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Detection and clinical application of circulating cancer cells, using highy pricise cancer cell determination system

Research Project

Project/Area Number 13470241
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

MAEHARA Yoshihiko  Kyushu University, Graduate School of Medical Science, professor, 大学院・医学研究院, 教授 (80165662)

Co-Investigator(Kenkyū-buntansha) KAKEJI Yoshihiro  Kyushu University, Graduate School of Medical Science, Assistant professor, 病院・助教授 (80284488)
OKI Eiji  Kyushu University, Hospital, Instructor, 病院・助手 (70380392)
馬場 秀夫  九州大学, 大学院・医学研究院, 助教授 (20240905)
佐伯 浩司  九州大学, 大学院・医学研究院, 助手 (80325448)
北村 薫  九州大学, 医学部・附属病院, 講師 (70234276)
Project Period (FY) 2001 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2002: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2001: ¥9,000,000 (Direct Cost: ¥9,000,000)
KeywordsReal-time PCR / CEA / CK18 / CK19 / CK20 / Bone marrow / Peripheral blood / 標的遺伝子 / サイトケラチン18 / 定量的RT-PCR / 臨床病理学的解析 / リアルタイムPT-RCT / 微小転移
Research Abstract

Real time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect disseminated cancer cells in bone marrow and peripheral blood. First of all, we compared CEA, CK18 and CK20 expression using 4 gastric cancer cell lines and 3 normal tissue cell lines in order to select the most appropriate marker for detection of disseminated gastric cancer cell in bone marrow. CK20 proved to be the most promising marker since the expression level of normal cell lines was extremely low and about 50- to 100-fold differences were found between gastric carcinoma cell lines and normal tissue cell lines. We also screened bone-marrow RNA of 47 patients with gastric cancers, using this system. Among the three markers we tested, with only about CK20 could we find that 27 of 47 patients were positive.
Next, we studied the detection of circulating tumor cells in peripheral blood in patients with gastric cancer using Quantitative RT-PCR. Common mRNA targets for RT-PCR for detection of small numbers of cancer cells in gastric cancer are CK18,CK19,CK20, and CEA. The number of CK19 and CK20 mRNA copies was significantly increased in patients with a non-curative operation or recurrence of gastric cancer (CK19;p=0.0087, CK20;p=0.0022) compared with healthy volunteers. There was a significant difference in tumor stages between CK19 positive and negative patients with curative disease on preoperative diagnosis. Five-year survival rates of patients with CK19 positive or negative cases were 50.0% or 79.0%, respectively (p=0.0347). In conclusion, micrometastases of gastric cancer can be detected in circulating peripheral blood using quantitative real-time RT-PCR. CK19 is a better marker than CK18,CK20 and CEA for peripheral blood, and could be clinically useful to estimate prognosis or to make a postoperative strategy of adjuvant treatment.

Report

(5 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (49 results)

All 2005 2004 2003 2002 2001 Other

All Journal Article (32 results) Book (5 results) Publications (12 results)

  • [Journal Article] p53 mutation profiling of multiple esophageal carcinoma using laser capture microdissection to demonstrate field carcinogenesis.2005

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

      Int J Cancer. 113

      Pages: 22-28

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Two modes of microsatellite instability in human cancer : differential connection of defective DNA mismatch repair to dinucleotide repeat instability.2005

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

      Nucleic Acids Res. 33

      Pages: 1628-1636

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] p53 mutation profiling of multiple esophageal carcinoma using laser capture microdissection to demonstrate field carcinogenesis.2005

    • Author(s)
      Ito S, Ohga T, Saeki H, Nakamura T, Watanabe M, Tanaka S, Kakeji Y, Maehara Y
    • Journal Title

      Int J Cancer 113

      Pages: 22-28

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Two modes of microsatellite instability in human cancer : differential connection of defective DNA mismatch repair to dinucleotide repeat instability.2005

    • Author(s)
      Oda S, Maehara Y, Ikeda.Y, Oki E, Egashira A, Okamura Y, Takahashi I, Kakeji Y, Sumiyoshi Y, Miyashita K, Yamada Y, Zhao Y, Hattori H, Taguchi K, Ikeuchi T, Tsuzuki T, Sekiguchi M, Karran P, Yoshida MA
    • Journal Title

      Nucleic Acids Res. 33

      Pages: 1628-1636

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Frequent loss of heterozygosity but rare microsatellite instability in oesophageal cancer in Japanese and Chinese patients.2004

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

      Oncology. 67

      Pages: 151-158

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Frequent loss of heterozygosity but rare microsatellite instability in oesophageal cancer in Japanese and Chinese patients.2004

    • Author(s)
      Araki K, Wang B, Miyashita K, Cui Q, Ohno S, Baba H, Zhang RG, Sugimachi K, Maehara Y, Oda S
    • Journal Title

      Oncology 67

      Pages: 151-158

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Prognostic significance of tumor markers in peritoneal lavage in advanced gastric cancer2004

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

      Oncology 67(1)

