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

Lung cancer is a major cause of cancer-related death in the developed countries and the overall survival rate has still an extremely poor. Cigarette smoking is an established risk factor for lung cancer although a possible role for genetic susceptibility in the development of lung cancer has been inferred from familial clustering of the disease and segregation analyzes. Everyone may have a unique combination of polymorphic traits that modify genetic susceptibility and response to drugs, chemicals and carcinogens. Developments in molecular biology have led to growing interest in investigation of biological markers, which may increase predisposition to lung carcinogenesis. Therefore, the high-risk genotype of an individual could be determined easily. As there are the great number of carcinogen-activating and -detoxifying enzymes, the variation in their expression and the complexity of exposures to tobacco carcinogens, the existence of multiple alleles at loci of those enzymes may result in differential susceptibilities of individuals. This review summarize data addressing the relationships of lung cancer to markers of genetic susceptibility genes, including metabolic polymorphisms other than well-investigated cytochrome P450s or glutathione S-transferases, DNA repair genes and the p53 tumor suppressor gene. Among genetic polymorphisms reviewed here, myeloperoxidase gene (a G to A mutation) and microsomal epoxide hydrolase exon 4 polymorphism (substitution of Arg for His) were significantly associated with lung cancer risk. As lung cancer is a multifactorial disease, an improved understanding of the interplay of environmental and genetic polymorphisms at multiple loci may help identify individuals who are at increased risk for lung cancer. Hopefully, in the future we will be able to screen for lung cancer susceptibility by using specific biomarkers.
Lung Cancer 2002 Sep
PMID:Genetic polymorphisms and lung cancer susceptibility: a review. 1223 92

Manganese superoxide dismutase (SOD2) and myeloperoxidase (MPO) are polymorphic enzymes involved in reactive oxidative species metabolism. In this case-control study (830 non-small cell lung carcinoma (NSCLC) patients; 1119 controls) we evaluated whether the MPO -G463A polymorphism (associated with a novel estrogen receptor binding site) modifies the association between the SOD2 Ala16Val polymorphism and NSCLC risk differently by gender. For women carrying the MPO variant genotypes, the adjusted odds ratio of the SOD2 polymorphism (Val/Val vs. Ala/Ala) was 3.26 (95% CI, 1.55-6.83). No associations were found in men or in women carrying the MPO GG wildtype genotype.
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PMID:MPO and SOD2 polymorphisms, gender, and the risk of non-small cell lung carcinoma. 1533 Nov 75

The genetic susceptibility hypothesis has been used to explain why only a minority of smokers develop lung cancer. Only few studies have studied the role of polymorphisms in phase-I and II metabolizing genes, among young lung cancer patients. We have pooled the individual data of three studies from Denmark and Norway, including 320 patients diagnosed with non-small cell lung cancer at age 59 or below, and 618 age and gender matched controls. A questionnaire was used to determine relevant demographic and lifestyle characteristics, and polymorphisms in following genotypes were determined GSTM1, GSTM3, GSTP1, GSTT1, GPX1, MPO, NQO1 and NAT2. Based on the literature, the alleles of the genotypes were categorised as high- or low-risk alleles. No individual effect of the genotypes was found on the risk of lung cancer. Given a smoking exposure, the presence of high-risk alleles (or phenotypes) was generally found to increase the risk of lung cancer, although the effect modification did not reach statistical significance. A pattern of stronger protective effect was observed in carriers of more than one allele associated with lower risk of lung cancer, and a higher risk of lung cancer in carriers of one or more alleles associated with higher risk of lung cancer, but the results did not reach statistical significance. The effect modification was generally strongest at lower levels of smoking.
Lung Cancer 2005 May
PMID:Polymorphisms in genes involved in xenobiotic metabolism and lung cancer risk under the age of 60 years. A pooled study of lung cancer patients in Denmark and Norway. 1582 18

Available data indicate that there are significant differences in individual susceptibility to lung cancer within the human population. It is believed to be underlie by inherited genetic predispositions related to the genetic polymorphism of several enzymes involved in the detoxification and xenobiotic metabolism. In this review, we collect and discuss the evidence reported up to date on the association between lung cancer and genetic polymorphism of cytochromes P450, N-acetyltransferase, glutathione S-transferases, microsomal epoxide hydrolase, NAD(P)H:quinone oxidoreductase, myeloperoxidase and glutathione peroxidase. All these genes might appear to be candidates for lung cancer susceptibility genes, nevertheless, the present state of the art still offers only a limited explanation of the link between such polymorphisms and increased risk of lung cancer.
Lung Cancer 2007 Jul
PMID:Polymorphism of selected enzymes involved in detoxification and biotransformation in relation to lung cancer. 1733 85

