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

Eleven small cell lung carcinoma cell lines of human origin were exposed to different colony stimulating factors (CSFs) to study whether CSFs could enhance the spontaneous cell proliferation and modify the action of cytotoxic drugs. In ten cell lines no suppressive or stimulative effect was observed when measured in a [3H]thymidine assay and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. However, one cell line (GLC-20) could be stimulated by interleukin 3 (IL-3) when measured with a proliferative as well as a clonogenic assay. This enhancing effect was cell concentration dependent in the [3H]thymidine assay. Additional CSFs such as granulocyte-macrophage-CSF, granulocyte-CSF, IL-4, IL-6, insulin, or bombesin could not further augment the IL-3 supported proliferation. In addition, IL-3 binding studies demonstrated the presence of IL-3 receptors on the GLC-20 cells. Two types of receptors were demonstrated by Scatchard analysis: high affinity receptors (59 +/- 4 sites/cell) with a dissociation constant (Kd) of 31 +/- 9 pmol/liter; and low affinity receptors (1915 +/- 91 sites/cell) with a Kd of 2.0 +/- 0.8 nmol/liter. Finally, it was shown that the toxic effects of adriamycin and cisplatin on the proliferation of the GLC-20 cell line could partially be abrogated in the presence of IL-3. These data indicate that in some cases CSFs can modulate the proliferation of small cell lung carcinoma cell lines and interfere with the effects of chemotherapeutic drugs.
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PMID:The effects of five hematopoietic growth factors on human small cell lung carcinoma cell lines: interleukin 3 enhances the proliferation in one of the eleven cell lines. 170 41

We established a human carcinoma cell line (KHC 287) from a patient with large-cell-typing lung carcinoma associated with marked leukocytosis. The culture supernatant of KHC 287 cells promoted granulocytic colony formation of human bone-marrow cells in semi-solid culture. Colony formation was almost completely suppressed by treatment of the supernatant with a monoclonal anti-granulocyte colony-stimulating factor (G-CSF) antibody. Not only G-CSF but also interleukin-1 alpha (IL-I alpha), IL-I beta and IL-6 were detected in the culture supernatant by an ELISA method. Northern blot analysis of KHC 287 cells revealed distinct expression of these cytokine genes. Southern blot hybridization of KHC 287 DNA showed 20- and 40-fold co-amplification of c-myc and c-ki-ras, respectively. The chloramphenicol acetyl transferase (CAT) activity was distinctly enhanced in the KHC 287 cells which were transfected with the 360 bp upstream region of G-CSF gene inserted into pSV00CAT, but not in non-G-CSF-producing tumor cell lines. These results suggest that overproduction of the transactivating factor(s) which binds to the 360 bp of the G-CSF upstream region is responsible for the abnormal expression of G-CSF gene in KHC 287 cell line.
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PMID:Analysis of abnormal expression of g-csf gene in a novel tumor cell line (KHC 287) elaborating G-CSF, IL-1 and IL-6 with co-amplification of c-myc and c-ki-ras. 171 Feb 8

We have reported that tumours producing colony-stimulating factor (CSF) also secrete interleukin-1 (IL-1) and IL-6. In the present study, we characterised the role played by IL-1 in CSF production. IL-1 receptor antagonist inhibited the production of granulocyte (G)-CSF and IL-6 by approximately 90% in CSF-producing human lung carcinoma cell lines. Similar results were obtained with hydrocortisone, which suppresses IL-1 gene expression. In contrast, 15 non-CSF-producing human lung carcinoma cell lines did not show detectable IL-1 production, although seven of them were induced to produce G-CSF and IL-6 by exogenous IL-1 alpha. Cell lines that responded to IL-1 alpha, including the CSF-producing lines, expressed receptors for IL-1 alpha. These results indicate that CSF-producing tumours can be characterised by their constitutive IL-1 production, IL-1 receptor expression and IL-1-dependent excess production of G-CSF and IL-6. Furthermore, transcription factor(s) may be involved in the abnormal IL-1 alpha production.
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PMID:Colony-stimulating factor-producing tumours: production of granulocyte colony-stimulating factor and interleukin-6 is secondary to interleukin-1 production. 753 91

