| Project/Area Number |
09671094
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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 |
Hematology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MAEKAWA Taira The Institute of Medical Science, The University of Tokyo, Assistant Professor, 医科学研究所, 講師 (80229286)
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Akira Kyoto Institute of Technology, Professor, 繊維学部, 教授 (60210001)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | antisense / hematological malignancy / leukemia / gene rearrangement / cell therapy |
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| Research Abstract |
In this research project, we have clarified followings concerning the mechanism of suppression of the proliferation of human leukemic cells by antisense oligodeoxynucleotides (AS ODN) for rearranged and over-expressed oncogenes.
1) BCR-ABL AS ODN could effectively suppress the proliferation of chronic myeloid leukemia (CML) cells by the induction of apoptosis of these leukemia cells. c-myc AS ODN could inhibit the proliferation of human leukemia cells HL6O, and the abrupt up-regulation of number of leukemia cells in G_1/S boundary. c-myc AS ODN also inhibited the proliferation of synovial cells from patients with rheumatoid arthritits and induced the apoptosis through Fas/Fas ligand system.
2) We have established the synthesis and purification methods of AS ODN with chimeric backbone structure of phosphorothioate and phosphodiester linkages. The first three linkages of both 5'- and 3'-end are synthesized by phosphorothioate chemistry. We have shown these chimeric analogues were resistant to the degradation by nuclease.
3) The above chimeric analogue have much less non-specific effects or aptamer effects that are often encountered when AS ODNs with all-phosphorothioate linkages are used.
4) We have shown that AS ODNs with chimeric backbones against Bcl-2, c-myc, erythropoietin receptor, and stromal-derived factor 1 effectively work as functional antisense molecules, and we have found the novel target antisense sequence to reduce the Bcl-2 expression.
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