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 mechanisms which control the production of erythropoietin (Epo) remain enigmatic. Recent data suggest that the half-time of Epo messenger RNA (mRNA) is increased by hypoxia in Hep 3B cells, a human hepatoma line. The post-transcriptional regulation of other rapidly degraded mRNAs is mediated by sequence-specific mRNA binding proteins. In order to determine if Epo mRNA specific binding proteins exist, we probed cytosolic lysates from Hep 3B cells and mouse tissues with radiolabeled Epo RNA. A cytosolic protein that binds specifically to Epo RNA was identified in the Epo-producing, hepatoblastoma Hep 3B cell line by gel mobility shift assay. This protein was identified in both normoxic and hypoxic cells and bound specifically to a 120-base fragment of the 3'-untranslated region (3'-UTR) of Epo mRNA. Binding was completed with unlabeled Epo RNA, but not with granulocyte-macrophage colony-stimulating factor RNA. Ultraviolet light cross-linked Epo RNA-protein complexes migrated as two bands of 70 and 135-140 kD on sodium dodecyl sulfate-polyacrylamide gels. Binding activity was markedly increased in brain and spleen lysates from mice subjected to 24 h of hypoxia. Therefore, the post-transcriptional regulation of Epo expression in response to hypoxia may in part be due to the interaction of Epo RNA with its specific binding protein.
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PMID:Hypoxia up-regulates the activity of a novel erythropoietin mRNA binding protein. 165 42

Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) secreted by a hepatoma cell line, HA22T/GVH, was purified and assessed for its effects in vivo on blood leukocytes and bone marrow granulocyte-macrophage progenitor cells (CFU-GM) in ICR mice pretreated with a sublethal dose of cyclophosphamide (cytoxan). The hGM-CSF preparations were natural and had no detectable endotoxin. Five days after the administration of 300 mg/kg cytoxan, severe leukopenia with marked myelopoietic suppression was induced. The cytoxan-treated mice were then injected intraperitoneally with 10,000 units of purified hGM-CSF/mouse daily for three days. Leukopenia was totally abrogated and the leukocyte number greatly increased to a level 2- to 3-fold higher than in GM-CSF-uninjected mice. Differential white cell count showed that the subpopulations of leukocytes responsive to hGM-CSF stimulation were mainly of neutrophils and monocytes, while the lymphocytes remained unaffected. Meanwhile, in the bone marrow, hGM-CSF administration induced an apparent (3-fold) increase in the number of myeloid progenitor cells, CFU-GM. However, the effect in vivo of a single hGM-CSF injection could only maintain for 48 hrs. In addition, the loss in body weight caused by cytoxan was less in the mice with subsequent hGM-CSF than those without CSF. These results suggest that injection of GM-CSF can effectively reconstitute the cytotoxic drug-damaged myelopoiesis without apparent in vivo toxic reaction.
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PMID:In vivo stimulation of myelopoiesis in cyclophosphamide-treated mice by purified human GM-CSF. 165 33

The expression of granulocyte colony-stimulating factor (G-CSF) mRNA was studied in human non-hematopoietic tumors, including 18 cases of lung cancers 10 cases of stomach cancers, three cases of glioblastomas, and one case each of breast phyllode sarcoma, thyroid cancer, and hepatocellular carcinoma. Northern blot analysis detected G-CSF mRNA in two of the lung cancer cases, in one of the glioblastoma cases, and in both the breast phyllode sarcoma and hepatocellular carcinoma cases. Since G-CSF receptors were not detected on the tumor cells by 125I-G-CSF binding assay, G-CSF autocrine loop are probably not involved in the growth of these G-CSF-producing tumors. Interestingly, granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA was concomitantly expressed in most of these G-CSF-producing tumors. No major gene deletions or rearrangements of G-CSF and GM-CSF genes were demonstrated by Southern blot analysis in the tumors expressing G-CSF and GM-CSF mRNAs except for one of the glioblastomas (G3) in which one chromosome 17 allele was deleted. Although the mechanism of the concomitant expression of G-CSF and GM-CSF mRNA is unknown, relatively high frequency of this phenomenon suggests the presence of common transcriptional factors acting on regulatory regions of G-CSF and GM-CSF genomes.
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PMID:Expression of granulocyte and granulocyte-macrophage colony-stimulating factors by human non-hematopoietic tumor cells. 170 53