Various molecular epidemiological studies have been performed to find genetic etiology for lung cancer. Particularly, genetic polymorphisms in NAD(P)H-quinone oxidoreductase (NQO1), cytochrome P450 (CYP)1A1, myeloperoxidase (MPO), glutathione-S-transferase (GST)P1, GSTT1, and GSTM1, and have been suspected to affect lung cancer risk. However, there was no study that examined the combined effects of these genes on lung cancer risk. We studied the combined genetic effects on lung cancer risk in 671 Korean subjects including 318 lung cancer patients and 353 controls. They filled questionnaires, which included lifestyle and childhood- and current environment data. Based on single nucleotide polymorphisms and gene deletions, genetic polymorphisms of the above six genes were determined with PCR-RFLP and TaqMan methods. As results, genetic polymorphisms in the GSTP1, MPO, and CYP1A1 among the genetic factors showed associations with lung cancer risk. The reference, which is supposed to have the lowest risk for cancer, was subjects who were homozygous wild type of the GSTP1 and CYP1A1 and had the MPO- mutant allele. After combination study of the three gene-polymorphism, the subjects who were most different with the reference, i.e. had the mutant allele of the GSTP1 and CYP1A1 and homozygous wild type of the MPO, showed approximately 5-fold-higher risk for lung cancer than the reference (95% CI, 2.05-12.05). Therefore, our study suggests that the combination of the GSTP1, MPO, and CYP1A1 variations affects susceptibility to lung cancer.
Lung Cancer 2007 Aug
PMID:Combined effects of genetic polymorphisms in six selected genes on lung cancer susceptibility. 1742 72

Polymorphisms in metabolic genes encoding phase I and phase II enzymes are thought to modulate the risk of lung cancer via changes in enzymatic activity. Recently, the effect of these metabolic enzymes and their interaction with environmental factors has been studied in both smokers and also never-smokers, since never-smokers are a good model in which to study genetic susceptibility at low-dose carcinogen exposure. Here, we investigated the association of CYP1A1 Ile462Val, CYP1B1 Leu432Val, GSTP1 Ile105Val, MPO G-463A polymorphisms and lung cancer risk in never-smoking Korean women. In this case-control study of 213 lung cancer patients and 213 age-matched healthy controls, we found that carrying one variant allele of the CYP1A1 Ile462Val polymorphism was associated with a significantly decreased risk of lung adenocarcinoma (adjusted odds ratio (OR)=0.63; 95% confidence interval (CI), 0.41-0.99). Furthermore, the combination of risk genotypes of CYP1B1 Leu432Val with CYP1A1 Ile462Val was associated with the risk of lung adenocarcinoma (adjusted OR=2.16; 95% CI, 1.02-4.57) as well as overall lung cancer (adjusted OR=2.23; 95% CI 1.01-4.89). The polymorphisms of GSTP1 Ile105Val and MPO G-463A showed no significant association with lung cancer. Theses results suggest that the CYP1A1 Ile462Val polymorphism is associated with a reduced risk of lung adenocarcinoma in never-smoking Korean women, whereas specific combinations of variant genotypes for metabolic enzymes increase lung cancer risk considerably.
Lung Cancer 2008 Apr
PMID:CYP1B1, CYP1A1, MPO, and GSTP1 polymorphisms and lung cancer risk in never-smoking Korean women. 1798 Sep 33

Healthy rats had been treated for 2 or 6 weeks with 1.0 mL of 10(-8) and 10(-16) mg/mL of cisplatin. After 2 weeks of treatment, a significant increase in leukocyte and erythrocyte count and also in hematocrit was observed. Among leukocytes the number of neutrophils and eosinophils significantly increased. Biochemical analyses indicated a decrease in the glycogen content in the liver and kidneys after 2 weeks of treatment with low doses of cisplatin but at the end of the experiment (8th week of experiment) the stores of glycogen increased significantly. Biochemical analyses concerning the activity of some enzymes in the liver revealed a significant increase of peroxidase and acid phosphatase as well as catalase activities after 2 weeks of treatment. However, catalase was induced by a very low concentration of cisplatin, 10(-16) mg/mL. After the cessation of cisplatin treatment the activity of enzymes returned to normal values.Human lung carcinoma cell line A(549) (ECACC No 86012804) was also studied after treatment with the same doses of cisplatin and inhibition of its growth was observed. The results of these experiments strongly indicated that low doses of cisplatin could be stimulating for healthy cells but cytostatic for tumor cells.Possible mechanisms involved in the biological activity of very low cisplatin concentrations are discussed.
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PMID:The influence of very low doses of Cisplatin on tumor cell proliferation in vitro and on some hematological and enzymatic parameters of healthy rats. 1933 Jan 15

