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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human cell lines with neuronal and neuroendocrine features were examined for their expression of pp60c-src, the cellular homolog of the transforming gene product pp60v-src of Rous sarcoma virus. Four neuroblastoma (LA-N-5, SH-SY5Y, Paju, and SK-N-MC) and three small-cell lung carcinoma (U-2020, U-1690, and U-1285) cell lines were selected on the basis of their stage of neurocrine differentiation, as determined by the expression of neuron-specific enolase. In an immune complex protein kinase assay, all seven cell lines displayed c-src kinase activity which was considerably higher than that found in nonneurocrine cells (human diploid fibroblasts, glioma, and non-small cell lung carcinoma cell lines). Furthermore, the c-src kinase activity, as determined by autophosphorylation or phosphorylation of an exogenous substrate, enolase, correlated with the stage of neurocrine differentiation. There was an approximately 30-fold difference in c-src kinase autophosphorylation activity between the cell lines representing the highest and lowest stages of neurocrine differentiation. A similar variation was found in the steady-state levels of the c-src protein of these cell lines. Highly differentiated neuroblastoma cells expressed two forms of the src protein. Digestion by Staphylococcus aureus V8 protease did reveal structural diversity in the amino-terminal ends of these c-src molecules. In summary, we found a clear correlation between c-src kinase activity and the stage of neuronal and neuroendocrine differentiation. Thus, the phenotypic similarity between neurons and neuroendocrine cells includes high c-src expression.
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PMID:Expression of c-src in cultured human neuroblastoma and small-cell lung carcinoma cell lines correlates with neurocrine differentiation. 283 Apr 84

Increasing interest is shown in the determination of the serum neuron-specific enolase for the diagnosis and the follow-up studies of small cell lung cancers. We report results obtained by an enzymatic procedure that permits the simultaneous determination of the neuron and nonneuron-specific enolase and the calculation of the ratio of these two components. The utility of this ratio which characterizes elevations of the serum neuron-specific enolase from a poor or rich source of this component was tested in 38 patients with small cell lung carcinoma and in 57 subjects suffering from other bronchogenic cancers. The control group consisted of 37 blood donors and 56 patients with respiratory disease. For the diagnosis, the sensitivity and the specificity of the enzymatically determined neuron-specific enolase compared well with published results obtained by radioimmunoassay and enzymoimmunoassay. The use of the ratio clearly increases the specificity of the test, since only 5.3 percent of false positive results are found when bronchogenic tumors other than small cell carcinoma are studied. The sensitivity was 76 and 100 percent in diagnosis of limited and extensive forms, respectively. The use of this ratio in the follow-up of the patients and for the determinations in hemolyzed samples is set out.
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PMID:Enzymatic determination of serum neuron-specific enolase in small cell lung cancers. Utility of the serum neuron-specific enolase/serum nonneuronal enolase ratio. 283 36

Small cell lung carcinoma (SCLC) is histologically simple, and shows a characteristic ultrastructure and very complex functions. Recently, a large amount of information has been accumulated by fundamental research, largely involving studies on many cultured cell lines. Now their potential application to the therapy of SCLC is being sought. A characteristic ultrastructural feature is the presence of dense-cored neurosecretory-type granules 100-200 nm in diameter. In addition, epithelial cell characteristics are noted. Predominance of either a neurosecretory or epithelial nature may affect the responsiveness of tumors to therapy. Many kinds of brain-gut hormones are produced by SCLC. Gastrin-releasing peptide (GRP) has attracted much attention as an autocrine growth factor for SCLC. Aromatic L-amino acid decarboxylase (AADC), neuron-specific enolase (NSE) and creatine kinase BB (CK-BB) are rather specific to SCLC. NSE and CK-BB together with GRP are good monitoring markers during treatment. Amplification of c-myc, N-myc and L-myc is seen in SCLCs. Areas both with and without N-myc amplification are found in both the primary site and metastatic sites in a single case. Del 3p(14-23) is characteristic for SCLC but SCLCs without such deletion are also present. A cytologically "variant" type is composed of cells simulating "large cells", in which the doubling time is short, AADC and GRP are undetectable, granules are rare, and the cells are resistant to radiation. However, one cell line of the classic type has revealed reversible squamous cell change in the absence of retinoic acid, becoming radioresistant without showing any remarkable changes in AADC, NSE or CK-BB. Since SCLC mixed with "large cells" or "small cell carcinoma of undifferentiated type" is resistant to therapy and possesses a more epithelial nature, small cell carcinoma with a large cell component has been proposed as a subtype. The question of whether this subclassification is practical should be confirmed by prospective study.
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PMID:[Pathology and biology of small cell lung cancer]. 283 14

