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

Expression of myc, fos, src, ras and sis oncoproteins was studied in biopsy material of tumors, metastases and "normal" surrounding tissues from patients with different histological types of stomach and lung cancer, melanoma and other malignancy using immunoblotting. Besides, the immunohistochemical distribution of these oncoproteins under lung cancer and precancer conditions was analysed. The oncoproteins expression was significantly higher in cancer as compared with precancer and "normal' surrounding tissues. C-myc and c-fos gene products were detected in all the malignant tissues irrespectively to histogenesis of tumors, while the level of c-myc expression was rather high. The high level of c-fos expression was observed in stomach carcinomas and at early stages of lung tumor progression. C-src and c-sis genes expression varied in tumors of different histogenesis. C-src proteins were found in 60% of lung cancer but it was practically absent in stomach carcinomas and in melanomas. C-sis gene product was observed in some melanomas and lung carcinomas. Ras gene can be activated at early stages of tumor progression of stomach carcinomas and lung adenocarcinomas and at later stages of tumor progression in melanomas and small-cell lung carcinomas. Thus, there are some correlations between oncoprotein expression and tumor tissue histogenesis and progression.
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PMID:[Synthesis and distribution of oncoproteins in tumor tissue]. 183 74

Six families of activated protooncogenes, ras, raf, fur, neu, jun and myc have so far been associated with human lung cancer. Human bronchial epithelial cells in vitro are being used to investigate the functional role of these specific oncogenes and growth regulatory genes in carcinogenesis and tumour progression. When transferred into normal human bronchial epithelial cells by the highly efficient protoplast fusion method, the v-Ha-ras oncogene initiates a cascade of events leading to decreased responsiveness of these cells to inducers of squamous differentiation, aneuploidy and, less frequently, 'immortality' and tumorigenicity with metastasis in athymic nude mice. Transfection of the SV40 T antigen gene results in nontumorigenic cell lines that have a nearly normal pathway of terminal squamous differentiation and can be transformed into malignant cells by transfected Ha-ras, N-ras or Ki-ras. The combination of transfected c-myc and c-raf-1 also transforms human bronchial epithelial cells into neoplastic cells that exhibit some phenotypic traits found in small-cell carcinomas. These and other results indicate that proto-oncogenes dysregulate the pathways of growth and differentiation of human bronchial epithelial cells and play an important role in human carcinogenesis. Analyses of allelic deletion and somatic cell hybrids are being used to identify the chromosomal localization of tumour suppressor genes. We have examined 54 non-small-cell bronchogenic carcinomas with 13 polymorphic markers. Loss of heterozygosity was more frequent than among 23 squamous-cell carcinomas than among 23 adenocarcinomas or eight large-cell carcinomas. Loss of heterozygosity for chromosome 17p was found in 89% of cases of squamous-cell carcinoma and 18% of adenocarcinomas. Analysis of chromosome 11 for allelic deletions revealed two commonly deleted regions (11p13 and 11p15.5). Somatic cell hybrids between normal human bronchial epithelial cells and Hut292DM, a lung carcinoma cell line, had a finite lifespan in vitro and were nontumorigenic in athymic nude mice. Tumour suppressive effects of individual or combinations of specific human chromosomes on Hut292DM are being examined by formation of microcell-cell hybrids. Chromosome 11 has tumour suppressor activity in these hybrids. Both of these studies suggest that tumour suppressor genes play a dominant role in lung carcinogenesis and provide in-vitro model systems for isolating these genes by subtraction library and insertional mutagenesis techniques.
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PMID:Role of oncogenes and tumour suppressor genes in human lung carcinogenesis. 185 68

An understanding of the molecular pathogenesis of lung cancer has evolved from classic cytogenetic studies and the use of restriction fragment length polymorphisms to encompass the definition of specific genetic abnormalities associated with this disease. Activation of the dominant class of oncogenes is frequent, with involvement of the ras and myc families of genes being the best defined. Several examples of inactivation at specific loci exist and have been related to the presence of tumor suppressor genes, most notably the retinoblastoma gene, p53, and a putative gene located on the short arm of chromosome 3. As our understanding of the nature and interactions between these numerous genetic events evolves, new opportunities for early diagnosis, prevention, and treatment will arise.
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PMID:Dominant oncogenes and tumor suppressor genes in the pathogenesis of lung cancer. 196 50

We have examined DNA restriction fragment length polymorphisms (RFLP) of the Ha-ras-1 gene in DNA from 118 lung cancer patients and 123 unaffected controls. When DNA samples were digested with MspI/HpaII restriction endonucleases. Southern blot analysis demonstrated 4 common, 4 intermediate and 7 different rare alleles in the combined population after hybridization to the pGDa1 probe. Six of the rare alleles were unique for the lung cancer group and 1 rare allele for the control group. The frequency of rare alleles in lung cancer patients (10/236) was significantly different (P less than 0.01) from the control group (1/246). The lung cancer group also had a significantly lower frequency of the common 2.57 kb fragment than the controls (P less than 0.02). The results thus indicate that Ha-ras genotyping may be of value in lung cancer risk assessment.
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PMID:Ha-ras-1 alleles in Norwegian lung cancer patients. 197 5

