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)

Using postmitotic granulocytes (PMGs) with low neutrophil alkaline phosphatase activity (NAP activity), factor(s) having the capacity to increase their NAP activity were examined in vitro. A high activity of the factor was demonstrated in the cystic fluid of a human squamous cell carcinoma, which is known to produce a large amount of granulocyte-macrophage colony-stimulating factor (GM-CSF). The NAP-stimulating factor increased NAP values both in PMGs from normal bone marrow and PMGs from patients with chronic myeloid leukemia (CML), and NAP values in cells treated with the factor approached or rose above those of normal peripheral granulocytes after 48 hr of culture. The effect of the factor was specific in that the factor caused stimulation only in granulocytic series. These findings may indicate that increases in NAP activity reflect maturation or granulocytes and that low NAP activity of neutrophils derived from patients with CML is due to the immaturity of these cells. The relationship between the factor responsible for the increase in NAP activity and GM-CSF is also discussed.
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PMID:Factor(s) responsible for the increase in alkaline phosphatase activity of postmitotic granulocytes from normal individuals and patients with chronic myeloid leukemia. 697 95

The possibility that production of some cytokines in the carcinoma microenvironment is associated with the presence and differentiation of cells belonging to the dendritic cell (DC)/Langerhans' cell (LC) lineage was investigated. Immunohistochemical examination showed the presence of intraepithelial LCs (CD1a- and S100-positive cells) in 6 of 10 squamous cell carcinomas and in 8 of 10 adenocarcinomas. Langerhans' cells were mainly located close to lymphoid aggregates. In situ hybridization performed in four cases (three LC positive and one LC negative) of squamous cell carcinoma and in five cases (four LC positive and one LC negative) of adenocarcinoma showed that some mononuclear cells in the interstitium displayed hybridization with granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF alpha), and interleukin 1-beta (IL1 beta) cDNA probes. Only in LC-positive carcinomas did epithelial cells close to lymphoid aggregates display small amounts of GM-CSF and TNF alpha mRNA expression. Immunohistochemical analysis performed in the 20 cases of lung carcinoma showed that epithelial cells in tumors with lymphoid aggregates and LCs were immunoreactive with antihuman GM-CSF monoclonal antibody. Specimens negative for GM-CSF contained very few LCs. Northern blot analysis was used to investigate GM-CSF, TNF alpha, IL1 alpha, and IL1 beta mRNA expression in six human lung carcinoma cell lines. A constitutive expression of TNF alpha mRNA was found in all of them, whereas only three showed a low constitutive expression of GM-CSF mRNA. In the latter three cell lines treatment with phytohemagglutinin (PHA)-stimulated peripheral blood lymphocyte (PBL) supernatant (PHA-SUP) upregulated GM-CSF mRNA expression and induced that of IL1 alpha mRNA. Carcinomatous epithelial cells producing small amounts of cytokines could promote the recruitment of cells of DC/LC lineage. Subcellular factors produced by reactive lymphocytes and/or macrophages may influence the production of GM-CSF and IL1 alpha by various epithelia. Up-regulation of this production could favor the arrival and differentiation of DCs and activate LC functions.
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PMID:Role of cytokines in distribution and differentiation of dendritic cell/Langerhans' cell lineage in human primary carcinomas of the lung. 763 48

The effect of biological response modifiers on macroscopic tumor growth and on tumor cell proliferation of a human renal cell carcinoma and a squamous cell carcinoma (hypopharynx) in nude mice has been studied. Tumor necrosis factor alpha (TNF-alpha) and interferon alpha (IFN-alpha) as well as granulocyte-macrophage colony-stimulating factor (GM-CSF) were applied either alone or in combination, and TNF-alpha was also combined with etoposide (ETP). TNF-alpha and IFN-alpha alone or in combination did not substantially affect the course of tumor growth, however, they did influence the pattern of tumor growth. There was also only a marginal effect on tumor cell proliferation. However, IFN-alpha protects the animals from tumor growth associated weight loss. ETP and ETP plus TNF-alpha leads to a deceleration of tumor growth, a decrease of the labeling index and to a significant decrease of the animal weight which indicates that the first two effects may be partly due to the toxicity of the treatment. GM-CSF modifies cell proliferation in a dose-dependent manner, i.e. stimulation at low doses and tendency to inhibition at higher doses. Although there is no substantial direct antineoplastic effect of the agents studied, the results make clear that indirect effects of therapeutic agents due to therapy induced cachexia should always be regarded. It is interesting that IFN-alpha has a protective effect against cachexia.
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PMID:Effect of biological response modifiers on growth and cell proliferation of human tumor xenografts in nude mice. 777 38

