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Phosphatidylinositol 3-kinase and TIMP-3 genes were found to be related to the progression of colon cancer during laparoscopic surgery in a murine model.

Research Project

Project/Area Number 15591411
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

UTSUNOMIYA Tohru (2004)  Kyushu University, Kyushu Univ.Hospital, Assistant Professor, 大学病院, 講師 (30304801)

白石 猛 (2003)  九州大学, 医学部附属病院, 助手 (30315139)

Co-Investigator(Kenkyū-buntansha) TANAKA Fumiaki  Kyushu University, Kyushu Univ.Hospital, Research Associate, 大学病院, 助手 (30332836)
MORI Masaki  Kyushu University, Medical Institute of Bioregulation, Professor, 生体防御医学研究所, 教授 (70190999)
YOSHITAKE Shinichirou  Kyushu University, Kyushu Univ.Hospital, Research Associate, 大学病院, 助手 (80315142)
宇都宮 徹  九州大学, 医学部附属病院, 講師 (30304801)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsLaparoscopic suergery / Colorectal cancer / Cytokines / DNA microarray / Gene expression / Mouse / colon26細胞 / DNAマイクロアレイ法 / Real time PCR / Pik3ca / Pk3r1 / TIMP3
Research Abstract

Objective : The aim of this study was to determine the gene expression patterns of laparoscopic procedures to identify any benefits in comparison with laparotomy procedures.
Summary and background data : Laparosopic surgery has been performed on a wide variety of patients because of the clinical benefits of perioperative recovery, result in a better survival than an open colectomy. However, no basic and molecular-biological examinations have yet to elucidate the mechanisms of such an increased survival.
Methods : To examine the gene expression profiles of mice innoculated with colon cancer cells, the tumors, the livers and the lungs of mice were analyzed using a microarray after either laparoscopic treatment, an open laparotomy or anesthesia alone.
Results : In the laparotomy and control group, we observed a significant enhancement of tumor growth in comparison to the laparoscopic group. When analyzing the genes became more remarkably upregulated or downregulated in the laparoscopic group in comparison to those in the laparotomy or control group, we focused our attention on the TIMP-3 gene and PI3-kinase gene expression. The downregulation of TIMP-3,which played an important role in enhancing invasion the activity of the tumor cells, and the upregulation of PI3-kinase were observed. To confirm the downstream signal of the PI3-kinase gene, we examined the expression of Skp-2 gene and p27 protein, which were key molecules for regulating the cell cycle. We observed that the expression level of the Skp-2 to be upregulated, while the expression level of p27 protein decreased.
Conclusion : These results suggest that the surgical procedures of a laparotomy induced a dwonregulation of TIMP-3 and an upregulation of PI3-kinase, which together resulted in an enhancement of cancer cell growth leading to an increased invasion activity and cell cycle in comparison to treatment using a laparoscopic approach.

Report

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

    (22 results)

All 2005 2004 2003 Other

All Journal Article (16 results) Publications (6 results)

  • [Journal Article] Global analysis of altered gene-expressions during the process of esophageal squamous cell carcinogenesis in the rat.2005

    • Author(s)
      Nishida K, Utsunomiya T, et al.
    • Journal Title

      Cancer Res 65

      Pages: 401-409

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Global analysis of altered gene-expressions during the process of esophageal squamous cell carcinogenesis in the rat : a study combined with a laser microdissection and a cDNA microarray.2005

    • Author(s)
      Nishida K, Utsunomiya T, et al.
    • Journal Title

      Cancer Res 65

      Pages: 401-409

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Global analysis of altered gene-expressions during the process of esophageal squamous cell carcinogenesis in the rat2005

    • Author(s)
      Nishida K, Utsunomiya T, et al.
    • Journal Title

      Cancer Res 65

      Pages: 401-409

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A gene-expression signature can quantify the degree of rat hepatic fibrosis.2004

    • Author(s)
      Utsunomiya T, et al.
    • Journal Title

      J Hepatol 41

      Pages: 399-406

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of cancer testis antigen (CTA) genes in intrahepatic cholangiocarcinoma.2004

    • Author(s)
      Utsunomiya T, et al.
    • Journal Title

      Ann Surg Oncol 11

      Pages: 934-940

    • 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 elongation factor-1 delta mRNA expression in esophageal cancer.2004

