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Relation between nm23-H1 expression and effect of chemotherapy for hepatocellular carcinoma

Research Project

Project/Area Number 12671230
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

OKA Masaaki  Yamaguchi University School of Medicine, Professor, 医学部, 教授 (70144946)

Co-Investigator(Kenkyū-buntansha) IIZUKA Norio  Yamaguchi University School of Medicine, Lecturer, 医学部, 寄附講座教員 (80332807)
MORI Noahide  Yamaguchi University Hospital, Lecturer, 医学部附属病院, 助手 (70325231)
HAZAMA Shoichi  Yamaguchi University Hospital, Assistant Professor, 医学部附属病院, 講師 (50253159)
前田 義隆  山口大学, 医学部, 助手 (30291488)
西田 峰勝  山口大学, 医学部・附属病院, 講師 (80243666)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsHepatocellular carcinoma / nm23-H1 / Chemotherapy / Intrahepatic recurrence / Microarray / Immunohistochemical staining / NM23-H1遺伝子 / 肝再発 / 免疫染色 / 肝細胞癌 / テロメラーゼ活性 / RT-PCR
Research Abstract

(1) Hepatocellular carcinoma (HCC) has a poor prognosis because of the high intrahepatic recurrence rate. 24 Patients with hepatocellular carcinoma (HCC) treated with CDDP/5FU. This chemotherapy was continued for 5 days, discontinued 2 days, and repeated 4 weeks at least. Ten of 24 patients responded to this therapy. Nm23-H1 protein expression was determined by immunohistochemistry. 8 of 10 reponders had nm23-H1 positive (> 50% of HCC having nm23-H1 positive), whereas, 5 of 14 nonresponders had nm23-H1 negative. This result suggest that nm23-H1 expression may be a useful marker for the effect of CDDP/5FU chemotherapy.
(2) We investigated messenger RNA expression profiles in tissue specimens from a training set comprising 33 HCC patients with high-density oligonucleotide microarrays representing approximately 6000 genes. We used this training set in a supervised learning manner to construct a predictive system consisting of 12 genes with the Fisher linear classifier. We then compared the predictive performance of our system with that of a predictive system with a support vector machine (SVM-based system) on a blinded set from 27 newly enrolled HCC patients. Early intrahepatic recurrence within 1 year after curative surgery occurred in 12 (36%) and eight (30%) patients in the training and blinded sets, respectively. Our system correctly predicted early intrahepatic recurrence or nonrecurrence in 25 (93%) of 27 samples in the blinded set and had a positive predictive value (PPV) of 88% and a negative predictive value (NPV) of 95%. In contrast, the SVM-based system predicted early intrahepatic recurrence or nonrecurrence correctly in only 16 (60%) in the blinded set, and the result yielded a PPV of only 38% and a NPV of 79%. Our system could predict early intrahepatic recurrence or nonrecurrence for individual HCC patients much more accurately than the SVM-based system, suggesting that our system may serve as a new tool for characterizing the metastatic potential of HCC.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (39 results)

All Other

All Publications (39 results)

