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Intracellular damage caused by anti-cancer drugs and radiation, analysis of regulatory mechanism of apoptosis in topoisomerase mutant cells

Research Project

Project/Area Number 09670826
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionYokohama City University School op Medicine

Principal Investigator

FUNABIKI Tetsunori  Yokohama City University School of Medicine, Pediatrics, Assistant Professor, 医学部・付属病院, 講師 (20264616)

Co-Investigator(Kenkyū-buntansha) IKUTA Koichiro  Yokohama City University School of Medicine, Pediatrics, Assistant Professor, 医学部・付属病院, 講師 (80159590)
SASAKI Hideki  Yokohama City University School of Medicine, Pediatrics, Associate Professor, 医学部・付属病院, 助教授 (50106316)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Keywordstopoisomerase II / apoptosis / drug resistance / cell cycle
Research Abstract

(1) We established the method of quantification of apoptotic cells, i.e. BrdU was incorporated to fixed cells by TdT, and apoptotic cell were identified by enzyme linked immunoassay with anti-BrdU antibody conjugated with FITC.
(2) We quantified the apoptotic human leukemia cells which have wild type topoisomerase II (topo II) and drug-resistant sublines which carries mutation in topo II after the exposure of anti-cancer drugs. The degree of resistance to anti-cancer drug was inversely proportional to the number of apoptotic cells.
(3) We found that both of wild type cells and drug resistant cells accumulated in G2-M phase when treated with anti-topo II drugs such as doxorubicin or VP-16. Thus, doxorubicin and VP-16 seem to cause apoptosis of cells at G2-M phase.
(4) Recently the expression of topo II was shown to be down regulated before the apoptotic change of the cell. We examined the regulatory mechanism between cell cycle progression and the expression of topo II. The expression of topo II was slightly decreased in both wild type cell and drug resistant cell lines, one with low expression of normal protein and the other with wild type cell equivalent expression of mutant protein. These results suggested the existence of the apoptotic pathway which induced by the suppression of topo II activity.

Report

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

    (38 results)

All Other

All Publications (38 results)

