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)

A hundred and twenty-five cases of bronchiolo-alveolar cell carcinomas observed between 1954 and 1978 were histopathologically analysed, some of them also histoenzymatically. The material comprised 93 lung resections (56 lobectomies and 37 pulmonectomies). 11 intraoperatory biopsies in inoperable cases, and 21 autopsies. The early discovery and treatment of the overwhelming majority of cases allow the observation of uncomplicated lesions, the bronchiolar involvement followed by alveolar invasion due to sliding of neoplastic cells on denuded alveolar walls often thickened by cell and fibril accumulation, the papillary formations, as well as the histoenzymatic behaviour. The latter evidenced the strong relations of neoplastic cells with the normal bronchiolar cells (glucose-6-phosphate dehydrogenase. Mg-dependent ATP-ase, oxidoreductases). Some peculiarities also point to the existence of a possible second parallel origin of neoplastic cells at the level of large alveolocytes during the morphogenesis of this multicentric lung carcinoma.
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PMID:Bronchiolo-alveolar cell carcinomas. A histopathologic analysis of 125 cases. 22 60

Mechanisms contributing to reduced cytotoxic drug accumulation were studied in two multidrug-resistant (MDR) human lung cancer cell lines without P-glycoprotein expression. In these (non-small cell) SW-1573/2R120 and (small cell) GLC4/ADR MDR cells, the steady-state accumulation of [14C]daunorubicin was 30 and 12%, respectively, of that in the parent cells. When cells, at steady state, were permeabilized with digitonin, the amount of daunorubicin binding increased only in the resistant cells. The reduced accumulation of daunorubicin in the SW-1573/2R120 and GLC4/ADR cells was accompanied by a lower initial (2 min) uptake rate of this drug. No difference in initial efflux rate of daunorubicin from preloaded cells could be detected between sensitive and resistant SW-1573 cells. However, daunorubicin was extruded 5-fold faster from GLC4/ADR cells than from the parental cells. In the presence of the energy metabolism inhibitors sodium azide and deoxyglucose, the reduced daunorubicin accumulations in the SW-1573/2R120 and GLC4/ADR MDR cells were (almost) completely reversed. The effects of these inhibitors on drug uptake were already apparent during the earliest measured time points (less than 15 s). Also, the enhanced efflux of daunorubicin from GLC4/ADR cells was inhibited. In ATP-depleted cells, the intracellular pH was lowered by approximately 0.3 units in resistant as well as in sensitive cells. The lower intracellular pH, however, could not account for the increase in daunorubicin accumulation in the resistant cells. Also, for vincristine and etoposide, the increases in drug accumulation under energy-deprived conditions were more pronounced in the resistant SW-1573/2R120 cells than in the parent SW-1573 cells. These results suggest that accumulation of drugs in the non-P-glycoprotein MDR human lung carcinoma cell lines SW-1573/2R120 and GLC4/ADR is reduced by an energy-dependent drug export mechanism which prevents efficient transport of drug to the target. Since P-glycoprotein expression in lung tumors is generally low, these MDR lung cancer cell lines can be used as a model to study alternative mechanisms leading to multidrug resistance in this tumor type.
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PMID:Energy-dependent processes involved in reduced drug accumulation in multidrug-resistant human lung cancer cell lines without P-glycoprotein expression. 130 22

