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)

The murine myeloproliferative syndrome induced by the myeloproliferative sarcoma virus (MPSV) has numerous similarities to human primary myelofibrosis. We have shown that medium conditioned by spleen cells of MPSV-infected mice has the capacity to support the growth of primitive blast cell colonies. The detection of this activity associated with MPSV infection stimulated us to characterize the hematopoietins responsible for this activity. Northern blot analysis showed a large increase, or induction, of interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage-CSF (CSF-1), and granulocyte-CSF (G-CSF) transcripts in the hematopoietic organs of MPSV-infected mice; however, no IL-3 transcript could be detected in either MPSV-infected or normal mice. Significant levels of IL-1 alpha, IL-6, G-CSF, and CSF-1 bioactivities were found in the serum of MPSV-infected mice, but not in controls. Additionally, analysis of medium conditioned by spleen cells of MPSV-infected mice showed the presence of tumor necrosis factor alpha bioactivity. The increased production of cytokines that are able to stimulate pluripotent hematopoietic stem cells corroborates the hypothesis of a possible involvement of hematopoietic growth factors in the development of some myeloproliferative disorders.
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PMID:Enhanced hematopoietic growth factor production in an experimental myeloproliferative syndrome. 137 44

To investigate whether autoimmunity against thyroid antigens is induced or exacerbated by granulocyte-macrophage colony-stimulating factor, thyroid function and thyroid autoantibodies were studied in 14 patients with advanced breast cancer and 11 with soft-tissue sarcoma who received several cycles of doxorubicin and cyclophosphamide plus GM-CSF 250 micrograms/m2 intravenously daily for 10 days in every 21 day cycle. All patients had normal thyroid function before treatment. In 2 patients with pre-existing thyroid antibodies, thyroid dysfunction developed but disappeared after cessation of GM-CSF. No other autoimmune abnormalities appeared. Stimulation of antigen-presenting cells by GM-CSF may bring about this phenomenon.
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PMID:Reversible thyroid dysfunction during treatment with GM-CSF. 168 46

The expression of granulocyte colony-stimulating factor (G-CSF) mRNA was studied in human non-hematopoietic tumors, including 18 cases of lung cancers 10 cases of stomach cancers, three cases of glioblastomas, and one case each of breast phyllode sarcoma, thyroid cancer, and hepatocellular carcinoma. Northern blot analysis detected G-CSF mRNA in two of the lung cancer cases, in one of the glioblastoma cases, and in both the breast phyllode sarcoma and hepatocellular carcinoma cases. Since G-CSF receptors were not detected on the tumor cells by 125I-G-CSF binding assay, G-CSF autocrine loop are probably not involved in the growth of these G-CSF-producing tumors. Interestingly, granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA was concomitantly expressed in most of these G-CSF-producing tumors. No major gene deletions or rearrangements of G-CSF and GM-CSF genes were demonstrated by Southern blot analysis in the tumors expressing G-CSF and GM-CSF mRNAs except for one of the glioblastomas (G3) in which one chromosome 17 allele was deleted. Although the mechanism of the concomitant expression of G-CSF and GM-CSF mRNA is unknown, relatively high frequency of this phenomenon suggests the presence of common transcriptional factors acting on regulatory regions of G-CSF and GM-CSF genomes.
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PMID:Expression of granulocyte and granulocyte-macrophage colony-stimulating factors by human non-hematopoietic tumor cells. 170 53

We have previously reported on stimulation of clonal growth of cell lines from human solid tumors by recombinant human interleukin 3, recombinant human granulocyte-macrophage colony-stimulating factor, and recombinant human granulocyte colony-stimulating factor (W. E. Berdel et al., Blood, 73: 80-83, 1989; Exp. Hematol., 16: 510, 1988). Within an extensive screening program of hematopoietic growth factor activity on malignant cells, the effects of recombinant human interleukin 6 (rhIL-6) were tested on the growth (tritiated thymidine uptake and human tumor cloning assay) of 26 different human cell lines derived from a wide range of solid tumors (head and neck, 4; lung, 1; pancreatic, 1; gastric, 1; colorectal, 3; renal, 3; bladder, 1; prostate, 1; breast, 2; ovary, 2; choriocarcinoma, 1; sarcoma, 2; glioblastoma, 2; neuroblastoma, 2). rhIL-6 (dose range up to 10(4) IU/ml) caused no reproducible enhancement or inhibition of tritiated thymidine uptake by tumor cell lines from nonhematopoietic origin. Furthermore, 19 of the tumor cell lines were clonogenic in a capillary modification of the human tumor cloning assay. No reproducible stimulation of clonal growth by rhIL-6 was observed in any of the cells tested. Particularly, there was no sensitivity of those cell lines for rhIL-6, which were previously shown to be sensitive for recombinant human interleukin 3 and recombinant human granulocyte-macrophage colony-stimulating factor in this assay. On the other hand, there were no significant growth-inhibitory effects of rhIL-6 on the cell lines tested in this study. Further experiments showed no influence of neutralizing monoclonal anti-hIL-6 antibody on the growth of 3 kidney carcinoma cell lines, making autocrine growth-modulating loops for IL-6 in these lines unlikely. In conclusion, no major interactions between hIL-6 and the growth of the human malignant cell lines from nonhematopoietic origin tested were detected in this study.
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PMID:Studies on the interaction between interleukin 6 and human malignant nonhematopoietic cell lines. 185 4

