN-positive cells, leading to the diagnosis of GNTNI. Target sequencing revealed a genetic alteration similar to glioblastoma, IDH-wild type, which suggested adjuvant therapies. There are few previous reports on the treatment of this disease, and the patient should be followed carefully.

    DOI: 10.18926/AMO/63907

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  • Response to entrectinib in a malignant glioneuronal tumor with ARHGEF2-NTRK fusion 査読 国際誌

    Kurozumi K, Fujii K, Washio K, Ishida J, Otani Y, Sudo T, Tahara M, Ichimura I, Ennishi D, Date I

    Neuro-oncology advances   Jun 13;4(1):vdac094. ( 1 )   vdac094   2022年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/noajnl/vdac094.

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  • Homogeneity of antibody-drug conjugates critically impacts the therapeutic efficacy in brain tumors. 査読 国際誌

    Yasuaki Anami, Yoshihiro Otani, Wei Xiong, Summer Y Y Ha, Aiko Yamaguchi, Kimberly A Rivera-Caraballo, Ningyan Zhang, Zhiqiang An, Balveen Kaur, Kyoji Tsuchikama

    Cell reports   39 ( 8 )   110839 - 110839   2022年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Glioblastoma multiforme (GBM) is the most aggressive and fatal disease of all brain tumor types. Most therapies rarely provide clinically meaningful outcomes in the treatment of GBM. Although antibody-drug conjugates (ADCs) are promising anticancer drugs, no ADCs have been clinically successful for GBM, primarily because of poor blood-brain barrier (BBB) penetration. Here, we report that ADC homogeneity and payload loading rate are critical parameters contributing to this discrepancy. Although both homogeneous and heterogeneous conjugates exhibit comparable in vitro potency and pharmacokinetic profiles, the former shows enhanced payload delivery to brain tumors. Our homogeneous ADCs provide improved antitumor effects and survival benefits in orthotopic brain tumor models. We also demonstrate that overly drug-loaded species in heterogeneous conjugates are particularly poor at crossing the BBB, leading to deteriorated overall brain tumor targeting. Our findings indicate the importance of homogeneous conjugation with optimal payload loading in generating effective ADCs for intractable brain tumors.

    DOI: 10.1016/j.celrep.2022.110839

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  • Rat and Mouse Brain Tumor Models for Experimental Neuro-Oncology Research. 査読 国際誌

    Upasana Sahu, Rolf F Barth, Yoshihiro Otani, Ryan McCormack, Balveen Kaur

    Journal of neuropathology and experimental neurology   2022年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Rodent brain tumor models have been useful for developing effective therapies for glioblastomas (GBMs). In this review, we first discuss the 3 most commonly used rat brain tumor models, the C6, 9L, and F98 gliomas, which are all induced by repeated injections of nitrosourea to adult rats. The C6 glioma arose in an outbred Wistar rat and its potential to evoke an alloimmune response is a serious limitation. The 9L gliosarcoma arose in a Fischer rat and is strongly immunogenic, which must be taken into consideration when using it for therapy studies. The F98 glioma may be the best of the 3 but it does not fully recapitulate human GBMs because it is weakly immunogenic. Next, we discuss a number of mouse models. The first are human patient-derived xenograft gliomas in immunodeficient mice. These have failed to reproduce the tumor-host interactions and microenvironment of human GBMs. Genetically engineered mouse models recapitulate the molecular alterations of GBMs in an immunocompetent environment and "humanized" mouse models repopulate with human immune cells. While the latter are rarely isogenic, expensive to produce, and challenging to use, they represent an important advance. The advantages and limitations of each of these brain tumor models are discussed. This information will assist investigators in selecting the most appropriate model for the specific focus of their research.

    DOI: 10.1093/jnen/nlac021

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  • HOX and PBX gene dysregulation as a therapeutic target in glioblastoma multiforme. 査読 国際誌

    Einthavy Arunachalam, William Rogers, Guy R Simpson, Carla Möller-Levet, Gemma Bolton, Mohammed Ismael, Christopher Smith, Karl Keegen, Izhar Bagwan, Tim Brend, Susan C Short, Bangxing Hong, Yoshihiro Otani, Balveen Kaur, Nicola Annels, Richard Morgan, Hardev Pandha

    BMC cancer   22 ( 1 )   400 - 400   2022年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Glioblastoma multiforme (GBM) is the most common high-grade malignant brain tumour in adults and arises from the glial cells in the brain. The prognosis of treated GBM remains very poor with 5-year survival rates of 5%, a figure which has not improved over the last few decades. Currently, there is a modest 14-month overall median survival in patients undergoing maximum safe resection plus adjuvant chemoradiotherapy. HOX gene dysregulation is now a widely recognised feature of many malignancies. METHODS: In this study we have focused on HOX gene dysregulation in GBM as a potential therapeutic target in a disease with high unmet need. RESULTS: We show significant dysregulation of these developmentally crucial genes and specifically that HOX genes A9, A10, C4 and D9 are strong candidates for biomarkers and treatment targets for GBM and GBM cancer stem cells. We evaluated a next generation therapeutic peptide, HTL-001, capable of targeting HOX gene over-expression in GBM by disrupting the interaction between HOX proteins and their co-factor, PBX. HTL-001 induced both caspase-dependent and -independent apoptosis in GBM cell lines. CONCLUSION: In vivo biodistribution studies confirmed that the peptide was able to cross the blood brain barrier. Systemic delivery of HTL-001 resulted in improved control of subcutaneous murine and human xenograft tumours and improved survival in a murine orthotopic model.

    DOI: 10.1186/s12885-022-09466-8

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  • Implications of immune cells in oncolytic herpes simplex virotherapy for glioma. 招待 査読

    Yoshihiro Otani, Ji Young Yoo, Toshihiko Shimizu, Kazuhiko Kurozumi, Isao Date, Balveen Kaur

    Brain tumor pathology   2022年4月

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    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)  

    Despite current progress in treatment, glioblastoma (GBM) remains a lethal primary malignant tumor of the central nervous system. Although immunotherapy has recently achieved remarkable survival effectiveness in multiple malignancies, none of the immune checkpoint inhibitors (ICIs) for GBM have shown anti-tumor efficacy in clinical trials. GBM has a characteristic immunosuppressive tumor microenvironment (TME) that results in the failure of ICIs. Oncolytic herpes simplex virotherapy (oHSV) is the most advanced United States Food and Drug Administration-approved virotherapy for advanced metastatic melanoma patients. Recently, another oHSV, Delytact®, was granted conditional approval in Japan against GBM, highlighting it as a promising treatment. Since oncolytic virotherapy can recruit abundant immune cells and modify the immune TME, oncolytic virotherapy for immunologically cold GBM will be an attractive therapeutic option for GBM. However, as these immune cells have roles in both anti-tumor and anti-viral immunity, fine-tuning of the TME using oncolytic virotherapy will be important to maximize the therapeutic efficacy. In this review, we discuss the current knowledge of oHSV, with a focus on the role of immune cells as friend or foe in oncolytic virotherapy.

    DOI: 10.1007/s10014-022-00431-8

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  • NOTCH induced MDSC recruitment after oHSV virotherapy in CNS cancer models modulates anti-tumor immunotherapy. 査読 国際誌

    Yoshihiro Otani, Ji Young Yoo, Cole T Lewis, Samantha Chao, Jessica Swanner, Toshihiko Shimizu, Jin Muk Kang, Sara A Murphy, Kimberly Rivera-Caraballo, Bangxing Hong, Joseph C Glorioso, Hiroshi Nakashima, Sean E Lawler, Yeshavanthh Banasavadi-Siddegowda, John D Heiss, Yuanqing Yan, Guangsheng Pei, Michael A Caliguri, Zhongming Zhao, E Antonio Chiocca, Jianhua Yu, Balveen Kaur

    Clinical cancer research : an official journal of the American Association for Cancer Research   2022年1月

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    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: Oncolytic herpes simplex virus-1 (oHSV) infection of brain tumors activates NOTCH, however the consequences of NOTCH on oHSV induced immunotherapy is largely unknown. Here we evaluated the impact of NOTCH blockade on virus induced immunotherapy. EXPERIMENTAL DESIGN: RNA sequencing (RNA-seq), TCGA data analysis, flow cytometry, Luminex- and ELISA-based assays, brain tumor animal models, and serum analysis of recurrent glioblastoma (GBM) patients treated with oHSV was used to evaluate the effect of NOTCH signaling on virus induced immunotherapy. RESULTS: TCGA data analysis of patients with grade IV glioma and oHSV treatment of experimental brain tumors in mice showed that NOTCH signaling significantly correlated with a higher myeloid cell infiltration. Immunofluorescence staining and RNA-seq uncovered a significant induction of Jag1 (NOTCH ligand) expression in infiltrating myeloid cells upon oHSV infection. Jag1 expressing macrophages further spread NOTCH activation in the tumor microenvironment (TME). NOTCH activated macrophages increased the secretion of CCL2 which further amplified myeloid derived suppressor cells (MDSCs). CCL2 and IL-10 induction was also observed in serum of recurrent GBM patients treated with oHSV (rQnestin34.5) (NCT03152318). Pharmacologic blockade of NOTCH signaling rescued the oHSV induced immunosuppressive TME and activated a CD8 dependent anti-tumor memory response, resulting in a therapeutic benefit. CONCLUSIONS: NOTCH induced immunosuppressive myeloid cell recruitment limited anti-tumor immunity. Translationally, these findings support the use of NOTCH inhibition in conjunction with oHSV therapy.

    DOI: 10.1158/1078-0432.CCR-21-2347

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  • Targeting protein arginine methyltransferase 5 sensitizes glioblastoma to trametinib.

    Banasavadi-Siddegowda YK, Namagiri S, Otani Y, Sur H, Rivas S, Bryant JP, Shellbourn A, Rock M, Chowdhury A, Lewis CT, Shimizu T, Walbridge S, Kumarasamy S, Shah AH, Lee TJ, Maric D, Yan Y, Ji Young Yoo, Kumbar SG, John Heiss, Kaur B

    Neuro-oncology advances   2022年1月

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    掲載種別:研究論文(学術雑誌)  

    <h4>Background</h4>The prognosis of glioblastoma (GBM) remains dismal because therapeutic approaches have limited effectiveness. A new targeted treatment using MEK inhibitors, including trametinib, has been proposed to improve GBM therapy. Trametinib had a promising preclinical effect against several cancers, but its adaptive treatment resistance precluded its clinical translation in GBM. Previously, we have demonstrated that protein arginine methyltransferase 5 (PRMT5) is upregulated in GBM and its inhibition promotes apoptosis and senescence in differentiated and stem-like tumor cells, respectively. We tested whether inhibition of PRMT5 can enhance the efficacy of trametinib against GBM.<h4>Methods</h4>Patient-derived primary GBM neurospheres (GBMNS) with transient PRMT5 knockdown were treated with trametinib and cell viability, proliferation, cell cycle progression, ELISA, and western blot were analyzed. In vivo, NSG mice were intracranially implanted with PRMT5-intact and -depleted GBMNS, treated with trametinib by daily oral gavage, and observed for tumor progression and mice survival rate.<h4>Results</h4>PRMT5 depletion enhanced trametinib-induced cytotoxicity in GBMNS. PRMT5 knockdown significantly decreased trametinib-induced AKT and ERBB3 escape pathways. However, ERBB3 inhibition alone failed to block trametinib-induced AKT activity suggesting that the enhanced antitumor effect imparted by PRMT5 knockdown in trametinib-treated GBMNS resulted from AKT inhibition and not ERBB3 inhibition. In orthotopic murine xenograft models, PRMT5-depletion extended the survival of tumor-bearing mice, and combination with trametinib further increased survival.<h4>Conclusion</h4>Combined PRMT5/MEK inhibition synergistically inhibited GBM in animal models and is a promising strategy for GBM therapy.

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  • A Case of Relapsed Primary Central Nervous System Lymphoma Treated with CD19-directed Chimeric Antigen Receptor T Cell Therapy. 査読

    Ryo Mizuta, Yoshihiro Otani, Kentaro Fujii, Atsuhito Uneda, Joji Ishida, Takehiro Tanaka, Shuntaro Ikegawa, Nobuharu Fujii, Yoshinobu Maeda, Isao Date

    NMC case report journal   9   275 - 280   2022年

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    記述言語:英語  

    Although high-dose methotrexate (HD-MTX) is the standard therapy for primary central nervous system lymphoma (PCNSL), the prognosis remains poor. Because 90% of PCNSL is diffuse large B-cell lymphoma (DLBCL), chimeric antigen receptor (CAR)-T cell therapy is expected to be beneficial. However, there are limited reports on CAR-T cell therapy for PCNSL because of the concern of neurotoxicity. Here, we report a case of relapsed PCNSL treated with anti-CD19 CAR-T cell therapy. A 40-year-old woman presenting with visual disturbance in her left eye was initially diagnosed with bilateral uveitis. Her histological diagnosis was DLBCL, and she was positive for CD19. Although she received chemotherapy including HD-MTX, the tumor relapsed in her right occipital lobe. She underwent remission induction therapy and then anti-CD19 CAR-T cell therapy. Cytokine release syndrome (CRS) grade 2 occurred, but there were no complications of CAR-T cell-related encephalopathy syndrome (CRES). She has achieved complete response for more than 1 year. Anti-CD19 CAR-T cell therapy is a revolutionary immunotherapy for treating relapsed or refractory (R/R) B lineage malignancies. Although there are concerns regarding CRS and CRES in central nervous system lymphoma, the use of anti-CD19 CAR-T cells to treat R/R PCNSL is safe and feasible.

    DOI: 10.2176/jns-nmc.2022-0134

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  • Combination of Ad-SGE-REIC and bevacizumab modulates glioma progression by suppressing tumor invasion and angiogenesis. 査読 国際誌

    Yasuhiko Hattori, Kazuhiko Kurozumi, Yoshihiro Otani, Atsuhito Uneda, Nobushige Tsuboi, Keigo Makino, Shuichiro Hirano, Kentaro Fujii, Yusuke Tomita, Tetsuo Oka, Yuji Matsumoto, Yosuke Shimazu, Hiroyuki Michiue, Hiromi Kumon, Isao Date

    PloS one   17 ( 8 )   e0273242   2022年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is a tumor suppressor and its overexpression has been shown to exert anti-tumor effects as a therapeutic target gene in many human cancers. Recently, we demonstrated the anti-glioma effects of an adenoviral vector carrying REIC/Dkk-3 with the super gene expression system (Ad-SGE-REIC). Anti-vascular endothelial growth factor treatments such as bevacizumab have demonstrated convincing therapeutic advantage in patients with glioblastoma. However, bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma. In this study, we examined the effects of Ad-SGE-REIC on glioma treated with bevacizumab. Ad-SGE-REIC treatment resulted in a significant reduction in the number of invasion cells treated with bevacizumab. Western blot analyses revealed the increased expression of several endoplasmic reticulum stress markers in cells treated with both bevacizumab and Ad-SGE-REIC, as well as decreased β-catenin protein levels. In malignant glioma mouse models, overall survival was extended in the combination therapy group. These results suggest that the combination therapy of Ad-SGE-REIC and bevacizumab exerts anti-glioma effects by suppressing the angiogenesis and invasion of tumors. Combined Ad-SGE-REIC and bevacizumab might be a promising strategy for the treatment of malignant glioma.

    DOI: 10.1371/journal.pone.0273242

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  • Antibody-drug conjugates with dual payloads for combating breast tumor heterogeneity and drug resistance. 査読

    Yoshihiro Otani

    Nature communications   12 ( 1 )   2021年6月

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

    <title>Abstract</title>Breast tumors generally consist of a diverse population of cells with varying gene expression profiles. Breast tumor heterogeneity is a major factor contributing to drug resistance, recurrence, and metastasis after chemotherapy. Antibody-drug conjugates (ADCs) are emerging chemotherapeutic agents with striking clinical success, including T-DM1 for HER2-positive breast cancer. However, these ADCs often suffer from issues associated with intratumor heterogeneity. Here, we show that homogeneous ADCs containing two distinct payloads are a promising drug class for addressing this clinical challenge. Our conjugates show HER2-specific cell killing potency, desirable pharmacokinetic profiles, minimal inflammatory response, and marginal toxicity at therapeutic doses. Notably, a dual-drug ADC exerts greater treatment effect and survival benefit than does co-administration of two single-drug variants in xenograft mouse models representing intratumor HER2 heterogeneity and elevated drug resistance. Our findings highlight the therapeutic potential of the dual-drug ADC format for treating refractory breast cancer and perhaps other cancers.

