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Possibility of new treatment modality by inhibition of anti-apoptotic molecule XIAP

Research Project

Project/Area Number 14370506
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionYamagata University Faculty of Medicine

Principal Investigator

TOMITA Yoshihiko  Yamagata University, Faculty of Medicine, Professor, 医学部, 教授 (90237123)

Co-Investigator(Kenkyū-buntansha) KATO Tomoyuki  Yamagata University, Faculty of Medicine, Assistant, 医学部, 講師
OJI Hiroshi  Yamagata University, Faculty of Medicine, Assistant, 医学部, 助手 (30302293)
ビリム ラジーミル  新潟大学, 大学院・医歯学総合研究科, 講師 (50334686)
鈴木 泰宏  山形大学, 医学部, 助手 (50261699)
一柳 統  山形大学, 医学部, 助手
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 2004: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2003: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥5,900,000 (Direct Cost: ¥5,900,000)
KeywordsUrological cancer / apoptosis / renal cell cancer / XIAP / FAs / urinary bladder cancer / Bcl-2 / 尿路上皮癌 / カスペース / 遺伝子治療
Research Abstract

Detailed study of inter-molecular mechanism in apoptotic machinery of tumor cells may contribute to invention of new modality of cancer therapy. In the present study, a putative anti-apoptotic molecule, XIAP, was investigated in terms its expression and action for new modality of treatment. < design and examination of its action of short interference (si) RNA to XIAP> Previous study revealed insufficient inhibition of XIAP tempted us to use siRNA instead. Three sequences were used to siRNA and cloned into a plasmid vector good for siRNA. One of the three siRNA was most potent to knock down XIAP expression. <stable transfectant> Ten to twelve clones each were isolated from transfection of the vector to Caki-1 or LNCap, and under investigation of its function. <XIAP expression and its relation to CRP, interleukin (IL)-6 and tumor necrosis factor(TNF) pathway> Statistically significant correlation between XIAP expression and serum CRP was noticed in renal cell cancer patients. Among cultured cell lines, some of them secreted high titer of IL-6 and TNF-alpha, and frequently expressed XIAP. This indicates that possibility of double inhibition of XIAP expression itself and TNF pathway render more complete inhibition of XIAP leading to more susceptible to apoptotic stimuli. Further examination was being performed.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (6 results)

All 2004 2003 Other

All Journal Article (5 results) Publications (1 results)

  • [Journal Article] Impact of frequent Bcl-2 expression on better prognosisin renal cell carcinoma patients.2004

    • Author(s)
      T.Itoi et al.
    • Journal Title

      Br.J.Cancer 90

      Pages: 200-205

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Impact of frequent Bcl-2 expression on better prognosisin renal cell carcinoma patients.2004

    • Author(s)
      T.Itoi, K.Yamana, V.Bilim, K.Takahashi, Y.Tomita
    • Journal Title

      Br.J.Cancer 90

      Pages: 200-205

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The role of IRF-1 and caspase-7 in IFN-gamma enhancement of Fas-mediated apoptosis in ACHN renal cell carcinoma cells.2003

    • Author(s)
      Y.Tomita et al.
    • Journal Title

      Int.J.Cancer 104

      Pages: 400-408

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The role of IRF-1 and caspase-7 in IFN-gamma enhancement of Fas-mediated apoptosis in ACHN renal cell carcinoma cells.2003

    • Author(s)
      Y.Tomita, V.Bilim, T.Kasahara, N.Hara, K.Takahashi
    • Journal Title

      Int.J.Cancer 104

      Pages: 400-408

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] ROLE OF XIAP IN THE MALIGNANT PHENOTYPE OF TRANSITIONAL CELL CANCER (TCC) AND THERAPEUTIC ACTIVITY OF XIAPANTISENSE OLIGONUCLEOTIDES AGAINST MULTIDRUG-RESISTANT TCC IN VITRO2003

    • Author(s)
      Vladimir Bilim他
    • Journal Title

      International Journal of Cancer 103, 1

      Pages: 29-37

    • Related Report
      2004 Annual Research Report
  • [Publications] Bilim V, 他: "Role of XIAP in the malignant phenotype,【triple bond】"International Journal of Cancer. 103巻1号. 29-37 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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