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Development of molecular targeted therapy for primary central nervous system lymphomas

Research Project

Project/Area Number 24390347
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Cerebral neurosurgery
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Ryuya YAMANAKA  京都府立医科大学, 医学部, 教授 (20323991)

Co-Investigator(Kenkyū-buntansha) IKENAKA Kazuhiro  生理学研究所, 分子神経生理部門, 教授 (00144527)
KAWAGUCHI Atsush  佐賀大学, 医学部, 教授 (60389319)
HAYANO Azusa  京都府立医科大学, 医学研究科, 博士研究員 (10379018)
Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2015: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Keywords脳リンパ腫 / ゲノム解析 / エクソーム解析 / 分子標的療法 / 脳腫瘍 / バイオマーカー / エクソーム / 脳神経疾患 / トランスレーショナルリサーチ / 外科 / 遺伝子 / 中枢神経系原発悪性リンパ腫 / 全エクソンキャプチャーシーケンス / ゲノム / 癌 / 臨床 / 中枢神経原発悪性リンパ腫 / 遺伝子発現 / miRNA / 薬剤耐性 / 脳原発リンパ腫 / シーケンス
Outline of Final Research Achievements

To delineate the genetic basis of PCNSL pathogenesis, we performed a comprehensive genetic study. We first analyzed paired tumor/normal DNA from 35 PCNSL cases by whole-exome sequencing (WES). Significantly mutated genes identified by WES and previously known mutational targets in PCNSL and systemic DLBCL were further screened for mutations using SureSelect-based targeted deep sequencing (Agilent) in an extended cohort of PCNSL cases (N = 90). Copy number alterations (CNAs) have been also investigated using SNP array-karyotyping (N =54).
WES, SNP array karyotyping and follow-up targeted sequencing of a large cohort of PCNSL cases revealed the genetic landscape of PCNSL, which were more homogeneous than that of systemic DLBCL, and thought to be involved in activation of constitutive NF-KB/TLR/BCR signaling, escape from immunosurveillance, as well as highly frequent SHMs.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (37 results)

All 2016 2015 2014 2013 2012 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results,  Open Access: 5 results,  Acknowledgement Compliant: 4 results) Presentation (10 results) (of which Int'l Joint Research: 2 results) Book (9 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Prognostic significance of S-phase fractions in peritumoral invading zone analyzed by laser scanning cytometry in patients with high-grade glioma (preliminary study).2016

    • Author(s)
      Nakajima S, Morii K, Takahashi H, Fujii Y, Yamanaka R
    • Journal Title

      ONCOLOGY LETTERS

      Volume: 11 Issue: 3 Pages: 2106-2110

    • DOI

      10.3892/ol.2016.4205

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Secondary glioma following acute lymphocytic leukemia: Therapeutic implications.2016

    • Author(s)
      Yamanaka R,Hayano A
    • Journal Title

      Neurosurg Rev

      Volume: in press

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Thr160 of Axin1 is critical for the formation and function of the β-catenin destruction complex.2015

    • Author(s)
      Koyama-Nasu R, Hayashi T, Nasu-Nishimura Y, Akiyama T, Yamanaka R
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 459 Issue: 3 Pages: 411-415

    • DOI

      10.1016/j.bbrc.2015.02.118

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Assessment of autonomic nervous system function in nursing students using an autonomic reflex orthostatic test by heart rate spectral analysis.2015

    • Author(s)
      Hasegawa M, Hayano A, Kawaguchi A and Yamanaka R
    • Journal Title

      Biomedical Reports

      Volume: 3 Issue: 6 Pages: 831-834

    • DOI

      10.3892/br.2015.512

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of S-phase fractions in peritumoral invading zone analysed by Laser Scanning Cytometry in patients with high grade glioma (preliminary study)2015

    • Author(s)
      Nakajima S, Ken Morii K, Takahashi H, Fujii Y, Yamanaka R
    • Journal Title

      Oncology Letters

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The concept of health among Japanese nursing students: comparisons between 1st-year and 4th-year students among nursing and non-nursing undergraduates.2015

    • Author(s)
      Mizuno A, Hasegawa M, Hayano A, Takishita Y, Iwawaki Y, Yamanaka R
    • Journal Title

      Sch. J. Arts. Humanit. Soc. Sci.

      Volume: 3(1A) Pages: 36-40

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A study of lifestyle and dietary habits in Japanese nursing students.2015

    • Author(s)
      Fukumoto R, Hasegawa M, Takishita Y, Iwawaki Y, Kawaguchi A, Yamanaka R
    • Journal Title

      Sch. J. Arts. Humanit. Soc. Sci.