    DOI: 10.1038/s41467-021-23793-7

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    その他リンク: http://www.nature.com/articles/s41467-021-23793-7

  • [Gene Therapy and Viral Therapy for Malignant Glioma].

    Yoshihiro Otani

    No shinkei geka. Neurological surgery   2021年5月

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    掲載種別:研究論文(学術雑誌)  

    Malignant gliomas have a poor prognosis despite advances in surgical procedures, radiotherapy, and the emergence of new treatments have improved outcomes. One of these new treatments is gene therapy, which has been developed as a new therapeutic strategy. Recently, new methods and approaches have been developed. Gene therapy involves the introduction of genes or cells into a glioma, or the human body, to treat gliomas; various genes such as cancer-suppressing genes, immunomodulation cytokine-related genes, and suicide genes are used in this treatment. Viral therapy is a treatment that oncolytic viral replicates in tumor cells to destroy tumors. Various viral genes can also be used as therapeutic genes. Currently, the most well-studied and accumulated viruses are adenoviruses and HSV-1. Various clinical trials have been conducted using gene therapy and viral therapy, some of which are scheduled to be approved in the near future. Gene therapy and viral therapy have dramatically improved and have developed progressively since their first clinical use.

    DOI: 10.11477/mf.1436204434

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  • MicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD44. 査読

    Yoshihiro Otani

    Scientific reports   11 ( 1 )   2021年4月

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

    <title>Abstract</title>Tumor suppressive microRNAs (miRNAs) are increasingly implicated in the development of anti-tumor therapy by reprogramming gene network that are aberrantly regulated in cancer cells. This study aimed to determine the therapeutic potential of putative tumor suppressive miRNA, miR-138, against glioblastoma (GBM). Whole transcriptome and miRNA expression profiling analyses on human GBM patient tissues identified miR-138 as one of the significantly downregulated miRNAs with an inverse correlation with CD44 expression. Transient overexpression of miR-138 in GBM cells inhibited cell proliferation, cell cycle, migration, and wound healing capability. We unveiled that miR-138 negatively regulates the expression of CD44 by directly binding to the 3′ UTR of CD44. CD44 inhibition by miR-138 resulted in an inhibition of glioblastoma cell proliferation in vitro through cell cycle arrest as evidenced by a significant induction of p27 and its translocation into nucleus. Ectopic expression of miR-138 also increased survival rates in mice that had an intracranial xenograft tumor derived from human patient-derived primary GBM cells. In conclusion, we demonstrated a therapeutic potential of tumor suppressive miR-138 through direct downregulation of CD44 for the treatment of primary GBM.

    DOI: 10.1038/s41598-021-88615-8

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    その他リンク: http://www.nature.com/articles/s41598-021-88615-8

  • Differentiated glioblastoma cells accelerate tumor progression by shaping the tumor microenvironment via CCN1-mediated macrophage infiltration. 査読 国際誌

    Atsuhito Uneda, Kazuhiko Kurozumi, Atsushi Fujimura, Kentaro Fujii, Joji Ishida, Yosuke Shimazu, Yoshihiro Otani, Yusuke Tomita, Yasuhiko Hattori, Yuji Matsumoto, Nobushige Tsuboi, Keigo Makino, Shuichiro Hirano, Atsunori Kamiya, Isao Date

    Acta neuropathologica communications   9 ( 1 )   29 - 29   2021年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Glioblastoma (GBM) is the most lethal primary brain tumor characterized by significant cellular heterogeneity, namely tumor cells, including GBM stem-like cells (GSCs) and differentiated GBM cells (DGCs), and non-tumor cells such as endothelial cells, vascular pericytes, macrophages, and other types of immune cells. GSCs are essential to drive tumor progression, whereas the biological roles of DGCs are largely unknown. In this study, we focused on the roles of DGCs in the tumor microenvironment. To this end, we extracted DGC-specific signature genes from transcriptomic profiles of matched pairs of in vitro GSC and DGC models. By evaluating the DGC signature using single cell data, we confirmed the presence of cell subpopulations emulated by in vitro culture models within a primary tumor. The DGC signature was correlated with the mesenchymal subtype and a poor prognosis in large GBM cohorts such as The Cancer Genome Atlas and Ivy Glioblastoma Atlas Project. In silico signaling pathway analysis suggested a role of DGCs in macrophage infiltration. Consistent with in silico findings, in vitro DGC models promoted macrophage migration. In vivo, coimplantation of DGCs and GSCs reduced the survival of tumor xenograft-bearing mice and increased macrophage infiltration into tumor tissue compared with transplantation of GSCs alone. DGCs exhibited a significant increase in YAP/TAZ/TEAD activity compared with GSCs. CCN1, a transcriptional target of YAP/TAZ, was selected from the DGC signature as a candidate secreted protein involved in macrophage recruitment. In fact, CCN1 was secreted abundantly from DGCs, but not GSCs. DGCs promoted macrophage migration in vitro and macrophage infiltration into tumor tissue in vivo through secretion of CCN1. Collectively, these results demonstrate that DGCs contribute to GSC-dependent tumor progression by shaping a mesenchymal microenvironment via CCN1-mediated macrophage infiltration. This study provides new insight into the complex GBM microenvironment consisting of heterogeneous cells.

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  • Inhibiting protein phosphatase 2A increases the antitumor effect of protein arginine methyltransferase 5 inhibition in models of glioblastoma. 査読 国際誌

    Yoshihiro Otani, Hannah Sur, Guruprasad Rachaiah, Sriya Namagiri, Ashis Chowdhury, Cole T Lewis, Toshihiko Shimizu, Arunakumar Gangaplara, Xiang Wang, Amélie Vézina, Dragan Maric, Sadhana Jackson, Yuanqing Yan, Zhuang Zhengping, Abhik Ray-Chaudhury, Sachin Kumar, Leomar Y Ballester, Prashant Chittiboina, Ji Young Yoo, John Heiss, Balveen Kaur, Yeshavanth Kumar Banasavadi-Siddegowda

    Neuro-oncology   2021年2月

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

    BACKGROUND: Despite multi-model therapy of maximal surgical resection, radiation, chemotherapy, and tumor treating fields, the median survival of Glioblastoma (GBM) patients is less than 15 months. Protein Arginine Methyltransferase 5 (PRMT5) catalyzes the symmetric di-methylation of arginine residues and is overexpressed in GBM. Inhibition of PRMT5 causes senescence in stem-like GBM tumor cells. LB100, a first-in-class small molecular inhibitor of Protein Phosphatase 2A (PP2A) can sensitize therapy-resistant tumor cells. Here, we tested the anti-GBM effect of concurrent PRMT5 and PP2A inhibition. METHODS: Patient-derived primary GBM neurospheres (GBMNS), transfected with PRMT5 target-specific siRNA were treated with LB100 and subjected to in vitro assays including PP2A activity and western blot. The intracranial mouse xenograft model was used to test the in vivo antitumor efficacy of combination treatment. RESULTS: We found that PRMT5-depletion increased PP2A activity in GBMNS. LB100 treatment significantly reduced the viability of PRMT5-depleted GBMNS compared to PRMT5 intact GBMNS. LB100 enhanced G1 cell cycle arrest induced by PRMT5-depletion. Combination therapy also increased the expression of phospho-MLKL. Necrostatin-1 rescued PRMT5-depleted cells from the cytotoxic effects of LB100, indicating that necroptosis caused the enhanced cytotoxicity of combination therapy. In the in vivo mouse tumor xenograft model, LB100 treatment combined with transient depletion of PRMT5 significantly decreased tumor size and prolonged survival, while LB100 treatment alone had no survival benefit. CONCLUSION: Overall, combined PRMT5 and PP2A inhibition had significantly greater antitumor effects than PRMT5 inhibition alone.

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  • Spinal Cord Diffuse Midline Glioma, H3K27M- mutant Effectively Treated with Bevacizumab: A Report of Two Cases. 査読

    Satoru Yabuno, Satoshi Kawauchi, Michiari Umakoshi, Atsuhito Uneda, Kentaro Fujii, Joji Ishida, Yoshihiro Otani, Yasuhiko Hattori, Nobushige Tsuboi, Shohei Kohno, Mai Noujima, Tomohiro Toji, Hiroyuki Yanai, Takao Yasuhara, Isao Date

    NMC case report journal   8 ( 1 )   505 - 511   2021年

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    記述言語:英語  

    "Diffuse midline glioma (DMG), H3K27M-mutant" was newly classified in the revised World Health Organization (WHO) 2016 classification of central nervous system tumors. Spinal cord DMG, H3K27M-mutant is relatively rare, with poor prognosis, and there are no effective treatment protocols. In this study, we report two cases of spinal cord DMG, H3K27M-mutant treated with bevacizumab. The two patients were women in their 40s who initially presented with sensory impairment. MRI showed spinal intramedullary tumors, and each patient underwent laminectomy/laminoplasty and biopsy of the tumors. Histological examination initially suggested low-grade astrocytoma in case 1 and glioblastoma in case 2. Upon further immunohistochemical examination in case 1 and molecular examination in case 2, however, both cases were diagnosed as DMG, H3K27M-mutant. Case 1 was treated with radiation therapy and temozolomide (TMZ) chemotherapy, which induced a transient improvement of symptoms; 3 months after surgery, however, the patient's symptoms rapidly deteriorated. MRI showed tumor enlargement with edema to the medulla. Triweekly administration of bevacizumab improved her symptoms for the following 12 months. Case 2 was treated with bevacizumab from the beginning because of acute deterioration of breathing. After bevacizumab administration, both cases showed tumor regression on MRI and drastic improvement of symptoms within a few days. Although spinal cord DMG, H3K27M-mutant has an aggressive clinical course and poor prognosis, bevacizumab administration may offer the significant clinical benefit of alleviating edema, which improves patient's capacity for activities of daily life.

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  • Glioma and temozolomide induced alterations in gut microbiome. 査読 国際誌

    Anthony Patrizz, Antonio Dono, Soheil Zorofchian, Gabriella Hines, Takeshi Takayasu, Nuruddin Husein, Yoshihiro Otani, Octavio Arevalo, H Alex Choi, Jude Savarraj, Nitin Tandon, Bhanu P Ganesh, Balveen Kaur, Louise D McCullough, Leomar Y Ballester, Yoshua Esquenazi

    Scientific reports   10 ( 1 )   21002 - 21002   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The gut microbiome is fundamental in neurogenesis processes. Alterations in microbial constituents promote inflammation and immunosuppression. Recently, in immune-oncology, specific microbial taxa have been described to enhance the effects of therapeutic modalities. However, the effects of microbial dysbiosis on glioma are still unknown. The aim of this study was to explore the effects of glioma development and Temozolomide (TMZ) on fecal microbiome in mice and humans. C57BL/6 mice were implanted with GL261/Sham and given TMZ/Saline. Fecal samples were collected longitudinally and analyzed by 16S rRNA sequencing. Fecal samples were collected from healthy controls as well as glioma patients at diagnosis, before and after chemoradiation. Compared to healthy controls, mice and glioma patients demonstrated significant differences in beta diversity, Firmicutes/Bacteroides (F/B) ratio, and increase of Verrucomicrobia phylum and Akkermansia genus. These changes were not observed following TMZ in mice. TMZ treatment in the non-tumor bearing mouse-model diminished the F/B ratio, increase Muribaculaceae family and decrease Ruminococcaceae family. Nevertheless, there were no changes in Verrucomicrobia/Akkermansia. Glioma development leads to gut dysbiosis in a mouse-model, which was not observed in the setting of TMZ. These findings seem translational to humans and warrant further study.

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  • Oncolytic HSV-Infected Glioma Cells Activate NOTCH in Adjacent Tumor Cells Sensitizing Tumors to Gamma Secretase Inhibition. 査読 国際誌

    Yoshihiro Otani, Ji Young Yoo, Samantha Chao, Joseph Liu, Alena Cristina Jaime-Ramirez, Tae Jin Lee, Brian Hurwitz, Yuanqing Yan, Hongsheng Dai, Joseph C Glorioso, Michael A Caligiuri, Jianhua Yu, Balveen Kaur

    Clinical cancer research : an official journal of the American Association for Cancer Research   26 ( 10 )   2381 - 2392   2020年5月

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

    PURPOSE: To examine the effect of oncolytic herpes simplex virus (oHSV) on NOTCH signaling in central nervous system tumors. EXPERIMENTAL DESIGN: Bioluminescence imaging, reverse phase protein array proteomics, fluorescence microscopy, reporter assays, and molecular biology approaches were used to evaluate NOTCH signaling. Orthotopic glioma-mouse models were utilized to evaluate effects in vivo. RESULTS: We have identified that herpes simplex virus-1 (HSV-1; oncolytic and wild-type)-infected glioma cells induce NOTCH signaling, from inside of infected cells into adjacent tumor cells (inside out signaling). This was canonical NOTCH signaling, which resulted in activation of RBPJ-dependent transcriptional activity that could be rescued with dnMAML. High-throughput screening of HSV-1-encoded cDNA and miRNA libraries further uncovered that HSV-1 miR-H16 induced NOTCH signaling. We further identified that factor inhibiting HIF-1 (FIH-1) is a direct target of miR-H16, and that FIH-1 downregulation by virus encoded miR-H16 induces NOTCH activity. FIH-1 binding to Mib1 has been reported, but this is the first report that shows FIH-1 sequester Mib1 to suppress NOTCH activation. We observed that FIH-1 degradation induced NOTCH ligand ubiquitination and NOTCH activity. REMBRANDT and The Cancer Genome Atlas data analysis also uncovered a significant negative regulation between FIH-1 and NOTCH. Furthermore, combination of oHSV with NOTCH-blocking gamma secretase inhibitor (GSI) had a therapeutic advantage in two different intracranial glioma models treated with oncolytic HSV, without affecting safety profile of the virus in vivo. CONCLUSIONS: To our knowledge this is the first report to identify impact of HSV-1 on NOTCH signaling and highlights the significance of combining oHSV and GSI for glioblastoma therapy.

    DOI: 10.1158/1078-0432.CCR-19-3420

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  • Enhancing Antitumor Efficacy of Heavily Vascularized Tumors by RAMBO Virus through Decreased Tumor Endothelial Cell Activation. 査読 国際誌

    Mitra Nair, Maninder Khosla, Yoshihiro Otani, Margaret Yeh, Flora Park, Toshihiko Shimizu, Jin Muk Kang, Chelsea Bolyard, Jun-Ge Yu, Yeshavanth Kumar Banasavadi-Siddegowda, Gonzalo Lopez, Balveen Kaur, Raphael E Pollock, Tae Jin Lee, Matthew Old, Ji Young Yoo

    Cancers   12 ( 4 )   2020年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Vascularization is a common pathology for many solid tumors, and therefore anti-angiogenic strategies are being investigated as a therapeutic target for treatment. Numerous studies are also being conducted regarding the effects of oncolytic viruses, including ImlygicTM, an FDA approved oncolytic herpes simplex virus-1 (oHSV) for the treatment of highly vascularized tumors such as Kaposi sarcoma (NCT04065152), and brain tumors. To our knowledge, the effects of combining oncolytic HSV with angiogenesis inhibition on endothelial cell activation has not been previously described. Here, we tested the effects of Rapid Antiangiogenesis Mediated By Oncolytic Virus (RAMBO), an oHSV which expresses a potent anti-angiogenic gene Vasculostatin on endothelial cell activation in heavily vascularized solid tumors. oHSV treatment induces endothelial cell activation, which inhibits virus propagation and oncolysis in adjacent tumor cells in vitro. Consistently, this was also observed in intravital imaging of intracranial tumor-bearing mice in vivo where infected tumor endothelial cells could efficiently clear the virus without cell lysis. Quantitative real-time PCR (Q-PCR), leukocyte adhesion assay, and fluorescent microscopy imaging data, however, revealed that RAMBO virus significantly decreased expression of endothelial cell activation markers and leukocyte adhesion, which in turn increased virus replication and cytotoxicity in endothelial cells. In vivo RAMBO treatment of subcutaneously implanted sarcoma tumors significantly reduced tumor growth in mice bearing sarcoma compared to rHSVQ. In addition, histological analysis of RAMBO-treated tumor tissues revealed large areas of necrosis and a statistically significant reduction in microvessel density (MVD). This study provides strong preclinical evidence of the therapeutic benefit for the use of RAMBO virus as a treatment option for highly vascularized tumors.

