| Project/Area Number |
13670836
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Kyorin University |
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Principal Investigator |
BESSHO Fumio KYORIN UNIVERSITY, DEPARTMENT of PEDIATRICS, PROFESSOR, 医学部, 教授 (40010285)
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| Co-Investigator(Kenkyū-buntansha) |
ENDOU Hitoshi KYORIN UNIVERSITY, DEPARTMENT of PHARMACOLOGY, PROFESSOR, 医学部, 教授 (20101115)
KANAI Katsuyoshi KYORIN UNIVERSITY, DEPARTMENT of PHARMACOLOGY, PROFESSOR, 医学部, 教授 (60204533)
YAN Kunimasa KYORIN UNIVERSITY, DEPARTMENT of PEDIATRICS, ASSOCIATE PROFESSOR, 医学部, 助教授 (70255389)
YOSHINO Hiroshi KYORIN UNIVERSITY, DEPARTMENT of PEDIATRICS, ASSISTANT, 医学部, 助手 (30333032)
宮嶋 伸一郎 杏林大学, 医学部, 助手
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| Project Period (FY) |
2001 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | LAT1 / BCH / inhibitor / bone marrow cells / acute lymphocytic leukemia / acute myeloid leukemia / cell lines / hematopoietic stem cells / 小児白血病 / 4F2hc / アミノ酸トランスポーター / MTTアッセイ / LD50 / 凍結切片 / ウェスタンブロット / 細胞内局在 / ゼラチンカプセル / 抗原特異性 / 抗LAT1モノクローナル抗体 / 倫理委員会 / インフォームドコンセント |
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| Research Abstract |
Expression of LAT1 was investigated for childhood leukemia cell lines and bone marrow cells from children with various kinds of leukemia at the diagnosis and during remission by Western blotting method, fluorescence-labeled antibody method and RT-PCR.
Effect of BCH, one of inhibitors of LAT1, on cell liability was also investigated using MTT assay.
Expression of LAT1 was found for all cell lines and bone marrow cells at diagnosis with all kinds of employed methods. Difference of expression of LAT1 was not observed among investigate leukemic cell lines with various biological natures and bone marrow leukemic cells with different prognoses and different cell types. Expression of LAT1 was also observed some of bone marrow cells during the remission phase.
BCH could reduce liability of leukemic cell lines by dose-dependent manner. However, rate of reduction of liability decreased during increasing dose and LC_<50> could not be obtained by the BCH concentration of above 300 microM.
Above result indicates necessity of stronger inhibitors to treat leukemia. Moreover, LAT1 was expressed on bone marrow cells during the remission. Since LAT1 is known to express on peripheral leukocytes and bone marrow, proliferation of normal bone marrow cells might be inhibited with LAT1 inhibitor. Other inhibitors with higher selectivity may be able to decrease liability more efficiently. Since currently available inhibitors with such characteristics are water insoluble, new inhibitors should be searched. Effects of inhibitors on hematopoietic stem cells are also needed to be tested in further studies.
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