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

The pathogenesis of mesenchymal and epithelial lung reactions was studied after a single intratracheal instillation of quartz into rats. Relationships between transforming growth factor beta1 (TGF-beta1) and the ras and p53 genes were investigated in silicosis and associated lung cancer. Immunohistochemical reactivity to mature TGF-beta1 was localized intracellularly in fibroblasts and macrophages at the periphery of silicotic granulomas and in stroma adjacent to hyperplastic alveolar type II cells and extracellularly in connective tissue matrix adjacent to hyperplastic alveolar type II cells. TGF-beta1 precursor was localized intracellularly in hyperplastic alveolar type II cells adjacent to granulomas and in the cells of adenomas, but not in carcinomas. Hematite-treated controls showed no reactivity to TGF-beta1. Immunohistochemical localization of pan-reactive p21 ras protein in quartz-treated rat lungs was increased in hyperplastic alveolar type II cells adjacent to granulomas, but not in adenomas and carcinomas. Foci of nuclear immunoreactivity to p53 protein were observed in 25% of the carcinomas.
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PMID:Transforming growth factor beta1, ras and p53 in silica-induced fibrogenesis and carcinogenesis. 892 85

Grb2 is an SH2/SH3 domain-containing adaptor protein that links receptor tyrosine kinases to the ras signaling pathway. The Grb2-SH2 domain binds phosphotyrosine sequences on activated tyrosine kinases, and one target of the SH3 domains is the ras-nucleotide-exchange factor Sos1. We have examined Grb2-protein interactions in human cancer cells that over-express the receptor tyrosine kinase erbB2. Our results show that the 2 Grb2-SH3 domains complex with Sos1, dynamin and at least 4 other proteins (p228, p140, p55, p28) in these cells. The 2 Grb2-SH3 domains bind these proteins differently, with the N-terminal SH3 domain interacting preferentially with p228, Sos1, p140 and dynamin. The C-terminal SH3 domain has higher affinity toward p28. The Grb2-SH3 domain interactions appear to be similar in erbB2 over-expressing breast, ovarian and lung cancer cells. Also, the major tyrosine-phosphorylated proteins that associate with Grb2 in erbB2 over-expressing cancer cells appear to be erbB2 and Shc. The multiple Grb2-SH3 domain interactions in these cells may mediate novel cellular functions.
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PMID:Multiple Grb2-protein complexes in human cancer cells. 900 62

Adducts, formed by carcinogens of tobacco smoke with DNA, can be detected by means of molecular techniques and are used as marker of internal exposure. Carcinogen-DNA adducts produce specific mutations in tumor-suppressor genes (e.g. p53) and oncogenes (e.g. ras), which can be involved in tumor initiation or in later stages of tumor progression (e.g. evolution of an invasive phenotype). Benzo(a)-pyrene, an important carcinogen of tobacco smoke, induces GT transversions, as demonstrated in in vitro systems and animal models. Mutations in the p53- or ras-gene are more common in human tumors of the lung, head and neck, bladder and pancreas in smokers than in non-smokers. Molecular biology of cancer gains increasing significance in clinical practice since 1.) the presence of certain mutations confers an unfavorable prognosis to malignant disease (e.g. ras mutations in lung cancer), 2.) ras and p53 mutations often occur early during tumor development and can thus facilitate diagnosis of malignant disease, and 3.) minimal residual disease can be detected using molecular techniques. After resection of cancer of the head and neck, tumor recurred more frequently in patients with no evidence of residual disease as assessed by pathohistologic criteria than in patients with no evidence of residual disease as evaluated by p53 immunostaining.
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PMID:[Molecular biology of tobacco smoke associated neoplasia]. 901 41

K-ras mutation appears in about 60% of patients with non-small-cell lung cancer (NSCLC). This frequency and its presence in normal appearing tissues point to the potential of ras oncogene mutation to serve as a good biomarker. Using enriched PCR (EPCR), which enables the detection of one mutant allele in the presence of 10,000 normal alleles, we have determined the frequency of mutant ras alleles in the sputum samples of patients with or without lung cancer. Samples were collected from 17 patients with NSCLC and from 40 controls who suffered from non-oncological lung diseases, including bronchitis, asthma, and pneumonia. Of the 37 samples obtained from patients with lung cancer, 18 were found to harbor ras oncogene mutations (48%). Of the 40 cases that were free of lung cancer, five were found to harbor this mutation (12.5%). The difference between the two frequencies was found to be significant (P < 0.01). These findings indicate that (a) K-ras oncogene mutation can be identified in routinely obtained sputum samples of patients who may be at risk of developing lung cancer and (b) the higher frequency of these mutations in samples of patients with lung cancer points to the potential use of the ras mutation as a biomarker for either exogenous or endogenous exposure to carcinogens. Thus, the ability to examine sputum provides a powerful and convenient source of sampling and may be adapted for future large-scale screening.
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PMID:K-ras mutation in sputum of patients with or without lung cancer. 902 15

