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Basic Research for Hyperthermia in Prostate Cancer

Research Project

Project/Area Number 09671648
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionSaitama Medical School

Principal Investigator

DEGUCHI Nobuhiro  Saitama Medical School, Professor, 医学部, 教授 (90118977)

Co-Investigator(Kenkyū-buntansha) UENO Munehisa  Saitama Medical School, Assistant Professor, 医学部, 助教授 (60167286)
OHIGASHI Takashi  Keio University School of Medicine, Instructor, 医学部, 講師 (80185371)
NAKANOMA Takashi  Saitama Medical School, Assistant, 医学部, 助手 (50198173)
塚本 拓司  埼玉医科大学, 医学部, 講師
野中 昭一  埼玉医科大学, 医学部, 助手 (70255537)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsHeat / Prostate cancer / Cell cycle / Heat shock protein 70 / Apoptosis / Quercetin / HSP70 / 温熱療法
Research Abstract

It has been demonstrated that prostate cancer cells are relatively sensitive to heat stress. Heat treatment at 43℃ inhibited the cell growth of three different prostatic cell lines, LNcap, JCA-1, and PC-3. Heat treatment at 43℃ increased the expression of heat shock protein 70 (hsp70) in prostate cancer cells, leading to cell death through apoptosis. Hsp70 is known to be a protein that protect cells against heat damage. Cells with lower levels of hsp70 have been shown to have a higher sensitivity to heat stress. Therefore down-regulation of hsp70 is expected to enhance heat-induced inhibitory effects on cell growth. Quercetin has been reported to be an agent that inhibits hsp70 expression. The cells were treated with quercetin and/or heat. Treatment with quercetin alone resulted in an apparent decrement of hsp70-positive cells and an increment of subG1 cells in JCA-1 and LNcap cells. Quercetin inhibited an increment of hsp70 expression after heat treatment and increased in the number of subG1 cells with lower levels of hsp70 in JCA-1 and LNcap cells. Quercetin was found to enhance the heat-induced inhibitory effects on cell growth and heat-induced apoptosis in both JCA-1 and LNcap cells. These results suggest that quercetin may enhance heat-induced cytotoxicity in prostate cancer cell lines through the inhibition of hsp70 production.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] 中野間隆: "ヒト前立腺癌細胞における温熱刺激の抗腫瘍効果"Human cell. 11. 167-174 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fuller KJ, Issels RD, Slosman DO, Guillet JG, Soussi T, Polla BS.: "Cancer and heat-shock response."Europ.J.Cancer.. 30A. 1884-1891 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Szmigielski S, Zielinski H, Stawarz B et al.: "Local microwave hyperthermia in treatment of advanced prostatic adenocarcinoma."Urol.Res.. 16. 1-7 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Honma T.: "Characteristics of hyperthermia-induced apoptotic cell death."Nihon Rinsho.. 54. 223-228 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakanoma T, Ueno M, Ohigashi T et al.: "Anti-proliferative effects of heating on the human prostatic carcinoma cells in culture."Human Cell.. 11. 167-174 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Elia H, Santoro MG: "Regulation of heat shock protein synthesis by quercetin in human erythroleukaemia cells."Biochem.J.. 300. 301-209 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kim JH, Kim SH, Alfieri AA, Young CW.: "Quercetin, an inhibitor of lactate transport and a hyperthermic sensitizer of Hela cell."Cancer Res.. 44. 102-106 (1984)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Agullo GA, Gamet-Payrastre L, Fernandez Y, Anciaux N, Demigne C, Remesy C.: "Comparative effects of flavonoids on the growth, viability and metabolism of a colonic adenocarcinoma cell line (HT29 cells)."Cancer Letters.. 105. 61-70 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kuo SM.: "Antiproliferative potency of structurally distinct dietary flavonoids on human colon cancer cells."Cancer Letters.. 110. 41-48 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Larocca LM, Ranelletti FO, Maggiano N et al.: "Differential sensitivity of leukemic and normal hematopoietic progenitors to the killing effect of hyperthermia and quercetin used in combination : Role of heat-shock protein-70."Int.J.Cancer.. 73. 75-83 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nagai N, Nakai A, Nagata K: "Quercetin suppresses heat response by down regulation of HSF1."Biochem.Biophys.Res.Commun.. 208. 1099-1105 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hansen RK, Oesterreich S, Sarge KD, Fuqua SSW.: "Quercetin inhibits heat shock protein induction but not heat shock factor DNA-binding in human breast carcinoma cells."Biochem.Biophys.Res.Comm.. 239. 851-856 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Rokhlin OW, Bishop GA, Hostager BS et al.: "Fas-mediated apoptosis in human prostatic carcinoma cell lines."Cancer Res.. 57. 1758-1768 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Paulson DP.: "Impact of radical prostatectomy in the management of clinically localized disease."J.Urol.. 10. 60-72 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Li WX, Franklin WA.: "Radiation and heat-induced apoptosis in pc-3 prostate cancer cells."Radiat.Res.. 150. 190-194 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Moriyama Y, Hashimoto S, Goto T et al.: "In vitro purging of clonogenic leukemic cells from human bone marrow by heat : simulation experiments for autologus bone-marrow transplantation."Leu.Res.. 16. 973-977 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Armor EP, McEachern D, Wang Z et al.: "Sensitivity of cells to mild hyperthermia."Cancer Res.. 53. 2740-2744 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Murphy PB, Richman CM: "Normal and malignant human myeloid progenitors differ in their sensitivity to hyperthermia."Exp.Hematol.. 17. 1105-1109 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Li GC, Li L, Liu RY et al.: "Heat shock protein hsp70 protects cells from thermal stress even after deletion of its ATP-binding domain."Proc.Natl.Acad.Sci.USA.. 89. 2036-2040 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hosokawa N, Hirayoshi K, Kudo H et al.: "Inhibition of the activation of heat shock factor in vivo and in vitro by flavonoids."Mol.Cell.Biol.. 12. 3490-3498 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fujita M, Nagai M, Murata M, Kawakami K, Irino S, Takahara J.: "Synergistic cytotoxic effect of quercetin and heat treatment in a lymphoid cell line (OZ) with low hsp70 expression."Leu.Res.. 21. 139-145 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hosokawa N, Hirayoshi K, Nakai A et al.: "Flavonoids inhibits the expression of heat shock proteins."Cell.Struct.Funct.. 15. 393-401 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Wei YQ, Zhao X, Kariya Y, Fukata H, Teshigawara K, Uchida A.: "Induction of apoptosis by quercetin : Involvement of heat shock protein."Cancer Res.. 54. 4952-4957 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] He L, Fox M.: "Variation of heat shock protein 70 through the cell cycle in HL-60 and its relationship to apoptosis"Exp.Cell.Res.. 232. 64-71 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 中野間隆: "ヒト前立腺癌細胞における温熱刺激の抗腫瘍効果" HUMAN CELL. 11(3). 167-174 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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