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)

During pregnancy, a complex cytokine network is present at the maternal-fetal interface in order to support normal growth and development of the placenta and fetus. HIV can frequently infect placental trophoblast but the impact of cytokines produced locally by the placenta and decidua on virus expression and replication is unknown. We comprehensively assayed the cytokines typically present in the placental microenvironment for their potential to modulate HIV transcriptional activation in the isolated trophoblast cells employing a transient transfection assay with luciferase as a reporter gene. Long terminal repeats (LTRs) of two divergent virus strains, HIV-1 LAI and HIV-1 NDK, were used to analyze virus-specific features. Four cytokines, epidermal growth factor (EGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF-alpha), were found to stimulate promoters of both viruses, whereas interferon alpha (IFN-alpha) and IFN-beta were found to suppress the transcription driven from both promoters. The differences observed between the two viruses did not reach a statistically significant level. None of the remaining cytokines, including EGF; GM-CSF; insulin-like growth factor I (IGF-I); IFN-alpha, IFN-beta, and IFN-gamma; IL-1 alpha, IL-1 beta, IL-2, IL-6, and IL-10; leukemia inhibitory factor (LIF); macrophage colony-stimulating factor (M-CSF); platelet-derived growth factor BB (PDGF-BB); transforming growth factor beta (TGF-beta); and TNF-alpha, affected transcriptional expression of the promoter constructs. Our results demonstrate that the local balance of cytokines may be critical for activation of HIV in the syncytiotrophoblast-cytotrophoblast layer and thus play an important role in the transmission of virus across the placental barrier.
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PMID:Role of placental cytokines in transcriptional modulation of HIV type 1 in the isolated villous trophoblast. 1220 6

Autologous peripheral blood stem cell transplantation for multiple myeloma offers higher response rates and improved survival compared with conventional chemotherapy. However, successful autografting requires effective cytoreduction and rapid hematologic reconstitution. We conducted a prospective randomized clinical trial to assess the efficacy of 2 cycles of priming chemotherapy with either granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) for peripheral blood stem cell mobilization followed by autologous transplantation. The major study end points were the comparative utility of G-CSF versus GM-CSF, the percentage of patients achieving complete response after transplantation, and overall and progression-free survival. Priming chemotherapy included cyclophosphamide (4 g/m2), mitoxantrone (8 g/m2 every day for 2 days), and dexamethasone (20 mg/m2 every 12 hours for 2 days) followed by randomization to either G-CSF or GM-CSF daily until completion of leukapheresis. Conditioning for transplantation included cyclophosphamide (75 mg/kg every day for 2 days) plus total body irradiation (165 cGy twice daily for 3 days), and patients received maintenance immunotherapy with interferon alpha. Seventy-two patients were randomized, and 64 underwent autologous transplantation. The median age at transplantation was 52 years, and the median time from diagnosis to transplantation was 10 months; 58% of the patients had received >4 cycles of pretransplantation chemotherapy. The median number of CD34+ cells obtained after mobilization was 16.4 x 10(6)/kg in the G-CSF arm versus 12.8 x 10(6)/kg in the GM-CSF arm (P = .8). Neutrophil recovery was faster in the G-CSF group after both cycle 1 (median, 13 days with G-CSF and 16 days with GM-CSF; P < .01) and cycle 2 (median, 13 days versus 17 days in the 2 groups, respectively; P = .03). Although platelet recovery was similar after cycle 1, platelet recovery to >100000/microL was notably faster in the G-CSF group both after cycle 2 and after transplantation (P = .03). Response and overall and disease-free survival were similar in both cohorts. Overall, 23% of the patients achieved a complete response after priming chemotherapy, which improved to 33% after transplantation. An additional 47% attained a partial response after transplantation, for a total response rate of 80%. With a median follow-up of 2 years (range, 0.7-8 years), the overall survival was 88% (95% confidence interval [CI], 80%-96%) at 1 year and 65% (95% CI, 51%-79%) at 3 years. Progression-free survival was 73% (95% CI, 62%-84%) at 1 year and 40% (95% CI, 26%-54%) at 3 years. Relapse or progressive disease was the most common cause of death (25 [83%] of 30 deaths). We conclude that mobilization with chemotherapy plus G-CSF versus GM-CSF results in similar CD34+ progenitor collections, even in patients exposed to multiple cycles of alkylator-based chemotherapy. Earlier neutrophil and platelet recovery was seen with G-CSF priming. Two cycles of priming chemotherapy plus autologous transplantation yields survival rates similar to those in published reports, including those using tandem transplantation.
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PMID:Randomized comparison of granulocyte colony-stimulating factor versus granulocyte-macrophage colony-stimulating factor plus intensive chemotherapy for peripheral blood stem cell mobilization and autologous transplantation in multiple myeloma. 1514 93

