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)

Type beta transforming growth factor (TGF-beta) was shown to be the serum factor responsible for inducing normal human bronchial epithelial (NHBE) cells to undergo squamous differentiation. NHBE cells were shown to have high-affinity receptors for TGF-beta. TGF-beta induced the following markers of terminal squamous differentiation in NHBE cells: (i) increase in Ca ionophore-induced formation of crosslinked envelopes; (ii) increase in extracellular activity of plasminogen activator; (iii) irreversible inhibition of DNA synthesis; (iv) decrease in clonal growth rate; and (v) increase in cell surface area. The IgG fraction of anti-TGF-beta antiserum prevented both the inhibition of DNA synthesis and the induction of differentiation by either TGF-beta or whole blood-derived serum. Therefore, TGF-beta is the primary differentiation-inducing factor in serum for NHBE cells. In contrast, TGF-beta did not inhibit DNA synthesis of human lung carcinoma cells even though the cells possess comparable numbers of TGF-beta receptors with similar affinities for the factor. Epinephrine antagonized the TGF-beta-induced inhibition of DNA synthesis and squamous differentiation of NHBE cells. Although epinephrine increased the cyclic AMP levels in NHBE cells, TGF-beta did not alter the intracellular level in NHBE cells in either the presence or absence of epinephrine. Therefore, epinephrine and TGF-beta appear to affect different intracellular pathways that control growth and differentiation processes of NHBE cells.
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PMID:Type beta transforming growth factor is the primary differentiation-inducing serum factor for normal human bronchial epithelial cells. 287 53

Type beta transforming growth factor (TGF-beta) is a two-chain polypeptide of 25,000 daltons isolated from many tissues, including bovine kidney, human placenta, and human platelets. It has been characterized by its ability to stimulate reversible transformation of nonneoplastic murine fibroblasts, as measured by the formation of colonies of these cells in soft agar (ED50 = 4 pM TGF-beta for NRK fibroblasts). We now show that the response of cells to TGF-beta is bifunctional, in that TGF-beta inhibits the anchorage-dependent growth of NRK fibroblasts and of human tumor cells by increasing cell cycle time. Moreover, the anchorage-independent growth of many human melanoma, lung carcinoma, and breast carcinoma cell lines is inhibited by TGF-beta at concentrations in the same range as those that stimulate colony formation of NRK fibroblasts (average ED50 = 10-30 pM TGF-beta for inhibition). Whereas epidermal growth factor and TGF-beta synergize to induce anchorage-independent growth of NRK fibroblasts, their effects on the growth of A-549 human lung carcinoma cells are antagonistic. The bifunctional response of cells to TGF-beta is further demonstrated in Fischer rat 3T3 fibroblasts transfected with a cellular myc gene. In these cells TGF-beta synergizes with platelet-derived growth factor to stimulate colony formation but inhibits the colony formation induced by epidermal growth factor. The data indicate that the effects of TGF-beta on cells are not a function of the peptide itself, but rather of the total set of growth factors and their receptors that is operant in the cell at a given time.
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PMID:Type beta transforming growth factor: a bifunctional regulator of cellular growth. 387 21

Stimulation of prostaglandin production in C-9 rat liver cells by transforming growth factor (TGF)-alpha was synergistic with that of the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). TGF-alpha and TPA synergized the release of radiolabelled compounds from [3H]arachidonic acid prelabelled C-9 cells. 1-Oleoyl-2-acetyl-glycerol (OAG) and TGF-alpha also synergized prostaglandin production in the C-9 cells suggesting that the tumor promoter was mimicking the physiological activator of protein kinase C, 1,2-diacylglycerol. TGF-alpha and TPA also synergistically stimulated arachidonic acid metabolism by NRK-49F rat kidney cells. In A-549 human lung carcinoma cells, TGF-beta, but not TGF-alpha, stimulated arachidonic acid metabolism synergistically with TPA.
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PMID:The stimulation of prostaglandin production by transforming growth factor-alpha and 12-O-tetradecanoyl-phorbol-13-acetate or 1-oleoyl-2-acetyl-glycerol is synergistic. 392