We have comparatively analyzed the immune mechanisms induced by and the immunotherapeutic potentials of a highly metastatic clone of the Lewis lung carcinoma, D122, transduced with the interleukin-2 (IL-2), IL-6, or interferon-gamma (IFN-gamma) genes. All of the D122 cytokine gene-transduced cells induced antitumor CD8+ cytotoxic T lymphocytes (CTLs), as can be judged from in vivo depletion of CD8+ cells and in vitro CTL assays. In vivo depletion of CD4+ cells did not affect the malignant phenotypes of the different D122 gene-modified cells, but in vivo depletion of natural killer (NK) cells resulted in increased malignancy of both D122 cells and D122 gene-modified cells. In accordance with the effects of in vivo NK depletion, D122 as well as D122 derivative cells were sensitive to lysis by polyinosinic-polycytidylic acid (poly I:C)-induced activity. We discuss the immune responses generated by the different D122 gene-modified cells in view of their in vivo behavior in syngeneic and nude mice. We also performed comparative analysis of the capacity of vaccinations with irradiated D122 gene-modified cells to cure established micrometastases of parental D122 cells in tumor-operated mice. Vaccinations with D122-IL-2 or -IL-6 secretors did not generate a significant effect. Also, vaccinations with D122-IFN-gamma cells, which showed increased major histocompatibility complex class I expression but did not secrete detectable levels of IFN-gamma, did not cure established micrometastases. Only vaccination with D122-IFN-gamma high secretors efficiently cured postoperated mice carrying established micrometastases. We discuss the relevance of these results to the application of immunotherapy via cytokine gene therapy of human malignancy.
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PMID:Immunotherapy via gene therapy: comparison of the effects of tumor cells transduced with the interleukin-2, interleukin-6, or interferon-gamma genes. 790 86

The growth of inoculated colon 26 adenocarcinoma (colon 26) in mice gradually increased the platelet count owing to murine IL-6 secreted from the tumor, while Lewis lung carcinoma (LLC) decreased the platelet count in the hosts, depending on the tumor growth. Natural human IL-6 injections (hIL-6), 280 micrograms/kg/day, stimulated the platelet production in both types of carcinoma-bearing mice. When the administration of mitomycin C or cisplatin decreased the platelet number as a side reaction with a concomitant of suppressing the growth of colon 26 and LLC, respectively, hIL-6 could also increase the platelet count without the augmentation of tumor growth. However, loss of carcass weight was observed in colon 26-bearing mice treated with hIL-6, suggesting the development of cachexia is associated with hIL-6 administration. Despite the possibility of inducing cachexia in some types of tumors, our results suggest that IL-6 could be a useful means of restoring the decreased platelet number in cancer patients after intensive chemotherapy.
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PMID:Effects of natural human interleukin-6 on thrombopoiesis and tumor progression in tumor-bearing mice. 818 58

Adherent lymphokine-activated killer (A-LAK) cells are purified IL-2 activated natural killer (NK) cells with potent anti-tumor cytotoxic activity. They have been used in the adoptive immunotherapy of metastatic cancers. However, it has been shown that intravenously transferred LAK cells have a poor homing capacity to tumor sites. For the present study, the effects of tumor-derived factors on the in vitro migratory capacity of A-LAK cells was investigated. In a micropore migration assay the conditioned medium from 3LL Lewis lung carcinoma cell cultures was found to exert a strong chemotactic, but not chemokinetic effect on A-LAK cells. This effect was partially inhibited by neutralizing antibodies against the cytokines TGF-beta 1 and IL-6. A combination of the 2 antibodies completely suppressed the chemotactic activity of tumor-cell-conditioned medium. Purified TGF-beta 1 and recombinant IL-6 were chemotactic for A-LAK cells. Biological activities of both cytokines were detectable in the tumor-cell-conditioned medium. The in vivo relevance of these findings, with respect to tissue infiltration of NK cells and LAK cells in inflammation or cancer, remains to be elucidated.
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PMID:Tumor-derived transforming growth factor-beta 1 and interleukin-6 are chemotactic for lymphokine-activated killer cells. 819 78

Tissue inhibitor of metalloproteinases (TIMP-1) is a potent inhibitor of activated matrix metalloproteinases (MMP) such as collagenase, stromelysin, and gelatinase, and thus helps to control extracellular matrix metabolism and deposition by connective tissue cells. Since various cytokines and growth factors can modify the production of MMP and TIMP-1, we explored the action of oncostatin M (OM), a unique lymphocyte- and monocyte-derived cytokine, on expression of these proteins. We examined the regulation of TIMP-1 expression in cultured human fibroblasts by cytokines including OM, IL-6, leukemia inhibitory factor (LIF), and IL-1 alpha. When used at levels of 5 to 50 ng/ml, OM, IL-6, LIF, and IL-1 alpha elevated the TIMP-1 expression at the RNA level in fibroblasts of lung or synovial origin. Interestingly, OM stimulation resulted in highest levels of TIMP-1 RNA and protein synthesis. However, unlike IL-1 alpha, the cytokines OM, IL-6, and LIF did not induce MMP or PGE2 release. OM also enhanced TIMP-1 mRNA levels in the H2981 lung carcinoma and HepG2 hepatoma cell lines. The results suggest that OM as well as IL-6 and LIF, other cytokines acting through similar receptor pathways, may act to inhibit net MMP activity by specifically up-regulating TIMP-1 expression. The selective induction of TIMP-1 by OM may be influential in altering matrix destruction in chronic inflammation and tumor metastasis.
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PMID:Selective regulation of metalloproteinase inhibitor (TIMP-1) by oncostatin M in fibroblasts in culture. 851 78

