Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutated p53 proteins accumulate in the nuclei of tumor cells, and anti-p53 autoantibodies are found in the sera of patients with non-small-cell lung carcinoma (NSCLC). We analyzed the correlation among serum anti-p53 autoantibodies, immunohistochemical staining for p53, and clinical features (age, gender, smoking history, histological type, differentiation, stage, T factor, tumor size, and N factor) in resected non-small-cell lung carcinomas. A total of 62 cases of resected NSCLC were studied (43 men and 19 women; 33 adenocarcinomas, 21 squamous cell carcinomas, 8 large-cell carcinomas). Preoperative serum titers of anti-p53 autoantibodies were detected in 13/62 cases (21.0%). A correlation between histological type and positive titers of serum p53 autoantibodies was seen (large-cell carcinoma versus squamous cell carcinoma and adenocarcinoma, P = 0.031, chi2-test). Out of 25 cases, 10 (40%) with positive immunohistochemical staining for p53 had positive titers, whereas 3 positive titers were found in 37 patients with negative immunohistochemical staining for p53 (P = 0.0025, chi2-test). Serum titers of anti-p53 autoantibodies were present in approximately 20% of the cases of NSCLC, and overexpression of p53 protein in tumor cells was detectable in approximately 40%. Serum anti-p53 autoantibodies may be a clinical parameter for the presence of p53 mutations and p53 overexpression in NSCLC patients.
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PMID:Serum anti-p53 autoantibodies in primary resected non-small-cell lung carcinoma. 975 19

Three deletion mutants of the structural protein region of the Semliki Forest virus (SFV) genome, including one which encompassed all the viral structural protein genes, induced apoptosis in BHK cells at 48 h after transfection, as shown by DNA laddering and TUNEL staining, as did the wild-type SFV4 RNA. A similar result was obtained for the SFV1 expression vector, which has a multicloning site inserted in place of the structural protein genes. However, in cells transfected with viral RNA containing a deletion of the nsP2 gene, neither viral RNA synthesis nor the induction of apoptosis occurred. Both SFV1 vector and wild-type SFV4 RNA induced apoptosis in human H358a lung carcinoma cells, which have a homozygous deletion of the p53 gene. It is concluded that the SFV vector encodes a function in the nonstructural coding region which induces p53-independent apoptosis and is dependent on viral RNA synthesis.
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PMID:The Semliki Forest virus vector induces p53-independent apoptosis. 978 45

Uncontrolled proliferation is the characteristic of cancer. Several kinds of genes control the cell cycle: oncogenes, tumor suppressor genes, and genes implicated in apoptosis or survival. Two major pathways of control are frequently disrupted in human cancer. The first one is the RB pathway with inactivation of the RB protein (retinoblastoma protein), either by alteration of the retinoblastoma gene itself, or by genetic alterations of the genes implicated in RB phosphorylation. The second one is the inactivation of the p53 protein. Both of these abnormalities are described in human lung carcinoma but differ according to histologic subtype.
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PMID:[Cell cycle, tumor suppressor genes and lung cancers]. 980 56

In an attempt to understand the histogenesis and molecular pathogenesis of multifocal bronchioloalveolar lung carcinoma (BAC) we studied 28 cases of BAC using a topographic genotyping approach for the presence of K-ras exon 1 mutations and p53 loss of heterozygosity (LOH). This analytical approach demonstrated K-ras exon 1 mutations in 12.5% of solitary BACs, 40% of BACs with microscopic or macroscopic satellite lesions, and 60% of BACs with intrathoracic metastases. In all cases with K-ras mutations, the identical point mutation was present in the primary, satellite, and intrathoracic metastatic lesions. When p53 LOH was demonstrated in the primary lesion, it was also detected in the satellites and intrathoracic metastases. No significant association was noted between the presence of K-ras mutations and p53 LOH. The results strongly support a monoclonal origin of multifocal BACs. Furthermore, the findings support the theories explaining the origin of multifocal BAC by intraalveolar route of spread, intrapulmonary lymphatic spread, or aerosolization leading to implantation at different sites. A trend toward an increased frequency of K-ras mutations and p53 LOH in BACs with satellites or metastases compared to solitary BACs was noted.
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PMID:Bronchioloalveolar adenocarcinoma of lung: monoclonal origin for multifocal disease. 980 26

