| Budget Amount *help |
¥3,750,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥450,000)
Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2008: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
In microglia, peripheral benzodiazepine receptor (PBR) is expressed from the earliest stages of activation and appears to exert a pro-inflammatory function. This molecule is commonly up-regulated in inflammatory, degenerative, infective and ischemic lesions of the central nervous system but it has never been reported in glioma-infiltrating microglia. We examined anaplastic astrocytomas showing minimal contrast-enhancement and therefore little damage of the blood brain barrier to minimize the presence of blood borne macrophages within tumor tissue. The lesions were studied in vivo using positron emission tomography (PET) with the specific PBR ligand [^<11>C](R)-PK11195 and the corresponding tumor tissue was investigated with an anti-PBR antibody. Glioma-infiltrating microglia were characterized for molecules involved in antigen presentation and cytotoxic activity. PET studies showed that [^<11>C](R)-PK11195 binding was markedly lower in tumors than in the contralateral grey matter. Pathological investigation revealed that glioma-infiltrating microglia failed to express PBR and cytotoxic molecules although some cells still expressed antigen presenting molecules. Evaluation of microarray datasets confirmed these differences. Our results demonstrated PBR suppression in glioma-infiltrating microglia and suggested that PBR may have a relevant role in modulating the anti-tumour inflammatory response in astrocytic tumors.
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