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)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor that stimulates myeloid cell proliferation and maturation and enhances the function of terminally differentiated effector cells. Phase I and II clinical trials have demonstrated mild to moderate toxicities at doses of less than 30 micrograms/kg/day. These studies suggest a potential role for this growth factor to stimulate myelopoiesis in patients with aplastic anemia, myelodysplastic syndromes, AIDS, chemotherapy-induced myelosuppression, chronic neutropenia, and following bone marrow transplantation. The potential clinical uses of GM-CSF will depend on results of studies designed to optimize its therapeutic efficacy.
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PMID:Clinical applications of human granulocyte-macrophage colony-stimulating factor. 177 Feb 27

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is one of the four major colony-stimulating factors (CSFs) that regulate hematopoiesis. GM-CSF can stimulate a single bone marrow stem cell to proliferate and differentiate into mature neutrophils, eosinophils, granulocytes or macrophages. The outcome of recent clinical trials indicates that GM-CSF has the prospect of being clinically effective in augmenting the recovery of hematopoiesis in recipients of autologous bone marrow transplantation, in cancer patients suffering from the hematopoietic toxicity associated with chemotherapy and radiation therapy, and in patients with acquired immunodeficiency syndrome (AIDS).
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PMID:Granulocyte-macrophage colony-stimulating factor (GM-CSF) in the management of cancer. 181 Apr 41

Ganciclovir is effective in halting or delaying the progression of cytomegalovirus (CMV) retinitis in patients with acquired immune deficiency syndrome (AIDS). However, the development of neutropenia necessitates the interruption of ganciclovir therapy in 40-50% of AIDS patients. In an ongoing randomized, controlled trial, AIDS patients with CMV retinitis are receiving standard ganciclovir therapy or ganciclovir plus recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). rHuGM-CSF is administered by daily subcutaneous injections and is given in ascending doses based on the neutrophil response in the individual patient. Preliminary data obtained from 36 evaluable patients (21 receiving ganciclovir alone, 15 receiving ganciclovir plus rHuGM-CSF) suggest that rHuGM-CSF administration is associated with a trend toward a decrease in the proportion of patients developing an absolute neutrophil count (ANC) of less than 750 cells/microliter (40% vs. 59%), in the overall incidence of such neutropenic episodes (20 vs. 68), and in the duration of ganciclovir treatment interruption due to the development of an ANC of less than 500 cells/microliter (5.5 days vs. 10.1 days). rHuGM-CSF administration has been generally well tolerated, and no consistent proliferative effect of this agent on human immunodeficiency virus infection has been observed. Definitive conclusions regarding the coadministration of rHuGM-CSF and ganciclovir await completion of the trial.
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PMID:Combined ganciclovir and recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of cytomegalovirus retinitis in AIDS patients. 184 18

Ganciclovir currently is the only agent approved for use in the treatment of cytomegalovirus (CMV) retinitis in immunocompromised patients, including those with the acquired immune deficiency syndrome (AIDS). Its effect against CMV in vitro and in vivo suggests its usefulness in other types of CMV infection as well. Investigations of the use of this agent in the treatment of AIDS patients with CMV gastrointestinal disease and in the treatment or prevention of CMV disease in transplant recipients are ongoing. In other studies, issues important to the management of patients receiving ganciclovir therapy are being addressed. Particular objectives include characterizing the scope of ganciclovir resistance in CMV, detailing the prospects for the tolerance of coadministered ganciclovir and zidovudine, and determining the plausibility of enhancing drug delivery through the concomitant use of recombinant human granulocyte-macrophage colony-stimulating factor and through oral administration of the agent.
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PMID:Future directions in the management of cytomegalovirus infections. 184 23

