Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have established cell lines from a large cell carcinoma of the lung accompanied by marked granulocytosis and thrombocytosis, and have analyzed the factors with colony stimulating factor (CSF) activity produced by them. Analysis of the CSF activity present in the culture medium of the established cell lines demonstrated growth-stimulating activity on CMK cells, a human megakaryoblastic cell line and mouse bone marrow cells. A neutralization test with antibodies against G-, M- and GM-CSF indicated the stimulation for the proliferation of CMK and mouse bone marrow cells to be mediated partially by the CSFs. Furthermore, the measurement of GM-CSF and interleukin(IL)6 by enzyme-linked immunosorbent assay (ELISA) and northern blotting analysis indicated productions of G-, GM- and M-CSF and of IL6 from the cell lines but failed to exhibit IL3 gene expression. It is suggested that the cell lines could be of use in the study of CSFs and, also, that lymphokines act on leukocyte and platelet progenitor cells.
 ...
PMID:Establishment of large cell lung cancer cell lines secreting hematopoietic factors inducing leukocytosis and thrombocytosis. 128 95

Macrophage colony-stimulating factor (CSF-1) increases the tissue invasive potential of the CSF-1 receptor-bearing lung carcinoma cell lines A549 and Calu-1 by increasing the number of endogenously bound urokinase-type plasminogen activators (u-PA)s on these cells. CSF-1, at concentrations which optimize invasion of A549 and Calu-1 cells into human amnion membranes (250 ng/ml), maximally augments the number of u-PA receptors occupied by endogenously produced urokinase. Preincubation of A549 and Calu-1 cells with the anti-u-PA monoclonal antibody MPW5UK (25 micrograms/ml) or with a 20- to 40-fold stoichiometric excess of fluid phase type 2 plasminogen activator inhibitor abrogates invasiveness, indicating that functionally active cell surface u-PA is essential for tissue invasion. In contrast, fluid phase type 1 plasminogen activator inhibitor (PAI-1, 5-15 units/ml) does not inhibit invasiveness unless preincubated with the amnion membranes. Inhibition of invasion by PAI-1 is abolished by presaturating the amnion membranes with antiitronectin monoclonal antibody (10 micrograms/ml) which prevents binding of PAI-1 to tissue-associated vitronectin. Binding of PAI-1 to tissue vitronectin is therefore a prerequisite for its inhibitory action. Thus, endogenously receptor-bound u-PA is the primary protease mediating CSF-1-induced tissue invasiveness of the lung carcinoma cell lines A549 and Calu-1.
 ...
PMID:Endogenous receptor-bound urokinase mediates tissue invasion of the human lung carcinoma cell lines A549 and Calu-1. 137 33

We have identified two lung carcinoma cell lines, A549 and Calu-1, expressing low levels of the macrophage colony-stimulating factor (CSF-1) receptor (CSF-1R), encoded by the c-fms oncogene. The effect of CSF-1 on the invasive potential of these CSF-1R-positive tumor cell lines and on two other CSF-1R-bearing cell lines, the BT-20 breast carcinoma cell line and the CSF-1 growth-dependent murine macrophage cell line BAC1.2F5, was examined using a human amnionic basement membrane invasion model. Culture of A549, Calu-1, and BAC1.2F5 cells with CSF-1 (250 ng/ml) resulted in a maximal 12-, 5-, and 12-fold enhancement of invasion, respectively, compared to control cells cultured in medium alone. Larger concentrations of CSF-1 (750 ng/ml) reduced A549 and Calu-1 invasiveness compared to the effect of the 250-ng/ml dose. Maximal enhancement in invasion of A549 and Calu-1 cells occurred after a 24- and 48-h exposure to CSF-1, respectively. CSF-1 increased invasiveness 6-fold in BT-20 cells induced by glucocorticoids to express high levels of CSF-1R, in comparison to control cells not exposed to glucocorticoids or CSF-1. In contrast, CSF-1 had no effect on invasion in the CSF-1R-negative MCF-7 cell line. Culture of A549 and Calu-1 cells with other cytokines and growth factors including GM-CSF (500 units/ml), IL-3 (1 ng/ml), interferon-gamma (500 units/ml), and tumor necrosis factor (50 units/ml) had no significant effect on invasiveness. Thus, CSF-1 increases invasiveness in CSF-1R-positive tumor cell lines, suggesting a role in enhancing the metastatic potential of tumor cells expressing the CSF-1R.
 ...
PMID:Macrophage colony-stimulating factor (CSF-1) enhances invasiveness in CSF-1 receptor-positive carcinoma cell lines. 153 51

