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Development of genetic diagnosis system for pancreatic cancer using modified telomeric repeat amplification protocols and electrochemical array chip

Research Project

Project/Area Number 15390399
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

MIZUMOTO Kazuhiro  Kyushu University Hospital, Surgery and Oncology, Assistant Professor, 大学病院, 講師 (90253418)

Co-Investigator(Kenkyū-buntansha) NAGAI Eishi  Kyushu University Hospital, Surgery and Oncology, Research Associate, 大学病院, 助手 (30264021)
TANAKA Masao  Kyushu University, Graduate School of Medical Sciences, Surgery and Oncology, Professor, 大学院・医学研究院, 教授 (30163570)
TAKENAKA Sigeori  Kyushu Institute of Technology, Department of Materials Science, Applied Chemistry Course, Professor, 工学部物質工学科, 教授 (60188208)
IDE Toshinori  Hiroshima University, Department of Cellular & Molecular Biology, Professor, 医歯薬総合研究科, 教授 (60012746)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2005: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2004: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥6,500,000 (Direct Cost: ¥6,500,000)
KeywordsPancreatic cancer / pancreatic juice / TRAP / HPA / hTERT / real time PCR / ECA chip
Research Abstract

To establish highly sensitive assays for the diagnosis of pancreatic cancer, we developed HPA/TRAP assay, real time TRAP assay, methods for quantitative measurements of mRNA in pancreatic juice, and electrochemical analysis of k-ras mutations.
Telomeric repeat amplification protocol combined with hybridization protection assay (HPA/TRAP) was highly sensitive and rapid to detect telomerase activity in pancreatic juice. HPA/TRAP assay was useful to differentiate pancreatic cancer from IPMN or pancreatitis. TRAP with real-time PCR (real time TRAP) was also sensitive and more rapid to detect the telomerase activity. Futhermore, we quantitatively measured mRNA of hTERT, subunits of telomerase, in pancreatic juice. We found significant difference in hTERT expression among pancreatic cancer, IPMN and chronic pancreatitis.
Several mRNAs of pancreatic cancer related genes were also quantitatively measured in pancreatic juice. MUC1 and MUC5AC were highly expressed in pancreatic cancer and quantitative assessment of MUC1 and MUC5AC mRNA in pancreatic juice has high potential for preoperative diagnosis of pancreatic cancer. S100A6,a member of S100 family, was significantly higher in microdissected pancreatic cancer cells. Quantification of S100A6 mRNA in pancreatic juice is also a promising tool for diagnosis of pancreatic cancer.
To investigate the validity of the electrochemical array (ECA) chip, k-ras muations were detected with ECA chip in pancreatic cancer tissues. K-ras mutations were identified in 85% of pancreatic cancer, which was identical to the results obtained by PCR-dependent preferential homoduplex formation assay. We found that ECA chip is a sensitive, rapid, and reliable for screening point mutations in clinical samples.

Report

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

    (16 results)

All 2006 2005 2004

All Journal Article (15 results) Book (1 results)

  • [Journal Article] Quantitative Analysis of Human Telomerase Reverse Transcriptase in Pancreatic Cancer2006

    • Author(s)
      Ohuchida K et al.
    • Journal Title

      Clinical Cancer Research 12・7

      Pages: 2066-2069

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Rapid and sensitive assay of k-ras mutations in pancreatic cancer by electrochemical detection with ferrocenyl-naphtalene-diimide2006

    • Author(s)
      Ishikawa N et al.
    • Journal Title

      Cancer Genomics & Proteomics 3

      Pages: 47-54

    • 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] Quantitative analysis of MUC1 and MUC5AC mRNA in pancreatic juice for preoperative diagnosis of pancreatic cancer2006

    • Author(s)
      Ohuchida K et al.
    • Journal Title

      International Journal of Cancer 118

      Pages: 405-411

    • 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] Quantitative Analysis of Human Telomerase Reverse Transcriptase in Pancreatic Cancer2006

    • Author(s)
      K.Ohuchida, et al.
    • Journal Title

      Clinical Cancer Research 12(7)

      Pages: 2066-2069

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Rapid and sensitive assay of k-ras mutations in pancreatic cancer by electrochemical detection with ferrocenyl-naphtalene-diimide2006

    • Author(s)
      N.Ishikawa, et al.
    • Journal Title

      Cancer Genomics & Proteomics 3

      Pages: 47-54

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Quantitative analysis of MUC1 and MUC5AC mRNA in pancreatic juice for preoperative diagnosis of pancreatic cancer2006

    • Author(s)
      K.Ohuchida, et al.
    • Journal Title

      International Journal of Cancer 118

      Pages: 405-411

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Quantitative Assessment of Telomerase Activity and Human Telomerase Reverse Transcriptase Messenger RNA Levels in Pancreatic Juice Samples for the Diagnosis of Pancreatic Cancer2005

    • Author(s)
      Ohuchida K et al.
    • Journal Title

      Clinical Cancer Research 11

      Pages: 2285-2292

    • 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] The role of S100A6 in pancreatic cancer development and its clinical implication as a diagnostic marker and therapeutic target2005

    • Author(s)
      Ohuchida K et al.
    • Journal Title

      Clinical Cancer Research 11・21

      Pages: 7785-7793

    • 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] Quantitative Assessment of Telomerase Activity and Human Telomerase Reverse Transcriptase Messenger RNA Levels in Pancreatic Juice Samples for the Diagnosis of Pancreatic Cancer2005

    • Author(s)
      K.Ohuchida, et al.
    • Journal Title

      Clinical Cancer Research 11

      Pages: 2285-2292

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The role of S100A6 in pancreatic cancer development and its clinical implication as a diagnostic marker and therapeutic target2005

    • Author(s)
      K.Ohuchida, et al.
    • Journal Title

      Clinical Cancer Research 11・21

      Pages: 7785-7793

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Pancreatic cancer ; Methods and Protocols2005

    • Author(s)
      K.Mizumoto, M.Tanaka, et al.
    • Journal Title

      Human Press

      Pages: 199-205

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Quantitative Assessment of Telomerase activity and hTERT mRNA Levels in Pancreatic Juice Samples for the Diagnosis of Pancreatic Cancer2005

    • Author(s)
      Ohuchida K et al.
    • Journal Title

      Clin Cancer Res. (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A Highly Sensitive and Quantitative Telomerase Activity Assay with Pancreatic Juice Is Useful for Diagnosis of Pancreatic Carcinoma without Problems due to Polymerase Chain Reaction2004

    • Author(s)
      Ohuchida K et al.
    • Journal Title

      Cancer 101/10

      Pages: 2309-2317

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A Highly Sensitive and Quantitative Telomerase Activity Assay with Pancreatic Juice Is Useful for Diagnosis of Pancreatic Carcinoma without Problems due to Polymerase Chain Reaction2004

    • Author(s)
      K.Ohuchida, et al.
    • Journal Title

      Clinical 101(10)

      Pages: 2309-2317

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A Highly Sensitive and Quantitative Telomerase Activity Assay with Pancreatic Juice Is Useful for Diagnosis of Pancreatic Carcinoma without Problems due to Polymerase Chain Reaction2004

    • Author(s)
      Ohuchida K et al.
    • Journal Title

      Cancer 101(10)

      Pages: 2309-2317

    • Related Report
      2004 Annual Research Report
  • [Book] Pancreatic cancer; Methods and Protocols2005

    • Author(s)
      Mizumoto K, Tanaka M
    • Total Pages
      352
    • Publisher
      Human Press
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary

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

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