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)

Myelosuppression following intensive chemotherapy in cancer patients is associated with increased morbidity and mortality. Hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), alone or in combination with interleukin-1 (IL-1), have been shown to counteract myelosuppression resulting from some, but not all, chemotherapeutic regimens. In an attempt to apply these findings to intensive therapy with proliferation-dependent chemotherapeutic drugs such as fluorouracil (5-FU), we investigated combination biochemotherapy in a murine model. Female CD8F1 [(BALB/c X DBA/8)F1] mice bearing first-passage transplants of spontaneous CD8F1 breast tumors were treated intraperitoneally once a week for 3 successive weeks with a course of 5-FU alone or with a course of 5-FU in combination with recombinant human interleukin-1 beta (rHuIL-1 beta) alone or in combination with CSFs. rHuIL-1 beta alone or in combination with rHuG-CSF or recombinant murine GM-CSF significantly improved tumor growth inhibition (60% vs. 90%) and survival (20% vs. 90%-100%), increased the maximally tolerated dose of 5-FU, accelerated recovery of neutrophil counts in peripheral blood, and reduced duration of significant neutropenia and loss of body weight (29% vs. 10% loss). Clinical trials of IL-1 have been initiated in patients with advanced cancer receiving multiple courses of high-dose 5-FU.
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PMID:Hematologic effects of interleukin-1 beta, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor in tumor-bearing mice treated with fluorouracil. 169 5

We have studied the ability of three different Mycoplasma species to induce proliferation of bone marrow-derived macrophages (BMM). We observed a significant mitogenic effect when BMM cells from BALB/c, DBA/2J, SJL, and C57BL/6 mice were incubated with membranes derived from Mycoplasma arginini or M. arthritidis but not when they were incubated with an equivalent amount of M. pulmonis membrane. We also determined that pretreatment of mycoplasma membrane preparations with papain eliminated the ability of these preparations to induce BMM proliferation. To determine whether these membrane fractions acted indirectly by stimulating the production of soluble factors known to stimulate proliferation of BMM cells, we performed blocking studies with antibodies directed against colony-stimulating factor 1 (CSF-1), interleukin-3 (IL-3), and granulocyte-macrophage colony-stimulating factor. Our results indicate that antibodies directed against either CSF-1 or IL-3 failed to block mycoplasma-initiated proliferation of BMM cells. However, when anti-GM-CSF was added to proliferative cultures at the time of initiation, we saw a dose-dependent reduction of mycoplasma-initiated proliferation. We conclude that the ability of mycoplasma membranes to initiate the proliferation of BMM is not shared by all species of mycoplasma and that it involves the production of GM-CSF by an as yet undetermined cell.
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PMID:Differential induction of bone marrow macrophage proliferation by mycoplasmas involves granulocyte-macrophage colony-stimulating factor. 222 27

The frequencies of precursors of C57BL/6 T lymphocytes that respond to DBA/2 alloantigens by secreting the lymphokines interleukin 2 (IL-2), macrophage-activating factor (MAF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been directly compared with cytolytic T lymphocyte precursor (CTL-P) frequencies in limiting dilution microcultures established from spleen cells positively or negatively selected on the basis of Lyt-2 phenotype. A clear dichotomy was observed between CTL-P, which were contained in the Lyt-2+ fraction, and precursors of IL-2-secreting cells, which were detected almost exclusively in the Lyt-2- population. In contrast, precursors of cells secreting MAF and GM-CSF were found in both populations: almost all responding cells from the Lyt-2- fraction produced both these factors, whereas the precursor frequency of MAF-secreting and GM-CSF-secreting cells was three- to fourfold lower in the Lyt-2+ population. These frequency data were consistent with quantitative differences observed in the average production of these lymphokines by Lyt-2+ and Lyt-2- populations.
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PMID:Precursor frequency analysis of lymphokine-secreting alloreactive T lymphocytes. Dissociation of subsets producing interleukin 2, macrophage-activating factor, and granulocyte-macrophage colony-stimulating factor on the basis of Lyt-2 phenotype. 675 27

The biological properties of TNF-alpha make it a candidate therapeutic target in RA. Our studies have demonstrated that TNF-alpha and its receptors are up-regulated and co-expressed in the synovium and cartilage-pannus junction of RA joints. Neutralizing TNF-alpha antibodies reduce the production of the many pro-inflammatory cytokines, including IL-1 and granulocyte-macrophage colony-stimulating factor (GM-CSF), produced by mononuclear cells from RA in culture. When injected into DBA/1 mice with collagen-induced arthritis and TNF-alpha transgenic mice with arthritis, anti-TNF MoAbs decrease inflammatory damage of joints. Clinical trials employing cA2, a chimaeric anti-TNF-alpha MoAb, in open-label and randomized placebo-controlled studies have demonstrated a dose-dependent efficacy with impressive improvement in disease activity and acute-phase responses lasting several weeks. We conclude that TNF-alpha is a critical mediator of inflammation in RA, and is an important therapeutic target in this disease.
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PMID:Beneficial effects of tumour necrosis factor-alpha (TNF-alpha) blockade in rheumatoid arthritis (RA) 764 5