31P nuclear magnetic resonance (NMR) spectra of cells and of cell extract revealed high levels of phosphorylcholine (PC) and phosphocreatine (PCr) in an adriamycin-resistant human small cell lung carcinoma cell line (GLC4/ADR) and the adriamycin-sensitive parental cell line (GLC4). PCr levels in extracts of GLC4/ADR were increased compared to extracts of GLC4. We estimated that 11% of the total intracellular ATP is not bound to Mg2+ in both cell lines. This value corresponded to an intracellular free Mg2+ of 0.30 mM. The effects of different adriamycin concentrations, 0.05, 1 and 30 microM for GLC4 and 1, 30 and 200 microM for GLC4/ADR, on the phosphorus metabolite levels in continuously perfused cells were monitored. Significant differences between GLC4 and GLC4/ADR included: (a) a strong increase in the beta ATP level in the presence of 30 microM adriamycin in GLC4 only, followed by a fast decrease after 5 h of perfusion. (b) a less dramatic increase in the PC level in GLC4/ADR and an unchanged ATP level in the presence of increasing adriamycin concentrations. (c) an increased GPC level in GLC4/ADR in the presence of adriamycin. The changes in PC and GPC levels in the presence of adriamycin suggested that the phospholipid turnover was increased in GLC4/ADR and could be stimulated in the presence of adriamycin. In both cell lines, PCr levels decreased faster than the ATP levels after adriamycin treatment. Thus, biochemical markers for adriamycin resistance can be detected with NMR spectroscopy. However, more studies are necessary to obtain parameters to distinguish drug-sensitive from drug-resistant tumours in patients by NMR spectroscopy.
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PMID:NMR spectroscopy analysis of phosphorus metabolites and the effect of adriamycin on these metabolite levels in an adriamycin-sensitive and -resistant human small cell lung carcinoma cell line. 184 46

In [3H]inositol-labeled membranes prepared from Swiss mouse 3T3 and human small cell lung carcinoma cells, [Tyr4]-bombesin stimulated production of water-soluble inositol phosphates. The reaction was stimulated by guanosine 5'-O-[3-thiotriphosphate] and was specifically inhibited by both [Leu13-psi-CH2NHLeu14]-bombesin and the antibombesin antibody 2A11. [Tyr4]-bombesin-induced activation of phospholipase C is most apparent in Ca2(+)-depleted conditions (less than 1 microM[Ca2+]free). The kinetics of activation by ligand also demonstrate that [Tyr4]-bombesin-dependent phospholipase C activation is most apparent at [Mg2+]free of approximately 0.2 microM. At millimolar concentrations of [Mg2+]free, there is considerably less dependence on [Tyr4]-bombesin for activation of phospholipase C. ATP is not necessary for initial activation of phospholipase C, and beta, gamma-imidoadenosine-5'-triphosphate does not inhibit the reaction. These results demonstrate that in these cell types [Tyr4]-bombesin activates phospholipase C in conjunction with guanine nucleotides. Phospholipase C-coupled guanine nucleotide regulatory proteins would be appropriately considered as novel targets for the development of therapeutic strategies in small cell lung carcinoma.
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PMID:Effect of guanine and adenine nucleotides on bombesin-stimulated phospholipase C activity in membranes from Swiss 3T3 and small cell lung carcinoma cells. 216 51

It has been hypothesized that bombesin-like peptides produced by small cell lung carcinomas may sustain deregulated proliferation through an autocrine mechanism. We have shown that the neuropeptide bombesin leads to the activation of a protein-tyrosine kinase that phosphorylates a 115-kDa protein (p115) associated with the bombesin receptor complex in mouse Swiss 3T3 fibroblasts. We now report that phosphotyrosine antibodies recognize a 115-kDa protein, phosphorylated on tyrosine, in four human small cell lung carcinoma cell lines producing bombesin but not in a nonproducer "variant" line. p115 from detergent-treated small cell lung carcinoma cells binds to bombesin-Sepharose and can be phosphorylated on tyrosine in the presence of radiolabeled ATP and Mn2+. As for the p115 immunoprecipitated from mouse fibroblast, the small cell lung carcinoma p115 can be phosphorylated in an immunocomplex kinase assay. However, the latter does not require the presence of exogenous bombesin for activity. Binding data, obtained by using radiolabeled ligand, suggest receptor occupancy in the cell lines producing bombesin. These observations are consistent with the hypothesis that proliferation in some human small cell lung carcinoma lines is under autocrine control, regulated through activation of bombesin receptors.
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PMID:Activation of the protein-tyrosine kinase associated with the bombesin receptor complex in small cell lung carcinomas. 245 Dec 42

