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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)

Filgrastim and sargramostim are hematopoietic growth factors that are now produced on a large scale through recombinant DNA technology. Both agents are effective in increasing blood cell counts following chemotherapy and bone marrow transplantations. Investigational work is still being conducted to determine their potential use.
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PMID:G-CSF and GM-CSF. 171 32

Human recombinant colony-stimulating factors may be used to treat or prevent neutropenia caused by marrow toxic chemotherapeutic agents administered to patients with cancer. Despite their common clinical use, little is known about the potential adverse effects that these cytokines may have on the growth of malignant cells. Indeed, several in vitro reports have indicated that colony-stimulating factors may act as stimulating growth factors in some human malignancies. To evaluate these effects in ovarian cancer, we investigated the possible growth effects of granulocyte colony-stimulating factor (G-CSF/Filgrastim) and granulocyte-macrophage colony-stimulating factors (GM-CSF/Sargramostim) on four established ovarian cancer cell lines, as well as five primary ovarian cancer cultures over a wide range of pharmacologic doses. Cell viability was measured by an ATP bioluminescence assay and expressed as a percentage of untreated control cultures. G-CSF showed no growth-stimulating effects in any of the four established cell lines tested. In the OVCAR-3 cell line, a decrease in growth (> 10%) was seen at 10, 100, and 1000 ng/ml after 5 days of continuous treatment. In the same cell line, GM-CSF caused an increase (> 10%) in growth at the same doses. However, these changes did not demonstrate statistical significance in a dose-dependent fashion. In the five primary cultures treated with G-CSF, only one demonstrated statistically significant increases in growth in a dose-dependent manner. GM-CSF treatment had no significant growth alterations in these same five primary cultures. These results would suggest that colony-stimulating factors may act as growth factors in some but not all ovarian cancer cells. Further investigations into the receptor status of ovarian cancer cells for these cytokines are underway to clarify this issue.
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PMID:In vitro growth effects of colony-stimulating factors in ovarian cancer. 751 21

The clinical use of the biologic response modifiers filgrastim, sargramostim, and regramostim is reviewed. All circulating blood cells are derived from totipotent hematopoietic stem cells. Various biologic response modifiers, including lymphokines and colony-stimulating factors, regulate and activate the lymphoid and myeloid cells of the blood. One of the more important types of blood cell for fighting infection is the neutrophil. Patients with low neutrophil concentrations are at high risk of developing neutropenic fevers and infections. The colony-stimulating factors filgrastim, sargramostim, and regramostim increase the production of circulating neutrophils, and this action is clinically useful in patients undergoing myelosuppressive antineoplastic therapy or bone marrow transplantation and in patients with the acquired immunodeficiency syndrome. Clinical studies of these agents in comparison with antimicrobial prophylaxis or placebo have shown a decreased rate of neutropenic-associated hospitalizations and infections. These agents are also under study for dose intensification of antineoplastics in patients with various solid tumors and for augmenting patient responses to antimicrobial therapy in situations where there is high risk of morbidity and mortality. Sargramostim and regramostim are both granulocyte-macrophage colony-stimulating factors that differ in their degree of glycosylation and source of production, and at high doses they can cause life-threatening adverse effects because they stimulate the production of a broad range of leukocytes. Filgrastim, which stimulates only the production of neutrophils, has been better tolerated, especially at higher doses. Biologic response modifiers hold much promise for improving therapy of certain clinical conditions by decreasing myelosuppressive complications and enhancing responses to other drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical effects of biologic response modifiers. 768 88

This article familiarizes the practitioner with the clinical nursing implications of the colony stimulating factors that have been approved for use. The process of hematopoiesis is reviewed with a focus on the mechanisms of action for Sargramostim, Filgrastim, and Epoetin Alfa. Each agent is discussed individually and information is presented regarding indications, pharmacologic properties, routes of administration, and potential adverse reactions. Nursing interventions for care of the patient receiving colony stimulating factors are discussed.
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PMID:Clinical implications for the administration of colony stimulating factors. 816 90

Neutropenia frequently complicates infection due to human immunodeficiency virus (HIV). The etiology of neutropenia in this setting includes bone marrow infection or infiltration, myelosuppressive therapies, the presence of antibodies to HIV, and accelerated apoptosis. Protection against microbial invaders by neutrophils is further compromised by impaired chemotaxis and phagocytosis, production of toxic oxygen species, and expression of cellular adhesion molecules. Neutropenia is a significant risk factor for bacterial infection in HIV-infected patients. Endogenous cytokines, such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor, regulate neutrophil count and function. Treatment with recombinant human methionyl G-CSF (filgrastim) has lessened neutropenia in patients with HIV infection. Clinical trials have shown that the incidence of bacterial infections and the number of consequent days of hospitalization for HIV-infected patients receiving filgrastim therapy are lower. Filgrastim treatment also allows administration of larger doses of myelosuppressive agents.
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PMID:Neutropenia, neutrophil dysfunction, and bacterial infection in patients with human immunodeficiency virus disease: the role of granulocyte colony-stimulating factor. 1067 24

