Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tests of 12 popular brands of cigarettes manufactured by 6 companies from the United States have shown that fibers were released from the filters and that there exists probable cause to suggest that fibers are inhaled and/or ingested. Filter fibers, made of cellulose acetate, were implanted in mice for 6 months. The fibers withstood degradation and retained the tobacco-brown color and bright fluorescence of the tobacco tar that had been adsorbed from cigarette smoke. With a confocal laser scanning microscope, we have observed cigarette filter fibers in lung tissue from patients with lung cancer and who were known to be habitual smokers. These findings raise the question as to whether fibers released from cigarettes further jeopardize the health of smokers and document the need to test components of cigarette filters for toxicity and tumorigenicity.
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PMID:Fibers released from cigarette filters: an additional health risk to the smoker? 781 54

The occurrence of inflammatory processes and of cancer in the human respiratory tract is intimately associated. One of the major factors in this is probably the recruitment of and stimulated activity of polymorphonuclear leukocytes (PML) in conjunction with the ability of these cells to convert various carcinogens to their ultimate active metabolites. In this study, we demonstrate that nitrite and sulfite, the major dissolution products of the environmental pollutants nitrogen dioxide and sulfur dioxide in water enhance the metabolic activation of trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-dihydrodiol), the proximal carcinogen of benzo[a]pyrene, to trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and tetraols, the corresponding hydrolysis products, in human PML prestimulated with 12-O-tetradecanoylphorbol-13-acetate. Nitrite was more efficient than sulfite in stimulating the formation of reactive intermediates of BP-7,8-dihydrodiol in PML that covalently bind to extracellular DNA and, in particular, to intracellular proteins. The mechanism by which sulfite stimulates the metabolism of BP-7,8-dihydrodiol most probably involves the intermediate formation of a sulfur trioxide radical anion (SO3.-) the subsequent formation of the corresponding sulfur peroxyl radical anion (.OOSO3-) in the presence of oxygen. The mechanism underlying the stimulatory action of nitrite is less clear but the major pathway seems to involve myeloperoxidase. These results offer an explanation for the increased incidence of lung cancer in cigarette smokers living in urban areas. The major glutathione transferase (GST) isoenzyme in human PML is GST P1-1, a Pi-class form. The GST activity of PML was found to be inversely correlated with the extent of binding of BP-7,8-dihydrodiol products to exogenous DNA. These results suggest that individuals exhibiting high GST-activity in the PML may be better protected against the type of carcinogenic dealt with in this study.
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PMID:Stimulatory effects of sulfur and nitrogen oxides on carcinogen activation in human polymorphonuclear leukocytes. 782 Dec 91

Previously, we have shown that opioids acting via specific receptors inhibit the growth of human lung cancer cells while nicotine, acting through nicotinic acetylcholine receptors, reverses this inhibition. Therefore, we studied the role of apoptosis in these processes. Treatment of human lung cancer cells with 0.1-1 microM morphine or methadone resulted in morphological changes and cleavage of DNA into nucleosome-sized fragments characteristic of apoptosis. Quantitation of DNA fragmentation showed that a dose-dependent increase occurred within 2 h of opioid treatment and was blocked by the antagonist naloxone. The apoptotic effect of opioids was suppressed by nicotine, while the nicotinic acetylcholine receptor antagonists, hexamethonium and decamethonium, reversed this suppression. In contrast, sphingosine, a protein kinase C inhibitor, caused significant DNA fragmentation which was not suppressed by nicotine. Unexpectedly, the combination of hexamethonium and opioids or hexamethonium and nicotine stimulated apoptosis. We found that nicotine, like phorbol 12-myristate 13-acetate, increased total protein kinase C (PKC) activity, while morphine and sphingosine decreased PKC activity, and nicotine reversed morphine inhibition of PKC activity. In contrast, methadone unexpectedly increased PKC activity. These results indicate that engagement of opioid receptors in human lung cancer cells induces apoptosis, while engagement of nicotine receptors suppresses apoptosis, which in some cases appear to be working through a PKC pathway. They also suggest complexities in the system where blockade of C6 or C10 nicotinic receptors can lead to facilitation of apoptosis. These findings suggest new strategies for treatment and prevention of cancer using opioids or nicotine receptors antagonists and are consistent with the idea that nicotine functions as a tumor promoter.
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PMID:Opioids induce while nicotine suppresses apoptosis in human lung cancer cells. 784 4

Starting with observations that were first published in 1982, a series of additional findings led to the discovery of an important property of cells in late G2/mitosis. In addition to being the most sensitive to killing, cells in this age-interval were also shown to be the most sensitive to radiation-induced neoplastic transformation. In this work, C3H mouse cells, designated 10T1/2, were irradiated with fission-spectrum neutrons and assayed in vitro via the endpoint focus formation on a monolayer of normal cells. From these observations, a biophysical model was developed to explain the anomalous finding that the frequency of transformation by low doses was enhanced when the exposure was protracted. In contrast to transformation by X- and gamma-rays where repair and kinetics during exposure play dominant roles, with radiations like reactor neutrons and alpha-particles repair has a minimal effect; only cell kinetics acts significantly to modify transformation due to protracted doses. In this report, the lack of responsiveness of mitotic cells to promotion by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate is shown further to agree with the findings with fission-neutrons and the model that, at low dose rate, enhanced transformation is due principally to the progression of cells into the window of sensitivity. Implications of this model for lung cancer due to environmental radon are also discussed.
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PMID:Enhanced tumorigenesis by small, protracted doses of densely ionizing radiation. 795 79

