Development of novel therapy against glioma stem cells using super catalytic antibodies.

• Project/Area Number: 15K10337
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Saga University
• Principal Investigator: Abe Tatsuya 佐賀大学, 医学部, 教授 (40281216)
• Co-Investigator(Kenkyū-buntansha): 宇田 泰三 公益財団法人九州先端科学技術研究所, ナノテク研究室, 特別研究員 (20232837) ; 籾井 泰朋 大分大学, 医学部, 助教 (20534192) ; 河島 雅到 佐賀大学, 医学部, 准教授 (20383565) ; 増岡 淳 佐賀大学, 医学部, 助教 (50359949) ; 中原 由紀子 佐賀大学, 医学部, 講師 (50380770)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 脳腫瘍 / 幹細胞 / スーパー抗体酵素 / 腫瘍幹細胞 / 創薬

Outline of Final Research Achievements

Malignant brain tumor shows poor prognosis.MASUOKA any papers about glioblastoma (GBM) stem cells (GSCs) are reported to be an important factor. Our collaborative research produced super catalytic antibodies possessing serine protease-like characteristics. We perfumed screening with various super catalytic antibodies in human glioma cell lines and several GSCs. We found several clones showing anti-tumor effects against human glioma cell lines and GSCs in vitro. One clone against tight junction may suppress GSC’s growth to inhibit sphere formation. However, further studies are required to confirm whether these clones could be new anticancer drug in vivo. We would like to develop novel anticancer agents in brain and other solid tumor through translational research in the future.

Research Products

• [Int'l Joint Research] Massachusetts General Hospital(米国)
• [Journal Article] Curved Planar Reformation for the Evaluation of Hydromyelia in Patients With Scoliosis Associated With Spinal Dysraphism (2018)
  • Author(s): Yoshioka Fumitaka、Shimokawa Shoko、Koguchi Motofumi、Ito Hiroshi、Ogata Atsushi、Inoue Kouhei、Takase Yukinori、Tanaka Tatsuya、Nakahara Yukiko、Masuoka Jun、Abe Tatsuya
  • Journal Title: SPINE Volume: 43 Issue: 3 Pages: E177-E184
  • DOI: 10.1097/brs.0000000000002270
  • Peer Reviewed
• [Journal Article] Transbrachial Angioplasty and Stenting without Crossing the Aortic Arch for Right Carotid Artery Stenosis Patients with Complex Aortic Plaques (2018)
  • Author(s): Ogata A, Ebashi R, Suzuyama K, Okamoto H, TakaseY, Masuoka J, Nakahara Y, Inoue K, Abe T
  • Journal Title: Journal of Neuroendovascular Therapy Volume: 12 Issue: 6 Pages: 309-313
  • DOI: 10.5797/jnet.tn.2017-0093
  • NAID: 130007398382
  • ISSN: 1882-4072, 2186-2494
  • Peer Reviewed
• [Journal Article] Possible involvement of pericytes in intra-plaque hemorrhage of carotid stenosis. (2018)
  • Author(s): Tanaka T, Ogata A, Masuoka J, Mizokami T, Wakamiya T, Nakahara Y, Inoue K, Shimokawa S, Yoshioka F, Momozaki N, Sakata S, Abe T
  • Journal Title: Journal of Neurosurgery Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Posterior Cerebral Artery Aneurysms with Common Carotid Artery Occlusion: A Report of Two Cases (2017)
  • Author(s): Ebashi R, Ogata A, Inoue K, Takase Y, Masuoka J, Nakahara Y, Shimokawa S, Kawashima M, Abe T
  • Journal Title: Journal of Neuroendovascular Therapy Volume: 11 Issue: 7 Pages: 371-375
  • DOI: 10.5797/jnet.cr.2016-0114
  • NAID: 130005815371
  • ISSN: 1882-4072, 2186-2494
  • Peer Reviewed
