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

Research on dominant oncogenes and tumor suppressor genes has characterized differences in genetic lesions between small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) and identified associations with clinical parameters. More than one half of all lung cancers contain a mutation of the p53 tumor suppressor gene. There does not appear to be an association between the presence of this mutation and survival. A ras family oncogene was found to be mutated in approximately 20 percent of tumors and tumor cell lines from patients with NSCLC in contrast to none of 45 tumors and tumor cell lines from patients with SCLC. The presence of a K-ras mutation was determined to be an adverse prognostic factor for survival in retrospective studies of patients with NSCLC. Mutations of K-ras are more common in tumors from smokers than nonsmokers and have not been detected in lung cancers resulting from occupational exposure to radon. Mutations in both the p53 gene and K-ras oncogene are most commonly G to T transversions in lung cancer vs G to A transitions in other cancers. Prospective studies of these mutations in resected tumor specimens taken from patients with accurate follow-up may continue to provide important clues about their potential clinical and biologic significance.
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PMID:Overview of genetic and molecular events in the pathogenesis of lung cancer. 838 Jan 30

We investigated point mutational activation of the ras genes (K-ras codons 12, 13 and 61; N-ras codons 12, 13 and 61; H-ras codons 12 and 61) in primary, resected lung cancer by dot blotting and oligonucleotide hybridization. K-ras mutations were found in 14 (29%) of the 48 lung tumour specimens examined, but no N-ras or H-ras mutations were found. The highest frequency of K-ras mutation was observed in adenocarcinoma: 12 of the 21 samples studied (57%) had a mutation, which is one of the highest frequencies reported for lung adenocarcinoma. The commonest type of mutation in these lung tumour samples consisted of transversions: we observed 11, of which 8 (57% of all mutations) were G to T transversions. Most of the 48 patients studied had a history of heavy smoking, either with or without evidence of occupational exposure to asbestos. Statistical analysis revealed--in addition to the highly significant association between the adenocarcinoma type of lung cancer and K-ras mutation--a clear association of K-ras mutations with heavy life-time smoking (> or = 50 pack-years of cigarette smoking; odds ratio (OR) 4.9, 90% CI 1.2-19.5, multivariate analysis). In addition, occupational asbestos exposure showed an elevated, but non-significant, OR of 2.2 (90% CI 0.6-8.7) with the presence of K-ras mutation. We conclude that the occurrence of K-ras mutations in adenocarcinoma of the lung is frequent, and that such mutations are associated with heavy life-time exposure to tobacco smoke, possibly in combination with occupational exposure to asbestos fibres.
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PMID:K-ras mutations in human adenocarcinoma of the lung: association with smoking and occupational exposure to asbestos. 842 62

We are only beginning to understand the importance of lung cancer tumor biology in relation to prognosis and response to therapy. Many of the biologic and genetic changes we have described are preliminary observations and require further confirmation before clinical use. However, information concerning three oncogenes may soon prove to be helpful in the clinical arena: the myc genes in SCLC, and the ras genes and c-erbB-2 in NSCLC. In general their presence identifies poor patient response to therapy and poor survival. These markers are currently being used in a clinical setting at some research centers, but are not recommended for general diagnostic or prognostic use without further confirmation of their utility. Incorporation of this information with that learned by standard staging procedures may result in improved understanding of patient prognosis and challenge current concepts of lung cancer treatment. For example, surgically resected stage I NSCLC patients may benefit from adjuvant therapy if found to have these adverse biologic factors, and require more stringent follow-up after therapy. Finally the understanding of the pathogenesis of lung cancer may enable the development of novel therapy directed against these growth pathways. Our ultimate goal is to derive a therapeutic and prognostic paradigm involving both molecular-genetic and clinical factors to arrive at an optimal staging model and treatment plan.
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PMID:Oncogenes and growth factors in human lung cancer. 846 46