This study was designed to analyze the possible immunomodulation induced in vivo by haematopoietic growth factors following anti-cancer chemotherapy. Haematologic and cytokine kinetics (IL-1, IL-6, TNF alpha and soluble interleukin-2 receptor (sIL-2R)) were studied in patients with SCLC receiving high dose regimens of chemotherapy and recombinant human GM-CSF (group A), or standard doses of chemotherapy without rhGM-CSF (group B). Six patients were prospectively enrolled and randomized in each group. The kinetics of haematopoiesis following chemotherapy did not significantly differ between the two groups. In group A, the plasma sIL-2R level increased regularly during rhGM-CSF treatment reaching a 2.5-fold elevation at day 12 whereas it remained stable in group B. Conversely, IL-1 alpha decreased to an undetectable level in group A whereas it increased slightly from day 14 to day 18 in group B. As sIL-2R could compete with lymphocyte surface receptors and as IL-I is an important cytokine involved in acute phase response, our results might be regarded as reflecting a transient decrease in the cell-mediated immune response in small cell lung cancer patients receiving high dose chemotherapy combined with rhGM-CSF.
Lung Cancer 1995 Oct
PMID:Interleukin-1 alpha and soluble interleukin-2 receptor during small cell lung cancer chemotherapy: comparison of high chemotherapy dose with rhGM-CSF and standard chemotherapy dose without rhGM-CSF. 858 94

The purpose of this study was to assess the phenotypic and functional characteristics of pulmonary microvascular endothelial cells (MVEC) in the acute respiratory distress syndrome (ARDS). Pulmonary MVEC were isolated from the lungs of five patients who developed ARDS, and from four patients who had undergone a lobectomy for lung carcinoma, as controls. Adhesion molecules and other surface molecules were quantitated on these cells by flow cytometry and the cytokines IL-6 and IL-8 were measured in the supernatants by ELISA. The constitutive expression of intercellular adhesion molecule and, to a lesser extent, vascular adhesion molecule-1, was significantly increased on MVEC isolated from all ARDS patients, as compared with control MVEC. CD14 and TNF receptor p75 were also increased on the surface of MVEC isolated from most patients with ARDS. The expression of ELAM-1 and TNF receptor p55 (TNF-R1) was not significant on the surface of either ARDS-derived or control pulmonary MVEC. The constitutive ability of ARDS-derived MVEC to secrete IL-6 and IL-8 was markedly enhanced as compared with control MVEC. Upon in vitro restimulation by TNF, pulmonary MVEC from ARDS patients showed lower ICAM-1 upregulation, but similar IL-6 and IL-8 production capacity, when compared with control MVEC. Selective differences were found in cell adhesion molecules and TNF receptor p75 expression on pulmonary MVEC isolated from patients with ARDS. These pulmonary MVEC spontaneously overexpress some adhesion molecules and produce greater amounts of the pro- and anti-inflammatory cytokines IL-8 and IL-6. These findings suggest that ICAM-1 and TNF receptor p75 may have a particular involvement in the pathogenesis of acute lung injury, and that the endothelium may be an important source of cytokines detected in broncho-alveolar lavage during this syndrome. It is tempting to hypothesize that the differences observed result from either a genetic predisposition to ARDS based on MVEC phenotype or to a long-lived MVEC phenotypic change induced by ARDS. By allowing the monitoring of phenotypic and functional parameters, cultures of pulmonary MVEC isolated from ARDS patients may thus represent a useful system to analyze further the mechanisms of acute lung injury and to evaluate the efficacy of drugs, including inhibitors of cytokines and of adhesion molecules.
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PMID:Phenotypic and functional analysis of pulmonary microvascular endothelial cells from patients with acute respiratory distress syndrome. 860 86

Retinoids show promise for prevention and treatment of cancers. In most cases, the mechanisms of their anticancer effects are poorly defined, but interactions with cytokine genes have been postulated in several systems. The effects of trans-retinoic acid (RA) on proliferation and cytokine gene expression in the human lung carcinoma Lu-CSF-1 are reported. RA exhibited cell-cycle independent inhibition of Lu-CSF-1 growth while stimulating endogenous interleukin-1 beta and suppressing granulocyte-macrophage colony-stimulating factor and IL-6 mRNAs. Reduction in granulocyte-macrophage colony-stimulating factor and IL-6 message was associated with reduced RNA stability and was translated into reduced protein levels. IL-1 beta mRNA stability was not decreased, and elevation in IL-1 beta protein levels was of a comparable magnitude to the increased amounts of its RNA. Growth inhibition similar to that following RA treatment could be reproduced by exposing cells to exogeneous IL-1 beta alone. These data suggest that changes in autologous cytokine gene expression might contribute to growth inhibition of lung cancer cells by RA.
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PMID:The antiproliferative effect of trans-retinoic acid is associated with selective induction of interleukin-1 beta, a cytokine that directly inhibits growth of lung cancer cells. 886 67


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