Antibodies develop to varying degrees during treatment with human proteins, including insulin, growth hormone, granulocyte-macrophage colony-stimulating factor, factor VIII, erythropoietin, and interferons. These antibodies may reduce the clinical efficacy of these agents by blocking or neutralizing their biologic activity and may have other biologic effects. For example, antibodies develop in 20 % to 40% of patients with severe hemophilia treated with human factor VIII; the presence of these antibodies can result in tolerance to the clotting effects of this agent. Similarly, a proportion of patients treated with interferon alpha develop antibodies, which inhibit its therapeutic effects. Therefore, it is important to test for neutralizing antibodies during treatment with these agents, particularly in patients who are unresponsive to treatment or have breakthrough disease. This article reviews the incidence and clinical impact of antibodies that develop in response to some of the commonly used protein therapeutic agents.
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PMID:Immunogenicity of recombinant human proteins: causes and consequences. 1526 6

Blastic natural killer (NK) cell lymphoma corresponding to CD4+CD56+ malignancies is a novel disease entity, according to the results of clinical, morphologic, and immunologic studies. It is especially noteworthy that this disease likely arises from plasmacytoid dendritic cells (pDCs), described previously as plasmacytoid T-cells, which have an important role in innate and adaptive immunity. However, the exact relationship between the tumor cells and pDCs remains to be elucidated. We encountered a patient with typical blastic NK cell lymphoma, which later converted to leukemic manifestations, and tried to establish a cell line using the leukemic cells. We succeeded in establishment of a novel cell line, CAL-1, which originated from the primary malignant cells. The genetic and phenotypic features of CAL-1 cells bear a similarity to those of pDCs, namely, plasmacytoid morphology at light and electron microscopy; negative results for CD11c and lineage-associated markers of CD3, CD14, CD19, and CD16; positive results for HLA-DR, CD4, CD56, CD45RA, and CD123; and negative results for TCR and IgH gene rearrangements. An interesting finding was that CAL-1 cells change morphologically into the mature DC appearance with many long dendrites after short-term culture in the presence of granulocyte-macrophage colony-stimulating factor and interleukin 3. CAL-1 cells can secrete tumor necrosis factor alpha but not interferon alpha. Thus although they do not share in part phenotypic and functional features with their normal counterparts, CAL-1 cells mostly exhibit a striking pDC phenotype. We describe the first novel pDC cell line of CAL-1. This cell line should open the opportunity for study not only of CD4+CD56+ tumor cells but also of pDCs in vitro.
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PMID:A novel plasmacytoid dendritic cell line, CAL-1, established from a patient with blastic natural killer cell lymphoma. 1576 84

The study was aimed to investigate the influence of interferon alpha (IFN-alpha) on the expressions of Fas and Fas ligand (FasL) in dendritic cells (DCs) from patients with chronic myeloid leukemia (CML). In addition to adding stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNF-alpha) and interleukin 4 (IL-4), the IFN-alpha was added to the serum-free medium for DCs. After culturing for 10 - 14 days, cell phenotype and percentage of Ph(1) chromosome were detected by different methods. The expression of Fas or FasL on CML-DCs and cell cycle of DCs labeled with propidium iodine (PI) were measured by flow cytometry. The concentration of sFas in supernatants was analyzed by enzyme-linked immunosorbent assay (ELISA). The results indicated that the expression of co-stimulatory molecules were improved significantly while the percentages of Ph(1) positive cells decreased. The level of Fas on cells was up-regulated and the concentration of sFas decreased. However, the expression of FasL was negative. The ratio of apoptosis rose gradually while the concentration of IFN-alpha increased. It is concluded that IFN-alpha can accelerate the apoptosis of Ph(1) positive cells through Fas/FasL pathway, so the number of Ph(1) negative cells increases relatively.
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PMID:Influence of interferon alpha on expression of Fas and Fas ligand in dendritic cells from patients with chronic myeloid leukemia. 1854 17

Various cytokines, including interferon alpha (IFNalpha), tumor necrosis factor alpha (TNFalpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF), have been used as adjuvant therapy for advanced-stage melanoma with some success but with marked toxicity, which appears to be related to higher doses. We investigated the efficacy of IFNalpha, GM-CSF, and TNFalpha in various combinations to induce antitumor and immune responses in a B16F10 murine melanoma model. These studies showed that GM-CSF, IFNalpha, and TNFalpha, when injected together intratumorally, mediated significant inhibition of tumor growth. Tumor regression correlated with local tumor necrosis and significant infiltration of T cells. In addition, this injected intralesional cytokine cocktail also induced lymphadenopathy, with an increase in both CD4(+) and CD8(+) T cells in the draining lymph nodes. Furthermore, tumor-specific CD8(+) T cells were identified from draining lymph nodes. These investigations identify the combined effects of IFNalpha, GM-CSF, and TNFalpha in induction of the adaptive immune response and generation of antigen-specific T-cell reactivity. These results support potential clinical trials of the low-dose cytokine combination as adjuvant therapy for melanoma.
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PMID:Combination cytokine therapy inhibits tumor growth by generation of tumor-specific T-cell responses in a murine melanoma model. 2006 Jul 41


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