• [Journal Article] 味覚障害で発症した小脳血管芽腫の１例 (2017)
  • Author(s): 中城博子、河島雅到、吉岡史隆、中原由紀子、高瀬幸徳、緒方敦之、下川尚子、増岡 淳、阿部竜也、松島俊夫
  • Journal Title: 脳神経外科 Volume: 45 Pages: 219-224
  • Peer Reviewed
• [Journal Article] Outcome of microvascular decompression for hemifacial spasm associated with the vertebral artery. (2017)
  • Author(s): asuoka J, Matsushima T, Nakahara Y, Inoue K, Yoshioka F, Kawashima M, Abe T
  • Journal Title: Neurosurg Rev Volume: 未定 Issue: 2 Pages: 267-273
  • DOI: 10.1007/s10143-016-0759-y
  • Peer Reviewed / Open Access
• [Journal Article] Carotid artery stenosis with a high-intensity signal plaque on time-of-flight magnetic resonance angiography and association with evidence of intraplaque hypoxia. (2017)
  • Author(s): Ogata A, Kawashima M, Wakamiya T, Nishihara M, Masuoka J, Nakahara Y, Ebashi R, Inoue K, Takase K, Irie H, Abe T
  • Journal Title: Journal of Neurosurgery Volume: 126 Issue: 6 Pages: 1873-1878
  • DOI: 10.3171/2016.4.jns16349
  • Peer Reviewed
• [Journal Article] Typical Symptoms of Normal-Pressure Hydrocephalus Caused by Choroid Plexus Papilloma in the Cerebellopontine Angle (2017)
  • Author(s): Ito Hiroshi、Nakahara Yukiko、Kawashima Masatou、Masuoka Jun、Abe Tatsuya、Matsushima Toshio
  • Journal Title: World Neurosurgery Volume: 98 Pages: 875.e13-875.e17
  • DOI: 10.1016/j.wneu.2016.11.106
  • Peer Reviewed
• [Journal Article] Dural arteriovenous fistula manifesting as pontine hemorrhage at the craniocervical junction (2017)
  • Author(s): Liu Xuan、Ogata Atsushi、Masuoka Jun、Inoue Kohei、Nakahara Yukiko、Shimokawa Shoko、Takase Yukinori、Yakushiji Yusuke、Hara Hideo、Abe Tatsuya
  • Journal Title: Acta Neurochir (Wien) Volume: 159 Issue: 5 Pages: 831-834
  • DOI: 10.1007/s00701-017-3135-y
  • Peer Reviewed
• [Journal Article] Brain metastasis from primary peritoneal carcinoma: Case report and literature review (2017)
  • Author(s): Liu Xuan、Masuoka Jun、Ebashi Ryo、Koguchi Motofumi、Inoue Kohei、Ogata Atsushi、Takase Yukinori、Nakahara Yukiko、Shimokawa Shoko、Kawashima Masatou、Yoshihara Masahiro、Abe Tatsuya
  • Journal Title: J Clin Neurosci. Volume: 40 Pages: 120-122
  • DOI: 10.1016/j.jocn.2017.02.023
  • Peer Reviewed
• [Journal Article] Ruptured dissecting aneurysm of the recurrent artery of Heubner: Consideration of pathological findings. (2017)
  • Author(s): Ogata A, Sakata S, Okamoto H, Abe T
  • Journal Title: Neurol India Volume: 65 Issue: 3 Pages: 623-625
  • DOI: 10.4103/neuroindia.ni_1034_16
  • Peer Reviewed
• [Journal Article] Differences in the Genotype Frequency of the RNF213 Variant in Patients with Familial Moyamoya Disease in Kyushu, Japan (2017)
  • Author(s): TAKAMATSU Yuichiro、HIGASHIMOTO Ken、MAEDA Toshiyuki、KAWASHIMA Masatou、MATSUO Muneaki、ABE Tatsuya、MATSUSHIMA Toshio、SOEJIMA Hidenobu
  • Journal Title: Neurologia medico-chirurgica Volume: 57 Issue: 11 Pages: 607-611
  • DOI: 10.2176/nmc.oa.2017-0036
  • NAID: 130006201788
  • ISSN: 0470-8105, 1349-8029
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic relevance of genetic alterations in diffuse lower-grade gliomas (2017)
  • Author(s): Aoki Kosuke、Nakamura Hideo、Suzuki Hiromichi et al.
