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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)

In vitro proliferation of leukemic cells purified from 10 cases of acute myeloblastic leukemia (AML) was analyzed in basal conditions or in the presence of exogenous recombinant (r) Interleukin (IL) 1. In parallel, blasts from 5 of these patients were studied for granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte-CSF (G-CSF) mRNA. IL-1 augmented the spontaneous AML cell proliferation in all cases and induced de novo expression or increased amounts of GM-CSF and/or G-CSF transcripts in 4 of the 5 cases evaluated. IL-1-induced AML cell proliferation was modulated by neutralizing anti-GM-CSF or anti-G-CSF antibodies in those cases in which CSF mRNAs were induced or increased by exogenous cytokine. In the same cases, biosynthetic labelling and immunoprecipitation studies using monospecific anti-GM-CSF antibodies showed that IL-1 also increased the levels of GM-CSF protein synthesis. Addition of neutralizing anti-IL-1 antibodies to AML cell cultures completely abolished ongoing GM-CSF synthesis, suggesting that endogenous IL-1 is needed to maintain autocrine production of CSFs. The effects of rIL-2 were investigated in a larger series of 21 patients. The cytokine reduced spontaneous AML cell proliferation in 8 cases. It caused complete disappearance of GM-CSF mRNA in 1 case, and marked reduction of G-CSF mRNA in 2 cases. Increased AML cell proliferation was observed in 2 of 21 cases. These findings suggest that expression of CSF genes and cell proliferation in AML are under the control of different cytokines acting in autocrine or paracrine fashion.
Int J Cancer 1990 Nov 15
PMID:Interleukin-1 and interleukin-2 control granulocyte- and granulocyte-macrophage colony-stimulating factor gene expression and cell proliferation in cultured acute myeloblastic leukemia. 169 3

Although under study to alleviate chemotherapy-induced bone marrow toxicity, cytokines can stimulate in vitro growth of solid human tumour cell lines. The effects of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF) and interleukin-3 (IL-3) on in vitro colony formation of primary human tumours was studied in a capillary soft-agar cloning system. Of 108 tumour specimens from 100 patients, 85 specimens were tested against all three factors at concentrations ranging from 0.1 to 1000 ng/ml. 44 of 100 tumours showed adequate growth in controls. 8 out of 43 (19%) specimens were significantly stimulated by GM-CSF, 6 of 40 (15%) by G-CSF and 10 of 44 (23%) by IL-3. Sensitivity to all three cytokines was observed in 4 of 44 (9%) specimens. By light microscopy the appearance of colonies from stimulated specimens was identical to that of controls. Sensitivity to cytokines was independent from sensitivity to epidermal growth factor, transferrin or insulin. Sensitivity to GM-CSF, G-CSF and IL-3 may be aberrantly expressed in a subgroup of solid human tumours.
Eur J Cancer 1990
PMID:Effects of cytokines on in vitro colony formation of primary human tumour specimens. 170 19

Immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells results in significant tumor regression in patients with advanced cancer. We have investigated the kinetics of circulating erythroid (BFU-E) and granulocytic-macrophage (CFU-GM) progenitors after IL-2 therapy in 11 cancer patients, mainly affected by metastatic melanoma and renal cell carcinoma. Administration of IL-2 from day 1 through day 5 constantly induced a dramatic decrease of the number of circulating BFU-E and CFU-GM, which then showed a striking rebound (up to values fourfold and sevenfold higher, respectively, than the pretherapy levels) on discontinuation of IL-2, ie, from day 5 through day 10. A similar kinetic pattern was observed during and after the second cycle of IL-2 administration. 3[H]-thymidine killing experiments showed that the cycling activity of the progenitors was virtually unmodified in the rebound phases. To explore the mechanism(s) underlying this kinetic pattern, we have analyzed the plasma concentration of several hematopoietic growth factors, including IL-1 beta, IL-3, IL-4, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, and erythropoietin (Ep). No modifications in the levels of IL-3, GM-CSF, or IL-1 beta were observed, whereas a pronounced increase of IL-6 and G-CSF concentration was monitored, starting at day 3 and peaking at day 5 of treatment (a parallel, but modest, increase of Ep level was also observed). The elevation of IL-6 and G-CSF concentration is directly correlated with and may, at least in part, underlie the subsequent rebound of circulating hematopoietic progenitors. Furthermore, the increase in IL-4 level observed at day 10 of therapy may mediate the eosinophilia gradually starting at this stage of treatment.
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PMID:Adoptive immunotherapy with high-dose interleukin-2: kinetics of circulating progenitors correlate with interleukin-6, granulocyte colony-stimulating factor level. 170 62

