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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is apparent that progress is being made in the diagnosis of mesothelioma on the basis of morphological studies. It is also obvious that in almost every area uncertainties and deficiencies still exist. The significance of fibrous substances other than asbestos in the etiology of the various lesions is a field to be explored. The role of pulmonary fibrosis in the pathogenesis of carcinoma of the lung in those exposed to asbestos remains ill-defined. Morphological study of mesothelioma variants and imitators must continue. The accumulation of further ultrastructural data is desirable. Attempts should be made to clarify certain ambiguities in histochemical features. Recently devised staining methods and chemical, immunochemical and immunological diagnostic techniques must be further tried to establish their reliability. The utility of mesothelioma diagnostic panels seems fairly widely accepted, but persistent efforts to reconcile observer variation and to reduce subjectivity are necessary. The pursuit of immunological testing has both theoretical and practical importance. A method for the detection of susceptible persons has long been sought. The value of electron microscopy in the investigation of fibres in relation to carcinogenesis is manifest. Data is accumulating regarding fibre quantity, type and dimensions in relation to the various related lesions. The predominant role of amphiboles in the formation of asbestos bodies appears to be established. Further studies of regional distribution of fibres with their types and sizes in the lung and pleura would seem essential. Whether this will alter the concepts of the significance of exposure as indicated by analysis of the parenchymal component alone is an important question.
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PMID:Recent advances and perspectives relevant to the pathology of asbestos-related diseases in man. 701 57

The present series of experiments was carried out in order to see what role pre-existing localized fibrosis plays in carcinogenesis of the lung. Hemorrhagic infarction was produced in the lung of 180 male Wistar rats by injecting 0.05 ml of hexachlorotetrafluorobutane into the tail vein. This resulted in localized fibrosis in the lung 3 months later. One hundred and fiften rats were alive 3 months after administration of the chemical. Of these animals, 30 were given no further treatment (control). The remaining 85 rats were given intratracheal instillation of 0.2 microCi of polonium-210 once a week, a total of 15 times. It was subsequently found that lung carcinoma was induced in close proximity to the localized pulmonary fibrosis in 3 of 26 rats (11.5%) during the period from completion of the 15 weekly administrations of polonium-210 until the end of this experiment (21 months after the 1st instillation of polonium-210). Polonium-210 was found to be deposited in the fibrous thickening of the alveolus around the subpleural fibrotic lesion, bronchial epithelium, and peribronchial lymph apparati at the initial period of administration of polonium-210, but during the period of pulmonary carcinogenesis, it was deposited in the localized fibrotic lesion in the lung and in a few cancer cells. This suggests that polonium-210 deposited in the pulmonary fibrotic lesion remains there over a long period of time, indicating a reduced clearance ability at this site.
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PMID:An experimental study on carcinogenesis related to localized fibrosis in the lung. 741 73

The carcinogenic effects of crystalline silica in rat lungs were extensively demonstrated by many experimental long-term studies, showing a marked predominance for adenocarcinomas originating from alveolar type II cells and associated with areas of pulmonary fibrosis (silicosis). In contrast with its effects in rats, silica did not induce alveolar type II hyperplasia and lung tumors in mice and hamsters, pointing to a critical role for host factors. Using these animal models, we are investigating the role of cytokines and other cellular mediators on the proliferation of alveolar type II cells. Immunohistochemical localization of TGF-beta 1 precursor in alveolar type II cells adjacent to silicotic granulomas was shown to occur in rats, but not in mice, and hamsters, suggesting a pathogenetic role for this regulatory growth factor. Recent investigations in our laboratory on the biologic mechanisms of crystalline silica included determination of anionic sites on crystalline silica surfaces by binding of the cationic dye Janus Green B; binding of crystalline silica to DNA, demonstrated by infrared spectrometry; production of oxygen radicals by crystalline silica in aqueous media; induction of DNA strand breakage and base oxidation in vitro and its potentiation by superoxide dismutase and by hydrogen peroxide; and induction by crystalline silica of neoplastic transformation and chromosomal damage in cells in culture. On the basis of these in vitro studies, we propose that DNA binding to crystalline silica surfaces may be important in silica carcinogenesis by anchoring DNA close to sites of oxygen radical production on the silica surface, so that the oxygen radicals are produced within a few A from their target DNA nucleotides.
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PMID:Mechanisms of carcinogenesis by crystalline silica in relation to oxygen radicals. 770 91

