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ANALYSIS OF BIOLOGICAL MARKERS BENEFICIAL TO PREDICT BIOLOGIC BEHAVIOR S OF THE RENAL CELL CARCINOMAS BASED ON GENE EXPRESSION PROFILING.

Research Project

Project/Area Number 13670184
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionYOKOHAMA CITY UNIVERSITY SCHOOL OF MEDICINE

Principal Investigator

NAGASHIMA Yuji  YOKOHAMA CITY UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF PATHOLOGY TITLE OF POSITION ASSOCIATE PROFESSOR, 医学部, 助教授 (10217995)

Co-Investigator(Kenkyū-buntansha) YAO Masahiro  YOKOHAMA CITY UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF UROLOGY TITLE OF POSITION ASSOCIATE PROFESSOR, 医学部, 助教授 (00260787)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsRenal cell carcinoma (RCC) / cDNA Micro array / VHL gene / VEGF / HIF1?, 2? / adipophilin / IGFBP-3 / マウクロアレイ
Research Abstract

(OBJECT)
Renal cell carcinomas (RCCs) contain several histopathological subtypes with markedly different clinical features and biological behaviors. Therefore, establishment of strategic treatments is necessary for each cases to obtain more favorable clinical outcomes. In this research, we aimed to exploration of useful biological marker for precise path biological diagnosis of RCCs based on gene expression profiling.
(MATERIALS AND METHODS)
1. Materials; RCC tissues and simultaneously nonneoplastic renal tissues were obtained from nephrectomy specimens performed at the Yokohama City University Hospital and the affiliated hospitals. Informed consents were obtained from the patients on examination of the molecular biological analyses. The collected samples were stored in liquid nitrogen until use.
2. Total RNAs were extracted from the materials according to the routine procedures, and then reverse-transcribed. The resultant cDNAs derived from RCC and nonneoplastic tissues were separately la … More beled with fluorescent dyes. The cDNAs of which qualities were confirmed using the Test Chip (Test 2 array, Affirm etrix), were subjected to micro array analyses using HuGeneFL array (Affirm etrix).
3. Based on differences of the fluorescent intensities, genes differently expressed were analyzed between RCCs and nonneoplastic tissues, and among RCCs of different subtypes.
(RESULTS)
1. Clear cell RCCs tended to highly express audiophile, insulin-like growth factor binding protein (IGFBP3), vascular endothelial growth factor (VEGF) and hypoxia-inducible factors(HIFs) 1αand 2α. Immunohistochemically, preferential expression Is confirmed for adipophylin.
1. Chromophobe RCCs and collecting duct carcinoma showed high expression for E-cadherin, a marker for the distalnephron.
2. Simultaneously preformed Clinicopathological study form RCC with and without von Hippel-Lindau (VHL) disease gene mutation revealed more favorable outcome in RCCs with gene mutation.
(CONCLUSION)
Because RCCs are not a uniform disease entity, biological behaviors in each case should be carefully evaluated. Based on this fact, adipophilin and VHL gene mutations were considered to be important marker to investigate RCCs. Less

Report

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

    (44 results)

All Other

All Publications (44 results)

