大学ホーム医学研究科教育・研究指導教員紹介:永根 基雄

教員紹介:永根 基雄


氏名
 
永根 基雄
ナガネ モトオ NAGANE, Motoo
職位 教授
学内の役職・委員等 杏林大学医学部付属病院がんセンター副センター長
所属教室

専攻・専門分野
 (大学院)
担当科目(学部) 脳腫瘍
担当科目(大学院) 脳神経腫瘍学
兼務・兼担 実験動物施設部門長
専門分野 悪性脳腫瘍、分子生物学
研究テーマ 悪性脳腫瘍の治療、化学療法、薬剤耐性、分子生物学、臨床試験
略歴 1984年 東京大学医学部医学科卒
1990年 日本脳神経外科学会専門医
1991年 国立がんセンター中央病院脳神経外科医員
1994年 東京大学医学部医学博士
1995年-2000年 Ludwig Institute for Cancer Research at San Diego, CA, U.S.A.にてpostdoctoral fellow.2000年 杏林大学医学部脳神経外科講師
2005年 同助教授.
2007年 同准教授.
2012年 同教授
所有する学位 博士(医学)
指導医・専門医・認定医、その他の資格等 日本脳神経外科学会脳神経外科専門医・指導医、日本がん治療認定医機構暫定教育医・がん治療認定医
論文・著書等を含む主要研究業績 1. Oyama H, Nagane M, Mukai K et al: Skull Base Malignant Lymphoma. A Case Report and Review of the Literature. Jpn J Clin Oncol 22: 131-135, 1992
2. Nagane M, Asai A, Kuchino Y, et al: Expression of O6-methylguanine-DNA Methyltransferase and Chloroethylnitrosourea Resistance of Human Brain Tumors. Jpn J Clin Oncol 22: 143-149, 1992
3. Oyama H, Nagane M, Mukai K, et al: Intracellular Distribution of CPT-11 in CPT-11-resistant Cells with Confocal Laser Scanning Microscopy. Jpn J Clin Oncol 22: 331-334, 1992
4. Tokuuye K, Nagane M, Hara T, et al: Linac-based small-field radiotherapy for brain tumors. Radiother Oncol 27: 55-58, 1993
5. Nagane M, Nomura K, et al. Investigation of chemoresistance-related genes mRNA expression for selecting anticancer agents in successful adjuvant chemotherapy for a recurrent glioblastoma. Surg Neurol 44: 462-470, 1995
6. Nagane M, Nomura K, et al. Triple primary malignant neoplasms including a malignant brain tumor. Report of two cases and review of the literature. Surg Neurol 45: 219-229, 1996
7. Cheng S-Y, Nagane M, Cavenee WK, et al. Suppression of glioblastoma angiogenicity and tumorigenicity by inhibition of endogenous expression of vascular endothelial growth factor. Proc Natl Acad Sci, USA 93: 8502-8507, 1996
8. Prigent SA, Nagane M, Huang H-JS, et al. Enhanced tumorigenic behavior of glioblastoma cells expressing a truncated EGF receptor is mediated through the Ras-Shc-Grb2 pathway. J Biol Chem 271: 25639-25645, 1996
9. Nagane M, Huang H-JS, et al. A common mutant epidermal growth factor receptor confers enhanced tumorigenicity on human glioblastoma cells by increasing proliferation and reducing apoptosis. Cancer Res 56: 5079-5086, 1996
10. Huang H-JS, Nagane M, Cavenee WK, et al. Constitutive tyrosine phosphorylation and unattenuated signalling is essential for the enhanced tumorigenic activity of a mutant epidermal growth factor receptor common in human cancers. J Biol Chem 272: 2927-2935, 1997
11. Nagane M, Kuchino Y, et al. Application of antisense RNA complementary to O6-methylguanine-DNA methyltransferase (MGMT) cDNA for the therapy of malignant gliomas. Neurosurgery 41 (2): 434-441, 1997
12. Cheng S-Y, Nagane M, Cavenee WK, et al: Intracerebral tumor-associated hemorrhage caused by overexpresseion of the vascular endothelial growth factor isoforms VEGF121 and VEGF165 but not VEGF189. Proc Natl Acad Sci, USA 94: 12081-12087, 1997
13. Nagane M, Cavenee W K, et al: Advances in the molecular genetics of gliomas. Cur Opin Oncol 9 (3): 215-222, 1997
14. Nagane M, Huang H-JS, et al: Drug resistance of human glioblastoma cells conferred by a tumor-specific mutant epidermal growth factor receptor through modulation of Bcl-XL and caspase-3-like proteases. Proc Natl Acad Sci, USA 95: 5724-5729, 1998
15. Roberts WG, Nagane M, Palade GE, et al: Host microvasculature influence on tumor vascular morphology and endothelial gene expression. Am J Pathol 153: 1239-1248, 1998
16. Bögler O, Nagane M, Cavenee WK, et al: Malignant transformation of p53-deficient astrocytes is modulated by environmental cues in vitro. Cell Growth Differ 10: 73-86, 1999
17. Robertson GP, Nagane M, Cavenee WK, et al: The chromosome 10 monosomy common in human melanomas results from the loss of two separate tumor suppressor loci. Cancer Res 59: 3596-3601,1999
18. Nagane M, Kuchino Y, et al. Expression pattern of chemoresistance-related genes in human malignant brain tumors: a working knowledge for proper selection of anticancer drugs. Jpn J Clin Oncol 29 (11): 527-534, 1999.
