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Research for cancer therapy based on cross-talk between intracellular apoptotic signals

Research Project

Project/Area Number 13670785
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionTokyo Medical and Dental University

Principal Investigator

NAGASAWA Masayuki  Tokyo Medical and Dental University, Department of Pediatrics and Developmental Biology, Assistant Professor, 発達病態小児科学, 講師 (90262196)

Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsp53 / NFkB / lkBa / apoptosis / cdk / 細胞損害活性 / monosomy7 / アポトーシス / granulysin / CTL / NK細胞 / 神経芽細胞腫 / NFKB / IKBα
Research Abstract

1: To investigate the differential roles of cdk2 and cdk4, 3T3 cell lines with stably expressing dominant negative cdk2 (cdk2dn) and dominant negative cdk4 (cdk4dn) were established. GuS transition were delayed by two hours in both cell lines when cell cycle was stimulated by serum stimulation. In cdk4dn cells, both of cdk2 and cdk4 kinase activities were reduced, but only cdk2 activity was reduced in cdk2dn cells. In the serum starved condition, cdk4dn cells were more sensitive to apoptosis compared to parent 3T3 cells, but cdk2dn cells were not. These results indicate that both of cdk2 and cdk4 are involved in G1/S cell cycle progression, but onlycdk4 is important in cell survival signal induced by serum stimulation. On the contrary, 3T3 cells with stably expressing dominant negative cdk6 (cdk6dn) showed no delay in G1/S transition. These date indicate that cdk4 and cdk6 have different biological roles, although they are considered to have redundant functions in the cell cycle progression.
2:IL2-dependent allo-specific CTL lines against wild type p53 expressing A2058 melanoma cells were established. To investigate the relevance of p53 and NFkB to the cytolytic signals, cytotoxicity against A2085 with mutant p53 and dominant negative 1kB was compared to that against parent A2085. There were no significant differences in cytotoxicity between these cell lines. Considering that the amount of secreted granulysin, which is a cytolytic effector molecule, is equal, p53 and NFkB are possibly not involved in the death signals induced by CTL.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Masayuki Nagasawa et al.: "Accumulation of high levels of the p53 and p130 growth-suppressing proteins in cell lines stably over-expressing cyclin-dependent kinase 6"Oncgene. 20. 2889-2899 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ogawa, K, Y.Takamori, Masayuki Nagasawa et al.: "Granulysin in human serum as a a marker of cell-mediated immunity"European Journal of Immunology. 33. 1925-1933 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masayuki Nagasawa et al.: "Pancytopenia presenting with monosomy 7 which disappeared after immunosuppressive therapy"Leukemia Research. 28. 315-319 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masayuki Nagasawa et al.: "Cogulopathy in a patient with X-linked hyper-IgM syndrome who developed Kaposi's sarcoma."American Journal of Hematology. 75. 116-117 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tomizawa.D, Masayuki Nagasawa, et al.: "Allogenic hematopoietic stem cell transplantation for seven children with X-linked hyper-IgM syndrome : A single center experience"American Journal of Hematology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masayuki Nagasawa, E.W.Gelfand, J.J.Lucas: "Accumulation of high levels of the p53 and p130 growth-suppressing protein in cells stably over-expressing cyclin-dependent kinase 6 (cdk6)."Oncogene. 20. 2889-2899 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ogawa K, Y.Takamori, K.Suzuki, Masayuki Nagasawa, S.Takano, Y.Kasahara, Y.Nakamura, S.Kondo, K.Sugamura, M.Nakamura, K.Nagata.: "Granulysin in human serum as a marker of cell-mediated immunity"Eur.J.Immunol.. 33. 1925-1933 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masayuki Nagasawa, D.Tomizawa, Y.Tsuji, M.Kajiwara, T.Mono, S.Nonoyama, M.Asada, S.Mizutani.: "Pancytopenia presenting with monosomy 7 which disappeared after immunosuppressive therapy"Leukemia Research. 28. 315-319 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masayuki Nagasawa, S.Itoh, Y.Sawada, I.Mono, S.Nonoyama, S.Mizutani.: "Coagulopathy in a patient with X-linked hyper-IgM syndrome who developed Kaposi' s sarcoma"Am.J.Hematol.. 75. 116-117 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Daisuke Tomizawa, K.Imai, S.Itoh, M.Kajiwara, Y.Minegishi, Masayuki Nagasawa, I.Mono, S.Nonoyama, S.Mizutani.: "Allogenic hematopoietic stem cell transplantation for seven children with X-linked hyper-IgM syndrome: A single center experience"Am.J.Hematol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ogawa K, Y.Takamori, K.Suzuki, Masayuki Nagasawa et al.: "Granulysin in human serum as a marker of cell-mediated immunity"European Journal of Immunology. 33. 1925-1933 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masayuki Nagasawa et al.: "Pancytopenia presenting with monosomy 7 which disappeared after immuno suppressive therapy"Leukemia Research. 28. 315-319 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masayuki Nagasawa et al.: "Coagulopathy in a patient with X-linked hyper-IgM syndrome who develop ed Kaposi's sarcoma"American journal of Hematology. 75. 116-117 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Daisuke Tomizawa, Masayuki Nagasawa et al.: "Allogenic hematopoietic stem cell transplantation for seven children with X-linked hyper-IgM syndrome"American journal of Hematology. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masayuki NAgasawa, et al.: "Accumulation of high levels of the p53 and p130 growth-suppressing proteins in cell lines stably over-expressing cyclin-dependent kinase 6"Oncgene. 20. 2889-2899 (2001)

    • Related Report
      2001 Annual Research Report

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

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