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Investigation of molecular genetic alterations and prognostic factors of primary central nervous system lymphoma

Research Project

Project/Area Number 23592140
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cerebral neurosurgery
Research InstitutionKyorin University

Principal Investigator

SHIOKAWA YOSHIAKI  杏林大学, 医学部, 教授 (20245450)

Co-Investigator(Renkei-kenkyūsha) NAGANE Motoo  杏林大学, 医学部, 教授 (60327468)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords悪性リンパ腫 / 脳腫瘍 / 遺伝子解析 / 予後因子 / 治療感受性 / Germinal center / MGMT / Mismatch repair / ゲノム解析
Research Abstract

We investigated prognostic markers for primary central nervous system lymphoma (PCNSL) using immunohistochemistry. Age and KPS were strong prognosticators as reported previously. Methotrexate-based chemoradiotherapy achieved a high rate of complete response (83%), improving survival of PCNSL patients. Multiplicity of PCNSL lesions was significantly associated with a short survival. High expression of LRP, drug efflux pump protein, was associated with a poor response to chemotherapy and shorter overall survival, suggesting that LRP may be a clinically relevant drug-resistance factor in PCNSL. Expression of a germinal center marker Bcl-6 was a favorable prognostic factor, whereas c-myc high protein expression was associated with an inferior survival. Low protein expression of mismatch repair proteins, MLH1, MSH2 and MSH6, was a significant indicator for a short survival in patients with PCNSL.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (40 results)

All 2014 2013 2012 2011 Other

All Journal Article (16 results) (of which Peer Reviewed: 10 results,  Open Access: 1 results) Presentation (21 results) (of which Invited: 2 results) Book (2 results) Remarks (1 results)

  • [Journal Article] C 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 nuclei2014

    • Author(s)
      Shishido-Hara Y, Yazawa T, Nagane M, Higuchi K, Abe-Suzuki S, Kurata M, Kitagawa M, Kamma H, Uchihara T
    • Journal Title

      J Neuropathol Exp Neurol

      Volume: 73 Issue: 5 Pages: 442-453

    • DOI

      10.1097/nen.0000000000000066

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 高齢者中枢神経系原発悪性リンパ腫に対する大量methotrexate基盤初期治療の成績と展望2014

    • Author(s)
      永根基雄,塩川芳昭
    • Journal Title

      Geriatric Neurosurgery

      Volume: 26 Pages: 63-70

    • Related Report
      2013 Final Research Report
  • [Journal Article] 脳神経外科医が解説する血液腫瘍:悪性リンパ腫2014

    • Author(s)
      永根基雄
    • Journal Title

      脳神経外科速報

      Volume: (in press)

    • Related Report
      2013 Final Research Report
  • [Journal Article] 高齢者中枢神経系原発悪性リンパ腫に対する大量methotrexate規模案初期治療の成績と展望2014

    • Author(s)
      小林啓一,永根基雄,河合拓也,野口明男,塩川芳昭
    • Journal Title

      Geriatric Neurosurgery

      Volume: 26 Pages: 63-70

    • Related Report
      2013 Annual Research Report
  • [Journal Article] 脳神経外科医が解説する血液腫瘍:悪性リンパ腫2014

    • Author(s)
      永根基雄
    • Journal Title

      脳神経外科速報

      Volume: in press

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Predictive value of mean apparent diffusion coefficient value for responsiveness of temozolomide-refractory malignant glioma to bevacizumab.2013

    • Author(s)
      Nagane M, et al.
    • Journal Title

      Int J Clin Oncol

      Volume: 19 Issue: 1 Pages: 16-23

    • DOI

      10.1007/s10147-013-0517-x

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multidrug immunochemotherapy (R-MPV-A) for newly diagnosed and recurrent primary central nervous system lymphomas (abstr NO-097)2013

    • Author(s)
      Nagane M, Shiokawa S
    • Journal Title

      Neuro-Oncology

      Volume: 15 Pages: 122-122

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] evacizumab for glioblastoma – a promising drug or not?2013

