| Project/Area Number |
08407044
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | KUMAMOTO UNIVERSITY |
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Principal Investigator |
USHIO Yukitaka KUMAMOTO UNIV.MED.SCH., PROFESSOR, 医学部, 教授 (20028583)
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| Co-Investigator(Kenkyū-buntansha) |
TAKESHIMA Hideo KUMAMOTO UNIV.MED.SCH., INSTRACTOR, 医学部, 助手 (70244134)
NISHI Tohru KUMAMOTO UNIV.HOSP., INSTRACTOR, 医学部・附属病院, 助手 (00264309)
KOCHI Masato KUMAMOTO UNIV.MED.SCH., PROFESSOR, 医学部, 助教授 (70178218)
KURATSU Jun-ichi KAGOSHIMA UNIV.MED.SCH., PROFESSOR, 医学部, 教授 (20145296)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥25,100,000 (Direct Cost: ¥25,100,000)
Fiscal Year 1998: ¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1997: ¥9,800,000 (Direct Cost: ¥9,800,000)
Fiscal Year 1996: ¥9,600,000 (Direct Cost: ¥9,600,000)
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| Keywords | malignant glioma / MCP-1 / monocyte / MCP-1 receptor / gene therapy / drug delivery / chemotherapy / グリオーマ / CCR2 / ケモカイン / 単球 / リンパ球 / 転写因子 / プロモーター / 脳腫瘍 / マクロファージ / MCP-1レセプター / 免疫 / 遺伝子療法 / サイトカイン / 抗癌剤 / 増殖因子 |
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| Research Abstract |
This study aimed to establish a new specific drug delivery system to malignant gliomas using monocyte chemoattractant protein 1 gene (MCP-1) and manipulated monocytes as drug carriers. We were successful in transfecting MCP-1 gene efficiently into tumor cells of glioma mice by in vivo electroporation and intraarterial plasmid DNA injection (Cancer Res , 1996, Human Cell, 1997). Long lasting expression of MCP-1 protein was obtained in the tumor tissue and accordingly infiltration of a large number of macrophages were observed in the tumor (Cancer Res, 1996, Int J Oncol, 1997, Int Arch Allergy Immunol 1998). We also found that MCP-1 expression was highly enhanced by stimulation with tumor necrosis factor-alpha and interleukin-1beta (Int J Oncol, 1996). In parallel to the above studies we searched the way to enhance the expression of the MCP-1 receptor of monocytes and were able to clear the microbiological mechanism of activation of the MCP-1 receptor (J Biol Chem, 1999). We studied several drugs to be loaded in the monocytes including ACNU that is encapsulated into hybrid liposomes and found the liposome ACNU expresses cytocidal effect against malignant glioma cells (Cancer Res, 1996, J Neuro Oncol, 1998). We were now in the final process integrating these findings toward the clinical trial for the establishment of this unique drug delivery system.
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