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)

Five patients with resistant non-Hodgkin lymphoma (NHL) were given granulocyte-macrophage colony-stimulating factor (GM-CSF, 250 micrograms/m2 daily) after the BEAM pretransplant chemotherapy regimen (carmustine 300 mg/m2, etoposide 1.2 g/m2, cytarabine 800 mg/m2, melphalan 140 mg/m2) because persistent lymphoma cell infiltration of the bone marrow precluded autologous bone-marrow transplantation (BMT). In three patients full haemopoietic reconstitution occurred, with similar kinetics to that seen after autologous BMT. The other two patients died without sustained haemopoietic recovery. GM-CSF may replace autologous BMT in highly selected cases of NHL with progressive disease and bone-marrow involvement.
Lancet 1991 Sep 07
PMID:GM-CSF instead of autologous bone-marrow transplantation after the BEAM regimen. 167 55

Chromosomes of bone marrow cells obtained from nine patients with myelodysplastic syndrome (MDS) were assessed after in vitro co-culture (48 hours culture) with recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), or recombinant human erythropoietin. Three of the nine MDS cases showed no cytogenetic abnormalities with or without any recombinant human hematopoietic growth factors; one MDS patient with a t(3;4) did not show any change in the proportion of cells with this cytogenetic change. The remaining five cases exhibited changes in the frequency of subclones after the treatment. An increasing number of metaphase cells with less complex chromosome abnormalities was observed in two of the five cases by treatment with rhG-CSF; one of them also showed an increasing number of cells with normal karyotypes. After rhGM-CSF treatment, cells with nonclonal hyperdiploid abnormalities appeared in one MDS patient. After erythropoietin treatment, an increasing number of cells with a prototypic change was observed in one MDS patient, whereas one patient showed an increasing number of cells with an additional chromosome abnormality. These observations indicate that hematopoietic growth factors possibly modify the constitution of marrow cells with multiple chromosome abnormalities and the degree is different in each MDS patient. Furthermore, a chromosome analysis using an in vitro culture system with human recombinant hematopoietic growth factors may be able to detect metaphase cells with additional chromosome abnormalities in some MDS patients.
Cancer Genet Cytogenet 1990 Sep
PMID:In vitro cytogenetic effects of recombinant human hematopoietic growth factors on cells derived from myelodysplastic syndromes. 169 82

We have studied the effects of recombinant hematopoietic growth factors, granulocyte-macrophage colony-stimulating factor (GM-CSF) and/or interleukin-3 (IL-3) on the globin program of adult human erythroid progenitors (BFUe) stimulated to terminal differentiation by erythropoietin under fetal bovine serum (FBS)-supplemented or FBS-deprived culture conditions. Fetal globin production by BFUe-derived erythroblasts was assessed at the protein and mRNA level and its cellular distribution was evaluated by immunofluorescence. Although hemoglobinization and maturation of BFUe-derived erythroblasts was by and large comparable in FBS-replete versus FBS-deprived cultures, the latter had significantly less (up to 20-fold) gamma-globin and gamma-globin mRNA levels. Reduced gamma-globin in serum-deprived cultures was also reflected by a smaller proportion of erythroblasts with detectable gamma-globin by immunofluorescence. Erythroid bursts induced by either GM-CSF or IL-3 produced similar levels of gamma-globin both in FBS-supplemented and in FBS-deprived cultures. These results, obtained even in cultures of highly enriched BFUe, suggest that GM-CSF and IL-3, although they significantly increase the number and size of erythroid bursts, do not by themselves exert a direct influence on the level of fetal globin synthesis. By contrast, factor(s) present in FBS appear to exert a dominant influence on fetal globin synthesis in vitro. Although FBS-deprived conditions appear to largely abrogate the in vitro activation of fetal hemoglobin (Hb F) in normal samples, they do support increased Hb F production in samples from patients with hereditary persistence of fetal hemoglobin or from cord blood.
Blood 1990 Sep 15
PMID:Influence of recombinant hematopoietins and of fetal bovine serum on the globin synthetic pattern of human BFUe. 169 99