      Pages: 19-26

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Correlation with bone metastasis and high expression of CK 19 mRNA measured by quantitative RT-PCR in the bone marrow of breast cancer patients.2003

    • Author(s)
      Tokunaga E et al.
    • Journal Title

      Breast J. 9

      Pages: 440-442

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Human WISP1v, a member of the CCN family, is associated with invasive cholangiocarcinoma.2003

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

      Hepatology. 37

      Pages: 1122-1129

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A loss of function mutation in WISP3 derived from microsatellite unstable gastric carcinoma.2003

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

      Gastroenterology. 125

      Pages: 1563-1564

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Correlation with bone metastasis and high expression of CK 19 mRNA measured by quantitative RT-PCR in the bone marrow of breast cancer patients.2003

    • Author(s)
      Tokunaga E, Ishida M, Kimura Y, Maehara Y
    • Journal Title

      Breast J. 9

      Pages: 440-442

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Human WISP1v, a member of the CCN family, is associated with invasive cholangiocarcinoma.2003

    • Author(s)
      Tanaka S, Sugimachi K, Kameyama T, Maehara S, Shirabe K, Shimada M, Wands JR, Maehara Y
    • Journal Title

      Hepatology 37

      Pages: 1122-1129

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A loss of function mutation in WISP3 derived from microsatellite unstable gastric carcinoma.2003

    • Author(s)
      Tanaka S, Sugimachi K, Maehara S, Shimada M, Maehara Y
    • Journal Title

      Gastroenterology 125

      Pages: 1563-1564

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Correlation with bone metastasis and high expression of CK 19 mRNA measured by quantitative RT-PCR in the bone marrow of breast cancer patients.2003

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

      Breast Journal 9(5)

      Pages: 440-442

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Detection of disseminated cancer cells in bone marrow of gastric cancer using real time quantitative reverse transcriptase polymerase chain reaction.2002

    • Author(s)
      Oki E et al.
    • Journal Title

      Cancer Lett. 188

      Pages: 191-198

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Variant WISPs as targets for gastrointestinal carcinomas.2002

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

      Gastroenterology. 123

      Pages: 392-393

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Clinical significance of vascular endothelial growth factor expression in gastric cancer.2002

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

      J Exp Clin Cancer Res. 21

      Pages: 125-129

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] DNA ploidy and its clinical implications in gastric cancer.2002

    • Author(s)
      Baba H et al.
    • Journal Title

      Surgery. 131

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Detection of disseminated cancer cells in bone marrow of gastric cancer using real time quantitative reverse transcriptase polymerase chain reaction.2002

    • Author(s)
      Oki E, Maehara Y, Tokunaga E, Shibahara K, Hasuda S, Kakeji Y, Sugimachi K
    • Journal Title

      Cancer Lett. 188

      Pages: 191-198

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Variant WISPs as targets for gastrointestinal carcinomas.2002

    • Author(s)
      Tanaka S, Sugimachi K, Shimada M, Maehara Y, Sugimachi K
    • Journal Title

      Gastroenterology 123

      Pages: 392-393

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Clinical significance of vascular endothelial growth factor expression in gastric cancer.2002

    • Author(s)
      Kakeji Y, Koga T, Sumiyoshi Y, Shibahara K, Oda S, Maehara Y, Sugimachi K
    • Journal Title

      J Exp Clin Cancer Res. 21

      Pages: 125-129

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] DNA ploidy and its clinical implications in gastric cancer.2002

    • Author(s)
      Baba H, Korenaga D, Kakeji Y, Haraguchi M, Okamura T, Maehara Y
    • Journal Title

      Surgery 131(1 Suppl) (Review)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Detection of disseminated cancer cells in bone marrow of gastric cancer using real time quantitative reverse transcriptase polymerase chain reaction.2002

    • Author(s)
      Oki E et al.
    • Journal Title

      Cancer letter 188(1)

      Pages: 191-198

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Angiogenesis as a target for gastric cancer.2002

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

      Surgery 131(1suppl)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Tumor growth patterns and biological characteristics of early gastric carcinoma.2001

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

      Oncology 61(2)

      Pages: 102-112

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Genetic Mutual Relationship between PTEN and p53 in Gastric Cancer.

    • Author(s)
      Oki E et al.
    • Journal Title

      Cancer Lett. in press

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Impact of Loss of Heterozygosity of PTEN on the Prognosis of Gastric Cancer.

    • Author(s)
      Oki E et al.
    • Journal Title

      J of Gastroentel Hepatol. in press

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] AKT Phosphorylation associates with LOH of PTEN and Leads to Chemoresistance for Gastric Cancer.

    • Author(s)
      Oki E et al.
    • Journal Title

      Int J Cancer. in press

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Genetic Mutual Relationship between PTEN and p53 in Gastric Cancer.

