• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The anticancer effects of 5-aza-2'deoxycytidine as a DNA demethylation agent on NNK-induced rat hepatocellular carcimonas

Research Project

Project/Area Number 15590667
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionSapporo Medical University

Principal Investigator

SASAKI Shigeru  Sapporo Medical University, School of Medicine, Instructor, 医学部, 助手 (10305229)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Hiroyuki  Sapporo Medical University, School of Medicine, Instructor, 医学部, 助手 (40332910)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsmethylation / NNK / DNA array / hepatocellular carcinoma / DNA demethylation agent / NNKラット
Research Abstract

Hepatocellular tumors were induced in male Fischer 344 rats by treatment with the 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) three times a week (50 mg/kg intraperitoneally injection) for 20 weeks. Based on histopathological analysis, these tumors were diagnosed as carcinomas (12 nodules/total 28 nodules) and adenomas (16 nodules/total 28 nodules).
RNA and DNA were isolated from these hepatocellular carcinomas. To determine gene expression changes associated with NNK exposure to genotoxic carcinogens, these RNA were subjected to microarray analysis. A number of genes were down-regulated by NNK exposure compared with controls. The methylation status of these down-regulated genes were determined by methylation-specific PCR (MSP). Overall, the promoter region hypermethylation of the p16 and E-cadherin genes were detected. The protein expression levels of p16 and E-cadherin were examined by immunohistochemical staining. The expression levels of these proteins were also down-regulated.
The anticancer effects of 5-aza-2'deoxycytidine once a week (1 mg/kg intraperitoneally injection) as a DNA demethylation agent on NNK-induced rat hepatocellular carcimonas were investigated. Our results suggested that 5-aza-2'deoxycytidine did not influence on the potency of hepatocarcinogenesis induced by NNK, the progression of hepatocellular carcinomas and the methylation status of p16 and E-cadherin genes methylated with NNK treatment.

Report

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

    (8 results)

All 2004 2003 Other

All Journal Article (6 results) Publications (2 results)

  • [Journal Article] Monoclonal antibodies as effective therapeutic agents for solid tumors.2004

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

      Cancer Sci. 95

      Pages: 621-625

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Monoclonal antibodies as effective therapeutic agents for solid tumors2004

    • Author(s)
      Hinoda Y, Sasaki S, Ishida T, Imai K.
    • Journal Title

      Cancer Sci. 95(8)

      Pages: 621-625

    • NAID

      80016809427

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Integration of interferon-α/β signaling to p53 responses in tumour suppression and antiviral defence.2003

    • Author(s)
      Takaoka A. et al.
    • Journal Title

      Nature 424

      Pages: 516-523

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Differential roles of alterations of p53, p16, and SMAD4 expression in the progression of intraductal papillary-mucinous tumors of the pancreas.2003

    • Author(s)
      Sasaki S. et al.
    • Journal Title

      Oncol Rep. 10

      Pages: 21-25

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Integration of interferon-α/β signaling to p53 responses in tumour suppression and antiviral defence2003

    • Author(s)
      Takaoka A, Hayakawa S, Yanai H, Stoiber D, Negishi H, Kikuchi H, Sasaki S, Imai K, Shibue T, Honda K, Taniguchi T.
    • Journal Title

      Nature 424(6948)

      Pages: 516-523

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Differential roles of alterations of p53, p16, and SMAD4 expression in the progression of intraductal papillary-mucinous tumors of the pancreas2003

    • Author(s)
      Sasaki S, Yamamoto H, Kaneto H, Ozeki I, Adachi Y, Takagi H, Matsumoto T, Itoh H, Nagakawa T, Miyakawa H, Muraoka S, Fujinaga A, Suga T, Satoh M, Itoh F, Endo T, Imai K.
    • Journal Title

      Oncol Rep. 10(1)

      Pages: 21-25

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Takaoka A., Sasaki S., et al.: "Integration of interferon-alpha/beta signaling to p53 in tumour suppression and antiviral defence."Nature. 424. 516-523 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sasaki S., et al.: "Differential roles of alterations of p53, p16, and SMAD4 expression in the progression of intraductal papillary-mucinous tumors of the pancreas."Oncol.Rep.. 10. 21-25 (2003)

    • Related Report
      2003 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi