UNIPROT:P04141 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A dog with a pulmonary papillary carcinoma and a cat with a dermal tubular adenocarcinoma had profound paraneoplastic neutrophilic leukocytosis with no clinically detectable inflammatory foci. To investigate the mechanism of the leukocytosis, oligonucleotide primers were designed from the cDNA sequences of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) of dogs. Reverse transcription polymerase chain reaction was performed on tumor tissues, and specific amplification of G-CSF and GM-CSF was obtained with the tumor RNA in the dog. The tumor RNA in the cat demonstrated specific amplification of G-CSF but not GM-CSF. These findings are consistent with the production of G-CSF and/or GM-CSF by neoplasms as a mechanism for paraneoplastic leukocytosis in small animals.
...
PMID:Production of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor by carcinomas in a dog and a cat with paraneoplastic leukocytosis. 929 84

In this study, we provide the first report on the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by human thyroid epithelial cells. Primary cultures of highly purified thyrocytes and thyroid-derived fibroblasts (n = 3) and three thyroid anaplastic and one largely papillary carcinoma cell lines were exposed to different potent GM-CSF stimulators, employing interleukin 1 alpha (Il-1 alpha) and tumour necrosis factor-alpha (TNF-alpha). Cytokine mRNA levels were monitored by semi-quantitative reverse transcriptase-PCR including an internal heterologous competitor fragment after 3, 6 and 18 h of culture. Culture supernatants were assayed for GM-CSF using a highly sensitive ELISA (detection limit < or = 0.5 pg/ml) after 24 h. Basal GM-CSF mRNA expression was higher in fibroblasts and SW 1736 cells compared with thyrocytes, C 634, 8505 C and HTh 74 cells. GM-CSF was spontaneously secreted by fibroblasts (means +/- S.E.M.; 43 +/- 15 pg/ml), SW 1736 (59 +/- 4 pg/ml), HTh 74 (34 +/- 4 pg/ml) and C 643 cells (12 +/- 1 pg/ml) but not by thyrocytes and 8505 C cells. Treatment with Il-1 alpha (10 U/ml) resulted in a marked increase of GM-CSF mRNA within 3 h and an increase or induction of protein expression in thyrocyte (2350 +/- 214 pg/ml), fibroblast (5242 +/- 1400 pg/ml), SW 1736 (20016 +/- 280 pg/ml) and C 643 cultures (1285 +/- 79 pg/ml). Stimulation with TNF-alpha (10 U/ml) yielded divergent results. No significant increase of GM-CSF mRNA or protein expression was found in thyrocytes although TNF-alpha receptor expression in these cells is well documented. Stimulation with TNF-alpha resulted in an increased GM-CSF production in fibroblasts (361 +/- 14 pg/ml), HTh 74 (148 +/- 51 pg/ml) and SW 1736 cultures (235 +/- 43 pg/ml). TSH (10 mU/ ml) did not stimulate GM-CSF secretion in thyrocytes and HTh 74 cells, both expressing the TSH receptor. Phorbol 12-myristate 13-acetate (10 ng/ml) enhanced GM-CSF mRNA and protein levels in all cell types investigated. Our data suggest that both thyrocytes and fibroblasts synthesize GM-CSF in response to Il-1 alpha, but only fibroblasts respond to TNF-alpha with a significant increase in GM-CSF. Anaplastic thyroid carcinomas are potential GM-CSF producers.
...
PMID:Differential regulation of granulocyte-macrophage colony-stimulating factor mRNA and protein expression in human thyrocytes and thyroid-derived fibroblasts by interleukin-1 alpha and tumor necrosis factor-alpha. 895 88