The localization of bombesin gene products in neuroendocrine tumors was achieved by a number of techniques used in combination. These included immunocytochemistry, radioimmunoassay, and chromatographic procedures using a variety of region-specific antibodies recognizing separate portions of probombesin. In situ hybridization using cRNA probes was employed to analyze bombesin gene expression at a cellular level. A novel procedure using a divalent form of bombesin and gold-labeled monoclonal antibodies for the localization of bombesin binding sites at the ultrastructural level was employed in this study. Antibodies to neuron-specific enolase and electron microscopy were employed for the determination of neuroendocrine differentiation. Surgical samples of pulmonary (n = 250) and nonpulmonary (n = 28) small cell carcinomas, 49 carcinoids, and 62 atypical lung carcinoids were investigated and compared with 169 control tumors, including lymphomas, adenocarcinomas, squamous cell carcinomas, and non-small-cell undifferentiated tumors. Cell lines cultured from pulmonary small cell carcinoma and smear preparations of pleural effusions from patients with small cell carcinoma of the lung were also investigated. Strong immunostaining for neuron-specific enolase was noted in all neuroendocrine tumors investigated, and no immunoreactivity was noted in control cases. Electron-dense neurosecretory granules were abundant in carcinoid tumors, scattered in small cell carcinoids, and absent in control cases. Immunostaining for bombesin was particularly strong in benign carcinoids, whereas the more malignant neuroendocrine tumors (e.g., small cell carcinomas) stained best with antibodies to the carboxyl-terminal flanking portion of human probombesin (proGRP). These findings were further validated by radioimmunoassay and chromatography of tissue extracts. Specific binding sites for bombesin were demonstrated on the surface of small cell carcinoma cells maintained in culture. In situ hybridization demonstrated mRNA for preprobombesin in all small cell carcinomas investigated, including surgical samples, cytological preparations, and cell lines. Hybridization reactions varied in intensity, with some cells in autoradiograms almost masked by silver grains and others showing much lighter deposits.
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PMID:Localization of bombesin-like peptides in tumors. 285 95

Primary rat hepatocellular tumours, induced by a combination of diethylnitrosamine and 2-acetylaminofluorene, were examined for the presence of neuroendocrine peptides by immunocytochemical methods. Two-thirds of the tumours showed positive immunostaining for either neuron-specific enolase (NSE), protein S-100 or bombesin. NSE was commonly observed both in hepatocarcinomas and in neoplastic nodules, whereas protein S-100 was more frequently seen in carcinomas (49% positive) than in nodules (13% positive). Bombesin, previously shown to function as an autocrine growth factor in small-cell carcinoma of the lung, was present in neurosecretory granules in 13% of the nodules and 29% of the carcinomas. Normal, preneoplastic and peritumorous liver tissue, including the frequent atypical foci present in the latter two categories, was uniformly negative for all neuroendocrine markers. The foci, like the nodules and carcinomas, generally stained positively for the liver tumour marker glutathione S-transferase type P (GSTP). The results suggest that dysdifferentiation of altered hepatocytes in a neuroendocrine direction may be a common, late event in liver carcinogenesis which could possibly contribute to tumour formation, e.g. by establishing autocrine or paracrine circuits.
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PMID:Neuroendocrine dysdifferentiation and bombesin production in carcinogen-induced hepatocellular rat tumours. 291 May 24

We have described the establishment and biochemical characterization of 50 small cell lung carcinoma (SCLC) cell lines. Further analysis of these data, combined with studies of morphology and growth characteristics, indicates that 35 (70%) of the lines retained typical morphology (SCLC, intermediate subtype), growth characteristics (growth as tightly packed floating cellular aggregates, long doubling times and low colony-forming efficiencies), and biochemical profile (presence of L-dopa decarboxylase, bombesin-like immunoreactivity, neuron-specific enolase, and high concentrations of brain isoenzyme of creatine kinase). They are referred to as classic SCLC lines. The remaining 15 (30%) lines had discordant expression of the biochemical markers; they retained high concentrations of brain isozyme of creatine kinase, but had significantly lower concentrations of neuron-specific enolase and lacked L-dopa decarboxylase and bombesin-like immunoreactivity. These cell lines are called variants. SCLC variant lines could further be divided into (a) biochemical variant lines having variant biochemical profile but retaining typical SCLC morphology and growth characteristics; and (b) morphological variant (SCLC-MV) lines having variant biochemical profile, altered morphology (features of large cell undifferentiated carcinoma) and altered growth characteristics (growth as loosely attached floating aggregates, relatively short doubling times and cloning efficiencies). Fifty-five clones derived from the three SCLC subclasses retained their parental phenotypes. In SCLC-MV lines there was a near constant relationship between variant morphology, altered growth characteristics and amplification of the c-myc oncogene; classic SCLC and biochemical variant SCLC lines were not amplified. Variant morphologies frequently are present in SCLC tumors at autopsy, and most SCLC-MV lines reflect changes that had occurred in the tumors from which they were derived. Because SCLC-MV tumors behave more virulently in the patient and are radioresistant in vitro, these findings are of considerable biological and clinical interest.
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PMID:Characterization of variant subclasses of cell lines derived from small cell lung cancer having distinctive biochemical, morphological, and growth properties. 298 58