    • Author(s)
      Nagane M, Nishikawa R
    • Journal Title

      Cancers

      Volume: 5 Issue: 4 Pages: 1456-1468

    • DOI

      10.3390/cancers5041456

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of distinct subgroup of glioma and novel genes related to malignant progression by genome-wide methylation analysis2013

    • Author(s)
      Saito K, Mukasa A, Nagae G, Nagane M, Aihara K, Takayanagi S, Tanaka S, Aburatani H, Saito N
    • Journal Title

      Neuro-Oncology

      Volume: 15 Supplement 3

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Combination treatment with the anti-EGFR monoclonal antibody, nimotuzumab, and temozolomide causes synergistic growth suppression of mutant EGFR expressing glioma xenografts2013

    • Author(s)
      Nagane M, Nitta Y, Shimizu S, Shishido-Hara Y, Shiokawa Y
    • Journal Title

      Proceedings of 104th Annual Meeting of the American Association for Cancer Research

      Volume: 54

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multidrug immunochemotherapy (R-MPV-A) for newly diagnosed and recurrent primary central nervous system lymphomas2013

    • Author(s)
      Nagane M, Kobayashi K, Takayama N, Shiokawa S
    • Journal Title

      Neuro-Oncology

      Volume: 15 Supplement 3

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synergistic growth suppression of mutant epidermal growth factor receptor (EGFR)-expressing glioma xenograft by combination of temozolomide and anti-EGFR monoclonal antibody nimotuzumab2012

    • Author(s)
      Nitta Y, Shimizu S, Shishido-Hara Y, Shiokawa Y, Nagane M
    • Journal Title

      Neuro-Oncology

      Volume: 14 Supplement 6

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reduced Estimated Glomerular Filtration Rate is Associated with Stroke Outcome after Intravenous rt-PA:The Stroke Acute Management with Urgent Rsk-Factor Assessment and Improvement (SAMURAI) rt-PA Registry2011

    • Author(s)
      Naganuma M, Koga M, Shiokawa Y, Nakagawa J, Furui E, Kimura K, Yamagami H, Okada Y, Hasegawa Y, Kario K, Okuda S, Nishiyama K, Minematsu K, Toyoda K
    • Journal Title

      Cerebrovasc Dis

      Volume: 31 Pages: 12-129

    • Related Report
      2011 Research-status Report
  • [Journal Article] Early Ischemic Change on CT Versus Diffusion-Weighted Imaging for Patients With Stroke Receiving Intravenous Recombinant Tissue-Type Plasminogen Activator Therapy2011

    • Author(s)
      Nezu T, Koga M, Nakagawara J, Shiokawa Y, Yamagami H, Furui E, Kimura K, Hasegawa Y, Okada Y, Okuda S, Kario K, Naganuma M, Maeda K, Minematsu K, Toyoda K
    • Journal Title

      Stroke

      Volume: 42 Pages: 2196-2200

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] 齢者初発膠芽腫に対する放射線化学療法の治療成績と因子解析2011

    • Author(s)
      永根 基雄,小林 啓一,林 基高,清水 早紀,塩川 芳昭
    • Journal Title

      Geriatric Neurosurgery

      Volume: 23 Pages: 3-11

    • Related Report
      2011 Research-status Report
  • [Journal Article] Predictive value of mean apparent diffusion co-efficient value for responsiveness of temozolomide-refractory malignant glioma to bevacizumab2011

    • Author(s)
      Nagane M, Kobayashi K, Tanaka M, Tsuchiya K, Shiokawa Y
    • Journal Title

      J Clin Oncol

      Volume: 29: suppl

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 原発性中枢神経系悪性リンパ腫の予後規定因子の検討2013

