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

Small cell lung carcinoma is an aggressive neuroendocrine tumor that secretes several hormones, some of which act as autocrine growth factors. In order to obtain more information on the process of hormone secretion from this tumor, we have studied the role of intracellular free Ca2+ concentrations and voltage-operated calcium channels in the control of [3H]serotonin release from in vitro growing cell lines. We found that the Ca2+ ionophore ionomycin and the Ca(2+)-ATPase antagonist thapsigargin induced a dose-dependent increase of intracellular Ca2+ and a parallel enhancement of [3H]serotonin release. KCl-induced depolarization also stimulated a dose- and Ca(2+)-dependent [3H]serotonin release that in the GLC8 cell line was effectively inhibited by Ca2+ channel antagonists (Cd2+, nitrendipine, verapamil, omega-conotoxin GVIA, and omega-agatoxin IVA) and potentiated by the Ca2+ channel agonist BayK8644. Autoantibodies against Ca2+ channels present in the sera of Lambert-Eaton myasthenic patients antagonized KCl- but not ionomycin-induced [3H]serotonin release. Polymerase chain reaction analysis indicated that GLC8 cells express L-, N-, and P-type neuronal Ca2+ channel alpha 1 subunits, together with two types of Ca2+ channel beta subunits. The presence of three functionally distinct high threshold Ca2+ channels was also revealed by patch clamp experiments; high threshold Ca2+ channels were identified as dihydropyridine-sensitive (L-type), omega-conotoxin GVIA-sensitive (N-type), and omega-agatoxin IVA-sensitive (P-type). Our data demonstrate that [3H]serotonin is released by small cell lung carcinoma cells in a Ca(2+)-dependent manner and that depolarization-induced [3H]serotonin release is mediated by Ca2+ influx through distinct, neuron-like, Ca2+ channel subtypes.
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PMID:Calcium channel subtypes controlling serotonin release from human small cell lung carcinoma cell lines. 825 45

High levels of loss of distal markers on 17p13.3 in breast cancer suggested the presence within the region of at least one tumour-suppressor gene. Here we describe the derivation of two biallelic polymorphisms from the 17p telomeric yeast artificial chromosome (YAC) TYAC98. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and multiplex PCR analysis demonstrated that the high level of allelic imbalance observed in breast tumours represented loss of constitutional heterozygosity (LOH) and that this LOH extended to the telomere. Lung carcinoma (but not Wilms' tumour)-derived DNA again revealed a high level of loss of subtelomeric 17p sequences. Telomeric microsatellite polymorphisms from other chromosome arms did not show such elevated loss in either tumour type. This suggested that the 17p loss observed did not reflect a general telomeric instability and provided further evidence for the presence of a breast cancer tumour-suppressor gene in the distal region of 17p13.3.
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PMID:High levels of loss at the 17p telomere suggest the close proximity of a tumour suppressor. 882 50

This trial was undertaken to determine the prognostic role of K-ras (p21), c-erb B-2 (p185) protein expression, and the presence or nonpresence of a K-ras gene mutation in patients with adenocarcinoma of the lung. This was a retrospective study of 103 patients with adeno- or large-cell carcinoma of the lung who had available paraffin-stored tumor material. The relation of several clinical variables to survival was analyzed. Immunohistochemical techniques were used to determine expression of p21 and p185. Polymerase chain reaction (PCR) and sequencing were used to determine K-ras mutation status. Tumor stage was the only nonmolecular clinical variable predictive of survival (p=0.0001). A combination of K-ras mutation and p 185 expression (p=0.0144), ras mutation and strong p21 expression (p=0.0137), and K-ras mutation and the combined expression of p21 and p185 were predictive of poor survival (p=0.0415) in univariate analysis of all patients. The sole presence of K-ras mutation was predictive of survival. Additionally, when combined with elevated p21 or p185 expression in a subset of patients with 4 or more years of follow-up, negative correlation with survival was observed.
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PMID:Prognostic value of K-ras mutations, ras oncoprotein, and c-erb B-2 oncoprotein expression in adenocarcinoma of the lung. 953 3