19. Nagane M, Cavenee W K, et al: Causes of drug resistance and novel therapeutic opportunities for the treatment of glioblastoma. Drug Resistance Updates 2: 30-37, 1999
20. Nagane M, Huang H-JS, et al. Increased Death Receptor 5 (DR5) Expression by Chemotherapeutic Agents in Human Gliomas Causes Synergistic Cytotoxicity with Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) In Vitro and In Vivo. Cancer Res 60: 847-853, 2000
21. Cavenee WK, Nagane M, Noble M, et al. Diffuse Astrocytomas. In Pathology and Genetics of Tumours of the Nervous System, Second Edition. (P. Kleihues and W. Cavenee, eds.) IARC Press, Lyon, France, 2000. p. 10-21
22. Nagane M, Huang H-JS, et al. Human glioblastoma xenografts overexpressing a tumor-specific mutant epidermal growth factor receptor sensitized to cisplatin by the AG1478 tyrosine kinase inhibitor. J Neurosurg 95: 472-479, 2001
23. Guo P, Xu L, Nagane M, Cheng SY, et al. Vascular endothelial growth factor isoforms display distinct activities in promoting tumor angiogenesis at different anatomic sites. Cancer Res 61(23):8569-77. 2001
24. Nagane M, Huang H-JS, et al. Aberrant receptor signaling in human malignant gliomas: Mechanisms and therapeutic implications. Cancer Lett 162 Suppl 1:S17-S21, 2001
25. Nagane M, Huang H-JS, et al. The Potential of TRAIL for Cancer Chemotherapy. Apoptosis 6: 191-197, 2001
26. Narita Y, Nagane M, Cavenee WK, et al. Mutant Epidermal Growth Factor Receptor signaling down-regulates p27 through activation of the Phosphatidylinositol 3-kinase/Akt pathway in Glioblastomas. Cancer Res 62: 6764-6769, 2002
27. Hu B, Nagane M, Shi-Yuan Cheng S-Y, et al. Angiopoietin-2 induces human glioma invasion through the activation of matrix metalloprotease-2. Proc Natl Acad Sci, USA 100 (15): 8904-8909, 2003
28. Nagane M, Shiokawa Y, et al. Synergistic cytotoxicity through the activation of multiple apoptosis pathways in human glioma cells induced by combined treatment with ionizing irradiation and tumor necrosis factor-related apoptosis-inducing ligand. J Neurosurg 106: 407-416, 2007.
29. Nagane M, Shiokawa Y, et al. Prognostic significance of O6-methylguanine-DNA methyltransferase protein expression in patients with recurrent glioblastoma treated with temozolomide. Jpn J Clin Oncol 37(12): 897-906, 2007
30. Kobayashi K, Nagane M, et al. Enhanced tumor growth elicited by L-type amino acid transporter 1 in human malignant glioma cells. Neurosurgery 62 (2): 493-504, 2008
31. Nagane M, Shiokawa Y, et al. Combined treatment with histone deacetylase inhibitors enhances cytotoxic activity of anti-DR5/TRAIL-R2 monoclonal antibodies in human glioma cells (Abst). Neuro-Oncology 10 (5): 788-789, 2008
32. Nagane M, Shiokawa Y, et al. Prolonged and severe thrombocytopenia with pancytopenia induced by radiation-combined temozolomide therapy in a patient with newly-diagnosed glioblastoma---analysis of O6-methylguanine-DNA methyltransferase status. J Neuro-Oncol 92: 227-232, 2009
33. Nagane M, Shiokawa Y, et al. Predominant antitumor effects by fully human anti-TRAIL-receptor2 (DR5) monoclonal antibodies in human glioma cells in vitro and in vivo. Neuro-Oncology 12: 687-700, 2010
34. Liu K-W, Nagane M, Cheng S-Y, et al. SHP-2/PTPN11 mediates gliomagenesis driven by PDGFRA and Ink4a/Arf aberrations in mice and humans. J Clin Invest 121(3): 905-917, 2011
35. Feng H, Nagane M, Cheng SY, et al. Activation of Rac1 by Src-dependent phosphorylation of Dock180(Y1811) mediates PDGFRα-stimulated glioma tumorigenesis in mice and humans. J Clin Invest 121(12): 4670-84, 2011.
36. Nagane M. Multidisciplinary progress in neuro-oncology 2010.Lancet Neurol 10 (1): 18-20, 2011
37. Nagane, M: Recent progress in Neuro-oncology. J Jpn S Clin Oncol 46 (3): 1344-1347, 2011
38. Bonavia R, Nagane M, Furnari FB, et al. EGFRvIII promotes glioma angiogenesis and growth through the NF-κB, interleukin-8 pathway. Oncogene 31(36): 4054-66, 2012.