Calcitonin gene-related peptide (CGRP) inhibits antigen presentation by Langerhans cells (LC) and macrophages, and LC are anatomically associated with CGRP-containing epidermal nerves. To determine whether CGRP may produce some of its functional effects through regulation of cytokine expression, we utilized enzyme-linked immunosorbent assay (ELISA) of conditioned supernatants to examine production of interleukin (IL)-10 and IL-1 beta protein in the LC-like cell line XS52 as well as the reverse transcriptase-polymerase chain reaction (RT-PCR) to examine levels of mRNA for IL-10, IL-1 beta, and the 40-kDa subunit (p40) of IL-12. CGRP augmented the lipopolysaccharide (LPS) and granulocyte-macrophage colony-stimulating factor (GM-CSF) -induced release of IL-10 protein and the induced expression of IL-10 mRNA in these cells. However, it suppressed the induction of release of IL-1 beta protein and the induction of mRNA for IL-12 p40 and IL-1 beta by LPS and GM-CSF. Regulation of cytokine expression in peritoneal macrophages was also examined. By ELISA, the LPS-induced expression of IL-10 was augmented by CGRP, whereas the induction of IL-1 beta was suppressed. Northern analysis demonstrated augmentation of LPS-induced IL-10 mRNA levels and inhibition of LPS-induced IL-1 beta mRNA by CGRP. CGRP inhibited the LPS-induced induction of IL-12 mRNA as assessed by RT-PCR. Up-regulation of B7-2 expression by LPS and GM-CSF was suppressed by CGRP in both XS52 cells and macrophages, as previously reported. This suppression, however, could be abrogated by co-culture with neutralizing antibodies to IL-10. Furthermore, the presence of neutralizing antibodies to IL-10 during exposure of epidermal cells (EC) to CGRP prevented the CGRP-mediated suppression of EC presentation of tumor-associated antigens (from the S1509a spindle cell carcinoma) for elicitation of delayed-type hypersensitivity in S1509a-immune mice. These data suggest that suppression of antigen-presenting function by CGRP is mediated, at least in part, by changes in cytokine expression that favor less robust antigen presentation for cell-mediated immunity.
...
PMID:Regulation of cytokine expression in macrophages and the Langerhans cell-like line XS52 by calcitonin gene-related peptide. 902 28

Cytotoxicity is an important function of the immune system that results in destruction of cellular targets by humoral and cellular mechanisms. The functional capacity of granulocytes, lymphocytes and macrophages are of significance for cancer patients because of the ability of these cells to exhibit anti-tumor activity. The hallmark of immune cytotoxicity is the recognition and destruction of selected targets by humoral and cellular effects that distinguish between targets and normal cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine with potential to be an anti-neoplastic cytokine. GM-CSF induces: (1) differentiation of monocytes to large macrophage like cells; (2) augmentation of MHC class II antigen expression on monocytes; (3) enhancement in vitro of macrophage and granulocyte natural cytotoxicity and ADCC; and (4) increased expression of adhesion molecules and granulocytes and monocytes. GM-CSF also cooperates with other cytokines in the expansion of specific T cells. Several experimental and clinical studies have demonstrated the anti-neoplastic effects of GM-CSF alone or in combination with cytokines or/and monoclonal antibody. Interestingly, the future might see the combination of GM-CSF and mouse monoclonal antibody MAb17-1A in the adjuvant setting in colon- and/or rectal carcinoma patients.
...
PMID:Anti-tumoral effect of GM-CSF with or without cytokines and monoclonal antibodies in solid tumors. 910 76

Bladder cancer cells have been shown to secrete a variety of factors that are not related to cells of urothelial origin. The histogenesis of these tumour developments is uncertain, and a variety of theories have been previously reported. In the present manuscript, we identify the factors constitutively produced by a human bladder cancer cell line (KU-19-19) that was found to produce beta human chorionic gonadotrophin (beta-hCG), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 1alpha (IL-1alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8). The cells were obtained from a case of metastatic carcinoma that was originally diagnosed to be a grade 3 (WHO classification), invasive transitional cell carcinoma of the bladder. On microscopic observation, the cultured cells exhibited an epithelial appearance with vacuole formation in their cytoplasm. Ultrastructural observations revealed relatively marked microvilli and a tight junction. Significant amounts of beta-hCG, G-CSF, GM-CSF, IL-1alpha, IL-6 and IL-8 concentrations in the supernatant from cultured cells were demonstrated by enzyme-linked immunosorbent assays, while the expression of mRNA of these marker proteins in cancer cells was also significantly exhibited by reverse transcription polymerase chain reaction (RT-PCR). In addition, the expression of G-CSF receptor and IL-6 receptor mRNA was also shown by RT-PCR. Xenograft transplantability using nude mice was observed in association with the presence of severe neutrophilia in the peripheral blood. These results indicate that this cell line appears to be an effective model for the study of transitional cell carcinoma of the bladder with multipotent differentiation potentials.
...
PMID:Constitutive production of multiple cytokines and a human chorionic gonadotrophin beta-subunit by a human bladder cancer cell line (KU-19-19): possible demonstration of totipotential differentiation. 923 15

