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)

WWOX (WW domain containing oxidoreductase), a putative tumor suppressor gene that maps to the common fragile site FRA16D on chromosome 16q23.3-24.1, is altered in breast, esophageal, and ovarian cancer. Because the FRA3B/FHIT locus at 3p14.2 is a preferential target for genetic changes caused by tobacco smoke, we intended to evaluate the status of the FRA16D/WWOX gene in non-small cell lung cancer; we have analyzed 27 paired normal and tumor lung tissues and 8 lung cancer cell lines for WWOX alterations by reverse transcriptase-PCR, loss of heterozygosity, and mutation analysis. Transcripts missing WWOX exons were detected in 7 primary tumors (7 of 27; 25.9%) and 5 of 8 cell lines. In addition, loss of heterozygosity at the WWOX locus was observed in 10 primary tumors (10 of 27; 37.0%). We conclude that WWOX alterations occur in a significant fraction of lung cancers and may contribute to the pathogenesis of non-small cell lung cancer.
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PMID:WW domain containing oxidoreductase gene expression is altered in non-small cell lung cancer. 1259 41

The current authors previously identified circulating cells expressing carcinoembryonic antigen (CEA) messenger ribonucleic acid (mRNA) in 80% of lung cancer patients bearing distant metastases. The current study prospectively validated the data on a novel cohort and extended the study to other mRNAs expressed by neoplastic cells. CEA, cytokeratin 19 and 20, aldolase A and epithelial glycoprotein 2 (EPG2) mRNA was analysed by reverse transcriptase-polymerase chain reaction in circulating cells from 19 healthy controls, and in biopsies and blood at diagnosis from 32 lung cancer patients monitored for 24 months. Aldolase A and cytokeratin 19 mRNA occurred in circulating cells of all controls; cytokeratin 20 was not expressed by any lung cancer biopsy. EPG2 mRNA occurred in all biopsies but not in the patients' circulating cells. CEA mRNA occurred in 29/32 (90.6%) biopsies and in 17/32 mRNA samples from circulating cells from lung cancer patients. Of these positive patients 12/17 developed metastases within 9 months of mRNA analysis. Three positive patients died, one was lost to follow-up, and one did not develop metastases within 24 months. Of the negative patients 12/15 did not develop metastases during the 24-month follow-up; one patient was lost to follow-up, one did not express CEA, and another developed metastases. Unlike in other neoplasias, cytokeratin 19 and 20, aldolase A and epithelial glycoprotein 2 messenger ribonucleic acid are not useful for the detection of circulating cancer cells in lung cancer. Carcinoembryonic antigen messenger ribonucleic acid analysis in circulating cells helps to identify lung cancer patients at a greater risk of metastases.
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PMID:Carcinoembryonic antigen mRNA analysis detects micrometastatic cells in blood from lung cancer patients. 1451 29

Cytokeratin 8 (CK8) is one of the cytoskeletal components and shows caspase-mediated degradation when cells undergo apoptosis. We previously reported that CK8 is highly expressed in non-small cell lung cancer (NSCLC) cell lines and increasing values of serum CK8 are significantly associated with tumor progression in patients with NSCLC. In this investigation, reverse transcriptase-polymerase chain reaction (RT-PCR) analysis in lung cancer cell lines, revealed a shorter PCR product, which differed from the wild-type product of CK8. The nucleotide sequence of the shorter PCR products and genomic DNA for CK8 demonstrated that the shorter product was an aberrantly spliced form of CK8 (AS-CK8) which lacked a caspases cleavage site within the linker lesion in exon 5. The putative protein products predicted by the mRNA of AS-CK8 were demonstrated by Western blotting with monoclonal antibodies for CK8. In addition, AS-CK8 mRNA and its protein products were highly expressed in NSCLC cell lines compared with small-cell lung cancer (SCLC) cell lines. Tissue samples obtained from NSCLC patients also expressed mRNA of AS-CK8. In conclusion, we identified aberrantly spliced CK8 (AS-CK8) which lacked a caspases cleavage site in lung cancer cell lines and primary tumors of NSCLC. AS-CK8 was preferentially expressed in NSCLC, rather than SCLC. These findings lead to speculation that cancer cells expressing AS-CK8 may have a resistance to apoptosis and may perturb keratin network formation.
Lung Cancer 2003 Nov
PMID:Aberrant messenger RNA splicing of the cytokeratin 8 in lung cancer. 1456 82

