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Leptomeningeal metastasis and liquid biopsy for medulloblastoma

Research Project

Project/Area Number 19K08345
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionOsaka University

Principal Investigator

Kijima Noriyuki  大阪大学, 大学院医学系研究科, 助教 (80534627)

Co-Investigator(Kenkyū-buntansha) 金村 米博  独立行政法人国立病院機構大阪医療センター(臨床研究センター), その他部局等, 機関長・部門長クラス (80344175)
Project Period (FY) 2019-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords髄芽腫 / 髄膜播種 / リキッドバイオプシー
Outline of Research at the Start

本研究では小児悪性脳腫瘍の代表である髄芽腫における予後不良因子であるとされる髄膜播種について、そのメカニズムを同定しさらに治療標的分子の同定を行う。また髄芽腫においては血液および髄液中を循環する腫瘍細胞の存在(CTC)も確認されており、本研究ではこのCTCを用いて、髄芽種の診断(リキッドバイオプシー)への応用と治療効果評価のバイオマーカーとしての可能性についての検討も行う。

Outline of Final Research Achievements

In this study, we first injected patient-derived medulloblastoma cells into the brains of immunodeficient mice and examined the frequency of leptomeningeal and hematogenous metastasis. We found that both leptomeningeal and hematogenous metastasis frequently occurs in medulloblastoma. Next, we isolated the tumor cells from primary tumor and metastasis from mice. RNA was extracted from each organ and identified the molecules whose expression was increased compared to the primary tumor using RNA sequencing. Furthermore, we also aim to isolate circulating tumor cells (CTCs) from tumor cells, their blood, and cerebrospinal fluid from mice. Although it was possible to extract tumor cells and RNA from cerebrospinal fluid, it was difficult to extract CTCs and RNA in the blood.

Academic Significance and Societal Importance of the Research Achievements

本研究により髄芽腫の髄膜播種に関与する標的分子が同定され、この標的分子を標的とした治療方法の開発につながることが期待される。また髄液中からの腫瘍細胞の採取は可能であるが、血液中からの腫瘍細胞の採取は困難であることから、こちらを用いたリキッドバイオプシーについては今後さらなる改良が必要であることが示唆された。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (33 results)

All 2023 2022 2021 2020 2019

All Journal Article (15 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 14 results,  Open Access: 10 results) Presentation (18 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] 総説 4K3D外視鏡を用いた脳神経外科手術2022

    • Author(s)
      Kijima N, Kishima H.
    • Journal Title

      Neurological Surgery 脳神経外科

      Volume: 50 Issue: 4 Pages: 889-901

    • DOI

      10.11477/mf.1436204644

    • ISSN
      0301-2603, 1882-1251
    • Year and Date
      2022-07-10
    • Related Report
      2022 Research-status Report
  • [Journal Article] Cerebellopontine angle metastasis of a neuroendocrine tumor mimicking vestibular schwannoma: A case report.2022

    • Author(s)
      Yamada S, Kijima N†, Kinoshita M, Shinzaki S, Sato K, Kido K, Hirayama R, Kagawa N, Takehara T, Morii E, Kishima H.
    • Journal Title

      Surgical Neurology International

      Volume: 13 Pages: 264-264

    • DOI

      10.25259/sni_117_2022

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] How Much Tumor Volume Is Responsible for Development of Clinical Symptoms in Patients With Convexity, Parasagittal, and Falx Meningiomas?2021

    • Author(s)
      Yamada S, Kijima N, Nakagawa T, Hirayama R, Kinoshita M, Kagawa N, Kishima H.
    • Journal Title

      Front Neurol

      Volume: 12 Pages: 769656-769656

    • DOI

      10.3389/fneur.2021.769656

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Subgroup and Subtype Specific Outcomes in Adult Medulloblastoma.2021

    • Author(s)
      Coltin H, Sundaresan L, Kijima N, Taylor MD, Ramaswamy V, et al.
    • Journal Title

      Acta Neuropathol

      Volume: 142(5) Issue: 5 Pages: 859-871

    • DOI

      10.1007/s00401-021-02358-4

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distinct difference in tumor-infiltrating immune cells between Wilms’ tumor gene 1 peptide vaccine and anti-programmed cell death-1 antibody therapies2021