Platelet aggregation, plasma beta-thromboglobulin (beta-TG) concentration and coenzyme Q10 content in serum and platelets were measured in 45 patients with unresectable carcinoma of the lung and in 7 patients with metastatic pulmonary tumor before and after receiving chemotherapy. A significant increase in the plasma beta-TG concentration in cancer patients (47.4 +/- 18.7 ng/ml) was observed (p less than 0.001) compared to the controls (30.3 +/- 9.2 ng/ml). Serum coenzyme Q10 content was lower in cancer patients (0.42 +/- 0.19 micrograms/ml) (p less than 0.05) compared to the controls (0.57 +/- 0.24 micrograms/ml). The reason of decrease in serum coenzyme Q10 content in cancer patients was difficult to explain. No significant difference of the coenzyme Q10 content in platelets (1 X 10(8) cells) was observed either cancer patients (12.5 +/- 2.8 ng) or the controls (12.6 +/- 2.1 ng). No significant correlation was noted among platelet aggregation, plasma beta-TG concentration and coenzyme Q10 content in serum and platelets. Administration of either vindesine or KW2083 did not influence the coenzyme Q10 content in platelets. These results suggest that ATP synthetic pathway by oxidative phosphorylation in platelet be maintained in cancer patients, although a significant increase of plasma beta-TG concentration appears to be associated with an acceleration in the metabolic turnover of platelet.
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PMID:[Platelet aggregation and coenzyme Q10 content in platelets in cancer patients]. 623 57

Until recently, the signal transduction pathways involved in the processes of tumor growth have been poorly understood. In the present study, we investigated cell surface receptors which utilize phosphatidylinositol (Pl) turnover/Ca2+ mobilization as a signal transduction pathway to regulate cell growth in a metastatic human lung carcinoma cell line, PG. We found that purinoceptor agonists, including ATP and its analogs, and bombesin, an amphibian tetradeca-peptide of mammalian homology gastrin-releasing peptide, induced rapid transient increase of cytoplasmic-free Ca2+ in PG cells loaded with fura-2. The Ca2+ responses were derived both from release from internal stores and the opening of plasma membrane Ca2+ channels. HPLC analysis of inositol 1,4,5-triphosphate (Ins(1,4,5)P3) and its isomers showed a receptor-linked phospholipase C activation by ATP and bombesin. Although ATP and bombesin were both able to induce Pl turnover and Ca2+ mobilization in PG cells, they had differential growth regulatory effects on PG cells. Treatment with bombesin stimulated PG cell growth while treatment with ATP inhibited significantly PG cell growth. Pharmacological studies showed that the purinoceptors on PG cells were of the P2 subtype. Other hydrolysis-resistant P2 purinoceptor agonists, including ATP gamma S and AMP-PNP, were as effective as ATP in stimulating Pl turnover and Ca2+ mobilization as well as in inhibiting PG cell growth in vitro, suggesting the potential usefulness of such ATP analogs in clinical trials. Preliminary results suggest G protein involvement in the differential regulation of ATP and bombesin signal transduction pathways.
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PMID:Differential growth regulation of a metastatic human lung carcinoma cell line through activation of phosphatidyl inositol turnover signal transduction pathway. 831 79

