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)

The difference between the effects of administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was studied in 39 children with neutropenia secondary to chemotherapy (absolute neutrophil count (ANC) less than 1,500/microliters. The children were divided into two groups. The first group (G-CSF) included 25 children (12 with acute lymphoblastic leukemia [ALL]-non-Hodgkin's lymphoma [NHL] and 13 with solid tumors) and the second group (GM-CSF) included 14 children (5 with ALL-NHL and 9 with solid tumors). All 39 children received of either G-CSF or GM-CSF (5 micrograms/kg/day) subcutaneously at the end of each chemotherapy course for a maximum duration of 14 days. The effect of G-CSF and GM-CSF on the ANC, the antibiotic therapy administration, and the length of hospital stay were studied for both groups at two cycles of chemotherapy. During both cycles a faster rise of ANC was observed in the children of the first group (G-CSF) compared with those of the second group (GM-CSF), but there was no difference in either the incidence of antibiotic therapy administration between the two groups (26% vs 25%) or the length of hospitalization. Both growth factors were well tolerated by all children studied with minimal side effects observed (including bone pain with G-CSF in 2 of 25 children and pruritus with GM-CSF in 1 of 14). We conclude that G-CSF reduces the duration of neutropenia more than does GM-CSF, but the incidence of severe infection and the duration of hospitalization do not differ between children receiving either G-CSF or GM-CSF.
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PMID:Efficacy of recombinant human granulocyte colony-stimulating factor and recombinant human granulocyte-macrophage colony-stimulating factor in neutropenic children with malignancies. 858

Recombinant human interleukin-3 (rhIL-3), granulocyte-macrophage colony-stimulating factor (rhGM-CSF), and granulocyte colony-stimulating factor (rhG-CSF) enhance neutrophil recovery following autologous bone marrow transplantation (ABMT) for malignant lymphoma. Based on findings in preclinical studies, a phase I-II trial was conducted to assess the safety and efficacy of the sequential administration of rhIL-3 and rhGM-CSF after bone marrow ablative cytotoxic therapy and ABMT for patients with malignant lymphoma. Thirty-seven patients (20 with non-Hodgkin's lymphoma and 17 with Hodgkin's disease) were treated with intensive cytotoxic therapy before ABMT. Patients were treated in one of four cohorts to receive rhIL-3 (2.5 or 5.0 microg/kg/d) administered by subcutaneous injection for either 5 or 10 days following ABMT. Twenty-four hours after the last dose of rhIL-3, rhGM-CSF (250 microg/m2/d as a 2-hour intravenous infusion) administration was initiated. Sequential cytokine therapy post-ABMT resulted in fewer days of platelet and red blood cell transfusions than seen in historic controls with rhIL-3, rhGM-CSF, or rhG-CSF monotherapy. These data suggest that the sequential administration of rhIL-3 and rhGM-CSF after ABMT results in rapid recovery of multilineage hematopoiesis.
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PMID:Recombinant human interleukin-3 and granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for malignant lymphoma. 860 May 45

We investigated the in vitro antitumor activity of monocytes derived from autologous bone marrow transplanted (ABMT) patients treated in vivo with granulocyte-macrophage colony-stimulating factor (GM-CSF). Thirty-four patients (17 female, 17 male), median age 42 (range 3-57) years, were enrolled in the study. Fourteen patients were diagnosed with non-Hodgkin's lymphoma (NHL), eight with Hodgkin's disease (HD), nine with breast cancer and three with neuroblastoma. Six patients who did not receive GM-CSF post-ABMT served as controls. We assessed cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC), expression of the activation antigen CD16, and cytokine production by an enriched population of monocytes (> 90% CD+14) pre-, during and post-GM-CSF administration. Within the group of patients receiving treatment, ADCC was significantly higher during in vivo GM-CSF administration than post-therapy (P < 0.05) and in 50% of these patients, ADCC increased during in vivo GM-CSF administration over pretreatment values. In addition, in vivo GM-CSF administration caused the monocytes to secrete elevated levels of tumor necrosis factor-alpha (TNF-alpha) and GM-CSF (P < 0.05). We conclude that GM-CSF augments monocyte-mediated cytotoxicity post-ABMT, and therefore may have a role in controlling minimal residual disease post-transplant.
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PMID:Granulocyte-macrophage colony-stimulating factor dependent monocyte-mediated cytotoxicity post-autologous bone marrow transplantation. 891 16

