| Co-Investigator(Kenkyū-buntansha) |
MIHARA Yosuke Kumamoto Univ. Hospital, Instructor Neurosrugery, 医学部・附属病院, 助手 (60209848)
KOCHI Masato Kumamoto Univ. Hospital, Instructor Neurosurgery, 医学部・附属病院, 助手 (70178218)
NAGAHIRO Shinji Kumamoto Univ. Hospital, Lecturer Neurosurgery, 医学部・附属病院, 講師 (60145315)
KURATSU Jun-ichi Kumamoto Univ. Med. Sch., Lecturer Neurosurgery, 医学部, 講師 (20145296)
UEMURA Shozaburo Kumamoto Univ. Med. Sch., Associate Professor Neurosurgery, 医学部, 助教授 (00128258)
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| Research Abstract |
Chemotherapy against malignant glioma is not still satisfactory. We need the exploitation of new drugs, methods of administration and the combined treatment with other adjuvants against gliomas which are resistant to ACNU. We examined the antiproliferative effect of YM881, which is coupled with Neocarzinostatin and copolymer, and MX-2, Which is a new morpholinoanthoracycline drug, on the ACNU-resistant glioma cells in vitro and in vivo. Early phase II studies are in progress at present.
We have demonstrated that cultured human glioma cell line U251MG produce Platelet-derived growth factor (PDGF) and U105MG cells do not produce PDGF. We also clarified that the growth of U251MG cells depend on PDGF and that Trapidil, a PDGF antagonist, can inhibit the proliferation of U251MG cells in vitro. With frow cytometric study, we found that Trapidil are capable of influencing the transition of a PDGF-dependent glioma cell line from G_0-G_1 to G_2-M. We also clarified that the growth of U251MG glioma transplanted in subcutaneous tissue of nude mouse was inhibited by the repeated intraperitoneal administration of Trapidil. We assume Trapidil is effective in the treatment of glioma.
Patients with intrathecal dissemination of glioma is increasing in number, however, no effective treatment is available at present. Therefore we studied toxicity and pharmacokinetics of intrathecal perfusion of ACNU and proved that perfusion could achieve wide distribution of ACNU in the subarachnoid space at the effective level of concentration and that it is not toxic. We performed phase I and early phase II studies of this treatment and further study of this treatment has been warranted.
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