山下 真治 (ヤマシタ シンジ)

YAMASHITA Shinji

写真a

所属

医学部 附属病院 脳神経外科

職名

講師

外部リンク

学位 【 表示 / 非表示

  • 博士(医学) ( 2020年3月   宮崎大学 )

  • 学士(医学) ( 2000年3月   宮崎医科大学 )

研究分野 【 表示 / 非表示

  • ライフサイエンス / 脳神経外科学

 

論文 【 表示 / 非表示

  • PBRM1 and BAP1: novel genetic mutations in malignant transformation of craniopharyngioma—a case report 査読あり

    Tamura M., Yokogami K., Watanabe T., Kawano T., Muta J., Yamashita S., Oguri N., Sato Y., Takeshima H.

    Brain Tumor Pathology   40 ( 1 )   40 - 44   2023年1月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Brain Tumor Pathology  

    Malignant craniopharyngioma is especially rare, so the causes and genetic mutations associated with the malignant transformation have not been explained in detail. We investigated the molecular genetic characteristics of malignant transformation in craniopharyngioma. A 53-year-old man with a history of adamantinomatous craniopharyngioma presented with complaints of subcutaneous swelling. Magnetic resonance imaging showed a less enhanced intradural supra-sellar lesion and a heterogeneously well-enhanced extradural invasive lesion infiltrating the dura mater, brain, frontal bone, and subcutaneous tissue. Histopathological examination of the recurrent tumor revealed typical findings of both craniopharyngioma (intradural supra-sellar lesion) and malignant transformation, such as marked nuclear atypia with mitosis (invasive extradural lesion), which were not present in the primary tumor. A genetic panel test with the Oncopanel system was performed to investigate the genetic mutations responsible for the malignant transformation. Four genetic mutations were identified: CTNNB1 c.C98T, TP53 p.C135fs*35(PLS = 3 UPD/LOH), PBRM1 p.R1000*(PLS = 3 UPD/LOH), and BAP1 p.L650fs*5(PLS = 3 UPD/LOH). Sanger sequencing showed CTNNB1 in both the intradural supra-sellar and extradural invasive lesions, but TP53, PBRM1, and BAP1 only in the extradural invasive lesion. The genetic mutations of PBRM1 and BAP1 may be genetic factors in the malignant transformation of adamantinomatous craniopharyngioma.

    DOI: 10.1007/s10014-022-00444-3

    Scopus

  • Methionine regulates self-renewal, pluripotency, and cell death of GIC through cholesterol—rRNA axis 査読あり

    Yokogami K., Kikuchi T., Watanabe T., Nakatake Y., Yamashita S., Mizuguchi A., Takeshima H.

    BMC Cancer   22 ( 1 )   2022年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BMC Cancer  

    Background: Glioma-initiating cells (GICs) are the source of glioma cells that can self-renew, have pluripotency, and are treatment-resistant, so are the starting point for relapse and eventual death despite multimodality therapy. L-[methyl-11C] methionine PET has observed high accumulation at the time of recurrence, it is important to understand the mechanism of tumor cell activation caused by the reorganization of methionine metabolism. Methods: We cultured cells in methionine-deprived culture medium for comprehensive analysis. Based on the obtained results, the possible target molecules were chemically inhibited and the respective markers were analyzed. Results: Methionine depletion markedly decreased proliferation and increased cell death of GICs. Decreased S-adenosyl-methionine, which is synthesized intracellularly by catalyzed by methionine adenosyltransferase using methionine, triggered the following: (i) global DNA demethylation, (ii) hyper-methylation of signaling pathways regulating pluripotency of stem cells, (iii) decreased expression of the core-genes and pluripotent markers of stem cells including FOXM1, SOX2, SOX4, PROM1, and OLIG2, (iv) decreased cholesterol synthesis and increased excretion mainly through decreased SREBF2, and (v) down-regulation of the large subunit of ribosomal protein configured 28S and ACA43, small nucleolar RNA guiding the pseudouridylation of 28S rRNA, which is essential for translation. In addition, inhibition of cholesterol synthesis with statin resulted in a phenotype similar to that of methionine depletion and decreases in stem cell markers and small nucleolar RNA ACA43. Moreover, suppression of FOXM1 decreased stem cell markers such as SOX4 and PROM1. The gene expression profile for cholesterol production was obtained from the Ivy Glioblastoma Atlas Project database and compared between tumor cells with relatively low methionine levels in areas of pseudopalisading arrangement around necrosis and tumor cells in the infiltrating region, showing that cells in the infiltrating region have higher capacity to produce cholesterol. Conclusions: Methionine metabolism is closely related with self-renewal, pluripotency, and cell death in GICs through modification of cholesterol biosynthesis, especially in the SREBF2-FOXM1 and ACA43 axis with modification of rRNA.