    DOI: 10.3390/cancers12041040

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  • Annexin A2-STAT3-Oncostatin M receptor axis drives phenotypic and mesenchymal changes in glioblastoma. 査読 国際誌

    Yuji Matsumoto, Tomotsugu Ichikawa, Kazuhiko Kurozumi, Yoshihiro Otani, Atsushi Fujimura, Kentaro Fujii, Yusuke Tomita, Yasuhiko Hattori, Atsuhito Uneda, Nobushige Tsuboi, Keisuke Kaneda, Keigo Makino, Isao Date

    Acta neuropathologica communications   8 ( 1 )   42 - 42   2020年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Glioblastoma (GBM) is characterized by extensive tumor cell invasion, angiogenesis, and proliferation. We previously established subclones of GBM cells with distinct invasive phenotypes and identified annexin A2 (ANXA2) as an activator of angiogenesis and perivascular invasion. Here, we further explored the role of ANXA2 in regulating phenotypic transition in GBM. We identified oncostatin M receptor (OSMR) as a key ANXA2 target gene in GBM utilizing microarray analysis and hierarchical clustering analysis of the Ivy Glioblastoma Atlas Project and The Cancer Genome Atlas datasets. Overexpression of ANXA2 in GBM cells increased the expression of OSMR and phosphorylated signal transducer and activator of transcription 3 (STAT3) and enhanced cell invasion, angiogenesis, proliferation, and mesenchymal transition. Silencing of OSMR reversed the ANXA2-induced phenotype, and STAT3 knockdown reduced OSMR protein expression. Exposure of GBM cells to hypoxic conditions activated the ANXA2-STAT3-OSMR signaling axis. Mice bearing ANXA2-overexpressing GBM exhibited shorter survival times compared with control tumor-bearing mice, whereas OSMR knockdown increased the survival time and diminished ANXA2-mediated tumor invasion, angiogenesis, and growth. Further, we uncovered a significant relationship between ANXA2 and OSMR expression in clinical GBM specimens, and demonstrated their correlation with tumor histopathology and patient prognosis. Our results indicate that the ANXA2-STAT3-OSMR axis regulates malignant phenotypic changes and mesenchymal transition in GBM, suggesting that this axis is a promising therapeutic target to treat GBM aggressiveness.

    DOI: 10.1186/s40478-020-00916-7

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  • Oncolytic HSV therapy increases trametinib access to brain tumors and sensitizes them in vivo. 査読 国際誌

    Ji Young Yoo, Jessica Swanner, Yoshihiro Otani, Mitra Nair, Flora Park, Yeshavanth Banasavadi-Siddegowda, Joseph Liu, Alena Cristina Jaime-Ramirez, Bangxing Hong, Feng Geng, Deliang Guo, Darlene Bystry, Mitch Phelphs, Haroon Quadri, Tae Jin Lee, Balveen Kaur

    Neuro-oncology   21 ( 9 )   1131 - 1140   2019年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Hyperactivation of the RAS-RAF-MEK-ERK signaling pathway is exploited by glioma cells to promote their growth and evade apoptosis. MEK activation in tumor cells can increase replication of ICP34.5-deleted herpes simplex virus type 1 (HSV-1), but paradoxically its activation in tumor-associated macrophages promotes a pro-inflammatory signaling that can inhibit virus replication and propagation. Here we investigated the effect of blocking MEK signaling in conjunction with oncolytic HSV-1 (oHSV) for brain tumors. METHODS: Infected glioma cells co-cultured with microglia or macrophages treated with or without trametinib were used to test trametinib effect on macrophages/microglia. Enzyme-linked immunosorbent assay, western blotting, and flow cytometry were utilized to evaluate the effect of the combination therapy. Pharmacokinetic (PK) analysis of mouse plasma and brain tissue was used to evaluate trametinib delivery to the CNS. Intracranial human and mouse glioma-bearing immune deficient and immune competent mice were used to evaluate the antitumor efficacy. RESULT: Oncolytic HSV treatment rescued trametinib-mediated feedback reactivation of the mitogen-activated protein kinase signaling pathway in glioma. In vivo, PK analysis revealed enhanced blood-brain barrier penetration of trametinib after oHSV treatment. Treatment by trametinib, a MEK kinase inhibitor, led to a significant reduction in microglia- and macrophage-derived tumor necrosis factor alpha (TNFα) secretion in response to oHSV treatment and increased survival of glioma-bearing mice. Despite the reduced TNFα production observed in vivo, the combination treatment activated CD8+ T-cell mediated immunity and increased survival in a glioma-bearing immune-competent mouse model. CONCLUSION: This study provides a rationale for combining oHSV with trametinib for the treatment of brain tumors.

    DOI: 10.1093/neuonc/noz079

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  • Clinicopathological and Genetic Features of Supratentorial Cortical Ependymomas. 査読 国際誌

    Yuji Matsumoto, Tomotsugu Ichikawa, Kazuhiko Kurozumi, Yoshihiro Otani, Isao Date

    World neurosurgery   129   e417-e428   2019年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: Supratentorial cortical ependymomas (CEs) are rare. These lesions, selectively occurring in the superficial cortex, have not been fully characterized. We analyzed the clinicopathological and genetic features of CEs. METHODS: Eight patients with CEs from our institution and 84 other reported CE cases were included in the present study. We retrospectively reviewed their clinical characteristics, imaging findings, treatment methods, pathological features, molecular status, and clinical outcomes. RESULTS: The median age at diagnosis of our 8 patients was 7.5 years. The mean tumor diameter was 70 mm. All the tumors had a cystic appearance, and calcification was observed in 6. Gross total resection was achieved in 6 patients and subtotal resection in 2 patients. Of the 8 tumors, 7 were World Health Organization grade III and 1 was World Health Organization grade II. Six tumors were immunopositive for L1 cell adhesion molecule (L1CAM). We investigated the presence of C11orf95-RELA fusion in 5 patients, all of whom exhibited it. Postoperative radiotherapy was performed for all patients with grade III tumors, except for children aged <3 years. Although 4 patients developed recurrence, all were alive throughout the follow-up period. Compared with previously reported CEs, our patients were younger and had larger tumors; however, the clinical outcomes did not differ significantly. CONCLUSIONS: Although most CEs in our group were immunopositive for L1CAM and showed C11orf95-RELA fusion, which have been associated with a poor prognosis in supratentorial ependymomas, all our patients had good outcomes. Gross total resection and adjuvant radiotherapy contributed to the relatively favorable prognosis of CEs compared with other supratentorial ependymomas.

    DOI: 10.1016/j.wneu.2019.05.166

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  • Oncolytic Herpes Virus Armed with Vasculostatin in Combination with Bevacizumab Abrogates Glioma Invasion via the CCN1 and AKT Signaling Pathways. 査読 国際誌

    Yusuke Tomita, Kazuhiko Kurozumi, Ji Young Yoo, Kentaro Fujii, Tomotsugu Ichikawa, Yuji Matsumoto, Atsuhito Uneda, Yasuhiko Hattori, Toshihiko Shimizu, Yoshihiro Otani, Tetsuo Oka, Balveen Kaur, Isao Date

    Molecular cancer therapeutics   18 ( 8 )   1418 - 1429   2019年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Anti-VEGF treatments such as bevacizumab have demonstrated convincing therapeutic advantage in patients with glioblastoma. However, bevacizumab has also been reported to induce invasiveness of glioma. In this study, we examined the effects of rapid antiangiogenesis mediated by oncolytic virus (RAMBO), an oncolytic herpes simplex virus-1 expressing vasculostatin, on bevacizumab-induced glioma invasion. The effect of the combination of RAMBO and bevacizumab in vitro was assessed by cytotoxicity, migration, and invasion assays. For in vivo experiments, glioma cells were stereotactically inoculated into the brain of mice. RAMBO was intratumorally injected 7 days after tumor inoculation, and bevacizumab was administered intraperitoneally twice a week. RAMBO significantly decreased both the migration and invasion of glioma cells treated with bevacizumab. In mice treated with bevacizumab and RAMBO combination, the survival time was significantly longer and the depth of tumor invasion was significantly smaller than those treated with bevacizumab monotherapy. Interestingly, RAMBO decreased the expression of cysteine-rich protein 61 and phosphorylation of AKT, which were increased by bevacizumab. These results suggest that RAMBO suppresses bevacizumab-induced glioma invasion, which could be a promising approach to glioma therapy.

    DOI: 10.1158/1535-7163.MCT-18-0799

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  • Dynamic Reorganization of Microtubule and Glioma Invasion. 招待 査読

    Yoshihiro Otani, Tomotsugu Ichikawa, Kazuhiko Kurozumi, Isao Date

    Acta medica Okayama   73 ( 4 )   285 - 297   2019年8月

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

    Gliomas are characterized as highly diffuse infiltrating tumors, and currently available treatments such as surgery, radiation and chemotherapy are unfeasible or show limited efficacy against these tumors. Recent genetic and epigenetic analyses of glioma have revealed increasing evidence of the role of driver genetic alterations in glioma development and led to the identification of prognostic factors. Despite these findings, the survival rates of glioma patients remain low, and alternative treatments and novel targets are needed. Recent studies identified neural stem cells as the possible origin of gliomas, and some evidence has revealed shared functions and mechanisms between glioma cells and neurons, also supporting their similarity. The cytoskeleton plays important roles in the migration of normal cells as well as cancer cells. Recent reports have described a role for microtubules, a component of the cytoskeleton, in glioma invasion. Notably, several factors that regulate microtubule functions, such as microtubule-associated proteins, plus-end tracking proteins, or motor proteins, are upregulated in glioma tissues compared with normal tissue, and upregulation of these factors is associated with high invasiveness of glioma cells. In this review, we describe the mechanism of microtubules in glioma invasion and discuss the possibility of microtubule-targeted therapy to inhibit glioma invasion.

    DOI: 10.18926/AMO/56930

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  • δ-Catenin Promotes Bevacizumab-Induced Glioma Invasion. 査読 国際誌

    Toshihiko Shimizu, Joji Ishida, Kazuhiko Kurozumi, Tomotsugu Ichikawa, Yoshihiro Otani, Tetsuo Oka, Yusuke Tomita, Yasuhiko Hattori, Atsuhito Uneda, Yuji Matsumoto, Isao Date

    Molecular cancer therapeutics   18 ( 4 )   812 - 822   2019年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The combination of bevacizumab with temozolomide and radiotherapy was shown to prolong progression-free survival in newly diagnosed patients with glioblastoma, and this emphasizes the potential of bevacizumab as a glioma treatment. However, although bevacizumab effectively inhibits angiogenesis, it has also been reported to induce invasive proliferation. This study examined gene expression in glioma cells to investigate the mechanisms of bevacizumab-induced invasion. We made a human glioma U87ΔEGFR cell xenograft model by stereotactically injecting these cells into the brain of animals. We administered bevacizumab intraperitoneally three times per week. At 18 days after tumor implantation, the brains were removed for histopathology and mRNA was extracted. In vivo, bevacizumab treatment increased glioma cell invasion. qRT-PCR array analysis revealed upregulation of δ-catenin (CTNND2) and several other factors. In vitro, bevacizumab treatment upregulated δ-catenin expression. A low concentration of bevacizumab was not cytotoxic, but tumor cell motility was increased in scratch wound assays and two-chamber assays. Overexpression of δ-catenin increased the tumor invasion in vitro and in vivo However, δ-catenin knockdown decreased glioma cell invasiveness. The depth of tumor invasion in the U87ΔEGFR cells expressing δ-catenin was significantly increased compared with empty vector-transfected cells. The increase in invasive capacity induced by bevacizumab therapy was associated with upregulation of δ-catenin expression in invasive tumor cells. This finding suggests that δ-catenin is related to tumor invasion and migration.

    DOI: 10.1158/1535-7163.MCT-18-0138

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  • Comparative Histologic and Molecular Analysis of 2 Recurrent Lesions Showing Different Magnetic Resonance Imaging Responses After Bevacizumab Treatment: Report of a Case of Anaplastic Astrocytoma. 査読 国際誌

    Yoshihiro Otani, Tomotsugu Ichikawa, Atsuhito Uneda, Kazuhiko Kurozumi, Joji Ishida, Isao Date

    World neurosurgery   116   464 - 471   2018年8月

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

    BACKGROUND: We report the case of a patient with anaplastic astrocytoma whose 2 recurrent lesions showed different imaging responses from one another after bevacizumab treatment. Histologic and genetic features of this patient are also described. CASE DESCRIPTION: A 31-year-old patient with left temporal anaplastic astrocytoma had surgery, local radiotherapy, and chemotherapy. Recurrent lesions appeared in the cerebellar vermis and left cerebellar hemisphere, and the patient was started on biweekly bevacizumab. Subsequently, the 2 enhanced lesions showed different response patterns on magnetic resonance imaging. Although the lesion in the cerebellar vermis showed an enlargement of enhancing mass, the lesion in the left cerebellar hemisphere showed disappearance of enhancement. We resected the cerebellar vermis lesion and performed biopsy on the cerebellar hemisphere lesion. The specimens were investigated. Both recurrent lesions showed higher Ki-67 labeling indices and pericyte proliferation, and less angiogenesis compared with the initial specimen. Transmission electron microscopy showed a reduction in the distance between the endothelial cells and tumor cells in both recurrent lesions, compared with the initial lesion. However, the tight junctions in the vermian lesion were still disrupted compared with the initial lesion and the cerebellar hemispheric lesion. Genetic analysis of the initial specimen showed proneural signature; however, the recurrent vermian lesion exhibited decreased expression of proneural markers. CONCLUSIONS: We report a case of anaplastic astrocytoma with 2 different imaging responses to bevacizumab. Our analysis suggests that differences in tight junctions possibly contributed to the changes on magnetic resonance imaging observed after bevacizumab treatment.

    DOI: 10.1016/j.wneu.2018.05.036

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  • Fibroblast growth factor 13 regulates glioma cell invasion and is important for bevacizumab-induced glioma invasion 査読

    Y Otani, T Ichikawa, K Kurozumi, S Inoue, J Ishida, T Oka, T Shimizu, Y Tomita, Y Hattori, A Uneda, Y Matsumoto, H Michiue, I Date

    Oncogene   37 ( 6 )   777 - 786   2018年2月

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    担当区分:筆頭著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    Glioblastoma has the poorest prognosis, and is characterized by excessive invasion and angiogenesis. To determine the invasive mechanisms, we previously used two glioma cell lines (J3T-1 and J3T-2) with different invasive phenotypes. The J3T-1 showed abundant angiogenesis and tumor cell invasion around neovasculature, while J3T-2 showed diffuse cell infiltration into surrounding healthy parenchyma. Microarray analyses were used to identify invasion-related genes in J3T-2 cells, and the expressed genes and their intracellular and intratumoral distribution patterns were evaluated in J3T-2 cell lines, human glioma cell lines, human glioblastoma stem cells and human glioblastoma specimens. To determine the role of the invasion-related genes, invasive activities were evaluated in vitro and in vivo. Fibroblast growth factor 13 (FGF13) was overexpressed in J3T-2 cells compared to J3T-1 cells, and in human glioma cell lines, human glioblastoma stem cells and human glioblastoma specimens, when compared to that of normal human astrocytes. Immunohistochemical staining and the RNA-seq (sequencing) data from the IVY Glioblastoma Atlas Project showed FGF13 expression in glioma cells in the invasive edges of tumor specimens. Also, the intracellular distribution was mainly in the cytoplasm of tumor cells and colocalized with tubulin. Overexpression of FGF13 stabilized tubulin dynamics in vitro and knockdown of FGF13 decreased glioma invasion both in vitro and in vivo and prolonged overall survival of several xenograft models. FGF13 was negatively regulated by hypoxic condition. Silencing of FGF13 also decreased in vivo bevacizumab-induced glioma invasion. In conclusion, FGF13 regulated glioma cell invasion and bevacizumab-induced glioma invasion, and could be a novel target for glioma treatment.

