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1999 Fiscal Year Final Research Report Summary

Induction of apoptosis against cytokine-producing urological cancer

Research Project

Project/Area Number 10671493
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKeio University

Principal Investigator

TACHIBANA Masaaki  Keio Univ., Dept.of Urology, Associate Professor, 医学部, 助教授 (70129526)

Co-Investigator(Kenkyū-buntansha) MURAI Masaru  Keio Univ., Dept.of Urology, Professor, 医学部, 教授 (90101956)
ASAUKRA Hirotaka  Keio Univ., Dept.of Urology, Assistant Professor, 医学部, 専任講師 (50175840)
NAKASHIMA Jun  Keio Univ., Dept.of Urology, Assistant Professor, 医学部, 専任講師 (10167546)
Project Period (FY) 1998 – 1999
Keywordscytokine-producing cancer cells / NF κ B / gene therapy / adenovirus / IKB
Research Abstract

This study was designed to investigate cancer gene therapy against cytokine producing cells. Firstable, we succeeded establishment of cytokine producing human urological cancer cells including kidney (KU-19-20) and bladder (KU-19-19) as a target model. These cells have been shown to secrete a variety of cytokines such as granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interleiukin-6 (IL-6) and IL-8. Then we investigated whether the cell growth and apoptosis of cytokine-producing cells can be regulated by nuclear factor kappa B (NFκB). When IκB stable form cDNA (which is known to be the NFκB inhibitor) was transfected into the cells with adenovirus vector, the production of several cytokines was significantly suppressed in these cells by the gene delivery. Notably, the significant induction of apoptosis was also observed by the gene therapy. These results suggest that NFκB activation maintains the cell viability as well as regulates cytokine production in cytokine-producing cancer cells and therefore these in vitro experiments support a rationale for preclinical in vivo studies to demonstrate growth inhibition in established tumors.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Sumitomo M, Tachibana M et al.,: "Induction of apoptosis of cytokine-producing bladder cancer cells by adenovirus-mediated kappa alpha overexpression"Hum Gene Ther. 10:1. 37-47 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sumitomo M, Tachibana M et al.,: "Overexpression of IL-1ra gene up-regulates interleukin-1beta converting enzyme(ICE) gene expression: possible mechanism underlying IL-1beta-resistance of cancer cells"Br J Cancer. 81:2. 277-86 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tachibana M et al: "Prognostic significance of flow cytometric deoxyribonucleic acid analysis for patients with superficial bladder cancers: a long-term follow-up study."Cancer Detect Prev.. 23:2. 155-62 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tachibana M et al: "G-CSF production in human bladder cancer and its ability to promote autocrine growth: a review."Cytokines Cell Mol. Ther. 4:2. 113-20 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sumitomo M, Tachibana M et al: "An essential role for nuclear factor kappa B in preventing TNF-A-induced cell death in prostate cancer cells."J. Urol.. 161. 674-679 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakashima J, Tachibana M et al: "Association between tumor necrosis factor in serum and cachexia in patients with prostate cancer."Clin Cancer Res. 4. 1743-1748 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sumitomo M; Tachibana M; Ozu C; Asakura H; Murai M; Hayakawa M; Nakamura H; Takayanagi A; Shimizu N: "Induction of apoptosis of cytokine-producing bladder cancer cells by adenovirus-mediated IkappaBalpha overexpression."Hum Gene Ther. 10:1. 37-47 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sumitomo M; Tachibana M; Murai M; Hayakawa M; Nakamura H; Takayanagi A; Shimizu N: "Overexpression of IL-1ra gene up-regulates interleukin-1beta converting enzyme (ICE) gene expression: possible mechanism underlying IL-1beta-resistance of cancer cells."Br J Cancer. 81:2. 277-286 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tachibana M; Miyakawa A; Miyakawa M; Saito S; Nakamura K; Baba S; Murai M: "Prognostic significance of flow cytometric deoxyribonucleic acid analysis for patients with superficial bladder cancers: a long-term follow-up study."Cancer Detect Prev. 23:2. 155-162 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tachibana M; Murai M: "G-CSF production in human bladder cancer and its ability to promote autocrine growth: a review."Cytokines Cell Mol Ther. 4:2. 113-120 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sumitomo M; Tachibana M; Nakashima J; Murai M; Miyajima A; Kimura F; Hayakawa M; Nakamura H: "An essential role for nuclear factor kappa B in preventing NF- α -induced cell death in prostate cancer cells."J Urol. 161. 674-679 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakashima J; Tachibana M; Ueno M; Miyajima A; Baba S; Murai M: "Association between tumor necrosis factor in serum and cachexia in patients with prostate cancer."Clin Cancer Res. 4. 1743-1748 (1998)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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