Serum levels of soluble intercellular adhesion molecule-1, soluble interleukin-2 receptor, and cytokines such as interleukin-3, interleukin-4, interleukin-6, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor were examined in patients with oral disorders with 20 healthy persons used as control subjects. Patients studied included 30 with squamous cell carcinoma, 26 with oral lichen planus, 20 with recurrent aphthous ulcer, 19 with acute odontogenic bacterial infection, 16 with pseudomembranous candidiasis, and 16 with herpetic gingivostomatitis. Compared with levels in control subjects, detectable serum levels of interleukin-3 (> or = 10 pg/ml) existed more frequently in pseudomembranous candidiasis (13/16), acute odontogenic bacterial infection (14/19), and squamous cell carcinoma (24/30) and of granulocyte-macrophage colony-stimulating factor (> or = 4 pg/ml) more frequently in recurrent aphthous ulcer (15/20) and squamous cell carcinoma (21/30). These cytokine levels were increased with T stage of squamous cell carcinoma. About 20 pg/ml of interleukin-4 was detected in serum from one third to one fourth of patients with oral lichen planus, recurrent aphthous ulcer, and squamous cell carcinoma. Tumor necrosis factor-alpha was hardly detected in most patients except those with oral lichen planus and squamous cell carcinoma in which about one third of the patients had more than 40 pg/ml of tumor necrosis factor-alpha in serum. More than 10 pg/ml of interleukin-6 was frequently detected in all disorders, especially recurrent aphthous ulcer (18/20), pseudomembranous candidiasis (12/16), and acute odontogenic bacterial infection (17/19).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum cytokines, interleukin-2 receptor, and soluble intercellular adhesion molecule-1 in oral disorders. 789 9

Murine squamous cell carcinoma (SCCVII) cells were genetically engineered to produce marine granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF immunotherapy, based on the peritumoral injection of lethally irradiated GM-CSF-producing SCCVII cells, was examined as adjuvant to photodynamic therapy (PDT) treatment of this tumor. The GM-CSF immunotherapy administered three times in 48-h intervals, starting 2 days before the light treatment, substantially improved the curative effect of Photofrin-mediated PDT. A comparable effect of GM-CSF immunotherapy was observed in the combination with benzoporphyrin derivative-mediated PDT. The tumor-localized GM-CSF immunotherapy alone had no obvious effect on the growth of parental SCCVII tumors. This treatment did not significantly alter the differential peripheral WBC count and appeared not to affect tumor leukocyte infiltration. However, GM-CSF treatment did increase the cytotoxic activity of tumor-associated macrophages against SCCVII tumor cells. It appears, therefore, that tumor-localized immune stimulation by GM-CSF amplifies a PDT-induced antitumor immune reaction, which has a potentiating effect on tumor control.
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PMID:Potentiation of photodynamic therapy-elicited antitumor response by localized treatment with granulocyte-macrophage colony-stimulating factor. 876 22

Twenty-nine previously untreated patients with squamous cell carcinoma of the oral cavity and pharynx underwent a treatment program with four courses of chemotherapy alternated with three courses of radiotherapy. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered at a dose of 5 micrograms/mg subcutaneously on the same day as radiation treatment in order to prevent mucositis. No grade 4 mucositis was reported; only four episodes of grade 2 mucositis and thirteen grade 2. Comparing these results with historical patients treated with the same chemotherapy-radiation program but without GM-CSF, the authors concluded that GM-CSF is an effective treatment for preventing mucositis produced by chemotherapeutic and/or radiotherapeutic interventions in patients at high risk of oropharyngeal mucosal damage.
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PMID:Effect of granulocyte-macrophage colony-stimulating factor on prevention of mucositis in head and neck cancer patients treated with chemo-radiotherapy. 937 95

Patients with head and neck squamous cell carcinoma (HNSCC) have profound immune deficiencies. In 65% of these patients, there is an increased intra-tumoral presence of immune-suppressive CD34+ progenitor cells. The goal of the present study was to determine whether CD34+ cell levels were also increased in the peripheral blood of HNSCC patients and if these immune-suppressive cells could be differentiated into dendritic cells. Our results showed that CD34+ cell levels are increased in the peripheral blood of HNSCC patients. To assess if these CD34+ cells could differentiate into dendritic cells, they were isolated from the blood of HNSCC patients and cultured for 12 days with various cytokine combinations. Culturing CD34+ cells with stem cell factor (c-kit ligand) plus granulocyte-macrophage colony-stimulating factor resulted in the appearance of a significant proportion of cells expressing phenotypic markers characteristic of dendritic cells. Also, including tumor necrosis factor-alpha yielded a significant proportion of cells resembling the bipotential precursor cells for dendritic cells and monocytes (CD14+CD1a+), in addition to the dendritic-like cells. When the differentiation inducer 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] was added along with the cytokine combinations, the yield of cells having characteristics of dendritic cells was further increased. Cells that were derived from CD34+ cell cultures containing 1,25(OH)2D3 had a more potent capacity to present the recall antigen tetanus toxoid to autologous peripheral blood leukocytes and to stimulate a mixed leukocyte response compared to cultures to which 1,25(OH)2D3 had not been added. Our results show that CD34+ cells, whose frequency is increased in HNSCC patients, can be differentiated into cells that phenotypically and functionally resemble dendritic cells and that 1,25(OH)2D3 accentuates this differentiation.
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PMID:Increased presence of CD34+ cells in the peripheral blood of head and neck cancer patients and their differentiation into dendritic cells. 939 43