In order to explore the significance of ras oncoproteins in plasma in the carcinogenic process, we have examined samples from 40 Polish human lung cancer patients prior to treatment. They were compared with 35 healthy donors and have been screened using a direct analysis of the plasma. Proteins were separated by gel electrophoresis, transferred to a nitrocellulose membrane by Western blotting and detected by chemiluminescence, using monoclonal ras antibody as the primary antibody. Elevated increases in ras oncoproteins were determined where an increase was considered to be greater than 2 standard deviations above the mean negative control values. The results showed that in 45% of cancer patients ras oncoprotein levels were statistically significantly increased (P < 0.001, pooled two-sample t-test untransformed, and non-parametric Mann-Whitney test) in the plasma by comparison with 6% in the controls. This would suggest that an increase in ras oncoproteins in plasma could be a possible prognostic marker or biomarker for lung cancer.
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PMID:ras oncoproteins in human plasma from lung cancer patients and healthy controls. 856 84

A ras oncogene-amplified recombinant BHK-21 cell line (ras-rBHK-IgG) has been established, and was shown to hyperproduce the recombinant IgG chimeric human monoclonal antibody (hMAb) AE6F4, which recognizes lung cancer cells. We found that the ras-rBHK-IgG cell could be easily cultured in a protein-free ERDF medium supplemented with iron(III) nitrate, hydroxyethyliminodiacetic acid, and non-protein synthetic attachment factor as well as in a serum-free ERDF medium supplemented with insulin, transferrin, ethanolamine, and sodium selenite. The productivity of recombinant hMAb from the cells cultured in dishes at high cell densities was higher in protein-free medium than in serum-containing medium. True high density culture of the ras-rBHK-IgG cells was done in protein-free medium using the Tecnomouse, which is a novel hollow fiber bioreactor system. After culture for 30 days in protein-free culture, a total amount of about 14 mg of the recombinant hMAb AE6F4 was obtained, and was shown to be reactive against lung cancer cells in tissues.
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PMID:Production of recombinant human monoclonal antibody using ras-amplified BHK-21 cells in a protein-free medium. 870 11

To evaluate the possible use of mutant ras as a biomarker for lung cancer, we have analyzed "normal appearing" lung tissue, lung tumor, lung metastases and sputum samples from patients with non-small cell lung cancer (NSCLC). As a control, we used lung tissue and sputum samples from patients without oncological diseases or lung disorders. Our analyses were performed with the aid of enriched PCR (EPCR), a method which enables detection of ras mutation even if present at low incidence. EPCR identified K-ras codon 12 mutations in 10% of lung tissues obtained from patients with no lung diseases, whereas the same mutation was detected in 60% of samples of normal appearing lung tissues obtained from patients with NSCLC, 62% of NSCLC tumors and 80% of metastases. Analysis of sputum samples of patients with NSCLC identified 47% to harbor mutant ras allele, whereas 12.5% of controls diagnosed with non-oncological lung diseases carried this mutation. Most of these mutations were detected with the aid of EPCR only, indicating that a minority of cells in a given sample harbor this mutation. The ability to detect K-ras codon 12 mutation in 60% of lung tissue samples and in 47% of sputum samples taken from patients with lung cancer (as compared with 10% and 12.5% of respective controls) points to the potential use of ras mutation as a biomarker for exposure and possible identification of patients who may be at higher risk of developing lung cancer.
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PMID:High frequency of K-ras mutations in normal appearing lung tissues and sputum of patients with lung cancer. 884 39

Proto-oncogenes are genes coding for factors involved in cellular growth, reproduction, and differentiation. Cancer results through mutations of proto-oncogenes or through other mechanisms involving the products of proto-oncogenes. This study asks whether serum proteins immunologically related to the products of proto-oncogenes distinguish older men and women who manifest a new cancer during a 2-year follow-up. The authors conducted a nested case-control study that involved 248 men and women selected from a larger group of older (age > or = 65 years) healthy volunteers in a randomized clinical trial of preventive clinical services. Study subjects included 37 with a fatal cancer, 59 non-fatal breast, prostate, colon, or lung cancer, 58 hospitalized with at least one discharge diagnosis that coded to benign neoplasia (International Classification of Diseases, 9th Revision codes 210-239), and 94 randomly selected controls. Using seven monoclonal antibodies prepared against ras, erb-B, FES, myb, and SIS polypeptide sequences, immunoblots detected 17 proteins in serum collected from subjects before the clinical recognition of cancer. Five oncogene-related serum proteins appeared to distinguish older persons who manifested fatal (but not non-fatal) cancer over a brief (2-year) follow-up. Older persons hospitalized with benign neoplasia also had higher levels of these serum proteins. Relative to the 94 control subjects, a 52,000 dalton SIS-related protein (odd ratio (OR) = 5.9, 95% confidence interval (CI) 1.4-24.9) and a 35,000 dalton k-ras-related protein (OR = 11.3, 95% CI 1.2-104) were particularly common in serum from the 37 subjects who manifested a fatal cancer.
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PMID:Oncogene-related serum proteins and cancer risk: a nested case-control study. 885 20