In all tissues that have been studied to date, dendritic leucocytes constitute only a small proportion of total cells and are difficult both to isolate and purify. This study reports on a method for the propagation of large numbers of dendritic cells (DC) from mouse spleen using granulocyte-macrophage colony-stimulating factor (GM-CSF) and their characteristics. Within a few days of liquid culture in GM-CSF, B10 BR (H-2k, I-E+) mouse splenocytes formed loosely adherent myeloid cell clusters. Mononuclear progeny released from these clusters at and beyond 4 days exhibited distinct dendritic morphology and strongly expressed leucocyte common antigen (CD45), CD11b, heat-stable antigen, Pgp-1 (CD44) and intercellular adhesion molecule-1 (ICAM-1; CD54). The intensity of expression of the DC-restricted markers NLDC 145 and 33D1, the macrophage marker F4/80, and Fc gamma RII (CDw32) was low to moderate, whereas the cells were negative for CD3, CD45RA and NK1.1. High and moderate levels, respectively, of cell surface staining for major histocompatibility complex (MHC) class II (I-Ek) and the B7 antigens (counter-receptors of CTLA4, a structural homologue of CD28) were associated with potent stimulation of unprimed, allogeneic T cells (B10; H-2b, I-E-). DC propagated in a similar fashion from DBA/2 mouse spleen proved to be strong antigen-presenting cells (APC) for MHC-restricted, syngeneic T-helper type 2 (Th2) cell clones specifically responsive to sperm whale myoglobin. Footpad or intravenous injection of GM-CSF-stimulated B10.BR spleen-derived DC into B10 (H-2b, I-E-) recipients resulted in homing of the allogeneic cells to T-cell-dependent areas of lymph nodes and spleen, where they strongly expressed donor MHC class II antigen 1-2 days later. These findings indicate that cells can be propagated from fresh splenocyte suspensions that exhibit distinctive features of DC, namely morphology, motility, cell-surface phenotype, potent allogeneic and syngeneic APC function and in vivo homing ability. Propagation of DC in this manner from progenitors present in lymphoid tissue provides an alternative and relatively convenient source of high numbers of these otherwise difficult to isolate but functionally important APC.
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PMID:Generation of DC from mouse spleen cell cultures in response to GM-CSF: immunophenotypic and functional analyses. 789 Feb 96

Blastocysts were flushed from CD1 mice and were cultured in plastic or laminin-coated plates as an in vitro model of implantation. The purified cytokines epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) markedly stimulated 3H-thymidine incorporation; but recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF), which might be produced by alloantigen-stimulated T cells at the feto-maternal interface, had no growth-stimulating effect. Indeed, higher nonphysiological concentrations of GM-CSF manifested a toxic inhibition. Surprisingly, a purified nonrecombinant murine GM-CSF preparation induced proliferation of both blastocyst and ectoplacental cone trophoblast whereas recombinant murine (and human) GM-CSF had no effect, indicating that the growth stimulation may have been due to a contaminant. Decidual supernatants prepared on Days 5.5-6.5 of pregnancy from mice with high abortion rates (DBA/2-mated CBA/J) had no toxic or stimulating effect on blastocyst trophoblast outgrowth compared to similarly prepared supernatants from low-abortion-rate DBA/2-mated C3H/HeJ mice. These data suggest that it is not GM-CSF that is crucial for the trophoblast proliferation that determines the success of pregnancy.
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PMID:Effects of decidual cell supernatants and lymphokines on murine trophoblast growth in vitro. 848 59

Injection of 10(6) immortalized, but non-leukemic, granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent FDC-P1 cells into GM-CSF transgenic hybrid mice with elevated GM-CSF levels led to death within three months with elevated blast cell numbers in the blood, massive organ infiltration by blast cells, and associated anemia and thrombocytopenia. No disease developed within this period in littermate mice injected with 10(6) FDC-P1 cells. All moribund transgenic recipients contained transformed FDC-P1 cells able to produce rapidly-growing transplanted leukemias in syngeneic normal DBA/2 recipients. The leukemias appeared to arise in the primary recipients by independent transformation events. The transformed cells from different mice differed in their in vitro growth characteristics, their ability to produce GM-CSF or multipotential CSF, and in the nature of the transplanted tumors derived from the primary cells. While all primary recipients at death contained fully transformed leukemic cells, the bulk of the large population of FDC-P1 cells appeared either to be untransformed or to have altered characteristics not yet representing full transformation. If the FDC-P1 engrafted model has some validity for myelodysplasia, the results suggest that sustained CSF administration to myelodysplastic patients possessing abnormal, potentially preleukemic, granulocyte-macrophage populations may increase the risk of death either from accumulated pretransformed or from fully transformed leukemic cells.
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PMID:Leukemic transformation of immortalized FDC-P1 cells engrafted in GM-CSF transgenic mice. 850 82