A correlation between natural killer (NK) cell activity and growth inhibition (GI), as measured in an in vitro assay with B16 melanoma cells, mediated by a serum growth-inhibitory factor (GIF), among various strains of mice has been demonstrated. Beige mice (bg/bg), known to express low NK-activity, were also low in GIF activity and showed increased susceptibility to both B16 melanoma cells and another solid tumor (Lewis lung carcinoma) in vivo. In vivo treatment with various protease inhibitors that reduced NK-activity, also reduced growth inhibition mediated by GIF. Protease inhibitors that did not affect NK-activity did not affect GIF either. All of 4 B16 melanoma clones selected against GIF in vitro and resistant to GIF showed both resistance to NK-cells in vitro and increased growth potential in vivo. However, P-815, an NK-resistant cell line, was sensitive to GIF.
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PMID:Natural killer cell activity is closely associated with a growth-inhibitory serum protein with protease-like activity. 641 Jun 83

The antineoplastic activity of an organometallic complex of ruthenium(II), [cis-RuCl2(DMSO)4]o, has been examined in comparison with that of cis-PDD, using three metastasizing tumors of the mouse: Lewis lung carcinoma, B16 melanoma and MCa mammary carcinoma. [cis-RuCl2(DMSO)4]o significantly reduces primary tumor growth in all the tumors tested, and its activity is similarly pronounced at three different dosages in mice bearing Lewis lung carcinoma. On the contrary, the survival time of animals having i.v. or i.m. tumor implants are only moderately increased, and also in the case of combined treatments with surgery. The antineoplastic activity of cis-PDD appears to be less pronounced than that of [cis-RuCl2(DMSO)4]o, and is limited to mice bearing B16 melanoma, which, among the three tumors used, appears to be naturally more responsive to cis-PDD and [cis-RuCl2(DMSO)4]o. The use of [cis-RuCl2(DMSO)4]o appears advantageous over that of cis-PDD since, unlike cis-PDD, its antineoplastic effects have been obtained at dosages with reduced host toxicity, indicated by the absence of significant hematological toxicity and toxicity for normal proliferating tissues.
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PMID:Antineoplastic activity and toxicity of an organometallic complex of ruthenium(II) in comparison with cis-PDD in mice bearing solid malignant neoplasms. 654 Jan 84

The effects of square planar rhodium, [RhacacCOD]o and iridium, [IracacCOD]o complexes and of octahedral ruthenium, [cis-RuCl2 (DMSO)4]o complex have been examined in comparison with cis-dichlorodiammino platinum(II) (cis-PDD). The toxicity in BDF1 mice varies widely and decreasing LD50-values, ranging from 0.94 mg/kg to 1000 mg/kg, have been obtained for cis-PDD, [RhacacCOD]o, [IracacCOD]o and [cis-RuCl2(DMSO)4]o, respectively. All the tested complexes similarly inhibit the growth of subcutaneous Lewis lung carcinoma and the development of spontaneous as well as of artificial metastases, with the exception of [IracacCOD]o which is inactive on metastases. The antitumor activity of [RhacacCOD]o and [cis-RuCl2(DMSO)4]o appears interesting, since it is of the same magnitude as that of cis-PDD, considering also that they were found to be only marginally nephrotoxic.
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PMID:Antitumor effects of rhodium(I), iridium(I) and ruthenium(II) complexes in comparison with cis-dichlorodiammino platinum(II) in mice bearing Lewis lung carcinoma. 668 95