We studied the expression and function of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor in the human prostate carcinoma cell line LNCaP and looked for its presence in normal and neoplastic human prostatic tissue. The GM-CSF receptor is composed of two subunits, alpha and beta. While the isolated alpha subunit binds GM-CSF at low-affinity, the isolated beta subunit does not bind GM-CSF by itself; but complexes with the alpha subunit to form a high-affinity receptor. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) showed expression of mRNAs encoding the alpha and beta subunits of the GM-CSF receptor in LNCaP cells, and the presence of the alpha and beta proteins was confirmed by immunolocalization with anti-alpha and anti-beta antibodies. Receptor binding studies using radiolabeled GM-CSF showed that LNCaP cells have about 150 high-affinity sites with a kd of 40 pmol/L and approximately 750 low-affinity sites with a kd of 2 nmol/L. GM-CSF signaled, in a time- and dose-dependent manner, for protein tyrosine phosphorylation and induced the proliferation of the LNCaP cells. Immunolocalization studies showed low level expression of GM-CSF alpha and beta subunits in normal prostate tissue, with substantial expression in benign prostatic hyperplasia and prominent expression in neoplastic prostate tissue. Maximal expression of both subunits was observed in prostatic carcinomas metastatic to lymph node and bone. Tumor cells that stained positively with anti-alpha subunit antibodies were also reactive with anti-beta subunit antibodies, indicating that they express high-affinity GM-CSF receptors. Our data show that the LNCaP cells express functional GM-CSF receptors and that prostatic carcinomas have prominent GM-CSF receptor expression. These findings imply that both hyperplastic and neoplastic prostatic tissues may be responsive to GM-CSF.
...
PMID:Expression of granulocyte-macrophage colony-stimulating factor receptors in human prostate cancer. 944 67

In recent years, tumor immunotherapy has begun to exploit the emerging knowledge of the mechanisms of T cell activation to enhance the immune responses to tumors. However, many tumors, despite genetic modification to express co-stimulatory molecules or cytokines, are not readily rejected due to their inherently poor immunogenicity. In the present study, we tested whether expression of the co-stimulatory ligand B7-1 and the immunostimulatory cytokines interferon gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) by a mammary carcinoma (SM1) would sufficiently augment its immunogenicity to obtain rejection and immunity. Our findings demonstrate that expression of B7, IFN-gamma, or GM-CSF alone, or co-expression of B7 and GM-CSF did not result in rejection of SM1. However, co-expression of B7 and IFN-gamma was sufficient to result in regression of SM1 tumors by a CD8+ T cell-dependent mechanism. Rejection of the B7/IFN-gamma-expressing SM1 tumor resulted in protection from rechallenge not only with the unmodified SM1 tumor but with another syngeneic mammary tumor. Our data support the idea that although B7 expression alone may not be sufficient for rejection of certain tumors, the immune system may be stimulated to mount an effective anti-tumor immune response by the co-expression of both the co-stimulatory ligand and a cytokine.
...
PMID:Enhancement of the anti-tumor immune response using a combination of interferon-gamma and B7 expression in an experimental mammary carcinoma. 963 1

