NOVEL CYTOKINE-LIKE ACTIVITY OF SERUM NM23 PROTEINS
| Project/Area Number |
15591033
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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 | SAITAMA CANCER CENTER |
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Principal Investigator |
KADO Junko SAITAMA CANCER CENTER, RESEARCH INSTITUTE FOR CLINICAL ONCOLOGY, CHIEF RESEARCHER, 臨床腫瘍研究所, 専門研究員 (30161136)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Cancer / Protein / Phisiological activity / Ezpression regulation / Nm23 / Cytokine / Serum diagnosis / Prognostic factor / NM23蛋白質 / 白血病細胞 / 単球 / 増殖 / 生存 |
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| Research Abstract |
Overexpression of the nm23 gene that is found in many hematological malignancies, predicts poor treatment outcome, and the elevated serum level of NM23-H1 protein is also a poor prognostic factor in patients with the diseases. We hypothesize that the extracellular NM23-H1 proteins secreted from tumor cells may positively affect tumor cells as an autocrine growth factor or negatively affect normal immune cells, like some cytokines. In this study, we focused on the role of extracellular NM23-H1 protein derived from tumor cells.
1)Effects of exracellular NM23 proteins on normal peripheral blood mononuclear cells (PBMNC)
Exogenously added NM23-H1 protein inhibited the survival of normal PBMNC but not normal endotherial cells. It inhibited the survival of adherent PBMNC (mainly CD68-positive monocytes) at the concentrations, which were detected in serum of patients with malignant hematological neoplasm. Exogenously added NM23-H1 protein also modulated the cytokine expression patterns of PBMNC. These results suggest that the inhibitory effect of NM23-H1 protein on normal monocytes may be associated with a poor prognosis of hematological malignancies.
2)Effects of exracellular NM23 proteins on acute myeloid leukemia (AML) cells
Exogenously added NM23-H1 protein promoted the growth/survival of primary cultured human AML cells. It also induced various cytokines and chemokines in primary cultured AML cells. Some cytokine antibodies inhibited the NM23-stimulated growth/survival of AML cells. These results suggest that the effect of extracellular NM23 protein is mediated by the induction of some cytokines.
The activities of extracellular NM23 protein on tumor cells and normal PBMNC might contribute to the poor outcome of patients with elevated serum levels of NM23-H1 protein.
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Report
(4 results)
Research Products
(22 results)