  • Journal Title: Neuro-Oncology Volume: 20 Issue: 1 Pages: 66-77
  • DOI: 10.1093/neuonc/nox132
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Elevation of autoantibody level against PDCD11 in patients with transient ischemic attack (2017)
  • Author(s): Yoshida Y, Wang H, Hiwasa T, Machida T, Takiguchi M, Iwadate Y, et al.
  • Journal Title: Oncotarget Volume: 9 Issue: 3 Pages: 8836-8848
  • DOI: 10.1007/s11060-018-2831-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] SLC44A1–PRKCA fusion in papillary and rosette-forming glioneuronal tumor. (2016)
  • Author(s): Nagaishi M, Nobusawa S, Matsumura N, Kono F, Ishiuchi S, Abe T, Ebato M, Wang Y, Hyodo A, Yokoo H, Nakazato Y.
  • Journal Title: J Clin Neurosci. Volume: 23 Pages: 73-75
  • DOI: 10.1016/j.jocn.2015.04.021
  • Peer Reviewed / Open Access
• [Journal Article] A prospective multicenter single-arm clinical trial of bevacizumab for patients with surgically untreatable symptomatic brain radiation necrosis. (2016)
  • Author(s): Furuse M, Nonoguchi N, Kuroiwa T, Miyamoto S, Arakawa Y, Shinoda J, Miwa K, Iuchi T, Tsuboi K, Houkin K, Terasaka S, Tabei Y, Nakamura H, Nagane M, Sugiyama K, Terasaki M, Abe T, Narita Y, Saito N, Mukasa A, Ogasawara K, Beppu, T Kumabe T, Nariai T, Tsuyuguchi N, Nakatani E, Kurisu S, Nakagawa Y, Miyatake SI.
  • Journal Title: Neuro-Oncology Practice. Volume: 3 Pages: 272-280
  • Peer Reviewed / Open Access
• [Journal Article] Dedifferentiated chordoid meningioma with rhabdomyosarcomatous differentiation on the middle cranial fossa. (2016)
  • Author(s): Fudaba H, Abe T, Morishige M, Momii Y, Kashima K, Yamada A, Nagatomi H, Natsume A, Hirato J, Nakazato Y, Fujiki M
  • Journal Title: Neuropathology, Volume: 36 Issue: 6 Pages: 579-583
  • DOI: 10.1111/neup.12310
• [Journal Article] A prospective multicenter single-arm clinical trial of bevacizumab for patients with surgically untreatable symptomatic brain radiation necrosis. (2016)
  • Author(s): Furuse M, Nonoguchi N, Kuroiwa T, Miyamoto S, Arakawa Y, Shinoda J, Miwa K, Iuchi T, , Terasaka S, Tabei Y, Nakamura H, Nagane M, Tsuboi K, Houkin K Sugiyama K, Terasaki M, Abe T, Narita Y, Saito N, Mukasa A, Ogasawara K, Beppu, T Kumabe T, Nariai T, Tsuyuguchi N, Nakatani E, Kurisu S, Nakagawa Y, Miyatake SI.
  • Journal Title: Neuro-Oncology Practice Volume: ３
  • Peer Reviewed
• [Journal Article] Mutational landscape and clonal architecture in grade II and III gliomas (2015)
  • Author(s): Suzuki H, Aoki K, Natsume A, Ogawa S. et al.
