1995 Fiscal Year Final Research Report Summary
Reversal of multidrug resistance using mdrl antisense DNA on blasts cells in acute myelogenous leukemia.
| Project/Area Number |
06671114
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Tokyo Women's Medical College |
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Principal Investigator |
MOTOJI Toshiko Tokyo Women's Medical College, Department of Hematology, assistant professor, 医学部, 講師 (00101808)
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| Co-Investigator(Kenkyū-buntansha) |
MORI Naoki Tokyo Women's Medical College, Department of Hematology, M.D., 医学部, 助手 (20241078)
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| Project Period (FY) |
1994 – 1995
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| Keywords | multidrug resistance / antisense / Acute myelogenous leukemia |
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| Research Abstract |
Over expression of multidrug resistance (MDR) gene mdrl, and p-glycoprotein which is the product of mdrl is considered to be main cause for treatment failure in acute myelogenous leukemia. To reverse MDR,mdrl antisense DNA was synthetized and treated to multidrug resistance human leukemia cell line K562/ADM and multidrug resistance leukemia blast cells taken from patients with acute myelogenous leukemia (AML). Antisense DNA used was 24 mer phosphorothioate type, and encapsulated with lipopolyamine. The positivity of p-glycoprotein by fluorescence microscopy and flow cytometry on K562/ADM and AML blast cells apparently reduced by the addition of antisense DNA.The reduction of p-glycoprotein posotivity was dose-dependent of antisense DNA,and the maximam suppression were obtained with 20 uM in K562/ADM and 2,5 uM in AML blast cells. This suppression of p-glycoprotein was specific by antisense DNA,and was not observed by sense DNA and random control DNA.Inrement of dauorubicin accumulation and retetion of K562/ADM and AML blast cells were observed by antisense DNA.These results suggest promising possibility using antisense DNA in the future treatment of AML.
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