  • [Publications] Iizuka N, Oka M, et al.: "Use of oligonucleotide microarray as a novel approach for prediction of early intrahepatic recurrence in hepatocellular carcinoma after curative resection"Lancet. 361. 923-929 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iizuka N, Mori H, Tamesa T, Tangoku A, Oka M: "Nm23-H2 protein expression and telomerase activity in hepatocellular carcinoma"Anticancer Research. 23. 43-47 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maeda Y, Nishida M, Takao T, Mori T, Tamesa, T, Oka M: "Risk Factors for Postoperative Liver Failure after Hepatectomy for Hepatocellular Carcinoma"Hepato-Gastroenterology. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iizuka N, Oka M, et al.: "Differential Gene Expression in Distinct Virologic Types of Hepatocellular Carcinoma : Association with Liver Cirrhosis"Oncogene. 22. 3007-3014 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamesa T, Iizuka N, Mori N, Okada T, Takemoto N, Oka M: "High Serum Levels of Vascular Endothelial Growth Factor after Hepatectomy are Associated with Poor Prognosis in Hepatocellular Carcinoma"Hepato-Gastroenterology. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iizuka N, Oka M, et al.: "Comparison of Gene Expression Profiles between Hepatitis B Virus-and Hepatitis C Virus-infected Hepatocellular Carcinoma by Oligonucleotide Microarray Data on the Basis of a Supervised Learning Method"Cancer Research. 62. 3939-3944 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iizuka N, Tangoku A, Hazama S, Yoshino S, Mori N, Oka M: "Nm23-H1 gene as a molecular switch between the free-floating and adherent states of gastric cancer cells"Cancer Lett. 174. 65-71 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshino S, Tabata T, Hazama S, Iizuka N, Yamamoto K, Tangoku A, Oka M: "Immunoregulatory effects of the antitumor polysaccharide lentinan on Th1/Th2 balance in patients with digestive cancers"Anticancer Research. 20. 4707-4711 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iizuka N, Oka M, et al.: "Downregulation of intracellular nm23-H1 prevents cisplatin-induced DNA damage in oesophageal cancer cells : possible association with Na(+), K(+)-ATPase"British J Cancer. 83. 1209-1215 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ueda T, Sakabe T, Oka M, Maeda Y, Nishida M, Murakami F, Maekawa T: "Levels of interleukin (IL)-6, IL-8, and IL-1 receptor antagonist in the hepatic vein following liver surgery"Hepato-Gastroenterology. 47. 1048-1051 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohno R, Oka M, et al.: "A dose-escalation and pharmacokinetic study of subcutaneously administered recombinant human interleukin 12 and its biological effects in Japanese patients with advanced malignancies"Clinical Cancer Research. 6. 2661-2669 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oka M, Nishida M, Maeda Y: "Progression in Hepatocellular Carcinoma Treatment Surgical Treatment of Hepatocellular Carcinoma"Okita K, Springer-Verlag Tokyo. 165(56-63) (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iizuka N, Oka M, et al: "Use of oligonucleotide microarray as a novel approach for prediction of early intrahepatic recurrence in hepatocellular carcinoma after curative resection."Lancet. Mar 15;361(9361). 923-929 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iizuka N, Mori H, Tamesa T, Tangoku A, Oka M.: "Nm23-H2 protein expression and telomerase activity in hepatocellular carcinoma"Anticancer Research. Jan-Feb;23(1A). 43-47 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maeda Y, Nishida M, Takao T, Mori T, Tamesa, T, Tangoku A, Oka M.: "Risk Factors for Postoperative Liver Failure after Hepatectomy for Hepatocellular Carcinoma"Hepato-Gastroenterology. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iizuka N, Oka M, et al.: "Differential Gene Expression in Distint Virologic Types of Hepatocellular Carcinoma: Association with Liver Cirrhosis"Oncogene. 22(May). 3007-3014 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamesa T, Iizuka N, Mori N, Okada T, Takemoto N, Tangoku A, Oka M.: "High Serum Levels of Vascular Endothelial Growth Factor after Hepatectomy are Associated with Poor Prognosis in Hepatocellular Carcinoma."Hepato-Gastroenterology. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iizuka N, Oka M, et al.: "Comparison of Gene Expression Profiles between Hepatitis B Virus- and Hepatitis C Virus-infected Hepatocellular Carcinoma by Oligonucleotide Microarray Data on the Basis of a Supervised Learning Method."Cancer Research. 62. 3939-3944 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iizuka N, Tangoku A, Hazama S, Yoshino S, Mori N, Oka M.: "Nm23-H1 gene as a molecular switch between the free-floating and adherent states of gastric cancer cells"Cancer Lett.. 174(1). 