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Molecular detection of kidney cancers with VHL gene mutation in the blood, urine or lymph node

Research Project

Project/Area Number 11557118
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Urology
Research InstitutionKochi Medical School

Principal Investigator

SHUIN Taro  Kochi Medical School, Urology, Professor, 医学部, 教授 (80179019)

Co-Investigator(Kenkyū-buntansha) YAO Masahiro  Yokohama City University, School of Medicine, Urology Assistant Professor, 医学部, 講師 (00260787)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥11,200,000 (Direct Cost: ¥11,200,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥7,200,000 (Direct Cost: ¥7,200,000)
Keywordshuman kidney cancer / VHL gene / detection of cancers in the blood / detection of cancers in the urine / detection of cancer in the lymph node / 腎細胞癌 / 血中幡種 / VHL遺伝子異常 / nested RT-PCR / 腫瘍マーカー / リンパ節転移 / 血中播種 / nested PCR / VHL癌抑制遺伝子 / somatic mutation / 腎静脈血 / nestedPCR
Research Abstract

According to the development of CT, MRI or ultrasonography. Human kidney cancer is detected as smaller size tumor in these days than it used to be. However, tumor metastasis to the lung, bone, brain or liver often develops more than 10 years after surgery for primary tumors. Tumor metastasis has been a major cause of death at late postoperative time. It is often stated that human kidney cancer metastatize mainly hematogeously. It is estimated that tumor cells that are living in the blood vessles is a major risk factor for tumor metastasis. We utilized tumor specific mutation in the von Hippel-Lindau disease (VHL) gene and devfeloped tumor specific PCR primer to detect cancer cells in the blood vessels just after surgery. In order to detect floating cancer cells in the blood vessels lymph node or urine in patients with kidney cancer, nested PCR were performed using specific PCR primer for specific VHL mutation. We examiined 20 patients with kidney cancer that have specific VHL mutation. We extracted RNA from the patients before during and just after surgery, at 7 days and 1 month after surgery. According to our experiment tumors specific mutation in the RNA from the blood that means tumor cells is detected more than 40 %. Tumor specific mutations are detected at a low frequency in the urine (20 %) or lymph node (5 %), respectively. It is interesting to note that tumor specific mutation is detected in the urine with single strand conformational polymorphism methods. It maskes possible to detect cancer cells before surgery without examining the site of mutation in the. We attempted to detect any tumor specific proteins that are good tumor marker. However, we could not find any promising one in the present study.
Our results suggest that this molecular method for detecting cancer cell in the blood, urine or lymph node is a promising for estimating tumor invasion, or metastasis before clinical detection of kidney cancers.

Report

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

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Kato Y, Sakai N et al.: "Stimulation of motility of human renal cell carcinoma by SPARC/Osteonectin/BM-40 associated with type IV collagen"Invasion Metastasis. 18(2). 105-114 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shuin T, Kondo K et al.: "Germline and somatic mutations in von Hippel-Lindau disease gene and its significance in the development of kidney cancer"Contrib Neplirol. 128. 1-10 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ashida S, Okuda H et al.: "Detection of circulating cancer cells with von hippel-lindau gene mutation in peripheral blood of patients with renal cell carcinoma"Clin Cancer Res. 6. 3817-3822 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kuroda N, Naruse K et al.: "Mod Vinculin: its possible use as a marker of normal collecting ducts and renal neoplasms with collecting duct system"Pathol. 13(10). 1109-1114 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nishie A, Masuda K et al.: "High expression of the Cap43 gene in infiltrating macrophages of human renal cell carcinomas"Clin Cancer Res. 7(7). 2145-2151 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ashida S, Nishimori I et al.: "Effects of von Hippel-Lindau gene mutation and methylation status on expression of transmembrane carbonic anhydrases in"J Cancer Res Chin Oncol. 128(10). 561-568 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kuroda N, Inoue K: "Expression of CD9/motffity-reIated protein I (MRP-1) in renal parenchymal neoplasms: consistent expression in papillary and"Hum Pathol. 32(10). 1071-1077 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ashida S, Furihata M: "Molecular detection of von Hippel-Lindan gene mutations in urine and lymph node samples patients with renal cell"J Urol. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kato Y, Sakai N et al.: "Stimulation of motility of human renal cell carcinoma by SPARC/Osteonectin/BM-40 associated with type IV collagen"Invation Metastasis. 18(2). 105-14 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shuin T, Kondo K et al.: "Germline and somatic mutations in von Hippel-Lindau disease gene and its significance in the development of kidney cancer"Contrib Nephrol. 128. 1-10 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ashida S, Okuda H et al.: "Detection of circulating cancer cells with von Hippel-lindau gene mutation in peripheral blood of patients with renal cell carcinoma"Chin Cancer Res. 6. 3817-3822 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kuroda N, Naruse K et al.: "Mod Vinculin : its possible use as a marker of normal collecting ducts and renal neoplasma with collecting duct system phenotype"Pathol. 13(10). 1109-1114 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nishie A, Masuda K et al.: "High expression of the Cap43 gene in infiltrating macrophages of human renal cell carcinomas"Clin Cancer Res. 7(7). 2145-2151 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ashida S, Nishimori I et al.: "Effects of von Hippel-Lindau gene mutation and methylation status on expression of transmembrane carbonic anhydrases in renal cell carcinoma"J Cancer Res Clin Oncol. 128(10). 561-8 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kuroda N, Inoue K et al.: "Mod Vinculin : its possible use as a marker of normal collecting ducts and renal neoplasma with collecting duct system phenotype"Hum Pathol. 32(10). 1071-7 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ashida S, Furihata M: "Molecular detection of von Hippel-Lindau gene mutations in urine and lymph node samples patients with renal cell carcinoma potential biomarkers for early diagnosis and postoperative metastatic status"J Urol. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shuin T: "Germline and somatic mutations in von Hippel-Lindan disease gene and its significance in the development of kidney cancer"Contrib Nephrol. 128. 1-10 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okuda H: "Direct interaction of the beta-domain of VHL tumor suppressor protein with the regulatory domain of atypical PKC isotypes"Biochem Biophys Res Commun. 263(2). 491-497 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shuin T: "Molecular genetic mechanism of hereditary human kidney cancer development"Nippon Hinyokika Gakkai Zasshi. 90(5). 533-540 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shuin T: "Germline Mutation in the von Hippel-Lindau disease gene in Japan:its Epidemiology and Molecular Genetic study"Gann Monograph in Cancer Research. 175-182 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshida M: "Germline Mutation Analysis in Patients with von Hippel-Lindau Diseasein Japan:An Extended of 77 Families"Jpn J Cancer Res.. 91. 204-212 (2000)

    • Related Report
      1999 Annual Research Report

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

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