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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytogenetic and molecular genetic studies have implicated many chromosomal aberrations in the pathogenesis of lung cancer. Deletions on 3p and 9p are presently the primary target for positional cloning of putative tumor suppressor genes. We have recently reported frequent loss of heterozygosity in three separate regions (HRAS, D11S12, D11S16) on 11p in freshly resected lung cancer specimens. Here we report cytogenetic and molecular genetic analyses of 26 permanently growing human lung cancer cell lines. Deletions indicating regions which may harbor potential tumor suppressor genes were found in 5/9 cell lines on 2p, 5/9 on 2q, 6/9 on 3p, 7/9 on 3q, 5/9 on 6q, 3/9 on 9p, 5/9 on 11p, and 6/9 on 13q. Reduction to hemizygosity or a statistically significant increase in the frequency of homozygosity on 11p was found for all markers investigated except for ST5 (D11S832E). Eight of twenty-six (31%) cell lines were hemizygous for D11S12 and 9/26 (35%) for D11S16. Seventeen of eighteen (94%) cell lines were homozygous for PTH (expected homozygosity, 53%), 15/15 (100%) for WT1 (expected homozygosity, 55%), and 16/18 (89%) for CAT (expected homozygosity, 50%). These results confirm the notion that 11p harbors several putative tumor suppressor genes which may become inactivated at different stages of tumor development and progression. They also provide a basis for selecting cell lines for genetic complementation specifically targeted at the regions described.
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PMID:Multiple chromosomal aberrations and 11p allelotyping in lung cancer cell lines. 749 41

Non-small cell lung cancer (N-SCLC) is generally unresponsive to chemotherapy even without previous drug treatment, as opposed to small cell lung cancer (SCLC), which is initially responsive to chemotherapy. The mechanisms of this intrinsic resistance are unknown. This study was designed to investigate the role of DNA repair in intrinsic resistance of N-SCLC to cisplatin. A panel of primary N-SCLC cell cultures and established cell lines were examined and compared to SCLC cell lines established previously from untreated patients. The overall DNA repair capacity was estimated by the ability of cells to reactivate the pRSV-CAT plasmid damaged by cisplatin ("host cell reactivation" assay). Cytotoxicity was determined for cisplatin in vitro. N-SCLC cells were found to be significantly more resistant to cisplatin than SCLC cell lines isolated from untreated patients (P < 0.01). The capacity of N-SCLC cells to reactivate pRSV-CAT plasmid damaged with cisplatin and transfected into cells was higher in N-SCLC cells than in SCLC cells originating from patients who were untreated previously (P < 0.05). Correlation was also observed between chloramphenicol acetyltransferase activity and intrinsic resistance to cisplatin. However, no significant difference was observed between primary N-SCLC cultures and established cell lines. This study indicates that elevated DNA repair capacity is associated with drug resistance in lung cancer and suggests that modulation of DNA repair mechanism(s), such as the incorporation of specific DNA repair inhibitor(s) in therapeutic regimens, may help to improve therapeutic strategies of N-SCLC.
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PMID:Elevated DNA repair capacity is associated with intrinsic resistance of lung cancer to chemotherapy. 758

The HER2/neu (c-erbB2) protooncogene, which encodes a transmembrane receptor (p185neu), contributes to tumor cell invasion/metastasis through mechanism(s) which are, at present, poorly defined. Since basement membrane degradation is a prerequisite for tumor progression, we undertook a study to determine if the expression of urokinase, a key protease implicated in extracellular matrix proteolysis, was regulated by this oncogene. Stable overexpression of a cDNA encoding HER2/neu in H460 lung cancer cells led to elevated secretion of urokinase which was a consequence of a higher level of protease mRNA. Transfection of the HER2/neu-overexpressing B 104-1 cells with a CAT reporter construct driven by the urokinase promoter, gave rise to increased CAT activity when compared with parental NIH3T3 cells, which have low levels of HER2/neu, suggesting that the protooncogene can enhance urokinase promoter activity. Since the enhanced expression of HER2/neu results in increased tumor invasion/metastasis (1), these data suggest that, at least in vitro, HER2/neu-induced expression of urokinase may contribute to tumor progression in p185neu-positive cancers.
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PMID:Up-regulation of urokinase-type plasminogen activator expression by the HER2/neu proto-oncogene. 765 95