    DOI: 10.1038/onc.2017.373

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    その他リンク: http://www.nature.com/articles/onc2017373

  • Combination of the tubular retractor and brain spatulas provides an adequate operative field in surgery for deep-seated lesions: Case series and technical note. 査読 国際誌

    Yoshihiro Otani, Kazuhiko Kurozumi, Joji Ishida, Masafumi Hiramatsu, Masahiro Kameda, Tomotsugu Ichikawa, Isao Date

    Surgical neurology international   9   220 - 220   2018年

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

    Background: Surgeries for deep-seated lesions are challenging because making a corridor and observing the interface between lesions and normal brain tissue are difficult. The ViewSite Brain Access System, which is a clear plastic tubular retractor system, is used for resection of deep-seated lesions. However, the tapered shape of this system may result in limitation of the surgical field and cause brain injury to observe the interface between lesions and normal tissue. In this study, we evaluated the usefulness of the combination of ViewSite and brain spatulas. Methods: Nine patients were retrospectively identified who underwent resection of deep-seated lesions with the combination of Viewsite and brain spatulas. We assessed the extent of resection, prognosis, and quantitative brain injury from postoperative diffusion-weighed imaging (DWI). Results: There were four total radiographically confirmed resections. Subtotal resection in four patients and partial resection in one with central neurocytoma were achieved because these tumors were strongly adherent to the choroid plexus and ependymal veins. Only one case of metastatic tumor relapsed 6 months after surgery. The mean postoperative high signal on DWI was 3.68 ± 0.80 cm3. Conclusions: The combination of ViewSite and brain spatulas provides wide and adequate operative fields to observe the interface between lesions and normal tissue, and to prevent brain injury from excessive retraction pressure on the brain derived from repositioning of the ViewSite. Postoperative 3D volumetric analysis shows minimal damage to normal brain tissue. This report may provide new insight into the use of the ViewSite tubular retractor.

    DOI: 10.4103/sni.sni_62_18

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  • PIK3R1Met326Ile germline mutation correlates with cysteine-rich protein 61 expression and poor prognosis in glioblastoma. 査読 国際誌

    Yoshihiro Otani, Joji Ishida, Kazuhiko Kurozumi, Tetsuo Oka, Toshihiko Shimizu, Yusuke Tomita, Yasuhiko Hattori, Atsuhito Uneda, Yuji Matsumoto, Hiroyuki Michiue, Shuta Tomida, Takehiro Matsubara, Tomotsugu Ichikawa, Isao Date

    Scientific reports   7 ( 1 )   7391 - 7391   2017年8月

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

    Despite therapeutic advances, glioblastoma represents a lethal brain tumor. Recently, research to identify prognostic markers for glioblastoma has intensified. Our previous study demonstrated that median progression-free survival (PFS) and overall survival (OS) of patients with high cysteine-rich protein 61 (CCN1) expression was significantly shorter than that of patients with low CCN1 expression. To understand the molecular mechanisms that regulate CCN1 expression, we examined 147 tumour samples from 80 patients with glioblastoma and 67 patients with lower grade glioma. Next-generation and Sanger sequencing showed that PIK3R1Met326Ile was more frequent in the CCN1 high expression group (10/37 cases, 27.0%) than the CCN1 low expression group (3/38 cases, 7.9%) in glioblastoma. This mutation was also detected in corresponding blood samples. In multivariate analysis, high CCN1 expression and PIK3R1Met326Ile in glioblastoma patients were prognostic factors for OS [HR = 2.488 (1.298-4.769), p = 0.006] and [HR = 2.089 (1.020-4.277), p = 0.0439], respectively. Thus, the PIK3R1Met326Ile germline appears to be correlated with CCN1 expression and poor prognosis in glioblastoma.

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  • Congenital Glioblastoma with Distinct Clinical and Molecular Characteristics: Case Reports and a Literature Review. 査読 国際誌

    Masahiro Kameda, Yoshihiro Otani, Tomotsugu Ichikawa, Akira Shimada, Koichi Ichimura, Isao Date

    World neurosurgery   101   817.e5-817.e14   2017年5月

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

    BACKGROUND: The molecular diagnosis of brain tumors is important in classifying tumors and determining appropriate treatment. Congenital glioblastoma multiforme (GBM) is a rare tumor that occurs in infants, and the prognosis is poor. Approximately 60 patients diagnosed with congenital GBM have been reported. However, few reports have conducted molecular analyses of congenital GBM. CASE DESCRIPTION: We describe 2 congenital GBM patients treated in our hospital, and report results of immunohistochemistry, fluorescent in situ hybridization (FISH), direct sequencing, and methylation analyses. Surgery was performed on both patients at 2 months old, and the cases were diagnosed as glioblastoma. Immunohistochemical staining, FISH, and direct sequencing were positive for glial fibrillary acidic protein and ATRX, partially positive for p53, showed no alteration of isocitrate dehydrogenase 1 R132H, H3F3A, HIST1H3B, and BRAF, and indicated no codeletion of 1p and 19q. Methylation analysis of 1 patient identified copy number aberrations of 4 genes: deletions of CDK6 and CDKN2A/B, and a fusion of MET. One patient received chemotherapy consisting of ranimustine, interferon-beta, carboplatin, and etoposide, whereas the other patient received chemotherapy with the modified Children's Cancer Group study-9921 protocol. Residual tumors in both patients were decreased, and they achieved 18-year- and 9-month progression-free survival, respectively. In addition, we reviewed 65 previously reported congenital GBM patients, and found they have better prognosis than pediatric and adult GBM, and long-term survival can be expected. CONCLUSIONS: Congenital GBM demonstrates clinical and molecular characteristics that are different from those of pediatric or adult GBM.

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  • [Prognostic Impact of Radiation Therapy and Molecular Classification of Infant Atypical Teratoid/Rhabdoid Tumors]. 査読

    Yoshihiro Otani, Tomotsugu Ichikawa, Kazuhiko Kurozumi, Takao Yasuhara, Kana Washio, Akira Shimada, Norihisa Katayama, Kuniaki Katsui, Hiroyuki Yanai, Isao Date

    No shinkei geka. Neurological surgery   45 ( 2 )   147 - 154   2017年2月

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

    Atypical teratoid/rhabdoid tumor(AT/RT)is a rare and lethal childhood cancer. Although radiation therapy in children less than three years of age is generally deferred because of its neural toxicity, recent studies have shown that multimodal therapies, including radiation therapy, are effective in pediatric patients with AT/RT less than three years of age. We treated four infant AT/RT patients and investigated the impact of radiation therapy and genetic classification on the prognosis. The mean age at the time of the operation was 9.3 months and all patients were female. All patients underwent surgical resection. Of the four patients, two received combined irradiation and chemotherapy. Specifically, one patient received conformal craniospinal radiation therapy and the other received craniospinal irradiation with proton beams. Immunohistochemical analyses of tumor specimens revealed that the two patients were positive for ASCL1, a regulator of Notch signaling. Patients who received radiation therapy and exhibited ASCL1-positive tumors had a better prognosis. We conclude that radiation therapy may prolong survival in AT/RT patients who are less than 3 years of age. However, further study is required to evaluate long-term functional outcomes.

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  • Quantitative analysis of brain edema in patients with malignant glioma treated with BCNU wafers. 査読 国際誌

    Satoshi Murai, Tomotsugu Ichikawa, Kazuhiko Kurozumi, Yosuke Shimazu, Tetsuo Oka, Yoshihiro Otani, Toshihiko Shimizu, Isao Date

    Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia   33   148 - 153   2016年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BCNU wafers are a form of interstitial chemotherapy that is expected to improve the survival of patients with malignant glioma. However, their adverse events, especially brain edema, sometimes cause significant clinical symptoms. In this study, we performed a volumetric analysis of brain edema after the implantation of BCNU wafers and reported on the clinical course, and exacerbation factors of brain edema. Twelve patients who underwent surgical resection of supratentorial malignant glioma and BCNU wafer implantation, were enrolled. Radiographic quantitative analysis was conducted and compared with a historical control. The volume change in brain edema was divided into three groups and correlation with clinical symptoms was then evaluated. Compared with the control group, the brain edema in the BCNU wafer implantation group was significantly prolonged after surgery. Radiographic volumetric analysis revealed an increase of more than 25% at any time after surgery in four patients (33%) and a reduction of less than 25%, 1month after surgery in three patients (25%). Grade 3 clinical deterioration related to brain edema occurred in two patients and Grade 2 in one patient. Univariate analysis revealed that the radiographic deterioration of brain edema had no correlation with age, sex, diagnosis, tumor grade, preoperative volume of brain edema and tumor, residual tumor volume, or number of BCNU wafers. Radiographic quantitative analysis of brain edema indicated that BCNU wafer implantation may induce the prolongation and enlargement of brain edema with or without neurological deterioration. Brain edema may be controlled by intensive perioperative treatment with diuretics and corticosteroids.

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  • Cerebral Infarction Arising from Takotsubo Cardiomyopathy: Case Report and Literature Review. 査読

    Yoshihiro Otani, Koji Tokunaga, Satoshi Kawauchi, Satoshi Inoue, Kyoichi Watanabe, Hideki Kiriyama, Kosuke Sakane, Kiyoaki Maekawa, Isao Date, Kengo Matsumoto

    NMC case report journal   3 ( 4 )   119 - 123   2016年10月

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    担当区分:筆頭著者   記述言語:英語  

    Although most patients with takotsubo cardiomyopathy have a favorable outcome, complications are not uncommon. Recent studies have reported an increase in incidence of cardioembolic complications; however, the association between takotsubo cardiomyopathy and stroke, in particular thromboembolic cerebral infarction, remains unclear. We reported a 44-year-old woman who had a cerebral infarction resulting from takotsubo cardiomyopathy. She had felt chest discomfort a few days prior to infarction, and later developed left hemiparesis. Head magnetic resonance imaging (MRI) revealed acute infarction in the right insular cortex and occlusion of the right middle cerebral artery at the M2 segment. Echocardiogram revealed a takotsubo-like shape in the motion of the left ventricular wall, and coronary angiography showed neither coronary stenosis nor occlusion. Cerebral infarction resulting from takotsubo cardiomyopathy was diagnosed and treatment with anticoagulant was started. MRI on the eighth day after hospitalization showed recanalization of the right middle cerebral artery and no new ischemic lesions. The findings of the 19 previously published cases who had cerebral infarction resulting from takotsubo cardiomyopathy were also reviewed and showed the median interval between takotsubo cardiomyopathy and cerebral infarction was approximately 1 week and cardiac thrombus was detected in 9 of 19 patients. We revealed that thromboembolic events occurred later than other complications of takotsubo cardiomyopathy and longer observation might be required due to possible cardiogenic cerebral infarction. Anticoagulant therapy is recommended for patients with takotsubo cardiomyopathy with cardiac thrombus or a large area of akinetic left ventricle.

    DOI: 10.2176/nmccrj.cr.2016-0034

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  • A super gene expression system enhances the anti-glioma effects of adenovirus-mediated REIC/Dkk-3 gene therapy. 査読 国際誌

    Tetsuo Oka, Kazuhiko Kurozumi, Yosuke Shimazu, Tomotsugu Ichikawa, Joji Ishida, Yoshihiro Otani, Toshihiko Shimizu, Yusuke Tomita, Masakiyo Sakaguchi, Masami Watanabe, Yasutomo Nasu, Hiromi Kumon, Isao Date

    Scientific reports   6   33319 - 33319   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is a tumor suppressor and therapeutic gene in many human cancers. Recently, an adenovirus REIC vector with the super gene expression system (Ad-SGE-REIC) was developed to increase REIC/Dkk-3 expression and enhance therapeutic effects compared with the conventional adenoviral vector (Ad-CAG-REIC). In this study, we investigated the in vitro and in vivo effects of Ad-SGE-REIC on malignant glioma. In U87ΔEGFR and GL261 glioma cells, western blotting confirmed that robust upregulation of REIC/Dkk-3 expression occurred in Ad-SGE-REIC-transduced cells, most notably after transduction at a multiplicity of infection of 10. Cytotoxicity assays showed that Ad-SGE-REIC resulted in a time-dependent and significant reduction in the number of malignant glioma cells attaching to the bottom of culture wells. Xenograft and syngeneic mouse intracranial glioma models treated with Ad-SGE-REIC had significantly longer survival than those treated with the control vector Ad-LacZ or with Ad-CAG-REIC. This study demonstrated the anti-glioma effect of Ad-SGE-REIC, which may represent a promising strategy for the treatment of malignant glioma.

    DOI: 10.1038/srep33319

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  • Phenotypic Transition as a Survival Strategy of Glioma.

    Tomotsugu Ichikawa, Yoshihiro Otani, Kazuhiko Kurozumi, Isao Date

    Neurologia medico-chirurgica   56 ( 7 )   387 - 95   2016年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Malignant glioma is characterized by rapid proliferation, invasion into surrounding central nervous system tissues, and aberrant vascularization. There is increasing evidence that shows gliomas are more complex than previously thought, as each tumor comprises considerable intratumoral heterogeneity with mixtures of genetically and phenotypically distinct subclones. Heterogeneity within and across tumors is recognized as a critical factor that limits therapeutic progress for malignant glioma. Recent genotyping and expression profiling of gliomas has allowed for the creation of classification schemes that assign tumors to subtypes based on similarity to defined expression signatures. Also, malignant gliomas frequently shift their biological features upon recurrence and progression. The ability of glioma cells to resist adverse conditions such as hypoxia and metabolic stress is necessary for sustained tumor growth and strongly influences tumor behaviors. In general, glioma cells are in one of two phenotypic categories: higher proliferative activity with angiogenesis, or higher migratory activity with attenuated proliferative ability. Further, they switch phenotypic categories depending on the situation. To date, a multidimensional approach has been employed to clarify the mechanisms of phenotypic shift of glioma. Various molecular and signaling pathways are involved in phenotypic shifts of glioma, possibly with crosstalk between them. In this review, we discuss molecular and phenotypic heterogeneity of glioma cells and mechanisms of phenotypic shifts in regard to the glioma proliferation, angiogenesis, and invasion. A better understanding of the molecular mechanisms that underlie phenotypic shifts of glioma may provide new insights into targeted therapeutic strategies.

    DOI: 10.2176/nmc.ra.2016-0077

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  • Hybrid Microscopic-Endoscopic Surgery for Craniopharyngioma in Neurosurgical Suite: Technical Notes. 査読 国際誌

    Tomotsugu Ichikawa, Yoshihiro Otani, Joji Ishida, Kentaro Fujii, Kazuhiko Kurozumi, Shigeki Ono, Isao Date

    World neurosurgery   85   340 - 8   2016年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: The best chance of curing craniopharyngioma is achieved by microsurgical total resection; however, its location adjacent to critical structures hinders complete resection without neurologic deterioration. Unrecognized residual tumor within microscopic blind spots might result in tumor recurrences. To improve outcomes, new techniques are necessary to visualize tissue within these blind spots. We examined the success of hybrid microscopic-endoscopic neurosurgery for craniopharyngioma in a neurosurgical suite. METHODS: Four children with craniopharyngiomas underwent microscopic resection. When the neurosurgeon was confident that most of the visible tumor was removed but was suspicious of residual tumor within the blind spot, he or she used an integrated endoscope-holder system to inspect and remove any residual tumor. Two ceiling monitors were mounted side by side in front of the surgeon to display both microscopic and endoscopic views and to view both monitors simultaneously. RESULTS: Surgery was performed in all patients via the frontobasal interhemispheric approach. Residual tumors were observed in the sella (2 patients), on the ventral surface of the chiasm and optic nerve (1 patient), and in the third ventricle (1 patient) and were resected to achieve total resection. Postoperatively, visual function was improved in 2 patients and none exhibited deterioration related to the surgery. CONCLUSIONS: Simultaneous microscopic and endoscopic observation with the use of dual monitors in a neurosurgical suite was ergonomically optimal for the surgeon to perform microsurgical procedures and to avoid traumatizing surrounding vessels or neural tissues. Hybrid microscopic-endoscopic neurosurgery may contribute to safe, less-invasive, and maximal resection to achieve better prognosis in children with craniopharyngioma.

    DOI: 10.1016/j.wneu.2015.08.058

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  • Evaluation of extracellular matrix protein CCN1 as a prognostic factor for glioblastoma. 査読

    Joji Ishida, Kazuhiko Kurozumi, Tomotsugu Ichikawa, Yoshihiro Otani, Manabu Onishi, Kentaro Fujii, Yosuke Shimazu, Tetsuo Oka, Toshihiko Shimizu, Isao Date

    Brain tumor pathology   32 ( 4 )   245 - 52   2015年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Recently, research efforts in identifying prognostic molecular biomarkers for malignant glioma have intensified. Cysteine-rich protein 61 (CCN1) is one of the CCN family of matricellular proteins that promotes cell growth and angiogenesis in cancers through its interaction with several integrins. In this study, we investigated the relationships among CCN1, O(6)-methylguanine-DNA methyltransferase expression, the tumor removal rate, and prognosis in 46 glioblastoma patients treated at the Okayama University Hospital. CCN1 expression was high in 31 (67 %) of these patients. The median progression-free survival (PFS) and overall survival (OS) times of patients with high CCN1 expression was significantly shorter than those of patients with low CCN1 expression (p < 0.005). In a multivariate Cox analysis, CCN1 proved to be an independent prognostic factor for patient survival [PFS, hazard ratio (HR) = 3.53 (1.55-8.01), p = 0.003 and OS, HR = 3.05 (1.35-6.87), p = 0.007]. Moreover, in the 31 patients who underwent gross total resection, the PFS and OS times of those with high CCN1 expression were significantly shorter than those with low CCN1 expression. It was concluded that CCN1 might emerge as a significant prognostic factor regarding the prognosis of glioblastoma patients.

