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Query: UMLS:C0149925 (small cell lung cancer)
 6,491 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To analyze the region upstream of c-myc, a number of novel probes were established. These were generated by chromosomal walking starting from the breakpoint of the chromosomal translocation of the B-cell line 380 and by cloning the breakpoint of the translocation of the Burkitt lymphoma cell line IARC/BL72. Using the newly isolated probes a detailed physical map of 500 kilobases of the region upstream of c-myc was established applying pulsed-field gel electrophoresis. The chromosomal breakpoint of IARC/BL72 cells was mapped to a site 55 kilobases 5' of c-myc. A region 20 kilobases in length and containing the breakpoints of 380, EW36, P3HR-1, and Daudi cells was identified 170-190 kilobases upstream of c-myc. In addition the HPV18 integration site in HeLa cells was located between 340 and 500 kilobases 5' of c-myc. The probes were used to define the c-myc amplification units in Colo320-HSR and HL60 cells as well as in four cases of small cell lung cancer. Evidence is provided that the amplicon of HL60 cells is discontinuously organized.
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PMID:Mapping chromosomal breakpoints of Burkitt's t(8;14) translocations far upstream of c-myc. 133 Feb 96

Small cell lung cancer (SCLC) manifests a number of neuroendocrine differentiation features and antigenic characteristics that distinguish the tumour from non-small cell lung cancer (NSCLC). Several surface antigens on SCLC cells, identified by clusters of monoclonal antibodies (MAbs), distinguish SCLC and other neuroendocrine tumours of NSCLC. Stable transfection of the c-myc proto-oncogene has been reported to confer upon classic SCLC cells the growth properties and morphology of the variant subtype of SCLC (SCLC-v). Furthermore, insertion of the v-Ha-ras oncogene into such SCLC-v cells has been found to induce features typical of NSCLC. We have used classic SCLC cells transfected with c-myc, or co-transformed with c-myc and v-Ha-ras, to examine the expression of characteristics SCLC cluster antigens. Flow cytometric assays reveal that SCLC cells co-transformed with c-myc and v-Ha-ras oncogenes down-modulate SC-1, SC-2 and SC-5A surface antigens to levels approaching, in some cases, those seen with NSCLC cells. The SC-4 surface antigen is not modulated by activation of these oncogenes. These findings support clinical and laboratory observations that important transitions can occur between subtypes of human lung cancer cells, and that these shifts may play a role in the clinical progression of lung cancer.
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PMID:Modulation of neuroendocrine surface antigens in oncogene-activated small cell lung cancer lines. 164 69

The mechanism(s) by which the c-myc nuclear protein and the membrane-associated ras protein interact to mediate phenotypic changes is unknown. We now find that c-mcy gene expression is associated with alterations in the principal signal transduction pathway through which the ras protein is thought to function. We studied the transcript and protein expression of protein kinase C (PKC) isoforms in a culture line of human small cell lung cancer cells (NCI H209) in which expression of inserted c-myc and Ha-ras genes together, but not alone, causes a transition to a large cell phenotype. In control H209 cells, at the transcript and cell membrane protein levels, PKC-alpha is the dominant PKC species. In this cell line, the expression of an exogenous c-myc gene, but not of a viral Ha-ras gene, causes a 5- to 10-fold increase in the PKC-beta isoform transcript and protein. The insertion of ras into the exogenous myc-expressing 209 cells, in addition to causing phenotypic transition, results in the translocation of the PKC-beta protein from the cytosol to the membrane fraction and a decrease in membrane-associated PKC-alpha. Concomitant with these changes, the increased PKC isoform transcript levels induced by myc alone are completely reversed. These observations suggest that a complex set of PKC transcript and protein alterations, most prominently involving an increased PKC-beta protein level in the cell membrane, a decrease in PKC-alpha protein, and a decrease in all PKC isoform transcripts, may represent a fundamental event(s) for c-myc collaboration with Ha-ras to alter cell phenotype.
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PMID:c-myc gene-induced alterations in protein kinase C expression: a possible mechanism facilitating myc-ras gene complementation. 165 53