      Volume: 3(1B) Pages: 139-143

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The concept of health among Japanese nursing students (Part 2).2015

    • Author(s)
      Mizuno A, Hasegawa M, Hayano A, Takishita Y, Iwawaki Y, Yamanaka R
    • Journal Title

      Sch. J. Arts. Humanit. Soc. Sci.

      Volume: 3(1E) Pages: 323-327

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Non-deep-seated primary CNS lymphoma – therapeutic responses and a molecular signature2014

    • Author(s)
      Iwadate Y, Suganami A, Ikegami S, Shinozaki N, Matsutani T, Tamura Y, Saeki N, Yamanaka R
    • Journal Title

      J Neurooncol

      Volume: 117 Issue: 2 Pages: 261-268

    • DOI

      10.1007/s11060-014-1379-4

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gene expression signature-based prognostic risk score in patients with glioblastoma.2013

    • Author(s)
      Kawaguchi A, Yajima N, Tsuchiya N, Homma J, Sano M, Natsumeda M, Takahashi H, Fujii Y, Kakuma T, Yamanaka R
    • Journal Title

      Cancer Sci

      Volume: 104 Issue: 9 Pages: 1205-1210

    • DOI

      10.1111/cas.12214

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phase II study of personalized peptide vaccination for refractory bone and soft tissue sarcoma patients.2013

    • Author(s)
      Takahashi R, Ishibashi Y, Hiraoka K, Matsueda S, Kawano K, Kawahara A, Kage M, Ohshima K, Yamanaka R, Shichijo S, Shirouzu K, Itoh K, Sasada T.
    • Journal Title

      Cancer Sci.

      Volume: 104 Issue: 10 Pages: 1285-1294

    • DOI

      10.1111/cas.12226

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Radiation-Induced Glioblastoma Following Radiotherapy for Pituitary Adenomas: Marked Response to Chemotherapy.2013

    • Author(s)
      Kon T, Natsumeda M, Takahashi H, Taki T,Fujii Y, Yamanaka R
    • Journal Title

      J Neurol Neurophysiol

      Volume: 4 Issue: 03 Pages: 155-155

    • DOI

      10.4172/2155-9562.1000155

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification and Validation of a Gene Expression Signature That Predicts Outcome in Malignant Glioma Patients2012

    • Author(s)
      Kawaguchi A, Yamanaka R, 他
    • Journal Title

      Int J Oncol

      Volume: 40(3) Pages: 721-30

    • DOI

      10.3892/ijo.2011.1240

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene expression signature-based prognostic risk score in patients with primary central nervous system lymphoma2012

    • Author(s)
      Kawaguchi A, Yamanaka R, 他
    • Journal Title

      Clin Cancer Res

      Volume: 18(20) Issue: 20 Pages: 5672-81

    • DOI

      10.1158/1078-0432.ccr-12-0596

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Genetic Basis of Primary Central Nervous System Lymphoma.2015

    • Author(s)
      Yoshida K, Yamanaka R, Ogawa S et al.
    • Organizer
      57th ASH Annual Meeting and Exposition.
    • Place of Presentation
      Orland, FL
    • Year and Date
      2015-12-05
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 外来化学療法を受けるがん患者の就労の有無による気がかりの相違2015

    • Author(s)
      田村沙織、光木幸子、山中龍也、阪口晃一、黒星晴夫、中西正芳、栗生宜明、村山康利
    • Organizer
      第53回日本癌治療学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2015-10-29
    • Related Report
      2015 Annual Research Report
  • [Presentation] Genetic basis of primary central nervous system lymphoma.2015

    • Author(s)
      Yoshida K, Yamanaka R, Ogawa S et al.
    • Organizer
      13th INTERNATIONAL CONFERENCE ON MALIGNANT LYMPHOMA
    • Place of Presentation
      Lugano, Switzerland
    • Year and Date
      2015-06-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 中枢神経原発悪性リンパ腫患者の予後予測方法の探索2014

    • Author(s)
      山中龍也、川口淳、岩立康男、菰原 義弘、梶原浩司、藤井幸彦
    • Organizer
      第73回日本癌学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 中枢神経原発悪性リンパ腫の予後に関与するマイクロRNAの探索2014

    • Author(s)
      田村裕、菅波晃子、池上史郎、篠崎夏樹、松谷智郎、佐伯直勝、山中龍也、岩立康男
    • Organizer
      第73回日本癌学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 中枢神経原発悪性リンパ腫患者の予後予測方法の探索2014

