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

To define the role of cellular oncogenes in human cancers, we studied the prevalence of mutational activation of ras oncogenes in untreated non-small-cell lung cancer. Genomic DNA was extracted from 39 tumor specimens obtained by thoracotomy and was examined for activating point mutations in codons 12, 13, and 61 of the H-ras, K-ras, and N-ras genes. A novel, highly sensitive assay based on oligonucleotide hybridization following an in vitro amplification step was employed. The K-ras gene was found to be activated by point mutations in codon 12 in 5 of 10 adenocarcinomas. Two of these tumors were less than 2 cm in size and had not metastasized. No ras gene mutations were observed in 15 squamous-cell carcinomas, 10 large-cell carcinomas, 1 carcinoid, 2 metastatic adenocarcinomas from primary tumors outside the lung, and 1 small-cell carcinoma. An approximately 20-fold amplification of the unmutated K-ras gene was observed in a tumor that proved to be a solitary lung metastasis of a rectal carcinoma. We conclude that mutational K-ras activation may be an important early event in the pathogenesis of adenocarcinoma of the lung but that amplification of ras genes or mutational activation of H-ras or N-ras does not play a major part in non-small-cell lung cancer.
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PMID:Mutational activation of the K-ras oncogene. A possible pathogenetic factor in adenocarcinoma of the lung. 304 Dec 18

Recent molecular genetic experiments conducted in the USA and The Netherlands have isolated specific mutations in human lung cancer cells. These data implicate the activation of the K-ras oncogene in the pathogenesis of adenocarcinoma of the lungs of heavy smokers and the deletion of DNA from the short arm of chromosome 3 in small-cell and non-small-cell carcinoma of the lung. The implications of these results are discussed and explained in the light of current DNA-manipulative technology which is now available in RSA.
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PMID:Smoking, oncogenes and human lung cancer. A review of recent laboratory evidence linking smoking and lung cancer. 328 28

After looking back upon the progress in both basic and clinical lung cancer researches in the past twenty-some years, what is to come in the future was anticipated. In the diagnostic field, interpretation of chest X-ray films became more accurate, scraping cytology for peripheral carcinoma was developed, and then fiberoptic bronchoscope was devised, all of which contributed to more accurate diagnosis of lung cancer. In lung cancer therapy, extended surgery and bronchoplasty were introduced, resulting in an increase in the 5 year survival rate. Chemotherapy for small cell carcinoma was much improved. Pathologically, adenocarcinoma and squamous cell carcinoma of the peripheral type appear to have increased in incidence. In the field of basic research, both K-ras and myc-oncogenes were found to be amplified in a case of giant cell carcinoma. Several human monoclonal antibodies were produced, each of which has some interesting characteristics. In the future, the results of basic researches will be applied to prevention, diagnosis and therapy, hopefully reducing the morbidity and mortality of lung cancer.
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PMID:[Progress and prospect in basic and clinical lung cancer researches]. 632 98

Beryllium (Be) metal and several of its analogues have been shown to be carcinogenic in rats. In addition, workers employed at Be processing plants have been shown to have a slight excess of lung cancer. In this study, a single inhalation exposure to Be metal produced a 64% incidence of lung tumors in the F344/N rat. The most frequent tumor type observed was adenocarcinoma. These Be metal-induced lung carcinomas were examined for genetic alterations in the K-ras, p53, and c-raf-1 genes. DNA isolated from lung neoplasms was analyzed by PCR amplification and direct DNA sequence analysis, immunohistochemical analysis and Southern blot analysis. No K-ras codon 12, 13 or 61 mutations were detected in 24 lung tumors by direct sequencing. Using a more sensitive K-ras codon 12 mutation selection assay, K-ras codon 12 GGT-GTT transversions were detected in two of 12 adenocarcinomas. These results suggest that activation of the K-ras protooncogene is both a rare and late event, possibly stemming from genomic instability during the progression of some Be-induced rat adenocarcinomas of the lung. No mutant p53 nuclear immunoreactivity was observed in any Be-induced tumor. Because immunohistochemical analysis of the p53 protein only detects missense mutations, exons 5-8 of this gene were also analyzed by direct DNA sequencing. In order to perform the p53 sequence analysis, it was necessary to first characterize and sequence the p53 intron sequences flanking exons 5-8 and their splice sites. Details of this expanded intron DNA sequence information are given here. No mutations were detected within exons 5-8 of the p53 gene. No rearrangement of the c-raf-1 protooncogene was detected by Southern blot analysis. These results indicate that the mechanisms underlying the development of Be-induced lung cancer in rats do not involve gene dysfunctions commonly associated with human non-small-cell lung cancer.
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PMID:Analysis of K-ras, p53 and c-raf-1 mutations in beryllium-induced rat lung tumors. 754 9