Previous studies of c-mvc DNA amplification in lung cancer have focused primarily on analysis of small cell carcinoma or its tumor cell lines. There are few data about c-myc DNA amplification in histological types of lung cancer other than small cell carcinoma. Therefore the present study was conducted to investigate c-myc oncogene amplification in non-small cell lung carcinoma. We studied 46 lung tumor specimens for c-myc DNA amplification (15 adenocarcinomas, 15 squamous cell carcinomas, 6 large cell carcinomas, and 10 small cell carcinomas). Polymerase chain reaction, digoxigenin DNA labeling, and electrophoresis were utilized to investigate the c-myc copy number in the lung tumor specimens. The c-myc copy number of non-small cell carcinoma ranged from 1.5 to more than 20.0 in adenocarcinoma and squamous cell carcinoma, and from 6.0 to 12.0 in large cell carcinoma. That of small cell carcinoma ranged from 1.8 to 12.0. The c-myc copy number of non-small cell carcinoma was significantly higher than that of small cell carcinoma (Wilcoxon rank sum test, Z=2.06 P=0.040). However, the differences in c-myc copy number among these four histological types were not statistically significant. Amplification of c-myc (more than 4 copies) was observed not only in small cell carcinoma but also in nonsmall cell carcinoma at similarly high frequency (12/15 in adenocarcinoma and squamous cell carcinoma, 6/6 in large cell carcinoma, and 9/10 in small cell carcinoma).
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PMID:Analysis of c-myc DNA amplification in non-small cell lung carcinoma in comparison with small cell lung carcinoma using polymerase chain reaction. 1169 27

Glutathione transferases (GSTs), a multiple gene family of phase II enzymes, catalyze detoxifying endogenous reactions with glutathione and protect cellular macromolecules from damage caused by cytotoxic and carcinogenic agents. Glutathione S-transferase p1 (GSTP1), the most abundant GST isoform in the lung, metabolizes numerous carcinogenic compounds including benzo[a]pyrene, a tobacco carcinogen. Previous studies suggest that genetic polymorphisms of GSTP1 exon 5 (Ile105Val) and exon 6 (Ala114Val) have functional effects on the GST gene product resulting in reduced enzyme activity. Individuals with reduced GST enzymatic activity may be at a greater risk for cancer due to decreased detoxification of carcinogenic and mutagenic compounds. Utilizing a hospital-based case-control study, we investigated the association between GSTP1 polymorphisms at exons 5 and 6 with lung cancer risk. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was used to successfully genotype the GSTP1 exons 5 and 6 polymorphism in 582 Caucasian lung cancer cases and 600 frequency matched Caucasian controls. There was no association between the exon 5 variant genotypes (A/G+G/G) and overall lung cancer risk (OR=1.09; 95% CI 0.82-1.45) nor when stratified by age, gender, and smoking status. However, the exon 6 variant genotypes (C/T+T/T) were associated with a statistically significant elevated lung cancer risk (OR=1.40; 95% CI 1.06-1.92). Additionally, there was an increase in lung cancer risk for the exon 6 variant genotypes in younger individuals (<62 years) (OR=1.63; 95% C.I. 1.07-2.49) but no effect in older individuals (OR=1.14; 95% CI 0.72-1.81). A statistically significant increased risk of lung cancer was also observed for the exon 6 variant genotypes among men (OR=2.17; 95% CI 1.41-3.33), but not among women (OR=0.80; 95% CI 0.51-1.28). Among ever smokers, the exon 6 variant genotypes were associated with an elevated lung cancer risk (OR=1.58; 95% CI 1.14-2.19), which was not evident for never smokers (OR=0.53; 95% CI 0.21-1.33). These data demonstrate that the GSTP1 exon 6 polymorphism, but not the exon 5 polymorphism, is associated with lung cancer risk that is especially evident in men, younger individuals, and ever smokers.
Lung Cancer 2003 Apr
PMID:Association between glutathione S-transferase p1 polymorphisms and lung cancer risk in Caucasians: a case-control study. 1266 4

