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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)

Treatment of neoplastic diseases is followed by a variety of infectious complications. Neutropenia and functional defects of phagocytes are common consequences of cancer and its treatment and contribute to an increased susceptibility to infections. Cytokines with hematopoietic growth stimulatory and/or immunoenhancing properties, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), interleukin-3, interferon-gamma, macrophage colony-stimulating factor, interleukin-1, and interleukin-6 have been shown to either have clinical utility in patients with cancer and neutropenia or offer the promise to do so. GM-CSF and G-CSF, for example, have been shown to reduce the incidence of fever and infectious complications in patients with cancer and neutropenia. The role of cytokines for the treatment of defined infections (e.g., invasive mycoses) is under investigation.
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PMID:Perspectives on the use of cytokines in the management of infectious complications of cancer. 750 61

Immunotherapy can be defined as treatment directed at augmenting host immune defence mechanisms. Non-antimicrobial therapies and immunoprophylaxis in bone marrow transplantation (BMT) can be subdivided into three broad categories: passive immunotherapy with intravenous immunoglobulin (IVIG); cytokine therapy; and anti-endotoxin-directed treatments. Most studies using IVIG in BMT are prophylactic and suffer from variability in study design, type of IVIG and dosing regimens. Various effects on viral and bacterial infections and graft-versus-host disease (GVHD) have been reported but few if any have shown benefit in terms of improved patient survival. Moreover the immunomodulatory effect of immunoglobulin G preparations is frequently overlooked. With the exception of cytomegalovirus (CMV) pneumonitis, there is little evidence of benefit in the treatment of established infections and the relative benefits of hyperimmune preparations are poorly established. The development of haemopoietic growth factors has led to the widespread use of cytokines in BMT. The benefits of these agents both in the prevention of fever and infection and as adjuvants to standard antimicrobial therapy in established infection (e.g. invasive mycoses) are rapidly becoming apparent. Both human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and granulocyte colony-stimulating factor (rhG-CSF) have been shown to accelerate granulocyte recovery following BMT and reduce fever days, antibiotic usage and hospitalization. RhGM-CSF appears superior in these respects. The roles of interleukin 1 (IL1), IL3, IL6 and interferons are also under evaluation. As with the much publicised studies using anti-endotoxin antibodies as therapy in sepsis, there is little evidence of benefit in the few studies performed in BMT patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunotherapy and immunoprophylaxis in bone marrow transplantation. 756 Sep 54

We evaluated the efficacies of serum catalase (CAT), 5'-nucleotidase (5'NT), and tumor necrosis factor-alpha (TNF) as diagnostic markers of acute graft-vs-host disease (GVHD) in 28 allogeneic bone marrow transplant recipients by comparing their abilities to discriminate between GVHD-related and non-GVHD-related complications. Mean peak serum CAT concentrations for patients with GVHD-related complications (n = 17) were about fivefold higher than concentrations in patients with non-GVHD-related complications (n = 25; P = 0.003), whereas the mean peak concentrations of serum 5'NT and TNF were not substantially different. Similarly, the sensitivity and specificity of serum CAT (100% and 88%, respectively) for use as a diagnostic marker of GVHD were much better than those of serum 5'NT (88% and 24%, respectively) or serum TNF (65% and 4%, respectively). Receiver-operating characteristic plots of all possible sensitivity-specificity pairs obtained over the whole range of results also showed that serum CAT has the best diagnostic accuracy. Low specificities of serum TNF and 5'NT were caused mainly by their increase in septicemia, fungal infection, and veno-occlusive disease and after the use of granulocyte-macrophage colony-stimulating factor to stimulate donor cell engraftment. Serum CAT may prove to be a rapid and relatively noninvasive test for the diagnosis of acute GVHD.
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PMID:Serum catalase as marker of graft-vs-host disease in allogeneic bone marrow transplant recipients: pilot study. 758 45

We studied the influence of human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and Candida albicans (CA) components, either alone or in combination, on the proliferation of human bone marrow cells in vitro (colony-forming assay). The number of colonies per 10(5) bone marrow cells after cultivation with rhGM-CSF [maximal (plateau) colony formation] was: 46.2 +/- 9.1 (n = 6); after cultivation with rhGM-CSF in combination with CA components the numbers of colonies were as follows: 0.05 mg protein/ml, 33.4 +/- 4.6 (n = 3); 0.10 mg protein/ml, 20.8 +/- 3.6 (n = 3). The mechanisms responsible for this inhibition of colony formation are still unknown. They may be of pathogenetic significance in CA infection.
Mycoses
PMID:Proliferation of human bone marrow cells in vitro: inhibition by Candida albicans components. 793 67

