Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new serum-free culture (SFC) system for human AML-CFU was established and the colony-promoting activity of four recombinant human hematopoietic growth factors (rhHGFs) including granulocyte-macrophage colony-stimulating factor (rhGM-CSF), interleukin-3 (rhIL-3), erythropoietin (rhEPO) and newly developed stem cell factor (rhSCF) were investigated in this SFC system. Under the orthogonal design condition, it was found that human AML-CFU presented optimal clonal growth in an environment of bovine serum albumin (0.6%), saturated human transferrin (2 x 10(-6) mol/L), cholesterol (2.8 micrograms/ml), bovine insulin (15 micrograms/ml), bovine hemin (0.05 mmol/L), linoleic acid (2.8 micrograms/ml), and IMDM. Spontaneously growing colonies were observed in 11 out of 14 cases studied. The plating efficiencies obtained by culturing with rhGM-CSF, rhIL-3, and rhSCF were 0.776 +/- 0.621%, 0.574 +/- 0.510%, and 0.647 +/- 0.543% (mean +/- s), respectively. There was one case (M3b) showing no response to all HGFs in both SFC ad SCC. The clonal growth of AML-CFU obtained from peripheral blood of the patient with M6 was unexpectedly marked. As a whole, the newly designed SFC system has been demonstrated to be useful for culture of human AML-CFU from both bone marrow and peripheral blood.
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PMID:A newly developed serum-free culture system: clonal growth of human acute myelogeneous leukemia (AML) progenitors--a report of 14 AML cases. 780 5

We demonstrated recently that constitutive expression of proinflammatory cytokines interleukin (IL)-1alpha, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor in head and neck squamous cell carcinoma is correlated with activation of transcription factor nuclear factor (NF)-kappaB/Rel A (p50/p65), which binds the promoter region within each of the genes encoding this repertoire of cytokines. NF-kappaB can be activated after signal-dependent phosphorylation and degradation of inhibitor-kappaBalpha and has been reported to promote cell survival and growth. In the present study, we expressed a phosphorylation site mutant of inhibitor-kappaBalpha (IkappaBalphaM) in head and neck squamous cell carcinoma lines UM-SCC-9, -11B, and -38 to determine the effect of inhibition of NF-kappaB on cytokine expression, cell survival in vitro, and growth in vivo. After transfection with IKBalphaM, only a few UM-SCC-9 clones were obtained that stably expressed the mutant IkappaB, suggesting that expression of a mutant IkappaBalpha may affect survival of the transfected UM-SCC cell lines. After cotransfection of IkappaBalphaM with a Lac-Z reporter, we found that the number of surviving beta-galactosidase-positive cells in the three cell lines was reduced by 70-90% when compared with controls transfected with vector lacking the insert. In UM-SCC-9 cells that stably expressed IkappaBalphaM, inhibition of constitutive and tumor necrosis factor-a induced NF-kappaB activation, and production of all four cytokines was observed. Although UM-SCC-9 IkappaBalphaM-transfected cells proliferated at the same rate as vector-transfected cells in vitro, a significant reduction in growth of tumor xenografts was observed in SCID mice in vivo. The decreased growth of UM-SCC-9 IkappaBalphaM-transfected tumor cells accompanied decreased immunohistochemical detection of the activated form of NF-kappaB in situ. These results provide evidence that NF-KB and IkappaBalpha play an important role in survival, constitutive and inducible expression of proinflammatory cytokines, and growth of squamous cell carcinoma. NF-kappaB could serve as a potential target for therapeutic intervention against cytokine and other immediate-early gene responses that contribute to the survival, growth, and pathogenesis of these cancers.
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PMID:Expression of a dominant-negative mutant inhibitor-kappaBalpha of nuclear factor-kappaB in human head and neck squamous cell carcinoma inhibits survival, proinflammatory cytokine expression, and tumor growth in vivo. 1041 12