Two human cancer cell lines were established from metastatic lesions of an adenocarcinoma (RAL) and a squamous cell (CAEP) carcinoma of the lung. The clinical histories of the patients from whom the cell lines were derived are reported. The lines were maintained in continuous culture with doubling times of 65 (RAL) and 50 (CAEP) hours. The RAL and CAEP cell lines, whose morphology and ultrastructural features are presented, showed extensively rearranged karyotypes with modal number of 85 (RAL) and 98 (CAEP). In particular, chromosome 2 pentasomy and several clonal markers were evident in the RAL cells, whereas a telomeric deletion of chromosome 1, del (1)(q32), was observed in the CAEP cells. The morphologic data were confirmed by high expression of specific antigens for each histotype. A marked positivity of the neuron-specific enolase (NSE) levels was evident by immunoenzymatic assays in the cell lines cytosol with respect to those present in the respective patient's sera. No amplification or rearrangements were evident in the CMYC, LMYC, NMYC, INT-2, ERBB2, HRAS, KRAS, MOS, HST-1 genes by Southern blotting analysis in each cell line. Point mutations in exon 1 of KRAS and in exon 7 of TP53 were evident by polymerase chain reaction (PCR)-DNA sequencing in the RAL cell line, whereas no alterations were present in the HRAS and RB genes. The four genes studied did not show point mutations in the CAEP cell line. The RAL cell line was resistant to all the drugs tested, whereas the CAEP cells were sensitive to vinblastine. These cell lines may represent useful experimental models to investigate lung cancer biology and anticancer drug response.
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PMID:Molecular and biological features of two new human squamous and adenocarcinoma of the lung cell lines. 980 28

The prognostic value of p53 protein in tumor extracts as measured by ELISA was studied retrospectively in 228 non-small cell lung cancer (NSCLC) patients. The assay measures both wild-type and mutated p53. The specimens on which this study was performed have been used earlier to analyze the prognostic impact of components of the plasminogen activation system, which enabled an analysis of relationships between these components and p53 protein. The median of the p53 protein values in the 228 patients was 0.10 (range, 0-0.70) ng/mg protein. Survival analysis comparing patients with p53 levels below versus above the median showed no significant difference (P = 0.67). When analyzing the histological types, adenocarcinoma (n = 106), squamous cell carcinoma (n = 84), and large cell carcinoma of the lung (n = 38) separately, similarly, no significant differences in survival between patients having low versus high tumor p53 levels were found. When comparing levels of p53 protein in the three histological types, a significant difference (P < 0.0001) was found, with adenocarcinomas having the lowest levels. There was a weak positive correlation (r = 0.22) between p53 protein and plasminogen activator inhibitor type 1 (PAI-1). Multivariate analysis proved no impact of p53 on survival; tumor size, PAI-1, and lymph node involvement were the only variables with significant influence on survival. These data indicate that p53 protein quantitated with a sandwich ELISA in tumor extracts from NSCLC has no prognostic value, but the observed statistically significant difference of p53 protein content between histological subgroups may be related to differences in etiology and biology in different NSCLC subtypes. In addition, the weak association found between p53 protein and the independent prognostic marker PAI-1 could suggest yet undefined interactions in lung cancer.
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PMID:p53 protein in non-small cell lung cancer as quantitated by enzyme-linked immunosorbent assay: relation to prognosis. 981 2

The 5-year survival rate of non-small cell lung carcinoma (NSCLC) has only marginally improved during the past two decades, despite advances in surgery and chemoradiotherapy. Major efforts are currently directed toward biological characterization of these tumors to define biomarkers able to add further prognostic information, thus improving new therapeutic protocols. We analyzed the predictive relevance of the microvessel count (MC), bcl-2 and p53 proteins, proliferative activity, and usual postsurgical parameters on recurrence and overall survival in a series of 70 patients with NSCLC. The expression of biological parameters (p53, bcl-2, proliferative activity, and MC) was detected using immunohistochemistry on paraffin-embedded and frozen sections from the tumors treated with surgical resection alone until relapse. In the univariate analysis, the histotype, tumor status, node status, p53, bcl-2, and MC have been shown to significantly affect progression and death. In the multiple logistic regression analysis, the MC (P < 0.000001), tumor status (P < 0.005), and node status (P < 0.0002) influenced the overall survival while prediction of relapse was strongly revealed by tumor status (P < 0.005), nodal metastatic involvement (P < 0.000001), and the assessment of the vascular count (P < 0.0004). These data have allowed the creation of a multivariate model which may add more information on risk of recurrence and death in patients with NSCLC and can form the basis for future randomized clinical trials.
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PMID:Recurrence and death in non-small cell lung carcinomas: a prognostic model using pathological parameters, microvessel count, and gene protein products. 981 69

