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Molecular mechanisms by which cystatin-like metastasis-associated protein regulate liver metastasis of human cancer.

Research Project

Project/Area Number 13671311
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  Medical Institute of Bioregulation Kyushu Univ. lecturer, 生体防御医学研究所, 講師 (30304801)

Co-Investigator(Kenkyū-buntansha) YOSHITAKE Shinichirou  Medical Institute of Bioregulation Kyushu Univ. Research Associate, 生体防御医学研究所, 助手 (80315142)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsCystatin / Colorectal cancer / Hepatocellular carcinoma / Liver metastasis / Protease inhibitor / Gene transfection / DNA microarray / 遺伝子導入DNA / マイクロアレイ / 分子標的 / 予後因子
Research Abstract

Backgrounds: We previously reported that an increased expression of cystatin-like metastasis-associated protein (CMAP) mRNA is involved in liver-specific metastasis in a mouse model. We also identified its human homologue. However, there is still no information available on the clinical significance of CMAP expression in human cancer specimens.
Materials and Methods: We studied the CMAP expression levels of resected tumor and nontumor tissue specimens using a real-time quantitative reverse transcription polymerase chain reaction for 79 patients with colorectal cancer (CRC) and 65 patients with hepatocellular carcinoma (HCC). Furthermore, we identified the specific gene-expression profiles of HepG2 cells transfected with CMAP gene by cDNA microarray.
Results: The mean expression level of CMAP in tumor tissue specimens was significantly higher than in the corresponding normal tissue specimens (p<0.05). A higher expression of CMAP was significantly correlated with liver metastasis (p<0.01) of CRC. The prognosis of the patients with a higher expression of CMAP was significantly worse than those with a lower expression (p=0.038). Furthermore, an increased expression of CMAP was significantly associated with intrahepatic metastasis of HCC. A cDNA microarray analysis identified 261 genes that were up-regulated and 430 genes that were down-regulated in HepG2 cells with CMAP overexpression.
Conclusions: These findings imply that the expression level of CMAP in human cancer may be a new biomarker for both liver metastasis and the patient's outcome. A technique of cDNA microarray may elucidate the precise mechanisms by which increased expression of CMAP is associated with liver-specific metastasis.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Utsunomiya T et al.: "CMAP mRNA expression in human colorectal cancer is associated with both liver metastasis and the patient survival"Clin Cancer Res. 8. 2591-2594 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Utsunomiya T et al.: "Clinicopathological significance of G-Protein. γ7 expression in surgically resected intrahepatic cholangiocarcinoma"Arch Surg. 137. 181-185 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Utsunomiya T et al.: "Antioxidant and anti-inflammatory effects of diet supplemented with sesamin on hepatic ischemia-reperfusion injury in rats"Hepato-Gastroenterol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mori M, Utsunomiya T et al.: "Analysis of the gene-expression profile regarding progression of human gastric carcinoma"Surgery. 131. 39-47 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshinaga K, Utsunomiya T et al.: "Clinical significance of the expression of activin A in esopageal carcinoma"Int J Oncol. 22. 75-80 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mimori K, Utsunomiya T et al.: "MAL gene expression in esophageal cancer suppresses motility, invasion and tumorigenicity and enhances apoptosis through the Fas pathway"Oncogene. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Utsunomiya T, Emi Y, Ikejiri K, Suzuki M, Saitsu H, S. Yakabe S, Nonaka M, Saku M, Yoshida K, Sugimachi K.: "Retrrospective study on the effects of lipiodolization before a potentially curative hepatectomy for colorectal liver metastases: long-term results of a pilot study."Hepato-Gastroenterol. 48. 790-793 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Utsunomiya T, Shimada M, Shirabe K, Kajiyama K, Gion T, Takenaka K, Sugimachi K.: "Clinicopathological characteristics of patients with extrahepatic recurrence following a hepatectomy for hepatocellular carcinoma."Hepato-Gastroenterol. 48. 1083-1093 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chavali SR, Utsunomiya T, Forse RA.: "Increased survival after cecal ligation and puncture in mice consuming diets enriched with sesame seed oil."Crit Care Med. 29. 140-143 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hasegawa H, Shimada M, Yonemitsu Y, Utsunomiya T, Gion T, Kaneda Y, Sugimachi K.: "Preclinical and therapeutic utility of HVJ liposomes as a gene transfer vector for hepatocellular carcinoma using herpes simplex virus thymidine kinase."Cancer Gene Ther. 8. 252-258 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Etoh T, Ueo H, Inoue H, Sato K, Utsunomiya T, Barnard GF, Kitano S, Mori M.: "Clinical significance of K-Ras mutations in intraoperative tumor drainage blood from patients with colorectal carcinoma."Ann Surg Oncol. 8. 