Project/Area Number |
04454246
|
Research Category |
Grant-in-Aid for General Scientific Research (B)
|
Allocation Type | Single-year Grants |
Research Field |
Gastroenterology
|
Research Institution | Keio University |
Principal Investigator |
SAITO Hidetsugu Keio Univ., School of Med., Assist.Prof., 医学部, 講師 (80186949)
|
Co-Investigator(Kenkyū-buntansha) |
KUROSE Iwao Keio Univ., School of Med., Instructor, 医学部, 助手 (50234604)
TSUNEMATSU Satoshi Keio Univ., School of Med., Instructor, 医学部, 助手 (80217356)
|
Project Period (FY) |
1992 – 1994
|
Project Status |
Completed (Fiscal Year 1994)
|
Budget Amount *help |
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1992: ¥4,800,000 (Direct Cost: ¥4,800,000)
|
Keywords | hepatoma / differentiation / sodium butyrate / liver-specific antigen / laminin / lymphokine activated killer / nude mouse / 肝癌細胞 / 分化 / 分化誘導剤 / 細胞接着分子 / 細胞骨格蛋白 / LAK感受性 |
Research Abstract |
The possibility of induction of cellular differentiation in human hepatoma cells were investigated. Among the agents investigated, sodium butyrate (SB) is the most possible agent to differentiate human hepatoma cell lines, HCC-T and HCC M.The cell growth, anchorage-dependency and transplantability into a nude mouse of HCC-T and HCC-M were significantly inhibited by SB treatment. The RNA expression of albumin was increased, that of alphafetoprotein was decreased and that of myc was decreased by SB.Some antigen expressions on these cells were changed by SB.The liver-specific antigen which is detected by a mouse monoclonal antibody (H2) was significantly increased by SB treatment. The expression of laminin and fibronectin was significantly decreased and lymphokine-activated killer(LAK)sensitivity was decreased according to the decrease of laminin expression. The decrease of LAK sensitivity was abrogated by anti-laminin. The changes of calcium influx and DNA could not be detected by available instruments. SB did not decrease mitochondrial function and did not induce apoptosis in HCC-T and HCC-M.The in vivo administration of SB (50 mg X 3/nude mouse/w) did not decrease tumor size of transplanted HCC-M cells, although some histological shange was suggested. These results indicate that solid tumors such as hepatoma could be differentiated by SB.SB-treated hepatoma cells functionally came near to hepatocytes and some antigenic shange was induced.
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