Effective adoptive immunotherapy of immunocompetent DBA/2 mice challenged i.v. with the highly metastatic ESb T-cell lymphoma required the combined treatment of recipient mice with tumor-sensitized spleen cells and IFN-alpha/beta. In contrast, immune spleen cells and IFN-alpha/beta treatment did not increase the survival time of ESb-injected DBA/2-nu/nu mice, DBA/2-bg/bg mice, or normal DBA/2 mice injected with antibody to CD4. Treatment of immunocompetent DBA/2 mice with antibody to asialo-GM1, silica, dichloromethylene diphosphonate-containing liposomes, or 500 rads whole-body gamma-irradiation did not diminish the antimetastatic action of ESb-immune cells and IFN-alpha/beta. These results indicate that adoptively transferred immune T lymphocytes and IFN-alpha/beta act together with host CD4+ T lymphocytes/factors to inhibit ESb visceral metastases. Combined treatment with ESb-immune cells together with interleukin-1 beta (IL-1 beta), IL-2, tumor necrosis factor-alpha, or granulocyte-macrophage colony-stimulating factor did not increase the survival time of normal DBA/2 mice challenged with ESb cells. In contrast, IL-12, which had only a slight antimetastatic effect when administered alone, did synergize with ESb-immune spleen cells and increased the survival time of ESb-challenged mice to a similar extent as did IFN-alpha/beta and immune spleen cells. Treatment of DBA/2 mice with potent antibody to IFN-alpha/beta did not abrogate the capacity of IL-12 and ESb-immune spleen cells to inhibit ESb metastases. Unlike immunotherapy with ESb-immune cells and IFN-alpha/beta, ESb-immune cells together with IL-12 inhibited ESb metastases in immunodeficient DBA/2-bg/bg mice.
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PMID:Host CD4+ T lymphocytes are required for the synergistic action of interferon-alpha/beta and adoptively transferred immune cells in the inhibition of visceral ESb metastases. 852 4

We have previously reported that granulocyte-macrophage colony-stimulating factor (GM-CSF)- and interleukin-3 (IL-3)-dependent FDC-P1 cells undergo leukemic transformation when injected into sublethally irradiated DBA/2 mice. Transformation is related to aberrant activation of growth-regulatory genes by insertion of intracisternal A-particle (IAP) genomes. To elucidate the transformation process further, a subtracted cDNA library was constructed from a factor-independent leukemic FDC-P1 variant and the parental FDC-P1 cells. Screening for clones that were preferentially recognized by a total cDNA probe from the transformed cell line (in comparison to a similar probe from untransformed FDC-P1 cells) led to the isolation of 14 clones, of which six contained cDNA inserts encoding so-called B2 repeats, a class of short interspersed nucleotide elements. The expression of B2 repeats was significantly increased not only in the cell line from which the subtracted library was constructed, but also in all other leukemic FDC-P1 variants analyzed. B2 repeats can act as insertional mutagens and may have a role in the stabilization of certain oncogene and cytokine mRNAs. Interestingly, B2 repeats contain a 14-nucleotide region that is almost completely complementary to an AU-rich sequence in a region of the IAP mRNA encoding the enzyme reverse transcriptase. Although preliminary experiments to demonstrate stabilization of IAP mRNA by hybridization to B2 repeat sequences remained inconclusive, it is intriguing to speculate that B2 repeat sequences may have a causative role in the transformation process.
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PMID:Indirect radiation leukemogenesis in DBA/2 mice: increased expression of B2 repeats in FDC-P1 cells transformed by intracisternal A-particle transposition. 954 Jul 58

We studied differences in ectopic osteoinduction in eight mouse inbred strains and an outbred strain. Antigen-extracted autolyzed rat bone gelatin was implanted under hind limb muscle fascia of 12-week-old males, and new bone formation was morphologically assessed on serial sections. Four weeks after implantation, less than half of the implants from CBA/J, A/J, BALB/cJ, and C3Hf/Bu mice showed induction of only cartilage. New cartilage was observed in all, and bone and bone marrow in 80% of the implants from AKR/J, C57BL/6J, DBA/2J, and RFM/Rij mice. Volume of the newly formed tissue ranged from 1.3% of the old matrix in A/J strain to 74.6% in DBA/2J strain. Outbred CD1 mice showed only weak cartilage induction. The "good" responders differed among themselves in the volume and type of newly induced tissue: DBA/2J, RFM/Rij, and AKR/J mice had a similar ratio of new bone and cartilage and abundant bone marrow, whereas the predominant newly induced tissue in C57Bl/6J mice was cartilage. The pattern of the expression of BMP-2, -4, and -7, alkaline phosphatase, osteocalcin, interferon-gamma, and granulocyte-macrophage colony-stimulating factor, measured by reverse transcriptase polymerase chain reaction, did not correlate with the type and the quantity of the newly induced tissue. Our results show that adult mice of inbred strains differ not only in the peak bone mass and morphology, but also ability to form new bone after an osteoinductive stimulus. Ectopic osteoinduction may be a useful in vivo model to investigate genetic determinants of endochondral osteogenesis, especially its immunological component.
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PMID:Genetic variability of new bone induction in mice. 1042 18


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