The present study is aimed to evaluate the genetic evidence for multicentricity of synchronous and metachronous multiple lung carcinomas. Nineteen cases of synchronous multiple lung carcinomas and 11 cases of metachronous multiple lung carcinomas were analyzed for p53 protein overexpression by immunohistochemistry (DO-7) and for genetic abnormality of the p53 gene by loss of heterozygosity (LOH) at chromosome 17p and by polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis. They were also analyzed for K-ras mutation. DNA from three patients was also sequenced by the dideoxy sequencing method to confirm the presence of mutations and determine the base substitutions. Different spectrums of genetic changes, which were evaluated by a combination of p53 mutation, LOH at chromosome 17p and p53 overexpression, were observed in 11 of 19 cases of synchronous multiple lung carcinomas (57.9%) in the present study. Similarly, five of 11 cases of metachronous multiple lung carcinomas (45.4%) showed a different pattern of genetic changes. The present data suggest that some of the multiple carcinomas have different clonal origins, although their histological types are identical, and support the use of genetic markers in the differential diagnosis between metastasis and second primary carcinoma of the lung.
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PMID:Synchronous and metachronous lung carcinomas: molecular evidence for multicentricity. 983 55

p21waf1/cip1 mRNA and protein accumulate in intact cells exposed to oxidizing agents through a p53-independent, MAPK-dependent mechanism. Treatment with oxidizing agents also yields a second form of this protein (FM p21), characterized by a faster migration on SDS-PAGE. This phenomenon depends on the modification of intracellular redox conditions induced by diethylmaleate, a glutathione-depleting agent, being prevented by the pretreatment with the glutathione precursor N-acetylcysteine. The appearance of this FM p21 form is very early, being observed 5 min after exposure to diethylmaleate, long before the already observed accumulation of p21 induced by oxidative stress. Furthermore, experiments with dominant negative mutants of MEK demonstrate that, in contrast with that observed for the oxidative stress-induced accumulation of p21 mRNA and protein, the appearance of FM p21 form is not dependent from the activation of the MAPK pathway. It was previously observed (Tchou et al, 1996) that in some lung carcinoma cells long exposure to high doses of phorbol esters also induces the appearance of a faster-migrating p21 electrophoretic band and it was suggested that this could result from a different phosphorylation or from a proteolytic processing at the C-terminus of the protein. The latter is not the case for the diethylmaleate-induced FM p21 whose C-terminus is intact, as demonstrated by the expression of a C-terminus tagged p21 cDNA. On the contrary, the observed migration shift seems to be dependent on the hypophosphorylation of the protein; in fact, a pretreatment of cells with okadaic acid, an inhibitor of (serine/threonine) phosphatases, inhibits the oxidation-dependent appearance of the FM p21 and the block of protein synthesis, caused by cycloeximide, does not affect the appearance of FM p21, that thus could derive from the dephosphorylation of preexisting protein.
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PMID:A new p21waf1/cip1 isoform is an early event of cell response to oxidative stress. 984 80

Spontaneous apoptosis was assessed in ten small-cell (SCLC) and five non-small cell (NSCLC) lung carcinoma cell lines by the TUNEL assay and chromatin cleavage. TUNEL staining showed significantly higher apoptotic index (AI) in SCLC (2-20%) compared with NSCLC lines (0.2-1%) in untreated exponentially growing cells. Six out of ten SCLC and none of the NSCLC showed DNA fragmentation when analysed by agarose gel electrophoresis. Field inversion pulse gel electrophoresis was used in a subset of cell lines and showed the presence of high molecular weight fragments in untreated SCLC lines U-1285 and U-1906 cells, but not in the NSCLC line U-1810. Important molecular determinants of apoptosis were studied by Western blot. Bcl-2 was detected at highest level in SCLC. There was no correlation between the ratio Bcl-2/Bax and AI in all tested cell lines. Neither p53 nor c-Myc protein status correlated to AI. Pro-caspase-3 was expressed in all cell lines without correlation to AI and no difference between the SCLC and NSCLC groups was found. In conclusion, this study shows a high degree of spontaneous apoptosis in SCLC lines compared to NSCLC lines unrelated to Bcl-2/Bax ratio.
Lung Cancer 1998 Oct
PMID:Higher spontaneous apoptotic index in small cell compared with non-small cell lung carcinoma cell lines; lack of correlation with Bcl-2/Bax. 986 2


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