We examined 60 non-small-cell lung cancer (NSCLC) patients for evidence of genetic alterations on chromosome 11 with nine polymorphic markers by Southern blot and microsatellite marker analysis. These analyses detected genetic alterations at both the 11p and 11q arms. At the 11p15 Ha-ras locus, the loss of heterozygosity (LOH) occurred in three out of 11 (27.3%) of the informative cases; at the 11p11-q12 D11S149 locus, the LOH occurred in two out of nine (22.2%) of the informative cases; and at the 11q13 INT-2 locus, the LOH occurred in four out of 18 (22.2%) of the informative cases. Microsatellite markers in the 11q12-q13 region revealed genetic alterations for PYGM in eight out of 54 (14.8%) of the specimens studied and 10 out of 55 (18.2%) of the specimens for the INT-2 marker. The data suggest genetic alterations occur in some of the lung cancer patients in both the 11p and 11q regions.
Lung Cancer 1996 Aug
PMID:Chromosomal 11 alterations in non-small-cell lung carcinomas in Hong Kong. 886 23

Mice of the A/J strain are useful models of lung cancer because they develop tumors spontaneously or after treatment with ethyl carbamate. These tumors are thought to arise from either Clara cells (papillary tumors) or alveolar type 2 cells (alveolar tumors); like many human lung adenocarcinomas, the mouse tumors involve Kiras activation. Transformation with Ki-ras can be reversed by coexpression of the Krev-1 gene in tissue culture. To test the tumor suppressor activity of Krev-1 in vivo, we produced transgenic A/J mice expressing Krev-1 under the control of the rabbit uteroglobin promoter, which directs expression of heterologous genes to the lung Clara cells. Krev-1 was expressed specifically in the lungs of transgenic mice. Sixty-six mice (35 transgenic and 31 nontransgenic) from three lines were given ethyl carbamate, and the numbers of resulting lung tumors were compared between transgenic and nontransgenic animals. The mean number (+/-standard deviation) of ethyl carbamate-induced lung tumors was 21.7 +/- 1.3 in transgenic mice and 26.9 +/- 1.3 in their nontransgenic littermates (P < 0.01). Sequencing of polymerase chain reaction-amplified ras DNA from 15 transgenic mouse tumors and 16 nontransgenic mouse tumors (controls) detected mutations in codon 61 in 13 tumors from the transgenic group and 11 tumors in the control group, whereas mutations in codon 12 were detected in only one tumor in the transgenic group and in four tumors in the controls. Together, these data demonstrate for the first time the tumor suppressor activity of Krev-1 in vivo and suggest that Krev-1 tumor suppressor activity may be specific for cells harboring mutations in codon 12 of ras.
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PMID:Expression of human Krev-1 gene in lungs of transgenic mice and subsequent reduction in multiplicity of ethyl carbamate-induced lung adenomas. 889 Sep 57

An adenoviral vector carrying a 2-Kb fragment of the K-ras proto-oncogene inserted in antisense orientation with respect to the cytomegalovirus promoter was constructed and used to infect H460a lung cancer cells (codon 61 K-ras mutation). The gene was efficiently transferred, and a high level of expression of antisense K-ras was achieved. At a multiplicity of infection to achieve 65% transduction of cells, the expression of K-ras protein was reduced by 70% in the lung cancer cell line H460a as compared with cells infected with control vectors or noninfected cells. This reduction produced a 47% inhibition of monolayer growth and a 90% inhibition of colony formation. At a similar level of transduction in the cell line H358 (codon 12 K-ras mutation), a 59% inhibition of monolayer growth compared with control vectors occurred; however the inhibition of H322 cells (wild-type k-ras) growth was no different than control vector infected cells. These data suggest that the adenoviral K-ras H322a antisense vector may have therapeutic potential in tumors in which K-ras is mutated.
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PMID:Growth inhibitory effect of anti-K-ras adenovirus on lung cancer cells. 889 48


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