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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)

In early studies, recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) has been found to reduce the depth and duration of granulocytopenia in the settings of cancer chemotherapy and autologous bone marrow transplantation. In patients with myelodysplastic syndrome or aplastic anemia. GM-CSF has produced increased marrow cellularity and marked leukocyte responses, and multilineage effects have been observed in some patients. The available data suggest that the use of GM-CSF in these settings is associated with a decreased incidence of infection as compared with that in historical controls or pretreatment periods and that it may enhance the ability to deliver optimal doses of cancer chemotherapy. Other findings suggest that GM-CSF may be useful in regulating host response to infection when used in combination with antimicrobial therapy in neutropenic patients. However, a precise determination of the ability of this agent to significantly affect patient morbidity or mortality in these various contexts awaits the results of larger, longer-term, randomized, controlled trials.
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PMID:Effects of granulocyte-macrophage colony-stimulating factor in iatrogenic myelosuppression, bone marrow failure, and regulation of host defense. 219 60

One hundred eighty-nine human tumor specimens were tested in a human tumor cloning assay to determine their growth response to human recombinant granulocyte-macrophage colony-stimulating factor. Of these samples 48 were evaluable for response. Growth stimulation to greater than 150% of controls was noted in 1 of 12 lung cancers (8%) and 1 of 14 breast cancers (7%) but in no other instances for an overall rate of 2 of 48 (4.2%). A dose-response effect was not seen with each of the two stimulated samples responding only at the two lowest concentrations tested. In addition, 7 cell lines derived from human tumors were tested using a metabolic CO2 production assay without evidence of growth stimulation. Samples of normal bone marrow displayed the usual dose-dependent stimulation whether grown in agar or assayed metabolically. We conclude that human recombinant granulocyte-macrophage colony-stimulating factor has minimal effect on the growth of the solid tumors tested and that clinical trials to reduce chemotherapy-associated myelo-suppression may proceed without undue concern for enhancement of tumor growth.
Cancer Res 1990 Oct 01
PMID:In vitro assessment of the effects of granulocyte-macrophage colony-stimulating factor on primary human tumors and derived lines. 220 78

We administered Escherichia coli-derived recombinant human granulocyte-macrophage colony-stimulating factor to 61 patients with malignancy, 36 of whom had normal peripheral blood counts and 25 of whom had peripheral cytopenia due to underlying bone marrow disease, to compare the efficacy of two different routes of administration to stimulate the in vivo granulopoiesis: i.e., continuous i.v. infusion and s.c. injection. Three well-tolerated dose levels were investigated. Application of granulocyte-macrophage colony-stimulating factor resulted in dose-dependent increases in circulating neutrophils, eosinophils, and monocytes and an increase in bone marrow cellularity, irrespective of route of administration. In some patients, mild side effects, including bone pain, dyspnea, flu-like symptoms, and a decrease of platelet counts, were recorded, but they were less pronounced when the hormone was administered subcutaneously.
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PMID:Stimulation of granulopoiesis in patients with malignancy by recombinant human granulocyte-macrophage colony-stimulating factor: assessment of two routes of administration. 225 59

We have examined the ability of bryostatin 1 (bryo), an activator of protein kinase C, to induce differentiation of chronic myelogenous leukemia (CML) cells obtained from peripheral blood. Bryo induced a prompt and persistent macrophage-like differentiation, as evidenced by functional, morphological, and immunological criteria. Differentiated cells remained viable for at least 21 days with little change in cell number. CML cell cultures treated in semisolid medium with bryo showed diffuse infiltration with single macrophages, as well as discrete macrophage, mixed, and granulocytic colonies. Supernatants of suspension cultures of bryo-treated CML cells contained granulocyte-macrophage colony-stimulating factor (GM-CSF) by enzyme-linked immunosorbent assay. Furthermore, colony formation could be significantly inhibited by the addition of antibodies to GM-CSF. Prolonged liquid culture of CML cells in bryo reduced colony-forming unit, granulocyte-macrophage content. Bryo-induced differentiation was associated with a decrease in lactoferrin, a marker of granulocyte differentiation, and an increase in both c-fms and interleukin-1 beta RNA, both of which are expressed by monocytes/macrophages. These data demonstrate that bryostatin 1 is capable of inducing macrophage-like differentiation in maturing CML cells. Furthermore, bryostatin induces secretion of GM-CSF by such cells in suspension and semisolid medium and also promotes clonal extinction of granulocyte-macrophage progenitors. Bryostatin may be a possible therapeutic agent for CML.
Cancer Res 1990 Sep 01
PMID:Differentiation and growth modulation of chronic myelogenous leukemia cells by bryostatin. 238 56