We have investigated the ability of aqueous cigarette tar extracts to promote human polymorphonuclear leukocyte (PMNL)- and hydrogen peroxide (H2O2)-induced DNA single-strand breaks (DNA-SSB) in cultured human lung cells. Tar extract itself did not cause any DNA-SSB formation, whereas PMNL (activated with phorbol myristate acetate (PMA)) and H2O2 both caused a small but significant DNA-SSB formation on their own. On the other hand, if cells were first treated with tar extract and then exposed to PMA-activated PMNL or H2O2, the DNA-SSB formation increased considerably. Pretreatment with iron-loaded tar extracts caused a greater increase after PMNL exposure than pretreatment with regular tar extracts. No DNA-SSB formation was found if catalase was present during the PMNL exposure, indicating that H2O2 was important for the PMNL-induced DNA damage. These findings suggest that cigarette tar promotes neutrophil-induced DNA damage in human lung cells and that this effect can be further potentiated by iron. This can be of importance in explaining the carcinogenic effects of cigarette smoking and the increased risk of lung cancer among asbestos workers and iron miners who smoke.
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PMID:Cigarette tar promotes neutrophil-induced DNA damage in cultured lung cells. 830 45

C-fibres probably represent the common final pathway in both ACE inhibitors and neoplastic cough. A recent report demonstrated that inhaled sodium cromoglycate is an effective treatment for ACE inhibitors' cough; this effect might be due to the suppression of afferent unmyelinated C-fibres. We tested the hypothesis that inhaled sodium cromoglycate might also be effective in lung cancer patients who presented with irritative neoplastic cough. Twenty non-small-cell lung cancer (NSCLC) patients complaining of cough resistant to conventional treatment were randomised to receive, in a double-blind trial, either inhaled sodium cromoglycate or placebo. Patients recorded cough severity daily, before and during treatment, on a 0 to 4 scale. The efficacy of treatment was tested with the Mann-Whitney U-test for non-parametric measures, comparing the intergroup differences in the measures of summary of symptom scores calculated in each patient before and after treatment. We report that inhaled sodium cromoglycate can reduce cough, also in NSCLC patients and that such reduction, observed in all patients treated, is statistically significant (P < 0.001). Inhaled sodium cromoglycate appears to be a cost-effective and safe treatment for lung cancer-related cough.
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PMID:Inhaled sodium cromoglycate to treat cough in advanced lung cancer patients. 868 42

Vasoactive intestinal peptide (VIP) is a neuropeptide of multiple functions affecting development and aging. In cancer, for example, VIP was found to function as an autocrine growth factor in nonsmall cell lung cancer (NSCLC) promotion. Furthermore, a VIP hybrid antagonist (neurotensin(6-11)-VIP(7-28)) was found to inhibit NSCLC growth. In the present study, the expression of VIP mRNA was studied using human lung cancer cells. RNA prepared from 19 cell lines was fractionated by 1% agarose gel electrophoresis followed by blotting onto nitrocellulose membranes and hybridization to a VIP-specific RNA probe. VIP mRNA was detected in about 50% of the cell lines tested with a greater abundance in NSCLC. Cultures of the NSCLC NCI-H727 cell line were treated with forskolin, an activator of cyclic AMP (cAMP), and separately with the tumor promoter phorbol 12-myristate 13-acetate (PMA). Northern blot hybridization analysis showed an increase in VIP mRNA levels after 4 h treatment with 50 microM forskolin. Incubation with PMA also showed a significant increase in the levels of VIP transcripts. Cultures were then incubated with PMA in the presence of actinomycin D, a transcription blocker. Results indicated that PMA treatment may induce both VIP mRNA synthesis as well as VIP mRNA stabilization, and suggested a 4-5 h half-life for the VIP mRNA in the absence of PMA. Thus, lung cancer tumor proliferation may be regulated, in part, at the level of VIP gene expression.
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PMID:Regulation of VIP gene expression in general. Human lung cancer cells in particular. 887 94