  • [Publications] Kondo Ki, Yao M, Nagashima Y, et al.: "PTEN/MMAC1/TEP1 mutations in human primary renal-cell carcinomas and renal carcinoma cell lines"Int J Cancer. 91 2. 219-224 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Otani M, Nagashima Y et al.: "Intrarenal mature cystic teratoma associated with renal dysplasia : A case report with a review of literature"Pathol Int. 51 7. 560-563 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Otani M, Nagashima Y et al.: "Low-grade renal cell carcinoma arising from the lower nephron. A case report with immunohistochemical, histochemical and ultrastructural studies"Pathol Int. 51 12. 954-960 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hamazaki S, Yao M, Nagashima Y, et al.: "Somatic von Hippel-Lindau gene mutation in a sporadic endolymphatic sac tumor"Hum Pathol. 32 11. 1272-1276 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kato Y, Nagashima Y, et al.: "Induction of SPARC by VEGF in human vascular endothelial cells"Biochem Biophys Res Comm. 287 2. 422-426 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakai N, Nagasima Y, Yao M et al.: "SPARC expression in primary human renal cell carcinoma : Upregulation of SPARC in sarcomatoid renal carcinoma"Hum Pathol. 32 10. 1064-1070 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 大谷方子, 長嶋洋治 他: "腎臓に発生した良性奇形腫の1症例"日本臨床細胞学会誌. 40 6. 644-645 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Horikawa S, Nagashima N et al.: "Prior induction of heme oxygenase-1 with glutathione depletor ameliorates the renal ischemia and reperfusion injury in the rat"FEBS Lett. 510 2. 221-224 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kondo K, Yao M, Nagashima Y, et al.: "Comprehensive analysis of the VHL gene in sporadic renal cell carcinoma ; relationship to clinico-pathological parameter"Genes Chromosomes Cancer. 34 1. 58-68 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoneya R, Nagashima Y et al.: "Hemolysate pretreatment ameliorates the ischemic acute renal injury in rats"Nephron. 92 2. 407-413 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Murata H, Nagashima Y, Yao M et al.: "von Hippel-Lindau tumor suppressor protein transforms human neuroblastoma cells into functional neuron-like cells"Cancer Res. 62 23. 7004-7010 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida M, Yao M, Nagashima Y et al.: "Somatic VHL mutation in clear cell renal carcinomas associated with end-stage renal disease/acquired cystic disease of the kidney"Genes Chromosomes Cancer. 35 4. 359-364 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yao M, Nagashima Y et al.: "VHL alterations associated with good prognosis in sporadic clear-cell renal carcinoma"J Natl Cancer Inst. 94 20. 1569-1575 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 長嶋洋治 他: "色素嫌性腎細胞癌の圧挫細胞診所見"日本臨床細胞学会誌. 41 6. 461-462 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 長嶋洋治, 稲山嘉明, 矢尾正祐: "von Hippel-Lin dau病と腎腫瘍の病理"細胞. 35 1. 23-25 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kondo Ki, Yao M, Kobayashi K, Ota S, Yoshida M, Kaneko S, Baba M, Sasaki N, Kishida T, Kawakami S, Uemura H, Nagashima Y, Nakatani Y, Hosaka M: "PTEN/MMAC1/TEP1 mutations in human primary renal-cell carcinomas and renal carcinoma cell lines."Int J Cancer. 91(2). 219-224 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Otain M, Tsujimoto S, Miyake M, Nagashima Y: "Intrarenalmature cystic teratoma associated with renal dysphasia: A case report with a review of literature."Pathol Int. 51(7). 560-563 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Otani M, Shimaizu T, Serizawa T, Ebihara Y, Nagashima Y: "Low-grade renal cell carcinoma arising from the the lower nephron. A case report with immunohistochemical, histochemical and Ultrastructural studies."Pathol Int. 51(12). 956-960 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hamazaki S, Yoshida M, Yao M, Nagashima Y, Taguchi K, Nakashima H, Okada S: "Somatic von Hippel-Lindau gene mutation in a sporadic endolymphatic sac tumor."Hum Pathol. 32(11). 1272-1276 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kato Y, Lewalle J-M, Baba B, Tsukuda M, Sakai N, Baba M, Kobayashi K, Koshika S, Nagashima Y, Frankenne F, Noel A, Foidart J-M, Hata R-I: "Induction of SPARC by VEGF in human vascular endothelial cells."Biochem Biophys Res Comm. 287(2). 422-426 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakai N, Baba M, Nagashima Y, Kato Y, Hirai K, Kondo KI, Kobayashi K, Yoshida M, Kaneko S, Kishida T, Kawakami S, Hosaka M, Inayama Y, Yao M: "SPARC expression in primary human renal cell carcinoma: Up regulation of SPARC in scrcomatoid renal carcinoma."Hum Pathol. 32(10). 1064-1070 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Horikawa S, Yoneya R, Nagashima Y, Hagiwara K and Ozasa H.: "Prior induction of heme oxygenase-1 with glutathione depletory am eliorates the renal ischemia and reperfusion injury in the rat."FEBS Lett. 510(2). 