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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A clinicopathological analysis was carried out on 50 cases of lung cancer with silicosis diagnosed from April 1975 to March 1988. All patients were males and the age distribution ranged from 47 to 85 years with a mean of 63.5 at diagnosis. They had been exposed to silica in tunneling for 3 to 42 years, with an average of 15.1. Forty eight cases smoked. Histologically, squamous cell carcinoma was the most common with 29 cases, followed by 10 small cell carcinomas, 6 adenocarcinomas, 4 large cell carcinomas and one adenosquamous carcinoma. Thirty seven tumors were located in peripheral regions, mostly upper lobe or S6, while 13 tumors were in large bronchi. As the most common histological types of lung cancer with silicosis were squamous cell carcinoma and small cell carcinoma, some carcinogens might be involved in tumorigenesis. Silica alone is not considered to be a carcinogen, however, silica containing adsorbed polycyclic aromatic hydrocarbons from cigarette smoking or from industrial pyrolysis can act as a carcinogen or promoter.
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PMID:[Silicosis and lung cancer]. 255 44

Silica is not generally considered to be a carcinogen, however, occupations characterized by high exposure to crystalline silica have excessive rates of lung cancer mortality. Respiratory cancer excesses have been reported from North America and from Europe for the following dusty trades in which exposure to silica is a common factor: iron and steel foundry workers, steel casting workers, sand blasters, metal molders, non-uranium miners, and ceramic workers. These findings have been reinforced by two reports from the Swedish Pneumoconiosis Register and the Ontario Ministry of Labor indicating that silicotics have statistically significant risks of lung cancer mortality. Animal studies suggest that silica can be an initiating carcinogen or can act as a cocarcinogen or promoter when combined with benzo(a)pyrene. We propose three candidate hypotheses and two pathways for silicocarcinogenesis.
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PMID:Does occupational exposure to silica cause lung cancer? 630 Dec 70

The question whether silica is carcinogenic is not new, but there has been a resurgence of research over the last two decades with the use of more powerful epidemiological methodologies. There is sufficient evidence for the carcinogenicity of crystalline silica in animals. A large number of cohort and case-control studies consistently suggest a modest excess of lung cancer in workers with occupational silica exposure (relative risk less than 2). However, in many studies, the association is confounded by exposures to cigarette smoke, and environmental cocarcinogens like radon daughters, polyaromatic hydrocarbons and asbestos. The excess risk of lung cancer is more pronounced in workers with silicosis (relative risk of 2 to 4). Silica may act as a direct carcinogen or indirectly by the adsorption of cocarcinogens such as polyaromatic hydrocarbons from cigarette smoke or industrial pyrolysis products, and/or by impairing pulmonary clearance, thereby increasing the effective dose and duration of exposure to these carcinogens. Pulmonary fibrosis itself may be a precursor to the development of lung cancer.
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PMID:Silica and lung cancer: a continuing controversy. 784 60

Approximately three million workers in the United States are estimated to be exposed to silica, man-made mineral fibers, and asbestos. The lung is the primary target organ of concern. Each of these substances is composed predominantly of silicon and oxygen; asbestos and silica are crystalline, and asbestos and man-made mineral fibers are fibers. Man-made mineral fibers and asbestos are used as insulating agents, with the former having generally replaced the latter in recent years. Silica is used in foundries, pottery, and brick making, and is encountered by miners. A meta-analysis of 16 of the largest studies with well-documented silica exposure and low probability of confounding by other occupational exposures, indicates a relative risk (RR) of 1.3 (95 percent confidence interval [CI] = 1.2-1.4). Lung cancer risks are highest and most consistent for silicotics, who have received the highest doses (RR = 2.3, CI = 2.2-2.4, across 19 studies). The data for mineral fibers continue to support the International Association for Research on Cancer's 1988 judgment that mineral fibers are a possible human carcinogen (Group 2B). Recent epidemiologic studies provide little evidence for lung carcinogenicity for either glass wool or rock/slag wool. Ceramic fibers, a much less common exposure than glass wool and rock/slag wool, are of concern because of positive animal studies, but there are insufficient human data. Regarding asbestos, its carcinogenicity for the lung and mesothelium is well established. With regard to the controversy over chrysotile and mesothelioma, the data suggest chrysotile does cause mesothelioma, although it may be less potent than amphibole asbestos.
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PMID:Silica, asbestos, man-made mineral fibers, and cancer. 949 6