It is generally accepted that asbestos exposure causes pulmonary fibrosis and carcinogenesis. Several studies have suggested that TNF alpha is produced principally by mononuclear phagocytes and that it may play a role in inflammation, fibrosis and anti-tumor activity. We studied TNF alpha production by alveolar macrophages and the TNF alpha concentration in bronchoalveolar lavage fluid harvested from asbestos-exposed subjects and healthy controls. TNF alpha production by alveolar macrophages was significantly higher in the asbestos-exposed subjects than in healthy controls (3696 +/- 1606, 1938 +/- 753 pg/ml; p < 0.01). The period from first exposure correlated inversely with TNF alpha production (r = -0.6; p < 0.05). The TNF alpha concentration in bronchoalveolar lavage fluid was also significantly higher in the asbestos-exposed subjects than in healthy controls. These results suggest that abnormal TNF alpha production by alveolar macrophages may be related to fibrosis and carcinogenesis due to asbestos.
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PMID:[Tumor necrosis factor alpha in bronchoalveolar lavage fluid and its production by alveolar macrophages with asbestos exposure]. 818 39

Hepatic silicosis, cirrhosis, liver cell adenoma, and carcinomas developed in nude mice (NCr-Nu) given quartz by the subcutaneous and intraperitoneal routes. Syrian golden hamsters (15:16 EHS:cr) given quartz by both routes developed extensive fibrosis and cirrhosis and had higher morbidity and mortality rates after 3 months. Crystalline silica (quartz) induces fibrosis, adenomas, and carcinomas in the lungs of Fisher 344 rats, but certain strains of mice and hamsters are resistant to quartz-induced pulmonary carcinogenesis. Pulmonary fibrosis, however, is minimal in mice and absent in hamsters who received quartz intratracheally. To determine whether species differences are due to organ-specific rather than species-specific factors, susceptibility of the liver to quartz toxicity was investigated in nude mice and hamsters. The present study shows that the differential manifestations of quartz toxicity by these rodent species are dependent on factors that are organ-specific rather than host-specific. At 3 months, hepatocytes in mice were immunostained with intracellular transforming growth factor (TGF) beta 1 (LC 1-30) but not with TGF-beta 1 latency-associated peptide (LAP) protein (266-278); at 12 months, hepatocytes were immunostained with TGF-beta 1 LAP (266-278) but not with TGF-beta 1 (LC1-30). The hepatocytes of hamsters at 3 months showed immunoreactivities to TGF-beta 1 LAP (266-278) and TGF-beta 1 (LC1-30); immunostaining to TGF-beta 1 (LC1-30) was detected in nonparenchymal cells. Extracellular TGF-beta 1 (CC1-30) was detected in the silicotic granulomas and fibrous tissue in livers of both species. Quartz-induced liver carcinoma did not express TGF-beta 1 LAP (266-278) and LC (1-30) proteins, but these were detected in the cells of the adenoma in the same liver. Control animals showed no hepatic lesions nor immunoreactivity to TGF-beta 1. The spatial and temporal patterns of expression of TGF-beta 1, TGF-beta 2, TGF-beta receptor type II messenger RNAs (mRNAs), and TGF-beta 1 proteins in the different hepatic lesions suggests that TGF-beta isoforms may play a role in the pathogenesis of quartz-induced fibrosis, cirrhosis, liver cell adenoma, and carcinoma.
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PMID:Hepatic silicosis, cirrhosis, and liver tumors in mice and hamsters: studies of transforming growth factor beta expression. 862 Nov 63

Asbestos fibers have genotoxic effects and are a potential carcinogenic hazard to occupationally exposed workers. The ability of inhaled asbestos fibers to induce the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the DNA of white blood cells (WBC) of workers highly exposed at the workplace has been studied. The 8-OHdG adduct level of asbestos-exposed workers was significantly increased (p<0.001) compared to that in the control group in all three years of the study. Asbestos-exposed individuals showed a mean value of 2.61+/-0.91 8-OHdG/10(5) dG (median 2.49, n=496) in 1994-1995, 2.96+/-1.10 8-OHdG/10(5) dG (median 2.76, n=437) in 1995-1996 and 2.55+/-0.56 8-OHdG/10(5) dG (median 2.53, n=447) in 1996-1997. For the control subjects, a mean of 1.52+/-0.39 (median 1.51, n=214) was determined. The results indicate that human DNA samples from exposed individuals contain between 1.7 times and twice the level of oxidative damage relative to that found in control samples in all 3 years of the study. The studies presented here show that asbestos exposure can result in oxidative DNA damage. Our data confirm that oxidative DNA damage occurs in the WBC of workers highly exposed to asbestos fibers, thus supporting the hypothesis that asbestos fibers damage cells through an oxidative mechanism. These in vivo findings underline the importance of oxidative damage in asbestos-induced carcinogenesis and highlight the need for exploring the molecular basis of asbestos-induced diseases, and for more effective diagnosis, prevention and therapy of mesothelioma, lung cancer and pulmonary fibrosis. In addition, preventive and therapeutic approaches using antioxidants may be relevant.
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PMID:Levels of 8-hydroxy-2'-deoxyguanosine in DNA of white blood cells from workers highly exposed to asbestos in Germany. 1088 96

