| Project/Area Number |
61571067
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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 |
Biological pharmacy
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| Research Institution | Showa University |
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Principal Investigator |
TAKEDA Ken Showa University, School of Medicine, 医学部, 助教授 (80054013)
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| Co-Investigator(Kenkyū-buntansha) |
IWAMOTO Sanju Showa University, School of Medicine, 医学部, 助手 (50176567)
SAKAGAMI Hiroshi Showa University, School of Medicine, 医学部, 講師 (50138484)
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| Project Period (FY) |
1986 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1988: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1987: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1986: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Human myelogenous leukemic cells / Differentiation inducing factor / Tumor necrosis factor / Interleukin-6 / インターロイキン-6 / インターロイキンー6 |
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| Research Abstract |
Human myelogenous leukemic cells can be induced to differentiate into the monocyte/macrophage pathway by various chemicals and protein inducers called differentiation inducing factors(DIF). However, human DIF has not yet been well characterized. We have tried to purified DIFs from eadia conditioned by PHA-stimulated lymphocytes and fibroblasts in this project.
We have succeeded to purify a DIF homogeneity from lymphocyte conditioned medium. The purified DIF has a relative molecular mass of approximately 17,000, with an NH_2-terminal sequence the same as that of human tumor necrosis factor(TNF). We have also succeeded to purigy a fibroblast-derived differentiation inducing factor(F-DIF) from medium conditioned by a human fibroblast cell line(WI-26VA4). The purified DIF had a molecular weight of about 27,000 determined by SDS-PAGE, with an HN_2-terminal sequence the same as that of human interleukin-6(IL-6) except for the absence of the N-terminal proline. F-DIF synergistically induced differentiation of human myelogenous leukemic cell lines when combined with TNF.
F-DIF synergistically enhanced the differentiation of human myelogenous leukemic cell lines when combined with TNF. TNF and IL-6 synergistically enhanced the differentiation in combination with other biological response modifiers such as prostaglendin E_2, retinoic acid, vitamid D_3, interferon- , etc.
The results presented in this project point to another new biological effects of TNF and IL-6. This could be one of the regulatory signals that control cellular reactions during infection. Combination use of cytokines and BRM may play in effecting terminal differentiation of the clinical leukemias.
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