The relationship between crystalline silica and lung cancer has been the subject of many recent publications, conferences, and regulatory considerations. An influential, international body has determined that there was sufficient evidence to conclude that quartz and cristobalite are carcinogenic in humans. The present authors believe that the results of these studies are inconsistent and, when positive, only weakly positive. Other, methodologically strong, negative studies have not been considered, and several studies viewed as providing evidence supporting the carcinogenicity of silica have significant methodological weaknesses. Silica is not directly genotoxic and is a pulmonary carcinogen only in the rat, a species that seems to be inappropriate for assessing particulate carcinogenesis in humans. Data on humans demonstrate a lack of association between lung cancer and exposure to crystalline silica. Exposure-response relationships have generally not been found. Studies in which silicotic patients were not identified from compensation registries and in which enumeration was complete did not support a causal association between silicosis and lung cancer, which further argues against the carcinogenicity of crystalline silica.
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PMID:Silica, silicosis, and lung cancer: a response to a recent working group report. 1128 67

Chronic inflammation and production of DNA-damaging reactive oxygen species (ROS) may be involved in silica-induced lung cancer. Studies to date have largely focused on silica-induced production of ROS by lung phagocytes. In this study, we investigated the hypothesis that particulate silica (DQ12) can also induce elevations in intracellular ROS in a cancer-target cell type, i.e., human bronchial epithelial cells (BECs), via an indirect mechanism that involves ROS-inducing extracellular factor(s) that occur upon the interaction of silica with culture medium. The intracellular production of hydrogen peroxide (H(2)O(2)) in BECs was assessed by flow cytometry via monitoring dichlorofluorescein (DCF) fluorescence. Culture medium containing 10% human serum was incubated with silica particles in concentrations ranging from 10 to 50 microg/ml, and following incubation for 1 h and removal of the particles, the resulting supernatants were added to BECs. Silica-treated medium induced significant increases in intracellular H(2)O(2) after the medium had been treated with as little as 10 microg/ml of the particles. Further, the level of ROS increases in BECs in response to silica-treated medium was found to be virtually identical to that induced in cells that were directly treated with silica in suspension. Based on enzyme inhibitory studies, the mechanism for this increased generation of intracellular ROS appears to involve both mitochondrial respiration and a NAD(P)H oxidase-like system. Spectrofluorimetric experiments with the antioxidant enzymes superoxide dismutase and catalase showed that superoxide anions (O2*-) and H(2)O(2) are generated in silica-treated medium, but these ROS do not fully account for the induction of the intracellular ROS response. Iron, on the other hand, was found to be crucial to the process. Our collective results suggest silica-aqueous medium interactions can lead to the generation of factor(s) that induce the intracellular production of potentially DNA-damaging ROS in BECs in a manner that does not require direct particle-cell interactions.
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PMID:Silica-induced generation of extracellular factor(s) increases reactive oxygen species in human bronchial epithelial cells. 1201 87

It is estimated that about 4% of cancer mortality is attributed to occupational risk factors. Due to long latency periods it is often difficult to establish causal relationships. Thoracal cancer accounts for about 88% of all compensated occupational cancers in Germany. Most important exposures and diseases are asbestos-related lung cancer, asbestos-related malignant mesothelioma and radiation induced lung cancer (by Radon and its decay products). Lung cancer caused by nickel compounds, hexavalent chromium, arsenic and its compounds, coke oven gases and polycyclic aromatic hydrocarbons are rare. Silica-dust induced lung cancer can be compensated as occupational disease if a silicosis is present. In Germany every physician is obliged to notify a suspected occupational cancer as well as other occupational diseases.
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PMID:[Occupation related thoracic tumors]. 1510 80