    • Author(s)
      Yokota Chisato、Nakata Jun、Takano Koji、Nakajima Hiroko、Hayashibara Hiromu、Minagawa Hikaru、Chiba Yasuyoshi、Hirayama Ryuichi、Kijima Noriyuki、Kinoshita Manabu、Hashii Yoshiko、Tsuboi Akihiro、Oka Yoshihiro、Oji Yusuke、Kumanogoh Atsushi、Sugiyama Haruo、Kagawa Naoki、Kishima Haruhiko
    • Journal Title

      Neuro-Oncology Advances

      Volume: 3 Issue: 1 Pages: 1-10

    • DOI

      10.1093/noajnl/vdab091

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Necessity for craniospinal irradiation of germinoma with positive cytology but without spinal leision on magnetic resonance images -A controversy2021

    • Author(s)
      Kanamori M, Takami H, Suzuki T ,Kijima N, Ichimura K, Nishikawa R, et al.
    • Journal Title

      Neurooncol Adv

      Volume: 3(1) Issue: 1 Pages: 1-8

    • DOI

      10.1093/noajnl/vdab086

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Utility of a Novel Exoscope, ORBEYE, in Gravity-Assisted Brain Retraction Surgery for Midline Lesions of the Brain.2021

    • Author(s)
      Kijima N, Kinoshita M, Takagaki M, Kishima H.
    • Journal Title

      Surg Neurol Int

      Volume: 12 Pages: 339-339

    • DOI

      10.25259/sni_320_2021

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The impact of 5-year tumor doubling time to predict the subsequent long-term natural history of asymptomatic meningiomas.2021

    • Author(s)
      Yamada S, Kinoshita M, Nakagawa T, Hirayama R, Kijima N, Kagawa N, Kishima H.
    • Journal Title

      World Neurosurg

      Volume: 151 Pages: e943-e949

    • DOI

      10.1016/j.wneu.2021.05.023

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Maintenance of WT1 expression in tumor cells is associated with a good prognosis in malignant glioma patients treated with WT1 peptide vaccine immunotherapy2021

    • Author(s)
      Yokota Chisato、Kagawa Naoki、Takano Koji、Chiba Yasuyoshi、Kinoshita Manabu、Kijima Noriyuki、Oji Yusuke、Oka Yoshihiro、Sugiyama Haruo、Tsuboi Akihiro、Izumoto Shuichi、Kishima Haruhiko、Hashimoto Naoya
    • Journal Title

      Cancer Immunology, Immunotherapy

      Volume: 71 Issue: 1 Pages: 189-201

    • DOI

      10.1007/s00262-021-02954-z

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endovascular Treatment for Middle Cerebral Artery Aneurysms: Single-Center Experience and Review of Literatures2021

    • Author(s)
      Kijima Noriyuki、Miura Shimpei、Terada Eisaku、Nakagawa Ryota、Tachi Tetsuro、Murakami Koki、Okita Yoshiko、Kanemura Yonehiro、Nakajima Shin、Fujinaka Toshiyuki
    • Journal Title

      Journal of Neuroendovascular Therapy

      Volume: 15 Issue: 4 Pages: 213-219

    • DOI

      10.5797/jnet.oa.2019-0051

    • NAID

      130008027854

    • ISSN
      1882-4072, 2186-2494
    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impact of Inversion Time for FLAIR Acquisition on the T2-FLAIR Mismatch Detectability for IDH-Mutant, Non-CODEL Astrocytomas2021

    • Author(s)
      Manabu Kinoshita, Hideyuki Arita, Masamichi Takahashi, Takehiro Uda, Junya Fukai, Kenichi Ishibashi, Noriyuki Kijima, Ryuichi Hirayama, Mio Sakai, Atsuko Arisawa, Hiroto Takahashi, Katsuyuki Nakanishi, Naoki Kagawa, Kouichi Ichimura, Yonehiro Kanemura, Yoshitaka Narita, Haruhiko Kishima
    • Journal Title

      Frontiers in Oncology

      Volume: 10 Pages: 596448-596448

    • DOI

      10.3389/fonc.2020.596448

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] So-called bifocal tumors with diabetes insipidus and negative tumor markers: are they all germinoma?2021