Nicotine, a major component of cigarette smoke, plays an important role in the development of cardiovascular disease and lung cancer in smokers. The effect of nicotine on lipoprotein metabolism was studied using rats as the experimental animal. There was a significant increase in the total cholesterol, phospholipids, and triglycerides as well as the amount of lipids associated with very low density lipoprotein (VLDL) and low density lipoprotein (LDL) in sera of nicotine-treated rats. The incorporation of 3H labeled leucine into the apo B was found to be increased both in the medium and associated cells in the hepatocytes isolated from nicotine-treated rats indicating an increased synthesis and secretion of the apo B containing lipoproteins. This was further confirmed by the higher incorporation of 14C acetate into total and individual lipids of LDL and VLDL secreted into the medium as well as that associated with different lipids in the cell layer. The activity of lipoprotein lipase in extrahepatic tissues and plasma lecithin cholesterol acyl transferase activity were significantly lower in nicotine-treated rats. These results indicate that nicotine exerts hyperlipidemic effects particularly by increasing the synthesis and secretion of triglyceride-rich lipoproteins. Since nicotine is one of the major hazardous components present in cigarette smoke and tobacco, one can extrapolate that the deleterious effect exerted by nicotine on rats extends to cigarette smokers and those who use other forms of tobacco.
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PMID:Effect of nicotine on lipoprotein metabolism in rats. 907 68

Transforming growth factor-beta (TGF-beta) mediates the production of extracellular matrix proteins, proteases and protease inhibitors in epithelial cells. Both TGF-beta and phorbol-12-myristate-13-acetate (PMA) exert both positive and negative effects on mitogenesis in these as well as other cell types. Phorbol esters act through stimulation of protein kinase C (PKC) and are among the most potent tumor promoters known. The present study was conducted to determine whether the effect of TGF-beta in human non-small cell lung cancer (NSCLC) and normal human bronchial epithelial (NHBE) cells parallels that of the phorbol esters and whether this effect of TGF-beta involves PKC. TGF-beta 1 and PMA increased expression of TGF-beta 1 mRNA 24 hr after their addition to both NSCLC and NHBE cells. The effects of these agents on expression of the mRNAs for TGF-beta 2 and TGF-beta 3 were more complex; while TGF-beta 2 and TGF-beta 3 mRNAs increased transiently in response to TGF-beta 1 in NHBE cells and TGF-beta 3 mRNA increased transiently in some NSCLC cells, expression of these mRNAs decreased in most of these cells in response to PMA with the exception of the carcinoid NCI-H727 where TGF-beta 2 mRNA increased dramatically, TGF-beta 1 and PMA both caused a persistent increase in expression of the mRNAs for both plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator (PA) up to 24 hr in most NSCLC cells, with the increase in PAI-1 mRNA beginning several hours before that of PA mRNA. In contrast, while TGF-beta 1 also increased expression of PAI-1 mRNA in NHBE cells, the expression of PA mRNA decreased simultaneously. The effect of PMA on PAI-1 and PA mRNAs was opposite of TGF-beta 1 in these cells, with expression of PAI-1 mRNA decreasing and PA mRNA increasing after addition of PMA. These data show that there is parallel regulation of the genes for TGF-beta 1, PAI-1 and PA by TGF-beta 1 and PMA in NSCLC, but differential regulation of the genes for PAI-1 and PA by these agents in NHBE cells. The responses of the mRNAs and proteins of TGF-beta 1, PAI-1 and PA to TGF-beta 1 and PMA were inhibited by the serine/ threonine kinase inhibitor H7 in NSCLC cells. Treatment of NSCLC cells with TGF-beta 1 and PMA resulted in a persistent increase in the expression of fibronectin mRNA and protein. This response was blocked by the addition of H7. Inhibition of these effects by H7 in NSCLC cells suggests that H7 blocks TGF-beta responses by inhibiting a protein serine/threonine kinase(s). Because the effects of TGF-beta and PMA on the different TGF-beta isoforms, PA, PAI and fibronectin in NHBE and NSCLC cells are complex, our data suggest that there are distinct mechanisms for controlling the different TGF-beta isoforms, PA, PAI and extracellular matrix proteins in normal lung and lung cancer cells.
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PMID:Effects of transforming growth factor-beta 1 and phorbol ester on PAI-1 and PA genes in human lung cells. 925 8

During apoptosis, one of the first membrane changes that can be detected is exposure of phosphatidylserine residues at the outer plasma membrane leaflet, while early apoptosis is also accompanied by changes in the cytoskeletal organization. In this study we investigated the relationship between these two phenomena during olomoucine- and roscovitin-induced apoptosis in human lung cancer and neuroblastoma cell lines. Loss of membrane asymmetry was detected by biotin-labeled or FITC-labeled annexin V binding to negatively charged phosphatidylserine, while cytoskeletal components were visualized by immunocytochemistry. The apoptotic, annexin V-positive, cells were analyzed by flow cytometry, confocal scanning laser microscopy, and Western blotting. We report that cytokeratin and vimentin aggregation in early apoptosis occurs simultaneously with phosphatidylserine exposure and chromatin condensation. In contrast to these intermediate filament proteins, which were disassembled and proteolytically cleaved in early apoptosis, microfilaments and microtubuli were not proteolytically degraded but were found to be present as aggregated filaments in the apoptotic bodies. We also show that loss of membrane asymmetry and cytokeratin aggregation are independent processes, since N-ethylmaleimide-induced phosphatidylserine exposure does not cause cytokeratin disassembly. Vice versa, phorbol 12-myristate 13-acetate-induced cytokeratin filament aggregation does not result in phosphatidylserine exposure.
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PMID:Plasma membrane alterations and cytoskeletal changes in apoptosis. 929 67


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