The signal transduction involved in growth regulation of cells originally from a human giant cell lung carcinoma(PG) was investigated. The purinergic receptor agonists, ATP and its analogues, as well as bombesin all played a significant growth regulatory role on PG cells. ATP showed a growth inhibitory effect while bombesin showed a growth stimulatory effect on PG cells in vitro. Further investigation showed that ATP and bombesin activated phosphatidylinositol turnover/calcium mobilization signal transduction pathways in PG cells. and increased production of inositol-(1,4,5) trisphosphate and mobilization of intracellular free calcium, in which ATP and bombesin effects were dose-dependent. The purinergic receptor on PG cells was characterized by P2y subtype according to the order of PG cell responses to a series of ATP analogues. Pretreatment with cholera toxin showed different effects on the functions of ATP and bombesin, suggesting that the major difference between ATP and bombesin on signal transduction pathways may be at the G protein level.
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PMID:[Signal transduction study on the growth regulation of cells from human giant cell lung carcinoma in vitro]. 840 96

The biological effect of type 1 interferons is proposed to arise in part from the conjugation of ubiquitin cross-reactive protein (UCRP), the ISG15 gene product, to intracellular target proteins in a process analogous to that of its sequence homolog ubiquitin, a highly conserved 8.6-kDa polypeptide whose ligation marks proteins for degradation via the 26 S proteasome. Inclusion of CoCl2 during the purification of recombinant UCRP blocks the proteolytic inactivation of the polypeptide occurring by cleavage of the carboxyl-terminal glycine dipeptide required for activation and subsequent ligation. Intact UCRP supports a low rate of ubiquitin-activating enzyme (E1)-dependent ATP:PPi exchange but fails to form a stoichiometric E1-UCRP thiol ester or undergo transfer to ubiquitin carrier protein (E2). The binding affinity of E1 for UCRP is significantly diminished relative to that of ubiquitin. These results suggest that UCRP conjugation proceeds through an enzyme pathway distinct from that of ubiquitin, at least with respect to the step of activation. This was confirmed for an in vitro conjugation assay in which 125I-UCRP could be ligated in an ATP-dependent reaction to proteins present within an A549 human lung carcinoma cell extract and could be competitively inhibited by excess unlabeled UCRP but not ubiquitin. Other results demonstrate that 125I-UCRP conjugation is significantly increased in cell extracts after 24 h of incubation in the presence of interferon-beta, consistent with the late induction of UCRP conjugating activity. Thus, interferon-responsive cells contain a pathway for UCRP ligation that is parallel but distinct from that of ubiquitin.
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PMID:Conjugation of the 15-kDa interferon-induced ubiquitin homolog is distinct from that of ubiquitin. 855 May 81

Many previous studies have demonstrated that antisense oligodeoxynucleotides (ODNs) bind to surface proteins in a manner compatible with receptor-mediated endocytosis and, unless specifically modified, are internalized into endosomes with little access to the cytoplasmic structures or to the nucleus. Reports vary as to the specific proteins involved in the mechanism, and this study examines the conditions of binding, some proteins that might contribute to the process, and whether changes in binding patterns occur during differentiation. Native gel electrophoresis was used to optimize the surface binding of a phosphorothioate end-capped 16-mer to T15 mouse fibroblast cells, and comparisons are made with some human epithelial tumor cell lines. Binding to individual proteins was visualized using SDS-PAGE and autoradiography. Binding at 4 degrees C was almost exclusively to a 46 kDa protein and decreased in the presence of an excess of unlabeled ODN and heparin but not ATP. Increasing the temperature of ODN binding from 4 degrees C to 37 degrees C for 10 minutes changed the binding pattern observed. ODN binding to the total cytoplasmic and membrane proteins immobilized on a membrane showed a greater number of binding proteins, the most prominent being one of 30 kDa. Examination of the effects of serum on binding were made using the human lung carcinoma cell line COR-L23, which can be grown in serum-free conditions. Serum starvation led to an increased total binding seen on native gels coinciding with increased binding to a 46 kDa protein. Demonstration that changes in binding proteins occur when cells differentiate was made using the premacrophage cell line THP-1. Differentiation of these cells increased the total ODN binding and appeared to initiate the synthesis of some new binding proteins, although binding to a 46 kDa protein was reduced.
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PMID:Interaction of oligodeoxynucleotides with mammalian cells. 891 3


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