    DOI: 10.1186/s12885-022-10280-5

    Scopus

  • Epigenetic upregulation of Schlafen11 renders WNT- and SHH- activated medulloblastomas sensitive to cisplatin 査読あり

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

    Neuro-oncology   2022年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • T2-fluid-attenuated inversion recovery mismatch sign in lower grade gliomas: correlation with pathological and molecular findings 査読あり

    Yamashita S., Takeshima H., Kadota Y., Azuma M., Fukushima T., Ogasawara N., Kawano T., Tamura M., Muta J., Saito K., Takeishi G., Mizuguchi A., Watanabe T., Ohta H., Yokogami K.

    Brain Tumor Pathology   39 ( 2 )   88 - 98   2022年4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)   出版者・発行元:Brain Tumor Pathology  

    After the new molecular-based classification was reported to be useful for predicting prognosis, the T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign has gained interest as one of the promising methods for detecting lower grade gliomas (LGGs) with isocitrate dehydrogenase (IDH) mutations and chromosome 1p/19q non-codeletion (IDH mut-Noncodel) with high specificity. Although all institutions could use T2-FLAIR mismatch sign without any obstacles, this sign was not completely helpful because of its low sensitivity. In this study, we attempted to uncover the mechanism of T2-FLAIR mismatch sign for clarifying the cause of this sign’s low sensitivity. Among 99 patients with LGGs, 22 were T2-FLAIR mismatch sign-positive (22%), and this sign as a marker of IDH mut-Noncodel showed a sensitivity of 55.6% and specificity of 96.8%. Via pathological analyses, we could provide evidence that not only microcystic changes but the enlarged intercellular space was associated with T2-FLAIR mismatch sign (p = 0.017). As per the molecular analyses, overexpression of mTOR-related genes (m-TOR, RICTOR) were detected as the molecular events correlated with T2-FLAIR mismatch sign (p = 0.020, 0.030. respectively). Taken together, we suggested that T2-FLAIR mismatch sign could pick up the IDH mut-Noncodel LGGs with enlarged intercellular space or that with overexpression of mTOR-related genes.

    DOI: 10.1007/s10014-022-00433-6

    Scopus

    PubMed

  • Selection of surgical approach for cerebellar hemangioblastomas based on venous drainage patterns

    Watanabe T., Suematsu Y., Saito K., Takeishi G., Yamashita S., Ohta H., Yokogami K., Takeshima H.

    Neurosurgical Review   44 ( 6 )   3567 - 3579   2021年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Neurosurgical Review  