    DOI: 10.1007/s10014-015-0227-3

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  • Annexin A2 regulates angiogenesis and invasion phenotypes of malignant glioma. 査読

    Manabu Onishi, Tomotsugu Ichikawa, Kazuhiko Kurozumi, Satoshi Inoue, Tomoko Maruo, Yoshihiro Otani, Kentaro Fujii, Joji Ishida, Yosuke Shimazu, Koichi Yoshida, Hiroyuki Michiue, E Antonio Chiocca, Isao Date

    Brain tumor pathology   32 ( 3 )   184 - 94   2015年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We have established a pair of animal models (J3T-1 and J3T-2) with different invasive and angiogenic phenotypes, and demonstrated that annexin A2 is expressed at higher levels in J3T-1 than J3T-2 cells. The function of annexin A2 in relation to angiogenesis and invasion was investigated using these models. Stable silencing or overexpression of annexin A2 in J3T-1 and J3T-2 cells (J3T-1shA and J3T-2A cells) was established and used. Thirty human glioblastoma samples were evaluated for expression of annexin A2, vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). Immunohistochemical and quantitative reverse-transcription polymerase chain reaction analyses revealed higher expression of annexin A2, VEGF and PDGF in J3T-1 and J3T-2A cells. Cultured J3T-1 and J3T-2A cells exhibited higher adhesive ability to endothelial cells. Histopathological analysis of animal brain tumors revealed that J3T-1 and J3T-2A tumors displayed marked angiogenesis and invasion along the neovasculature, whereas J3T-2 and J3T-1shA tumors exhibited diffuse, infiltrative invasion without angiogenesis. Positive expression of annexin A2 was observed in tumor cells surrounding dilated vessels in 25/30 human glioblastoma specimens. Our results reveal that the phenotype of glioma invasion is closely related to angiogenesis. We identify annexin A2 as a factor regulating angiogenesis and invasion of malignant gliomas.

    DOI: 10.1007/s10014-015-0216-6

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  • 胸部大動脈解離術後の人工血管感染により椎骨-脳底動脈領域に限局する多発脳膿瘍を呈した1例

    大谷 理浩, 井上 智, 河内 哲, 畝田 篤仁, 梶谷 卓未, 渡邊 恭一, 出口 健太郎, 桐山 英樹, 徳永 浩司, 松本 健五

    Neurological Surgery   43 ( 3 )   235 - 240   2015年3月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

    62歳男。胸部大動脈解離および心筋梗塞を発症し、大動脈弓部置換術および冠動脈ステント留置術を施行された。術後に脊髄梗塞を発症し下肢対麻痺および膀胱直腸障害が出現し、リハビリテーションを行った。入院中に尿路感染症を発症し抗菌薬による治療を受けた。その後、下肢の対麻痺は完全麻痺の状態で改善なく、自宅退院となった。自宅退院後2ヵ月、発熱に対して抗菌薬を約1週間投与したが、意識障害が出現した。頭部MRIで頭蓋内病変を指摘された。血行性感染による脳腫瘍、特に左鎖骨下動脈起始部の人工血管に感染が疑われたことから、ここからの左鎖骨動脈・脳底動脈を介した多発脳膿瘍を疑った。人工血管置換部の感染の可能性が指摘されたが、同部位への外科的介入は困難で、抗菌薬による治療を開始した。最終的には軽度の右眼球運動障害(外転障害)は後遺したが、その他の症状は軽快した。

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  • [Multiple brain abscesses in the territory of the vertebral-basilar artery resulting from an infected aortic arch graft]. 査読

    Yoshihiro Otani, Satoshi Inoue, Satoshi Kawauchi, Atsuhito Uneda, Takumi Kajitani, Kyoichi Watanabe, Kentaro Deguchi, Hideki Kiriyama, Koji Tokunaga, Kengo Matsumoto

    No shinkei geka. Neurological surgery   43 ( 3 )   235 - 40   2015年3月

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

    A 62-year-old man with high fever and in a state of disorientation was transferred to our hospital. One year before this transfer, he had undergone total arch replacement surgery for thoracic aortic dissection. On admission to our hospital, head MRI revealed multiple brain abscesses in the territory of the vertebral-basilar artery, and chest CT showed gas around the aortic graft, in particular, at the origin of the left subclavian artery. We diagnosed him with brain abscesses in the left vertebral-basilar artery resulting from an infected aortic graft. We immediately began administration of intravenous antibiotics. Although his blood, urine, and cerebrospinal fluid cultures were negative, fortunately, the brain abscesses and ectopic gas disappeared. Since reports of only antibiotic use for treating brain abscesses due to aortic graft infection are rare, the appropriate duration of antibiotic administration has not been established yet. Therefore, careful observation is required in this case.

    DOI: 10.11477/mf.1436202993

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  • THE ANTI ANGIOGENIC AND INVASIVE EFFECTS OF AN INTEGRIN INHIBITOR AGAINST BEVACIZUMAB-INDUCED INVASIVE GLIOMA

    Yoshihiro Otani

    Neuro-Oncology   2014年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/NEUONC/NOU238.14

    Web of Science

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  • 急性硬膜下血腫の術後に繰り返す後出血 から第13因子欠乏症と診断した1例 査読

    大谷理浩, 井上智, 馬越通有, 高杉祐二, 渡邊恭一, 桐山英樹, 原嘉孝, 今城健二, 松本健五

    脳神経外科速報   23 ( 12 )   1390 - 1394   2013年12月

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    担当区分:筆頭著者   記述言語:日本語  

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  • Postoperative hemorrhage due to factor ⅩⅢ deficiency after surgery for acute subdural hematomas: Case report.

    Yoshihiro Otani

    Currently Practical Neurosurgery   2013年11月

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    掲載種別:研究論文(学術雑誌)  

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  • [A case of synovial sarcoma with brain metastasis treated with surgical resection and stereotactic radiosurgery]. 査読

    Yoshihiro Otani, Tomotsugu Ichikawa, Kazuhiko Kurozumi, Hiroyuki Yanai, Toshiyuki Kunisada, Toshifumi Ozaki, Isao Date

    No shinkei geka. Neurological surgery   41 ( 3 )   255 - 62   2013年3月

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

    Synovial sarcomas compromise between 5 to 10% of all soft tissue sarcomas in adults. Synovial sarcoma commonly occurs in the vicinity of the large joints and cranial metastasis is rare. Here, we describe a case with intracranial metastases of a synovial sarcoma. A 41-year-old woman was admitted to our department with sensory aphasia. She had a history of a left inguinal synovial sarcoma and underwent surgery and chemotherapy for primary and metastatic lesions. Head MRI revealed three gadolinium-enhancing lesions in the left frontal, parietal and parietotemporal lobe. Gross total resection was achieved in the left parietotemporal lesion and pathological diagnosis was synovial sarcoma. Two weeks after surgery, she received cyber-knife radiosurgery and her neurological deficit was almost completely resolved. Intracranial metastatic synovial sarcoma is rare. Surgical resection and stereotaxic radiosurgery was very effective in the present case.

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  • [Endovascular coiling of thrombosed basilar tip aneurysm using double stents in a y-configuration]. 査読

    Yoshihiro Otani, Kenji Sugiu, Koji Tokunaga, Tomohito Hishikawa, Hisakazu Itami, Masafumi Hiramatsu, Yu Okuma, Isao Date

    No shinkei geka. Neurological surgery   40 ( 11 )   1005 - 12   2012年11月

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

    Recent advances in endovascular techniques greatly improved the ability to treat complex cerebral aneurysms. However, patients with wide-necked cerebral aneurysms have posed a special challenge to conventional endovascular therapy. We report a novel method of embolizing wide-necked basilar apex aneurysms by employing a Y-configuration, double stent technique. A 40-year-old woman with a partially thrombosed basilar apex aneurysm transferred to our hospital after diagnosis of subarachnoid hemorrhage. Cerebral angiography revealed a wide-necked aneurysm which neck was incorporating the origins of both the posterior cerebral arteries. In treatment procedure, a microcatheter was inserted into the aneurysm followed by coiling of the upper half of the dome. Next, the first stent was deployed in the right P2 segment extending down to the mid basilar artery and the second stent was then deployed with half of the stent in the left P2 and the other half within the lumen of the previously placed stent. Finally, the microcatheter was withdrawn near the neck, and the rest of the aneurysmal dome was packed by additional coils. The result was favorable. Successful coil embolization of a wide-necked bifurcation aneurysm can be achieved by using the double stenting Y-configuration in this case. This result continues to provide highly encouraging support of this novel technique to treat a subset of complex, wide-necked aneurysms that until recently were considered poor candidates for endovascular therapies.

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  • 脳底動脈先端部血栓化動脈瘤に対してYステント併用コイル塞栓術を施行した1例

    大谷 理浩, 杉生 憲志, 徳永 浩司, 菱川 朋人, 伊丹 尚多, 平松 匡文, 大熊 佑, 伊達 勲

    Neurological Surgery   40 ( 11 )   1005 - 1012   2012年11月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

    症例は40歳女性で、突然の激しい頭痛後の意識障害で近医に救急搬送された。CTでクモ膜下出血と診断され、CTAで脳底動脈(BA)先端部に軽度膨隆が認められた。day1より意識清明となったが、左外転神経麻痺が出現した。CT・MRIでBA先端部に血栓化したmassを認め、破裂部分血栓化動脈瘤と診断され、day29に血管内治療のため当院に転院した。DSAでBA先端部にneck 4mm、高さ2mmの扁平型動脈瘤(血流腔)を認め、その上方の血栓内に火焔状に造影剤流入が認められた。両側後大脳動脈(PCA)にわたるwide-neck部分血栓化動脈瘤と判断し、抗血小板薬投与後のday36に全身麻酔科でコイル塞栓術を行った。瘤内火焔状の内部にHydroCoil、MicroPlex COSMOSを挿入・充填し、造影剤流入の消失を確認した。両側PCAから左右対称のYステントとして留置し、Neck近傍の血流腔を塞栓した。術後経過は良好でday47に独歩退院し、術後9ヵ月経過で元気に外来通院中である。

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2012&ichushi_jid=J01228&link_issn=&doc_id=20121112040013&doc_link_id=10.11477%2Fmf.1436101864&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1436101864&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

  • 側頭葉てんかんにおける海馬機能の評価に対する選択的後大脳動脈ワダテストの有用性

    上利 崇, 井上 拓志, 岡 牧郎, 佐々木 達也, 大谷 理浩, 大塚 頌子, 伊達 勲

    てんかん研究   30 ( 1 )   75 - 76   2012年6月

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    記述言語:日本語   出版者・発行元:(一社)日本てんかん学会  

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MISC

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講演・口頭発表等

  • 当院における中枢神経原発悪性リンパ腫に対する治療戦略

    水田 亮、大谷理浩、藤井謙太郎、石田穣治、坪井伸成、牧野圭悟、平野秀一郎、劒持直也、駿河和城、井本良二、家護谷泰仁、藤井伸治、遠西大輔、小林宏紀、伊達 勲

    第40回日本脳腫瘍学会学術集会(現地・Web併催)  2022年12月5日  国立がん研究センター中央病院 脳脊髄腫瘍科

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    開催年月日: 2022年12月4日 - 2022年12月6日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:鴨川  

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  • 橋実質内腫瘍に対する生検の有用性

    石田穣治、藤井謙太郎、大谷理浩、佐々木達也、坪井伸成、牧野圭悟、平野秀一郎、劒持直也、駿河和城、井本良二、水田 亮、家護谷泰仁、伊達 勲

    第40回日本脳腫瘍学会学術集会(現地・Web併催)  2022年12月5日  国立がん研究センター中央病院 脳脊髄腫瘍科

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    開催年月日: 2022年12月4日 - 2022年12月6日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:鴨川  

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  • 網羅的発現解析を用いた聴神経腫瘍における再発因子の検討

    牧野圭悟、大谷理浩、家護谷泰仁、井本良二、水田 亮、駿河和城、劒持直也、平野秀一郎、坪井伸成、石田穣治、藤井謙太郎、安原隆雄、伊達 勲

    第40回日本脳腫瘍学会学術集会(現地・Web併催)  2022年12月4日  国立がん研究センター中央病院 脳脊髄腫瘍科

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    開催年月日: 2022年12月4日 - 2022年12月6日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:鴨川  

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  • 腫瘍溶解ウイルスによるNOTCH経路活性化と腫瘍微小環境の解明 国際共著

    大谷理浩、Yoo Ji Young、Kaur Balveen

    第40回日本脳腫瘍学会学術集会(現地・Web併催)  2022年12月4日  国立がん研究センター中央病院 脳脊髄腫瘍科

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    開催年月日: 2022年12月4日 - 2022年12月6日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:鴨川  

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  • 大規模データ及びゲノムワイドメチル化解析による毛様細胞性星細胞腫の予後因子の検討

    駿河和城、冨田祐介、里見介史、大谷理浩、田中仁啓、家護谷泰仁、水田 亮、井本良二、劒持直也、平野秀一郎、牧野圭悟、坪井伸成、石田穣治、藤井謙太郎、安原隆雄、鷲尾佳奈、柳生広之、市村幸一、伊達 勲

    第40回日本脳腫瘍学会学術集会(現地・Web併催)  2022年12月4日  国立がん研究センター中央病院 脳脊髄腫瘍科

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    開催年月日: 2022年12月4日 - 2022年12月6日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:鴨川  

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  • 免疫チェックポイント阻害剤による転移性脳腫瘍発生率の低下と、抗腫瘍免疫機序の解明

    劒持直也、二宮貴一朗、大谷理浩、道上宏之、木浦勝行、伊達 勲、冨樫庸介

    第40回日本脳腫瘍学会学術集会(現地・Web併催)  2022年12月4日  国立がん研究センター中央病院 脳脊髄腫瘍科

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    開催年月日: 2022年12月4日 - 2022年12月6日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:鴨川  

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  • Diffuse hemispheric glioma, H3 G34-mutantにおける画像所見と予後についての検討

    家護谷泰仁、大谷理浩、井本良二、水田 亮、駿河和城、劒持直也、平野秀一郎、牧野圭悟、坪井伸成、石田穣治、藤井謙太郎、鷲尾佳奈 、伊達 勲

    第40回日本脳腫瘍学会学術集会(現地・Web併催)  2022年12月4日  国立がん研究センター中央病院 脳脊髄腫瘍科

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    開催年月日: 2022年12月4日 - 2022年12月6日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:鴨川  

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  • 小児脳腫瘍におけるゲノムワイドメチル化解析を用いた診断の有用性と限界

    井上陽平、大谷理浩、藤井謙太郎、石田穣治、家護谷泰仁、水田 亮、井本良二、駿河和城、劒持直也、平野秀一郎、牧野圭悟、坪井伸成、鷲尾佳奈、柳生広之、里見介史、市村幸一、伊達 勲

    第40回日本脳腫瘍学会学術集会(現地・Web併催)  2022年12月4日  国立がん研究センター中央病院 脳脊髄腫瘍科

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    開催年月日: 2022年12月4日 - 2022年12月6日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:鴨川  

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  • 膠芽腫幹細胞と分化型膠芽腫細胞を同時標的として薬剤併用療法の検討

    平野秀一郎、畝田篤仁、井本良二、水田 亮、駿河和城、劒持直也、牧野圭悟、坪井伸成、大谷理浩、石田穣治、藤井謙太郎、伊達 勲

    第40回日本脳腫瘍学会学術集会(現地・Web併催)  2022年12月4日  国立がん研究センター中央病院 脳脊髄腫瘍科

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    開催年月日: 2022年12月4日 - 2022年12月6日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:鴨川  

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  • 免疫チェックポイント阻害剤による転移性脳腫瘍発生率の低下と、その抗腫瘍免疫機序の解明(シンポジウム)

    劒持直也、二宮貴一郎、大谷理浩、道上宏之、木浦勝行、伊達 勲、冨樫庸介

    第10回Neuro-Oncology WEST(Web開催)  2022年11月5日  京都大学、和歌山県立医科大学

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    開催年月日: 2022年11月5日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:Web  

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  • 開頭経鼻合同頭蓋顔面切除術における神経内視鏡・外視鏡併用手術の有用性