    • Author(s)
      李政勲、塩川芳昭、永根基雄
    • Organizer
      第31回日本脳腫瘍学会学術総会
    • Place of Presentation
      宮崎
    • Year and Date
      2013-12-08
    • Related Report
      2013 Final Research Report
  • [Presentation] Multidrug immunochemotherapy (R-MPV-A) for newly diagnosed and recurrent primary central nervous system lymphomas2013

    • Author(s)
      Nagane M, Yoshiaki Shiokawa
    • Organizer
      The 4^<th> Quadrennial Meeting of the World Federation of Neuro-Oncology /The18th Annual Meeting of the Society for Neuro-Oncology
    • Place of Presentation
      San Francisco, CA, U.S.A
    • Year and Date
      2013-11-22
    • Related Report
      2013 Final Research Report
  • [Presentation] 悪性脳腫瘍治療の現状と展望2013

    • Author(s)
      永根基雄
    • Organizer
      第8回岐阜脳腫瘍研究会
    • Place of Presentation
      岐阜市,岐阜県
    • Year and Date
      2013-11-09
    • Related Report
      2013 Final Research Report
  • [Presentation] 初発中枢神経系原発悪性リンパ腫に対する多剤併用免疫化学療法(R-MPV-A)の治療効果2013

    • Author(s)
      永根基雄,塩川芳昭
    • Organizer
      第51回日本癌治療学会
    • Place of Presentation
      京都
    • Year and Date
      2013-10-26
    • Related Report
      2013 Final Research Report
  • [Presentation] 原発性中枢神経系悪性リンパ腫の予後規定因子の検討2013

    • Author(s)
      李政勲、塩川芳昭、永根基雄
    • Organizer
      第72回日本脳神経外科学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2013-10-18
    • Related Report
      2013 Final Research Report
  • [Presentation] 悪性脳腫瘍の化学療法up-to-date2013

    • Author(s)
      永根基雄
    • Organizer
      第3回長崎脳腫瘍研究会
    • Place of Presentation
      長崎市,長崎県
    • Year and Date
      2013-04-22
    • Related Report
      2013 Final Research Report
  • [Presentation] 中枢神経系原発悪性リンパ腫に対する大量methotrexate基盤初期治療の成績と展望2012

    • Author(s)
      永根基雄,小林啓一,塩川芳昭
    • Organizer
      第71回日本脳神経外科学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2012-10-19
    • Related Report
      2013 Final Research Report
  • [Presentation] 中枢神経系原発悪性リンパ腫に対する大量AraC単独療法2011

    • Author(s)
      永根基雄,塩川芳昭
    • Organizer
      第29回日本脳腫瘍学会
    • Place of Presentation
      下呂
    • Year and Date
      2011-11-28
    • Related Report
      2013 Final Research Report
  • [Presentation] CT及びMR perfusion imagesを用いた中枢神経系悪性リンパ腫と悪性神経膠腫の術前鑑別2011

    • Author(s)
      永根基雄,塩川芳昭
    • Organizer
      第70回日本脳神経外科学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2011-10-12
    • Related Report
      2013 Final Research Report
  • [Presentation] 中枢神経系原発悪性リンパ腫に対する大量AraC療法2011

    • Author(s)
      永根基雄,小林啓一,田中雅樹,畑中良,島田大輔,吉田裕毅,塩川芳昭
    • Organizer
      第15回 多摩脳腫瘍研究会
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Presentation] 中枢神経系原発悪性リンパ腫に対する大量AraC単独療法2011

    • Author(s)
      永根基雄,小林啓一,田中雅樹,塩川芳昭
    • Organizer
      第29回 日本脳腫瘍学会
    • Place of Presentation
      下呂、岐阜
    • Related Report
      2011 Research-status Report
  • [Presentation] Multidrug immunochemotherapy (R-MPV-A) for newly diagnosed and recurrent primary central nervous system lymphomas