    • Author(s)
      Oki E, Tokunaga E, Nakamura T, Ueda N, Futatsugi M, Mashino K, Yamamoto M, Ikebe M, Kakeji Y, Baba H, Maehara Y
    • Journal Title

      Cancer Lett. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Impact of Loss of Heterozygosity of PTEN on the Prognosis of Gastric Cancer.

    • Author(s)
      Oki E, Tokunaga E, Nakamura T, Ueda N, Futatsugi M, Mashino K, Yamamoto M, Ikebe M, Kakeji Y, Baba H, Maehara Y
    • Journal Title

      J of Gastroentel Hepatol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] AKT Phosphorylation associates with LOH of PTEN and Leads to Chemoresistance for Gastric Cancer.

    • Author(s)
      Oki E, Baba H, Tokunaga E, Nakamura T, Ueda N, Futatsugi M, Mashino K, Yamamoto M, Ikebe M, Kakeji Y, Maehara Y
    • Journal Title

      Int J Cancer (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] AKT Phosphorylation associates with LOH of PTEN and Leads to Chemoresistance for Gastric Cancer

    • Author(s)
      Oki E et al.
    • Journal Title

      International Journal of Cancer (in press)

    • Related Report
      2004 Annual Research Report
  • [Book] Microsatellite Instability in Cancer : Handbook of Immunohistochemistry and in situ hybridization of Human Carcinomas. Vol.22005

    • Author(s)
      Oda S et al.
    • Total Pages
      400
    • Publisher
      Academic Press
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Microsatellite Instability in Cancer : Handbook of Immunohistochemistry and in situ hybridization of Human Carcinomas. Vol.22005

    • Author(s)
      Oda S et al.
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 再発胃癌ガイドブック2004

    • Author(s)
      前原喜彦 他
    • Total Pages
      286
    • Publisher
      南江堂
    • Related Report
      2004 Annual Research Report
  • [Book] Circulating Cancer Cells : Handbook of Immunohistochemistry and in situ hybridization Vol.4

    • Author(s)
      Oki E et al.
    • Publisher
      Academic Press(in press)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Circulating Cancer Cells : Handbook of Immunohistochemistry and in situ hybridization Vol.4

    • Author(s)
      Oki E et al.
    • Publisher
      (in press)
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Maehara Y et al.: "Correlation with bone metastasis and high expression of CK 19 mRNA measured by quantitative RT-PCR in the bone marrow of breast cancer patients."Breast Journal. 9(5). 440-442 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Oki E et al.: "Detection of disseminated cancer cells in bone marrow of gastric cancer using real time quantitative reverse transcriptase polymerase chain reaction."Cancer letter. 188(1). 191-198 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kakeji Y et al.: "Angiogenesis as a target for gastric cancer."Surgery. 131(1 suppl). S48-S54 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Maehara Y et al.: "Tumor growth patterns and biological characteristics of early gastric carcinoma."Oncology. 61(2). 102-112 (2001)

    • Related Report
      2003 Annual Research Report
  • [Publications] Saeki H, Oda S, Kawaguchi H, Ohno S, Kuwano H, Maehara Y, Sugimachi K: "Concurrent overexpression of Ets-1 and c-Met correlates with a phenotype of high cellular motility in human oesophageal cancer"International Journal of Cancer. 98. 8-13 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Saeki H, Oda S, Ohno S, Miyazaki M, Araki K, Egashira A, Kawaguchi H, Watanabe M, Morita M, Sugimachi K: "p53 protein accumulation in multiple oesophageal squamous cell carcinoma : reference to risk factors"Oncology. 62. 175-179 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Maehara Y, Oda S, Sugimachi K: "The instability within : problems in current analysis of microsatellite instability"Mutation Research. 461(4). 249-263 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Noda H, Maehara Y, Irie K, Kakeji Y, Sugimachi K: "Growth pattern and expressions of cell cycle regulator proteins p53 and p21^<WAF1/CIP1> in early gastric carcinoma"Cancer. 92(7). 1828-1835 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ikeda Y, Oda S, Abe T, Ohno S, Maehara Y, Sugimachi K: "Features of microsatellite instability in colorectal cancer : Comparison between colon and rectum"Oncology. 61(2). 168-174 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Saeki H, Tanaka S, Tokunaga E, Kawaguchi H, Ikeda Y, Maehara Y, Sugimachi K: "Genetic alterations in human Tcf-4 gene in sporadic gastrointestinal cancers with microsatellite instability in the Japanese"Oncology. 61(2). 156-161 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tanaka S, Sugimachi K, Saeki H, Kinoshita J, Ohga T, Shimada M, Maehara Y. Sugimachi K: "A novel variant of WISP 1 lacking a von Willebrand type C module overexpressed in scirrhous gastric carcinoma"Oncogene. 20(39). 5525-5532 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shibahara K, Sugio K, Osaki T, Uchiumi T, Maehara Y. Kohno K, Yasumoto K, Sugimachi K, Kuwano M: "Nuclear expression of the Y-box binding protein, YB-1, as a novel marker of disease progression in non-small-cell lung cancer"Clin Cancer Res. 7(10). 3151-3155 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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