| Co-Investigator(Kenkyū-buntansha) |
SETO Hiroshi KUMAMOTO UNIV.HOSP., INSTRUCTORE, 医学部附属病院, 助手 (60209848)
TAKADA Akira KUMAMOTO UNIV.HOSP., INSTRUCTORE, 医学部附属病院, 助手 (10187966)
KOCHI Masato KUMAMOTO UNIV.MED.SCH., LECTURER, 医学部, 講師 (70178218)
NAGAHIRO Shinji KUMAMOTO UNIV.HOSP., LECTURER, 医学部附属病院, 講師 (60145315)
KURATSU Jun-ichi KUMAMOTO UNIV.MED.SCH., ASSOCIATE PROFESSOR, 医学部, 助教授 (20145296)
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| Research Abstract |
Glioma cells have been shown to produce various molecular forms of platelet-derived growth factor (PDGF) as well as PDGF receptors as constituents of presumed autocrine pathway. This led to the assumption that an autocrine loop consisting of PDGF and its receptor would lend itself to therapeutic interference. We previously reported that trapidil, a PDGF antagonist, inhibits the proliferation of PDGF producing glioma cells in vitro and in vivo. In this study, we attmpted to characterize the effect of trapidil on cell cycle kinetics in order to elucidate its biological mode of action in cycling tumors and on the intracellular transduction pathway to c-fos transcriptional activation via protein kinase C(PKC) activation. Cell cycle analysis showed that cell cycle perturbations induced by trapidil included a decreased transition rate from G_0-G_1 to S phase. Furthermore, we found trapidil affects the intracellular signal transduction pathway PKC activity and c-fos expression after the stimulation by serum containing of the growth factors. On the other hand, suramin, an inhibitor for many kinds of growth factors, showed pleiotrophic actions on the proliferation of glioma cells. At low concentration suramin had a stimulatory effect while at higher concentrations it had an inhibitory effect on the proliferation of glioma cells. Now we are processing a phase II study of trapidil in the treatment of patients with glioma and meningioma.
We have studied the toxicity, intrathecal pharmacokinetics, and therapeutic effect of the ventriculolumbar perfusion of ACNU against subarachnoid dissemination of tumor cells and established a new, safe and feasible treatment against subarachnoid dissemination of gliomas.
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