Conditioned medium (CM) obtained from a human hepatoma cell line, SK-HEP-1, contains colony-stimulating factors (CSFs) active on murine and human bone marrow-derived granulocyte and macrophage colony-forming units (CFU-GM) and a factor capable of inducing granulocyte-macrophage differentiation (GM-DF) of murine myelomonocytic leukemic cells WEHI-3B(D+) and human promyelocytic leukemic cells HL-60 when assayed in semisolid agar cultures. The human active granulocyte-macrophage colony-stimulating factor (GM-CSF) for day 7 CFU-GM and the GM-DF for WEHI-3B(D+) and for HL-60 are not separable by acrylamide agarose column chromatography, eluting at an apparent molecular weight between 20,000 and 35,000 daltons, or by isoelectric focusing (isoelectric point, pH 5.4). In addition, SK-HEP-1 CM contains erythroid burst-promoting activity (BPA) and a factor that promotes the growth of human mixed colonies. SK-HEP-1 cells, which grow as an adherent monolayer, appear not to be endothelial or monocytic in origin since by immunofluorescent staining they are negative for Ia (HLA-DR), monocyte antigen 1 and 2, lysozyme, and factor VIII-related antigen. Positive immunofluorescent staining for keratin and fibronectin suggests the possibility that SK-HEP-1 is an epithelial cell line. Constitutive production of GM-DF as well as other hematopoietic activities including GM-CSF, erythroid BPA, and an activity that promotes the growth of human mixed colony progenitors by a human epithelial tumor cell line, SK-HEP-1, suggests that this cell line is a valuable resource for both large-scale production of these factors and the cloning of the gene(s) that code for these regulators.
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PMID:Constitutive production of leukemia differentiation, colony-stimulating, erythroid burst-promoting, and pluripoietic factors by a human hepatoma cell line: characterization of the leukemia differentiation factor. 299 Jun 10

Interleukin-8 (IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are important mediators of inflammation and immune response in human disease. To demonstrate their importance in pathophysiological processes in liver disease, we measured the circulating levels of IL-8 and GM-CSF in patients with hepatocellular carcinoma (HCC) and chronic active hepatitis (CAH). IL-8 and GM-CSF levels in serum samples were determined with highly specific and sensitive enzyme-linked immunosorbent assays. IL-8 levels were more elevated in serum samples of patients with HCC and CAH associated with hepatitis C virus infection than HCC and CAH associated with hepatitis B virus infection. However, in all patients with autoimmune CAH and in some patients with HCC and CAH, GM-CSF levels were elevated over the baseline levels measured in all of the normals, but this difference was not statistically significant for any group. We conclude that IL-8 and GM-CSF are increased in some patients with liver diseases, and as such they may play a significant role in host defense and disease.
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PMID:Interleukin-8 and granulocyte-macrophage colony-stimulating factor secretion in hepatocellular carcinoma and viral chronic active hepatitis. 785 12

A panel of two poorly differentiated (HA22T/VGH and SK-Hep-1) and six well-differentiated (HuH-6-cl 5, HuH-7, PLC/PRF/5, Hep G2, Hep 3B, and Tong) human hepatocellular carcinoma (HCC) cell lines were studied for the production of colony-stimulating factors (CSFs) using the granulocyte and macrophage colony formation (CFU-GM) assay, immunocytochemical staining, and Northern blotting. Medium conditioned by untreated HA22T/VGH cells contained a high level of CSFs that could stimulate the in vitro colony formation of human myeloid progenitor cells. The HA22T/VGH cell-derived CSF had an apparent molecular weight of 23 kD. Its activity could be effectively neutralized by antiserum against granulocyte-macrophage CSF (GM-CSF) but not by antibodies to other hematopoietic growth factors, including G-CSF, M-CSF, interleukin-3 (IL-3), and IL-6. Correspondingly, immunocytochemical studies using monoclonal anti-GM-CSF showed a strong positive reaction in the cytoplasm of the HA22T/VGH cells. Northern blot analysis revealed that untreated HA22T/VGH cells expressed a considerable amount of GM-CSF mRNA, confirming that GM-CSF production was constitutive. At optimal concentrations, lipopolysaccharide (LPS), IL-1beta, interferon-gamma (IFN-gamma), and tumor-promoting phorbol diester (TPA) could all stimulate HA22T/VGH cells to secrete GM-CSF. In addition to HA22T/VGH, SK-Hep-1 cells could also produce GM-CSF, although less effectively, whereas all the well-differentiated HCC cell lines tested were negative for CSF production. Morphologic, cytochemical, and immunocytochemical examinations demonstrated that both poorly differentiated CSF-producing HCC cell lines (HA22T/VGH and SK-Hep-1) were macrophage-like in morphology, possessed nonspecific esterase (NSE) activity, and expressed CD14, CD68, and HLA-DR on their surface, while all the well-differentiated HCC cell lines were epithelioid and lacked myeloid differentiation antigens. These results suggest that monocytoid features and CSF production may be differentiation markers of hepatocytes at the immature stages, amd that the HA22T/VGH and SK-Hep-1 cell lines may be valuable tools for the study of hepatic function and differentiation.
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PMID:Constitutive production of colony-stimulating factors by human hepatoma cell lines: possible correlation with cell differentiation. 859 73