The idiotype (Id) of the Ig expressed on the surface of non-Hodgkin's lymphoma cells is a suitable target for immunotherapy. Indeed, treatment with monoclonal anti-Id antibodies (Abs) can induce long-lasting clinical remissions. However, some of the treated patients relapse with a tumor expressing Ig with point mutations in the idio recognized by the particular monoclonal antibody (MoAb). The alternative approach of active immunization with tumor Id can cure the disease in mice with established tumors and is now being studied in clinical trials. Here, we tested the hypothesis that active immunization with the idiotype would evoke a polyclonal immune response that would cover mutated tumor variants. As a test system, we chose the tumor from a patient who had achieved a complete remission after therapy with anti-Id Ab but subsequently relapsed with a mutated tumor variant no longer binding the treatment Ab. Mice were immunized with proteins and genetic vaccines derived from the original tumor, including (1) Id-keyhole limpet hemocyanin protein, (2) Id single-chain variable fragment (scFv) granulocyte-macrophage colony-stimulating factor (GM-CSF) protein, (3) DNA encoding the Id, and (4) an adenovirus encoding the Id. All immunized mice developed a specific immune response detecting tumor-derived Id proteins from the original tumor and from all tumor variants. We conclude that active immunization with tumor Id can induce a polyclonal immune response and therefore may prevent the escape of mutated tumor variants.
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PMID:Idiotype vaccines for non-Hodgkin's lymphoma induce polyclonal immune responses that cover mutated tumor idiotypes: comparison of different vaccine formulations. 934 55

Proliferating human medullary thymocytes can exhibit characteristic T helper cell type 1 cytokine responses exemplified by the immediate early expression of interleukin-2, interferon-gamma, tumor necrosis factor-alpha, and lymphotoxin-beta. Here we report that cAMP-mediated attenuation of the transcription of T helper-1-specific cytokine genes in human medullary thymocytes correlates with the induction of the cAMP-mediated transcriptional repressor ICER (inducible cAMP early repressor). We show that ICER binds specifically to several NFAT/AP-1 (nuclear factor of activated T cells/activating protein-1) composite DNA sites essential for the activation of the interleukin (IL)-2 promoter as well as to a homologous DNA motif present in the proximal segment of the interferon-gamma promoter. In the presence of the minimal NFAT DNA-binding domain, which is sufficient for both DNA binding and AP-1 complex formation, ICER and NFAT form NFAT/ICER ternary complexes on several NFAT/AP-1 DNA composite sites previously identified as essential for the expression of the immunoregulatory cytokines such as IL-2, IL-4, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha. In extracts prepared from human medullary thymocytes treated with forskolin and ionomycin, these composite sites bind endogenously expressed ICER either singly or in complexes. Moreover, in Jurkat cells, ectopically expressed ICER represses transcription from NFAT-mediated, phorbol ester/ionophore-activated IL-2, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha promoters. We present evidence that ICER interactions with NFAT/AP-1 composite DNA sites correlate with its ability to repress transcription. These findings provide further insight into the mechanisms involved in cAMP-mediated transcriptional attenuation of cytokine expression.
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PMID:Role of transcriptional repressor ICER in cyclic AMP-mediated attenuation of cytokine gene expression in human thymocytes. 954 84

PIXY321, a granulocyte-macrophage colony-stimulating factor/interleukin 3 (GM-CSF/IL-3) genetically engineered hybrid, has shown greater biological activity in stimulating committed myeloid progenitors than either GM-CSF or IL-3 in vitro, in vivo, and in patients treated with high-dose chemotherapy. However, one concern is that PIXY321 may stimulate the proliferation of malignant cells which have functional GM-CSF or IL-3 receptors. Therefore, using a human tumor cloning assay, we have tested the effects of several concentrations of PIXY321 ranging from 0.1 to 100 ng/ml on tumor cells taken directly from 98 patients with solid tumors and Hodgkin's or non-Hodgkin's lymphomas. Of the 34 evaluable specimens, including 15 breast cancers, 5 ovarian cancers, 5 lung cancers, and 9 lymphomas, none showed stimulation of tumor growth. Interestingly, a significant inhibition of the tumor proliferation was seen in one breast cancer and in one large cell immunoblastic non-Hodgkin's lymphoma after continuous exposure of PIXY321. In conclusion, the use of PIXY321 to reduce myelosuppression after high-dose chemotherapy appears unlikely to result in stimulation of the growth of malignant cells in patients with lymphoma or cancers of the breast, lung, and ovary.
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PMID:Effects of PIXY321, a granulocyte-macrophage colony-stimulating factor/interleukin 3 fusion protein, on human tumor colony-forming units taken directly from patients. 981 21