Adherent cells (AdCs) in blood from normal volunteers produced granulocyte-macrophage (GM) colony-stimulating activity (CSA) in the presence of 10 ng/ml of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in vitro. GM-CSA produced by adherent cells in the presence of GM-CSF reached a plateau level on day 6. Colonies stimulated by adherent cell-conditioned medium (AdC-CM-GM-CSF), which had been harvested after 6 days of incubation of AdCs with rhGM-CSF, were granulocyte predominant. When phagocyte-depleted marrow mononuclear cells (PD-M-MNCs) were cultured with AdC-CM-GM-CSF and anti-rabbit serum against rhGM-CSF, 99% of the colonies on day 7 were exclusively composed of neutrophils. When 2 X 10(4) PD-M-MNCs were cultured in a medium containing AdC-CM-GM-CSF, AdC-CM-GM-CSF + anti-GM-CSF, AdC-CM-GM-CSF + anti-G-CSF, or AdC-CM-GM-CSF + both of the anti-bodies, the PD-M-MNCs formed (mean +/- SD) 100 +/- 2.0%, 64.3 +/- 2.5%, 38.6 +/- 0.4%, and 6.0 +/- 0.4% GM colonies, respectively. Furthermore, northern blot analysis revealed that AdCs incubated with 10 ng/ml of rhGM-CSF for 6 h expressed much more mRNA of G-CSF than those without the CSF. These data indicated that AdCs in blood produce G-CSF in the presence of GM-CSF.
Int J Cell Cloning 1990 Sep
PMID:Human G-CSF produced by adherent cells in the presence of human recombinant GM-CSF. 170 27

In this study, we investigated the role of interleukin-1 beta (IL-1 beta) in the malignant evolution of chronic myelogenous leukemia (CML) and the functional activity of IL-1 inhibitors. Bone marrow (BM) and peripheral blood (PB) low-density cells from 38 CML patients were studied in the colony-forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte colony culture assay. Samples from patients with early stage, interferon-alpha (IFN)-sensitive disease formed hematopoietic colonies in the presence of fetal calf serum (FCS), erythropoietin (Epo), and one of the following: granulocyte-macrophage colony-stimulating factor (10 ng/mL), IL-3 (15 ng/mL), both, or phytohemagglutinin-conditioned medium. The addition of IL-1 beta augmented IFN-sensitive CML colony growth in a dose-dependent manner at concentrations of 10 to 100 U/mL. In sharp contrast, addition of the above growth factors did not augment the colony growth-promoting effect of FCS and Epo in samples from IFN-resistant patients; further, adherent cell fractionation or T-lymphocyte depletion attenuated the "autonomous" colony growth. Lysates of 2.5 x 10(7) low-density cells from each of six IFN-resistant and six IFN-sensitive CML patients and three normal volunteers were tested for intrinsic IL-1 beta content in an enzyme-linked immunosorbent assay and yielded a mean of 610 pg, 54.6 pg, and 49.4 pg of IL-1 beta, respectively (P less than .045). Interestingly, both soluble IL-1 receptors (sIL-1R) and IL-1 receptor antagonist (IL-1RA) at concentrations of 5 to 100 ng/mL (sIL-1R) and 10 to 500 ng/mL (IL-1RA) inhibited CML colony growth in a dose-dependent fashion, with maximal inhibition of 64% and 65%, respectively. A similar effect was noted with the use of anti-IL-1 beta neutralizing antibodies. These data implicate IL-1 beta in CML disease progression and suggest that the inhibitory effects of molecules such as sIL-1R and IL-1RA could conceivably be the basis of a novel therapeutic strategy against this disorder.
Blood 1991 Sep 15
PMID:Suppression of chronic myelogenous leukemia colony growth by interleukin-1 (IL-1) receptor antagonist and soluble IL-1 receptors: a novel application for inhibitors of IL-1 activity. 171 91