A previous phase I study showed that in a 5-day combination of cisplatin (CDDP) 20 mg/m2/day and 5-fluorouracil (5-FU) intravenous bolus, the maximum tolerable dose of 5-FU is 200 mg/m2/day without the use of growth factors and 300 mg/m2/day with recombinant human granulocyte-monocyte colony-stimulating factor (rhGM-CSF) support. In the present phase II study, 26 patients with relapsed and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) were treated with CDDP, 20 mg/m2/day, and 5-FU, 300 mg/m2/day intravenous bolus, for 5 consecutive days every 3 weeks. Granulocyte-macrophage colony-stimulating factor, 5 mg/kg/day subcutaneously, was administered from days 8 to 19. All patients had previously undergone surgery and/or radiation treatment. None had previously received chemotherapy. Mucositis (19% of the patients) and thrombocytopenia (42%) were the most frequent, but generally mild, toxicities. Relevant, GM-CSF-related side effects were detected in 12% of the patients. The median number of cycles delivered was four. Three complete and five partial responses were recorded (31% overall response rate). Further investigation of this regimen is unwarranted because of both its lack of improvement in antitumoral activity and the high costs incurred with the use of growth factors.
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PMID:5-Fluorouracil dose intensification and granulocyte-macrophage colony-stimulating factor in cisplatin-based chemotherapy for relapsed squamous cell carcinoma of the head and neck: a phase II study. 962 7

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been suggested to be involved in the carcinogenesis of some types of tumours by autocrine or paracrine mechanisms. We examined GM-CSF/GM-CSF receptor (GM-CSFR) gene expression in 20 human non-small cell lung cancer (NSCLC) xenografts. The stimulatory effects of GM-CSF were examined using GM-CSF transgenic severe combined immunodeficient (SCID) mice (GM-Tg-SCID), which produce abundant human GM-CSF. A NSCLC xenograft (LC11-JCK), expressed GM-CSFR but not GM-CSF, and showed more rapid growth in GM-Tg-SCID than non-GM-CSF transgenic SCID mice (non-Tg-SCID). GM-CSF gene expression was detected in 48 of 90 (53%) primary NSCLC human specimens and GM-CSFR gene expression was detected in 42 specimens (47%). GM-CSF expression was detected in 13 of 30 squamous cell carcinoma specimens (43%) and GM-CSFR expression was detected in 10 specimens (33%). Patients with squamous cell carcinoma coexpressing GM-CSF and GM-CSFR showed significantly poorer prognosis than those expressing neither GM-CSF nor GM-CSFR (P < 0.05, Cox-Mantel test). These results suggest that GM-CSF can have a stimulatory effect on some NSCLC.
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PMID:Growth stimulation of non-small cell lung cancer xenografts by granulocyte-macrophage colony-stimulating factor (GM-CSF). 1002 22

Patients with head and neck squamous cell carcinoma (HNSCC) have increased levels of immune-suppressive peripheral blood CD34+ cells. This study showed that the peripheral blood CD34+ cells of HNSCC patients are capable of differentiating into dendritic cells. Because CD34+ cells can differentiate through several pathways into dendritic cell subpopulations, the intermediate cells through which the blood CD34+ cells of HNSCC patients differentiate were identified. After 6-7 days of culturing the CD34+ cells of HNSCC patients with granulocyte-macrophage colony-stimulating factor, stem cell factor, and tumor necrosis factor at, there appeared CD14+CD1a+ and a lesser proportion of CD14(-)CD1a+ cells resembling the precursor cells of the bipotential and committed dendritic cell differentiation pathways that have been described for cord blood CD34+ cells. To functionally analyze whether these populations were in fact precursor cells, they were isolated and cultured for an additional 10-12 days. Each of these populations was shown to function as precursor cells because they were able to develop into cells that resembled dendritic cells, although a higher proportion developed from the CD14-CD1a+ cells. In contrast, expression of the dendritic activation/maturation marker CD83 was highest on the cells that developed from CD14+CD1a+ cells. Thus, the CD34+ cells whose levels are increased in HNSCC patients can develop into both committed and bipotential dendritic precursor cells, which can subsequently give rise to dendritic cells.
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PMID:Dendritic cell differentiation pathways of CD34+ cells from the peripheral blood of head and neck cancer patients. 1033 90


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