The role of citric acid cycle and related metabolites in IDH1-mutated gliomas

• Project/Area Number: 24791490
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cerebral neurosurgery
• Research Institution: Kanazawa University
• Principal Investigator: WATANABE Takuya 金沢大学, 医学系, 協力研究員 (90399775)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 神経膠腫 / IDH1 / クエン酸サイクル / MRS / 免疫組織化学 / MGMT / テモゾロミド

Research Abstract

We analyzed the intratumoral metabolism of 19 glioma samples using the LC model that the third party software which can calculate quantitative MR spectrum value of each metabolites. We especially focused on citric acid related metabolites including N-acetyl-aspartate (NAA) and N-acetyl-aspartyl-glutamate (NAAG). Major metabolites in glial cells such as glucose, glutamate acid, GPC did not indicate significant change between IDH-mutated and wild-type glioma. NAA also did not indicate significant differences, whereas NAAG indicated 0.237 (35% reduction) in IDH-mutated glioma comparison to 0.362 in wild type glioma, suggesting that metabolic environment in glioma cells were significantly changed between IDH-mutated and wild-type glioma. Pre-operative MR analysis of glioma using LC model has the possibility of differential diagnosis of IDH-mutated glioma.

Research Products

• [Journal Article] Prognostic paradox : brain damage around the glioblastoma resection cavity (2014)
  • Author(s): Furuta T, Nakada M, Ueda F, Watanabe T, Arakawa Y, Higashi R, Hashimoto M, Nitta H, Hayashi Y, Hamada
  • Journal Title: JI.J Neurooncol Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] The mechanism of chemoresistance against tyrosine kinase inhibitors in malignant glioma (2014)
  • Author(s): Nakada M, Kita D, Watanabe T, Hayashi Y, Hamada
  • Journal Title: JI.Brain Tumor Pathol Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Characterizing invading glioma cells based on IDH1-R132H and Ki-67 immunofluorescence (2014)
  • Author(s): Sabit H, Nakada M, Furuta T, Watanabe T, Hayashi Y, Sato H, Kato Y, Hamada
  • Journal Title: JI.Brain Tumor Pathol Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Prognostic paradox: brain damage around the glioblastoma resection cavity. (2014)
  • Author(s): Furuta T, Nakada M, Ueda F, Watanabe T, Arakawa Y, Higashi R, Hashimoto M, Nitta H, Hayashi Y, Hamada JI.
  • Journal Title: J Neurooncol Volume: [Epub ahead of print]
  • Peer Reviewed
• [Journal Article] Characterizing invading glioma cells based on IDH1-R132H and Ki-67 immunofluorescence. (2014)
  • Author(s): Sabit H, Nakada M, Furuta T, Watanabe T, Hayashi Y, Sato H, Kato Y, Hamada JI.
  • Journal Title: Brain Tumor Pathol Volume: [Epub ahead of print]
  • Peer Reviewed
• [Journal Article] The mechanism of chemoresistance against tyrosine kinase inhibitors in malignant glioma. (2014)
  • Author(s): Nakada M, Kita D, Watanabe T, Hayashi Y, Hamada JI.
  • Journal Title: Brain Tumor Pathol Volume: [Epub ahead of print]
  • Peer Reviewed
• [Journal Article] Receptor tyrosine kinases : principles and functions in glioma invasion (2013)
  • Author(s): Nakada M, Kita D, Teng L, Pyko IV, Watanabe T, Hayashi Y, Hamada
  • Journal Title: J.Adv Exp Med Biol Volume: 986(Review) Pages: 143-70
  • Peer Reviewed
• [Journal Article] Right superior longitudinal fasciculus : implications for visuospatial neglect mimicking Gerstmann's syndrome (2013)
  • Author(s): Hayashi Y, Kinoshita M, Furuta T, Watanabe T, Nakada M, Hamada J
  • Journal Title: Clin Neurol Neurosurg Volume: 115(6) Pages: 775-7
  • Peer Reviewed
• [Journal Article] Visualization of angiographical arteriovenous shunting in perisylvian glioblastomas (2013)
  • Author(s): Yoshikawa A, Nakada M, Kita D, Watanabe T, Kinoshita M, Miyashita K, Furuta T, Hamada JI, Uchiyama N, Hayashi Y
  • Journal Title: Acta Neurochir (Wien) Volume: 155(4) Pages: 715-9
  • Peer Reviewed
• [Journal Article] Visualization of angiographical arteriovenous shunting in perisylvian glioblastomas. (2013)
  • Author(s): Yoshikawa A, Nakada M, Kita D, Watanabe T, Kinoshita M, Miyashita K, Furuta T, Hamada JI, Uchiyama N, Hayashi Y.