Human recombinant interleukin-4 (IL-4) was studied for its effects on the expression of granulocyte-colony stimulating factor (G-CSF) mRNA in human adherent monocytes in the absence and presence of endotoxin and interleukin 1 (IL-1). IL-4 (15 ng/ml) did not induce G-CSF transcripts in monocytes but suppressed the endotoxin-induced G-CSF expression when added simultaneously. Sequential treatment of monocytes with IL-4 followed by endotoxin suppressed G-CSF mRNA induction totally. This effect was independent of the presence of fetal bovine serum but dependent of the IL-4 dose. Comparable results were obtained with IL-1. IL-1 (50 U/ml) induced G-CSF expression in human adherent monocytes which could be counteracted by IL-4 pretreatment. In addition, it was shown that the induction of G-CSF mRNA by the calcium-ionophore A23187 or by c-AMP elevating agents could be blocked by IL-4. These suppressive effects of IL-4 were not related to changes in the half-life of G-CSF mRNA and were independent of protein synthesis. Finally it was demonstrated that IL-4 had comparable effects on the G-CSF secretion of endotoxin and IL-1 stimulated human monocytes by using a murine bone marrow assay. These results indicate that IL-4 down-regulates the expression of G-CSF gene and secretion of proteins in human activated monocytes.
Br J Haematol 1991 Sep
PMID:Interleukin-4 prevents the induction of G-CSF mRNA in human adherent monocytes in response to endotoxin and IL-1 stimulation. 171 62

Human hematopoietic cells can be maintained in vitro for many weeks in the absence of exogenously provided hematopoietic growth factors if an adequate stromal cell containing adherent layer is present. We have now extended the use of this type of long-term culture (LTC) system to create a model of perturbed hematopoiesis in which human tumor cells that constitutively produce a variety of factors are co-cultured together with normal human marrow cells. In the present study, we used the human bladder carcinoma cell line (5637) because these cells were known to produce not only a variety of factors active directly on hematopoietic cells but also factors that can stimulate hematopoietic growth factor production by human marrow stromal cells. Analysis of mRNA extracted from the adherent layer and measurement of growth factor bioactivity in the medium of established LTC of human marrow containing irradiated 5637 cells, showed increased levels of interleukin-1 and -6, as well as granulocyte and granulocyte-macrophage colony-stimulating factor production by comparison to control cultures. As in normal cultures, high proliferative potential clonogenic hematopoietic cells were found almost exclusively in the adherent layer of these co-cultures, but these primitive cells were maintained in a state of continuous turnover, in contrast to control cultures where the same cell types showed the expected oscillation between a quiescent and a proliferating state following each weekly change of the medium. A similar perturbation of primitive progenitor cycling was achieved by adding medium conditioned by 5637 cells twice a week to otherwise normal LTC. The presence of irradiated 5637 cells in the LTC or the addition of 5637 conditioned medium also resulted in modest (2- to 3-fold) but sustained increases in the total hematopoietic progenitor population, as well as in the final output of terminally differentiated granulocytes and macrophages. These findings indicate that primitive hematopoietic cells in LTC can be kept in a state of continuous activation for many weeks by appropriate endogenous or exogenous hematopoietic growth factor provision and that this does not necessarily lead either to their rapid exhaustion or to a large amplification in output of mature progeny.
J Cell Physiol 1991 Sep
PMID:Continuous activation of primitive hematopoietic cells in long-term human marrow cultures containing irradiated tumor cells. 171 96

