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Basic Strategy for the treatment of kidney cancer : identification and clinical utilization of new tumor suppressor genes or oncogenes closely correlated with VHL gene VHL

Research Project

Project/Area Number 16390465
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKochi University

Principal Investigator

SHUIN Taro  Kochi University, school of medicine, Professor, 医学部, 教授 (80179019)

Co-Investigator(Kenkyū-buntansha) INOUE Keiji  Kochi University, school of medicine, Associate Professor, 医学部, 助教授 (00294827)
KARASHIMA Takashi  Kochi University, Medical School Hospital, Instructor, 医学部附属病院, 助手 (60304672)
ASO Teijiro  Kochi University, school of medicine, Professor, 医学部, 教授 (20291289)
奥田 平和  高知大学, 医学部, 助手 (60325420)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2005: ¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 2004: ¥8,200,000 (Direct Cost: ¥8,200,000)
KeywordsVHL / HIG2 / HOXB13 / Methylation / Autocline / HIG2 / VHL遺伝子 / VEGF / Hypoxia Inducible Factor
Research Abstract

The first purpose is to search the growth factor protein using microarray from kidney cancer cells. With this viewpoint we collaborated with Human Genome Center in the Medical Science Institute, University of Tokyo. We identified HIG2, an oncofetal protein, that is expressed only human kidney cancer cells but not in other organ, which is secreted into blood stream. In addition we identified 3 more candidacy proteins. HIG2 works as a growth factor. It is a secretary protein. Since its antibody suppresses the growth of kidney cancer cells, it can control the multiplication of the human kidney cancer. As it is detected in the blood of the human kidney cancer patient, its usefulness is expected as a tumor marker for the human kidney cancers in the future. Presently this idea is the under examination. The 2nd purpose is to identify the gene that is specifically methylated in human kidney cancers, which has VHL gene mutation. The genes that are methylated works as tumor suppressor genes, lik … More e VHL. These genes are not identified yet. It is elucidated that RASSF1A is methylated in 40% kidney cell cancers. We collaborated with Dr.Minoru Toyota, Sapporo Medical School, for the screening of methylated genes in human kidney cancer. We identified methylated islands, MIRC-1, MIRC-2, MIRC-3 and MIRC-4. With the analyses of MIRC-1, we conformed MIRC-1 as a Homeobox gene, HOXB13. It is revealed this protein is expressed only in the proximal tubules in the kidney. When it is highly expressed, it induces apoptosis in the human kidney cell cancer. Methylation frequency in Hoxb13 is 30% in human kidney cancers. It is expected the application of this gene for gene therapy in the future. In addition it is also applicable as a tumor marker in the blood and the urine with use of methylation in this gene. We try to identify the responsible genes for 3 more methylated islands. The 3rd purpose is DNA comparative genomic hybridization or CGH microarray study for human kidney cancers in collaboration with Dr.Joji Inazawa at the Tokyo Medical and Dental College. The identification of the specifically deleted DNA portion in human kidney cancers was not successful difficult in 30 cell lines. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (14 results)

All 2006 2005 2004

All Journal Article (14 results)

  • [Journal Article] Epigenetic inactivation of the candidate tumor suppressor gene HOXB13 in human renal cell carcinoma.2006

    • Author(s)
      Okuda H, Shuin T., et al.
    • Journal Title

      Oncogene 25・12

      Pages: 1733-1742

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Epigenetic inactivation of the candidate tumor suppressor gene HOXB13 in human renal cell carcinoma.2006

    • Author(s)
      Okuda H, Toyota M, Ishida W, Furihata M, Tsuchiya M, Kamada M, Tokino T, Shuin T
    • Journal Title

      Oncogene 25-12

      Pages: 1733-1742

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Epigenetic inactivation of the candidate tumor suppressor gene HOXB 13 in human renal cell carcinoma.2006

    • Author(s)
      Okuda H, Shuin T., et al.
    • Journal Title

      Oncogene 25・12

      Pages: 1733-1742

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Levels of angiogenesis and expression of angiogenesis-related genes are prognostic for organ-specific metastasis of renal cell carcinoma.2005

    • Author(s)
      Fukata S, Shuin T., et al.
    • Journal Title

      Cancer 103・5

      Pages: 931-942

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Frequent expression of neuroendocrine markers in mucinous tubular and spindle cell carcinoma of the kidney.2005

    • Author(s)
      Kuroda S, Shuin T., et al.
    • Journal Title

      Histol Histopathol 21・1

      Pages: 7-10

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hypoxia-inducible protein 2 (HIG2), a novel diagnostic marker for renal cell carcinoma and potential target for molecular therapy.2005

    • Author(s)
      Togashi A, Shuin T., et al.
    • Journal Title

      Cancer Res 65・11

      Pages: 4817-4876

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Levels of angiogenesis and expression of angiogenesis-related genes are prognostic for organ-specific metastasis of renal cell carcinoma.2005

    • Author(s)
      Fukata S, Inoue K, Kamada M, Kawada C, Furihata M, Ohtsuki Y, Shuin T
    • Journal Title

      Cancer 103-5

      Pages: 931-942

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Frequent expression of neuroendocrine markers in mucinous tubular and spindle cell carcinoma of the kidney.2005

    • Author(s)
      Kuroda N, Hes 0, Miyazaki E, Shuin T, Enzan H
    • Journal Title

      Histology and Histopathology 21-1

      Pages: 7-10

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hypoxia-inducible protein 2 (HIG2), a novel diagnostic marker for renal cell carcinoma and potential target for molecular therapy.2005

    • Author(s)
      Togashi A, Katagiri T, Ashida S, Fujioka T, Maruyama 0, Wakumoto Y, Sakamoto Y, Fujime M, Kawachi Y, Shuin T, Nakamura Y
    • Journal Title

      Cancer Research 65-11

      Pages: 4817-4876

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Frequent expression of neuroendocrine markers in mucinous tubular and spindle cell carcinoma of the kidney.2005

    • Author(s)
      Kuroda S, Shuin T., et al.
    • Journal Title

      Pistol Histopathol 21・1

      Pages: 7-10

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hypoxia-Inducible Factor-1alpha Is Involved in the Attenuation of Experimentally Induced Rat Glomerulonephritis.2005

    • Author(s)
      Kudo Y
    • Journal Title

      Nephron Exp Nephrol. 100・(2)

      Pages: 95-103

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Levels of angiogenesis and expression of angiogenesis-related genes are prognostic for organ-specific metastasis of renal cell carcinoma.2005

    • Author(s)
      Fukata S
    • Journal Title

      Cancer 103・(5)

      Pages: 931-942

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Hypermethylation of the RASSFIA tumor suppressor gene in Japanese clear cell renal cell carcinoma.2004

    • Author(s)
      Tokinaga K
    • Journal Title

      Oncol Rep 12・(4)

      Pages: 805-810

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Recent advances in ideas on the molecular pathology and clinical aspects of Von Hippel-Lindau disease.2004

    • Author(s)
      Shuin T
    • Journal Title

      Int J Clin Oncol 9・(4)

      Pages: 283-287

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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