Transcriptional regulation of the human parathyroid hormone-related protein (PTHrP) gene by calcitonin was examined in a lung cancer line (BEN cells). Northern analysis demonstrated that calcitonin caused a rapid 4.5-fold elevation in PTHrP mRNA. Transient transfection of a construct containing 1119 base pairs of the human PTHrP gene 5' to the ATG start site of translation, fused to the CAT reporter sequence, was used to demonstrate a five-fold increase in transcription by calcitonin. Similar increases were also observed when transfected cells were exposed to a number of cAMP agonists including forskolin, as well as isobutyl-methylxanthine. A putative cAMP responsive element (5'-TGACTTCA-3') present within exon 4 was placed upstream of the heterologous SV40 promoter. Expression of this construct was elevated 4.5-fold in response to calcitonin and 7-fold in response to forskolin. Similar responses to calcitonin occurred with a smaller construct (pZMR30) containing 530 bp of sequence upstream of the ATG start site. Thus we postulate that calcitonin acts at least partially via cAMP through this element in exon 4 of the human PTHrP gene.
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PMID:Calcitonin increases transcription of parathyroid hormone-related protein via cAMP. 769 Jul 20

The finding of a cardiac tamponade (CT) as initial manifestation of lung cancer is rare, being its most frequent manifestations dyspnea, cough and edemas. The presence of alithiasic acute cholecystitis (AAC) as early manifestation of CT is extremely rare, despite this having being described related to other situations of low cardiac output. We present the case of a patient who underwent emergency surgery due to AAC as a form of presentation of CT, this being the initial manifestation of a pulmonary adenocarcinoma. The histopathological study of the liver and the vesicle were compatible with signs of short evolution venous stasis, and the diagnosis was established through pericardium biopsy and thoracic CAT.
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PMID:[Acute acalculous cholecystitis complicating the presentation of cardiac tamponade as the initial manifestation of a pulmonary carcinoma]. 774 16

Normal human bronchial epithelial (NHBE) cells are the putative progenitor cells of all types of lung cancer. NHBE cells immortalized by SV40 T-antigen retain many characteristics of the primary cells and are a useful model for investigating the role of oncogenes, tumor suppressor genes, and certain chemical carcinogens in the molecular pathogenesis of lung cancer. In this study, SV40 T-antigen-positive cells (BEAS-2B) were characterized for their metabolic functions and were shown to continue to express epoxide hydrolase, glutathione S-transferase pi, glutathione peroxidase, and catalase. To increase their metabolic activity towards human procarcinogens, human cytochrome P450 1A2 (CYP1A2) was stably expressed by introducing CYP1A2 cDNA into BEAS-2B cells either by infection with a high-titer recombinant retrovirus (pXT-1A2) or by transfection with a CYP1A2 expression vector (pCMV1A2), which produced the cell lines B-1A2 and B-CMV1A2, respectively. Cell lines established with either expression system expressed enzymatically active CYP1A2 protein and were 50- to 400-fold more sensitive to the cytotoxic effect of the carcinogen aflatoxin B1 (AFB1) than the corresponding control cell lines. The cytotoxic effects of AFB1 were paralleled by increased metabolism of AFB1 and enhanced formation of the AFB1-N7 guanine adduct in B-CMV1A2 cells. Cytotoxicity and adduct formation correlated with a significantly higher protein expression of CYP1A2 by the cytomegalovirus promoter-driven plasmid. Since this human epithelial cell line is the precursor cell type of lung cancer, has normal phase II enzymes, and exhibits highly reproducible expression of phase I enzymes, this in vitro model should aid in the evaluation of putative human carcinogens and anticarcinogens.
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PMID:Activation of promutagens in a human bronchial epithelial cell line stably expressing human cytochrome P450 1A2. 791 94