39. Tonari A, Nagane M, Takayama M, et al. Effects of artificial structures on postoperative irradiation therapy. –Skull reconstruction case–. J Kyorin Med Soc 43 (2): 11-16, 2012
40. Nagane M, Matsutani M, et al. Phase II study of single-agent bevacizumab in Japanese patients with recurrent malignant glioma. Jpn J Clin Oncol 42(10): 887-895, 2012
41. Shibui S, Nagane M, Todo T, et al: Randomized trial of chemoradiotherapy and adjuvant chemotherapy with nimustine (ACNU) versus nimustine plus procarbazine for newly diagnosed anaplastic astrocytoma and glioblastoma (JCOG0305). Cancer Chemother Pharmacol 71 (2): 511-521, 2013.
42. Nagane M, Nishikawa R: Bevacizumab for glioblastoma – a promising drug or not? Cancers 5(4): 1456-1468, 2013
43. Nagane M, Shiokawa Y, et al. Predictive significance of mean apparent diffusion coefficient value for responsiveness of temozolomide-refractory malignant glioma to bevacizumab: preliminary report. Int J Clin Oncol 19: 16-23, 2014
44. Shishido-Hara Y, Nagane M, Uchihara T, et al: JC viral inclusions in progressive multifocal leukoencephalopathy: Scaffolding promyelocytic leukemia nuclear bodies grow with cell cycle transition through an S-to-G2-like state in enlarging oligodendrocyte nuclei. J Neuropathol Exp Neurol 73 (5), 442-453, 2014
45. Feng H, Nagane M, Cheng S-Y, et al: EGFR Phosphorylation of DCBLD2 Recruits TRAF6 and Stimulates Akt-promoted Tumorigenesis. J Clin Invest. 2014 Sep 2;124(9):3741-56.
46. Nagane M: Dose-dense temozolomide – Is it still promising? Neurol Med Chir (Tokyo) 55: 38-49, 2015
47. Takami H, Nagane M, Matsutani M, et al: Human chorionic gonadotropin is expressed virtually in all intracranial germ cell tumors. J Neurooncol 124(1):23-32, 2015
48. Keino H, Nagane M, et al: Spectral-domain optical coherence tomography patterns in intraocular lymphoma. Ocul Immunol Inflamm. 2015 Mar 11:1-6. [Epub ahead of print]
49. Nitta Y, Nagane M, et al: Nimotuzumab enhances temozolomide induced growth suppression of glioma cells expressing mutant EGFR in vivo. Cancer Med 5 (3): 486-499, 2016
50. Fukumura K, Nagane M, Mano H, et al: Genomic characterization of primary central nervous system lymphoma. Acta Neuropathol 131: 865-875, 2016
51. Furuse M, Nagane M, Miyatake S, et al: A prospective multicenter single-arm clinical trial of bevacizumab for patients with surgically untreatable symptomatic brain radiation necrosis. Neuro-Oncol Practice 3(4), 272–280, 2016
52. Tsuchihashi K, Nagane M, Nagano O, et al: The EGF receptor promotes the malignant potential of glioma by regulating amino acid transport system xc(-). Cancer Res 76 (10): 2954-2963, 2016
53. Ichimura K, Nagane M, Nishikawa R, et al, The Intracranial Germ Cell Tumor Genome Analysis Consortium: Recurrent neomorphic mutations of MTOR in central nervous system and testicular germ cell tumors may be targeted for therapy. Acta Neuropathol 131: 889-901, 2016
54. 久米賢,永根基雄ら: 神経膠腫における 1H-Magnetic Resonance Spectroscopy (MRS)とLCModelを用いた2-hydroxyglutarate (2-HG)検出及びその定量的解析.杏林医会誌 47 (3): s21-25, 2016
55. Arita H, Nagane M, Ichimura K, et al: A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas. Acta Neuropathologica Communications 4:79, 2016
56. Yamagishi Y, Nagane M, et al: Black hairy tongue after chemotherapy for malignant brain tumors. Acta Neurochir 159: 169-172, 2017
57. Nakamura T, Nagane M, Ichimura K, et al: Genome-wide DNA methylation profiling identifies primary central nervous system lymphomas as a distinct entity from systemic diffuse large B-cell lymphomas. Acta Neuropathol (Feb) 133(2):321-324, 2017
58. Fukushima S, Nagane M, Ichimura K, et al. On behalf of The Intracranial Germ Cell Tumor Genome Analysis Consortium (The iGCTConsortium): Genome wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas. Acta Neuropathol 133: 445-462, 2017
59. Aihara K, Nagane M, Saito N, et al: Genetic and epigenetic stability of oligodendrogliomas at recurrence. Acta Neuropathol Comm 5: 18, 2017