Lung cancer is the leading cause of cancer-related deaths in western countries. The prognosis for patients with lung cancer depends primarily on the stage of the tumor at the time of clinical diagnosis. New understanding of tumor biology has turned attention away from detection of clinical lung cancer, usually metastatic at presentation, toward recognition of genetic and protein markers which precede malignancy. Mutations of four types of genes contribute to the process of epithelial carcinogenesis by modifying control of cell growth. Examples of three of these changes have been detected in pre-malignant sputum, and validated in subsequent tumor. We have identified gene products (tumor associated and differentiation protein antigens), mutations of k-ras and p53, and microsatellite alterations as potential markers of subsequent malignancy. We consider the morphologic progression seen in archived sputum cells as the paradigm of neoplastic development in the lung. Although the NCl collaborative trials had shown that this progression is not recognized sufficiently often (sensitive) to be useful for lung cancer screening, this progression may be used to assess the timing of gene and peptide markers of carcinogenesis. Previous work has shown that at the time Johns Hopkins Lung Project sputum cells express moderately atypical metaplasia, 53% (8/15) of sputum specimens expressed common (codon 12) k-ras or (codons 273 or 281) p53 mutations. Other investigators have reported that earlier morphologic changes (metaplasia) accompany 3p and 9p losses of heterozygosity. These observations suggest that 3p and 9p loss likely precede k-ras or p53 mutations. Our preliminary data demonstrate that over-expression of a 31 kD tumor associated antigen recently purified, sequenced, and identified as heterogeneous nuclear ribonucleoprotein (hnRNP) A2 (with cross reactivity to splice variant B1), is expressed in most lung cancer cases before any morphologic abnormality. Comparison of the accuracy of this marker with sputum cytology will determine its value for early lung cancer detection. Preliminary evidence confirms this marker greatly improves the accuracy of standard sputum cytology for detection of lung carcinogenesis. Clinical intervention trials must be undertaken to determine whether modulation of hnRNP overexpression is useful as an intermediate endpoint for chemoprevention.
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PMID:Clinical detection of lung cancer progression markers. 902 16

Mining and mineral processing are important industries in the United States. A large number of workers are potentially exposed to silica during mining and to glass fibers during manufacturing. There is a concern regarding lung cancer risk among workers exposed to silica and glass fibers. Our previous studies showed that both glass fibers and silica induced transformation of BALB/c-3T3 cells. In order to explore the relationship between silica and glass fiber-induced cell transformation and oncoprotein expression, the protein products of seven proto-oncogenes (c-K-ras, c-H-ras, c-sis, c-myc, c-myb, c-erb B1 and c-jun) and one tumor suppressor gene (p53) were examined in BALB/c-3T3 cells transformed by glass fibers or silica using immunoblotting with specific monoclonal or polyclonal antibodies. The results showed that all transformants, including eight induced by glass fibers and eight by silica (Min-U-Sil 5), were positive for c-jun protein expression; the level of c-jun protein was elevated 8-21-fold in these transformants. Other protooncogene proteins in transformed cells were either not detectable or not different from non-transformed cells. These results suggest that the overexpression of c-jun is common in BALB/c-3T3 transformed cells induced by glass fibers or silica. It seems, therefore, that the expression of c-jun may play an important role in the transformation process.
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PMID:Selective hyperexpression of c-jun oncoprotein by glass fiber- and silica-transformed BALB/c-3T3 cells. 902 70

Recent advance in cell-molecular biological studies have revealed various prognostic factors in lung cancer. The aim of this paper is to critically review the current status of molecular biological prognostic markers in non-small cell lung cancer. DNA ploidy, AgNORs and PCNA as marker of tumor cellular proliferative activity are reported to be a prognostic marker but still remain controversial. The proteases such as uPA, MMPs and CB catalyze degradation of the extracellular matrix and basement membranes. Although the prognostic implications of the uPA and MMPs still remain unclear, cathepsin B appears to be one of the most useful prognostic markers so far reported for non-small cell lung cancer. In a number of studies, genetic abnormalitis has been reported to be a prognostic marker in cancer patients. In non-small cell lung cancer, the prognostic implication of the altered p53 expression or ras p21 expression still remain unclear, especially p53 is conflicting. The most useful clinical prognostic marker may be obtained by the combined analysis of some prognostic information.
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PMID:[Molecular biological prognostic markers in lung cancer]. 904 11