We have previously reported that cancer chemotherapy prior to lymphokine activated-killer (LAK) cell-transfer gave synergistic increase in therapeutic effects of LAK adoptive immunotherapy on transplanted tumors, BMT-11 fibrosarcoma and 3LL lung carcinoma, in C57 BL/6 mice, and that transferred LAK cell-accumulation into tumor tissues was enhanced by treatment with anti-cancer drugs. The author tried to analyze mechanisms responsible for the enhanced LAK cell-accumulation into tumor tissues after chemotherapy by under agarose migration assay and LAK migration inhibitory assay. The author detected a chemotactic factor for LAK cells (LAK-attractant) and a migration inhibitory factor for LAK cells (LAK-MIF) in the conditioned medium of tumor tissues from mice treated with various anti-cancer drugs, which was not found in that of untreated tumor tissues. Since mRNA expression for transforming growth factor-beta 1 (TGF-beta 1) was found to enhance in tumor tissues after chemotherapy through RT-PCR, the author examined a possible participation of TGF-beta 1 as LAK-attractant in tumor tissues of mice treated with cyclophosphamide. Recombinant human TGF-beta 1 showed LAK-attractant activity, and anti-TGF-beta 1 antibody inhibited LAK-attractant activity in the conditioned medium. These findings indicate that TGF-beta 1 produced in tumor tissues of mice treated with anti-cancer drugs may be one of LAK-attractants. On the other hand, LAK-MIF activity was concentrated in the fraction of less than 3kDa which is a smaller molecule than that of TGF-beta 1. These findings suggest that both TGF-beta 1 and LAK-MIF produced in tumor tissues after chemotherapy contributed to the enhanced accumulation of transferred LAK cells into tumor tissues after the chemotherapy.
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PMID:[Mechanisms of enhanced accumulation of transferred LAK cells into tumor sites after chemotherapy]. 759 Jun 1

The receptor for urokinase-type plasminogen activator (uPAR) is an integral membrane protein that specifically binds urokinase-type plasminogen activator (uPA) and plays a crucial role in cell surface plasmin generation. We have previously found that transforming growth factor-beta, type 1 (TGF-beta 1), increases uPAR gene transcription in the human lung carcinoma cell line A549 and now report that also epidermal growth factor (EGF) and the tumour promoter phorbol 12-myristate 13-acetate (PMA) cause increased uPAR transcription and that PMA and TGF-beta 1 in addition increase the stability of uPAR mRNA, while EGF has no effect on this parameter. All three compounds also increase the uPAR protein level, as measured by cell-binding experiments with radiolabelled ligand. The increase in uPAR protein level was however considerably lower with all three compounds than the increase in mRNA level, suggesting that they also exert a translational or post-translational control. Accompanying the increase in the number of uPAR molecules there was a proportional decrease in their ligand-binding affinity, the mechanism of which is unknown. Platelet-derived growth factor, basic fibroblast growth factor and cyclic AMP analogues did not induce any change in the uPAR mRNA level in A549 cells. Previous studies have shown that expression of uPA and its type-1 inhibitor is regulated by a variety of cytokines in a cell-specific manner. The present study indicates that cytokines in addition influence cell surface plasminogen activation by regulating uPAR expression.
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PMID:Transcriptional and post-transcriptional regulation of the receptor for urokinase-type plasminogen activator by cytokines and tumour promoters in the human lung carcinoma cell line A549. 764 66

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

Mutations in the transforming growth factor beta-type II receptor (TGFbeta RII) gene have been detected in several types of human cancers that represent the phenotype of genomic instability. The TGFbeta RII gene has been mapped to chromosome 3p, on which loss of heterozygosity (LOH) was frequently detected in both small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). To investigate whether the TGFbeta RII gene on 3p22 is inactivated in lung cancers, we examined 35 sporadic lung cancers (15 SCLC and 20 NSCLC) with LOH on 3p for mutations of the TGFbeta RII gene. We previously produced eight intron based primer pairs for mutational analysis of the entire coding region of the TGFbeta RII gene. Using these primers, we screened for mutations of the TGFbeta RII gene by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis. A mutation was detected in a case of SCLC: one base insertion in the polyadenine tract of exon 3. This tumor showed the replication error (RER) phenotype. There were no mutations in exons 1, 2, 4, 5, 6 and 7. These results indicate that the polyadenine tract is a mutational hot spot in the TGFbeta RII gene in RER positive tumors, and that TGFbeta RII mutations occur rarely in lung cancers with LOH on chromosome 3p.
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PMID:Infrequent mutations of the transforming growth factor beta-type II receptor gene at chromosome 3p22 in human lung cancers with chromosome 3p deletions. 916 5


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