A pilot study was conducted to evaluate the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) as adjuvant therapy for fungal infections in patients with cancer. GM-CSF was added to amphotericin B in the treatment of cancer patients with proven major-organ or disseminated fungal infection. The dose of GM-CSF ranged from 100 to 750 micrograms/(m2.d). Of eight evaluable patients, six had a neutrophil response to GM-CSF. Four of these patients were completely cured of the fungal infection, and two had a partial response. However, a capillary-leak syndrome developed in three patients, an adverse effect suggesting that the dose of GM-CSF was excessive.
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PMID:Role of granulocyte-macrophage colony-stimulating factor as adjuvant therapy for fungal infection in patients with cancer. 826 54

Infectious microorganisms can differently induce or inhibit apoptosis of immunocompetent effector and host cells. In this study we examined the influence of an infection by Candida albicans (C. albicans) on programmed cell death of monocytic U937 cells and human monocytes. Basal and tumor necrosis factor alpha (TNF-alpha)-induced DNA fragmentation of U937 cells was significantly inhibited by an infection with C. albicans. Enhanced apoptosis of U937 cells, induced by TNF-alpha, caused a diminished candidacidal activity of the effector cells, whereas inhibition of apoptosis by granulocyte-macrophage colony-stimulating factor (GM-CSF) was paralleled by an intensified host defense. Pretreatment of U937 cells or monocytes with the cyclooxygenase blocker indomethacin completely abolished the reduction of DNA fragmentation induced by the yeast. Studying the underlying mechanisms we found that C. albicans induced formation of prostaglandin E2 (PGE2) by U937. Exogenous administration of PGE2 down-regulated apoptosis of U937 or human monocytes to a similar extent as did fungal infection. Activation of protein kinase A by the cAMP analogue 8-bromo-cAMP inhibited U937 apoptosis, as did PGE2. On the other hand, rp-cAMP, a blocker of the cAMP-dependent signal transduction, restored and elevated DNA fragmentation levels down-regulated by C. albicans. U937 cells expressed the bcl-2 protein but the infection with fungi or PGE2 treatment did not increase proto-oncogene expression. Monocytic effector cells may therefore strengthen the defense against C. albicans by an autocrine feedback regulation via a PGE2-dependent, cAMP-transduced inhibition of apoptosis.
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PMID:Infection by Candida albicans inhibits apoptosis of human monocytes and monocytic U937 cells. 897 76

The production of chemotactic cytokines (chemokines) and other cytokines by macrophages in response to fungal infection is thought to be critical during the course of candidiasis. However, the mechanism of cytokine synthesis by macrophages in response to fungi is not well understood. Therefore, the response of macrophages to Candida albicans was examined in terms of receptor-mediated chemokine and other cytokine mRNA induction. Attachment of C. albicans to murine thioglycollate-elicited peritoneal macrophages induced increased mRNA levels of the cytokines interleukin-1beta (IL-1beta), IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF) and the chemokines macrophage inflammatory protein 1beta (MIP-1beta), MIP-2, and KC (a member of the platelet factor 4 neutrophil chemoattractant family), as determined by quantitative reverse transcription-PCR. However, treatment of macrophages with alpha-methyl-D-mannoside significantly reduced the cytokine GM-CSF response to C. albicans but did not affect the chemokine MIP-2 response. Antisense oligodeoxynucleotide (ODN) to mannose receptor (MR) mRNA inhibited the expression and function of MR in macrophages as determined by Western blot analysis and 125I-labeled mannose-bovine serum albumin (BSA) binding, and also inhibited the elevation of cytokine IL-1beta, IL-6, and GM-CSF mRNA levels induced by C. albicans attachment. Elevation of chemokine MIP-1beta, MIP-2, and KC mRNA levels induced by C. albicans was not affected in macrophages whose MR expression was suppressed by antisense ODN treatment. Furthermore, IL-4 treatment of macrophages, which up-regulated MR expression as determined by Western blot analysis and fluorescein isothiocyanate-labeled mannose-BSA uptake, enhanced the level of cytokine GM-CSF mRNA induced by C. albicans but not the level of the chemokine MIP-2 mRNA. These results indicate that selected cytokine responses of macrophages to C. albicans are mediated by MR, while some chemokine responses may be mediated by other receptors.
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PMID:Involvement of mannose receptor in cytokine interleukin-1beta (IL-1beta), IL-6, and granulocyte-macrophage colony-stimulating factor responses, but not in chemokine macrophage inflammatory protein 1beta (MIP-1beta), MIP-2, and KC responses, caused by attachment of Candida albicans to macrophages. 903 18

