Project/Area Number |
16390411
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Cerebral neurosurgery
|
Research Institution | Kochi University |
Principal Investigator |
SHIMIZU Keiji Kochi Medical School, Dept.of Neurosurgery, Professor, 医学部, 教授 (50162699)
|
Co-Investigator(Kenkyū-buntansha) |
PARK Kae chang Kochi Meidical School Hospital, Dept.of Neurosurgery, Assistant Professor, 医学部附属病院, 講師 (60333514)
YAMADA Shoko Kochi Meidical School Hospital, Dept.of Neurosurgery, Assistant Professor, 医学部附属病院, 講師 (60287761)
IKENAKA Kazuhiro National Institutes of Natural Sciences, National Institute for Physiological Sciences, Professor, 生理学研究所, 教授 (00144527)
YAWATA Toshio Kochi Meidical School, Dept.of Neurosurgery, Research Associate, 医学部, 助手 (40380323)
土屋 孝弘 高知大学, 医学部, 助手 (60346715)
|
Project Period (FY) |
2004 – 2006
|
Project Status |
Completed (Fiscal Year 2006)
|
Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2006: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2005: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥6,400,000 (Direct Cost: ¥6,400,000)
|
Keywords | Glioblastoma / Retrovirus Vecter / Promoter / Gene Therapy / MAGE-D4 / Integrin α3 / Embryonic Stem Cell / Microglia / MAGE-E1 |
Research Abstract |
For more than 10 years, we have made some fundamental studies on brain-specific gene therapy controlled suicide gene (Herpes Simplex Virus thymidine kinase; HSV tK) with promoter expressed Myelin basic protein (MBP) gene. As these malignant gliomas show high or low MBP-expressed gene, we search a new high-titer glioma-specific gene therapy by using some new retroviral vectors transduced promoter expressing MAGE-D4 gene (Cancer Res 61: 4809-4814, 2001; Gene 277: 129-137, 2001), or other genes. And also selectively gene-inserted retroviral vectors are on-going. As most malignant brain tumors, glioblastomas multiforme (GBM) express Olig2 transcription factors in the very high level, they may be induced by distraction of Olig2-down-regulated differentiation cascade. Therefore, we start in investigate a new therapeutic strategy, which we can restore to the very high differentiated stage from the undifferentiated GBM by transduction of Olig2-down-regulated factors. The monoclonal antibody ONS-M21 recognizes an antigen, which is integrin □3, found on the surface of some gliomas (Br J Cancer 68: 831-837, 1993; Br J Cancer 79: 333-339, 1999). Then, we explore the correlation between integrin □3 expression and MAGE-D4 gene appearance in glioma patients. We had already published about Cystatin C, CDC25B and RCAS1 expressions in gliomas. Besides, we begin to investigate new immuno-cytotherapy by using migration activities of microglia induced from mouse embryonic stem cells.
|