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Development of new strategies for cancer treatment based in system biological-analysis of cancer system abnormality

Research Project

Project/Area Number 15390439
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionSaga University (2004)
佐賀医科大学 (2003)

Principal Investigator

TABUCHI Kazuo  Saga University, Faculty of Medicine, Professor, 医学部, 教授 (50116480)

Co-Investigator(Kenkyū-buntansha) SHIRAISHI Tetsuya  SONY Computer Science Laboratory, Researcher, 研究員 (70206275)
MINETA Toshihiro  Saga University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (20264187)
MASUOKA Jun  Saga University, Faculty of Medicine, Instructor, 医学部, 助手 (50359949)
KITANO Hiroaki  System biology Institute, President, 会長
SHIWA Mieko  Cyphagen Biosystems, Researcher, バイオシステムズ, 主任研究員
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2004: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2003: ¥9,600,000 (Direct Cost: ¥9,600,000)
Keywordsglioma / array-CGH / SELDI-TOF MS / detrended fluctuation analysis / pleiotrophin / transthyretin / systems biology / scale-free network / 脳腫瘍 / データベース / インターフェロン / トランスクリプトーム / システム生物学 / SELDI-TOF mass spectrometry
Research Abstract

The purpose of this research is to develop the new strategies of cancer treatment based on systems biological analysis of cancer system abnormality. New genomic aberrations were found in glioblastoma cells by microarray-based comparative genomic hybridization. The first attempts to apply detrended fluctuation analysis to copy number profiles by considering the reading direction as the time axis demonstrated that higher long-term fractal scaling exponents correlated well with longer survival of glioblastoma patients. Proteomic technique using both SELDI-TOF MS(surface enhanced laser desorption/ionization time-of-flight mass spectrometry) and MALDI(matrix assisted laser desorption/ionization) TOF MS identified pleiotrophin as a specific growth factor of neural stem cells and transthyretin as a brain ischemia-specific protein. Petri-Net simulation demonstrated that trimer formation of soluble FasL is essential to enhance apoptotic enhancing activity. The four molecular mechanisms of biological robustness such as redundancy, diversity, feedback, modularity and decoupling were found in glioblastoma biomolecular system. Molecular connection network established by PathwayAssist software had the characteristics of scale-free networks such as existence of hub, obligation of power law, so-called small world and bow-tie structure. The intentional attack to hub protein/subsystem seems to easily destroy the scale-free network of cancer.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (26 results)

All 2005 2004 2003 Other

All Journal Article (21 results) Book (2 results) Publications (3 results)

  • [Journal Article] マススペクロトメトリー法による脳脊髄液の病態解析2005

    • Author(s)
      田渕和雄
    • Journal Title

      臨床検査 49

      Pages: 375-386

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 悪性グリオーマ発生の分子機序2005

    • Author(s)
      田渕和雄
    • Journal Title

      脳外誌 14

      Pages: 115-120

    • NAID

      110003814016

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Detection of JC virus DNA sequence in brain tumors in pediatric patients.2005

    • Author(s)
      Okamoto H, Mineta T, Ueda S, Nakahara Y, Shiraishi T, Tamiya T, Tabuchi K
    • Journal Title

      J Neurosurg (Pediatrics) 102

      Pages: 294-294

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Increased cytotoxicity of soluble Fas ligand by fusing is oleucine zipper motif.2004

    • Author(s)
      Shiraishi T
    • Journal Title

      B.B.R.C 322

      Pages: 197-202

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of pleiotrophin in conditioned medium secreted from neural stem cells by SELDI-TOF and SELDI-tandemmass spectrometry.2004

    • Author(s)
      Furuta M
    • Journal Title

      Developmental Brain Research 152

      Pages: 189-197

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Combined proteomic approach with SELDI-TOF-MS and peptidemass fingerprinting identified the rapid increase of monomeric transthyretin in rat cerebrospinal fluid after transient focal cerebral ischemia.2004

    • Author(s)
      Suzuyama K
    • Journal Title

      Molecular Brain Research 129

      Pages: 44-53

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of pleiotrophin in conditioned medium secreted from neural stem cells by SELDI-TOF and SELDI-tandem mass spectrometry.2004

    • Author(s)
      Fuuta M, Shiraishi T, Okamoto H, Mineta T, Tabuchi K, Shiwa M
    • Journal Title

      Developmental Brain Research 152

      Pages: 189-197

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Detrended fluctuation analysis of genome-wide copy number profiles of glioblastomas using array-based comparative genome hybridization.2004