Altered and deregulated cellular oncogenes were found in many human solid tumors. Except for a few types of tumors that consistently exhibited specific altered proto-oncogenes, the majority of tumors are associated with a number of transcriptionally activated cellular oncogenes. In the heterologous group of non-small-cell lung cancer (NSCLC), nothing about a specific pattern of proto-oncogene expression is known. Therefore, we investigated the expression of a panel of cellular oncogenes in NSCLC cell lines. DNA and RNA from 11 established NSCLC cell lines (4 adenocarcinoma cell lines, 3 squamous cell carcinoma cell lines, 3 large-cell carcinoma cell lines and 1 mesothelioma cell line) were isolated and analysed using the Southern, dot blot and Northern hybridization technique. c-myc RNA expression was found in all NSCLC cell line, L-myc expression only in 1 adenocarcinoma cell line, N-myc and c-myb expression in none of the 11 cell lines examined. No c-myc amplification could be detected in the DNAs. v-sis-related mRNA was observed in 5/11 cell lines without association to a specific NSCLC subtype. v-src-related mRNA, found in all tested cells, exhibited increased levels in 1 adenocarcinoma cell line (A-549) compared to the other cell lines. Binding sites for epidermal growth factor (EGF) had been described previously in NSCL, therefore we found erbB homologue transcripts coding for the EGF receptor in all NSCLC cell lines. Also, c-raf1-, N-ras-, Ki-ras-, and H-ras-related RNA expression was observed in all lines. We conclude that L-myc, N-myc, and c-myb expression does occur less frequently in NSCLC than in SCLC. Also amplification does not appear to be an important mechanism by which the c-myc proto-oncogene is activated in NSCLC. A specific pattern of oncogene expression could not be detected in NSCLC cells; each cell line examined showed its own pattern. However, transcriptional activation of a proto-oncogene like erbB, ras, raf, src, and c-myc, which are all involved in the progression pathway of EGF, may be a common feature of NSCLC.
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PMID:Different pattern of expression of cellular oncogenes in human non-small-cell lung cancer cell lines. 169 Feb 10

We have previously described the neoplastic transformation of immortalized human bronchial epithelial cells (BEAS-2B) by the combination of the c-raf-1 and c-myc protooncogenes and the concomitant induction of neuron-specific enolase mRNA expression (A. Pfeifer et al., Proc. Natl. Acad. Sci. USA, 86: 10075-10079, 1989). In this paper we describe the morphological, biochemical, and immunohistochemical characteristics of the primary c-raf-1/c-myc tumors, xenografts of these tumors, and tumors that originated from cell lines of the primary neoplasm. The tumors were morphologically characterized by the appearance of desmosomes and tonofilaments, microvilli, and dense core granules representing markers of squamous, glandular, and neuroendocrine differentiation, respectively. A total of 11 of 13 tumors were positive by immunohistochemical techniques for neuron-specific enolase, serotonin (nine of 13), and calcitonin (six of 13). Keratins were expressed in 11 of 13 tumors, and while specific keratins (K5, K7, K16/K17) decreased, there was an increase of vimentin in the tumor cells. Gastrin-releasing peptide immunoreactivity was detectable in a small number of tumors (five of 13). BEAS-2B cells transfected with the c-raf-1 and c-myc protooncogenes and cell lines established from the primary tumors expressed major histocompatibility Class II antigen which has been found on small cell lung carcinoma cells. The tumors induced by the c-raf-1 and c-myc protooncogenes resemble the multidifferentiated phenotype of small cell lung cancer frequently detected in vivo and present a defined model to study the relation between molecular markers, phenotypical appearance, and response to chemotherapeutic agents and radiation.
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PMID:Human bronchial epithelial cells transformed by the c-raf-1 and c-myc protooncogenes induce multidifferentiated carcinomas in nude mice: a model for lung carcinogenesis. 171 50

Relationships among cytological features, doubling time, S-phase percentage, expression of myc-family oncogenes, DNA ploidy and biochemical properties were studied in thirteen small cell lung cancer cell lines. Six cell lines that grew slowly (average doubling time 99 h) and had lower S-phase percentages (average 32%) showed inconspicuous nucleoli (average area of 1.5 microns 2), and the remaining seven cell lines that grew quickly (average doubling time 45 h) and had higher S-phase percentages (average 44%) showed large and prominent nucleoli (average area of 6.1 microns 2). DNA index value obtained from flow cytometric DNA histograms showed that all cell lines except for H-69 cell line displayed aneuploidy. Ribbon-like cell arrangements were observed in the 7 cell lines that grew quickly, and in 1 cell line that grew slowly. Biochemically, six slow-growing cell lines and four fast-growing cell lines showed high levels of aromatic L-amino acid decarboxylase activity, while in the remaining three fast-growing cell lines its level was low. A high level of c-myc or N-myc oncogene expression was observed in all 7 cell lines that grew quickly, but not in any of the 6 cell lines that grew slowly. It appears that small cell lung cancer cell lines that grow quickly can be expected to have large nucleoli and ribbon-like cell arrangements and to express high levels of myc-family oncogenes, and that nucleolar size is a good indicator for growth characteristics.
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PMID:Relation between nucleolar size and growth characteristics in small cell lung cancer cell lines. 171 38

