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Development and clinical application of high-sensitive focused DNA array

Research Project

Project/Area Number 15591437
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionSaitama Medical School

Principal Investigator

ICHIKAWA Wataru  Saitama Medical School, Medicine, Associate professor, 医学部, 助教授 (70282738)

Co-Investigator(Kenkyū-buntansha) 北郷 邦昭  埼玉医科大学, 医学部, 講師 (00161472)
平山 廉三  埼玉医科大学, 医学部, 教授 (10014317)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥2,600,000 (Direct Cost: ¥2,600,000)
KeywordsDNA array / 5-FU / prediction / northern hybridization
Research Abstract

In this study, we successfully developed high-sensitive focused DNA array (FDA) and applied this FDA to predict the clinical outcome in patients treated with fluoropyrimidine-based chemotherapy.
1)Development of Focused DNA array :
We made the probes for specific targeted DNA to obtain high specificity, and prepared the spotting dose of the targeted DNA for high sensitivity, in 52 genes involving 5-fluorouracil pathway.
2)Validation study
We validated the sensitivity and specificity of this FDA in various cancer cell lines by the comparison with the results of northern hybridization.
We selected 34 5-FU pathway genes from all 52 genes, which correlated with 5-FU sensitivity determined by histo-drug culture assay (HDRA) using clinical samples.
3)Clinical application
We selected 26 genes and 16 genes to predict the clinical outcome in gastric and colorectal cancer patients, respectively, with the accuracy rates of 82% and 100% for survival.
In the validation set including independent cohorts, the accuracy rates of survival were 74% and 94% in gastric and colorectal cancer patients.
In conclusion, our developed FDA with high sensitivity and specificity might be a useful tool to predict the clinical outcome in patients treated with fluoropyrimidine-based chemotherapy.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (17 results)

All 2006 2005 2004 2003 Other

All Journal Article (16 results) Publications (1 results)

  • [Journal Article] Gene expression of ferredoxin reductase predicts outcome in patients with metastatic colorectal cancer treated by 5-fluorouracil plus leucovorin.2006

    • Author(s)
      W.Ichikawa, A.Ooyama, E.Toda, Y.Sugimoto, T.Oka, T.Takahashi, M.Shimizu, Y.Sasaki, R.Hirayama
    • Journal Title

      Cancer Chemother Pharmacol (Epub ahead of print)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 消化器癌の外来化学療法 消化器癌の外来化学療法のための副作用対策2006

    • Author(s)
      市川 度, 仁瓶善郎, 平山廉三
    • Journal Title

      消化器外科 28・11

      Pages: 1691-1699

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] 消化器癌の外来化学療法 消化器癌の外来化学療法で用いられる抗悪性腫瘍薬とその特徴2006

    • Author(s)
      市川 度, 加藤高晴, 平山廉三
    • Journal Title

      消化器外科 28・10

      Pages: 1557-1568

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] 【各種癌における予後因子と治療効果予測因子】 転移性消化器癌における治療効果予測因子2006

    • Author(s)
      市川 度, 高橋威洋, 須藤謙一, 平山廉三
    • Journal Title

      Biotherapy 19・3

      Pages: 248-254

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 抗癌剤感受性予測因子研究の進歩と今後の展開2006

    • Author(s)
      代田喜典, 市川 度
    • Journal Title

      G. I. Research 14・1

      Pages: 20-28

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Gene expression of ferredoxin reductase predicts outcome in patients with metastatic colorectal cancer treated by 5-fluorouracil plus leucovorin.2006

    • Author(s)
      Ichikawa W, Ooyama A, Toda E, Sugimoto Y, Oka T, Takahashi T, Shimizu M, Sasaki Y, Hirayama R.
    • Journal Title

      Cancer Chemother Pharmacol. May (Epub ahead of print)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Phase I/II study of s-1 combined with irinotecan for metastatic advanced gastric cancer.2006