A human lung cancer cell line (H460a) with a homozygous spontaneous K-ras mutation was transfected with a recombinant plasmid that synthesizes a 2-kilobase genomic segment of the K-ras protooncogene in antisense orientation. Translation of the mutated K-ras mRNA in H460a cells was specifically inhibited, whereas expression of H-ras and N-ras was unchanged. A 3-fold growth inhibition occurred in H460a cells when expression of the mutated ras p21 protein was down-regulated by antisense RNA. However, cells remained viable despite the absence of K-ras expression. The growth of H460a tumors in nu/nu mice was substantially reduced by expressed K-ras antisense RNA.
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PMID:Specific inhibition of K-ras expression and tumorigenicity of lung cancer cells by antisense RNA. 199 65

In this report, point mutations of the K-ras gene at codon 146 were analyzed in 25 cases of colon cancer, 4 cases of lung cancer, and 41 cases of lymphoid malignancy. A codon 146 mutation substituting threonine (ACA) for alanine (GCA) was detected in the tumor tissue of a patient with colon cancer and was not detected in the normal tissue of the same patient. Any additional mutations of the ras gene family were not detected in this patient. These results suggest that the codon 146 mutation of the K-ras gene could be involved in the development of naturally occurring human malignancies.
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PMID:A novel point mutation at codon 146 of the K-ras gene in a human colorectal cancer identified by the polymerase chain reaction. 201 78

We have examined the distribution of ras p21 oncoprotein expression in cytologic specimens from 73 primary bronchial carcinomas using an immunocytochemical analysis. The cytologic preparations studied represent the two major groups of histological types of lung cancer: Small Cell Lung Carcinoma (SCLC) and Non-Small Cell Lung Carcinoma (NSCLC) (squamous cell carcinoma and adenocarcinoma). The differential expression of ras p21 oncoprotein correlated with histological classification and was found in 30% of 23 small cell lesions, 61% of 28 squamous cell lung carcinomas and 32% of 22 adenocarcinomas. The ras p21 oncoprotein was commonly expressed in NSCLC cases (48%) as compared to SCLC cases (30%).
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PMID:Immunocytochemical study of RAS oncoprotein in cytologic specimens of primary lung tumours. 216 47

DNA from tumor samples of 54 patients with operable non-small cell lung cancer (NSCLC) was analyzed to determine whether proto-oncogene alterations could be correlated with the clinical behavior of lung cancer. Among seven proto-oncogenes tested, changes in the copy number of Ha-ras, c-myc and c-raf-1 were found in only seven tumors. Most of them were epidermoid carcinomas without lymph node involvement (N0). In spite of a localized disease with complete surgical resection, six of these patients relapsed within a mean disease-free interval (DFI) of only 6.5 months. There is a significant correlation between DNA alterations at proto-oncogene loci and clinical relapse within 12 months of surgical resection (P less than 0.025).
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PMID:DNA alterations at proto-oncogene loci and their clinical significance in operable non-small cell lung cancer. 216 42

The development of human lung cancer may require multiple genetic deletions affecting a number of chromosomes, e.g., 1, 3, 11, 13, and 17. These genetic aberrations may induce the activation of proto-oncogenes (c-jun, ras, c-raf1) and the loss of tumor suppressor genes (p53). Some of the activated proto-oncogenes and tumor suppressor genes are more selectively expressed or absent in small-cell lung cancer (L-myc, c-myb, c-scr, Rb gene) or non-small-cell lung cancer (c-erbB-2, c-sis, c-fes). These genes may thus be of importance for selection of differentiation pathway. The c-myc oncogene is frequently amplified in small-cell lung cancer cell lines in a much higher frequency than in vivo. This indicates that c-myc seems to be related to tumor progression and a relatively late event in the lung cancer development. The uncontrolled production of multiple growth factors has been identified in human lung cancer cell lines. These factors can promote and inhibit the proliferation via paracrine and autocrine loops via specific receptors. The products from some of the activated proto-oncogenes (c-sis, c-erbB-2) are sequences homologous to a certain growth factor (PDGF) and a receptor (EGF) identified in lung cancer. The production and action of these growth factors may be of major importance for further activation of proto-oncogenes via intracellular signal transduction and specific oncogenic activation leading to further tumor progression.
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PMID:Gene amplification in human lung cancer. The myc family genes and other proto-oncogenes and growth factor genes. 217 59

A simple, sensitive method of DNA analysis of nucleotide substitutions, namely, single-strand conformation polymorphism analysis of polymerase chain reaction products (PCR-SSCP analysis), was used for detection of mutated ras genes in surgical specimens of human lung cancer. Of a total of 129 tumors analysed, 22 contained a mutated ras gene. Of the 66 adenocarcinomas analysed, 14 contained an activated c-Ki-ras2 gene (the mutations in codon 12 in 6, in codon 13 in 4, in codon 18 in one, and in codon 61 in 3), one contained a c-Ha-ras1 gene with a mutation in codon 61 and 3 contained N-ras genes with mutations (in codon 12 in one and in codon 61 in 2). Mutated rats genes were also found in 2 of 36 squamous cell carcinomas (c-Ha-ras1 genes with mutations in codon 61) and 2 of 14 large cell carcinomas (c-Ki-ras2 genes with mutations in codon 12). No mutation of the ras gene was detected in 8 small cell carcinomas and 5 adenosquamous cell carcinomas. These results indicate that activation of the ras gene was not frequent (17%) in human lung cancers, that among these lung cancers mutation of the ras gene was most frequent in adenocarcinomas (27%) and 73% of the point mutations were in the c-Ki-ras2 gene in codon 12, 13, 18 or 61.
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PMID:Detection of ras gene mutations in human lung cancers by single-strand conformation polymorphism analysis of polymerase chain reaction products. 219 91


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