A Phase I study of bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was undertaken in 21 patients with advanced malignancy or neutropenia. rhGM-CSF was administered once daily by i.v. bolus injection (0.3 to 3 micrograms/kg/day) or 2-h i.v. infusion (3 to 20 micrograms/kg day) for 10 days. rhGM-CSF at all i.v. doses caused an immediate transient decrease in circulating neutrophils, eosinophils, and monocytes. By 6 h after rhGM-CSF, circulating leukocyte levels were restored. Daily i.v. bolus dosing (0.3 to 3 micrograms/kg/day) did not elevate leukocyte levels except in one neutropenic patient. Daily 2-h i.v. infusions (10 to 20 micrograms/kg/day) caused a dose-dependent leukocytosis with increased levels of neutrophils (up to 4.3-fold), eosinophils (up to 18-fold), and monocytes (up to 3.5-fold). Marrow aspirates showed increased proportions of promyelocytes and myelocytes during rhGM-CSF administration. Retreatment after 10 days without rhGM-CSF resulted in a more marked leukocytosis at doses greater than or equal to 10 micrograms/kg/day. Platelet levels decreased for the first 3 days and then increased during the first course of rhGM-CSF administration. Two patients with chronic lymphocytic leukemia had a transient reduction in lymphocytosis. Serum cholesterol and albumin levels decreased, and vitamin B12 levels increased during rhGM-CSF treatment. At doses of up to 15 micrograms/kg/day, rhGM-CSF was relatively well tolerated by the patients, but adverse effects included bone pain, lethargy, fever, rash, and weight gain. A first dose reaction characterized by hypoxia and hypotension was identified at dose levels greater than or equal to 1 microgram/kg. Dosing i.v. was less potent at inducing a leukocytosis than previously observed for equivalent s.c. doses and was associated with a higher incidence of generalized rash and first dose reactions. The maximal tolerated dose of i.v. rhGM-CSF was 15 micrograms/kg/day. Phase II studies in which the derived effect is to raise leukocyte levels should be undertaken at rhGM-CSF doses of 3 to 15 micrograms/kg/day.
Cancer Res 1990 Feb 01
PMID:Phase I study of intravenously administered bacterially synthesized granulocyte-macrophage colony-stimulating factor and comparison with subcutaneous administration. 240 73

Therapeutically efficacious doses of 131I-antibody result in a loss in circulating white blood cells; the granulocyte population is suppressed by 80-85% and the agranulocytes by 60-65% following 2 mCi of 131I-antibody in hamsters. The administration of 100,000 units of human recombinant interleukin 1 24 h prior to radioantibody can prevent the loss in WBC from 1 mCi of radioantibody and reduce the loss from 2 mCi of antibody. Recombinant murine granulocyte-macrophage colony-stimulating factor is also a potent stimulator of myelopoiesis and may also be useful as a method of reducing radioantibody-induced myelosuppression. The tumor uptake of radioantibody in animals treated with recombinant interleukin 1 is reduced by 30% 1 day after injection of radioantibody but returns to levels seen in animals not treated with the cytokine at 96 and 168 h. Therapeutic efficacy is not compromised by doses of interleukin 1 used to prevent myelosuppression. Therefore, the use of cytokines will permit the use of higher doses of radioantibody for greater tumor therapy with less myelotoxicity than in the absence of cytokine treatments.
Cancer Res 1990 Feb 01
PMID:Use of hematopoietic growth factors to control myelosuppression caused by radioimmunotherapy. 240 78

Febrile reactions often occur in cancer patients given various biological response modifiers such as alpha- or gamma-interferon or interleukin-2. The present studies were undertaken to determine the effects of moderately elevated temperatures (39 degrees C) on various immunological functions related to host defense against malignant cells. The production of the cytokines interleukin-1, interleukin-2, erythroid burst-promoting activity, and granulocyte-macrophage colony-stimulating factor from activated human mononuclear cells was assessed in vitro at 34, 37, and 39 degrees C and found to be reduced at 39 degrees C. The natural killer activity of human mononuclear cells preincubated for 18 h at various temperatures was also significantly reduced (P less than 0.001) at 39 degrees C. Although the addition of recombinant interleukin-1-beta, interleukin-2, and alpha-interferon during the 18-h incubation augmented natural killer activity at all temperatures, the enhancing effects were least apparent at 39 degrees C. Indomethacin increased cytokine-primed natural killer cell activity at all temperatures but did not reverse the inhibitory effects of elevated temperatures. These results suggest that the fever associated with treatment with pyrogenic cytokines may partially offset the direct stimulatory effects of these substances on cellular immune function.
Cancer Res 1986 Dec
PMID:Inhibitory effects of elevated temperature on human cytokine production and natural killer activity. 243 Jun 93