Silica particle-associated inflammation is implicated in the genesis of several pulmonary diseases, including silicosis and lung cancer. In this study we investigated the role of phosphatidylcholine-specific phospholipase C (PC-PLC) in silica-stimulated induction of TNF-alpha and IL-1beta and how PC-PLC activity is regulated by silica in a rat alveolar macrophage model. We demonstrated that inhibition of PC-PLC, which was achieved with tricychodecan-9-yl-xanthate (D609), blocked the silica-stimulated induction of TNF-alpha and IL-1beta in alveolar macrophage, suggesting that PC-PLC is involved in the silica-associated inflammatory response. PC-PLC activity was increased significantly by silica exposure, and this could be inhibited by MnTBAP, which catalyzes both the dismutation of O2.- to O2 and H2O2 and the dismutation of H2O2 to O2 and H2O, revealing that PC-PLC activity is regulated in a redox-dependent manner. This is further confirmed by the finding that PC-PLC activity was increased by exogenous H2O2. The intracellular calcium chelator BAPTA blocked the H2O2-increased PC-PLC activity, while the calcium ionophore, A23187, enhanced PC-PLC activity. The data indicate that PC-PLC plays critical roles in the silica-associated inflammatory response and that PC-PLC is regulated through redox- and calcium-dependent manners in alveolar macrophages.
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PMID:Silica induces macrophage cytokines through phosphatidylcholine-specific phospholipase C with hydrogen peroxide. 1715 58

For pathologists, pneumologists, and occupational and environmental physicians it is relevant to know silica levels in lung tissue to better define limits of exposure. Environmental Scanning Electron Microscopy (ESEM) has been employed to detect silica particles and to compare silica levels in subjects with and without Lung Cancer (LC). We investigated 25 paraffin-embedded tissue samples of patients with LC adenocarcinoma, and 20 fresh samples of subjects without LC deceased for extra-pulmonary diseases. Silica levels were quantified considering the Number of Spots of silica particles (NS), and the Number of Positive Zones (NPZ) in which there was at least one spot. Levels of NS and NPZ were assessed with Poisson-type regression models, and in two samples of silica-exposed workers with LC the performance of models were evaluated. LC patients displayed higher silica levels, as compared to controls; smoking, age and gender had no significant effects on this relationship. Values of NS and NPZ for the exposed workers were in agreement with model estimates. The fitted model between NS and NPZ might be useful in evaluating new observations and in the development of threshold limit values of silica in biological tissues. ESEM is a rapid, simple and valid tool for the determination of silica levels in lung tissues.
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PMID:Detection of silica particles in lung tissue by environmental scanning electron microscopy. 1901 58

F(2)-isoprostanes are lipid peroxidation products of arachidonic acid in cell membrane and are reliable biomarkers for oxidative stress and cell membrane damage. Nanomaterials are widely used as raw materials in many industries and will have high potentials to be used in life science and medical fields. However, the human health impact of nanoparticles has caused people's great concern. Unfortunately, the mechanisms of cytotoxicity of many nanoparticles are not well defined. By measuring the levels of F(2)-isoprostane isomers in cultured cells after nanoparticle exposure, the information can be used to explain whether the cytotoxicity of nanoparticles is caused by lipid peroxidation and to investigate the biological pathways. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to separate and quantify F(2)-isoprostane isomers in nanoparticle-treated human lung cancer cells. Silica oxide (15nm) and other four metal oxide nanoparticles including Fe(2)O(3) (30nm), Al(2)O(3) (13nm), TiO(2) (40nm) and ZnO (70nm) are chosen in this study. The isotope forms of F(2)-isoprostane isomers, 8-iso-PGF(2alpha)-d(4) and PGF(2alpha)-d(4), were used as internal standard (IS). After human lung epithelial cells were exposed to different nanoparticles for 24h, F(2)-isoprostanes were extracted by a single step solid phase extraction with Oasis HLB cartridge. For the first time, six F(2)-isoprostane isomers were tentatively identified and quantified in human lung epithelial cells. The levels of F(2)-isoprostane isomers in the cells increased after the treatment with nanoparticles. For SiO(2), Fe(2)O(3), and ZnO nanoparticles, F(2)-isoprostane isomers increasing are consistent with nanoparticles' cytotoxicity data. For Al(2)O(3) and TiO(2) nanoparticles, F(2)-isoprostane isomers levels increased even before nanoparticles showed significant cytotoxicity at 100microg/mL concentration in 24h. Based on our best knowledge, this is the first study on the F(2)-isoprostane isomers corresponding to nanoparticles' exposure in vitro. Our study demonstrates that SiO(2) (15nm) nanoparticle showed the highest degree of lipid peroxidation and cell membrane damage among the studied nanoparticles.
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PMID:Quantification of F(2)-isoprostane isomers in cultured human lung epithelial cells after silica oxide and metal oxide nanoparticle treatment by liquid chromatography/tandem mass spectrometry. 2044 45


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