The hematopoietic growth factors are under investigation for the treatment of patients with chemotherapy-induced bone marrow suppression. One such trial at the University of California, Los Angeles involves chemotherapy with or without granulocyte colony-stimulating factor (G-CSF) in patients with small cell lung cancer. The authors report a case of a patient who had bullous pyoderma gangrenosum at the site of previous eczema during treatment with G-CSF. The lesions resolved promptly when the drug was discontinued. Other investigators have recently reported inflammatory complications of G-CSF and granulocyte-macrophage colony-stimulating factor (GM-CSF) but this is the first case report of biopsy-proven neutrophilic dermatosis associated with administration of a hematopoietic growth factor. Patients should be monitored for development of inflammatory processes during G-CSF therapy and this therapy should be given with caution to those patients with existing inflammatory conditions.
Cancer 1991 Jul 15
PMID:Bullous pyoderma gangrenosum after granulocyte colony-stimulating factor treatment. 171 66

Cytokines have been of much interest in clinical cancer therapy research over the past decade. One important advance during the past year has been the clear demonstration, in large prospective randomized studies, that granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor reduce the neutropenia-related morbidity of cancer therapy.
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PMID:Cytokines in clinical cancer therapy. 172 23

A neutrophil chemotactic factor (human interleukin 8, human granulocyte-macrophage colony-stimulating factor)-producing cell line, named KHM-5M, was established from a patient with an undifferentiated thyroid carcinoma, neutrophilia, and malignant pleurisy with many neutrophils and a few malignant cells. The cell line was transplanted into nude rats, and the infiltration of neutrophils was observed in and around the transplanted tumor tissue. Neutrophil chemotactic activity was predicted from the clinical features and pathological findings in this case. The extreme chemotactic activity of the neutrophils was demonstrated in conditioned medium from KHM-5M cells using the modified Boyden chamber technique. With sodium dodecyl sulfate-polyacrylamide gel electrophoresis, at least two neutrophil chemotactic activities in conditioned medium from the cell line were observed. The levels of these activities derived from KHM-5M cells were screened by measuring conditioned medium from the COS cells, which expressed a complementary DNA library from the KHM-5M cells. Chemotactic activities (human interleukin 8, human granulocyte-macrophage colony-stimulating factor) were identified by DNA cloning. These results show that the KHM-5M cells derived from an undifferentiated thyroid carcinoma produce multicytokines and suggest that those cytokines modified some pathological features in this case.
Cancer Res 1992 Jan 15
PMID:Neutrophil chemotactic factors produced by a cell line from thyroid carcinoma. 172 17

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) is a regulatory glycoprotein that stimulates the production of granulocytes and macrophages from committed hematopoietic progenitor cells both in vitro and in vivo. In this report, we show that recombinant human GM-CSF enhances colony formation by nonhematopoietic human ovarian cancer cell lines, IGROV-1, A2774, ME-180, Pa-1 and A2780. GM-CSF also enhanced the colony formation by cells obtained from fresh ascites of a patient with ovarian mucinous cystadenocarcinoma and a patient with serous papillary ovarian carcinoma. Our observations were made with GM-CSF concentrations between 0.1 to 1 ng/ml; these concentrations are equivalent to the dosages generally used for bone marrow recovery after chemotherapy.
Jpn J Cancer Res 1991 Nov
PMID:Human granulocyte-macrophage colony-stimulating factor is a growth factor active on human ovarian cancer cells. 175 77