RhoE, a small G protein, is constitutively GTP bound within the cell and can regulate actin cytoskeleton reorganization, leading to the appearance of aggregates of actin filaments. Although emerging evidence suggests that RhoE is causally involved in cancer formation and progression, little is known about its significance in solid cancer, including lung cancer. In the present study, the expression of RhoE was analyzed using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR), real-time RT-PCR, immunohistochemistry and western blot in 30 patients with Non-small Cell Lung Cancer (NSCLC). Then the correlation of RhoE overexpression with clinical parameters was evaluated. Furthermore, the possible reasons contributing to the RhoE expression were examined by real-time genomic PCR and mutation analysis on DNA sequence and cDNA sequence. Our results revealed that RhoE expression was dramatically increased in lung cancer tissues compared with adjacent nontumoral lung tissues (p <0.01). Immunohistochemistry showed a strong cytoplasmic staining in cancer cells compared with positive membrane staining in adjacent nontumoral proliferative alveolar epitheliums. Moreover, the overexpression of RhoE was significantly associated with the patients' smoking history (p <0.05). 72% tumor tissues displayed DNA copy number changes based on the DNA levels in the matched adjacent nontumoral lung tissues and this copy number changes correlated significantly with RhoE expression and smoking history (p <0.05). Three polymorphisms were identified but no correlation was found with the clinicopathological features. To our knowledge, this is the first report demonstrating that overexpression of RhoE correlated with smoking and DNA copy number changes, suggesting that RhoE may serve as a molecular marker to identify high-risk individuals and assist in the identification of additional pathways of carcinogenesis.
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PMID:Overexpression of RhoE in Non-small Cell Lung Cancer (NSCLC) is associated with smoking and correlates with DNA copy number changes. 1731 84

We studied the expression and mutation of thyroid transcription factor-1 (TTF-1) gene in 92 cases of lung carcinomas comprised of lung adenocarcinoma (36 cases), squamous cell lung carcinoma (42 cases), small cell lung carcinoma (8 cases), and large cell lung carcinoma (6 cases) to investigate whether TTF-1 gene mutation predisposed to the development of lung cancer. Normal lung tissues were obtained from each of the 92 patients. The tissues served as controls. Polymerase chain reaction-single-strand conformation polymorphism, denaturing high-performance liquid chromatography, and DNA sequencing were used to analyze TTF-1 gene mutation and its relationship with the carcinogenesis of lung cancer. We detected the expression of TTF-1 protein and messenger RNA (mRNA) in paraffin-embedded lung carcinomas and their normal lung tissues by tissue microarray. TTF-1 protein and mRNA intensities were measured by Leica-Q500 MC Image Analysis System to reveal their correlation with TTF-1 mutation in lung carcinomas. TTF-1 gene missense and synonymous mutation are present in lung carcinomas with the mutation rate of 16%. TTF-1 protein and mRNA are higher in normal lung tissues than in different lung carcinomas. TTF-1 gene mutation is correlated with the loss of TTF-1 protein and mRNA. The analyses of TTF-1 gene missense mutation and synonymous mutation and the loss of TTF-1 protein and mRNA can be regarded as the important indexes of molecular pathology of lung carcinoma.
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PMID:Mutational analysis of thyroid transcription factor-1 gene (TTF-1) in lung carcinomas. 1807 37

Monascus -fermented red mold rice extract (RMRE) offers valuable therapeutic benefits and has been extensively used for centuries in East Asia. Monascus secondary polyketide metabolites, including monacolin K (MK) and ankaflavin (AK), have been reported to have antitumor-initiating effects on cancer progression. This paper reports that the oral administration of RMRE dramatically inhibited the metastatic ability of murine Lewis lung carcinoma (LLC) cells in syngeneic C57BL/6 mice caused by the decline of serum vascular endothelial growth factor (VEGF) levels compared with untreated metastatic groups. MK is a key antimetastatic and antiangiogenesis compound in RMRE, as shown by down-regulation of VEGF-stimulated invasive activity in LLC cells by Matrigel-coating transwell and tube-forming assays and reverse transcription-Polymerase Chain Reaction (RT-PCR). Therefore, application of RMRE may serve as a nontoxic natural chemopreventive or antineoplastic agent in the development of cancer adjuvant chemotherapy.
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PMID:The Monascus metabolite monacolin K reduces tumor progression and metastasis of Lewis lung carcinoma cells. 1975 67