Recombinant human (rhu) macrophage colony-stimulating factor (M-CSF) was evaluated for efficacy, either alone or in combination with local X-irradiation (LR), in mice inoculated subcutaneously (s.c.) with Lewis lung carcinoma (LLC) cells. The size of the primary tumor and numbers of lung metastases, 21 days after tumor inoculation and 15 days after the start of treatment, were reduced by 87% in tumor-bearing mice treated with 20 micrograms/dose M-CSF s.c. twice a day for 5 days. LR (800 cGy) to the tumor once a week for 2 weeks had a moderate anti-tumor effect and enhanced the anti-tumor effect of M-CSF. Hematological parameters, including nucleated cellularity in peripheral blood, femoral marrow, spleen and peritoneal exudate, as well as marrow and splenic granulocyte-macrophage progenitor cells, and numbers of splenic Thy 1.2+ cell and peritoneal mast cells, were perturbed in LLC-bearing mice, and were influenced by treatment with M-CSF and LR. Treatment with M-CSF plus LR, but not with either agent alone, was associated with a significant, although slight, enhancement in survival time for LLC-bearing mice. Inability to obtain a better survival-enhancing effect appeared to be related to the limited treatment, since the anti-tumor effects of M-CSF were more notable early on in disease progression and were related to the dose of M-CSF used. The effects of M-CSF were most probably indirect ones on the host immune system. M-CSF, in combination with LR, may be of benefit in the treatment of human tumors that have metastatic potential.
 ...
PMID:Anti-tumor effects of recombinant human macrophage colony-stimulating factor, alone or in combination with local irradiation, in mice inoculated with Lewis lung carcinoma cells. 198 70

In previous studies, we demonstrated that immune-suppressive bone marrow cells appeared during a period of myelopoietic stimulation in mice bearing Lewis lung carcinoma (LLC) tumors and could be induced from normal bone marrow cells during 3 days of culture with supernatants of LLC variant cells. We have now shown that the capacity of LLC variants to induce immune suppressor cells was associated with the capacity to produce colony-stimulating factor (CSF) activities. The LLC variants that secreted more CSF activities also produced more bone marrow immune suppressor cell-inducing activity. The induction of immune-suppressive bone marrow cells was dependent on bone marrow cell proliferation because irradiation of bone marrow cells prior to culture with the CSF-containing supernatants blocked induction of suppressor cells. Culture supernatants of WEHI-3 cells and of pokeweed mitogen-stimulated spleen cells, rich sources of interleukin 3 (IL-3) and granulocyte-monocyte-CSF (GM-CSF), as well as recombinant mouse GM-CSF and recombinant mouse IL-3, also stimulated bone marrow suppressor cell activity. The combination of GM-CSF with IL-3 resulted in a synergistic rather than simply an additive induction of bone marrow suppressor cells. Conditioned medium of CSF-1-producing L cells did not induce bone marrow immune suppressor cells. These results suggest that during heightened periods of myelopoiesis, induction of bone marrow-derived immune suppressor cells may be stimulated by CSFs, such as by the singular or combined effects of GM-CSF and IL-3.
 ...
PMID:Stimulation of immune-suppressive bone marrow cells by colony-stimulating factors. 214 38

