| Co-Investigator(Kenkyū-buntansha) |
TAKESHIMA Hideo KUMAMOTO UNIV., of SCH.MED INSTRACTORE, 医学部, 助手 (70244134)
NISHI Tohru KUMAMOTO UNIV., HOSPital INSTRACTORE, 医学部・附属病院, 助手 (00264309)
HAMADA Junichiro KUMAMOTO UNIV., HOSPital INSTRACTORE, 医学部・附属病院, 助手 (40253752)
KURATSU Junichi KUMAMOTO UNIV., of SCH.MED ASSOCIATE PROFESSOR, 医学部, 助教授 (20145296)
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| Research Abstract |
we previously reported that Trapidil, a Platelet-derived growth factor (PDGF) antagonist, could inhibit the proliferation of the PDGF-dependent glioma cells in vitro and in vivo. In this term, we found that Trapidil inhibited the Protein kinase C (PKC) dependent signal transduction pathway in the glioma cells and induced the differentaition of glioma cells. Meanwhile, the low concentration of Suramin, one of the growth factor antagonist, stimulated the activity of mitogen activated protein (MAP) kinase and the proloferation of the glioma cells.
In addition, we previously reported the glioma cells produced monocyte chemoattractant protein-1 (MCP-1) which had an important role on the macrophage infilitration in the glioma tissue. In this term we demonstrated that PDGF antagonist inhibited the peoduction of MCP-1 in glioma cells. We are going to elucidate how the growth factors regulate the immune response of glioma cells.
The previous our data that excessive expression of MCP-1 in tumor cell can inhibit tumor growth in vivo indicate the MCP-1 gene may be used for gene therapy of brain tumor. We have invunted an novel gene transfer method by conbining in vivo electropration and intraarterial plasmid DNA injection. We could successfully transfer expression plasmid encoding for MCP-1 cDNA.
Neurofibromatosis (NF) -1,2 proteins may play an important role on the tumorigenesis of certain types of brain tumor as a tumor suppressor gene. We generated the specific antibodies against NF1 or NF2 and found that the cellualr protein designated as p85 bound to NF2 protein and that these interaction seemed important for the tumor suppression. Further study for purification and molecular analysis is scheduled.
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