    Cerebellar hemangioblastomas remain surgically challenging because of the narrow, deep surgical corridors and tumor hypervascularity. Various surgical approaches are used according to the location, but optimal approaches have not been established. We propose a system of surgical approaches based on the venous drainage systems to facilitate surgical planning and achieve acceptable neurological outcomes. Cerebellar hemangioblastomas were divided into five types based on the main drainage systems: suboccipital hemangioblastomas draining to the transverse sinus (TS) or torcula, tentorial hemangioblastomas draining to the tentorial sinus or straight sinus, petrosal hemangioblastomas draining to the superior petrosal sinus (SPS), quadrigeminal hemangioblastomas draining to the galenic system, and tonsillar hemangioblastomas draining to the TS or torcula in conjunction with jugular bulb or SPS. Microsurgical approaches and patient outcome were retrospectively reviewed according to this classification. This study included 17 patients who underwent 21 operations for resection of 19 cerebellar hemangioblastomas, classified into 9 suboccipital, 4 tentorial, 2 petrosal, 2 quadrigeminal, and 2 tonsillar. Standard suboccipital craniotomies were utilized for suboccipital hemangioblastomas, the occipital transtentorial approach (OTA), and supracerebellar infratentorial approach for tentorial hemangioblastomas, the retrosigmoid approach for petrosal hemangioblastomas, OTA for quadrigeminal hemangioblastomas, and midline suboccipital approach for tonsillar hemangioblastomas. Gross total resection was achieved in all patients except one. Two patients with large hemangioblastomas (tonsillar and quadrigeminal) required second-stage operation which finally achieved gross total removal. No single approach had a significantly higher incidence of postoperative neurological deficits. Selection of the optimum surgical approach for cerebellar hemangioblastomas was successful based on the main drainage systems. Understanding of tumor growth and extension with respect to the venous drainage system is critical to select the appropriate surgical approach.

    DOI: 10.1007/s10143-021-01544-y

    Scopus

    PubMed

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書籍等出版物 【 表示 / 非表示

  • 悪性脳腫瘍のすべて 化学療法2 中枢神経系胚細胞腫

    山下真治  竹島秀雄( 担当: 共著)

    MC メディカ出版  2020年10月 

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    記述言語:日本語 著書種別:学術書

講演・口頭発表等 【 表示 / 非表示

  • 紹介脳生検で脳炎の診断となった悪性リンパ腫頭蓋内再発の1例

    山下 真治

    第39回日本脳腫瘍学会  2021年12月 

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    開催年月日: 2021年12月4日 - 2021年12月6日

    会議種別:ポスター発表  

  • オプチューン 長期使用例と再発例

    山下 真治

    第4回オプチューンラウンドテーブル  2021年11月23日 

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    開催年月日: 2021年11月23日

    会議種別:口頭発表(一般)  

  • T2-FLAIR mismatch signを呈するlower grade gliomaに関する臨床病理学的検討

    山下 真治

    第80回日本脳神経外科学会総会  2021年10月 

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    開催年月日: 2021年10月27日 - 2021年10月30日

    会議種別:ポスター発表  

  • ベバシズマブ投与終了後に発生し、急速な増大を認めた放射線誘発腫瘍の1例

    山下 真治

    第139回日本脳神経外科学会九州支部会 

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    開催年月日: 2021年9月4日

    会議種別:口頭発表(一般)  

  • 治療難治例に対するチラブルチニブ使用経験

    山下 真治

    九州PCNSL研究会  2021年8月 

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    開催年月日: 2021年8月20日

    会議種別:口頭発表(一般)  

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科研費(文科省・学振・厚労省)獲得実績 【 表示 / 非表示

  • EVI1によるPDGFRβ転写制御とグリオブラストーマ血管新生機構について

    研究課題/領域番号:22K09237  2022年04月 - 2027年03月

    独立行政法人日本学術振興会  科学研究費補助金  基盤研究(C)

    水口 麻子、

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    担当区分:研究分担者 

  • 代謝経路再編成が概日リズム経路を介し、幹細胞性維持、細胞死回避に及ぼす影響の解明

    研究課題/領域番号:22K09262  2022年04月 - 2025年03月

    独立行政法人日本学術振興会  科学研究費補助金  基盤研究(C)

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    担当区分:研究分担者 

  • オルガノイドーシングルセル解析法によるグリオーマ血管擬態の分子機構解明

    研究課題/領域番号:22K16692  2022年04月 - 2025年03月

    独立行政法人日本学術振興会  科学研究費補助金  若手研究

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    担当区分:研究代表者 

 

授業 【 表示 / 非表示

  • 環境と生命

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    科目区分:共通教育科目