In recent years the frequency of nonsmokers among lung cancer patients has increased to 10% to 15%. The measles virus has rarely been evoked as an etiological agent in malignant tumors and its role in carcinogenesis remains doubtful. It has been suggested that measles virus phosphoprotein may inhibit ubiquitination of Pirh2, which has been reported to be overexpressed in lung carcinoma and is responsible for degrading the cell cycle regulator p53. The authors conducted a clinicopathological study of newly diagnosed patients with non-small cell lung carcinoma of all stages seen in a 10-year period. Immunohistochemical studies for measles virus antigens, p53, and Pirh2 were performed using the avidin-biotin peroxidase complex. The authors found expression of measles virus antigens in 54 of 65 cases of non-small cell lung carcinoma. This finding is associated with the older age of the patients and with expression of Pirh2. The presence of Pirh2 itself was associated with improved survival.
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PMID:Measles virus: evidence for association with lung cancer. 1989 23

Atypical adenomatous hyperplasia (AAH) is postulated to be the earliest morphologic precursor lesion in lung carcinogenesis. The epidermal growth factor receptor (EGFR), one of the members of the Erb-2 family of receptors, is commonly expressed in non-small cell lung carcinoma (NSCLC). A subset of the patients with NSCLC has molecular abnormalities in the EGFR gene, including missense mutations and deletions and/or abnormal gene copy numbers, and the relative importance of each of these for patient outcome is an area of great interest. Recent reports show that EGFR mutations are rare or absent in AAH and are rare in bronchioloalveolar carcinoma (BAC). However, the EGFR gene copy number status in AAH is unknown. In this study, we examined the EGFR gene copy number status in lung adenocarcinomas, synchronous AAH, and BAC in surgical pathology resection specimens. EGFR gene copy number was analyzed by chromogenic in situ hybridization (CISH) using formalin fixed paraffin embedded tissue sections and EGFR probes as recommended by the manufacturer. A known positive case of high-grade glioma was used as a positive control. The results indicate that four of eight adenocarcinomas (50%) had more than five EGFR signals per nucleus, suggesting a gain in copy number. Interestingly, in four of nine cases of AAH (44.4%) more than three EGFR signals per nucleus were noted, with scattered cells showing up to 6 signals per nucleus. In addition, in five of 12 cases of BAC (42%), more than three EGFR signals per nucleus were noted. In the remaining cases two to three intranuclear dot-like peroxidase positive signals were present consistent with non-amplification of the gene. Our study reveals an abnormal EGFR gene copy gain in several cases of AAH. In our cohort, the rate of EGFR gene copy abnormalities in AAH appears similar to BAC and lower than in lung adenocarcinomas. These findings suggest that although EGFR gene copy abnormalities may be an early event in lung carcinogenesis, they are associated with tumor progression to invasive cancer and highlight the complexity of tumor morphogenesis.
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PMID:Epidermal growth factor receptor gene amplification in atypical adenomatous hyperplasia of the lung. 2058 69

The reliable and sensitive detection of cancer-specific biomarkers is important for the diagnosis and treatment of cancer. Hence, detection of these biomarkers has to be reliably and rapidly performed in diverse settings. A limitation of the conventional biomarker-screening method of enzyme-linked immunosorbent assay (ELISA) is the employment of labile components, such as hydrogen peroxide and horseradish peroxidase. Previously, we reported that nanoceria is able to oxidize various colorimertic dyes at acidic pH, such as 3,3',5,5'-tetramethylbenzydine (TMB) and 2,2-azinobis-(3-ethylbenzothizoline-6-sulfonic acid) (AzBTS), and an assay was designed for screening the folate receptor. Herein, we show that the ability of nanoceria to oxidize a substrate can be tuned by modulating the pH. Results showed that nanoceria can oxidize the nonfluorescent substrate ampliflu, either to the very stable fluorescent product resorufin at pH 7.0 or to the nonfluorescent resazurin at pH 4.0. On the basis of these findings, we conjugated Protein G to immobilize antibodies on the surface of nanoceria, in order to detect the expression of prototypic cancer biomarkers at pH 7.0, such as the folate receptor and EpCAM. We found that within 3 h, nanoceria identified the expression of the folate receptor and EpCAM on lung carcinoma and breast adenocarcinoma cells, respectively. Traditional ELISA had a readout time of 15 h and a higher detection threshold, while requiring multiple washing steps. Considering these results and nanoceria's ability to oxidize ampliflu to its stable fluorescent product at neutral pH, the use of antibody-carrying nanoceria in the lab and point-of-care molecular diagnostics is anticipated.
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PMID:pH-tunable oxidase-like activity of cerium oxide nanoparticles achieving sensitive fluorigenic detection of cancer biomarkers at neutral pH. 2137 Aug 17


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