60. Lee J, Nagane M, et al: Prognostic factors for primary central nervous system lymphomas treated with high-dose methotrexate-based chemo-radiotherapy. Jpn J Clin Oncol 47(10):925-934, 2017.
61. Wang W, Nagane M, Cheng C, et al: Internalized CD44s splice isoform attenuates EGFR degradation by targeting Rab7A. Proc Natl Acad Sci 114(31):8366-8371, 2017
62. Nomura M, Nagane M, Saito N, et al: Distinct molecular profile of diffuse cerebellar gliomas. Acta Neuropathol 134: 941-956, 2017
63. Takano S, Nagane M, Matsumura A, et al: MyD88 mutation in elderly predicts poor prognosis in primary central nervous system lymphoma; multi-institutional analysis. World Neurosurg 2017 Dec 16. pii: S1878-8750(17)32144-7
64. Wakabayashi T, Nagane M, Shibui S, et al: JCOG0911 INTEGRA study: a randomized screening phase II trial of interferonβ plus temozolomide in comparison with temozolomide alone for newly diagnosed glioblastoma. J Neuro-oncol 2018 Jul;138(3):627-636
65. Iijima S, Nagane M, et al: Hepatosplenic gamma-delta T cell lymphoma involving the brain. World Neurosurg 118: 139-142, 2018
66. Fukuoka K, Nagane M; Ichimura K, et al: Significance of molecular classification in ependymomas: C11orf95-RELA fusion-negative supratentorial ependymomas are a heterogenous group of tumor. Acta Neuropathol Comm 6:134, 2018.
67. Narita Y, Nagane M, Terasaki M, et al: A randomized, double-blind, phase III trial of personalized peptide vaccination for recurrent glioblastoma. Neuro-Oncology 21 (3): 348-359, 2019.
68. Nomura M, Nagane M, Mukasa A, et al: DNA demethylation is associated with malignant progression of lower-grade gliomas. Scientific Reports 9: 1903-1914, 2019
69. Nejo T, Nagane M, Kakimi K, et al: Reduced neoantigen expression revealed by longitudinal multiomics as a possible immune evasion mechanism in glioma. Cancer Immunol Res. 2019 Jul;7(7):1148-1161
70. Takami H, Nagane M, Ichimura K, et al. on behalf of the Intracranial Germ Cell Tumor Genome Analysis Consortium (the iGCT Consortium): Intratumoural immune cell landscape in germinoma reveals multipotent lineages and exhibits prognostic significance. Neuropathology and Applied Neurobiology, DOI:10.1111/nan.12570, accepted on 3 June, 2019, in press
71. Nagane M, Nishikawa R, et al: Safety and effectiveness of bevacizumab in Japanese patients with malignant glioma: a post-marketing surveillance study. Jpn J Clin Oncol 49 (11):1016-1023, 2019
72. Takami H, Nagane M, Ichimura K, et al: Integrated Clinical, Histopathological, and Molecular Data Analysis of 190 Central Nervous System Germ Cell Tumors from the iGCT Consortium. Neuro-Oncol 2019 Dec 17;21(12):1565-1577
73. Shishido-Hara Y, Nagane M, Kamma H, et al: Detection of t(14;18)(q32;q21) for IgH/BCL2 in CNS tumor-like lesions with chronic perivascular inflammation. Clinical and Experimental Neuroimmunology, in press
74. Guerreiro Stucklin AS, Nagane M, Hawkins C, et al: Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas. Nature Comm. 2019 Sep 25;10(1):4343.
75. Nagane M, Shiokawa Y, et al. Multiagent immunochemotherapy, R-MPV-A, for patients with secondary central nervous system lymphoma. Neuro-Oncology Advances, Volume 1, Issue Supplement_2, December 2019, Page ii32, https://doi.org/10.1093/noajnl/vdz039.145
76. Tateishi K, Nagane M, Ichimura K, et al. NF-kB canonical pathway activation drives glycolysis and tumor progression in primary central nervous system lymphoma. Neuro-Oncology Advances, Volume 1, Issue Supplement_2, December 2019, Page ii10, https://doi.org/10.1093/noajnl/vdz039.045
77. Natsume A, Nagane M, Wakabayashi T, et al, and members of Japan Clinical Oncology Group Brain Tumor Study Group (JCOG-BTSG). Genetic analysis in patients with newly diagnosed glioblastomas treated with interferon-beta plus temozolomide in comparison with temozolomide alone. J Neurooncol in press
78. Sasaki N, Nagane M. et al. Consecutive single-institution case series of primary central nervous system lymphoma treated by R-MPV or high-dose methotrexate monotherapy. Jpn J Clin Oncol in press