  • Journal Title: Acta Neurochir (Wien) Volume: 155(4) Issue: 4 Pages: 715-719
  • DOI: 10.1007/s00701-013-1650-z
  • Peer Reviewed
• [Journal Article] Integrin α3 is overexpressed in glioma stem-like cells and promotes invasion. (2013)
  • Author(s): Nakada M, Nambu E, Furuyama N, Yoshida Y, Takino T, Hayashi Y, Sato H, Sai Y, Tsuji T, Miyamoto KI, Hirao A, Hamada JI.
  • Journal Title: Br J Cancer Volume: 108 Pages: 2516-2524
  • DOI: 10.1007/978-94-007-4719-7_8
  • ISBN: 9789400747180, 9789400747197
  • Peer Reviewed
• [Journal Article] Right superior longitudinal fasciculus: implications for visuospatial neglect mimicking Gerstmann's syndrome. (2013)
  • Author(s): Hayashi Y, Kinoshita M, Furuta T, Watanabe T, Nakada M, Hamada J.
  • Journal Title: Clin Neurol Neurosurg Volume: 115(6) Issue: 6 Pages: 775-7
  • DOI: 10.1016/j.clineuro.2012.07.005
  • Peer Reviewed
• [Journal Article] Orbital cystic schwannoma originating from the frontal nerve (2012)
  • Author(s): Hayashi Y, Watanabe T, Kita D, Hayashi Y, Takahira M, Hamada J
  • Journal Title: Case Rep Ophthalmol Med
  • Peer Reviewed
• [Journal Article] Neuro-Sweet disease mimicking recurrent anaplastic astrocytoma associated with therapy-related myelodysplastic syndrome : a case report (2012)
  • Author(s): Shimizu Y, Watanabe T, Nakada M, Hayashi Y, Hamaguchi Y, Sugimori N, Hamada J
  • Journal Title: Clin Neurol Neurosurg Volume: 114(7) Pages: 1049-51
  • NAID: 120003959463
  • Peer Reviewed
• [Journal Article] Progressive adult primary glioblastoma in the medulla oblongata with an unmethylated MGMT promoter and without an IDH mutation (2012)
  • Author(s): Yoshikawa A, Nakada M, Watanabe T, Hayashi Y, Sabit H, Kato Y, Suzuki S, Ooi A, Sato H, Hamada J
  • Journal Title: Brain Tumor Pathol Volume: 30(3)(Review) Pages: 175-9
  • Peer Reviewed
• [Journal Article] Association between carotid plaque composition assessed by multidetector computed tomography and cerebral embolism after carotid stenting (2012)
  • Author(s): Uchiyama N, Misaki K, Mohri M, Watanabe T, Hirota Y, Nakada M, Hayashi Y, Ueda F, Hamada J
  • Journal Title: Neuroradiology Volume: 54(5) Pages: 487-93
  • Peer Reviewed
• [Journal Article] Progressive tentorial cavernous malformation (2012)
  • Author(s): Furuta T, Nakada M, Watanabe T, Hayashi Y, Hamada J
  • Journal Title: Surg Neurol Int Volume: 3 Pages: 18-18
  • NAID: 120004754692
  • Peer Reviewed
• [Journal Article] Progressive adult primary glioblastoma in the medulla oblongata with an unmethylated MGMT promoter and without an IDH mutation (2012)
  • Author(s): Yoshikawa A, Nakada M, Watanabe T, Hayashi Y, Sabit H, Kato Y, Suzuki S, Ooi A, Sato H, Hamada JI
  • Journal Title: Brain Tumor Pathol Volume: (in press) Issue: 3 Pages: 28-28
  • DOI: 10.1007/s10014-012-0118-9
  • Peer Reviewed
• [Journal Article] Neuro-Sweet disease mimicking recurrent anaplastic astrocytoma associated with therapy-related myelodysplastic syndrome: a case report. (2012)
  • Author(s): Shimizu Y, Watanabe T, Nakada M, Hayashi Y, Hamaguchi Y, Sugimori N, Hamada J.