The combination of cigarette smoke and high-level occupational asbestos exposure produces a synergistic increase in the incidence of lung cancer; however, smoking does not affect the incidence of mesothelioma. Here we present the results of tests of two theories that have been proposed to explain this phenomenon; namely, that pleural mesothelial cells are resistant to cigarette smoke-induced damage and that the pleural connective tissue acts as a barrier that prevents smoke from reaching the mesothelial cells. To test these hypotheses, excised whole rat lung preparations were exposed to either internal (intratracheal) or external (pleural surface) smoke. For comparison, additional excised lung preparations were exposed to solutions of hydrogen peroxide either externally or intratracheally. Mesothelial cells exposed to external smoke showed widespread, dose-dependent uptake of Trypan blue. Mesothelial cells did not take up Trypan blue after exposure to internal smoke. Bronchial epithelial cells exposed to internal smoke did show uptake, but to a lesser degree than externally exposed mesothelial cells. Examination by scanning and transmission electron microscopy showed that internal smoke did not affect mesothelial cell ultrastructure, whereas external smoke produced obvious mesothelial cell damage and mesothelial cell detachment. Catalase and deferoxamine, scavengers of active oxygen species, provided protection against smoke-induced mesothelial cell injury, but inactivated catalase did not. External hydrogen peroxide produced a very similar, dose-dependent pattern of Trypan blue uptake and ultrastructural changes. Intratracheal hydrogen peroxide also damaged mesothelial cells, but the extent of damage was always less than with comparable concentrations of external hydrogen peroxide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rat pleural mesothelial cells show damage after exposure to external but not internal cigarette smoke. 827 90

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

The expression of intrinsic resistance to cisplatin in two lung cancer cell lines, one derived from a small cell carcinoma (SW1271) and the other from an adenocarcinoma (A549), relative to a drug-sensitive small cell line SW900, was characterized by: (i) expression of cross-resistance to mitomycin C and cadmium chloride, but increased sensitivity to adriamycin and etoposide; (ii) significantly decreased cisplatin uptake; (iii) elevated levels of glutathione which could be reduced by buthionine L-sulfoximine resulting in significant sensitization of the cells to cisplatin; (iv) a lack of consistent modification of metallothionein content and expression of levels of glutathione S-transferase, glutathione reductase and glutathione peroxidase or of activities of DT-diaphorase or catalase; (v) significantly reduced total DNA-platination levels immediately following a 1 h cisplatin treatment with 10 micrograms/ml (33.3 microM); (vi) increased removal of Pt-GG and Pt-AG adducts by the A549 cells, consistent with increased repair capacity, but a lack of removal of these major adducts by the SW1271 cells indicative of tolerance of this drug-induced DNA damage. These data therefore provide evidence of differential formation, repair and tolerance of DNA damage following exposure of three human lung carcinoma cell lines to cisplatin.
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PMID:Evidence of differential cisplatin-DNA adduct formation, removal and tolerance of DNA damage in three human lung carcinoma cell lines. 840 Mar 52

We show that the expression of the human cytokeratin 8 (CK8) gene is regulated by wild-type p53. DNA sequence data indicate that the 5' untranslated region of the CK8 gene contains a putative p53-like binding site. In this study we focused on the effect of the p53 protein on the regulation and expression of the CK8 gene. Cotransfection of the H358 p53-negative human lung cancer cell line with a CK8 promoter CAT expression vector and a plasmid expressing the wildtype p53 indicated that p53 induces CK8 expression. A transient assay in which a p53-negative cell line was cotransfected with a CK8 promoter CAT expression vector and a plasmid expressing wildtype or mutant p53 indicated that only wildtype p53 induces the CK8 promoter. Deletion of the putative p53-binding site from the CK8 promoter or introduction of mutations in the p53-binding sequences abolished the wild-type p53-mediated transactivation of CK8. A gel-retardation assay was used to measure DNA binding by the wild-type p53 protein. A 24-bp oligonucleotide corresponding to the putative p53 binding site was used for this assay. The wild-type p53 protein bound weakly to this DNA sequence but much more strongly when three tandem repeat of the binding sequences was used. These studies suggest that the CK8 gene is a downstream target whose expression is regulated by wild-type p53.
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PMID:p53 involvement in activation of the cytokeratin 8 gene in tumor cell lines. 861 94


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