Increasing evidence suggests that an intimate correlation may exist between the production of a cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF) and the ability to metastasize spontaneously in the lungs in murine transplantable tumors. In the present study, we further examined the cytokine production by tumor cells with the ability to metastasize in the liver. Four out of 8 test tumors, which produced metastasis in the lungs but not in the liver, exhibited the ability to produce GM-CSF activity in culture. Three other tumors produced metastasis in the liver but not in the lungs. These tumor cells exhibited no ability to produce GM-CSF, but two of them expressed an interleukin-6 (IL-6) mRNA and also produced IL-6 activity in the culture fluids. One of the two IL-6-producing tumors and the remaining liver metastatic tumor produced interleukin-1 (IL-1) as revealed by bioassay and neutralization test. In the tumor cells producing pulmonary metastasis, neither IL-6 gene expression nor IL-1 production could be detected. The last test tumor, which produced no metastasis either in the lungs or liver, produced neither GM-CSF, IL-1 nor IL-6. Furthermore, injection of antisera reactive to recombinant murine IL-6 caused a marked decrease of the number of liver metastases of an IL-6-producing tumor, but not lung metastases of a GM-CSF-producing tumor, which could be markedly inhibited by injection of anti-recombinant murine GM-CSF sera. These results suggest the possibility that there may be a correlation between the cytokines produced by tumor cells and their organ specificity in spontaneous metastasis, and also indicate that these tumor models may provide a useful tool for studies on the role of cytokines in tumor metastasis.
Jpn J Cancer Res 1991 Nov
PMID:Murine tumor cells metastasizing selectively in the liver: ability to produce hepatocyte-activating cytokines interleukin-1 and/or -6. 175 86

Recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) may reduce myelosuppression and, thus, allow dose escalation of certain chemotherapeutic agents. We conducted two sequential phase I trials of escalating doses of carboplatin and a fixed dose and schedule of rHuGM-CSF in ovarian cancer patients who had not previously had chemotherapy, i.e., chemotherapy-naive patients. In the first trial, patients were assigned to regimens of increasing dose levels of carboplatin (starting at 400 mg/m2) and fixed doses and schedules of cyclophosphamide (600 mg/m2) and rHuGM-CSF (10 micrograms/kg given subcutaneously once daily on days 2-11). Chemotherapy was given every 3 weeks (regimen A). In the subsequent trial, the design was the same except that cyclophosphamide was omitted (regimen B). Fifteen patients received regimen A, and seven patients received regimen B. In regimen A, all three patients treated at the first dose level tolerated five cycles at full doses. Hematologic toxicity was dose limiting at the 600-mg/m2 dose level. When 500 mg/m2 carboplatin was given, six of eight patients tolerated three or four cycles at full doses before requiring dose reductions or treatment delays. In regimen B, doses could not be escalated above the first dose level (600 mg/m2) because of severe hematological toxicity. Nonhematological toxicity was tolerable and managed with acetaminophen, antihistamines, and/or nonsteroidal, anti-inflammatory medication. Compliance was excellent. We conclude that (a) rHuGM-CSF can be given safely and reliably to chemotherapy-naive ovarian cancer patients receiving these treatment regimens, (b) early and severe thrombocytopenia was a major problem with or without cyclophosphamide with doses of carboplatin at or above 600 mg/m2, and (c) 500 mg/m2 carboplatin administered every 3 weeks is the highest dose in regimen A that can be given safely in the outpatient setting.
J Natl Cancer Inst 1991 Dec 04
PMID:Two phase I studies of carboplatin dose escalation in chemotherapy-naive ovarian cancer patients supported with granulocyte-macrophage colony-stimulating factor. 177 May 54

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


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