Malignant transformation of cells is accompanied by multiple genetic abnormalities with aberrant expression of genes. By using the reverse transcriptase polymerase chain reaction (RT-PCR) assay, we have assessed the regulation of survivin gene expression in a prospectively collected series of 83 human non small-cell lung cancers. Survivin gene transcripts were identified in 71 (85.5%) of the tumor samples, while they were detected in only 10 (12%) of the paired histopathologically normal lung samples. Furthermore, a diminished overall survival was associated with survivin expression (Log-rank, P=0.01). This review discusses the structure, expression, and function of the survivin gene. It presents updated pooled data on survivin, analyzed by either immunochemistry or by RT-PCR, and the clinical correlates of aberrant expression in several tumors. We conclude that estimation of survivin gene transcripts by RNA techniques may have relevant applications in the prognostic and therapeutic assessment of lung cancer.
Clin Lung Cancer 1999 Nov
PMID:The anti-apoptosis survivin gene and its role in human cancer: an overview. 1473 65

The aim of this study was to determine whether nucleic acids are detectable in cell-free bronchial lavage supernatants, and whether it is possible to find alterations in this DNA and RNA of genes known to be present in lung tumour cells. DNA was isolated from cell-free lavage supernatants from 30 and RNA from 25 lung cancer patients. The DNA was examined for microsatellite alterations (MA) and the RNA analysed for the expression of seven tumour-associated genes. Intact DNA and mRNA could be isolated from all cell-free bronchial lavage supernatants. MA were found in lavage supernatants of 12/30 patients and in lavage cells of 6/30 patients. Altogether alterations were found in 14/30 patients. Analyses of tumour-associated gene expression showed positive results, with at least one marker in the lavage supernatants of all 25 patients. Thus, we could demonstrate, for the first time, that it is possible to isolate intact DNA and RNA from cell-free bronchial lavage supernatants. Their quantity and quality is sufficient for further amplification by polymerase chain reaction (PCR)/reverse transcriptase (RT)-PCR. Altogether, tumour-associated changes were detected in DNA samples from 47% of the patients and in RNA samples from all of the patients analysed.
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PMID:Detection of cell-free nucleic acids in bronchial lavage fluid supernatants from patients with lung cancer. 1474 65

Most of gastrointestinal, breast and lung cancer cells express carcinoembryonic antigen (CEA). Therefore, this protein represents a suitable target for innovative diagnostic and immunotherapeutic strategies of various tumours. Presently CEA can be involved in three main approaches concerning cancer detection and therapy, i.e. (a) detection of tumour cells in the peripheral blood, bone marrow or lymph node using reverse transcriptase-polymerase chain reaction (RT-PCR)-based measurement of CEA mRNA; (b) targeting of anticancer agents or radionuclides by tumour-selective anti-CEA monoclonal antibodies (mAbs); (c) use of antitumour vaccines capable of eliciting major histocompatibility complex (MHC)-restricted immune responses against CEA-derived peptides. Actually, it has been shown that the expression of CEA can be up-regulated by pharmacological agents including, antineoplastic drugs (i.e. 5-fluorouracil), cytokines (i.e. interferons or interleukin-6), differentiating agents (i.e. sodium butyrate) and protein kinase inhibitors (i.e. staurosporine). Therefore, the use of drugs capable of increasing CEA expression, could amplify the sensitivity of diagnostic procedures that rely on CEA determination. Moreover, the same agents could increase the efficacy of vaccines based on immunogenic CEA-derived peptides restricted by the MHC. The purpose of this review is to describe several agents that are able to increase CEA expression and to discuss the rational bases for new strategies in cancer detection and therapy aimed at increasing the expression of tumour-associated antigens.
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PMID:Drug-induced increase of carcinoembryonic antigen expression in cancer cells. 1499 48

There is accumulating evidence that peptides derived from the catalytic subunit of human telomerase reverse transcriptase (hTERT) are specifically recognized by CD8+ cytotoxic T lymphocytes. We investigated the cytotoxicity of a human leukocyte antigen (HLA)-A*2402-restricted hTERT-derived peptide 461-469 (hTERT461)-specific CD8+ T-cell clone, designated as K3-1, established from a healthy donor by repetitive peptide stimulation. This clone exhibited cytotoxicity against 4 out of 6 HLA-A24-positive lung cancer cell lines with positive telomerase activity but not 4 HLA-A24-negative examples. When the target cells were pretreated with 100 U/ml of interferon (IFN)-gamma for 48 hr, the susceptibility to K3-1 increased with PC9 cells but unexpectedly decreased with LU99 cells. However, in both cell lines, the expression of molecules associated with epitope presentation such as HLA-A24, transporters associated with antigen processing, low molecular weight polypeptide 7 and proteasome activator 28 was similarly increased after IFN-gamma treatment. Results of CTL assays using acid-extracted peptides indicated that the epitope increased on PC9 cells but not on LU99 cells after IFN-gamma treatment. Semi-quantitative reverse transcriptase polymerase chain reaction disclosed that the expression of hTERT was attenuated in LU99 but not in PC9 cells, accounting for the decreased cytotoxicity mediated by K3-1. The attenuation of the hTERT expression and K3-1-mediated cell lysis after IFN-gamma treatment was also observed in primary adenocarcinoma cells obtained from pulmonary fluid of a lung cancer patient. Our data underline the utility of peptide hTERT461 in immunotherapy for lung cancer, as with other malignancies reported earlier, and suggest that modulation of hTERT expression by IFN-gamma needs to be taken into account in therapeutic approach.
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PMID:Interferon-gamma differentially regulates susceptibility of lung cancer cells to telomerase-specific cytotoxic T lymphocytes. 1509 6