Filgrastim alone and sequential sargramostim and filgrastim have been shown to be more effective than sargramostim alone in the mobilization of CD34(+) cells after myelosuppressive chemotherapy (MC). We sought to compare costs and resource use associated with these regimens. Data were collected prospectively alongside a multicenter, randomized trial of filgrastim, sargramostim, and sequential sargramostim and filgrastim. Direct medical costs were calculated for inpatient and outpatient visits and procedures, including administration of growth factors and MC. We followed 156 patients for 30 days or until initiation of high-dose chemotherapy. The main outcome measures were resource use and costs of inpatient and outpatient visits, platelet and red blood cell transfusions, antibiotic use, and apheresis procedures. Hospital admissions, red blood cell transfusions, and use of i.v. antibiotics were significantly more common in the sargramostim group than in the other treatment arms. In univariate and multivariable analyses, total costs were higher for patients receiving sargramostim alone than for patients in the other groups. Mean costs in multivariable analysis for the filgrastim and sequential sargramostim and filgrastim arms were not significantly different. Filgrastim alone and sequential sargramostim and filgrastim are less costly than sargramostim alone after MC, as well as therapeutically more beneficial.
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PMID:Economic evaluation of filgrastim, sargramostim, and sequential sargramostim and filgrastim after myelosuppressive chemotherapy. 1185 Jul 11

The effects of sargramostim and filgrastim on hematopoietic cells are described. Filgrastim is a lineage-specific colony-stimulating factor (CSF), mainly affecting neutrophils. In addition to enhancing neutrophil recovery, filgrastim may also enhance neutrophil functional activity. Filgrastim does not have any meaningful effect on monocytes or macrophages; however, recent data indicate that filgrastim has a stimulatory effect on Th2 lymphocyte-inducing dendritic cells. These dendritic cells facilitate humoral immune responses, but they also produce inhibitory cytokines that diminish cell-mediated immunity. Sargramostim is a multilineage CSF, affecting neutrophils, monocytes, macrophages, and dendritic cells. Sargramostim has a greater impact on Th1 lymphocyte-inducing dendritic cells, which facilitate cell-mediated immune responses, including antitumor activity. The broader activity of sargramostim on both types of antigen-presenting cells (macrophages and dendritic cells) may account for the reports of benefit beyond enhanced neutrophil recovery that have been seen in clinical trials of patients with leukemia and patients undergoing stem-cell transplantation. Given the disparate activity of these two CSFs on the immune system and the types of immune responses generated, it is prudent for clinicians to consider these effects when choosing an agent for enhancing neutrophil recovery in various clinical settings.
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PMID:Colony-stimulating factors: beyond the effects on hematopoiesis. 1194 10

The development of the therapeutic roles of filgrastim and sargramostim over the past decade is reviewed. Filgrastim, a recombinant granulocyte colony-stimulating factor (G-CSF), and sargramostim, a recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF), have been available in the United States for over a decade to treat various types of neutropenia. In addition, data are available to support their use in a variety of clinical settings. Because of the high cost of these agents, clinical guidelines for their appropriate use have been developed. With respect to the comparability of filgrastim and sargramostim, the American Society of Clinical Oncology recommends that additional data be generated since current data are insufficient to adequately address this question in each clinical setting. A limited number of randomized, comparative trials have directly compared filgrastim with sargramostim. Outcomes data from these trials are reviewed. Further, there is evidence to suggest that, at least for GM-CSF, tolerability is dependent on the degree of protein glycosylation. A nonglycosylated protein, molgramostim, available in Europe appears to be associated with greater toxicity in clinical trials, although randomized comparative trials are lacking. The therapeutic equivalence of CSFs requires further study. While data show that the efficacy and tolerability of CSFs are similar in certain settings, there has been no definitive, randomized, large-scale clinical trial conducted to address this issue. Pharmacists should continue to evaluate clinical data to determine not only which CSF to use but also when a CSF should be used.
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PMID:Clinical applications of colony-stimulating factors: a historical perspective. 1194 13

Endogenous myeloid colony-stimulating factors (CSFs) have demonstrated the ability to enhance the clinical management of immunosuppressed patients with cancer. These agents are associated with significant decreases in chemotherapy-associated infections, antibiotic use, length of hospital stays, and mortality. Two major endogenous recombinant myeloid CSFs currently are being manufactured. Granulocyte macrophage CSF (GM-CSF) (sargramostim, Leukine, Immunex Corporation, Seattle, WA) has broad activity in the proliferation and differentiation of myeloid lineage progenitor cells, whereas granulocyte CSF (filgrastim, Neupogen, Amgen, Inc., Thousand Oaks, CA) acts selectively on cells of the granulocyte lineage. Clinical trials suggest that GM-CSF has clinical benefits beyond enhancing neutrophil recovery, including shortening the duration of mucositis and diarrhea, stimulating dendritic cells, preventing infection, acting as an adjuvant vaccine agent, and facilitating antitumor activity.
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PMID:Granulocyte macrophage colony-stimulating factor: current practice and novel approaches. 1208 15

Hematopoietic growth factors are commonly used in allogeneic and autologous stem cell transplantation. The growth factors most frequently used are human recombinant erythropoietin, filgrastim, and sargramostim, and a number of trials have been done using them either singly or in various combinations for mobilization, post-transplant, and for delayed engraftment. Filgrastim and sargramostim can shorten the neutropenic period and decrease infectious complications post-transplant, thus lowering the cost of both autologous and allogeneic transplants. Erythropoietin has not been particularly effective for mobilization, and studies have not shown its efficacy in reducing red blood cell transfusions in autologous transplants. However, they have been clinically beneficial in allogeneic transplantation and in delayed erythropoiesis post-transplantation. Stem cell factor remains investigational at this time but seems promising. The new long-acting erythropoietin and filgrastim are also introduced here and briefly discussed.
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PMID:Stem cell transplantation and hematopoietic growth factors. 1290 Nov 31


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