    • Author(s)
      Utsunomiya T, et al.
    • Journal Title

      Br J Cancer 91

      Pages: 282-286

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] N-cadherin is regulated by activin A and is associated with tumor aggressiveness in esophageal carcinoma.2004

    • Author(s)
      Yoshinaga K, Utsunomiya T, et al.
    • Journal Title

      Clin Cancer Res 10

      Pages: 5702-5707

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of cancer testis antigen (CTA) genes n intrahepatic cholangiocarcinoma.2004

    • Author(s)
      Utsunomiya T, et al.
    • Journal Title

      Ann Surg Oncol 11

      Pages: 934-940

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] N-cadherin is regulated by activin-A and is associated with tumor aggressiveness in esophageal carcinoma2004

    • Author(s)
      Yoshinaga K, Utsunomiya T, et al.
    • Journal Title

      Clin Cancer Res 10

      Pages: 5702-5707

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A gene-expression signathure can quantify the degree of rat hepatic fibrosis2004

    • Author(s)
      Utsunomiya T, et al.
    • Journal Title

      J Hepatol 41

      Pages: 399-406

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression of cancer testis antigen(CTA) genes in intrahepatic cholangiocarcinoma2004

    • Author(s)
      Utsunomiya T, et al.
    • Journal Title

      Ann Surg Oncol 11

      Pages: 934-940

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Clinical significance of elongation factor-1 delta mRNA expression in esophageal cancer2004

    • Author(s)
      Utsunomiya T, et al.
    • Journal Title

      Br J Cancer 91

      Pages: 282-286

    • Related Report
      2004 Annual Research Report
  • [Journal Article] N-cadherin is regulated by activin A and is associated with tumor aggressiveness in esophageal carcinoma2004

    • Author(s)
      Yoshinaga K, Utsunomiya T, et al.
    • Journal Title

      Clin Cancer Res 10

      Pages: 5702-5707

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cks1 gene expression is associated with poor prognosis in gastric carcinoma : possible involvement of Cks1 and Skp2 in regulation of p27 via ubiquitin-mediated proteolysis.2003

    • Author(s)
      Masuda T, Utsunomiya T, et al.
    • Journal Title

      Clin Cancer Res 9

      Pages: 5693-5698

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cks1 gene expression is associated with poor prognosis in gastric carcinoma : Possible involvement of Cks1 and Skp2 in regulation of p27 via ubiquitin-mediated proteolysis.2003

    • Author(s)
      Masuda T, Utsunomiya T, et al.
    • Journal Title

      Clin Cancer Res 9

      Pages: 5693-5698

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cks1 gene expression is associated with poor prognosis in gastric carcinoma : possible involvement of Cks1 and Skp2 in regulation of p27 via ubiquitin-mediated proteolysis2003

    • Author(s)
      Masuda T, Utsunomiya T, et al.
    • Journal Title

      Clin Cancer Res 9

      Pages: 5693-5698

    • Related Report
      2004 Annual Research Report
  • [Publications] Masuda TA, Inoue H, et al.: "Cyclin-dependent kinase 1 gene expression is associated with poor prognosis in gastric carcinoma."Clin Cancer Res. 15. 5693-5698 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsuyama A, Shiraishi T, et al.: "Fragile site orthologs FHIT/FRA3B and Fhit/Fra14A2:Evolutionarily conserved but highly recombinogenic"Proc Natl Acad Sci USA. 100. 14988-14993 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamashita K, Mimori K, et al.: "A tumor-suppressive role for trypsin in human cancer progression."Cancer Res. 63. 6575-6578 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamashita K, Sunil, et al.: "MAL gene expression in esophageal cancer suppresses motility, invasion and tumorigenicity and enhances apoptosis through the Fas pathway"Oncogene. 22. 3463-3471 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mimori K, Inoue H, et al.: "INI-1, a partner gene of ALL-1, is highly conserved in human acute leukemia"Oncology Rep. 10. 551-553 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 黒木 保, 井上 裕, 森 正樹: "消化器外科 レビュー:発癌機構(分担執筆)"総合医学社. 268 (2003)

    • Related Report
      2003 Annual Research Report

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

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