| 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)
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| 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.
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