競争的研究資金獲得歴(研究代表者のみ)
平成13年度
1. 科学研究費補助金 基盤研究(C)
研究課題名「悪性グリオーマにおけるTRAIL・抗癌剤併用による細胞死の分子機構の解明」
研究代表者 永根基雄
研究期間 平成13-14年度

平成15年度
3. 科学研究費補助金 基盤研究(C)
研究課題名「脳腫瘍における中性アミノ酸トランスポーター発現の生物学的意義及び新規治療法の開発」
研究代表者 永根基雄
研究期間 平成15-16年度

平成17年度
5.科学研究費補助金(基盤研究C)
研究課題名「悪性神経膠腫に対するヒト抗TRAIL受容体抗体による新規治療法の開発」
研究者代表者:永根基雄
研究期間 平成17-18年度

平成19年度
10.科学研究費補助金(基盤研究C)
研究課題名 「悪性神経膠腫に対する複合的シグナル阻害剤による新規治療法の開発」
研究者代表者:永根基雄
研究期間 平成19-21年度

平成22年度
14.科学研究費補助金(基盤研究C)
研究課題名 「悪性神経膠腫に対する新規抗EGFR抗体・抗癌剤併用による治療法の開発」
研究者代表者:永根基雄
研究期間 平成22-24年度

平成25年度
21.科学研究費補助金(基盤研究C)
研究課題名 「悪性神経膠腫に対するDNA修復機構阻害による抗癌剤増感治療法の開発」
研究者代表者:永根基雄
研究期間 平成25-27年度

平成28年度
30.科学研究費補助金(基盤研究B)
研究課題名 「中枢神経系悪性リンパ腫に特異的な遺伝子異常の機能解析と新規分子標的治療の開発」
研究者代表者:永根基雄
研究期間 平成28-31年度

平成29年度
34. 日本医療研究開発機構(革新的がん医療実用化研究事業):
研究開発課題名 「再発膠芽腫に対するテモゾロミド用量強化法を用いた標準治療確立に関する研究」
研究開発代表者:永根基雄
委託期間 平成29-31年度

令和2(2020)年度
42. 科学研究費補助金(基盤研究B)
研究課題名「中枢神経系悪性リンパ腫の腫瘍内多様性と微小環境解析による病態発生の解明と治療開発」
研究者代表者:永根基雄
研究期間 令和2年-5年度
所属学会 日本脳神経外科学会、日本脳腫瘍学会、米国臨床腫瘍学会(ASCO)、アメリカ癌学会(AACR)、北米脳腫瘍学会(SNO)、日本癌学会、日本癌治療学会、日本臨床腫瘍学会、日本脳腫瘍病理学会など
公的な委員会等の役員・委員歴 独立行政法人医薬品医療機器総合機構(PMDA)専門委員、日本癌治療学会がん診療ガイドライン統括・連絡委員会評価委員(脳腫瘍担当)
ひとことメッセージ 神経膠腫・中枢神経系悪性リンパ腫を主とした悪性脳腫瘍の治療・研究を専門.最新の医療技術を導入した手術,厚生労働省悪性脳腫瘍研究班に所属し大規模多施設共同臨床試験(化学療法)の計画・実施に従事,日本癌治療学会による脳腫瘍治療ガイドライン作成委員など行う傍ら,悪性神経膠腫に対する新規治療開発を目的とした基礎研究を薬剤耐性,分子生物学的観点より行っている.
付属病院ホームページ ドクター紹介(2012年8月16日公開)
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