Many chemotherapy regimens are associated with variable periods of myelosuppression. In cancer patients, neutropenia (less than 500 neutrophils/microL) is the most important risk factor for infections. The incidence and severity of infectious complications are related to depth and duration of neutropenia, with the highest risk if neutrophils are less than 100/microL for more than a week. The period required for neutrophil recovery is usually short with standard regimens, but prolonged after high dose chemotherapy followed by autologous bone marrow transplant (-ABMT) or peripheral blood stem cell (PBSC) infusion. Under these conditions, the administration of granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) accelerates neutrophil recovery and shortens the duration of hospitalization. In standard chemotherapy settings, prophylactic use of CSF's is a matter of debate. Several studies have reached contrasting conclusion, but, combining effectiveness and costs, it results that this use of CSF'S is not to be recommended unless the risk of infections (elderly patients, reduced marrow reserve) is high. The administration of G-CSF or GM-CSF to a febrile neutropenic patient (cfr CSF's therapy) shortens the duration of neutropenia, although no great clinical benefits are evident. Nevertheless the identification of subsets of patients with additional risk factors (i.e. absolute neutrophil count < 100/microL at the onset of fever or delayed neutrophil recovery) should be helpful in establishing the role of CSF's therapy. When prolonged periods of severe neutropenia (less than 500 neutrophils/microL) are expected, antibiotics should be prophylactically administered. Fluoroquinolones seem to be the optimal choice in heavily myelosuppressed patients (ie. bone marrow transplant recipients). Fluoroquinolones are effective in reducing the frequency of gram-negative bacteremia, but, because of incomplete coverage, gram-positive infections are becoming increasingly problematic. The association with an agent that can be absorbed orally, active against gram-positive cocci, seems to be an effective strategy. Fungal infections are an important cause of morbility and mortality in severely neutropenic patients. Safety and efficacy of antifungal triazoles and the lipid formulations of amphotericin B used prophylactically still require investigation. In patients at high risk for fungal infections, monitoring cultures are predictive for systemic mycoses and should guide prophylactic and therapeutic choices. The standard treatment of oncologic patients with potential infectious neutropenia complications is admission to the hospital and treatment with broad-spectrum intravenous antibiotics. Until third generation cephalosporin and carbapenems became available, most neutropenic febrile patients were treated with associations of an aminoglycoside plus a beta-lactam. Monotherapy with the new antibiotics has proven to be effective as an association therapy and offers advantages in terms of cost and tolerability. Whether or not vancomycin is included in the initial antibiotic regimen should be decided on the basis of epidemiological consideration (i.e. prevalence of meticillin-resistant Staphylococcus aureus or Staphylococcus mitis in certain centers). Antifungal therapy is indicated in neutropenic patients who remain febrile after one week of broad-spectrum antibiotics or have recurrent fever. Amphotericin B should be promptly administered in patients suspected of invasive mycoses. Selected patients with fever and neutropenia, that can be identified on the basis of reduced risk of severe complications, do not need hospitalization. In the first reports, outpatient treatment has proven to be effective, cost saving and well received by patients, but further studies are needed to accurately define low risk status and the optimal home antibiotic regimens.
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PMID:[Prevention and treatment of febrile neutropenia]. 923 24

In patients undergoing bone marrow transplantation cryptococcosis is rarely encountered. We report a fatal case of Cryptococcus meningitis in a 12-year-old girl with acute lymphoblastic leukemia (ALL) in second remission who had a transplant from a human leukocyte antigen (HLA)-identical unrelated bone marrow donor. The conditioning regimen was thiotepa, cyclophosphamide, and total body irradiation (TBI); graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A, methotrexate, and antilymphocyte globulin (ALG). The patient experienced stage III GVHD responsive to high-dose corticosteroids. On day +54 a thrombotic microangiopathy occurred. On day +64 neurological status worsened; a brain computed tomographic (CT) scan showed hyperdense lesions suggesting fungal infection. Detection of cryptococcal antigen by latex agglutination was positive but India ink stain and culture were negative. Despite treatment with amphotericin B, 5-flucytosine, and granulocyte-macrophage colony-stimulating factor, the patient died 13 days after the diagnosis.
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PMID:Cryptococcal meningitis following a thrombotic microangiopathy in an unrelated donor bone marrow transplant recipient. 926 80

The efficacy of dose-intensive chemotherapy in oncology is limited by the duration and severity of neutropenia. Several recombinant DNA factors that alter neutrophil proliferation and function, and are characterised by their ability to stimulate colony formation of myeloid progenitors in vitro, have been shown to alter clinical sequelae associated with neutropenia in vivo. Two of these factors, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), have been approved by the US FDA. One other factor, macrophage colony-stimulating factor (M-CSF), is approved as indicated therapy in Japan. The clinical effects of these agents are compared in this review. Results of clinical trials suggest that the efficacy of G-CSF is greatest when used as an agent to enhance circulation of stem cells and pre-colony-forming progenitor cells. It is also an effective agent in reducing the duration of neutropenia following dose-intensive chemotherapy, thereby leading to a reduction in the incidence of febrile neutropenia. Similar observations were made with GM-CSF, although toxicity with the latter agent appears to be moderately greater than that observed with G-CSF. Functional activity of GM-CSF is broader than that of G-CSF, in that macrophages are affected by GM-CSF. As a result, some data suggest that GM-CSF may be more applicable to patients with a high risk of infection. There is a suggestion that M-CSF assists neutrophil recovery, although this effect may be indirect, via the induction of other cytokines. The predominant effect of M-CSF appears to be enhancement of macrophage and monocyte function, which may reduce the severity and duration of fungal infection.
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PMID:A comparative review of colony-stimulating factors. 936 58


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