    大谷理浩、藤井謙太郎、石田穣治、坪井伸成、安原隆雄、安藤瑞生、牧原靖一郎、松本 洋、伊達 勲

    第29回一般社団法人日本神経内視鏡学会(現地・Web併催)  2022年11月4日  東京女子医科大学 脳神経外科学講座

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    開催年月日: 2022年11月3日 - 2022年11月4日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:軽井沢  

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  • 開頭と経鼻アプローチにより複数回の閉鎖術を要した自然発生髄液漏の1例

    石田穣治、水田 亮、冨田陽介、檜垣貴哉、坪井伸成、大谷理浩、藤井謙太郎、伊達 勲

    第29回一般社団法人日本神経内視鏡学会(現地・Web併催)  2022年11月4日  東京女子医科大学 脳神経外科学講座

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    開催年月日: 2022年11月3日 - 2022年11月4日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:軽井沢  

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  • DuraGenで鞍底形成し遅発性髄液漏をきたした1例

    藤井謙太郎、牧原靖一郎、坪井伸成、大谷理浩、石田穣治、伊達 勲

    第29回一般社団法人日本神経内視鏡学会(現地・Web併催)  2022年11月3日  東京女子医科大学 脳神経外科学講座

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    開催年月日: 2022年11月3日 - 2022年11月4日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:軽井沢  

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  • 橋発生gliomaに対する生検の有用性

    石田穣治、藤井謙太郎、大谷理浩、佐々木達也、坪井伸成、牧野圭悟、平野秀一郎、劒持直也、駿河和城、井本良二、水田 亮、細本 翔、永瀬喬之、伊達 勲

    第27回日本脳腫瘍の外科学会(現地・Web併催)  2022年10月15日  日本医科大学 脳神経外科

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    開催年月日: 2022年10月14日 - 2022年10月15日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:東京  

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  • 神経膠腫における術後早期MRIと比較した術中MRIの有用性と限界について(シンポジウム)

    大谷理浩、藤井謙太郎、石田穣治、坪井伸成、牧野圭悟、平野秀一郎、劒持直也、駿河和城、井本良二、水田 亮、檜垣文代、伊達 勲

    第27回日本脳腫瘍の外科学会(現地・Web併催)  2022年10月14日  日本医科大学 脳神経外科

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    開催年月日: 2022年10月14日 - 2022年10月15日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:東京  

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  • 高齢者下垂体腺腫の臨床像および外科的治療成績の検討

    平野秀一郎、大谷理浩、藤井謙太郎、石田穣治、坪井伸成、牧野圭悟、劒持直也、駿河和城、井本良二、水田 亮、伊達 勲

    (一社)日本脳神経外科学会第81回学術総会(現地・Web併催)  2022年9月30日  岩手医科大学 脳神経外科

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    開催年月日: 2022年9月28日 - 2022年10月1日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:横浜  

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  • Second look手術を行ったCNS LGDIT-INI1の1例

    五月女悠太、石田穣治、畝田篤仁、藤井謙太郎、大谷理浩、坪井伸成、平下浩司、西田賢司、柳井広之、信澤純人、伊達 勲

    (一社)日本脳神経外科学会第81回学術総会(現地・Web併催)  2022年9月28日  岩手医科大学 脳神経外科

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    開催年月日: 2022年9月28日 - 2022年10月1日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:横浜  

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  • 当院における中枢神経原発悪性リンパ腫に対する治療戦略

    水田 亮、藤井謙太郎、石田穣治、大谷理浩、坪井伸成、牧野圭悟、平野秀一郎、劒持直也、駿河和城、井本良二、藤井伸治、遠西大輔、小林宏紀、伊達 勲

    (一社)日本脳神経外科学会第81回学術総会(現地・Web併催)  2022年9月28日  岩手医科大学 脳神経外科

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    開催年月日: 2022年9月28日 - 2022年10月1日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:横浜  

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  • がん遺伝子パネル検査を用いた当院における小児グリオーマの診療について

    駿河和城、石田穣治、藤井謙太郎、大谷理浩、坪井伸成、牧野圭悟、平野秀一郎、劒持直也、水田 亮、井本良二、鷲尾佳奈、柳井広之、遠西大輔、山本英喜、伊達 勲

    (一社)日本脳神経外科学会第81回学術総会(現地・Web併催)  2022年9月28日  岩手医科大学 脳神経外科

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    開催年月日: 2022年9月28日 - 2022年10月1日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:横浜  

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  • ラトケ嚢胞治療と内分泌機能低下リスクの検討

    劒持直也、石田穣治、藤井謙太郎、大谷理浩、稲垣兼一、伊達 勲

    (一社)日本脳神経外科学会第81回学術総会(現地・Web併催)  2022年9月28日  岩手医科大学 脳神経外科

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    開催年月日: 2022年9月28日 - 2022年10月1日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:横浜  

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  • Tectal gliomaの臨床像および組織学的検討について

    井本良二、大谷理浩、水田 亮、劒持直也、駿河和城、平野秀一郎、牧野圭悟、坪井伸成、石田穣治、藤井謙太郎、鷲尾佳奈、柳井広之、伊達 勲

    (一社)日本脳神経外科学会第81回学術総会(現地・Web併催)  2022年9月28日  岩手医科大学 脳神経外科

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    開催年月日: 2022年9月28日 - 2022年10月1日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:横浜  

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  • 脳幹部・脳幹周囲病変における定位脳生検術の有用性と課題

    皮居巧嗣、佐々木達也、石田穣治、大谷理浩、藤井謙太郎、坪井伸成、岡崎洋介、谷本 駿、細本 翔、安原隆雄、伊達 勲

    (一社)日本脳神経外科学会第81回学術総会(現地・Web併催)  2022年9月28日  岩手医科大学 脳神経外科

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    開催年月日: 2022年9月28日 - 2022年10月1日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:横浜  

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  • 小児、AYA世代に対する網羅的メチル化解析による脳腫瘍診断の有用性と限界

    大谷理浩、藤井謙太郎、石田穣治、坪井伸成、牧野圭悟、平野秀一郎、劒持直也、駿河和城、井本良二、水田 亮、鷲尾佳奈、柳生弘之、里見介史、市村幸一、伊達 勲

    (一社)日本脳神経外科学会第81回学術総会(現地・Web併催)  2022年9月28日  岩手医科大学 脳神経外科

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    開催年月日: 2022年9月28日 - 2022年10月1日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:横浜  

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  • 下垂体部腫瘍に対しての、経鼻中隔法での試み

    藤井謙太郎、石田穣治、大谷理浩、牧原靖一郎、伊達 勲

    (一社)日本脳神経外科学会第81回学術総会(現地・Web併催)  2022年9月28日  岩手医科大学 脳神経外科

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    開催年月日: 2022年9月28日 - 2022年10月1日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:横浜  

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  • 聴神経腫瘍の最初における腫瘍微小環境の影響

    牧野圭悟、大谷理浩、藤井謙太郎、石田穣治、畝田篤仁、坪井伸成、平野秀一郎、劒持直也、駿河和城、水田 亮、井本良二、安原隆雄、伊達 勲

    (一社)日本脳神経外科学会第81回学術総会(現地・Web併催)  2022年9月28日  岩手医科大学 脳神経外科

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    開催年月日: 2022年9月28日 - 2022年10月1日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:横浜  

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  • 脳腫瘍周術期のけいれんマネジメントについて 招待

    大谷理浩

    Okayama Glioma Conference(Web開催)  2022年9月7日 

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    開催年月日: 2022年9月7日

    記述言語:日本語   会議種別:口頭発表(基調)  

    開催地:岡山  

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  • 悪性転化リスクのある低悪性度脳腫瘍central nervous system low-grade diffusely infiltrative tumors with INI1 deficiency(CNS LGDIT-INI1)の1例

    井本良二、石田穣治、坪井伸成、大谷理浩、藤井謙太郎、柳井広之、信澤純人、伊達 勲

    第36回中国四国脳腫瘍研究会  2022年9月2日  徳島大学大学院医歯薬学研究部 脳神経外科

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    開催年月日: 2022年9月2日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:広島  

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  • 聴神経腫瘍の再発における腫瘍微小環境の影響(シンポジウム)

    牧野圭悟、大谷理浩、藤井謙太郎、石田穣治、畝田篤仁、坪井伸成、平野秀一郎、劒持直也、駿河和城、井本良二、水田 亮、安原隆雄、伊達 勲

    第22回日本分子脳神経外科学会(現地・Web併催)  2022年7月23日  金沢大学 脳神経外科

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    開催年月日: 2022年7月22日 - 2022年7月23日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:金沢  

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  • Gliomaに対する第2世代REIC/Dkk-3遺伝子発現アデノウイルスとbevacizumabの併用療法

    井本良二、服部靖彦、黒住和彦、大谷理浩、坪井伸成、石田穣治、藤井謙太郎、公文裕巳、伊達 勲

    第28回日本遺伝子細胞治療学会学術集会(現地・Web併催)  2022年7月14日  九州大学大学院薬学研究院 革新的バイオ医薬創成学

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    開催年月日: 2022年7月14日 - 2022年7月16日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:福岡  

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  • 頭蓋底骨削除法─超音波手術器の有用性─(ビデオシンポジウム)

    安原隆雄、佐々田晋、大谷理浩、石田穣治、藤井謙太郎、伊達 勲

    第34回日本頭蓋底外科学会(現地・Web併催)  2022年7月7日  日本医科大学 脳神経外科

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    開催年月日: 2022年7月7日 - 2022年7月8日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:東京  

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  • パーキンソン病に対する新開発小型装置を用いた脊髄電気刺激

    安原隆雄、佐々田晋、佐々木達也、河内 哲、藪野 諭、菅原千明、永瀬喬之、金 一徹、桑原 研、伊達 勲

    第37回日本脊髄外科学会  2022年6月16日  いまえクリニック

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    開催年月日: 2022年6月16日 - 2022年6月17日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:和歌山  

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  • 小児、AYA世代の脳腫瘍に対する網羅的メチル化解析を用いた診断の有用性と限界(シンポジウム)

    大谷理浩、藤井謙太郎、石田穣治、坪井伸成、鷲尾佳奈、柳井広之、里見介史、市村幸一、伊達 勲

    第40回日本脳腫瘍病理学会(現地・Web併催)  2022年5月28日  埼玉医科大学 病理学

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    開催年月日: 2022年5月27日 - 2022年5月28日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:川越  

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  • 当院における毛様細胞性星細胞腫の予後因子に関する検討

    駿河和城、里見介史、大谷理浩、石田穣治、藤井謙太郎、安原隆雄、鷲尾佳奈、柳井広之、市村幸一、伊達 勲

    第40回日本脳腫瘍病理学会(現地・Web併催)  2022年5月28日  埼玉医科大学 病理学

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    開催年月日: 2022年5月27日 - 2022年5月28日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:川越  

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  • AYA世代の脳腫瘍病理 小児、AYA世代の脳腫瘍に対する網羅的メチル化解析を用いた診断の有用性と限界

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    Brain Tumor Pathology  2022年5月  日本脳腫瘍病理学会

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    開催年月日: 2022年5月

    記述言語:日本語  

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    水田 亮、藤井謙太郎、坪井伸成、大谷理浩、石田穣治、藤井伸治、伊達 勲

    第93回(一社)日本脳神経外科学会中国四国支部学術集会  2022年4月2日  愛媛大学医学部 脳神経外科

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    開催年月日: 2022年4月2日 - 2022年4月3日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:松山  

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    石田 穣治, 藤井 謙太郎, 大谷 理浩, 坪井 伸成, 畝田 篤仁, 鷲尾 佳奈, 柳井 広之, 遠西 大輔, 山本 英喜

    小児の脳神経  2022年4月  (一社)日本小児神経外科学会

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    開催年月日: 2022年4月

    記述言語:日本語  

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  • 当院における先端巨大症の総合的治療について

    石田穣治、大谷理浩、藤井謙太郎、畝田篤仁、稲垣兼一、伊達 勲

    第32回一般社団法人日本間脳下垂体腫瘍学会(現地・Web併催)  2022年2月18日  国家公務員共済組合連合会虎の門病院 間脳下垂体外科

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    開催年月日: 2022年2月18日 - 2022年2月19日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:東京  

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  • 高齢者下垂体腺腫の臨床像および外科的治療成績の検討

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    第32回一般社団法人日本間脳下垂体腫瘍学会(現地・Web併催)  2022年2月18日  国家公務員共済組合連合会虎の門病院 間脳下垂体外科

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    開催年月日: 2022年2月18日 - 2022年2月19日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:東京  

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  • 高齢者下垂体腫瘍の臨床像および外科的治療成績の検討

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    第89回岡山内分泌同好会  2022年2月9日  岡山内分泌同好会、岡山大学 腎・免疫・内分泌代謝内科学

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    開催年月日: 2022年2月9日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:岡山  

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    第61回日本定位・機能神経外科学会(現地・Web併催)  2022年1月28日  大阪大学大学院医学系研究科 脳神経外科

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    開催年月日: 2022年1月28日 - 2022年1月29日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:大阪  

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  • 定位脳手術の現在・将来の役割とスキル習得─DBS、脳生検、細胞移植、ウイルス・遺伝子治療、SEEG─(シンポジウム) 招待

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    第61回日本定位・機能神経外科学会(現地・Web併催)  2022年1月28日  大阪大学大学院医学系研究科 脳神経外科

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    開催年月日: 2022年1月28日 - 2022年1月29日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(指名)  

    開催地:大阪  

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  • あすを創る人材育成・働き方改革 定位脳手術の現在・将来の役割とスキル習得 DBS、脳生検、細胞移植、ウイルス・遺伝子療法、SEEG

    佐々木 達也, 細本 翔, 岡崎 洋介, 皮居 巧嗣, 大谷 理浩, 佐々田 晋, 石田 穣治, 藤井 謙太郎, 安原 隆雄, 伊達 勲

    日本定位・機能神経外科学会プログラム・抄録集  2022年1月  (一社)日本定位・機能神経外科学会

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    開催年月日: 2022年1月

    記述言語:日本語  

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  • がんゲノム医療時代における小児グリオーマ診療について

    石田穣治, 藤井謙太郎, 大谷理浩, 坪井伸成, 畝田篤仁, 鷲尾佳奈, 柳井広之, 遠西大輔, 山本英喜

    小児の脳神経(Web)  2022年 

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    開催年月日: 2022年

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    第25回関西脳神経外科手術研究会学術集会(現地・Web併催)  2021年12月18日  大阪大学脳神経外科、金沢大学脳神経外科

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    開催年月日: 2021年12月18日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:大阪  

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  • 高齢者high grade glioma患者に対する集学的治療の検討

    劒持直也、藤井謙太郎、駿河和城、平野秀一郎、牧野圭悟、坪井伸成、畝田篤仁、大谷理浩、石田穣治、島津洋介、伊達 勲

    第39回日本脳腫瘍学会学術集会(現地・Web併催)  2021年12月6日  東京女子医科大学 先端生命医科学研究所

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    開催年月日: 2021年12月5日 - 2021年12月7日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:神戸  

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    石田穣治、藤井謙太郎、大谷理浩、畝田篤仁、佐々木達也、坪井伸成、牧野圭悟、平野秀一郎、劒持直也、駿河和城、伊達 勲

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    開催年月日: 2021年12月5日 - 2021年12月7日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:神戸  

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  • 聴神経鞘腫における初回治療後の増大因子の検討

    牧野圭悟、大谷理浩、駿河和城、劒持直也、平野秀一郎、坪井伸成、畝田篤仁、石田穣治、藤井謙太郎、安原隆雄、伊達 勲

    第39回日本脳腫瘍学会学術集会(現地・Web併催)  2021年12月5日  東京女子医科大学 先端生命医科学研究所

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    開催年月日: 2021年12月5日 - 2021年12月7日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:神戸  

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  • NOTCH経路阻害による腫瘍微小環境の改善と抗腫瘍免疫療法の効果増強(シンポジウム) 国際共著

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    開催年月日: 2021年12月5日 - 2021年12月7日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:神戸  

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    開催年月日: 2021年12月5日 - 2021年12月7日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:神戸  

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    第39回日本脳腫瘍学会学術集会(現地・Web併催)  2021年12月5日  東京女子医科大学 先端生命医科学研究所

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    開催年月日: 2021年12月5日 - 2021年12月7日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:神戸  

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  • CyberKnifeでの定位放射線治療を施行した再発高悪性度神経膠腫における予後因子の検討(シンポジウム)

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    第39回日本脳腫瘍学会学術集会(現地・Web併催)  2021年12月5日  東京女子医科大学 先端生命医科学研究所