    • Author(s)
      山中龍也、川口淳、岩立康男、菰原 義弘、梶原浩司、藤井幸彦
    • Organizer
      第12回日本臨床腫瘍学会学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2014-07-17 – 2014-07-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] 悪性星細胞腫瘍患者の予後予測方法の探索2013

    • Author(s)
      山中龍也、川口淳、藤井幸彦、角間辰行
    • Organizer
      第11回日本臨床腫瘍学会学術集会
    • Place of Presentation
      仙台
    • Related Report
      2013 Annual Research Report
  • [Presentation] 悪性星細胞腫瘍の遺伝子発現プロファイルによる予後予測方の検討2013

    • Author(s)
      山中龍也、森吉英子、川口淳、藤井幸彦、角間辰行
    • Organizer
      第72回日本癌学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] 悪性神経膠腫患者の予後を予測する遺伝子群の探索2012

    • Author(s)
      山中龍也
    • Organizer
      第10回日本臨床腫瘍学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2012 Annual Research Report
  • [Presentation] 悪性神経膠腫患者の予後を予測する遺伝子群の探索2012

    • Author(s)
      山中龍也
    • Organizer
      第71回日本癌学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2012 Annual Research Report
  • [Book] Primary Central Nervous System Lymphoma (PCNSL): Incidence, Management and Outcomes2016

    • Author(s)
      Kanayama T, Hayano A, Yamanaka R
    • Publisher
      Nova Science Publishers
    • Related Report
      2015 Annual Research Report
  • [Book] Primary Central Nervous System Lymphoma (PCNSL): Incidence, Management and Outcomes2016

    • Author(s)
      Yamanaka R
    • Publisher
      Nova Science Publishers
    • Related Report
      2015 Annual Research Report
  • [Book] Primary Central Nervous System Lymphoma (PCNSL): Incidence, Management and Outcomes2016

    • Author(s)
      Yamanaka R, Yoshioka S, Fujimoto S, Iwawaki Y
    • Publisher
      Nova Science Publishers
    • Related Report
      2015 Annual Research Report
  • [Book] Molecular Considerations and Evolving Surgical Management Issues in the Treatment of Patients with a Brain Tumor2015

    • Author(s)
      Yamanaka R, Hayano A
    • Total Pages
      421
    • Publisher
      INTECH
    • Related Report
      2015 Annual Research Report
  • [Book] Molecular Considerations and Evolving Surgical Management Issues in the Treatment of Patients with a Brain Tumor,2015

    • Author(s)
      Yamanaka R, Hayano A
    • Total Pages
      421
    • Publisher
      INTECH
    • Related Report
      2014 Annual Research Report
  • [Book] Experiences and expectations for glioma immunotherapeutic approaches.2014

    • Author(s)
      Yamanaka R, Hayano A.
    • Total Pages
      4
    • Publisher
      Frontiers
    • Related Report
      2014 Annual Research Report
  • [Book] Brain Tumors.2013

    • Author(s)
      Yamanaka R
    • Publisher
      INTECH(In press)
    • Related Report
      2012 Annual Research Report
  • [Book] Glioma : Immunotherapeutic approaches.2012

    • Author(s)
      Yamanaka R
    • Publisher
      Landes Bioscience/Springer
    • Related Report
      2012 Annual Research Report
  • [Book] 分子標的薬-がんから他疾患までの治癒をめざして2012

    • Author(s)
      山中龍也
    • Publisher
      日本臨床社
    • Related Report
      2012 Annual Research Report
  • [Remarks] 医学講座HP

    • URL

      http://www.f.kpu-m.ac.jp/c/kouza/igaku/

    • Related Report
      2015 Annual Research Report
  • [Remarks] 京都府立医科大学 保健看護学研究科 医学講座

    • URL

      http://www.f.kpu-m.ac.jp/c/kouza/igaku/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 京都府立医科大学大学院保健看護学研究科医学講座

    • URL

      http://www.f.kpu-m.ac.jp/c/kouza/igaku/

    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] 悪性神経膠腫Grade4患者の予後予測方法及びキット2013

    • Inventor(s)
      山中龍也、藤井幸彦、角間辰之、川口淳
    • Industrial Property Rights Holder
      山中龍也、藤井幸彦、角間辰之、川口淳
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-124686
    • Filing Date
      2013-06-13
    • Related Report
      2013 Annual Research Report

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Published: 2012-04-24   Modified: 2023-03-23  

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