The major hematopoietic growth factors have been produced through recombinant DNA technology and have entered initial clinical trials; results of these trials will be reviewed here. Granulocyte colony-stimulating factor (G-CSF) has been tested in patients with bladder cancer and small-cell carcinoma of the lung. In these studies, G-CSF ameliorated the leukopenia associated with combination chemotherapy, reduced the incidence of mucositis in the bladder cancer patients, and nearly eliminated the occurrence of serious infections in the lung cancer patients. Trials involving another factor, granulocyte macrophage colony-stimulating factor (GM-CSF), have resulted in a marked increase in white blood cell (WBC) counts in patients with myelodysplastic syndromes, and has accelerated the appearance of leukocytes and platelets after autologous bone marrow transplants. GM-CSF can also increase the WBC counts in acquired immunodeficiency syndrome patients treated with zidovudine. Both G-CSF and GM-CSF may produce multilineage effects in certain clinical settings and dose ranges. Finally, interleukin-1 (IL-1) and IL-3, which commit very early stem cells to a myeloid pathway, may be used in combination with G-CSF or GM-CSF to produce a synergistic response to various clinical situations.
 ...
PMID:Status of colony-stimulating factors in cancer and AIDS. 240 93

The macrophage-specific colony stimulating factor CSF-1 is required for the growth and differentiation of monocytes. The cell surface receptor for CSF-1 is identical to the product of the c-fms proto-oncogene. The present studies have monitored CSF-1 and c-fms expression in human carcinoma cell lines. Two of three human ovarian carcinoma cell-lines expressed multiple species of CSF-1 mRNA. Furthermore, detection of CSF-1 transcripts was associated with secretion of CSF-1 protein that was increased after phorbol ester treatment. CSF-1 mRNA was also detectable in 4 breast and 2 lung carcinoma cell lines. In contrast, c-fms expression was found only in SK-Br-3 breast carcinoma cells. Similar studies in 2 human choriocarcinoma cell lines demonstrated the presence of c-fms, but not CSF-1, transcripts. While phorbol ester treatment was associated with increased c-fms mRNA levels in choriocarcinoma cells, this agent had no effect on CSF-1 expression. These findings indicate that: 1) CSF-1 expression is frequent in human ovarian, breast and lung carcinoma cells; and 2) coexpression of the CSF-1 and c-fms genes, as found in monocytes is infrequent in malignant epithelial and choriocarcinoma cell lines.
 ...
PMID:CSF-1 and C-FMS gene expression in human carcinoma cell lines. 297 87

Macrophage colony-stimulating factor (CSF-1) mRNA was detected in a wide range of murine tumour cell lines. Stable transfection with a CSF-1 receptor (c-fms) expression plasmid increased the number and size of colonies formed in soft agar by tumour cell lines that were already clonogenic, but did not induce transformation in non-clonogenic lines. To identify mechanisms that might lead to ectopic expression of c-fms, the regulation of the exon 2 promoter of the gene, which flanks the transcription start sites in macrophages, was examined. In transient and stable transfections this promoter was as active in non-macrophage tumour cell lines as it was in RAW264 macrophages. Promoter activity in non-macrophage lines was serum-dependent and was activated further in lines stably transfected with c-fms. Cis-acting elements required for serum-dependent activity lay outside the 300 bp proximal promoter that was sufficient for maximal activity in RAW264 macrophages, but the c-fms-responsive elements were retained in the proximal promoter. Exon 2 promoter activity was selectively suppressed in non-macrophage lines by inclusion of intron 2, which has been implicated in transcription attenuation. Lewis lung carcinoma cells were able to partly bypass this block and expressed c-fms mRNA when grown in limiting serum. The finding that c-fms promoter activity and c-fms mRNA levels are responsive to growth factor signalling pathways provides an insight into mechanisms that may lead to ectopic c-fms expression in tumour cells.
 ...
PMID:Regulation of the c-fms promoter in murine tumour cell lines. 747 59

