2004 Fiscal Year Final Research Report Summary
Detection and clinical application of circulating cancer cells, using highy pricise cancer cell determination system
| Project/Area Number |
13470241
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
MAEHARA Yoshihiko Kyushu University, Graduate School of Medical Science, professor, 大学院・医学研究院, 教授 (80165662)
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| 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)
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| Project Period (FY) |
2001 – 2004
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| Keywords | Real-time PCR / CEA / CK18 / CK19 / CK20 / Bone marrow / Peripheral blood / 標的遺伝子 |
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| 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.
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[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
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Journal Title
Nucleic Acids Res. 33
Pages: 1628-1636
Description
「研究成果報告書概要(欧文)」より
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[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
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Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
J of Gastroentel Hepatol. (in press)
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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