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    開催年月日: 2021年12月5日 - 2021年12月7日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:神戸  

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  • びまん性内在性橋神経膠腫モデルに対するMRガイド下集束超音波を用いた薬剤送達強化 低侵襲を目指した血液脳関門の克服

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    小児の脳神経  2021年4月  (一社)日本小児神経外科学会

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    開催年月日: 2021年4月

    記述言語:日本語  

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  • 膠芽腫におけるannexin A2-STAT3-oncostatin M receptor axisを介した表現型シフト

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    開催年月日: 2020年

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  • 腫瘍微小環境における多細胞間のパラクライン相互作用を介した分化型膠芽腫細胞の役割

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    日本脳腫瘍学会プログラム・抄録集  2020年 

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  • AN ANNEXIN A2-REGULATED PHENOTYPIC SHIFT IN GLIOMA

    Yuji Matsumoto, Tomotsugu Ichikawa, Kazuhiko Kurozumi, Yoshihiro Otani, Atsushi Fujimura, Kentaro Fujii, Yosuke Shimazu, Yusuke Tomita, Yasuhiko Hattori, Atsuhito Uneda, Nobushige Tsuboi, Keisuke Kaneda, Keigo Makino, Isao Date

    NEURO-ONCOLOGY  2019年11月  OXFORD UNIV PRESS INC

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    開催年月日: 2019年11月

    記述言語:英語  

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  • Annexin A2の発現変化により規定されるグリオーマ表現型シフトの分子機序解明

    松本 悠司, 市川 智継, 黒住 和彦, 大谷 理浩, 藤村 篤史, 藤井 謙太郎, 冨田 祐介, 服部 靖彦, 畝田 篤人, 伊達 勲

    Brain Tumor Pathology  2019年5月  日本脳腫瘍病理学会

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    開催年月日: 2019年5月

    記述言語:日本語  

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  • 微小環境 神経膠腫(2) Bevacizumab治療におけるグリオーマ浸潤関連因子の検索

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    Brain Tumor Pathology  2019年5月  日本脳腫瘍病理学会

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    開催年月日: 2019年5月

    記述言語:日本語  

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  • Vstat120を発現する腫瘍溶解ヘルペスウイルスはベバシズマブ誘発性グリオーマ浸潤を抑制する

    冨田 祐介, 黒住 和彦, 松本 悠司, 畝田 篤仁, 服部 靖彦, 清水 俊彦, 大谷 理浩, 藤井 謙太郎, Balveen Kaur, 伊達 勲

    Brain Tumor Pathology  2019年5月  日本脳腫瘍病理学会

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    開催年月日: 2019年5月

    記述言語:日本語  

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  • グリオーマにおけるannexin A2-STAT3-oncostatin M receptorを介したmesenchymal transition

    松本悠司, 市川智継, 市川智継, 黒住和彦, 大谷理浩, 大谷理浩, 藤村篤史, 藤井謙太郎, 冨田祐介, 服部靖彦, 畝田篤仁, 坪井伸成, 兼田圭介, 牧野圭悟, 伊達勲

    日本分子脳神経外科学会プログラム・抄録集  2019年 

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    開催年月日: 2019年

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  • 脳腫瘍溶解ヘルペスウイルスの併用はベバシズマブ誘発性のグリオーマ浸潤を抑制する

    牧野圭悟, 冨田祐介, 黒住和彦, 松本悠司, 畝田篤仁, 服部靖彦, 清水俊彦, 清水俊彦, 大谷理浩, 大谷理浩, 藤井謙太郎, 市川智継, 伊達勲

    日本脳腫瘍学会プログラム・抄録集  2019年 

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    開催年月日: 2019年

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  • Bevacizumabと脳腫瘍溶解ヘルペスウイルスの併用はCCN1とAKT経路を阻害することによりbevacizumab誘発性のグリオーマ浸潤を抑制する

    兼田圭介, 冨田祐介, 黒住和彦, 松本悠司, 畝田篤仁, 服部靖彦, 清水俊彦, 大谷理浩, 大谷理浩, 藤井謙太郎, 市川智継, KAUR Balveen, 伊達勲

    日本分子脳神経外科学会プログラム・抄録集  2019年 

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    開催年月日: 2019年

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  • Annexin A2-STAT3-oncostatin M receptorが規定するグリオーマ表現型シフト

    松本悠司, 市川智継, 市川智継, 黒住和彦, 大谷理浩, 大谷理浩, 藤村篤史, 藤井謙太郎, 冨田祐介, 服部靖彦, 畝田篤仁, 兼田圭介, 牧野圭悟, 伊達勲

    日本脳腫瘍学会プログラム・抄録集  2019年 

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    開催年月日: 2019年

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  • δ-cateninはbevacizumabによるグリオーマ浸潤の調整に関わる

    牧野圭悟, 清水俊彦, 黒住和彦, 石田穣治, 大谷理浩, 大谷理浩, 冨田祐介, 服部靖彦, 畝田篤仁, 松本悠司, 市川智継, 伊達勲

    日本分子脳神経外科学会プログラム・抄録集  2019年 

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    開催年月日: 2019年

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  • 腫瘍溶解ウイルスRAMBOはbevacizumab誘発性グリオーマ浸潤を抑制する

    冨田 祐介, 黒住 和彦, 松本 悠司, 服部 靖彦, 清水 俊彦, 大谷 理浩, 藤井 謙太郎, 市川 智継, Balveen Kaur, 伊達 勲

    Brain Tumor Pathology  2018年9月  日本脳腫瘍病理学会

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    開催年月日: 2018年9月

    記述言語:日本語  

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  • δ-cateninはbevacizumab誘導性glioma浸潤を調整する

    清水 俊彦, 黒住 和彦, 石田 穣治, 大谷 理浩, 冨田 祐介, 服部 靖彦, 畝田 篤仁, 松本 悠司, 市川 智継, 伊達 勲

    Brain Tumor Pathology  2018年9月  日本脳腫瘍病理学会

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    開催年月日: 2018年9月

    記述言語:日本語  

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  • Annexin A2が規定するグリオーマ表現型シフトの機序解明

    松本悠司, 市川智継, 市川智継, 黒住和彦, 大谷理浩, 大谷理浩, 藤村篤史, 坪井伸成, 畝田篤仁, 服部靖彦, 冨田祐介, 清水俊彦, 藤井謙太郎, 伊達勲

    日本分子脳神経外科学会プログラム・抄録集  2018年 

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    開催年月日: 2018年

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  • Vstat120を発現する腫瘍溶解ウイルスはCCN1/AKT経路を阻害しグリオーマ浸潤を抑制する

    冨田祐介, 黒住和彦, 松本悠司, 畝田篤仁, 服部靖彦, 清水俊彦, 大谷理浩, 大谷理浩, 藤井謙太郎, 市川智継, KAUR Balveen, 伊達勲

    日本脳腫瘍学会プログラム・抄録集  2018年 

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    開催年月日: 2018年

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  • 腫瘍溶解ウイルスRAMBOはAKTシグナル経路を阻害する事でグリオーマ浸潤を抑制する

    冨田祐介, 黒住和彦, 松本悠司, 畝田篤仁, 服部靖彦, 清水俊彦, 大谷理浩, 大谷理浩, 藤井謙太郎, 市川智継, KAUR Balveen, 伊達勲

    日本分子脳神経外科学会プログラム・抄録集  2018年 

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    開催年月日: 2018年

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  • 大脳皮質上衣腫の臨床的特徴

    市川智継, 市川智継, 松本悠司, 大谷理浩, 大谷理浩, 服部靖彦, 冨田祐介, 清水俊彦, 藤井謙太郎, 黒住和彦, 柳井広之, 伊達勲

    日本脳腫瘍学会プログラム・抄録集  2018年 

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    開催年月日: 2018年

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  • FIBROBLAST GROWTH FACTOR 13 REGULATES GLIOMA CELL INVASION

    Yoshihiro Otani, Tomotsugu Ichikawa, Kazuhiko Kurozumi, Satoshi Inoue, Joji Ishida, Tetsuo Oka, Toshihiko Shimizu, Yusuke Tomita, Yasuhiko Hattori, Atsuhito Uneda, Yuji Matsumoto, Hiroyuki Michiue, Isao Date

    NEURO-ONCOLOGY  2017年11月  OXFORD UNIV PRESS INC

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    開催年月日: 2017年11月

    記述言語:英語  

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  • delta-CATENIN REGULATES BEVACIZUMAB-INDUCED GLIOMA INVASION

    Toshihiko Shimizu, Kazuhiko Kurozumi, Joji Ishida, Tetsuo Oka, Yoshihiro Otani, Yusuke Tomita, Yasuhiko Hattori, Atsuhito Uneda, Yuji Matsumoto, Tomotsugu Ichikawa, Isao Date

    NEURO-ONCOLOGY  2017年11月  OXFORD UNIV PRESS INC

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    開催年月日: 2017年11月

    記述言語:英語  

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  • CORRELATION BETWEEN PIK3R1MET326ILE MUTATION, CYSTEINE-RICH PROTEIN 61 EXPRESSION AND POOR PROGNOSIS IN GLIOBLASTOMA

    Kentaro Fujii, Yoshihiro Otani, Joji Ishida, Kazuhiko Kurozumi, Tetsuo Oka, Toshihiko Shimizu, Yusuke Tomita, Yasuhiko Hattori, Atsuhito Uneda, Yuji Matsumoto, Hiroyuki Michiue, Tomotsugu Ichikawa, Isao Date

    NEURO-ONCOLOGY  2017年11月  OXFORD UNIV PRESS INC

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    開催年月日: 2017年11月

    記述言語:英語  

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  • δ-cateninはbevacizumab誘導性glioma浸潤を調節する

    清水 俊彦, 黒住 和彦, 石田 穣治, 岡 哲生, 大谷 理浩, 冨田 祐介, 服部 靖彦, 市川 智継, 伊達 勲

    Brain Tumor Pathology  2017年5月  日本脳腫瘍病理学会

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    開催年月日: 2017年5月

    記述言語:日本語  

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  • midline gliomaの長期治療成績の検討

    服部 靖彦, 黒住 和彦, 藤井 謙太郎, 大谷 理浩, 清水 俊彦, 冨田 祐介, 市川 智継, 柳井 広之, 伊達 勲

    Brain Tumor Pathology  2017年5月  日本脳腫瘍病理学会

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    開催年月日: 2017年5月

    記述言語:日本語  

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  • PIK3R1 germline mutationはGBMにおけるCCN1発現および予後と相関する

    大谷 理浩, 黒住 和彦, 石田 穣治, 岡 哲生, 清水 俊彦, 冨田 祐介, 服部 靖彦, 道上 宏之, 市川 智継, 伊達 勲

    Brain Tumor Pathology  2017年5月  日本脳腫瘍病理学会

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    開催年月日: 2017年5月

    記述言語:日本語  

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  • 腫瘍溶解ウイルスRAMBOはbevacizumab誘発性グリオーマ浸潤を抑制する

    冨田 祐介, 黒住 和彦, 服部 靖彦, 清水 俊彦, 岡 哲生, 大谷 理浩, 石田 穣治, 市川 智継, Balveen Kaur, 伊達 勲

    Brain Tumor Pathology  2017年5月  日本脳腫瘍病理学会

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    開催年月日: 2017年5月

    記述言語:日本語  

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  • 診断に苦慮している左前頭葉嚢胞性腫瘍の一例

    黒住 和彦, 石田 穣治, 市川 智継, 大谷 理浩, 清水 俊彦, 冨田 祐介, 服部 靖彦, 田中 健大, 柳井 広之, 伊達 勲

    Brain Tumor Pathology  2017年5月  日本脳腫瘍病理学会

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    開催年月日: 2017年5月

    記述言語:日本語  

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  • 第2世代REIC/Dkk-3遺伝子発現アデノウイルスとbevacizumab併用による抗腫瘍効果の検討

    服部靖彦, 黒住和彦, 大谷理浩, 藤井謙太郎, 清水俊彦, 冨田祐介, 畝田篤仁, 松本悠司, 市川智継, 公文裕巳, 伊達勲

    日本脳腫瘍学会プログラム・抄録集  2017年 

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    開催年月日: 2017年

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  • 動物モデルを用いた悪性グリオーマのangiogenesis-invasion shiftの機序解明

    松本悠司, 市川智継, 大谷理浩, 黒住和彦, 藤井謙太郎, 石田穣治, 清水俊彦, 冨田祐介, 服部靖彦, 畝田篤仁

    日本脳腫瘍学会プログラム・抄録集  2017年 

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    開催年月日: 2017年

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  • Microtubule dynamicsを介したグリオーマの浸潤に関与する遺伝子FGF13の機能解析

    松本悠司, 大谷理浩, 市川智継, 黒住和彦, 藤井謙太郎, 清水俊彦, 冨田祐介, 服部靖彦, 畝田篤仁, 道上宏之, 伊達勲

    日本分子脳神経外科学会プログラム・抄録集  2017年 

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    開催年月日: 2017年

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  • Bevacizumab治療におけるglioma浸潤規定因子δ-cateninの検討

    清水俊彦, 黒住和彦, 石田穣治, 岡哲生, 大谷理浩, 冨田祐介, 服部靖彦, 畝田篤仁, 松本悠司, 市川智継, 伊達勲

    日本脳腫瘍学会プログラム・抄録集  2017年 

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    開催年月日: 2017年

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  • PIK3R1 germline mutationはglioblastomaにおけるCCN1発現および予後と相関する

    畝田篤仁, 大谷理浩, 黒住和彦, 藤井謙太郎, 清水俊彦, 冨田祐介, 服部靖彦, 松本悠司, 道上宏之, 市川智継, 伊達勲

    日本脳腫瘍学会プログラム・抄録集  2017年 

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    開催年月日: 2017年

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  • 小児midline gliomaの長期治療成績

    黒住和彦, 亀田雅博, 石田穣治, 服部靖彦, 大谷理浩, 清水俊彦, 冨田祐介, 藤井謙太郎, 鷲尾佳奈, 嶋田明, 伊達勲

    小児の脳神経  2017年 

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    開催年月日: 2017年

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  • 診断と治療方針に苦慮した左前頭葉嚢胞性腫瘍の1例

    石田穣治, 黒住和彦, 市川智継, 大谷理浩, 服部靖彦, 清水俊彦, 冨田祐介, 鷲尾佳奈, 嶋田明, 田中健大, 柳井広之, 伊達勲

    小児の脳神経  2017年 

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    開催年月日: 2017年

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  • PIK3R1germline mutationはglioblastoma multiformeにおけるCCN1発現および予後と相関する

    畝田篤仁, 大谷理浩, 黒住和彦, 藤井謙太郎, 清水俊彦, 冨田祐介, 服部靖彦, 松本悠司, 道上宏之, 市川智継, 伊達勲

    日本分子脳神経外科学会プログラム・抄録集  2017年 

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    開催年月日: 2017年

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  • Gliomaに対する第2世代REIC/Dkk-3遺伝子発現アデノウイルスとbevacizmabの併用効果

    服部靖彦, 服部靖彦, 黒住和彦, 大谷理浩, 藤井謙太郎, 清水俊彦, 冨田祐介, 畝田篤仁, 松本悠司, 市川智継, 公文裕巳, 伊達勲

    日本分子脳神経外科学会プログラム・抄録集  2017年 

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    開催年月日: 2017年

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  • グリオーマ浸潤規定遺伝子FGF13の同定と動物モデルを用いた機能解析

    市川智継, 大谷理浩, 黒住和彦, 藤田謙太郎, 清水俊彦, 冨田祐介, 服部靖彦, 畝田篤仁, 松本悠司, 道上宏之, 伊達勲

    日本脳腫瘍学会プログラム・抄録集  2017年 

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    開催年月日: 2017年

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  • Congenital glioblastoma 2例の分子病理学的解析

    大谷 理浩, 市川 智継, 亀田 雅博, 黒住 和彦, 石田 穣治, 岡 哲生, 清水 俊彦, 冨田 祐介, 柳井 広之, 伊達 勲

    Brain Tumor Pathology  2016年5月  日本脳腫瘍病理学会

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    開催年月日: 2016年5月

    記述言語:日本語  

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  • 先天性膠芽腫の臨床的・分子生物学的特徴

    市川智継, 亀田雅博, 大谷理浩, 黒住和彦, 石田穣治, 嶋田明, 鷲尾佳奈, 柳井広之, 伊達勲

    小児の脳神経  2016年 

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    開催年月日: 2016年

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  • CAS 二刀流術者からの提言 二刀流術者のCASとCEAによる頸動脈狭窄症治療の有用性と限界