Bronchial epithelial cells are often exposed to airborne mutagens that have the potential to induce genetic changes involved in the development of lung cancer. Although lung tumors often display alterations in the expression of oncogenes and/or tumor suppressor genes, the role of specific chemicals and/or metabolites in causing these alterations is not well defined. The polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (B[a]P), a by-product of combustion, is a prevalent airborne environmental mutagen and a constituent of cigarette smoke. The primary objective of this study was to compare the effect of B[a]P and two of its reactive metabolites, benzo[a]pyrene diol epoxide (BPDE or bay region epoxide) and benzo[a]pyrene-4,5-dihydroepoxide (BPE or K-region epoxide), on expression of the proto-oncogene c-myc in normal human bronchial epithelial (NHBE) cells using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method. Changes in c-myc gene expression were compared with DNA adduct formation, growth inhibition, and cell-cycle progression as determined by (32)P-postlabelling, neutral red (NR), and flow cytometric analyses, respectively. None of the three test compounds altered the levels of 18S ribosomal RNA or beta-actin at the concentrations evaluated for c-myc expression, indicating that nonspecific changes in gene expression induced by cytotoxicity, for example, were not present at the concentrations evaluated. Cells exposed to B[a]P exhibited a dose-dependent increase in c-myc expression; conversely, a dose-dependent decrease in c-myc expression was observed following BPDE exposure. A marginal but concentration-dependent increase in c-myc mRNA levels was observed following exposure to the K-region epoxide. Our results demonstrated that, although B[a]P and its metabolites alter c-myc expression, the parent compound and its metabolites produce unequal and contrasting effects on the expression of this gene.
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PMID:Differential c-myc expression profiles in normal human bronchial epithelial cells following treatment with benzo[a]pyrene, benzo[a]pyrene-4,5 epoxide, and benzo[a]pyrene-7,8-9,10 diol epoxide. 1517 Aug 13

Loss of heterozygosity (LOH) studies indicate that genetic alterations of chromosome 9p occur in numerous tumor types, suggesting the presence of tumor suppressor genes (TSGs) on chromosome 9p critical in carcinogenesis. Our previous LOH analyses in primary lung tumors led us to propose that chromosome 9p harbors other TSGs important in lung tumorigenesis. In this study, 30 non-small-cell lung cancer and 12 small-cell lung cancer cell lines were screened with 55 markers to identify new regions of homozygous deletion (HD) on chromosome 9p. Three novel noncontiguous homozygously deleted regions were detected and ranged in size from 840 kb to 7.4 Mb. One gene identified in the deletion at D9S126, TUSC1 (tumor suppressor candidate 1), is an intronless gene. Multiplex polymerase chain reaction and Southern blot confirmed the HD of TUSC1. Northern blot analysis of TUSC1 demonstrated two transcripts of approximately 2 and 1.5 kb that are likely generated by alternative polyadenylation signals. Both transcripts are expressed in several human tissues and share an open-reading frame encoding a peptide of 209 amino acids. Analysing cell line cDNAs by reverse transcriptase (RT)-PCR demonstrated downregulation of TUSC1 in cell lines with or without HDs, suggesting that TUSC1 may play a role in lung tumorigenesis.
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PMID:Identifying novel homozygous deletions by microsatellite analysis and characterization of tumor suppressor candidate 1 gene, TUSC1, on chromosome 9p in human lung cancer. 1520 65

Bronchoscopy is a standard procedure in the workup of patients with suspicious pulmonary lesions. We wondered whether it is possible to isolate malignancy-associated mRNA from cell-free lavage supernatant. Extracellular mRNA from cell-free lavage supernatant of 25 patients with lung cancer (23 with non-small cell lung cancer, 2 with small cell lung cancer) was isolated, reverse-transcribed, and amplified by reverse transcriptase polymerase chain reaction. The quantity and quality of the isolated RNA were checked after cDNA synthesis by amplification with beta-actin-specific primers. Afterwards, a panel of eight genes known to be expressed in lung tumors was used for the detection of tumor-associated mRNA expression in lavage supernatant and serum. mRNA coding for beta-actin could be isolated from lavage supernatant of all 25 patients. In addition, the expression of at least one tumor-associated gene was detectable in all patients. These results show that intact mRNA can be isolated from cell-free lavage supernatant and that its quantity and quality are sufficient for the detection of tumor-associated gene expression alterations. This may open new possibilities for the diagnosis of lung cancer.
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PMID:Detection of tumor-specific mRNA in cell-free bronchial lavage supernatant in patients with lung cancer. 1525 53


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