We studied the effect of transforming growth factor-beta 1 (TGF-beta 1) on colony formation of leukemic blast progenitors from ten acute myeloblastic leukemia (AML) patients stimulated with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), interleukin-6 (IL-6), or interleukin-1 beta (IL-1 beta). These CSFs and interleukins by themselves stimulated the proliferation of leukemic blast progenitors without adding TGF-beta 1. G-CSF, GM-CSF, and IL-3 stimulated blast colony formation in nine patients, IL-6 stimulated it in five, and IL-1 beta stimulated in four. TGF-beta 1 significantly reduced blast colony formation stimulated by G-CSF, GM-CSF, or IL-6 in all patients. In contrast, TGF-beta 1 enhanced the stimulatory effect of IL-3 on blast progenitors from three cases, while in the other seven patients TGF-beta 1 reduced blast colony formation in the presence of IL-3. To study the mechanism by which TGF-beta 1 enhanced the stimulatory effect of IL-3 on blast progenitors, we carried out the following experiments in the three patients in which it occurred. First, the media conditioned by leukemic cells in the presence of TGF-beta 1 stimulated the growth of leukemic blast progenitors, but such effect was completely abolished by anti-IL-1 beta antibody. Second, the addition of IL-1 beta in the culture significantly enhanced the growth of blast progenitors stimulated with IL-3. Third, leukemic cells of the two patients studied were revealed to secrete IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) constitutively; the production by leukemic cells of IL-1 beta and TNF-alpha was significantly promoted by TGF-beta 1. Furthermore, the growth enhancing effect of TGF-beta 1 in the presence of IL-3 was fully neutralized by anti-IL-1 beta antibody. These findings suggest that TGF-beta 1 stimulated the growth of blast progenitors through the production and secretion of IL-1 beta by leukemic cells.
J Cell Physiol 1991 Sep
PMID:Enhancement by transforming growth factor-beta 1 (TGF-beta 1) of the proliferation of leukemic blast progenitors stimulated with IL-3. 171 97

The effects of the inhibitor for protein kinase A or C, or tyrosine kinase (H-8, staurosporine, or genistein, respectively) on the proliferation of leukemic and normal bone marrow cells stimulated by granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), or interleukin-3 (IL-3) were studied using the MTT assay. These inhibitors suppressed the proliferation of leukemic and normal bone marrow cells in a dose-dependent manner. Although the suppressive effect of each inhibitor on cell proliferation was varied in each instance, the effects were almost similar whichever CSF was added. A significant difference was not recognized between leukemic and normal bone marrow cells in terms of sensitivity to these inhibitors. The data indicate that protein kinase inhibitors have an inhibitory effect on leukemic and normal hematopoietic cell proliferation and that further studies are required to determine if this effect is due to the inhibition of protein kinases acting as the second messenger of CSFs.
Leukemia 1991 Sep
PMID:Effect of protein kinase inhibitors on the proliferation of leukemic cells stimulated by granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor or interleukin-3. 171 9

Colony-stimulating factors (CSF) are being increasingly used to accelerate hematopoietic recovery after bone marrow transplantation. To study the endogenous serum levels of CSF in bone marrow transplanted patients we have used immunoassays measuring granulocyte-macrophage colony-stimulating factor (GM-CSF) with a sensitivity of 0.10 ng/ml and granulocyte colony-stimulating factor (G-CSF) with a sensitivity of 0.05 ng/ml. Serum samples, taken from the conditioning treatment until engraftment, were analysed in 13 patients receiving allogeneic transplants and in eight patients receiving autologous transplants. Ten patients had acute myeloid leukemia, seven acute lymphoblastic leukemia, one acute undifferentiated leukemia, two non-Hodgkin's lymphoma and one multiple myeloma. Samples were taken 1-2 times before transplantation and 1-2 times per week after transplantation (median of 46 days in allotransplant recipients and 32 days in autotransplant recipients); 17% of the allogeneic transplanted patients and 35% of the autologous transplanted patients had detectable levels of G-CSF. In both types of transplantation the G-CSF concentrations were low: median 0.06 (range 0.05-0.14) and 0.08 (range 0.05-0.40) ng/ml respectively. GM-CSF was detected only in one analysed sample in all patients. There was no evidence of increased CSF levels related to engraftment or documented infections.
Bone Marrow Transplant 1991 Sep
PMID:Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in serum in bone marrow transplanted patients. 172 Mar 39


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