    • Author(s)
      Kanamori M, Takami H, Kijima N, Terashima K, Ichimura K, Nishikawa R, et al,
    • Journal Title

      Neuro-Oncology

      Volume: 23 Issue: 2 Pages: 295-303

    • DOI

      10.1093/neuonc/noaa199

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Chloride intracellular channel 1 cooperates with potassium channel EAG2 to promote medulloblastoma growth.2020

    • Author(s)
      Francisco MA, Wanggou S, Fan JJ, Dong W, Chen X, Momin A, Abeysundara N, Min HK, Chan J, McAdam R, Sia M, Pusong RJ, Liu S, Patel N, Ramaswamy V, Kijima N, Wang LY, Song Y, Kafri R, Taylor MD, Li X, Huang X.
    • Journal Title

      Journal of Experimental Medicine

      Volume: 217 Issue: 5

    • DOI

      10.1084/jem.20190971

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Surgical Treatment of Brain Metastasis of Extramammary Paget’s Disease: A Case Report2020

    • Author(s)
      Shimpei Miura, Noriyuki Kijima, Nagisa Fujimori, Tomoyoshi Nakagawa, Ryota Nakagawa, Tetsuro Tachi, Yoshiko Okita, Yonehiro Kanemura, Shin Nakajima, Masayuki Mano, Haruhiko Kishima, Kentaro Ozawa, Toshiyuki Fujinaka
    • Journal Title

      NMC Case Report Journal

      Volume: 7 Issue: 4 Pages: 189-193

    • DOI

      10.2176/nmccrj.cr.2019-0292

    • NAID

      130007921605

    • ISSN
      2188-4226
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Activated leukocyte cell adhesion molecule expression correlates with the WNT subgroup in medulloblastoma and is involved in regulating tumor cell proliferation and invasion2020

    • Author(s)
      Achiha T, Kijima N, Kodama Y, Kagawa N, Kinoshita M, Fujimoto Y, Nonaka M, Fukai J, Inoue A, Nishida N, Yamanaka T, Harada A, Mori K, Tsuyuguchi N, Uda T, Ishibashi K, Tomogane Y, Sakamoto D, Shofuda T, Yoshioka E, Kanematsu D, Mano M, Luu B, Taylor MD, Kanemura Y, Kishima H.
    • Journal Title

      PLoS One

      Volume: 15 Issue: 12 Pages: e0243272-e0243272

    • DOI

      10.1371/journal.pone.0243272

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Comprehensive analysis of mechanism of glioblastoma invasion using patient derived xenograft models2023

    • Author(s)
      Noriyuki Kijima, Tetsuro Tachi, Hideki Kuroda, Koki Murakami, Ryuichi Hirayama, Yoshiko Okita, Naoki Kagawa, Haruhiko Kishima
    • Organizer
      28th Society for Neuro-Oncology Annual Meeting
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 患者由来初代培養株を用いた膠芽腫の分子生物学的検討と新規治療の開発2023

    • Author(s)
      木嶋教行、黒田秀樹、館哲郎、村上皓紀、中河寛治、宇津木玲奈、川本有輝、平山龍一、沖田典子、香川尚己、貴島晴彦
    • Organizer
      第23回日本分子脳神経外科学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 小脳橋角部腫瘍に対する4K3D外視鏡手術2022

    • Author(s)
      木嶋教行 、香川尚己、沖田典子、平山龍一、館哲郎、黒田秀樹、木下学、貴島晴彦
    • Organizer
      第34回日本頭蓋底外科学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 4K3D外視鏡を用いたグリオーマに対するマルチモダリティ手術2022

    • Author(s)
      木嶋教行 、香川尚己、沖田典子、平山龍一、館哲郎、黒田秀樹、木下学、貴島晴彦
    • Organizer
      第81回日本脳神経外科学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 同一術者が一貫して行う脳腫瘍の栄養血管塞栓から摘出まで2022

    • Author(s)
      木嶋教行、高垣匡寿、平山龍一、沖田典子、西田武生、中村元、香川尚己、藤中俊之、貴島晴彦
    • Organizer
      第27回日本脳腫瘍の外科学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] グリオーマ手術における4K3D外視鏡の有用性と限界2022