In this study we tested whether the pattern of cytokines expressed by human carcinomas could account for a different in vivo recruitment of leukocyte subpopulations as a part of the anti-tumor immune response. Two carcinoma cell lines, SK-OV-3 ovary carcinoma and CALU-3 lung carcinoma, were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR), immunofluorescence and ELISA for the expression and in vitro production of cytokines with chemotactic, proinflammatory and growth-stimulating activity. Although both cell lines displayed a constitutive expression of granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage-CSF (GM-CSF), M-CSF, interleukin (IL-) 1 alpha and IL-8, only CALU-3 cell line expressed IL-10, RANTES (Regulated upon Activation, Normal T Expressed and Secreted) and monocyte-activating protein (MCP)-1. MCP-1 and IL-8 were detected by immunohistochemistry on sections from tumors xenografted in nude mice. To analyze whether the tumor-released cytokines modulate leukocytes in tumor infiltration, we studied the distribution of human peripheral blood leukocytes injected in the proximity of SK-OV-3 and of CALU-3 tumor xenografts. While SK-OV-3 was unable to recruit human leukocytes and appeared to be barely infiltrated by murine CD45+ cells, CALU-3 appeared to be rapidly and heavily infiltrated by human leukocytes which induced tumor necrosis within 18-24 hr.
 ...
PMID:An in vivo model to compare human leukocyte infiltration in carcinoma xenografts producing different chemokines. 766 28

By secreting granulocyte/macrophage colony-stimulating factor (GM-CSF), metastatic Lewis lung carcinoma (LLC-LN7) tumors induce the appearance of myelopoiesis-associated immune-suppressor cells that resemble granulocytic-macrophage (GM) progenitor cells. The presence of these GM-suppressor cells in mice bearing LLC-LN7 tumors was associated with a reduced capacity of splenic T cells to proliferate in response to interleukin-2 (IL-2). Administration of low doses of 100 U interferon gamma (IFN gamma) plus 10 U tumor necrosis factor alpha (TNF alpha) to the tumor bearers, a combination treatment that we previously showed to diminish the presence of GM-suppressor cells synergistically, restored proliferative responsiveness of the splenic T cells to IL-2. These LLC-LN7-bearing mice were also examined for whether cells that phenotypically resemble GM-progenitor cells (ER-MP12+ cells) infiltrate the tumor mass. ER-MP12+ cells composed approximately 10% of the cells isolated from dissociated tumors of mice that had been treated with placebo or with either IFN gamma or TNF alpha alone, but IFN gamma/TNF alpha therapy markedly reduced the number of tumor-infiltrating ER-MP12+ suppressor cells. The IFN gamma/TNF alpha treatment to eliminate GM-suppressor cells and restore T cell responsiveness to IL-2 was next coupled with low dose IL-2 therapy (100 U twice daily). Addition of IL-2 to the treatment regimen did not significantly influence the effectiveness of the IFN gamma/TNF alpha treatment in eliminating GM-suppressor cells from the LLC-LN7 tumor mass. However, inclusion of IL-2 with the IFN gamma/TNF alpha treatment regimen enhanced the CD8+, but not the CD4+, cell content within the tumor, and diminished the number of metastatic lung nodules within the mice. When these tumors were excised, dissociated, and bulk-cultured with a low dose of IL-2, an increased level of cytotoxic T lymphocyte (CTL) activity was generated in the TIL cultures from mice that had received IFN gamma/TNF alpha plus IL-2 treatments. A lesser but detectable level of CTL activity was generated in TIL cultures from mice that were treated with only IFN gamma/TNF alpha, while no CTL activity was generated in tumor cultures from mice receiving only placebo or low-dose IL-2. These results suggest the effectiveness of IFN gamma plus TNF alpha therapy in restoring IL-2 responsiveness in mice bearing GM-suppressor cell-inducing tumors and at enhancing both the intratumoral CD8+ cell content and the generation of CTL activity in bulk cultures of these tumors.
 ...
PMID:Increasing infiltration and activation of CD8+ tumor-infiltrating lymphocytes after eliminating immune suppressive granulocyte/macrophage progenitor cells with low doses of interferon gamma plus tumor necrosis factor alpha. 829 23


1 2 3 Next >>