Tumor-associated macrophages (TAM) represent a population of tissue macrophages with peculiar biological, biochemical and phenotypic properties. Here we have briefly analyzed two different mechanisms involved in the regulation of the levels of TAM: the production of tumor-derived chemotactic factors for mononuclear phagocytes and in situ proliferation of TAM. Two clones selected from the murine sarcoma line B77 showed a different capacity to produce the tumor-derived chemotactic factor known as JE. Studies with these clones demonstrated a correlation between in vitro production of the protein JE, expression of JE mRNA and macrophage content in tumor tissues, suggesting that the production of chemotactic factors can play a role in the regulation of TAM accumulation. Moreover, it has been shown that TAM had high levels of proliferative activity compared to peritoneal exudate macrophages. In an effort to elucidate the mechanisms responsible for the proliferative activity of TAM, the expression of c-fms and macrophage-colony-stimulating factor (M-CSF) was investigated in TAM and sarcoma cells. TAM had high levels of mRNA transcripts of the c-fms protooncogene, which encodes a tyrosine kinase probably identical to the M-CSF receptor, but did not express M-CSF transcripts, while sarcoma cells had high levels of M-CSF mRNA. Sarcoma-cell-conditioned medium had M-CSF activity on bone marrow cells: this activity was blocked by anti-M-CSF antibodies. These findings outline a paracrine circuit in the regulation of TAM proliferation, involving M-CSF secreted by sarcoma cells and acting on c-fms-expressing TAM. A better understanding of the regulation and function of TAM may provide a less empirical basis for a rationale design of therapeutic approaches.
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PMID:The role of macrophages in the regulation of primary tumor growth. 188 19

We investigated the effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) on the pool of circulating hemopoietic progenitor cells in 11 patients with hematological malignancies of nonmyeloid origin and 1 patient with sarcoma. These patients were eligible for autologous blood stem cell transplantation rather than autologous bone marrow transplantation because sufficient marrow aspirates could not be performed due to damage at the usual sites of bone marrow harvest by previous chemo- and/or radiotherapy. Recombinant human GM-CSF was given as continuous i.v. infusion via central venous line for a median time of 11.5 days (range 5-22 days), during which a median number of six aphereses were performed. In comparison to the pretreatment level the median increase in the number of granulocyte-macrophage colony-forming units (CFU-GM)/ml of peripheral blood was 8.5-fold. In all 12 patients a median decrease of the platelet count of 21% (range 7%-67%) was observed during rhuGM-CSF treatment prior to the start of the apheresis procedures. Six patients were treated with a myeloablative conditioning therapy consisting of total body irradiation and/or high-dose polychemotherapy followed by autografting with blood stem cells. Five of them achieved a sustained engraftment. Recombinant human GM-CSF proved to be highly efficient in increasing the number of circulating progenitor cells in these patients with severely compromised hemopoiesis. Blood stem cells harvested under a rhuGM-CSF treatment are capable of restoring hemopoiesis in man after a myeloablative pretransplant therapy.
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PMID:Successful autologous transplantation of blood stem cells mobilized with recombinant human granulocyte-macrophage colony-stimulating factor. 196 9

Hematopoietic recovery from chemotherapy may be associated with an increase in circulating myeloid progenitor cell concentration (CFU-GM); these cells may be harvested by apheresis and used for autologous transplantation after high-dose cytoreductive therapy. Not all patients will demonstrate this increase, possibly due to damage to the stem cell compartment from prior chemoradiotherapy. Elevated circulating CFU-GM has also been reported in patients after short-term administration of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF); whether elevation would persist during longer duration is unknown. We measured circulating CFU-GM (by both limiting dilution in liquid culture and colony formation in semisolid media) in patients with sarcoma who began infusion of rhGM-CSF during recovery from chemotherapy. Patients with elevated circulating CFU-GM did not sustain these levels during subsequent rhGM-CSF infusion. By contrast, patients without rebound elevation of circulating CFU-GM following chemotherapy recovery did increase CFU-GM levels with rhGM-CSF administration. The proportion of marrow CFU-GM in cell cycle during chemotherapy recovery was elevated in both patient groups and remained elevated with rhGM-CSF administration. Both marrow and peripheral blood limiting dilution assays demonstrated linear growth kinetics, indicating a direct effect of the in vitro growth factor (also rhGM-CSF) on progenitor cells without excessive influence or dependence on accessory cells in culture. The use of rhGM-CSF to restore circulating CFU-GM for apheresis during recovery in patients lacking such elevation merits further study.
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PMID:Circulating myeloid progenitor cell kinetics during hematologic recovery from chemotherapy and subsequent recombinant human granulocyte-macrophage colony-stimulating factor administration. 212 81