  • Journal Title: Nat Genet. Volume: 47 Issue: 5 Pages: 458-468
  • DOI: 10.1038/ng.3273
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] CBIO-27 Increase of mRNA expression of both fatty acid synthase (FASN) and carnitine palmitoyltransferase 1C (CPT1C) in starved human glioma cell lines． (2017)
  • Author(s): Abe T,Wakamiya T,Kouguchi M,Ito H,Nakahara Y
  • Organizer: 22ND ANNUAL SCIENTIFIC MEETING AND EDUCATION DAY OF THE SOCIETY FOR NEURO-ONCOLOGY.
  • Int'l Joint Research
• [Presentation] Multicenter randomized placebo-controlled trial of autologous formalin-fixed tumor vaccine for newly-diagnosed LTBK-03 glioblastomas. (2017)
  • Author(s): Muragaki Y, Maruyama T, Ishikawa E, Nitta M, Ikuta S, Tsuboi K, Matsumura A, Nakamura H, Abe T, Saito R, Tabei Y, Arakawa Y,Momii Y, Karasawa K, Matsutani M, Ohno T, Nakazato Y, Maebayashi K
  • Organizer: 22ND ANNUAL SCIENTIFIC MEETING AND EDUCATION DAY OF THE SOCIETY FOR NEURO-ONCOLOGY.
  • Int'l Joint Research
• [Presentation] End of Life Option Act（終末期選択法）：日本人独特のKinshipから産まれる国民皆保険制度から． (2017)
  • Author(s): 阿部 竜也
  • Organizer: （一社）日本脳神経外科学会第76回学術総会．
• [Presentation] 血管内治療直後のDual energy CTの検討． (2017)
  • Author(s): 江橋 諒，緒方 敦之，西原 正志，高瀬 幸徳，阿部 竜也，入江 裕之
  • Organizer: 第40回日本脳神経CI学会総会．
• [Presentation] 舌咽神経痛における責任血管と穿通枝の検討. (2017)
  • Author(s): 井上 浩平, 松島 俊夫, 河島 雅到, 緒方 敦之, 高瀬 幸徳, 中原 由紀子,下川 尚子, 増岡 淳, 阿部 竜也
  • Organizer: 一社）日本脳神経外科学会第76回学術総会．
• [Presentation] NDRG1/GSK3β/AKT/S6シグナルによるGlioblastoma生存・増殖の新しい制御機構． (2017)
  • Author(s): 伊藤 寛,渡 公佑,村上 雄一,柴田 智博,桑野 信彦,阿部 竜也,小野 真弓
  • Organizer: 第21回日本がん分子標的治療学会学術集会．
• [Presentation] 当院における神経膠腫の分子生物学的解析の現状． (2017)
  • Author(s): 高口 素史,中原 由紀子，伊藤 寛, 若宮 富浩，増岡 淳, 阿部 竜也
  • Organizer: 第35回日本脳腫瘍病理学会．
• [Presentation] gliomaにおける蛍光染色を用いたTETタンパクの細胞内局在の検討． (2017)
  • Author(s): 高口素史,中原由紀子,伊藤 寛,井上浩平,緒方敦之,高瀬幸徳,下川尚子,増岡 淳,阿部竜也
  • Organizer: 第18回日本分子脳神経外科学会．
• [Presentation] 中枢神経系浸潤型アスペルギルス症に対する外科治療． (2017)
  • Author(s): 増岡 淳, 桃崎 明彦, 坂本 祐史, 正島 弘隆, 高口 素史, 井上 浩平, 緒方 敦之,中原 由紀子, 高瀬 幸徳, 下川 尚子, 阿部 竜也
  • Organizer: （一社）日本脳神経外科学会第76回学術総会．
• [Presentation] 典型的なdiffuse midline gliomaだが、H3 K27M遺伝子変異を検出しなかった一例． (2017)
  • Author(s): 中原由紀子，若宮富浩，高口素史，山崎真希子，相島慎一，中野嘉子，北原麻衣，市村幸一，阿部竜也
  • Organizer: 第35回日本脳腫瘍病理学会．
• [Presentation] 膠芽腫腫瘍幹細胞に対するSTAT3 阻害剤の感受性についての検討． (2017)
  • Author(s): 中原 由紀子,高口 素史,伊藤 寛,増岡 淳,脇本 浩明,阿部 竜也
  • Organizer: 第35回日本脳腫瘍学会．