  • [Publications] 船曳哲典: "小児急性リンパ性白血病におけるTEL/AML1融合遺伝子"横浜医学. 50・1. 75-76 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 山崎桜子: "同種造血幹細胞移植後のサイトメガウイルス(CMV)感染の検討"日本小児血液学会雑誌. 13・3. 151-157 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 高橋浩之: "小児急性リンパ性白血病におけるTEL/AML1融合遺伝子の検討"日本小児血液学会雑誌. 13・3. 164-169 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shoko Goto: "Serum-free culture conditions for anolysis of secretory proteinases during myogenic differentiation of mouse C2C12 myoblasts"Analytical Biochemistry. 272・1. 135-142 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiroaki Goto: "Nevral differentiation of a novel cell line, YCUS-5, established from proximal-type epithelioid sarcoma of a child"Medical Pediatric Oncology. 33・1. 137-138 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hideki Sasaki: "Effects of recombinant thrombopoietin of the growth of murine Primitive and committed hematopoietic progenitors in serum-free culture"Pediatrics International. 41・6. 666-672 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 船曳哲典: "小児がん、小児のホジキン病"医薬ジャーナル(印刷中). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Xiao-Tank Konng, Kohmei Ida, Hitoshi Ichikawa, Kimiko Shimizu, Misao Ohki, Nobuo Maseki, Yasuyuki Kaneko, Masahiro Sako, Yukio Kobayashi, Arinobu Tojou, Ikuo Miura, Harumi Tsunoda, Tetsunori Funabiki, Keizo Horibe, Hiroyuki Hamaguchi, Yuichi Akiyama, Fumio Bessho, Masayoshi Yanagisawa and Yasuhide Hayashi: "Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identification of a novel transcript"Blood. 90. 1192-1199 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiroaki Goto, Shoko Goto Yuka Watanabe, Motoi Matsuda, Norio Hanzawa, Haruyuki Sekiguchi, Sumio Kai, Tetsunori Funabiki, Koichiro Ikuta, Hideki Sasaki, Syusuke Matsuyama: "Allogeneic peripheral Blood Stem-Cell Transplantation for Pediatric Acute Leukemia and Malignant Lymphoma"Jap J of Pediatr Hematol. 11. 356-362 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Koichiro Ikuta, Yuka Watanabe, Hiroaki Goto, Tetsunori Funabiki, Hideki Sasaki: "double allogeneic PBSCT for a girl with relapsed acute lymphocytic leukemia"Grant in aid of ministry of health and wellfare research report. 111-113 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S Kai, H Sumita, K Fujioka, H Takahashi, N Hanzawa, T Funabiki, K Ikuta, H Sasaki: "Loss of heterozygosity of NFl gene in juvenile chronic myelogenous leukemia with neurofibromatosis type 1"Int J Hematol. 68. 53-60 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiroaki Goto, Sakurako Yamazaki, Yuka Watanabe, Tetsunori Funabiki, Koichiro Ikuta, Hideki Sasaki, Seiko Ikuta: "A case report, epithelioid sarcoma in neck of a child"Jap J Pediatr Oncol. 35. 46-50 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tetsunori Funabiki, Motoi Matauda, Yuka Watanabe, Hiroaki Goto, Ken-ichiro Fujioka, Koichiro Ikuta, Hideki Sasaki: "Long term mechanical ventilation for chronic respitatory failure after allo-PBSCT"Transplanation Today. 11. 483-486 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] tomoko Nakamura, Tomoyuki Nakamura, Tetsunori Funabiki, Yuko Aihara, Yoshiyuki Yoshida: "Virus associated hemophagocytic syndrome (VAHS) in a case with rapidly progressive glomerular nephritis (RPGN)"Jap J pediatr renal failure. 18. 212-217 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tetsunori Funabiki, Shunpei Yokota: "Bone marrow transplantation, cord blood transplantation and bacterial infection"Jap J Pediatr Med. 31. 105-109 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tetsunori Funabiki, Hideki Sasaki: "TEL/AMLl fusion gene in acute lymphocytic leukemia in childhood"Yokohama Med Bulletin. 50. 75-76 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sakurako Yamazaki, Koichiro Ikuta, Hisaki Fujii, Yuka Watanabe, Motoi Matsuda, Hiroaki Goto, Ken-ichiro Fujioka, Tetsunori Funabiki, Hideki Sasaki: "Cytomegalovirus infection after allogenic stem cell transplantation"Jap J of Pediatr Hematol. 13. 151-157 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiroyuki Takahashi., Sumio Kai, Tetsunori Funabiki, Hiroaki Goto, Koichiro Ikuta, Hideki Sasaki: "TEL/AMLl fusion gene in Childhood Acute lymphoblastic leukemia"Jap J of Pediatr Hematol. 13. 164-169 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kumiko Okuda, Yuka Watanabe, Hiroyuki goto, Sumio Kai, Tetsunori Funabiki, Koichiro Ikuta, Hideki Sasaki, Shunsuke Matauyama: "Double BMT from HLA 1 locus mismatch sibling for refractory neuroblastoma"Jap J Pediatr Oncol. 36. 235-238 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shoko Goto, Kaoru Miyazaki, Tetsunori Funabiki, Hideraro Yasumitsu: "Serum-free culture conditions for analysis of secretary proteinases during myogenic differentiation of mouse C2C12 myoblasts"Anal Biochem. 272. 135-142 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiroaki Goto, Hiroyuki Takahashi, Tetsunori Funabiki, Koichiro Ikuta, Hideki Sasaki, Yoji Nagashima: "Neural differentiation of a novel cell line, YCUS-5, established from proximal-type epithelioid sarcoma of a child"Med Pediatr Oncol. 33. 137-138 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hideki Sasaki, Koichiro Ikuta, Tetsunori Funabiki, Ken-ichiro Fujioka, Motoi Matsuda: "Effects of recombinant thrombopoietin on the growth of murine primitive and committed hematopoietic progenitors in serum-free culture"Pediatrics International. 41. 666-672 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 船曳哲典: "小児急性リンパ性白血病におけるTEL/AML1融合遺伝子"横浜医学. 50・1. 75-76 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 山崎桜子: "同種造血幹細胞移植後のサイトメガロウイルス(CMV)感染の検討"日本小児血液学会雑誌. 13・3. 151-157 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 高橋浩之: "小児急性リンパ性白血病におけるTEL/AML1融合遺伝子の検討"日本小児血液学会雑誌. 13・3. 164-169 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shoko Goto: "Serum-free culture conditions for anolysis of secretory proteinases during myogenic differentiation of meuse C2C12 myohlasts"Analytical Biochemistry. 272・1. 135-142 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiroaki Goto: "Nevral differentiation of a novel cell line,YCUS-5,established from proximal-type epithelioid sarcoma of a child"Medical Pediatric Oncology. 33・1. 137-138 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hideki Sasaki: "Effects of recombinant thrombopoietin on the growth of murine primitive and committed hematopoietic progenitors in serum-freecvlture"Pediatrics International. 41・6. 666-672 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 船曳 哲典: "小児がん,小児のホジキン病"医薬ジャーナル社(印刷中). (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 後藤 裕明: "頚部に発症した小児類上皮肉腫の1例" 小児がん. 35. 46-50 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 船曳哲典: "同種末梢血幹細胞移植後の慢性呼吸不全に対する長期人工呼吸の経験" 今日の移植. 11. 483-486 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 船曳哲典: "骨髄移植,臍帯血移植と細菌感染症" 小児内科. 31. 105-109 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 船曳哲典: "骨髄移植後に腹痛を訴え,腹水 黄疸を認めた女児 症例に学ぶ肝臓病学" 新興医学出版社, 2 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Xiao-Tang・Kong: "Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(pll;422)and identification of a novel transcript" Blood. 90. 1192-1199 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 後藤 裕明: "小児急性白血病,悪性リンパ腫に対する同種末梢血幹細胞移植" 日本小児血液学会雑誌. 11. 356-361 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 生田 孝一郎: "double allogeneic PBSCTを施行した再発ALLの一女児例" 厚生省がん研究助成金 平成8年度研究報告書. 111-113 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 船曳 哲典: "症例に学ぶ肝臓病学、骨髄移植後に腹痛を訴え,腹水,黄疸を認めた女児" 新興医学出版社, 印刷中 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 船曳 哲典: "小児がん,小児のホジキン病" 医薬ジャーナル社, 印刷中 (1998)

    • Related Report
      1997 Annual Research Report

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

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