The combined use of zidovudine (ZDV) and interferon (IFN) alfa-2a has been shown to have antiretroviral and antitumor potential benefit in the treatment of acquired immune deficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS). However, the clinical use of this combination is frequently complicated by the overlapping myelotoxicity of these agents. We report here the results of a phase I/II study in which granulocyte-macrophage colony-stimulating factor (GM-CSF) was used for those KS patients who became neutropenic while receiving ZDV (1,200 mg/d) and IFN (9 x 10(6) U/d). Nineteen of 29 patients (66%) developed an absolute neutrophil count (ANC) of less than 1,000 cells per cubic millimeter and were begun on GM-CSF. All experienced a prompt increase in the ANC. Those patients receiving GM-CSF/ZDV/IFN alfa-2a had an improved end of study ANC when compared with the ZDV/IFN alfa-2a group, but did not have an increased rate of tumor response, end of study CD4 cell count, or improvement in any other hematologic variable. The use of GM-CSF was not associated with increased toxicity and, in particular, was not associated with a change in serum human immunodeficiency virus (HIV) p24 antigen. Tumor response was noted in 50% of the assessable patients (33% overall) despite "high-risk" characteristics in 80%. Of the responding patients, seven were on GM-CSF and might have otherwise required an alteration in ZDV/IFN alfa-2a dose level. Further study of GM-CSF as an alternate to dose modification of this (ZDV/IFN alfa-2a) and other combination therapies for AIDS patients is warranted.
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PMID:Granulocyte-macrophage colony-stimulating factor mitigates the neutropenia of combined interferon alfa and zidovudine treatment of acquired immune deficiency syndrome-associated Kaposi's sarcoma. 196 May 65

A number of studies have illustrated the effectiveness of hematopoietic growth factors in managing treatment-related cytopenias in patients with human immunodeficiency virus (HIV) infection. One of these factors, granulocyte-macrophage colony-stimulating factor, has been shown to restore absolute neutrophil counts in patients with acquired immunodeficiency syndrome (AIDS) and Kaposi's sarcoma receiving a combination of zidovudine (AZT) and interferon alfa. A combination of granulocyte colony-stimulating factor and erythropoietin has also been demonstrated to alleviate both neutropenia and anemia in patients with advanced AIDS or AIDS-related complex receiving zidovudine. Hematopoietic growth factors, in combination with each other and with antiretroviral agents, thus have an important supportive role to play in the treatment of patients with HIV disease.
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PMID:Antiretroviral therapy and immunomodulators in patients with AIDS. 201 46

Chronic ethanol ingestion predisposes to tuberculosis and bacterial pneumonia. Mycobacterium avium complex (MAC) organisms cause bacteremia in patients with AIDS. Cultured human monocyte-derived macrophages and murine Kupffer cells were exposed to 10-100 micrograms/dl ethanol; significantly greater intracellular growth of MAC strains 100 (serovar 8) and 101 (serovar 1) occurred in ethanol-treated cells than in controls (range, 58% +/- 7%-70% +/- 5%; P less than .05 for 50 and 100 micrograms/dl ethanol vs. control). Both cell types, when treated with 10(3) units/ml recombinant tumor necrosis factor (TNF) or 10(2) units/ml granulocyte-macrophage colony-stimulating factor (GM-CSF) in the presence of 10-100 micrograms/dl ethanol, killed significantly fewer MAC than controls (49% +/- 12% decrease for GM-CSF and 57% +/- 16% for TNF; P less than .05 for all comparisons). C57BL black mice infected intravenously with MAC strain 101 were given ethanol as 4% of total calories daily; after 21 days they had greater numbers of MAC in blood, liver, and spleen than controls. Ethanol's effects on the interaction between the host and MAC favor progressive infection.
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PMID:Ethanol augments intracellular survival of Mycobacterium avium complex and impairs macrophage responses to cytokines. 203 94

