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Analysis of micrometastasis formation using marker geno-tagged tumor cells and its clinical application

Research Project

Project/Area Number 11670236
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionAichi Cancer Center Research Institute

Principal Investigator

NAKANISHI Hayao  Aichi Cancer Center Research Institute, Division of Oncological Pathology, Section head, 腫瘍病理学部, 室長 (20207830)

Co-Investigator(Kenkyū-buntansha) IKEHARA Yuzuru  Aichi Cancer Center Research Institute, Division of Oncological Pathology, Researcher, 腫瘍病理学部, 研究員 (10311440)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsGFP gene / real-time analysis / Stomach Cancer / hematogenous metastasis / peritoneal metastasis / micro metastasis / integrin / マーカー遺伝子 / GFP / リアルタイムPCR / 腹腔洗浄細胞診 / 転移モデル / ルアルタイムPCR
Research Abstract

1. We established GFP-expressing metastatic and non-metastatic rat tongue carcinoma cell lines that permits the real-time analysis of micrometastasis formation in combination with intravital video microscopy (IVVM) and demonstrated that micrometastasis formation in the liver consists of size-constraint initial tumor cell arrest, stable attachment to subsinusoidal BM and subsequent intravascular growth before extravasation.
2. We established 3 peritoneal micrometastasis models including human gastric and colon cancercell lines tagged with GFP and found thatthere are two types ofperitoneal metastases. One is a omental metastasis type, in which tumorcells initially arrestonly in theomentumandtheotheris a peritoneal type, which form micrometastasis both in the ornentum and abdominal wall peritoneum at initial stage. In vitro analysis indicates that cytokines such as IL-1 beta, TNF-alpha may be responsible for peritoneal type metastasis via retraction of mesothelial lining.
3. We established a real-time RT-PCR method forquantification of CEA mRNA in the peritoneal washes of gastric cancer patients and demonstrated that this method is a sensitive, quantitative, specific and rapid method to detect free cancer cells in peritoneal washes. We revealed apositive correlation between CEA mRNA levels in peritoneal washes and patient prognosis, indicating its usefulness to evaluate the risk ofperitoneal recurrence in patients with gastric cancer.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Kodera, Y., Nakanishi, H., et al.: "Quantitative detection of disseminated free cancer cells in peritoneal washes with real-time RT-PCR : A sensitive predictor of outcome for gastric carcinoma patients"Ann.Surg.. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Munesue, S., Nakanishi, H., et al.: "The role of Syndecan 2 in regulation of actin-cytoskeletal organization of Lewis lung carcinoma-derived metastatic clones"Biochem.J.. 362(in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Inoue, T., Nakanishi, H., et al.: "Real-time reverse transcriptase polymerase chain reaction of urinary cytokeratin 20 detects transitional cell carcinoma cells"J.Urol.. 166・6. 2134-2141 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ito, S., Nakanishi, H., et al.: "Real-time observation of micrometastasis formation in the living mouse liver using a GFP-tagged rat tongue carcinoma cell line"Int.J.Cancer. 93・2. 212-217 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ogawa, K., Nakanishi, H., et al.: "Establishment of rat hepatocellular carcinoma cell lines with differing metastaticpotential in nude mice"Int.J.Cancer. 91・6. 797-802 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 中西速夫, 伊藤誠二, 立松正衛: "Green fluorescent protein遺伝子導入による転移過程のリアルタイム解析"Surgery Frontier. 8・2. 8-12 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakanishi, H., Kodera, Y., et al.: "Rapid quantitative detection of free cancer cells in the parkoneal cavity of gastric cancer patients with real-time CEA RT-PCR using hybridization probes.In "Rapid cycle real-times PCR : Methods and applications.Genetics and Oncology.ads Dermaler/Wittwer/Slva subramanian"Springer-Verlag.Heidelberg (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakanishi, H., Abe, A., Inada, K., et al: "Induction of apoptosis in cancer xenografts in nude mice and reduction of circulating tumor cells in blood by 5-FU and 1-hexylcarbamoyl-5-fluorouracil (HCFU)"Cancer Res. Clin. Oncol.. 125. 660-668 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakanishi, H., Kobayashi, K., Nishimura, T., et al: "Chemosensitivity of micrometastases and circulating tumor cells to uracil and tegafur as evaluated using LacZ gene-tagged Lewis lung carcinoma cell"Cancer Lett.. 142. 31-41 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakanishi, H., Kodera, Y., Yamamujra, Y., et al: "Molecular diagnostic detection of free cancer cells in the peritoneal cavity of patients with gastrointestinal and gynecologic malignancies"Cancer Chemother Pharmacol. 43. S32-S36 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ikehara, Y., Shimizu, N., Nakanishi, H., et al: "A novel glycosyltransterase with a polyglutamine repeat ; a new candidate for Gdl α synthase (ST6GalNAc V)"FEBS Lett.. 463. 92-96 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakanishi, H., Kodera, Y., Yamamura, Y., et al: "Rapid quantitative detection of carcinoembryonic antigen-expressing free tumor cells in the peritoneal cavity of gastric cancer patients with real-time RT-PCR on the LightCycler"Int. J. Cancer. 89. 411-417 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeuchi, S., Nakanishi, H., Yoshida, K., et al: "Isolation of differentiated squamous and undifferentiated spindle carcinoma cell lines with differing metastatic potential from a 4-nitroquinoline N-oxide-induced tongue carcinoma in a F344 rat"Jpn. J. Cancer Res.. 91. 