  • Journal Title: Clin Neurol Neurosurg Volume: 114(7) Issue: 7 Pages: 1049-1051
  • DOI: 10.1016/j.clineuro.2012.01.040
  • NAID: 120003959463
  • Peer Reviewed
• [Journal Article] Association between carotid plaque composition assessed by multidetector computed tomography and cerebral embolism after carotid stenting (2012)
  • Author(s): Naoyuki Uchiyama, Koichi Misaki, Masanao Mohri, Takuya Watanabe, Yuichi Hirota, Mitsutoshi Nakada, Yutaka Hayashi, Fumiaki Ueda, Jun-ichiro Hamada
  • Journal Title: Neuroradiology Volume: (in press) Issue: 5 Pages: 487-493
  • DOI: 10.1007/s00234-011-0920-9
  • Peer Reviewed
• [Journal Article] Right superior longitudinal fasciculus: Implications for visuospatial neglect mimicking Gerstmann's syndrome. (2012)
  • Author(s): Hayashi Y, Kinoshita M, Furuta T, Watanabe T, Nakada M, Hamada JI.
  • Journal Title: Clin Neurol Neurosurg Volume: [Epub ahead of print] Pages: 0-0
  • Peer Reviewed
• [Journal Article] Progressive tentorial cavernous malformation. (2012)
  • Author(s): Furuta T, Nakada M, Watanabe T, Hayashi Y, Hamada J.
  • Journal Title: Surg Neurol Int Volume: 3 Issue: 1 Pages: 18-18
  • DOI: 10.4103/2152-7806.92934
  • NAID: 120004754692
  • Peer Reviewed
• [Journal Article] Recurrent anaplastic meningioma treatedby sunitinib based on results fromquantitative proteomics (2011)
  • Author(s): Yoshikawa, A., Nakada, M., Ohtsuki, S., Hayashi, Y., Obuchi, W., Sato, Y., Ikeda, C., Watanabe, T., Kawahara, Y., Hasegawa, T., Sabit, H., Kita, D., Nakanuma, Y., Terasaki, T. and Hamada, J.
  • Journal Title: NeuropatholAppl Neurobiol Volume: 38 Issue: 1 Pages: 105-10
  • DOI: 10.1111/j.1365-2990.2011.01197.x
  • Peer Reviewed
• [Presentation] 高齢者中枢神経系悪性リンパ腫に対する定位放射線治療-地域環境にあわせた低侵襲治療- (2013)
  • Author(s): 渡邉 卓也, 南部 育, 橋本 正明
  • Organizer: 第72回日本脳神経外科学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2013-10-18
• [Presentation] GSK3β 阻害作用を有する既存薬剤を用いた再発膠芽腫治療の第I・II 相臨床試験における患者背景とバイオマーカーに関する検討 (2013)
  • Author(s): 宮下 勝吉, 中田光俊, 林 裕, 渡邉卓也, 木下 雅史, 田中 慎吾, 古田拓也, 淑瑠ヘムラサビット, 喜多 大輔, 源 利成, 濵田 潤一郎
  • Organizer: 第72回日本脳神経外科学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2013-10-18
• [Presentation] IDH1免疫組織化学による浸潤グリオーマ細胞の検討 (2013)
  • Author(s): 淑瑠ヘムラサビット、中田光俊、渡邉 卓也、林 裕、加藤 幸成、佐藤 博、濵田 潤一郎
  • Organizer: 第31回 日本脳腫瘍病理学会
  • Place of Presentation: 東京 KFC Hall 国際ファッションセンター
• [Presentation] 高齢者中枢神経系悪性リンパ腫に対する定位放射線治療 ―地域環境にあわせた低侵襲治療― (2013)
  • Author(s): 渡邉 卓也, 南部 育, 橋本 正明
  • Organizer: 第72回 日本脳神経外科学会学術総会