gP130 transducing receptor is involved in the formation of high affinity receptors for the cytokines of the interleukin-6 (IL-6) family. Recruitment of gp130 by IL-6 associated to its receptor leads to the dimerization of the transducing component. In the present study we did characterize the B-S12 monoclonal antibody raised against gp130 and able to elicit IL-6 type biological activities. B-S12 antibody triggered strongly the proliferation of TF1 and XGI hematopoietic cell lines and was able to increase the synthesis of acute phase proteins in HepG2 hepatoma cell line. B-S12 also behaved as a synergistic factor with granulocyte-macrophage colony-stimulating factor for both proliferation and differentiation of CD34-positive hematopoietic cell progenitors. By using a symmetric enzyme-linked immunosorbent assay, allowing the detection of dimeric forms of soluble gp130, we found that addition of B-S12 to gp130 led to its dimerization. Analysis of the tyrosine phosphorylation events in gp130 and Jak kinase family members revealed that B-S12 quickly induced the phosphorylation of gp130 in a neural derived cell line, and that Jak1 and Jak2 were also recruited. In conclusion, we show that gp130 cross-linking with the B-S12 monoclonal antibody was sufficient to generate functional IL-6 type responses in hematopoietic, neural, and hepatic cells.
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PMID:gp130 transducing receptor cross-linking is sufficient to induce interleukin-6 type responses. 866 9

The proliferation and differentiation of hematopoietic cells are stimulated by a group of glycoproteins called colony stimulating factors (CSFs). Previously, we found that the human hepatoma cell line HA22T/VGH secreted a high level of human granulocyte-macrophage colony-stimulating factor (hGM-CSF). The cDNA of hGM-CSF, including the signal peptide sequence, was amplified from the total RNA of HA22T/VGH by a reverse-transcription polymerase chain reaction and was cloned into the pUC18 vector. After confirming the nucleotide sequence, the cDNA was inserted into a pVL1393 baculovirus transfer vector. The recombinant baculovirus carrying hGM-CSF cDNA was generated by co-transfecting the hGM-CSF recombinant transfer vector and BaculoGold baculovirus DNA into the Sf9 insect cells. The expected hGM-CSF transcript was detected in the recombinant virus-infected Sf9 cells. The conditioned media of the infected cells were analyzed by a slot-blot immunoassay. The results indicate that the infected insect cells produced and secreted hGM-CSF. According to colony forming assay, a maximum titer of 2.1 x 10(6). U ml-1 of hGM-CSF in the medium was obtained on the third day after infection.
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PMID:Secretory production of bioactive recombinant human granulocyte-macrophage colony-stimulating factor by a baculovirus expression system. 898 79

The use of genetically modified tumor cells as vaccines has been successful in numerous animal models of grafted syngenic tumors and has provided the groundwork for many clinical trials of gene therapy in cancer patients. To investigate the real efficacy of ex vivo gene therapy-based vaccines, we used transgenic mice that express the SV40 large T and small t antigens under the control of hepatic antithrombin III (ASV-B)-regulatory sequences. These mice systematically develop hepatocarcinoma. Hepatoma cells, derived from ASV-B transgenic mice, were gene-transduced to express either interleukin-2, interleukin-4, the granulocyte-macrophage colony-stimulating factor, or the T-cell costimulatory molecule B7.1. First, we demonstrated the vaccine potential of engineered hepatoma cells by immunizing nontransgenic mice with these cells, which prevented the growth of subsequent grafted nontransduced hepatoma cells. However, vaccination of pretumoral transgenic animals with various combinations of engineered hepatoma cells failed to inhibit hepatoma onset and progression. Rather, tumor development in ASV-B mice appears to be dependent on the immune system, since neonatal induction of immunotolerance to tumor in ASV-B mice cells was associated with a moderate, but significant, acceleration of tumor development. These results seriously call into question the efficacy of this strategy of active vaccinotherapy against natural tumors.
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PMID:Does preventive vaccination with engineered tumor cells work in cancer-prone transgenic mice? 957 Mar

On investigating the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) and costimulatory molecule, B70, in antitumor immunity, we have found important effects of GM-CSF/B70 coexpression in the interaction with natural killer (NK) cells. We used the pLSN vector system to contain the neomycin-resistant gene and LTR promoter. The pLSNGM-CSF, pLSNB70 and pLSNB70/GM-CSF, pLSN vectors each containing GM-CSF, B70, and B70/GM-CSF cDNA, respectively, were constructed. They were transfected into human hepatocellular carcinoma cell (SK-HEP1), and stable cells (SK-pLSN, SK-GM, SK-B70 and SK-BG) were selected after neomycin treatment. According to enzyme-linked immunosorbent analysis and FACS, we showed that expression of GM-CSF was increased up to 23-fold in SK-GM and SK-BG cells, and also expression of B70 was induced at least 76-97% in SK-B70 and SK-BG cells. Expression of B70 was remarkably increased by autocrine effect of GM-CSF in SK-BG cells. Primary cytolytic ability of GM-CSF and B70 significantly increased almost 4-fold (effector/target ratio, 100:1) in SK-BG cells. In in vivo studies, SK-BG cells showed much less subcutaneous tumor formation in nude mice accompanying increased NK cell proliferation and cytotoxicity. Therefore, these results suggest that combining expression of GM-CSF and B70 may enhance NK-mediated cytotoxicity, and then induce the antitumor immunity in hepatoma transplanted into nude mice.
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PMID:Enhancement of natural killer cell-mediated cytotoxicity by coexpression of GM-CSF/B70 in hepatoma. 1129 84


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