In recent years, a group of new prognostic factors have been added to the list of well-known clinical prognostic factors of non-small cell lung cancer. Among these are mutations in the K-ras oncogene, abnormalities in p53, the presence of N-CAM expression as measured by Mab immunostaining and elevated serum levels of NSE. These factors have provided important clinical insights into the biology of lung cancer and prospective studies using these biomarkers are now warranted to provide further important clues about their potential significance in treatment selection of patients.
Lung Cancer 1995 Apr
PMID:Prognostic factors in NSCLC. Recent experiences. 755 31

The observation that the proteins encoded by ras genes play a central role in the signalling pathways used by cells to respond to growth factors and the fact that mutated ras proteins are constantly promoting cell division have led to a PCR-based hunt for additional clinical information. In the present study, K-ras analysis draws the following conclusions: (1) K-ras point mutation frequency was higher in the surgery group (10 of 24 patients) than in the chemotherapy-surgery group (3 of 20 patients). (2) Mutated K-ras was predominantly observed at codon 12 but five mutations appeared at codon 61. (3) Mutations were identified in the squamous cell carcinoma histological NSCLC subtype except in four cases corresponding to adenocarcinoma. (4) A multifarious pattern of substitutions, especially at codon 12, were noted with aspartic K 12 substitutions more prone to develop bone metastases. (5) Although a genotypic K-ras classification of NSCLC may not yet be formulated, our accumulated data (unpublished) suggest a trend toward it. (6) Patients with mutated K-ras tumors in the surgery group had no different survival than those with normal K-ras. However our pooled data as well as other authors' results assert that mutated K-ras constitute an additional prognostic datum that deserves to be included together with TNM classification. In the design of new preoperative (neoadjuvant) chemotherapy trials, stratification of tumors by K-ras status deserves to be further investigated in order to correlate with response, relapse and survival. Mutated K-ras genotype merits further research. Finally, the paradigm of uneven histological distribution and mutated K-ras spectra among researchers should serve as a stimulus to search for further contributions in this field.
Lung Cancer 1995 Apr
PMID:Mutated K-ras gene analysis in a randomized trial of preoperative chemotherapy plus surgery versus surgery in stage IIIA non-small cell lung cancer. 755 35

This paper reviews mutational activation of ras oncogenes and inactivation of the p53 tumor suppressor gene in human lung cancer. We discuss the frequency, type, and location of mutations in these genes in relation to known etiological factors for lung cancer. The most studied examples of these are exposure to tobacco smoke, and to radon and asbestos fibers at work. We summarize data from our laboratory on K-ras and p53 mutations in fresh tissue samples from patients with resected primary lung carcinoma whose smoking and occupational histories were known. Most of the tumors examined were histologically non-small cell carcinoma (NSCLC), mainly of the squamous cell carcinoma and adenocarcinoma types. We compare the prevalence and nature of mutations in the two histological types of NSCLC.
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PMID:p53 and ras gene mutations in lung cancer: implications for smoking and occupational exposures. 762 Sep 45