• [Presentation] パーキンソン病に対する視床下核DBSにおけるDirectional leadの初期使用経験． (2017)
  • Author(s): 中城 博子, 梅村 淳, 岩室 宏一, 三橋 匠, 大山 彦光, 下 泰司, 阿部 竜也,新井 一
  • Organizer: （一社）日本脳神経外科学会第76回学術総会．
• [Presentation] 頸動脈ステント留置術後フォローアップにおける非造影MRAの有用性と (2017)
  • Author(s): 緒方 敦之，江橋 諒，吉岡 史隆，井上 浩平，高瀬 幸徳，中原 由紀子，下川 尚子，増岡淳，阿部 竜也
  • Organizer: 第40回日本脳神経CI学会総会．
• [Presentation] 頸動脈狭窄症プラーク内出血におけるペリサイトと薬事療法の関連性． (2017)
  • Author(s): 緒方敦之,田中達也,溝上泰一朗,若宮富浩,増岡 淳,中原由紀子,下川尚子,高瀬幸徳,井上浩平,桃﨑宣明,坂田修治,阿部竜也
  • Organizer: 第18回日本分子脳神経外科学会．
• [Presentation] 頸動脈狭窄症プラーク内出血におけるペリサイトと薬剤療法の関連性． (2017)
  • Author(s): 緒方 敦之, 田中 達也1,2, 溝上 泰一朗, 若宮 富浩, 増岡 淳, 中原 由紀子,下川 尚子, 高瀬 幸徳, 井上 浩平, 桃崎 宣明, 坂田 修治, 阿部 竜也
  • Organizer: （一社）日本脳神経外科学会第76回学術総会．
• [Presentation] 前方循環破裂動脈瘤に対する塞栓術において急峻な内頚動脈例は合併症が多い． (2017)
  • Author(s): 緒方 敦之,井上浩平,高瀬幸徳,下川尚子,中原由紀子,増岡 淳,阿部竜也
  • Organizer: 第33回NPO法人日本脳神経血管内治療学会学術総会．
• [Presentation] Proximal protection にてステント留置術を行った鎖骨下動脈狭窄症の1 例． (2017)
  • Author(s): 乙木 祐介,緒方 敦之,桃﨑 明彦,坂本 祐史,井上 浩平,高瀬 幸徳,下川 尚子,中原 由紀子,増岡 淳,阿部 竜也
  • Organizer: 第33回NPO法人日本脳神経血管内治療学会学術総会．
• [Presentation] 当院における頸動脈海綿静脈洞瘻の治療成績． (2017)
  • Author(s): 高瀬 幸徳, 緒方 敦之, 増岡 淳, 中原 由紀子, 下川 尚子, 井上 浩平, 高口 素史,正島 弘隆, 坂本 祐史, 桃崎 明彦, 阿部 竜也
  • Organizer: （一社）日本脳神経外科学会第76回学術総会．
• [Presentation] 頸動脈海綿静脈洞瘻に対する治療成績． (2017)
  • Author(s): 高瀬 幸徳,緒方 敦之,増岡 淳,中原 由紀子,下川 尚子,井上 浩平,阿部 竜也
  • Organizer: 第33回NPO法人日本脳神経血管内治療学会学術総会．
• [Presentation] 飢餓状態のヒトグリオ-マ細胞株においてfatty acid synthase とcarnitine palmitoyltransferase 1C のmRNA 発現が亢進する. (2017)
  • Author(s): 若宮富浩、中原由紀子、高口素史、伊藤寛、阿部竜也
  • Organizer: 第76回日本癌学会．
• [Presentation] Expression of drug resistance genes associated with hypoxia. (2016)
  • Author(s): Abe T. １）, Nakahara Y. １）, Kouguchi M.１), Ito H１), Wakamiya T.１), Morisaki I.2), Momii Y2), Fudaba H.2), Fujiki S.2), Wakimoto H.3)
  • Organizer: 21st annual meeting of society of neuro-oncology
  • Place of Presentation: 米国
  • Year and Date: 2016-11-17
  • Int'l Joint Research
• [Presentation] Surgical treatment for glioma based on brain reorganization. (2016)
  • Author(s): Abe T
  • Organizer: 第7回世界華人神経外科学会．
  • Place of Presentation: 中国
  • Year and Date: 2016-05-06
  • Int'l Joint Research / Invited
• [Presentation] Coexpression of Fatty Acid Synthase（FASN） and Carnitine Palmitoyltransferase 1C（CPT1C） in Human Gliomas and Glioma Stem Cell Xenografts. (2016)
  • Author(s): Abe T
  • Organizer: 21st International Conference on Brain Tumor Research and Therapy.