65-71 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshino S, Tabata T, Hazama S, Iizuka N, Yamamoto K, Hirayama M, Tangoku A, Oka M.: "Immunoregulatory effects of the antitumor polysaccharide lentinan on Th1/Th2 balance in patients with digestive cancers"Anticancer Research. 20(6C). 4707-4711 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iizuka N, Miyamoto K, Tangoku A, Hayashi H, Hazama S, Yoshino S, Yoshimura K, Hirose K, Yoshida H, Oka M.: "Downregulation of intracellular nm23-H1 prevents cisplatin-induced DNA damage in oesophageal cancer cells: possible association with Na(+), K(+) ATPase."British J Cancer.. 83(9). 1209-1215 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ueda T, SakabeT, Oka M, Maeda Y, Nishida M, Murakami F, Maekawa T.: "Levels of interleukin (IL)-6, IL-8, and IL-1 receptor antagonist in the hepatic vein following liver surgery"Hepato-Gastroenterology. 47(34). 1048-1051 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohno R, Yamaguchi Y, Toge T, Knouchi T, Kotake T, Shibata M, Kiyohara Y, Ikeda S, Fukui I, Gohchi A, Sugiyama Y, Saji S, Hazama S, Oka M, Ohnishi K, Ohhashi Y, Tsukagoshi S, Taguchi T.: "A dose-escalationand pharmacokinetic study of subcutaneously administerd recombinant human interleukin 12 and its biological effects in Japanese patients with advanced malignancies."Clinical Cancer Research. 6(7). 2661-2669 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oka M, Nishida M, Maeda Y: "Surgical Treatment of Hepatocellular Carcinoma, Progression in Hepatocellular Carcinoma Treatment"Springer-Verlag. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iizuka N, Oka M, et al.: "Use of oligonucleotide microarray as a novel approach for prediction of early intrahepatic recurrence in hepatocellular carcinoma after curative resection"Lancet. 361. 923-929 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iizuka N, Mori H, Tamesa T, Tangoku A, Oka M.: "Nm23-H2 protein expression and telomerase activity in hepatocellular carcinoma"Anticancer Research. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Maeda Y, Nishida M, Takao T, Mori T, Tamesa, T, Oka M.: "Risk Factors for Postoperative Liver Failure after Hepatectomy for Hepatocellular Carcinoma"Hepato-Gastroenterology. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Iizuka N, Oka M, et al.: "Differential Gene Expression in Distinct Virologic Types of Hepatocellular Carcinoma : Association with Liver Cirrhosis"Oncogene. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Tamesa T, Iizuka N, Mori N, Okada T, Takemoto N, Oka M.: "High Serum Levels of Vascular Endothelial Growth Factor after Hepatectomy are Associated with Poor Prognosis in Hepatocellular Carcinoma"Hepato-Gastroenterology. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Iizuka N, Oka M, et al.: "Comparison of Gene Expression Profiles between Hepatitis B Virus-and Hepatitis C Virus-infected Hepatocellular Carcinoma by Oligonucleotide Microarray Data on the Basis of a Supervised Learning Method"Cancer Research. 62. 3939-3944 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iizuka N: "Use of oligonucleotide microarray as a novel approach for prediction of early intrahepatic recurrence in hepatocellular carcinoma after curative resection"Cancer Research. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Iizuka N: "Comparison of Gene Expression Profiles between Hepatitis B Virus and Hepatitis C Virus Infected Hepatocellular Carcinoma by Oligonucleotide Microarray Data Based on a Supervised Learning Method"Cancer Research. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Okada T: "Gene expression profile linked to P53 nuclear accumulation in HCC with hepatitis C virus infection"International Journal of Cancer. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Maeda Y: "Risk Factors for Postoperative Liver Failure after Hepatectomy for Hepatocellular Carcinoma"Hepato-Gastroloenterology. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Iizuka N: "Nm23-H1 genes as a molecular switch between the free-floating and adherent states of gastric cancer."Cancer Letter. 174. 65-71 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mori N: "Significance of telomerase activity in hepatocellular carcinoma."British Journal of Cancer,. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Iizuka N: "Downregulation of intracellular nm23-H1 prevents cisplatin-induced DNA damage in oesophageal cancer cells : possible association with Na+, K+-ATPase"British Journal of Cancer. 83(9). 1209-1215 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Iizuka N: "Anticachectic effects of Coptidis rhizoma ,an anti-inflammatory herb, on esophageal cancer cells that produce interleukin 6."Cancer Lettter. 158. 35-41 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Iizuka N: "Inhibitory effect of Coptidis and berberine on the proliferation of human esophageal cancer cell lines."Cancer Lettter. 148. 19-25 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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