Levels of erythropoietin and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured in sera of 28 HIV-seronegative heterosexual non-intravenous drug using controls, 57 HIV-seronegative and 42 HIV-seropositive asymptomatic intravenous drug users (IVDU) and 36 HIV-seronegative and 36 HIV-seropositive homosexuals, 79 patients with lymphadenopathy, 11 patients with AIDS-related complex (ARC) and 110 patients with AIDS. Serum erythropoietin levels were significantly elevated in HIV-seronegative and HIV-seropositive asymptomatic homosexuals and in patients with lymphadenopathy, ARC and AIDS when compared to controls. However, in asymptomatic HIV-seronegative and HIV-seropositive IVDU the erythropoietin levels were not significantly different from the control group. GM-CSF mean levels in both HIV-seronegative and HIV-seropositive IVDU were elevated compared with the level in controls, whereas the mean levels in both the HIV-seronegative and HIV-seropositive homosexuals were decreased relative to the level in controls. GM-CSF levels in patients with lymphadenopathy, ARC and AIDS were not significantly different from the control value. It appears that male homosexuals have mildly increased erythropoietin levels which rise substantially with the development of ARC and AIDS, which suggests that AIDS patients have intact capacity to produce erythropoietin. In contrast, GM-CSF levels are increased in association with IVDU but are not increased in association with HIV infection including ARC or AIDS. The difference in circulating levels of erythropoietin and GM-CSF may reflect the tissue sources of erythropoietin predominantly in the kidney and GM-CSF being a product of the immunological and inflammatory systems.
Int J STD AIDS
PMID:Erythropoietin and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels in sera of patients with HIV infection. 204 5

Recombinant technology has been harnessed to produce sufficient quantities of colony-stimulating factors (CSFs)--also known as hematopoietic growth factors--to make clinical trials with these agents possible. Endogenous CSFs are hormone-like glycoproteins that bind to receptors on target cells and stimulate processes within these cells that mediate their proliferation, maturation, differentiation, and functional activation. Several such CSFs cloned by recombinant DNA technology now are being tested clinically. Some are multilineage growth factors, such as interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF), which tend to affect cells early in the hematopoietic hierarchy. Others, such as granulocyte colony-stimulating factor (G-CSF), primarily stimulate the formation of neutrophilic granulocytes. Macrophage CSF predominantly affects monocytes/macrophages. These are late-stage, single-lineage growth factors. Numerous clinical trials with all of these agents are under way. The granulopoietic agents, including GM-CSF and G-CSF, are being tested for their potential use in preventing or ameliorating myelosuppression related to AIDS, antineoplastic chemotherapy, bone marrow transplantation, myelodysplastic syndromes, and aplastic anemia. Clinical trial results on G-CSF and GM-CSF are encouraging thus far. However, it is too early to characterize the effects of IL-3, which is just entering clinical trials.
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PMID:Future strategies in the control of myelosuppression: the use of colony-stimulating factors. 204 96

Hallmarks of central nervous system (CNS) disease in AIDS patients are headaches, fever, subtle cognitive changes, abnormal reflexes, and ataxia. Dementia and severe sensory and motor dysfunction characterize more severe disease. Autoimmune-like peripheral neuropathies, cerebrovascular disease, and brain tumors are also observed. Histological changes include inflammation, astrocytosis, microglial nodule formation, and diffuse de- or dysmyelination. Focal demyelination can also be seen. It is clear that AIDS-associated neurological diseases are correlated with greater levels of HIV-1 antigen or genome in tissues. In AIDS dementia, macrophages and microglial cells of the CNS are the predominant cell types infected and producing HIV-1. However, manifestations of the disease make it unlikely that direct infection by HIV-1 is responsible. It seems more likely that the effects are mediated through secretion of viral proteins or viral induction of cytokines that bind to glial cells and neurons. HIV-1 induction of such cytokines as interleukin 1 (IL 1) and tumor necrosis factor-alpha (TNF alpha) may lead to an autocrine feedback loop involving further productive virus replication and induction of other cytokines such as interleukin 6 (IL 6) and granulocyte-macrophage colony-stimulating factor (GMCSF). Interleukin 1 and TNF alpha in combination with IL 6 and GMCSF could account for many clinical and histopathological findings in AIDS nervous system diseases. As HIV-1 infected patients produce elevated levels of IL 1, TNF alpha, and IL 6, it will be important to make a formal connection between the presence of these factors in the CNS, which are all products of activated macrophages, astroglia, and microglia, their in vivo induction directly by virus or indirectly by virus-induced intermediates, and the clinical and pathological conditions seen in the nervous system in this disease.
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PMID:HIV-1, macrophages, glial cells, and cytokines in AIDS nervous system disease. 206 87


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