    徳永 浩司, 渡邊 恭一, 河内 哲, 大谷 理浩, 井上 智, 桐山 英樹, 菱川 朋人, 杉生 憲志, 松本 健五

    JNET: Journal of Neuroendovascular Therapy  2015年11月  (NPO)日本脳神経血管内治療学会

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    開催年月日: 2015年11月

    記述言語:日本語  

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  • 中枢神経原発リンパ腫に対する非照射治癒を目指した移植併用超大量化学療法

    市川 智継, 近藤 英生, 黒住 和彦, 大谷 理浩, 前田 嘉信, 吉野 正, 谷本 光音, 伊達 勲

    日本リンパ網内系学会会誌  2015年6月  (一社)日本リンパ網内系学会

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    開催年月日: 2015年6月

    記述言語:日本語  

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  • 浸潤性グリオーマモデルにおける血管新生とpericyteに関する病理学的検討

    松本悠司, 市川智継, 大谷理浩, 黒住和彦, 石田穣治, 島津洋介, 岡哲生, 清水俊彦, 冨田祐介, 伊達勲

    日本脳腫瘍学会プログラム・抄録集  2015年 

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    開催年月日: 2015年

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  • 浸潤性グリオーマモデルを用いた浸潤能規定遺伝子の同定と機能解析

    大谷理浩, 市川智継, 黒住和彦, 石田穣治, 島津洋介, 岡哲生, 清水俊彦, 冨田祐介, 松本悠司, 伊達勲

    日本脳腫瘍学会プログラム・抄録集  2015年 

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    開催年月日: 2015年

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  • 中枢神経原発リンパ腫に対する寛解導入後の地固め療法:3つのレジメンの比較

    市川智継, 近藤英生, 黒住和彦, 大谷理浩, 石田穣治, 島津洋介, 岡哲生, 清水俊彦, 冨田祐介, 松本悠司, 前田嘉信, 伊達勲

    日本脳腫瘍学会プログラム・抄録集  2015年 

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    開催年月日: 2015年

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  • THE ANTI ANGIOGENIC AND INVASIVE EFFECTS OF AN INTEGRIN INHIBITOR AGAINST BEVACIZUMAB-INDUCED INVASIVE GLIOMA

    Joji Ishida, Manabu Onishi, Kazuhiko Kurozumi, Tomotsugu Ichikawa, Kentaro Fujii, Yosuke Shimazu, Tetsuo Oka, Yoshihiro Otani, Toshihiko Shimizu, Isao Date

    NEURO-ONCOLOGY  2014年11月  OXFORD UNIV PRESS INC

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    開催年月日: 2014年11月

    記述言語:英語  

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  • テント上異所性上衣腫の臨床像と治療

    大谷理浩, 市川智継, 黒住和彦, 清水俊彦, 木谷尚哉, 嶋田明, 鷲尾佳奈, 小田慈, 藤井邦彰, 柳井広之, 小野成紀, 伊達勲

    日本小児血液・がん学会雑誌  2014年 

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    開催年月日: 2014年

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  • 神経線維腫症に合併した椎骨動静脈瘻の1例

    大谷 理浩, 杉生 憲志, 徳永 浩司, 菱川 朋人, 大熊 佑, 伊丹 尚多, 伊達 勲

    JNET: Journal of Neuroendovascular Therapy  2011年11月  (NPO)日本脳神経血管内治療学会

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    開催年月日: 2011年11月

    記述言語:日本語  

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▼全件表示

受賞

  • 岡山大学グローバル最先端異分野融合研究機構 研究拠点形成支援事業

    2024年   岡山大学  

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  • 令和4年 次世代研究育成グループ

    2023年2月   岡山大学  

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  • 学会奨励賞・特別賞

    2022年9月   日本脳神経外科学会  

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  • 大藤内分泌医学賞

    2022年8月  

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  • Outstanding Research Fellow Award

    2020年11月   University of Texas Health Science Center at Houston  

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  • Deans’ Excellence in Research Award Symposium for Postdoctoral Research Fellows

    2020年5月   University of Texas Health Science Center at Houston  

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  • がん研究奨励賞(林原賞・山田賞)

    2018年6月   岡山医学会  

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  • 海外留学助成金リサーチフェローシップ

    2018年   上原記念財団  

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共同研究・競争的資金等の研究

  • Radiogenomics解析による脳腫瘍代謝産物の可視化と、治療応用

    2025年

    公益財団法人カシオ科学振興財団 

    大谷 理浩、諸岡健一、松本悠司、井本良二

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  • マルチオミクス解析を用いた膠芽腫微小環境の解明と、新規免疫療法の開発

    2025年

    公益財団法人 武田科学振興財団  研究助成 

    大谷 理浩

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  • HDAC阻害薬によるtumor ecosystemの打破と、新規併用療法への応用

    研究課題/領域番号:24K12285  2024年04月 - 2027年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    藤井 謙太郎, 平野 秀一郎, 大谷 理浩, 石田 穣治

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

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  • 腸脳相関によるサイトカインを中心とした膠芽腫Cancer Stem Cell Theoryの解明

    研究課題/領域番号:24K12244  2024年04月 - 2027年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    平野 秀一郎, 駿河 和城, 藤井 謙太郎, 大谷 理浩, 石田 穣治

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

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  • 空間発現解析による脳腫瘍の形態診断と遺伝子診断の統合による悪性化マーカーの検索

    研究課題/領域番号:24K12222  2024年04月 - 2027年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    駿河 和城, 藤井 謙太郎, 大谷 理浩, 石田 穣治

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

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  • クロマチンリモデリングによる疲弊型T細胞の克服

    2024年 - 2025年

    上原記念生命科学財団 

    大谷理浩、松下博和、黒住和彦

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  • 腫瘍微小環境の再構築による、膠芽腫に対する新規免疫療法の開発

    2024年 - 2025年

    公益財団法人 中外創薬科学財団 

    大谷 理浩

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    担当区分:研究代表者 

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  • 腸脳相関による腫瘍微小環境の制御と、膠芽腫に対する免疫療法の効果改善

    2024年 - 2025年

    公益財団法人 野口研究所 

    大谷 理浩

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  • 性差による中枢神経系免疫の違いが脳腫瘍免疫療法に与える影響の解明

    2024年 - 2025年

    公益財団法人 神澤医学研究振興財団 

    大谷理浩、松下博和

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  • 腫瘍内因性PD L1 シグナルを標的とした膠芽腫に対する新規治療開発

    2024年

    興和生命科学振興財団 

    大谷理科浩、藤村篤史、松本悠司

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  • 空間マルチオミクス解析によるHigh-grade astrocytoma with piloid featuresに特異的な診断マーカーおよび治療標的の探索

    2023年08月 - 2024年03月

    日本脳腫瘍学会 

    大谷理浩

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    担当区分:研究代表者 

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  • 一細胞時空間解析を用いた膠芽腫微小環境の再構築機序の解明と新規免疫療法の開発

    2023年05月 - 2025年03月

    日本医療研究開発機構  次世代がん医療加速化研究事業 

    大谷理浩

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    担当区分:研究代表者 

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  • 小児脳幹神経膠腫に対する血液脳関門の障壁を克服する治療法の開発

    研究課題/領域番号:23K08569  2023年04月 - 2026年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    石田 穣治, 大谷 理浩

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

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  • 脳腫瘍の新規術中蛍光診断システムの構築と治療への応用

    研究課題/領域番号:23K27708  2023年04月 - 2026年03月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    田中 將太, 北川 陽介, 石田 穣治, 大谷 理浩, 高柳 俊作, 高見 浩数

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    配分額:18850000円 ( 直接経費:14500000円 、 間接経費:4350000円 )

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  • 機械学習を用いた腫瘍代謝産物の可視化による脳腫瘍の構造的脆弱性の検出と治療応用

    2023年03月

    公益財団法人 コニカミノルタ科学技術振興財団  令和4年度 コニカミノルタ画像科学奨励賞 

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    担当区分:研究代表者 

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  • 一細胞時空間解析による神経膠腫の構造的脆弱性を標的とした新規免疫法の開発

    2023年02月

    公益財団法人 高松宮妃癌研究基金  令和4年度 研究助成金 

    大谷 理浩

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    担当区分:研究代表者 

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  • びまん性正中神経膠腫のcell of originに着目した治療抵抗性の解明

    2023年 - 2024年

    公益財団法人 川野小児医学奨学財団 

    大谷理浩

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    担当区分:研究代表者 

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  • 空間トランスクリプトーム解析による小児脳腫瘍の悪性化予測マーカーの確立

    2023年 - 2024年

    公益財団法人 鈴木謙三記念医科学応用研究財団 

    大谷理浩

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    担当区分:研究代表者 

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  • 神経膠腫の構造的脆弱性とメチオニン代謝に着目した 新規免疫療法の開発

    2022年12月

    公益財団法人SGH財団  第34回SGHがん研究助成 

    大谷理浩

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    担当区分:研究代表者 

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  • エピゲノムおよびゲノム解析を用いた視床下部腫瘍の病態解明

    2022年08月

    大藤内分泌医学賞 

    大谷理浩

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  • 時空間的単細胞解析を駆使した膠芽腫に対する新規治療法の開発

    2022年07月 - 2023年06月

    一般財団フォーデイズ自立支援協会 

    大谷理浩

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    担当区分:研究代表者 

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  • 神経膠腫のpassenger deletionに伴う構造的脆弱性を標的とした治療

    研究課題/領域番号:22K16687  2022年04月 - 2025年03月

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    大谷 理浩

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

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  • 時空間単細胞解析によるTumor ecosystemを標的とした脳腫瘍に対する免疫チェックポイント阻害薬の効果増強

    2022年01月

    公益財団法人安田記念医学財団  令和3年度(2021年度)若手癌研究助成 

    大谷理浩

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    担当区分:研究代表者 

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  • 腸脳相関による骨髄系細胞のリプログラミングに着目した膠芽腫に対する新規治療標的の解明

    2022年

    公益財団法人 ヤクルト・バイオサイエンス研究財団  一般研究 助成金 

    大谷理浩

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  • 膠芽腫に対する遺伝子治療臨床検体を用いた網羅的空間発現解析による抗腫瘍免疫獲得機序の解明

    2022年

    公益財団法人がん研究振興財団  令和3年度(第54回)がん研究助成金 

    大谷理浩

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  • 単細胞解析による免疫抑制骨髄系細胞分化機序の解明と、新規腫瘍溶解ウイルスの開発

    研究課題/領域番号:21K20803  2021年08月 - 2023年03月

    日本学術振興会  科学研究費助成事業 研究活動スタート支援  研究活動スタート支援

    大谷 理浩

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    配分額:3120000円 ( 直接経費:2400000円 、 間接経費:720000円 )

    本研究の目的は、膠芽腫に対する腫瘍溶解ヘルペスウイルス療法(oncolytic herpes simplex virus, oHSV)によって活性化するNOTCH経路が抗腫瘍免疫に与える影響の解明である。まずNOTCH経路が膠芽腫微小環境に与える影響を評価するため、The Cancer Genome Atlas (TCGA)に登録された膠芽腫416症例についてNOTCH経路の活性化を調べ、NOTCH高発現群および低発現群に分類した。更に、CIBERSORT解析を用いてそれぞれの群における免疫細胞の頻度を調べたところ、NOTCH高発現群において特に免疫抑制型マクロファージであるM2型マクロファージが増加していた。同様に、GSEA解析でもM2マクロファージやMDSC等の免疫抑制型骨髄系細胞が増加していた。
    次に、担腫瘍マウスモデルを用いてin vivoにおける免疫細胞の評価を行った。担腫瘍マウスモデルに対してoHSVを投与したところNOTCH経路の活性化を認め、免疫細胞浸潤が確認された。一方でoHSVとNOTCH阻害薬を併用した群では、M2型マクロファージやMDSCの集簇が減少した。以上より、NOTCH経路は膠芽腫における免疫抑制型骨髄系細胞の集簇に関与していることが示唆された。
    我々は主に腫瘍細胞におけるNOTCH経路の活性化に着目してたが、腫瘍微小環境における免疫細胞等でもNOTCH経路は活性化しうると考えられた。NOTCH経路は細胞のプログラミングに関与する経路であるため、今後はこのプログラミング機構について解析を行う予定である。

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  • グリオーマにおける免疫微小環境関連germlineバリアントの解析

    研究課題/領域番号:21K09100  2021年04月 - 2024年03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)

    杉生 憲志, 黒住 和彦, 畝田 篤仁, 藤井 謙太郎, 石田 穣治, 大谷 理浩

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

    グリオーマは予後不良な脳腫瘍であり, その中で最も悪性度の高いグリオブラストーマの5年生存率はわずか10%である. 近年, 腫瘍細胞でのみ生じるsomatic(体細胞)遺伝子変異の解析が進んでいるが, 患者が生まれながらに持ち, 体内のすべての細胞で生じるgermline(生殖細胞系列)バリアントについては未だ不明な点が多い. 本邦で開発され, ノーベル賞にも輝いた免疫チェックポイント阻害剤をはじめとする様々な免疫療法が実臨床に応用されているが, グリオーマに対しては有効性を示せていない. 免疫療法の有効性を決定する要素の一つとして, 腫瘍の免疫微小環境が注目されているが, 体内の全細胞に存在するgermlineバリアントは, 腫瘍細胞のみならず免疫微小環境にも強い影響を与える可能性がある. しかし, germlineバリアントと, グリオーマの予後や免疫微小環境との関連に着目して解析を行ったという報告はこれまでにほとんどない. 本研究では, TCGAのグリオーマ患者約のゲノム配列データを用いて, PIK3R1 Met326Ile germline変異がグリオーマの発生率, 予後, さらには免疫微小環境に与える影響について解析を行う. PIK3R1 M326Ileのホモ変異型 (PIK3R1 M326Ile Homo MT)は, 予後が悪い傾向はあるが, 3群解析で有意差はつかず(Homo MT vs WT + Hetero MTで比較すると有意差あり), BLACK OR AFRICAN AMERICANで有意に多いことがわかった. また, 人種ごとに解析した場合も, PIK3R1 M326IleのHomo MTは, 予後が悪い傾向はあることがわかった. 人種ごとに健常人とGBMで比較すると, PIK3R1 M326Ile変異は, 疾患発症リスクには関与しないということがわかった. ホモ変異型 (PIK3R1 M326Ile Homo MT)では, MTAPやIFNの変異が多く, PIK3R1 M326Ile変異が免疫微小環境に影響を与える可能性が示唆された.

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  • 悪性神経膠腫に対する新規遺伝子療法の効果予測因子の解明

    2021年 - 2022年

    公益財団法人ウエスコ学術振興財団 

    大谷 理浩

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  • 膠芽腫に対する遺伝子療法により誘導される抗腫瘍免疫の検討

    2021年 - 2022年

    公益財団法人川崎医学・医療福祉学振興会 

    大谷 理浩

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  • 単細胞解析を用いた骨髄系細胞リプログラミングによる脳腫瘍に対する効果的な免疫療法の開発

    2021年 - 2022年

    公益財団法人 寺岡記念育英会 

    大谷 理浩

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  • 遺伝子治療製品「Ad-SGE-REIC」の再発悪性神経膠腫対象第I/IIa相試験

    研究課題/領域番号:20lm0203095h0002  2019年04月 - 2021年03月

    国立研究開発法人日本医療研究開発機構  橋渡し研究戦略的推進プログラムシーズC 

    伊達 勲, 黒住和彦, 藤井謙太郎, 石田穣治, 大谷理浩

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    資金種別:競争的資金

    配分額:22094000円

    Reduced Expression in Immortalized Cells/Dickkopf-3(REIC/Dkk-3)は岡山大学で発見され,様々ながんで発現が低下している“がん抑制遺伝子”であり,前立腺がん,悪性胸膜中皮腫においてERストレスを介してアポトーシスを誘導すると報告されている.また,前立腺がんにおいてはREIC/Dkk-3による免疫反応を介した抗腫瘍効果の報告もある.悪性神経膠腫細胞に関しては,REIC/Dkk-3がWnt/Dkk-3シグナル伝達経路を阻害し,caspaseを活性化することで細胞増殖を抑制することが報告されている.本研究開発の課題は,“再発悪性神経膠腫を対象とした遺伝子治療製品「Ad-SGE-REIC」の第I/IIa相試験”であり,令和2年度の目標は,症例登録を終了し,すべての症例の評価を終えることとする.

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担当授業科目

  • 臨床医歯科学概論 (2024年度) 集中  - その他