The present study analysed whether autologous peripheral blood stem cell transplantation (PSCT) improves engraftment, quality of life and cost-effectiveness when compared with autologous bone marrow transplantation (ABMT). Relapsing progressive lymphoma patients (n = 204; non-Hodgkin's lymphoma n = 166; Hodgkin's disease n = 38) were, after induction treatment with the DHAP-VIM (cisplatin, cytarabine, dexamethasone, etoposide, ifosfamide, methotrexate) regimen, randomly (2:1) assigned to the harvest of granulocyte-macrophage colony-stimulating factor-mobilized stem cells after the second DHAP course or autologous bone marrow cells before the second DHAP course. These stem cells were reinfused following high-dose myeloblative chemotherapy. After induction, 118 patients obtained a partial or complete response and were eligible for randomization. In the PSCT arm (n = 76) significantly faster engraftment of neutrophils [> or = 0.1 and > or = 0.5 x 10(9)/l: 10.7 d (7-36, median, range), 15 (9-45) versus 13 (8-25) and 26 (14-80), P < 0.01] and thrombocytes [> or = 20 x 10(9)/l: 13 d (7-51) versus 18 (11-65), P < 0.01] were observed. In addition, significantly fewer transfusions of red blood cells [6 (0-23) versus 8 (2-24), P < 0.01] and platelets [4 (0-60) versus 8 (2-55), P = 0.01] were required in the PSCT arm. These findings were associated with a significant reduction in the median days of intravenous antibiotics in patients with fever [8.5 (0-30) versus 14 (0-34), P = 0.04] and hospital stay [27 (8-51) versus 34 (24-78), P < 0.05]. Quality of life demonstrated a significant difference in favour of the PSCT arm. Total transplantation costs were significantly lower in the PSCT arm [$13,954 ($4913- 29,532) versus $17 668 ($10,170-44,083) P < 0.05], as a result of the reduced hospital stay and lower antibiotic costs. In summary, these results indicate that PSCT is superior to ABMT with regard to engraftment, supportive care, quality of life and cost.
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PMID:Autologous peripheral blood stem cell transplantation in patients with relapsed lymphoma results in accelerated haematopoietic reconstitution, improved quality of life and cost reduction compared with bone marrow transplantation: the Hovon 22 study. 1152 50

Dendritic cells (DC) are potent antigen-presenting cells that are integral to the initiation of T cell immunity. The ability to culture these cells in vitro has allowed DC immunotherapy to be investigated as a mechanism of enhancing immune responses against various malignancies. We examined the optimal time for generating DC and compared DC generated from normal donors for allogeneic blood stem cell transplantation, or patient's with non-Hodgkin's lymphoma or breast cancer undergoing high-dose chemotherapy and autologous stem cell transplantation. Experiments were conducted to compare DC cultured prior to and post mobilization chemotherapy. Blood was obtained from consenting patients prior to granulocyte colony-stimulating factor (G-CSF) administration with (non-Hodgkin lymphoma and breast cancer) or without (normal donors) chemotherapy. A sample of apheresis product (AP) was obtained at the time of apheresis. DC were generated from peripheral blood mononuclear cells by culturing the adherent cells in the presence of interleukin-4 and granulocyte-macrophage colony-stimulating factor. Resultant DC were harvested and examined for yield, morphology, phenotype, and function. All cell populations yielded highly pure DC, as assessed by light microscopy and flow cytometry. The average cellular yield was significantly greater from AP than steady-state blood in paired and unpaired samples. Yield did not correlate with the percentage of CD14(+) cells, and it negatively correlated with CD34 counts. DC from breast cancer patients functioned significantly better than DC from lymphoma patients in a mixed lymphocyte reaction. These data suggest that the optimal timing of culturing DC is after mobilization, and that differences may exist in the functional capabilities of DC derived from different patient populations.
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PMID:Generation of dendritic cells ex vivo: differences in steady state versus mobilized blood from patients with breast cancer, with lymphoma, and from normal donors. 1167 8