Small cell lung cancer (SCLC) tumor progression can involve partial or complete conversion to a more treatment-resistant non-small cell (NSCLC) phenotype. In a cell culture model of this phenomenon, we have previously demonstrated that insertion of the viral Harvey ras gene (v-Ha-ras) into SCLC cell lines with amplification and overexpression of the c-myc gene induced many NSCLC phenotypic features. We now report that the v-Ha-ras gene can also induce morphologic, biochemical, and growth characteristics consistent with the NSCLC phenotype in an N-myc amplified SCLC cell line, NCI-H249. We show that v-Ha-ras has novel effects on these cells, abrogating an SCLC-specific growth requirement for gastrin-releasing peptide, and inducing mRNA expression of three NSCLC-associated growth factors and receptors, platelet-derived growth factor B chain, transforming growth factor-alpha (TGF-alpha), and epidermal growth factor receptor (EGF-R). TGF-alpha secretion and EGF-R also appear, consistent with the induction of an autocrine loop previously shown to be growth stimulatory for NSCLC in culture. These data suggest that N-myc and v-Ha-ras represent functional classes of genes that may complement each other in bringing about the phenotypic alterations seen during SCLC tumor progression, and suggest that such alterations might include the appearance of growth factors and receptors of potential importance for the growth of the tumor and its surrounding stroma.
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PMID:v-rasH induces non-small cell phenotype, with associated growth factors and receptors, in a small cell lung cancer cell line. 216 28

Despite disappointing results in the treatment of small cell lung cancer (SCLC), major progress in our understanding of SCLC biology has occurred in the past decade. Advances in the technique for culturing SCLC tumours in vitro have greatly facilitated the study of the biological properties of this tumour. The major progress in our understanding of SCLC includes: 1) the availability of nonspecific biological tumour markers such as neuron-specific enolase (NSE), the BB isoenzyme of creatine phosphokinase (CPKBB), bombesin/gastrin releasing peptide (GRP) and chromogranin A; 2) the generation of monoclonal antibodies raised against the neural and epithelial features of SCLC tumours; 3) the identification of several autocrine growth factors such as bombesin/GRP, insulin-like growth factor (IGF), transferrin and physalaemin; 4) the close study of cytogenetic abnormalities leading to the discovery of a unique chromosomal deletion of the short arm of chromosome 3 (del 3p 14-21), and to changes in oncogenic expression, e.g. c-myc, L-myc and N-myc, accounting for known biological and treatment results. These data suggest that all lung cancers arise from a common stem cell of endodermal origin. The information derived from these biological studies represents the most promising avenue towards new treatment strategies in SCLC.
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PMID:Biology of small cell lung cancer: an overview. 216 19

Over the past ten years there has been fundamental progress in molecular biology, i.e. concerning the structure and function of genes. The understanding and diagnosis of several diseases, in particular those of the respiratory system, have been profoundly affected and changed. For example alpha-1-antitrypsin deficiency and the emphysema which results have now been dissected down to a molecular level and characterised by anomalies of certain critical portions of the gene coding for this protein. The same thing is found in cystic fibrosis where, thanks to recent technical progress, it is now possible to make a positive diagnosis in most unaffected carriers. The importance of molecular biology in lung cancer is equally established, and in small cell lung cancer one can already isolate a sub group of cancers presenting with an abnormal amplification of the c-myc oncogene. Finally, the role of inflammatory cells, in particular macrophages, in pulmonary fibrosis is best understood by studying the expression by macrophages of the genes coding for mediators which alter the replication of fibroblasts.
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PMID:[Application of molecular biology techniques to pneumology]. 217 33

Several mouse monoclonal antibodies which recognize carbohydrate sequences distinguish between different types of human lung cancer immunohistologically. These antibodies bind to glycolipid antigens produced by the cancer cells. When these glycolipids are separated by thin-layer chromatography, immunostaining of the chromatograms yields complex patterns of antigen-positive bands. To determine whether glycolipid patterns are useful in the classification of lung cancer, 16 human lung cancer cell lines comprising the major histological types of primary lung cancer were studied. Neutral glycolipids and gangliosides were isolated and separated by thin-layer chromatography. Six anti-carbohydrate antibodies which recognize structurally related antigens were used for immunostaining. Neuraminidase treatment of the chromatograms was used to detect "cryptic" sialylated antigens. All the cell lines were unique with regard to the type, amount, and chromatography pattern of the glycolipid antigens produced. Small cell lung cancer cell lines synthesized the greatest variety of antigens, whereas cell lines with large cell cytology synthesized the least. Interestingly, there was an inverse relationship between expression of some glycolipid antigens and DNA amplification of the c-myc oncogene. This suggests that enhanced c-myc expression may influence the types of glycolipids expressed at the surface of lung tumor cells.
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PMID:Glycolipid antigen expression in human lung cancer. 242 58


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