221-224 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kondo K, Yao M, Yoshida M, Kishida K, Shuin T, Miura T, Moriyama M, Kobayashi K, Sakai N, Kaneko S, Kawakami S, Baba M, Nakaigawa N, Nagashima Y, Nakatani Y and Hosaka M: "Comprehensive analysis of the VHL gene in sporadic renal cell carcinoma; relationship to clinico-pathological parameter."Genes Chromosomes Cancer. 34(1). 58-68 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoneya R, Nagashima Y, Sakaki K, Hagiwara K, Teraoka H, Ozasa H and Horikawa S: "Hemolysate pretreatment ameliorates the ischemic acute renal injury in rats."Nephron. 92(2). 407-413 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Murata H, Tajima N, Nagashima Y, Yao M, Goto M, Kawamoto S, Yamamoto I, Okuda K and Kanno H: "von Hippel-Lindau tumor suppressor protein transforms human neuroblastoma cells into functional neuron-like cells."Cancer Res. 62(11). 7004-7011 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida M, Yao M, Ishikawa I, Kishida T, Nagashima Y, Kondo K, Nakagawa N and Hosaka M.: "Somatic VHL mutation in clear cell renal carcinomas associated with end-stage renal disease/acquired cystic disease of the kidney."Genes Chromosomes Cancer. 35(4). 359-364 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yao M, Yoshida M, Kishida T, Nagaigawa N, Baba M, Kobayashi K, Moriyama M, Nagashima Y, Nakatani Y, Kubota Y and Kondo K.: "VHL alterations associated with good prognosis in sporadic clear-cell renal carcinoma."J Natl Cancer Inst. 94(20). 1569-1575 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kondo Ki, Yao M, Nagashima Y, et al.: "PTEN/MMAC1/TEP1 mutations in human primary renal-cell carcinomas and renal carcinoma cell lines"Int J Cancer. 91 2. 219-224 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Otani M, Nagashima Y et al.: "Intrarenal mature cystic teratoma associated with renal dysplasia : A case report with a review of literature"Pathol Int. 51 7. 560-563 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Otani M, Nagashima Y et al.: "Low-grade renal cell carcinoma arising from the lower nephron. A case report with immunohistochemical, histochemical and ultrastructural studies"Pathol Int. 51 12. 954-960 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hamazaki S, Yao M, Nagashima Y, et al.: "Somatic von Hippel-Lindau gene mutation in a sporadic endolymphatic sac tumor"Hum Pathol. 32 11. 1272-1276 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kato, Y, Nagashima Y, et al.: "Induction of SPARC by VEGF in human vascular endothelial cells"Biochem Biophys Res Comm. 287 2. 422-426 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sakai N, Nagasima Y, Yao M et al.: "SPARC expression in primary human renal cell carcinoma : Upregulation of SPARC in sarcomatoid renal carcinoma"Hum Pathol. 32 10. 1064-1070 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 大谷方子, 長嶋洋治 他: "腎臓に発生した良性奇形腫の1症例"日本臨床細胞学会誌. 40 6. 644-645 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Horikawa S, Nagashima N et al.: "Prior induction of heme oxygenase-1 with glutathione depletor ameliorates the renal ischemia and reperfusion injury in the rat"FEBS Lett. 510 2. 221-224 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kondo K, Yao M, Nagashima Y, et al.: "Comprehensive analysis of the VHL gene in sporadic renal cell carcinoma ; relationship to clinico-pathological parameter"Genes Chromosomes Cancer. 34 1. 58-68 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoneya R, Nagashima Y et al.: "Hemolysate pretreatment ameliorates the ischemic acute renal injury in rats"Nephron. 92 2. 407-413 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Murata H, Nagashima Y, Yao M et al.: "von Hippel-Lindau tumor suppressor protein transforms human neuroblastoma cells into functional neuron-like cells"Cancer Res. 62 23. 7004-7010 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshida M, Yao M, Nagashima Y et al.: "Somatic VHL mutation in clear cell renal carcinomas associated with end-stage renal disease/acquired cystic disease of the kidney"Genes Chromosomes Cancer. 35 4. 359-364 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yao M, Nagashima Y et al.: "VHL alterations associated with good prognosis in sporadic clear-cell renal carcinoma"J Natl Cancer Inst. 94 20. 1569-1575 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 長嶋洋治 他: "色素嫌性腎細胞癌の圧挫細胞診所見"日本臨床細胞学会誌. 41 6. 461-462 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 長嶋洋治, 稲山嘉明, 矢尾正祐: "vonHippel-Lindau病と腎腫瘍の病理"細胞. 35 1. 23-25 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sakai N, Nagashima Y et al.: "SPARC expression in human primary renal cell carcinoma. Up-regulation of SPARC in sarcomatoid renal carcinoma"Hum Pathol. 32 10. 1064-1070 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kondo K, Yao M, Nagashima Y et al.: "Comprehensive analysis of the VHL gene in sporadic renal cell carcinoma; relationshiD to clinico-pathological parameter"Genes Chromosomes Cancer. (in press).

    • Related Report
      2001 Annual Research Report

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

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