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1999 Fiscal Year Final Research Report Summary

APOPTOTIC CELL DEATH OF MALINGANT GLIOMA INDUCED BY HYPERTHERMIA : THE BASIC MECHANISMS AND CLINICAL APPLICATION

Research Project

Project/Area Number 10671311
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionNAGOYA CITY UNIVERSITY

Principal Investigator

MASAGO Atsuo  NAGOYA CITY UNIVERSITY, MEDICAL SCHOOL, INSTRUCTOR, 医学部, 教授 (70209419)

Co-Investigator(Kenkyū-buntansha) AIHARA Noritaka  NAGOYA CITY UNIVERSITY, MEDICAL SCHOOL, INSTRUCTOR, 医学部, 助手 (00264739)
KATO Taiji  NAGOYA CITY UNIVERSITY, MEDICAL SCHOOL, PROFESSOR, 医学部, 教授 (60094364)
YAMADA Kazuo  NAGOYA CITY UNIVERSITY, MEDICAL SCHOOL, PROFESSOR, 医学部, 教授 (90150341)
MASE Mitsuhito  NAGOYA CITY UNIVERSITY, MEDICAL SCHOOL, LECTURER, 医学部, 講師 (60238920)
Project Period (FY) 1999 – 2000
KeywordsHEAT SHOCK / APOPTOSIS / GLIOMA CELL / P53 / CYCLIN DEPENDENT KINASE / P21
Research Abstract

Hyperthermia is one of the effective therapeutic methods for malignant glioma. Many clinical trials are going on in the world. However, the details of anti-tumor mechanism haven't been well resolved. We already reported A172 glioma cells underwent G1 arrest and apoptotic cell death by heat shock stimulation. In the meantime, apoptosis related factors such as bax mRNA, Bax and p53 protein were induced. These phenomena had close relation with cell cycle. One of the cyclin dependent kinase inhibitors (CKIs), p21, was activated simultaneously (Fuse T et al, Biochem Biophys Res Commun, 1996). P53 has been reported to regulate p21 directly. We showed T98G glioma cells, which had mutant type p53, suffered apoptotic cell death by heat shock. The activation of p21 was not accompanied by p53 induction. Our data means there is alternative signal pathway to CKIs besides p53 related transduction (Fuse T et al, Neurosurgery 1998).
Malignant gliomas manifest resistance against many anti-tumor drugs. Prostaglandin A1 series (PGA1s) have anti-proliferative activity for many cancers in vivo and in vitro, and PGA1s are potentially useful in chemotherapy of malignant tumors. We showed PGA1 inhibited cell growth and caused G1 arrest in A172 glioma cells. PGA1 induced the expression of p21 mRNA and protein. On the other hand, cycline E dependent kinase activity was markedly reduced. PGA1 seem to inhibit tumor cell growth through two distinct pathways : the induction of p21 and the suppression of cyclin E (Tanikawa M et al, J Biol Chem 1998).
Although the molecular and cellular mechanisms remain elusive, p21 plays an important role in growth regulation of glioma cells and therapeutic strategy. Hyperthermia and PGA1 would be potentially useful in glioma therapy.

  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Tanikawa M, Yamada K,: "Potent Prostaglandin A1 analogs that suppress tumor cell growth through induction of p21 and reduction of cyclin E"J Biol Chem. 273. 18522-18527 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fuse T, Kato T: "Heat-induced apoptosis in human glioblastoma cell line A172"Neurosurgery. 42. 843-849 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fuse T, Yamada K,: "Heat shock-mediated cell cycle arrest is accompanied by induction of p21CK1"Biochem Biophys Res Commun. 225. 759-763 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiroyuki Katano, Taiji Kato^*: "Traumatic injury in vitro induces IEG mRNAs in cultured glial cells, suppressed by co-culture with neurons"NeuroReport. 10. 2439-2448 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 川村博康,真砂敦夫,: "ラットクモ膜下出血後のheat shock protein(hsp) 70 nRNA発現に対する低体温の影響"Progress in Research on Brain Edema and ICP(1999). 9-14 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 松本 隆,山田和雄,: "頭蓋内圧亢進と脳内遺伝子発現"脳循環代謝. 11. 77-93 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 片野広之,加藤泰治^*: "機械的損傷後のグリア単培養とニューロン・グリア共培養におけるIEGmRNA発現"神経組織の成長・再生・移植. 10. 45-46 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山田和雄,中塚雅雄,: "軽度脳虚血とアポトーシス関連遺伝子の発現"脳機能の解明. 557-563 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiroyuki Katano, Atsuo Masago,: "Differential induction of immediate early gene mRNAs follwing cryogenic and impact trauma with/without craniotomy in rats"Brain Res. 800. 69-77 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中塚雅雄,真砂敦夫^*: "ラットクモ膜下出血(SAH)後早期の海馬におけるp53mRNAの発現とアポトーシスの関連について"脳血管痙攣. 13. 261-266 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwata A, Masago A, Yamada K: "Angiotensin-converting enzyme cilazapril suppressed expression of basic fibroblast growth factor mRNA and protein in endothelial and tinimal smooth muscle cells in a vascular injury"Neurologia medico-chirurgica. 38. 257-265 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akira Iwata, Atsuo Masago,: "Expression of basic fibroblast growth factor mRNA after transient focal is chemia : Comparison with expression of c-fos, c-jun, and hsp70 mRNA"J Neurotrauma. 14. 201-210 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiroyuki Katano, Taiji Kato et al.: "Traumatic injury in vitro induces IEG mRNAs in cultured glial cells suppressed by co-culture with neurons"NeuroReport. 10. 2439-2448 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Motoki Tanikawa, Kazuo Yamada et al.: "Potent Prostaglandin A1 analogs that suppress tumor cell growth through induction of p21 and reduction of cyclin E"J Biol Chem. 273. 18522-18527 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahisa Fuse, Taiji Kato et al.: "Heat-induced apoptosis in human glioblastoma cell line A172"Neurosurgery. 42. 843-849 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoon KW, Worring Ve, Fuse T: "Multiple picrotoxinin effect on glycine channels in rat hippocampal neurons"Neuroscience. 87. 807-815 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoon KW, Takahisa Fuse et al.: "Indirect glutamate neurotoxicity"J Neurotrauma. 15. 141-147 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroyuki Katano, Atsuo Masago et al.: "Differential induction of immediate early gene mRNAs following cryogenic and impact trauma with/without craniotomy in rats"Brain Res. 800. 69-77 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akira Iwata, Atsuo Masago, Kazuo Yamada: "Angiotensin-converting enzyme cilazapril suppressed expression of basic fibroblast growth factor mRNA and protein in endothelial and intimal smooth muscle cells in a vascular injury"Neurol Med Chir. 38. 257-265 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akira Iwata, Atsuo Madago et al.: "Expression of basic fibroblast growth factor mRNA after transient focal ischemia : Comparison with expression of c-fos, c-jun and hsp70 mRNA"J Neurotrauma. 14. 201-210 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahisa Fuse, Kazuo Yamada et al.: "Heat shock-mediated cell cycle arrest is accompanied by induction of p21 CKI"Biochem Biophys Res Commun. 225. 759-763 (1996)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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