  • Place of Presentation: 沖縄
  • Year and Date: 2016-04-10
  • Int'l Joint Research
• [Presentation] Coexpression of fatty acid synthase (FASN) and carnitine palmitoyltransferase 1C (CPT1C) in human gliomas． (2015)
  • Author(s): Abe T, Wakamiya T, Nakahara Y, Suzuki SO, Honda H, Mizoguchi M, Yoshimoto Y, Iwaki T
  • Organizer: 20th Annual Scoentific Meeting and Education Day of the Society for Neuro-Oncology.
  • Place of Presentation: テキサス
  • Year and Date: 2015-11-19
  • Int'l Joint Research
• [Presentation] 当院における頭蓋骨縫合早期癒合症の手術とその工夫． (2015)
  • Author(s): 高口 素史,吉岡 史隆,中原 由紀子,下川 尚子,増岡 淳,河島 雅到,上村 哲司,阿部 竜也
  • Organizer: （一社）日本脳神経外科学会第74回学術総会．
  • Place of Presentation: 札幌
  • Year and Date: 2015-10-14
• [Presentation] Coexpression of fatty acid synthase (FASN) and carnitine (2015)
  • Author(s): 若宮 富浩,鈴木 諭,本田 裕之,岩城 徹,溝口 昌弘,吉本 幸司,阿部 竜也
  • Organizer: 第74回日本癌学会学術総会．
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-10
• [Presentation] 頸動脈狭窄症における放射線学的プラーク診断と免疫組織化学的検討． (2015)
  • Author(s): 緒方 敦之,河島 雅到,江橋 諒,古川 隆,高口 素史,若宮 富浩,吉岡 史隆,高瀬 幸徳,中原 由紀子、下川 尚子、増岡 淳、阿部 竜也
  • Organizer: 第16回日本分子脳神経外科学会．
  • Place of Presentation: 浜松
  • Year and Date: 2015-08-28
• [Presentation] 二分脊椎に伴う側弯症患者におけるCurved Planar Reconstruction画像の有用性 (2015)
  • Author(s): 吉岡 史隆,下川 尚子,高口 素史,古川 隆,伊藤 寛,緒方 敦之,高瀬 幸徳,中原 由紀子,増岡 淳,河島 雅到,阿部 竜也
  • Organizer: 第32回日本二分脊椎研究会．
  • Place of Presentation: 東京
  • Year and Date: 2015-07-04
• [Book] 脳腫瘍臨床病理カラーアトラス (2017)
  • Author(s): 阿部竜也
  • Total Pages: 1
  • Publisher: 医学書院
• [Book] 【脳腫瘍学-基礎研究と臨床研究の進歩-】 脳腫瘍の分子生物学と発生機序 分子生物学 EGFR(上皮成長因子受容体) (2016)
  • Author(s): 中原由紀子、伊藤寛、 阿部竜也
  • Total Pages: 4
  • Publisher: 日本臨床