| Project/Area Number |
15390446
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Hyogo College of Medicine |
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Principal Investigator |
ARITA Norio Hyogo College of Medicine, Faculty of Medicine, Professor, 医学部, 教授 (80159508)
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| Co-Investigator(Kenkyū-buntansha) |
IKEMOTO Hideyasu Hyogo College of Medicine, Faculty of Medicine, Assistant Professor, 医学部, 講師 (30278824)
MORI Kanji Hyogo College of Medicine, Faculty of Medicine, Research Associate, 医学部, 助手 (50360269)
KANEMURA Yonehiro Osaka National Hospital, National Hospital Organization, Institute for Clinical Research, Researcher, 臨床研究部・政策医療基盤技術開発研究室, 研究室員 (80344175)
FUJITA Shigekazu Hyogo College of Medicine, Faculty of Medicine, Research Associate, 医学部, 助手 (80388826)
中野 敦久 兵庫医科大学, 医学部, 助手 (70258151)
田村 和義 兵庫医科大学, 医学部, 講師 (40340971)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2005: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2004: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2003: ¥4,800,000 (Direct Cost: ¥4,800,000)
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| Keywords | brain tumor / lymphoma / chemotherapy / central nervous system / methotrexate |
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| Research Abstract |
Investigation of cultured cell line
We established a cell line from the surgical specimen of a PCNSL patient and characterized it. The population doubling time of the cultured cell was twenty hours. Using immunocytochemistry, we revealed that these cells expressed LCA, L26 and Bc16. But UCHL was negartive. These results showed this cell line was compared to lymphocytes derived from the germinal center. To investigate whether it could differentiate to neural cells, we cultured it under the addition of the retinoic acid to the medium. As its growth rate decreased, change of its appearance nor the expression of neural cell marker proteins were observed. Then, we studied the response of cells against methotrexate (MTX) and dexamethasone in vitro and analyzed apoptosis by Tunel method. Inhibition dose (ID50) of MTX was 6 nM and ID50 of dexamethasone was 2 nM. Apoptosis was detected after either MTX or dexamethasone treatment. About ten percent of treated cells survived and it suggested the existence of drug resistant cells.
Analysis of correlation between survival time and the expression of Bc16 protein
As it was reported that PCNSL patients live longer if their tumor cells express Bcl6 protein, we analyzed ten surgical cases. The expression of Bcl6 protein was investigated using immunohistochemistry. But no significant correlation between the results of immunohistochemistry and survival time as observed.
In these our research, we could not find the evidence that PCNSL originates from neural precursor cells. For further investigation, novel marker proteins or induction methods of differentiation will be needed. Characters and behavior of the cell line we established were very likely to those observed in clinical patients. We thought this cell line will be useful to clarify the nature of PCNSL and the mechanism of drug resistance.
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