Sputum cells from 44 lung cancer patients (22 adenocarcinoma, 19 squamous cell carcinoma and 3 small cell carcinoma cases) were examined to contain mutant K-ras genes. The mutant-allele-specific amplification (MASA) method was used for detection of K-ras point mutations. The reaction was designed to amplify only mutant codons with polymerase chain reaction (PCR). Codons 12, 13 and 61 were studied with synthesized primers. Two cases (primary adenocarcinoma of the lung and pancreas adenocarcinoma with lung metastasis) were positive for point mutations at codon 12. The mutation of GGT to GTT was found in the first case and to GAT in the second one. Further experiments with colony hybridization revealed the mutations were found in 1% of alleles in both cases. There were no point mutations found at codon 13 nor 61. Our experiments showed it is possible to detect K-ras mutation in sputum cells from lung cancer patients, with MASA method.
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PMID:[Detection of K-ras mutation from malignant cells in sputum with mutant-allele specific amplification (MASA) method]. 767 46

Polymerase chain reaction amplification and BstNI endonuclease digestion were performed on DNA isolated from cell lines that were either homozygous (SW480, A549) or heterozygous (Calu 1, SK-LU-1, A427) for K-ras codon 12 mutations. Polyacrylamide gel electrophoresis showed that both mutant and wildtype (WT) bands were present in Calu-1, SK-LU-1, and A427 cell DNA; only the mutant bands were observed with SW480 and A549 DNA. The percentages of mutant and WT fragments were measured using capillary electrophoresis (CE). Integration of mutant and WT peaks showed that the percentages of mutant alleles in Calu-1, SK-LU-1, and A427 cell lines were 73, 84, and 72, respectively. The sensitivity of the original BstNI assay for K-ras codon 12 in conjunction with analysis by CE was also tested by a series of titration experiments using one- and two-stage amplification-BstNI digestion protocols. CE was used to generate a calibration curve. The mutant allele was detected and the quantity was measured in the 1:100 and 1:10,000 dilutions in the one- and two-stage analysis, respectively. Four human lung adenocarcinomas were also analyzed. Two of these were homozygous normal, whereas the other two contained 63 and 32% codon 12 mutant alleles. These results showed that CE can separate and quantitate BstNI fragments containing K-ras codon 12 mutations. The high sensitivity and quantitative features of CE should enable detection and quantitation of mutant K-ras alleles in premalignant lung lesions, as well as exfoliated cells collected by cytology from persons at risk for lung cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection and quantitation of mutant K-ras codon 12 restriction fragments by capillary electrophoresis. 771 62

In order to define the roles of the K-ras and p53 genes in the development of lung cancer, especially in young adults, we compared the clinicopathological features of the patients between younger (< or = 45 years, n = 47) and older (< 55 years, n = 50) groups. The gene alterations were examined by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method. The K-ras gene alterations were detected only in adenocarcinomas, and the p53 gene alterations in all histologic types of lung cancer. There were no significant differences in the frequency of both K-ras and p53 gene alterations between the younger and older groups (9 vs. 11%, 36 vs. 32%). In the younger group, but not in the older one, the percentage for smokers was significantly higher in the p53 gene alteration-positive group than for the negative group (65 vs. 30%). As to the prognosis, there were no significant differences between the p53 gene alteration-positive and -negative cases in both the younger and older groups as well as in all subjects, while a tendency of poorer prognosis was observed in K-ras gene alteration-positive cases than for the -negative ones with adenocarcinomas. These results suggest that (1) the K-ras and p53 gene alterations would have no special roles in terms of the lung carcinogenesis in young adults; (2) a positive relationship between smoking and p53 gene alteration would exist in young adults with lung cancer, and (3) K-ras gene alteration would become a prognostic factor in lung cancer.
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PMID:Studies on clinicopathological features of lung cancer patients with K-ras/p53 gene alterations: comparison between younger and older groups. 771 5


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