    • Author(s)
      Inokuchi M, Yamashita T, Yamada H, Kojima K, Ichikawa W, Nihei Z, Kawano T, Sugihara K.
    • Journal Title

      Br J Cancer. May(Epub ahead of print)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Gene expression of ferredoxin reductase predicts outcome in patients with metastatic colorectal cancer treated by 5-fluorouracil plus leucovorin.2006

    • Author(s)
      W.Ichikawa, A.Ooyama, E.Toda, Y.Sugimoto, T.Oka, T.Takahashi, M.Shimizu, Y.Sasaki, R.Hirayama
    • Journal Title

      Cancer Chemother Pharmacol Epub ahead of print

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 【各種癌における予後因子と治療効果予測因子】転移性消化器癌における治療効果予測因子2006

    • Author(s)
      市川 度, 高橋威洋, 須藤謙一, 平山廉三
    • Journal Title

      Biotherapy 19・3

      Pages: 248-254

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 抗癌剤感受性予測因子研究の進歩と今後の展開2006

    • Author(s)
      代田喜典, 市川 度
    • Journal Title

      G.I.Research 14・1

      Pages: 20-28

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Predictive profiling of 5-fluorouracil (5-FU) resistance in metastatic colorectal cancer (mCRC)2005

    • Author(s)
      W.Ichikawa, T.Takahashi, K.Suto, Y.Okayama, E.Toda, T.Oka, S.Okayama, R.Hirayama
    • Journal Title

      J Clin Oncol 22・14S

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Thymidylate synthase and dihydropyrimidine dehydrogenase gene expression in relation to differentiation of gastric cancer.2004

    • Author(s)
      Ichikawa W, Takahashi T, Suto K, Nihei Z, Shirota Y, Shimizu M, Sasaki Y, Hirayama R.
    • Journal Title

      Int J Cancer. 20 ; 112(6)

      Pages: 967-973

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Thymidylate synthase predictive power is overcome by irinotecan combination therapy with S-1 for gastric cancer.2004

    • Author(s)
      Ichikawa W, Takahashi T, Suto K, Yamashita T, Nihei Z, Shirota Y, Shimizu M, Sasaki Y, Hirayama R.
    • Journal Title

      Br J Cancer. 4 ; 91(7)

      Pages: 1245-1250

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Thymidylate synthase predictive power is overcome by irinotecan combination therapy with S-1 for gastric cancer2004

    • Author(s)
      Ichikawa W.Takahashi T, Suto K, Yamashita T.Nihei Z, Shirota Y, Shimizu M, Sasaki Y, Hirayama R.
    • Journal Title

      Birtish Journal of Cancer 95

      Pages: 1245-1250

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Thymidylate synthase and dihyropyrimidine dehydrogenase gene expression in relation to differentiation of gastric cancer2004

    • Author(s)
      Ichikawa W, Takahashi T, Suto K, Nihei Z, Shirota Y, Shimizu M, Sasaki Y, Hirayama, R.
    • Journal Title

      International Journal of Cancer 112

      Pages: 967-973

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Both gene expression for orotate phosphoribosyltransferase and its ratio to dihydropyrimidine dehydrogenase influence outcome following fluoropyrimidine-based chemotherapy for metastatic colorectal cancer.2003

    • Author(s)
      Ichikawa W, Uetake H, Shirota Y, Yamada H, Takahashi T, Nihei Z, Sugihara K, Sasaki Y, Hirayama R.
    • Journal Title

      Br J Cancer 20 ; 89(8)

      Pages: 1486-1492

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Publications] W Ichikawa, H Uetake, Y Shirota, H Yamada, T Takahashi, et al.: "Both gene expression for OPRT and its ratio to DPD influence outcome following fluoropyrimidine-based chemotherapy for metastatic colorectal cancer"British Journal of Cancer. 89・8. 1486-1492 (2003)

    • Related Report
      2003 Annual Research Report

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

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