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2001 Fiscal Year Final Research Report Summary

Targeting chemotherapy with NM 23-H1 for carcinoma of the esophagus

Research Project

Project/Area Number 11671241
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionYamaguchi University

Principal Investigator

TANGOKU Akira  Yamaguchi University School of Medicine, Associate Professor, 医学部, 助教授 (10197593)

Co-Investigator(Kenkyū-buntansha) YOSHINO Shigefumi  Yamaguchi University School of Medicine, Research Associate, 医学部, 助手 (60294633)
HAZAMA Shoichi  Yamaguchi University School of Medicine, Research Associate, 医学部, 助手 (50253159)
OKA Masaaki  Yamaguchi University School of Medicine, Professor, 医学部, 教授 (70144946)
IIZUKA Norio  Yamaguchi University School of Medicine, Research Associate, 医学部, 寄附講座教員 (80332807)
Project Period (FY) 1999 – 2001
KeywordsEsophageal cancer / chemotherapy / nm23-H1 / chemosensitivity / cisplatin / prognosis
Research Abstract

The expression of nm23-H1 protein was examined immunohistochemically in 50 eligible patients with esophageal squamous cell carcinoma (OSCC). Reduced expression of nm23-H1 was associated with shorter overall survival in patients with involved lymph nodes. These data support the conclusion that reduced expression of nm23-H1 may be associated with poor prognosis of ESCC patients. Expression of nm23-H1 is associated inversely with sensitivity to cisplatin in human oesophageal squamous cell carcinoma. The nm23-H1 expression with cisplatin-induced DNA damage in OSCC using antisense nm23-H1 transfectants. YES-2/AS-12, an antisense nm23-H1-transfected OSCC cell line, showed significantly reduced expression of intracellular nm23-H1 protein compared with that in parental YES-2 cells and YES-2/Neo transfectants. Surface expression of nm23-H1 protein was not observed in any of the three cell lines. PCR analysis for DNA damage demonstrated that YES-2/AS-12 cells were more resistant to nuclear and m … More itochondrial DNA damage by cisplatin than were YES-2/Neo cells. In addition, mitochondrial membrane potentials and DNA fragmentation assays confirmed that YES-2/AS-12 was more resistant than YES-2/Neo to apoptosis induced by cisplatin. In contrast, YES-2/AS-12 was more sensitive to ouablain, a selective inhibitor of Na(+), K(+)-ATPase, than YES-2 and YES-2/Neo. Pre-treatment with ouabain resulted in no differences in cisplatin sensitivity between the three cell lines examined. Intracellular platinum level inYES-2/AS-12 was significantly lower than that in YES-2 and YES-2/Neo following incubation with cisplatin, whereas ouabain pre-treatment resulted in no differences in intracellular platinum accumulations between the three cell lines. Our data support the conclusion that reduced expression of intracellular nm23-H1 in OSCC cells is associated with cisplatin resistance via the prevention of both nuclear and mitochondrial DNA damage and suggest that it may be related to NA(+), K(+)-ATPase activity, which is responsible for intracellular cispla tin accumulation. Less

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Iizuka N: "Nm23-H1 gene as a molecular switch between the free-floating and adherent states of gastric cancer cells"Cancer letter. 174. 5-71 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iizuka N: "Downregulation of intracellular nm23-H1 prevents cisplatin-induced DNAdamage in oesophageal cancer cells : possible association with Na+, K+-ATPase"Br J Cancer. 83. 1209-1215 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iizuka N: "The nm23-H1 gene as a predictor of sensitivity to chemotherapeutic agents in oesophageal squamous cell carcinoma"Br J Cancer. 81. 469-475 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iizuka N: "The association between nm23-H1 expression and survival in patients with esophageal squamous cell carcinoma"Cancer Lett. 138. 139-144 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iizuka N: "Nm23-H1 gene as a molecular switch between the free-floating and adherent states of gastric cancer cells"Cancer letter. 174. 65-71 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iizuka N: "Downregulation of intracellular nm23-H1 prevents cisplatin-induced DNA damage in esophageal cancer cells : possible association with Na+, K+-ATPase"Br J Cancer. 83 (9). 1209-1215 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iizuka N: "The nm23-H1 gene as a predictor of sensitivity to chemotherapeutic agents in oesophageal squamous cell carcinoma"Br J Cancer. 81. 469-475 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iizuka N: "The association between nm23-H1 expression and survival in patients with esophageal squamous cell carcinoma"Cancer Lett. 144. 138-139 (1999)

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

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Published: 2003-09-17  

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