    • Author(s)
      Motoo Nagane, Keiichi Kobayashi, Nobuyuki Takayama, Yoshiaki Shiokawa
    • Organizer
      2013 The 4th Quadrennial Meeting of the World Federation of Neuro-Oncology /The18th Annual Meeting of the Society for Neuro-Oncology
    • Place of Presentation
      San Francisco, CA, U.S.A.
    • Related Report
      2013 Annual Research Report
  • [Presentation] 悪性脳腫瘍治療の現状と展望

    • Author(s)
      永根基雄
    • Organizer
      第8回岐阜脳腫瘍研究会
    • Place of Presentation
      岐阜市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 初発中枢神経系原発悪性リンパ腫に対する多剤併用免疫化学療法(R-MPV-A)の治療効果

    • Author(s)
      永根基雄,小林啓一,高山信之,塩川芳昭
    • Organizer
      第51回 日本癌治療学会
    • Place of Presentation
      京都市
    • Related Report
      2013 Annual Research Report
  • [Presentation] 悪性脳腫瘍の化学療法up-to-date

    • Author(s)
      永根基雄
    • Organizer
      第3回長崎脳腫瘍研究会
    • Place of Presentation
      長崎市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Combination treatment with the anti-EGFR monoclonal antibody, nimotuzumab, and temozolomide causes synergistic growth suppression of mutant EGFR expressing glioma xenografts

    • Author(s)
      Nagane M, Nitta Y, Shimizu S, Shishido-Hara Y, Shiokawa Y
    • Organizer
      104th Annual Meeting of American Association for Cancer Research 2013
    • Place of Presentation
      Washington D.C., U.S.A.
    • Related Report
      2013 Annual Research Report
  • [Presentation] 原発性中枢神経系悪性リンパ腫の予後規定因子の検討

    • Author(s)
      李政勲、原由紀子、塩川芳昭、永根基雄
    • Organizer
      第72 回 日本脳神経外科学会学術総会
    • Place of Presentation
      横浜市
    • Related Report
      2013 Annual Research Report
  • [Presentation] 原発性中枢神経系悪性リンパ腫の予後規定因子の検討

    • Author(s)
      李政勲、原由紀子、塩川芳昭、永根基雄
    • Organizer
      第31 回 日本脳腫瘍学会学術集会
    • Place of Presentation
      宮崎市
    • Related Report
      2013 Annual Research Report
  • [Presentation] CT及びMR perfusion imagesを用いた中枢神経系悪性リンパ腫と悪性神経膠腫の術前鑑別

    • Author(s)
      永根基雄,田中雅樹,小林啓一,土屋一洋,塩川芳昭
    • Organizer
      第17回 多摩脳腫瘍研究会
    • Place of Presentation
      三鷹市,東京都
    • Related Report
      2012 Research-status Report
  • [Presentation] 中枢神経系原発悪性リンパ腫に対する大量methotrexate基盤初期治療の成績と展望

    • Author(s)
      永根基雄,小林啓一,塩川芳昭
    • Organizer
      第71回 日本脳神経外科学会総会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
  • [Presentation] 中枢神経系原発悪性リンパ腫に対する大量methotrexate基盤初期治療の成績と展望

    • Author(s)
      永根基雄,小林啓一,塩川芳昭
    • Organizer
      第30回 日本脳腫瘍学会
    • Place of Presentation
      広島
    • Related Report
      2012 Research-status Report
  • [Book] ニムスチン.Inプロフェッショナルがんナーシング2013別冊.これだけは押さえておきたいがん化学療法の薬.古瀬純司(編)2013

    • Author(s)
      永根基雄
    • Total Pages
      150
    • Publisher
      メディカ出版
    • Related Report
      2013 Final Research Report
  • [Book] プロフェッショナルがんナーシング2013別冊.これだけは押さえておきたいがん化学療法の薬2013

    • Author(s)
      永根基雄
    • Total Pages
      150
    • Publisher
      メディカ出版
    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://plaza.umin.ac.jp/~kyorin-n/

    • Related Report
      2013 Final Research Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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