Generation of a T cell-mediated antitumor response depends on T cell receptor engagement by major histocompatibility complex/antigen as well as CD28 ligation by B7. CTLA-4 is a second B7 receptor expressed by T cells upon activation that, unlike CD28, appears to deliver an inhibitory signal to T cells. Recently, we and others demonstrated that administration of an anti-CTLA-4 antibody was sufficient to promote regression of several murine tumors. However, certain tumors, such as the SM1 mammary carcinoma, remain refractory to this type of immunotherapy. In the present study, we report that the combination of both CTLA-4 blockade and a vaccine consisting of granulocyte-macrophage colony-stimulating factor-expressing SM1 cells resulted in regression of parental SM1 tumors, despite the ineffectiveness of either treatment alone. This synergistic therapy resulted in long-lasting immunity to SM1 and depended on both CD4(+) and CD8(+) T cells. Interestingly, synergy was not observed between CTLA-4 and a B7-expressing SM1 vaccine. Given that granulocyte-macrophage colony-stimulating factor promotes differentiation and activation of dendritic cells as well as enhances cross-priming of T cells to tumor-derived antigens and that SM1 is major histocompatibility complex class II-negative, our findings suggest that CTLA-4 blockade acts at the level of a host-derived antigen-presenting cell. In addition, these results also support the idea that the most effective and synergistic vaccine strategy targets treatments that enhance T cell priming at the level of host-derived antigen-presenting cells.
...
PMID:CTLA-4 blockade synergizes with tumor-derived granulocyte-macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma. 970 1

We studied the constitutive production of hematopoietic cytokines in a large panel of human cell lines originating from a wide variety of solid tumors. Conditioned media (CM) from the carcinoma cell lines were collected and screened for proliferative activity using a bioassay with indicator cell lines. These indicator cell lines are dependent on hematopoietic growth factors and require the exogenous supply of at least one hematopoietic cytokine for proliferation. We found that CM of 27/70 cell lines were able to significantly and reproducibly stimulate [3H]-thymidine incorporation of the factor-dependent cell lines, indicating that the tumor cell lines secreted one or more functional cytokine(s). The CM-induced proliferation of the indicator cell lines was significantly inhibited by anti-serum against granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-CSF (G-CSF). ELISA confirmed the presence of one or several of the following cytokines in the CM of carcinoma cell lines: GM-CSF, G-CSF, macrophage-CSF (M-CSF), stem cell factor (SCF) and IL-6. A strikingly high percentage of GM-, G- or M-CSF-secreting cell lines was found among those lines derived from carcinomas of the kidney (100%), urinary bladder (85%) and pancreas (100%). The large majority of tumor cell lines derived from breast, colon, esophagus, lung, nervous system and melanomas did not produce significant amounts of the cytokines we investigated here. The cytokines secreted have been proven to be functionally active and can support growth and viability of cytokine-dependent hematopoietic cell lines.
...
PMID:Secretion of functional hematopoietic growth factors by human carcinoma cell lines. 972 3

CTL lines have now been generated against defined peptides of a range of human tumor-associated antigens (TAAs). One of the potential uses of these epitope-specific CTLs is in adoptive transfer immunotherapy. This is a modality, however, that will require long-term in vitro culture of CTLs. To date, little has been reported concerning the phenotypic stability of human epitope-specific CTLs as a consequence of long-term in vitro propagation via peptide stimulation. We report here the serial phenotypic characterization of a CTL line directed against an immunodominant epitope (YLSGANLNL, designated CAP-1) of human carcinoembryonic antigen (CEA). This CTL line was derived from peripheral blood mononuclear cells of a patient with metastatic carcinoma who had been treated with a recombinant CEA-vaccinia vaccine in a Phase I trial; the CTLs were analyzed through 20 in vitro cycle passages of stimulation with CAP-1 peptide and interleukin 2 in the presence of autologous antigen-presenting cells. The CTL line was shown to be phenotypically stable in terms of high levels of cytokine (IFN-gamma, tumor necrosis factor, and granulocyte-macrophage colony-stimulating factor) production, expression of homing-adhesion molecules, ability to lyse peptide-pulsed targets, and ability to lyse human carcinoma cells endogenously expressing CEA in a MHC-restricted manner. Vbeta T-cell receptor gene usage was also analyzed. These studies thus present a rationale for the use of long-term cultured epitope-specific human CTLs, directed against a human TAA for potential adoptive transfer immunotherapy protocols.
...
PMID:Phenotypic stability of a cytotoxic T-cell line directed against an immunodominant epitope of human carcinoembryonic antigen. 981 45

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>