Human granulocyte colony-stimulating factor (hG-CSF) cDNA was cloned, by using a synthetic oligonucleotide probe, from an Okayama-Berg cDNA library of lipopolysaccharide-stimulated human peripheral blood macrophages. The cDNA encodes a polypeptide with an amino acid sequence which completely matches that of the known polypeptide with hG-CSF activity derived from human tumor cell lines. Expression in E. coli of high levels of the protein (about 10% of total cellular proteins) was accomplished under control of the trp promoter, and the purified protein was proved to have hG-CSF activity. Our data provide evidence that human peripheral blood macrophages do produce hG-CSF mRNA when stimulated exogenously, suggesting they are the producer of naturally occurring hG-CSF.
Jpn J Cancer Res 1987 Nov
PMID:Cloning of granulocyte colony-stimulating factor cDNA from human macrophages and its expression in Escherichia coli. 244 47

Highly purified murine granulocyte-macrophage progenitor cells (CFU-GM) were used as target cells to assess the possible direct effects of purified preparations of recombinant murine gamma-interferon, prostaglandin E, recombinant human heavy chain (acidic) ferritin, and recombinant human tumor necrosis factor alpha (TNF-alpha) on progenitor cells in vitro. Target CFU-GM, with cloning efficiencies of up to 84% and containing 0-3% morphologically recognizable accessory cells at the initiation of the culture period, were plated at a density of 100-150 cells/dish in the presence or absence of pure suppressor molecules. Colony formation was stimulated with either crude pokeweed mitogen-stimulated mouse spleen conditioned medium, pure natural murine macrophage colony-stimulating factor, or pure recombinant murine granulocyte-macrophage colony-stimulating factor. All four suppressor molecules were active in vitro against purified CFU-GM as assessed by their ability to inhibit colony or cluster formation. No apparent difference in the degree of responsiveness to prostaglandin E, gamma-interferon, or human heavy chain (acidic) ferritin was noted in the presence of pokeweed mitogen-stimulated mouse spleen conditioned medium, granulocyte-macrophage colony-stimulating factor, or macrophage colony-stimulating factor. In contrast, TNF-alpha in cultures containing macrophage colony-stimulating factor slightly, but significantly, potentiated colony formation. TNF-alpha also appeared more active at suppressing colony formation at lower concentrations in pokeweed mitogen-stimulated mouse spleen conditioned medium than in granulocyte-macrophage colony-stimulating factor-stimulated cultures of purified CFU-GM. The results suggest that TNF-alpha, human heavy chain (acidic) ferritin, gamma-interferon, and prostaglandin E can act directly at the progenitor cell level.
Cancer Res 1988 Mar 15
PMID:Effects of hematopoietic suppressor molecules on the in vitro proliferation of purified murine granulocyte-macrophage progenitor cells. 244 53

The in vivo effect of yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was investigated in 29 patients with advanced malignancy in phase Ib trial. Patients were treated at six different dose levels (30-1000 micrograms/m2/day) with either daily intravenous bolus injection or 24 hours continuous infusion for 5 days or 2 weeks. Administration of rh GM-CSF resulted in a broad spectrum of dose-, route-, and schedule-dependent hematopoietic effects. Sustained infusion of rh GM-CSF elicited a maximum 17-fold average peak increase of the total white blood cell (WBC) count with mainly neutrophils, eosinophils, and monocytes accounting for this rise, and increases in bone marrow cellularity with a shift to immature myeloid elements. Elevation of lymphocytes, platelets and reticulocytes was not induced. Within one week after discontinuation of treatment the leukocytosis had disappeared. Adverse reactions encountered with rh GM-CSF seen in 65% of the patients studied were never life-threatening and always reversible. They included mild myalgias, facial flushing, low-grade fever, headache, bone discomfort, nausea, dyspnoea and transient decline of platelet counts. These results suggest that rh GM-CSF can be safely administered at the doses and schedules employed and that it can induce in vivo some of the biological effects reported in in vitro studies. Although no objective antitumour responses have been seen, the ability of rh GM-CSF to increase turnover and function of leukocytes in vivo may prevent neutropenia and infections, when GM-CSF is adjunctively added to cytotoxic cancer therapy.
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PMID:Yeast-expressed granulocyte-macrophage colony-stimulating factor in cancer patients: a phase ib clinical study. 246 45


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