    • Author(s)
      木嶋教行、香川尚己、沖田典子、平山龍一、館哲郎、黒田秀樹、木下学、貴島晴彦
    • Organizer
      第29回日本神経内視鏡学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 同一術者が一貫して行う脳腫瘍の栄養血管塞栓から摘出まで2022

    • Author(s)
      木嶋教行、高垣匡寿、平山龍一、沖田典子、西田武生、中村元、香川尚己、藤中俊之、貴島晴彦
    • Organizer
      第38回日本脳神経血管内治療学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] Genetic and molecular properties of long-term proliferating tumorsphere -forming glioma derived cells2021

    • Author(s)
      Noriyuki Kijima, Daisuke Kanematsu, Tomoko Shofuda, Hiroshi Suemizu, Yonehiro Kanemura, et al.
    • Organizer
      The 26th Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 中心前回近傍のグリオーマに対する摘出術の治療成績と覚醒下手術についての検討2021

    • Author(s)
      木嶋教行、木下学、沖田典子、平山龍一、中川智義、黒田秀樹、香川尚己、貴島晴彦
    • Organizer
      第19回awake surgery学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 脳正中病変に対するORBEYEを用いたGravity Assisted Brain Retraction Surgery2021

    • Author(s)
      木嶋教行、木下学、高垣匡寿、中川智義、黒田秀樹、平山龍一、沖田典子、香川尚己、貴島晴彦
    • Organizer
      日本脳神経外科学会 第80回学術総会
    • Related Report
      2021 Research-status Report
  • [Presentation] グリオーマにおける患者腫瘍組織由来初代培養細胞株の遺伝学的、分子生物学的解析2021

    • Author(s)
      木嶋教行 、兼松大介、正札智子、吉岡絵麻、山本篤世、半田有佳子、福角勇人、勝間亜沙子、隅田美穂、森内秀佑、埜中正博、沖田典子、露口尚弘、宇田武弘、川嶋俊幸、深井順也、児玉良典、眞能正幸、樋口裕一郎、末水洋志、金村米博
    • Organizer
      第39回日本脳腫瘍学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 脳正中病変に対するORBEYEを用いたGravity Assisted Brain Retraction Surgery2021

    • Author(s)
      木嶋教行、木下学、高垣匡寿、中川智義、黒田秀樹、平山龍一、沖田典子、香川尚己、貴島晴彦
    • Organizer
      第26回日本脳腫瘍の外科学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] グリオーマ手術におけるORBEYEの使用経験2020

    • Author(s)
      木嶋教行、木下 学、平山龍一、中川智義、香川尚己、貴島晴彦
    • Organizer
      第25回日本脳腫瘍の外科学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 中心前回のグリオーマに対する摘出術の治療成績と覚醒下手術の有効性についての検討2020

    • Author(s)
      木嶋教行、木下学、平山龍一、中川智義、香川尚己、貴島晴彦
    • Organizer
      日本脳神経外科学会 第79回学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 中心前回のグリオーマに対する摘出術の治療成績2020

    • Author(s)
      木嶋教行、木下学、平山龍一、香川尚己、貴島晴彦
    • Organizer
      第38回日本脳腫瘍学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] グリオブラストーマの浸潤における ALCAM の機能的役割についての検討2020

    • Author(s)
      木嶋教行、中川智義、阿知波孝宗、平山龍一、木下学、香川尚己、貴島晴彦
    • Organizer
      第38回日本脳腫瘍学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Establishment of patient-derived xenografts from rare primary brain tumors.2020

    • Author(s)
      Noriyuki Kijima, Yoshikazu Nakajima, Daisuke Kanematsu, Tomoko Shofuda, Yuichiro Higuchi, Hiroshi Suemizu, Kanji Mori, Yoshinori Kodama, Masayuki Mano, Haruhiko Kishima, Yonehiro Kanemura
    • Organizer
      The 25th Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 髄芽腫におけるcirculating tumor cellsの同定と新たな髄膜播種機構としての血行性転移の可能性2019

    • Author(s)
      木嶋 教行
    • Organizer
      第47回日本小児神経外科学会総会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2025-01-30  

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