407-412 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inoue H, Mimori K, Utsunomiya T, Sadanaga N, Barnard GF, Ueo H, Mori M.: "Heparanase expression in clinical digestive malignancies."Oncol Rep. 8. 539-542 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimada M, Hamatsu T, Yamashita Y, Rikimaru T, Taguchi K, Utsunomiya T, Shirabe K, Sugimachi K.: "Characteristics of multicentric hepatocellular carcinomas: comparison with intrahepatic metastasis."World J Surg. 25. 991-995 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Utsunomiya T, Hara Y, Kataoka A, Morita M, Arakawa H, Mori M, Nishimura S.: "Cystatin-like metastasis-associated protein mRNA expression in human colorectal cancer is associated with both liver metastasis and the patient survival."Clin Cancer Res. 8. 2591-2594 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Utsunomiya T, Inoue H, Taguchi K, Shimada M, Sugimachi K, Mori M.: "G-protein γ-7 expression as a new clinicopathological marker in partients with intrahepatic cholangiocarcinoma."Arch Surg. 137. 181-185 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mori M, Mimori K, Yoshikawa Y, Shibuta K, Utsunomiya T, Sadanaga N, Tanaka F, Matsuyama A, Inoue H, Sugimachi K.: "Analysis of the gene-expression profile regarding the progression of human gastric carcinoma."Surgery. 131(PT2). S39-S47 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshinaga K, Mimori K, Yamashita K, Utsunomiya T, Inoue H, Mori M.: "Clinical significance of the expression of activin A in esopageal carcinoma."Int J Oncol. 22. 75-80 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Utsunomiya T, Shimada M, Hasegawa H, Yamashita Y, Sugimachi K.: "Antioxidant and anti-inflammatory effects of diet supplemented with sesamin on hepatic ischemia-reperfusion injury in rats."Hepato-Gastroenterol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mimori K, Shiraishi T, Mashino K, Yoshinaga K, Masuda T, Yamashita K, Utsunomiya T, Barnard GF, Alonso MA, Inoue H, Mori M:: "MAL gene reexpression in esophageal cancer suppresses motility, invasion and tumorigenicity and enhances apoptosis through the Fas pathway."Oncogene. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshinaga K, Inoue H, Tanaka F, Mimori K, Utsunomiaya T, Mori M:: "Platelet derived endothelial cell growth factor (PD-ECGF) mediates Rho associated coiled-coil domain kinase (ROCK1) mRNA expression and promotes cell motility."Ann Surg Oncol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Utsunomiya T et al.: "CMAP rnRNA expression in human colorectal cancer is associated with both liver metastasis and the patient survival"Clin Cancer Res. 8. 2591-2594 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Utsunomiya T et al.: "Clinicopathological significance of G-Protein γ7 expression in surgically resected intrahepatic cholangiocarcinoma"Arch Surg. 137. 181-185 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Utsunomiya T et al.: "Antioxidant and anti-inflammatory effects of diet supplemented with sesamin on hepatic ischemia-reperfusion injury in rats"Hepato-Gastroenterol. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Mori M, Utsunomiya T et al.: "Analysis of the gene-expression profile regarding progression of human gastric carcinoma"Surgery. 131. 39-47 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshinaga K, Utsunomiya T et al.: "Clinical significance of the expression of activin A in esopageal carcinoma"Int J Oncol. 22. 75-80 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mimori K, Utsunomiya T et al.: "MAL gene expression in esophageal cancer suppresses motility, invasion and tumorigenicity and enhances apoptosis through the Fas pathway"Oncogene. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Utsunomiya T, et al.: "Clinicopathological characteristics of patients with extrahepatic recurrence following a hepatectomy for hepatocellular carcinoma"Hepato-Gastroenterol. 48. 1088-1093 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Utsunomiya T, et al.: "Retrospective study on the effects of lipiodolization before a potentially curative hepatectomy for colorectal liver metastases : long-term results"Hepato-Gastroenterol. 48. 790-793 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Utsunomiya T, et al.: "Clinicopathological significance of G-protein gamma 7 expression in surgically resected intrahepatic cholangiocarcinoma"Arch Surg. 137. 181-185 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Utsunomiya T, et al.: "Antioxidant and anti-inflammatory effects of diet supplemented with sesamin on hepatic ischemia-reperfusion injury in rats"Hepato-Gastroenterol. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Etoh T, Utsunomiya T, et al.: "Clinical significance of K-Ras mutations in intraoperative tumor drainage blood from patients with colorectal carcinoma"Ann Surg Oncol. 8. 407-412 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mori M, Utsunomiya T, et al.: "Analysis of the gene-expression profile regarding the progression of human gastric carcinoma"Surgery. 131. 39-47 (2002)

    • Related Report
      2001 Annual Research Report

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

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