Three new, well growing cell lines (GLC-1, GLC-2, and GLC-3) have been established from small cell lung carcinoma (SCLC) and characterized. A subclone (GLC-1-M13) markedly different from its parent line GLC-1 was also isolated and characterized. Cytogenetic analysis of the cell lines revealed deletions in the short arm of chromosome 3 as a most consistent chromosomal aberration. The deleted region was not identical in all metaphases, 3p(21-23) being the shortest region of overlap. Despite their SCLC origin GLC-1, GLC-2, and GLC-3 do not show pronounced SCLC differentiation features. Neurosecretory granula were very rare (GLC-1) or completely absent (GLC-2 and GLC-3), whereas the SCLC-related enzyme and hormone markers L-3,4-dihydroxyphenylalanine decarboxylase, neuron-specific enolase, creatine kinase BB, and bombesin-like immunoreactivity were variably expressed. Although the subclone GLC-1-M13 was derived from the poorly differentiated GLC-1, it behaved according to the above criteria as a differentiated "classic" SCLC cell line. When assessed with specific monoclonal antibodies the different cell lines appeared to express different subsets of intermediate filament proteins, indicative for different stages and directions of differentiation: "undifferentiated" (GLC-1 and GLC-2); "neural tissue related" (GLC-2); "simple epithelium" related (GLC-1-M13); and a combination of simple and squamous epithelium related (GLC-3). We conclude that GLC-1, GLC-2, and GLC-3 represent dedifferentiated forms of SCLC, related to the recently described "variant" type of SCLC, whereas the clonal derivate GLC-1-M13 behaves like a differentiated "classic" SCLC cell line.
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PMID:Characterization of three new variant type cell lines derived from small cell carcinoma of the lung. 299 91

The gamma-subunit of 2-phospho-D-glycerate hydrolyase, E.C. 4.2.1.11 (enolase), neuron-specific enolase (NSE), is present at high concentrations in neurons and neuroendocrine cells and has therefore recently been introduced as a marker for neuroendocrine tumors. By the indirect methods, immunocytochemistry and radioimmunoassay, NSE has been detected also in some nonneuroendocrine tumors, a finding that could reflect technical artifacts or the capacity for NSE expression in nonneuroendocrine tumor cells. This paper reports on the expression of NSE in human neuroendocrine and nonneuroendocrine tumor specimens and in a panel of permanent human cell lines, by using a direct (enzymatic) and an indirect (radioimmunoassay) method for determination of NSE. We detected NSE in all tested tumor specimens and neuroendocrine tumor cell lines and in a majority (21 of 24) of the nonneuroendocrine tumor cell lines. In general, neuroendocrine tumor specimens and derived tumor cell lines contained more NSE than the nonneuroendocrine tumor specimens and cell lines. However, some of the cultured hematopoietic cell lines (T leukemia and Epstein-Barr virus immortalized B lymphoblastoid cell lines) had NSE levels comparable to those found in some neuroblastoma and small-cell lung carcinoma cell lines. We conclude that NSE is not exclusively expressed in neuroendocrine tumor cells.
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PMID:Expression of gamma-subunit of enolase, neuron-specific enolase, in human non-neuroendocrine tumors and derived cell lines. 300 68

Serum levels of neuron-specific enolase (NSE), squamous cell carcinoma-related antigen (SCC antigen) and carcinoembryonic antigen (CEA) were measured in 53 untreated patients with carcinoma of the lung. The positive rates of serum NSE were 17.0% in all patients with lung cancer, 53.8% in small cell carcinoma, 6.7% in adenocarcinoma, 5.0% in squamous cell carcinoma and 0% in large cell carcinoma; 0% in stage I, 14.3% in stage III and 26.7% in stage IV. The positive rates of serum SCC antigen were 45.3% overall, 70.0% in squamous cell carcinoma, 40.0% in adenocarcinoma, 23.1% in small cell carcinoma and 0% in large cell carcinoma; 42.9% in stage I, 57.1% in stage III and 46.7% in stage IV. In comparison with serum CEA, serum NSE and SCC antigen were much more specific in small cell carcinoma and squamous cell carcinoma, respectively. Moreover, serum levels of NSE and SCC antigen changed in parallel with the clinical course during the treatments. In conclusion, serum NSE and SCC antigen were considered to be very useful markers of lung cancer, especially of small cell carcinoma and squamous cell carcinoma, respectively.
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PMID:[Clinical investigation of neuron-specific enolase, squamous cell carcinoma-related antigen and carcinoembryonic antigen in carcinoma of the lung]. 301 44

Three clinicopathologic cases with a remarkable pattern of extensive diffuse subependymal periventricular spread of cerebral metastases from solid systemic cancer are reported. Two patients had a small cell carcinoma of the lung. In the third case, the histologic features of the brain metastases were consistent with a neuron-specific enolase-positive, small cell anaplastic carcinoma. Involvement of the choroid plexus and leptomeninges was moderate or absent. Intraparenchymatous nodular metastases were not found except in one case in which rare nodular superficial cortical metastases were present. The clinical data were nonspecific except for orthostatic hypotension, in one patient, which was probably due to the infiltration of the floor of the third and fourth ventricles. Results of the cerebrospinal fluid examination, available in two cases, were normal. The only diagnostic investigation was contrast-enhanced computed tomography scanning.
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PMID:Diffuse subependymal periventricular metastases. Report of three cases. 302 12


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