    • Author(s)
      Nakahara Y, Shiraishi T, Okamoto H, Mineta T, Oishi T, Sasaki K, Tabuchi K
    • Journal Title

      Neuro-Oncology 6

      Pages: 281-289

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of the Wilms'tumor gene product WT1 in glioblastomas and medullobalstomas.2004

    • Author(s)
      Nakahara Y, Okamoto H, Mineta T, Tabuchi K
    • Journal Title

      Brain Tumor Pathology 21

      Pages: 113-116

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Increased cytotoxicity of soluble Fas ligand by fusing isoleucine zipper motif.2004

    • Author(s)
      Shiraishi T, Suzuyama K, Okamoto H, Mineta T, Tabuchi K, Nakayama K, Shimizu Y, Tohma J, Ogihara T, Ogihara T, Nabe H, Mochizuki H, Nagata S
    • Journal Title

      B.B.R.C 322

      Pages: 197-202

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Combined proteomic approach with SELDI-TOF-MS and peptide mass fingerprinting identified the rapid increase of monomeric transthyretin in rat cerebrospinal fluid after transient focal cerebral ischemia.2004

    • Author(s)
      Suzuyama K, Shiraishi T, Oishi T, Ueda S, Okamoto H, Mineta T, Tbuchi K
    • Journal Title

      Molecular Brain Research 129

      Pages: 44-53

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Induction of the DNA repair gene MGMT by dexamethasone in glioblastomas.2004

    • Author(s)
      Ueda S, Mineta T, Nakahara Y, Okamoto H, Shiraishi T, Tabuchi K
    • Journal Title

      J Neurosurg 101

      Pages: 659-663

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Increased cytotoxicity of soluble Fas ligand by fusing isoleucine zipper motif2004

    • Author(s)
      Shiraishi T
    • Journal Title

      B.B.R.C 322

      Pages: 197-202

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Detrended fluctuation analysis of genome-wide copy number profiles of gliobl astomas using array-based comparative genome hybridization2004

    • Author(s)
      Nakahara Y
    • Journal Title

      Neuro-oncology 6

      Pages: 281-289

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification of pleiotrophin in conditioned medium secreted from neural stem cells by SELDI-TOF and SELDI-tandem mass spectrometry2004

    • Author(s)
      Furuta M
    • Journal Title

      Developmental Brain Research 152

      Pages: 189-197

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Combined proteomic approach with SELDI-TOF-MS and peptide mass fingerprinting identified the rapid increase of monomeric transthyretin in rat cerebrospinal fluid after transient focal cerebral ischemia2004

    • Author(s)
      Suzuyama K
    • Journal Title

      Molecular Brain Research 129

      Pages: 44-53

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Induction of the DNA repair gene MGMT by dexamethasone in glioblastomas2004

    • Author(s)
      Ueda S
    • Journal Title

      Journal of Neurosurgery 101

      Pages: 659-663

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression of the Wilms'tumor gene product WT1 in glioblastomas and medullobalstomas2004

    • Author(s)
      Nakahara Y
    • Journal Title

      Brain Tumor Pathology 21

      Pages: 113-116

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Genetic alterations of human brain tumors as molecular prognostic factors.2003

    • Author(s)
      Shiraishi T, Tabuchi K
    • Journal Title

      Neuropathology 23

      Pages: 95-108

    • NAID

      50000792253

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Biological characterization of a secondary glioblastoma with extracranial progression and systemic metastasis.2003

    • Author(s)
      Ueda S, Mineta T, Suzuyama K, Furuta M, Shiraishi T, Tabuchi M
    • Journal Title

      Neuro-Oncology 5

      Pages: 14-18

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] ロバストシステムとしての癌とシステム生物学

    • Author(s)
      白石哲也
    • Journal Title

      バイオテクノロジージャーナル 5

      Pages: 66-72

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 脳神経外科大系6.脳腫瘍I2004

    • Author(s)
      田渕和雄
    • Total Pages
      10
    • Publisher
      中山書店
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 脳神経外科大系6.脳腫瘍I.2004

    • Author(s)
      田渕 和雄
    • Total Pages
      20
    • Publisher
      中山書店
    • Related Report
      2004 Annual Research Report
  • [Publications] 白石哲也: "脳腫瘍のシステムバイオロジー"蛋白質核酸酵素. 48. 795-801 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shiraishi, T.: "Genetic alterations of human brain tumors as molecular prognostic factors"Neuropathology. 23. 95-108 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 白石哲也: "脳腫瘍の最新医療"先端医療技術研究所. 460 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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