Evaluation of DNA repair proteins might provide meaningful information in relation to prognosis and chemotherapy efficacy in Non-Small Cell Lung Cancer (NSCLC) patients. The role of Poly(ADP-Ribose) Polymerase (PARP) in DNA repair of platinum adducts has not been firmly established. We used a DNA repair functional test based on antibody recognition of cisplatin intrastrand platinum adducts on DNA. We evaluated the effect of PARP inhibition on DNA repair functionality in a panel of cisplatin cell lines treated by the clinical-grade pharmacological inhibitor CEP8983 (a 4-methoxy-carbazole derivate) and the commercially available inhibitor PJ34 (phenanthridinone). We determined PARP1 protein expression in whole tumor sections from the International Adjuvant Lung cancer Trial (IALT)-bio study and tested a 3-marker PARP1/MSH2/ERCC1 algorithm combining PARP1 tumor status with previously published data. Chemosensitivity of cisplatin in NSCLC cell lines was correlated with the accumulation of cisplatin DNA adducts (P=0.0004). Further, the pharmacological inhibition of PARP induced a 1.7 to 2.3-fold increase in platinum adduct accumulation (24h) in A549 cell line suggesting a slow-down of platinum DNA-adduct repair capacity. In parallel, PARP1 inhibition increased the sensitivity to cisplatin treatment. In patient samples, PARP1 expression levels did not influence patient survival or the effect of platinum-based post-operative chemotherapy in the global IALT-bio population (interaction P=0.79). Among cases with high expression of all three markers (triple positive), untreated patients had prolonged survival with a median DFS of 7.8 years, (HR=0.34, 95%CI [0.19-0.61], adjusted P=0.0003) compared to triple negative patients (1.4 years). Remarkably, triple positive patients suffered from a detrimental effect (4.9-year reduction of median DFS) by post-operative cisplatin-based chemotherapy (HR=1.79, 95%CI [1.01-3.17], adjusted P=0.04, chemotherapy vs. control). Combinatorial sub-group analysis of the 3 markers further suggested that PARP1 tumor positivity might constitute a molecular context with high theranostic interest of ERCC1 and MSH2 in NSCLC. In conclusion, our data confirm that platinum DNA adduct accumulation is linked to chemosensitivity, which increase by pharmacological PARP inhibitors points to a role of PARP-dependent DNA repair in the process. We further suggest DNA repair biomarkers should be analyzed in a larger context of multiple DNA repair pathway regulation.
Lung Cancer 2013 May
PMID:PARP1 impact on DNA repair of platinum adducts: preclinical and clinical read-outs. 2341 Aug 25

Telomerase, undetectable in normal somatic cells, plays a critical role in carcinogenesis of the majority of human tumors including lung carcinoma. The aim of our study was to determine human telomerase reverse transcriptase (hTERT) mRNA expression in patients with non-small cell lung cancer (NSCLC) in order to estimate its usefulness as diagnostic and/or prognostic factor. hTERT expression was analyzed in a group of 12 females and 28 males with NSCLC using Quantitative Real-Time Polymerase Chain Reaction (QRT-PCR method) in cancerous and non-cancerous lung tissues. Results were analyzed according to clinical data and one-, two-, and five-year survival rates. hTERT expression in the cancerous tissue was significantly higher than in the lung parenchyma free from neoplasm infiltration (p<0.05). There was no significant association between hTERT expression in the tumor tissue and age, gender, grading or clinical stage. A significant difference in hTERT expression between two types of histopathological patterns (adenocarcinoma and squamous cell carcinoma) was detected (p=0.01). No association between hTERT expression in NSCLC specimens and survival rates was found. hTERT mRNA detection by QRT-PCR in tumor and corresponding cancer-free tissues can be used as a diagnostic marker in patients with NSCLC, but seems not to be a prognostic factor.
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PMID:Clinical and prognostic value of hTERT mRNA expression in patients with non-small-cell lung cancer. 2914 Oct 53


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