The association of malignancy with collagen diseases has been a focus of interest. Especially, relation between dermatomyositis and malignancy is well-recognized. I reviewed here about the coexistence of SSc and malignancy in literature. I would like to raise four points as characteristics of the relationship. (1) Special attention should be paid to the patients who is late-onset, with advanced skin sclerosis (ex. Barnett III type) and male. (2) There are three generalized mechanisms of the association. The first is the predisposition of the malignancy on the basis of organ fibrosis, such as pulmonary fibrosis and lung cancer. The second is the nature of paraneoplastic syndrome. Lastly, immunological derangement inherent to SSc might cause carcinogenesis. (3) It has been documented that the interval of the onsets of SSc and breast cancer is extremely short. (4) Longstanding reflux esophagitis and Barrett's esophagus with SSc is suspected to predispose to esophageal carcinoma.
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PMID:[Systemic sclerosis (scleroderma) and malignancy]. 1567 92

Transforming growth factor-beta (TGF-beta) proteins and their antagonists have entered clinical trials. These multi-functional regulators of cell growth and differentiation induce extracellular matrix proteins and suppress the immune system making TGF-betas useful in treatment of wounds with impaired healing, mucositis, fractures, ischemia-reperfusion injuries, and autoimmune disease. In diseases such as keloids, glomerulonephritis and pulmonary fibrosis, excessive expression of TGF-beta has been implicated as being responsible for accumulation of detrimental scar tissue. In these conditions, agents that block TGF-beta have prevented or reversed disease. Similarly, in carcinogenesis, blocking TGF-beta activity may be valuable in stimulating an immune response towards metastasis. As these blocking agents receive approval, we will likely have new therapies for previously recalcitrant diseases.
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PMID:Medical applications of transforming growth factor-beta. 1593 Dec 80

This articles aims to review epidemiological aspects related to lung cancer (LC). The risk factors for LC are external factors and host factors. One can note an increasing incidence of LC in women, related to considerable increase of smoking habits in this group. Mortality by LC is related to number of cigarettes smoked daily and how deep the smoke is inhaled. Air pollution and occupational factors increase the LC risk among industrial workers. Pre-existing lung diseases (pulmonary fibrosis, COPD or bronchial asthma) can increase the risk for LC. There are also genetic factors involved in LC. Carcinogenesis is a multi-stage process. In each stage exogenous and endogenous factors are involved, determining mutations on the dominant oncogenes and on genes suppressing tumor appearance.
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PMID:[Epidemiology of lung cancer]. 1706 13

Regulated generation of reactive oxygen species (ROS) is primarily accomplished by NADPH oxidases (Nox). Nox1 to Nox4 form a membrane-associated heterodimer with p22(phox), creating the docking site for assembly of the activated oxidase. Signaling specificity is achieved by interaction with a complex network of cytosolic components. Nox4, an oxidase linked to cardiovascular disease, carcinogenesis, and pulmonary fibrosis, deviates from this model by displaying constitutive H(2)O(2) production without requiring known regulators. Extensive Nox4/Nox2 chimera screening was initiated to pinpoint structural motifs essential for ROS generation and Nox subcellular localization. In summary, a matching B loop was crucial for catalytic activity of both Nox enzymes. Substitution of the carboxyl terminus was sufficient for converting Nox4 into a phorbol myristate acetate (PMA)-inducible phenotype, while Nox2-based chimeras never gained constitutive activity. Changing the Nox2 but not the Nox4 amino terminus abolished ROS generation. The unique heterodimerization of a functional Nox4/p22(phox) Y121H complex was dependent on the D loop. Nox4, Nox2, and functional Nox chimeras translocated to the plasma membrane. Cell surface localization of Nox4 or PMA-inducible Nox4 did not correlate with O(2)(-) generation. In contrast, Nox4 released H(2)O(2) and promoted cell migration. Our work provides insights into Nox structure, regulation, and ROS output that will aid inhibitor design.
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PMID:Structural insights into Nox4 and Nox2: motifs involved in function and cellular localization. 1999 13


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