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GENE THERAPY TARGETTING FOR GLUCOSE METABLOLISM IN PACREAS CANCER

Research Project

Project/Area Number 13670540
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionYokohama City University Hospital

Principal Investigator

SATOH Shinobu  Yokohama City University Hospital, University Hospital Assistant Professor, 医学部附属病院, 講師 (80244424)

Co-Investigator(Kenkyū-buntansha) SAITOH oshifumi  Yokohama City University Hospital, University Hospital Associate Professor, 医学部附属病院, 助教授 (30254163)
ITO Takaaki  Yokohama City University Hospital, School of Medicine Associate Professor, 医学部, 助教授 (70168392)
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: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsglucose transporter / pancreatic cancer / gene therapy / proliferation / invasion / p21 / MAPkinase / cell cycle / 糖輸送活性 / 細胞増殖
Research Abstract

We attempted to suppress glucose transporter 1 (GLUT1) expression by transfecting various human pancreas cancer cell line (Capan-2, PANC-1, AsPC-1, BxPC3) with cDNA for antisense GLUT1. Glucose transport was significantly decreased in cells with antisense GLUT1 compared with wild-type cells or cells with vector aione. The cell proliferation of the Capan-2 (aGLUT1) which controlled a GLUT1 expression was measured with MTT method. Compared in the wild strain (Wt), it shows about 35% of control. Glucose transport activity showed a decrease up to 24%. MAP Kinase activity with a aGLUT1 cell line revealed remarkably decrease. Suppression of GLUT1 mRNA resulted in a decreased number of cells in the S phase in the analysis of the cell cycle. This was accompanied by overexpression of p21 protein. The effect which even other human pancreas cancer cell lines, PANC-1, AsPC-1, and BxPC-3, were similar results and tend to depend on the amount of GLUT1 expression.
These results suggest that antisense GLUT1 mRNA inhibits tumor growth through a G(1) arrest and the expression of antisense GLUT1 mRNA via gene therapy can be used as a fool in the treatment of pancreas cancer.

Report

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

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Yasushi Kaburagi, Shinobu Satoh, et al.: "Insulin-independent and wortmannin-reisslant targeting of IRS-3 to the plasma membrane via its pleckstrin homology domain mediates a different interaction with the insulin receotor from that of IRS-I"Diabetologia. 44. 992-1004 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Youki Tsuji, et al.: "Subcellular localization of insulin receptor substrate family proteins associated with phosphatidylinositol 3-kinase activity and alterations in lipolysis in primary mouse adipocytes from IRS-1 null mice"Diabetes. 50. 1455-1463 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazutaka Aoki et al.: "mRNA and enzyme activity of hepatic 11b -hydroxysteroid dehydrogenasetype1 are elevated in C57bl/KsJ-db/db/mice"Life Sciences. 69. 2543-2549 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazuhiro Eto et al.: "Phosphatidylinositol 3-kinase Suppresses glucose-stimulated insulin secretion by affecting post-cytosolic [Ca(2+)] elevation signals"Diabetes. 51. 87-97 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Jun Togawa, et al.: "Lacioferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance"Am J Physiol Gastrointest Liver Physiol. 283・1. G187-G195 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yasushi Kaburagi, Shinobu Satoh et al.: "Protection of insulin receptor substrate-3 from staurosporine-induced apoptosis"Biochem Biophys Res Commun. 300・2. 371-377 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Youki Tsuji et al: "Subcellular localization of insulin receptor substrate family proteins associated with phosphatidylinositol 3-kinase activity and alterations in lipolysis in primary mouse adiposities from IRS-1 null mice."Diabetes 50 .6. 1455-1463 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yasushi Kaburagi, Shinobu Satoh, et al.: "Insulin-independent and wortmannin-resistant targeting of IRS-3 to the plasma membrane via its pleckstrin homology domain mediates a different interaction with the insulin receptor form that of IRS-1."Dialectologies 44. 8. 992-1004 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazuhiro Eto et al.: "Phosphatidylinositol 3-kinase suppresses glucose-stimulated insulin secretion by affecting post-cytosolic [Ca(2+)] elevation signals."Am J Physiol Gastrointestinal Liver Physiol 283.1. G187-G195 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yasuhi Kaburagi, Shinobu Satoh et al.: "Protection of insulin receptor substrate-3 from staurosporine-induced apoptosis."Biochem Biophys Res Commun 300. 2. 371-377 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yasushi Kaburagi, Shinobu Satoh et al.: "Protection of insulin receptor substrate-3 from staurosporine-induced apoptosis"Biochem Biophys Res Commun. 300・2. 371-377 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Jun Togawa, et al.: "Lactoferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance"Am J Physiol Gastrointest Liver Physiol. 283・1. G187-G195 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] YasushiKaburagi, Shinobu Satoh, et al.: "Insuliwindependent and wortmannin-reisstant targeting of IRS-3 to the plasma membrane via its pleckstrin homology domain mediates a different interaction with the insulin receptor from that of IRS-1"Diabetologia. 44. 992-1004 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Youki Tsuji, et al.: "Subcellular localization of insulin receptor substrate family proteins associated with phosphatidylinositol 3-kinase activity and alterations in lipolysis in primary mouse adipocytes from IRS-i null mice"Diabetes. 50. 1455-1463 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kazutaka Aoki et al.: "mRNA and enzyme activity of hepatic 11b-hydroxysteroid dehydrogenasetype 1 are elevated in C57b/IKaJ-db/db/mice"Life Sciences. 69. 2543-2549 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kazuhiro Eto et al.: "Phosphatidylinositol 3-kinase suppresses glucose-stimulated insulin secretion by affecting post-cytosolic [Ca(2+)] elevation signals"Diabetes. 51. 87-97 (2002)

    • Related Report
      2001 Annual Research Report

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

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