  • Place of Presentation: 横浜 パシフィコ横浜
• [Presentation] GSK3β阻害作用を有する既存薬剤を用いた再発膠芽腫治療の第I・II相臨床試験における患者背景とバイオマーカーに関する検討 (2013)
  • Author(s): 宮下 勝吉、中田光俊、林 裕、渡邉卓也、木下 雅史、田中 慎吾、古田拓也、淑瑠ヘムラサビット、喜多 大輔、源 利成、濵田 潤一郎
  • Organizer: 第72回 日本脳神経外科学会学術総会
  • Place of Presentation: 横浜 パシフィコ横浜
• [Presentation] GSK3β 阻害作用を有する既存薬剤を用いた再発膠芽腫の免疫組織学的検討 (2012)
  • Author(s): 宮下勝吉, 中田光俊, 林 裕, 渡邉 卓也, 古田 拓也, 淑瑠 ヘムラサビット, 源 利成, 濵田 潤一郎
  • Organizer: 第30回日本脳腫瘍学会学術集会
  • Place of Presentation: グランドプリンスホテル広島
  • Year and Date: 2012-11-27
• [Presentation] IDH 変異型神経膠腫の画像診断の試み (2012)
  • Author(s): 渡邉 卓也, 中田 光俊, 油野 裕之, 植田 文明, 淑瑠 ヘムラサビット, 北林 朋宏, 橋本正明, 林 裕, 濱田 潤一郎
  • Organizer: 第30回日本脳腫瘍学会学術集会
  • Place of Presentation: グランドプリンスホテル広島
  • Year and Date: 2012-11-26
• [Presentation] LC model MR Spectroscopy による IDH変異型神経膠腫の画像診断の試み (2012)
  • Author(s): 渡邉 卓也, 中田 光俊, 油野 裕之, 植田 文明, 淑瑠 ヘムラサビット, 北林 朋宏, 橋本正明, 林 裕, 濱田 潤一郎
  • Organizer: 第71回日本脳神経外科学会学術総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2012-10-19
• [Presentation] 絶対定量プロテオミクスによる膠芽腫の蛋白発現プロファイリンクとテーラーメイト分子標的療法の提唱 (2012)
  • Author(s): 中田 光俊, 林 裕, 小渕 航, 大槻 純男, 古田 拓也, 木下 雅史, 渡邉 卓也, 田中 慎吾, 宮下 勝吉, 喜多 大輔, 淑瑠 ヘムラサビット, 毛利 正直, 林 康彦, 内山 尚之, 寺崎 哲也, 濱田 潤一郎
  • Organizer: 第71回日本脳神経外科学会学術総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2012-10-17
• [Presentation] IDH1 免疫組織化学による浸潤グリオーマ細胞の検討 (2012)
  • Author(s): 淑瑠 ヘムラサビット, 中田 光俊, 渡邉 卓也, 林 裕, 加藤 幸成, 佐藤 博, 濵田 潤一郎
  • Organizer: 第30回日本脳腫瘍病理学会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2012-05-25
• [Presentation] LC model MR Spectroscopy による IDH変異型神経膠腫の画像診断の試み
  • Author(s): 渡邉 卓也、中田 光俊、油野 裕之、植田 文明、淑瑠 ヘムラサビット, 北林 朋宏、橋本 正明、林 裕、濱田 潤一郎
  • Organizer: 第71回日本脳神経外科学会学術総会
  • Place of Presentation: 大阪国際会議場
• [Presentation] IDH変異異型神経膠腫の画像診断の試み
  • Author(s): 渡邉 卓也、中田 光俊、油野 裕之、植田 文明、 淑瑠 ヘムラサビット, 北林 朋宏、橋本 正明、 河原 庸介、林 裕、濱田 潤⼀郎
  • Organizer: 第30回日本脳腫瘍学会
  • Place of Presentation: グランドプリンスホテル広島
• [Book] Advances in experimental medicine and biology, chapter 8, Receptor Tyrosine Kiases: Principles and Functions in Glioma Invasion (2013)
  • Author(s): Mitsutoshi Nakada, Daisuke Kita, Takuya Watanabe, Yutaka Hayashi, Jun-ichiro Hamada
  • Publisher: Science+Buisiness Media Dordrecht
• [Book] Advances in Experimental Medicine and Biology, chapter 8, Receptor Tyrosine Kinases: Principles and Functions in Glioma Invasion (2012)
  • Author(s): M. Nakada, D. Kita, L. Teng, I.V. Pyko, T. Watanabe, Y. Hayashi, J. Hamada
  • Total Pages: 29
  • Publisher: Springer Science+Business Media Dordrecht