Treatment for extensive indolent lymphoma should provide optimization of efficacy while avoiding excessive toxicity. Rituximab may be an ideal agent to combine with chemotherapy because of its lack of classical myelotoxicity. In this study, 27 patients with a variety of histologies of indolent B-cell non-Hodgkin's lymphoma have been treated utilizing a novel three-drug combination. Nine patients had relapsed disease and 18 were previously untreated. Patients first received cyclophosphamide 800 mg/m(2) and mitoxantrone 8 mg/m(2) i.v. on day 1, every 3 weeks for 2 cycles. Subsequently, patients received rituximab 375 mg/m(2) followed by mitoxantrone 8 mg/m2 every 2 weeks for 4 cycles. This regimen and, in particular, the rituximab infusion were extremely well tolerated. Only two of 27 patients experienced a grade 1/2, infusion-related reaction during the first rituximab infusion. Grade 4 neutropenia was noted at some point in 16 patients who were then offered granulocyte-macrophage colony-stimulating factor support for improvement of neutropenia. No infections were noted. Alopecia was minimal. Of 27 patients, 19 achieved a complete response (CR), one achieved an unconfirmed CR (CRu), and five patients achieved a partial response, for an overall response rate of 92.5%. Molecular remissions were noted in seven of 12 tested patients in CR. We concluded that the cyclophosphamide/mitoxantrone/rituximab (CyMiR) regimen is effective and extremely well tolerated. Furthermore, rituximab infusion-associated morbidity is markedly reduced.
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PMID:Excellent tolerance of rituximab when given after mitoxantrone/cyclophosphamide: an effective and safe combination for indolent non-Hodgkin's lymphoma. 1170 27

Chemotherapy regimens similar to those used for non-Hodgkin's lymphoma (NHL) not associated with human immunodeficiency virus (HIV) infection have been used for patients with HIV-associated NHL with less success. In a recent trial, patients with intermediate or high-grade NHL were randomized to either low-dose chemotherapy with methotrexate, bleomycin, doxorubicin, vincristine and dexamethasone (m-BACOD) or to standard-dose m-BACOD with sargramostim (granulocyte-macrophage colony-stimulating factor, GM-CSF). With low-dose m-BACOD 41% of patients achieved a complete remission and the median survival was 35 weeks. With standard-dose m-BACOD and sargramostim, the percentage of complete remissions was 52% with a median survival of 31 weeks (P=n.s.). Myelosuppression was greater with standard-dose chemotherapy. In univariate and multivariate analyses of 21 pretreatment features of patients in this trial, four factors emerged as adversely prognostic with respect to survival: age >35 years, intravenous drug use, CD4 counts < 100/mm3 and stage III/IV disease. In an analysis using the proportional hazards model, a "favorable" group was defined by patients with 0 or 1 adverse factor (median survival 46 weeks, survival at 144 weeks 29.5%) as compared with an unfavorable group with 3 or 4 adverse factors (median survival 18 weeks, survival at 144 weeks 0). The outcome of these patients may be improving with the use of highly active antiretroviral therapy (HAART), which seems to improve immune function and tolerance of chemotherapy. A recent trial of the AIDS Malignancy Consortium found that low-dose chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone: CHOP) and standard-dose chemotherapy had similar response rates, acceptable toxicity and minimal alterations in cyclophosphamide, doxorubicin and indinavir pharmacokinetics in HIV-associated lymphoma patients also on HAART (stavudine, lamivudine and indinavir). There is a suggestion that Burkitt-type lymphomas may tend to occur in HIV-infected patients with relatively well preserved immune function and CD4 cell counts. Recent results from our institution suggest that similar outcomes are achievable with intensive chemotherapy in patients with Burkitt's lymphomas with or without HIV infection. With improved immune status and improved bone marrow function with the use of HAART, it will probably become more possible to treat many patients with aggressive HIV-associated NHL with more intensive treatment regimens.
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PMID:Prognostic factors in the treatment of human immunodeficiency virus-associated non-Hodgkin's lymphoma. 1178 38


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