1211-1221 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ito, S., Nakanishi, H., Tatematsu, M., et al: "Real-time observation of micrometastatis formation in the living mouse liver using a GFP-tagged rat tongue carcinoma cell line"Int. J. Cancedr. 93. 212-217 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Raimundas, L., Nakanishi, H., Ito, S., et al: "Clinicopathological significance of fibrotic capsule formation around liver metastasis from colorectal cancer"J. Cancer Res. Clin. Oncol.. 127. 193-199 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Inoue, T., Nakanishi, H., Inada, K., et al: "Real-time reveerse transcriptase polymerase chain reaction of urinary cytokeratin 20 detects transitional cellcarcinoma cells"J. Urol.. 166(&). 2134-41 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ogawa, K., Nakanishi, H., Takeshita, F., et al: "Establishment of rat hepatocellular carcinoma cell lines with differing metastaticpotential in nude mice"Int. J. Cancer. 91(6). 797-802 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsukamoto, T., Fukami, H., Nakanishi, H., et al: "Hexosaminidase-altered aberrant crypts, carrying decreased hexosaminidase α and β subunit mRNA, in colon of 1,2-dimethylhydrazine-treated rats"Jpn. J. Cancer Res.. 92. 109-118 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ando, S., Gohara, R., Nakanishi, H., et al: "Measurement of protein tyrosine phosphatase activity using as substrates synthetic phosphotyrosine-containing peptides"Res. Communi. Biochem. Cell. Mol. Biol.. 5(1&2). 75-84 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kodera, Y., Nakanishi, H., et al.: "Quantitative detection of disseminated free cancer cells in peritoneal washes with real-time RT-PCR : A sensitive predictor of outcome for gastric carcinoma patients"Ann.Surg.. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Munesue, S., Nakanishi, H., et al.: "The role of syndecan 2 in regulation of actin-cytoskeletal organization of Lewis lung carcinoma-derived metastatic clones"Biochem.J.. 362(in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Inoue, T., Nakanishi, H., et al.: "Real-time reverse transcriptase polymerase chain reaction of urinary cytokeratin 20 detects transitional cell carcinoma cells"J.Urol.. 166・6. 2134-2141 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ito, S., Nakanishi, H., et al.: "Real-time observation of micrometastasis formation in the living mouse liver using a GFP-tagged rat tongue carcinoma cell line"Int.J.Cancer. 93・2. 212-217 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ogawa, K., Nakanishi, H., et al.: "Establishment of rat hepatocellular carcinoma cell lines with differing metastaticpotential in nude mice"Int.J.Cancer. 91・6. 797-802 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 中西速夫, 伊藤誠二, 立松正衞: "Green fluorescent protein遺伝子導入による転移過程のリアルタイム解析"Surgery Frontier. 8・2. 8-12 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakanishi, H., Kodera, Y., et al.: "Rapid quantitative detection of free cancer cells in the peritoneal cavity of gastric cancer patients with real-time CEA RT-PCR using hybridization probes in Rapid cycle real-time PCR : Method and applications. Genetics and Oncology, eds. Dietmaier /Wittwer /Siva subramanian"Springer-Verlag. Heidelberg (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ito,S.: "Real-time observation of micrometastasis formation in the living mouse liver using a GFP-tagged rat tongue'carcinoma cell line."Int J Cancer. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Raimundas,L.: "Clinicopathological significance of fibrotic capsule formation around liver metastasis from colorectal cancer."J.Cancer Res.Clin.Oncol.. 127. 193-199 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakanishi,H.: "Rapid quantitative detection of carcinoembryonic antigen-expressing free tumor cells in the peritonea cavity of gastric cancer patients with real-time RT-PCR on the LightCycler."Int.J.Cancer. 89. 411-417 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takeuchi,S.: "Isolation of differentiated squamous and undifferentiated spindle carcinoma cell lines with differing metastatic potential from a 4-nitroquinoline N-oxide-induced tongue carcinoma in a F344 rat."Jpn.J.Cancer Res.. 91. 1211-1221 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shimizu,N.: "Eradication diminishes enhancing effects of Helicobocter pylori infection on glandular stomach carcinogenesis in Mongolian gerbils."Cancer Res.. 60. 1512-1514 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakanishi, H., Kodera, Y. et al.: "Molecular diagnostic detection of free cancer cells in the peritoneal cavity of patients with gastrointestinal and gynecologic malignancies"Cancer Chemother Pharmacol. 43. S32-S36 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakanishi, H., Kobayashi, K. et al.: "Chemosensitivity of micrometastases and circulating tumor cells to uracil and tegatur as evaluated using LacZ gene-tagged Lewis lung carcinama cell"Cancer Letters. 142. 31-41 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakanishi, H., Abe A. et al.: "Induction of apoptosis in metastatic foci from human gastric cancer xenografts in nademice and reduction of circulating tumor cells in blood by 5-FU and 1-hexylcarbamoly-5-thorauracil (HCFU)"J. Cancer Res. Clin. Oncol.. 125. 660-668 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 中西速夫、立松正衛: "RT-PCR法による腹腔内遊離癌細胞の検出"医学のあゆみ. 192(4). 273-276 (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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