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a 23-kDa glycoprotein with remarkably diverse effects on immune and nonimmune cells. GM-CSF induces differentiation of granulocyte, macrophage, and eosinophil precursor cells. Proliferation of monocyte-macrophages, T lymphocytes, keratinocytes, and endothelial cells is also stimulated by GM-CSF. In addition, GM-CSF alters the functional properties of mature granulocytes, macrophages, eosinophils, and basophils. GM-CSF is produced by T lymphocytes, macrophages, and several cell types in extramedullary sites, where it may act in a paracrine manner to regulate the local response to antigenic challenge. Clinical trials of GM-CSF have been conducted in patients with AIDS, aplastic anemia, myelodysplastic syndromes, and sarcoma and following bone marrow transplantation and accidental radiation exposure. GM-CSF significantly increased circulating numbers of several myeloid cells and produced dose-dependent toxicity consisting primarily of myalgias, fever, fluid retention, and serosal effusions. Additional studies are needed to define the role of GM-CSF in treatment of patients with qualitative and quantitative dysfunction of immune cells.
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PMID:Granulocyte-macrophage colony-stimulating factor: pleiotropic cytokine with potential clinical usefulness. 240 68

Twenty patients with progressive metastatic solid tumours were entered into a study to evaluate the biological effects and toxicity of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF was given as half-hour intravenous infusions during two 10-day phases of daily treatments (separated by 10 days without GM-CSF) and over a final phase of 20 days of alternate day infusions. Doses were escalated in steps from 0.3 to 60 micrograms kg-1 day-1 between successive patient groups. Significant increases (P less than 0.005) of total leucocyte, neutrophil and eosinophil polymorph counts were seen over the periods of daily infusions (up to four-fold rises of total white count) at dose levels of 10 micrograms kg-1 and above. Counts produced at 30 micrograms kg-1 were significantly higher than at 10 micrograms kg-1 (P less than 0.025). Toxic side effects of GM-CSF included mild transient pyrexias, bone pain and pruritus. The maximum tolerated dose was 60 micrograms kg-1, which produced severe toxicity in 80% of patients. The toxicity at this dose included pericarditis and dyspnoea ascribed to a 'capillary-leak' syndrome. One patient receiving 60 micrograms kg-1 died as a result of a pulmonary embolus. Seven patients with previously rapidly progressive metastatic tumours experienced stabilisation of disease while receiving GM-CSF and one patient with a previously heavily pretreated metastatic soft tissue sarcoma underwent a greater than 50% reduction of tumour volume. Patients undergoing chemotherapy may benefit both from a reduction of the myelosuppressive effects of cytotoxic agents and from an antitumour effect if GM-CSF is incorporated into future regimens.
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PMID:Recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) given as daily short infusions--a phase I dose-toxicity study. 266 7

The present investigation demonstrates that leukoregulin, a cytokine secreted by natural killer (NK) lymphocytes up-regulates the sensitivity of tumor cells to lymphokine-activated killer (LAK) cell cytotoxicity. It has been previously established that leukoregulin increases the sensitivity of sarcoma, carcinoma and leukemia cells to natural killer (NK) cell cytotoxicity. Tumor cells were treated with leukoregulin for 1 h at 37 degrees C and tested for sensitivity to NK and LAK cytotoxicity in a 4-h chromium-release assay. NK-resistant Daudi, QGU and C4-1 human cervical carcinoma cells became sensitive to NK cytotoxicity after leukoregulin treatment, and their sensitivity to LAK was increased two- to sixfold. Y-79 retinoblastoma cells, which are moderately sensitive to NK and very sensitive to LAK, became increasingly sensitive (two- to four-fold) to both NK and LAK cell cytotoxicity. Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF), recombinant interleukin-1 (alpha and beta), recombinant interferon gamma, recombinant tumor necrosis factor or combinations of the latter two failed to up-regulate tumor cell sensitivity to NK and LAK cell cytotoxicity. However, treatment with recombinant interferon gamma for 16-18 h, GM-CSF and interleukin-1 beta for 1 h induced a state of target cell resistance to both NK and LAK cell cytotoxicity. Leukoregulin may have an important physiological function in modulating NK and LAK cell cytotoxicity by increasing the sensitivity of target cells to these natural cellular immunocytotoxicity mechanisms.
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PMID:Leukoregulin up-regulation of tumor cell sensitivity to natural killer and lymphokine-activated killer cell cytotoxicity. 268 71


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