We examined 159 consecutive cases of non-small-cell lung cancer (NSCLC) for a mutation at codon 12 of the K-ras gene and for a mutation of the p53 gene occurring in exons 5-8. Eleven (6.9%) had mutations of the K-ras (ras+) and 57 (35.8%) had mutations of the p53 (p53+). There were 95 cases (59.7%) with ras- p53-, seven cases (4.4%) with ras+/p53-, 53 cases (33.3%) with ras-/p53+ and four cases (2.5%) with ras+/p53+. The ras+ group had a worse prognosis than the ras group in all cases and in 107 early-stage cases (stage I-II, P<0.05). The p53+ group had a worse prognosis in 107 early-stage cases (P<0.01), but there was no statistically significant difference when 52 advanced-stage cases (stage III-IV) or all patients were considered. Both ras and p53 mutations were unfavourable prognostic factors in 94 cases with adenocarcinoma, but there was no statistical significance in 57 cases with squamous cell carcinoma. According to Cox's model, the pathological stage, ras mutation and p53 mutation were found to be independent prognostic factors. Our results suggest that ras and p53 mutations were independent unfavourable prognostic markers especially in the early stage of NSCLC or in adenocarcinoma.
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PMID:K-ras and p53 mutations are an independent unfavourable prognostic indicator in patients with non-small-cell lung cancer. 909 59

Recently, constitutively active mutants of MEK (MAP/ERK kinase) were shown to be capable of transforming cells to tumorigenicity suggesting that MEK can function as a dominant oncogene and potentially play a role in human carcinogenesis. Human lung cancer cells exhibit mutations in other components of the MAP kinase signaling pathway such as the Her-2/neu and ras oncogenes. Thus, the coding sequences of both MEK-1 and MEK-2 cDNAs from human lung cancer cell lines were screened by single strand conformation polymorphism analysis and DNA sequencing for alterations in these two genes. In 37 lung cancer cell lines we found: an allelic variant in MEK-1 cDNA, nt 783 G-->A, (no amino acid change); a MEK-2 cDNA change (nt 977 C-->T mutation leading to 298 Pro-->Leu change); a MEK-2 cDNA change nt 537 C-->T (no amino acid change); and a frequent MEK-2 cDNA germline polymorphism nt 744, A-->C (no amino acid change) with an allele frequency of 0.5 for each form. These results suggest that mutations in the MEK-1 and MEK-2 gene occur at a very low frequency in human lung cancer.
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PMID:Mutation analysis of the coding sequences of MEK-1 and MEK-2 genes in human lung cancer cell lines. 912 73

To better understand whether replication-error-type instability (RER+) is a frequent genetic alteration event in surgical-pathologic stage-I non-small-cell lung cancer (NSCLC) and identify whether it constitutes an independent prognostic parameter, we examined 35 surgical-pathologic stage-I-NSCLC patients with complete follow-up in all cases for at least 49 months. The tumor samples and the paired histopathologically normal lung samples for each patient were analyzed for 8 microsatellite markers located at chromosomes 3p and 2p to investigate microsatellite alterations such as RER+ and loss of heterozygosity (LOH). Single-strand-conformation-polymorphism analysis for detection of p53 and k-ras gene mutations was also carried out. Genetic data were correlated with clinical outcome and histopathologically established prognostic factors. RER+ at one or both chromosomes was identified in 24 of the 35 patients; 9 patients showed LOH. A statistically significant correlation was found between RER+ and poor prognosis (p = 0.001). Furthermore, RER+ proved to be an independent factor that predicted decreased survival, ranking first, followed by visceral pleural invasion. A trend towards worse survival was strongest in the group of patients with tumor size greater than 3 cm (T2). Patients with other genetic abnormalities, such as K-ras mutations, p53 mutations or LOH, had prognoses similar to those of patients without such aberrations. The data suggest that RER+ is common in NSCLC, that it may provide important prognostic information in stage-I NSCLC and serve as a useful marker for relapse-risk assessment in operable NSCLC patients.
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PMID:Reduced survival in patients with stage-I non-small-cell lung cancer associated with DNA-replication errors. 922 14


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