Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the first part of this study we have shown how the serum levels of four selected tumour markers, namely tissue polypeptide antigen (TPA), carcino-embryonic antigen (CEA), hyaluronic acid (HA) and ferritin, display patterns characteristic of mesothelioma (M) or bronchogenic carcinoma (BC) in asbestos-exposed workers, and we hypothesize that the differences in marker patterns correspond to differences in carcinogenesis mechanisms. In a preliminary study, we found these specific marker patterns in 5/19 exposed workers of whom only one demonstrated any radiological signs of disease. Thus these specific marker patterns may be early events, occurring long (possibly years) before the classical radiological signs of exposure to asbestos. Accordingly they afford an optimal opportunity for prevention which should be adapted to the carcinogenesis mechanism as it is revealed by the marker pattern; it is aimed at antagonizing free radical carcinogenesis in all persons with TPA levels in excess of 100 U/l or Ferritin in excess of 400 ng/ml, and at inhibiting chemical carcinogenesis in those having elevated CEA levels (over 3 ng/ml). The mechanisms involved in these inhibitory processes are described and discussed, as well as the practical implementations that proceed from them. A prevention trial is now being started among 300 active and retired workers of an asbestos-cement works in northern France; the design of the study is presented. This prevention programme should be maintained over many years and holds a strong potential for reducing the untoward effects of exposure to asbestos.
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PMID:Biomarker assessments in asbestos-exposed workers as indicators for selective prevention of mesothelioma or bronchogenic carcinoma: rationale and practical implementations. 146 74

Asbestos-associated malignancies are one of the major industrial hazards of recent decades and will continue to be so until beyond the end of the century. It has been estimated that, in the United States alone, there will be 131,200 cancer deaths as a result of asbestos exposure. At present the early lesions are detected radiologically, by which time intervention is no longer effective. The aim of this study was to test the value of a battery of serum biomarkers in the early detection of malignancy and in distinguishing between the early stages of mesothelioma and bronchogenic carcinoma. Many of the biomarkers had no discriminating value but on the basis of four such markers (namely TPA, CEA, HA and ferritin) it has been possible to distinguish between the late stages of the two malignancies and asbestosis. The results are discussed in terms of their possible application to the detection of early pre-malignant lesions in a screened population of asbestos-exposed persons, with the aim of attempting to prevent cancer death in such early detected cases.
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PMID:Biomarker assessments in asbestos-exposed workers as indicators for selective prevention of mesothelioma or bronchogenic carcinoma: rationale and practical implementations. 184 86

Ferritin was analysed with an immunoradiometric assay using anti-spleen ferritin antibodies, in pleural effusions (Pl) from 28 patients with malignant effusions (18 carcinoma, 10 mesothelioma), 15 patients with non-malignant exudative effusions of unknown aetiology, and from 12 patients with transudative effusions due to congestive cardiac failure. Geometric mean Pl-ferritin was 617 micrograms/l in carcinoma, 1301 micrograms/l in mesothelioma (p less than 0.01 against carcinoma), 931 micrograms/l in non-malignant exudates, and 178 micrograms/l in transudates (p less than 0.0001 against malignant and non-malignant exudates). There was no correlation between Pl-ferritin and Pl-protein, Pl-albumin or Pl-cell count. P1-ferritin displayed a wide overlap between the various groups, and was of no value in the discrimination between malignant and non-malignant exudates. In the differentiation between exudates and transudates, the diagnostic accuracy of Pl-ferritin was only slightly lower compared to Pl-protein and Pl-albumin. With the present method, analysis of Pl-ferritin appears to be of limited value in the routine diagnostic evaluation of pleural effusions.
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PMID:Diagnostic value of ferritin analysis in pleural effusions. 374 85

Four cases of mesothelioma were studied histologically and electron microscopically. One of them showed a pure epithelial type of the peritoneal origin, characterised by a tremendous production of hyaluronic acid. The other three tumors originated from the pleura revealed a histology of biphasic type mesothelioma, which showed an admixed tubular and fibrous pattern and consisted of small-sized cells with slight atypia. However, in some places of these tumors they showed considerable atypical features appearing like an anaplastic or squamoid carcinoma and/or spindle cell sarcoma. Hyaluronic acid was histologically demonstrated in the cytoplasmic vacuoles as well as in the luminal space surrounded by the tumor cells. Electron microscopically, varied numbers of microvilli and desmosome-like attachments were found on the surface of the tumor cells. Mitochondria were small and round. Well-developed rERs tended to encircle mitochondria and to dilate forming cisternae. Various amounts of microfilaments were found in the cytoplasm. The tumor cells which were rich in the latter two components, dilated rERs and microfilaments, resembled fibroblasts. Some tumor cells had phagosomes including dense and fine granules similar to ferritin, suggesting their phagocytotic activity. The hyaline matrix, common to the biphasic type tumor which was largely composed of dense collagenous tissues, was demonstrated to contain hyaluronic acid by histochemistry, and it was suggested that some secretory substances of the tumor cell may participate in composing the hyaline matrix to some extent.
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PMID:Mesothelioma. Histological and electron microscopic study of human cases. 608 95

Pleural effusion is a common diagnostic problem. The analysis of serum and body fluids for tumor markers has been intensively applied to clinical diagnosis. The aim of the present study was to determine the usefulness of simultaneous quantification of carbohydrate antigen 19.9, carbohydrate antigen 125, neuron specific enolase, mucinous-carcinoma-associated antigen, and ferritin in samples of pleural fluids in the malign pleural effusion and its differentiation from benign effusions. A total of 61 pleural effusions were collected from the patients, who were subjected either to simple needle aspiration or to tube drainage for the diagnosis of pleural effusion. Tumor markers were determined in benign patient groups with nonspecific pleurisy, tuberculous pleurisy, empyema, congestive heart failure and in malignancy groups consisting of adenocarcinoma, small cell lung carcinoma, mesothelioma, epidermoid lung cancer. The tumor markers CA-19.9, CA-125, NSE, and ferritin levels were quantified by the sandwich assay using the streptavidin technology of ELISA in an ES-300 Boehringer-Mannheim analyser. MCA was measured by employing a two-side solid phase EIA method. MCA measurements were done by the Cobas-Core. For all patients, the effusions correctly or incorrectly identified by the different procedures as being malignant or nonmalignant are defined as true positive, false positive, true negative, and false negative, the term 'positive' referring to histologically proven malignant pleural effusion while nonmalignant effusions are referred to as 'negative'. Therefore, sensitivity, specificity, positive predictive value, and negative predictive value were defined as diagnostic parameters. The cut-off values calculated were 352 U/ml for CA-125, 54 U/ml for CA-19.9, 555 for ferritin, 11.1 for MCA and 8.7 for NSE. In our study, the highest sensitivity is found to be MCA with 100%; specificity, CA-19.9 with 97%; PPV, CA-19.9 and MCA with 95% and NPV, MCA with 100%. Our data imply that the co-measurement of MCA+CA-19.9+CA-125 levels may further improve their diagnostic value in malignant pleural effusion compared with that of each tumour marker alone and may be useful in distinguishing malignant from benign pleural effusions.
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PMID:Diagnostic usefulness of tumour marker levels in pleural effusions of malignant and benign origin. 1095 62

Exposure to asbestos is a known etiological factor in malignant mesothelioma (MM). However, in vitro cell culture studies have provided paradoxical evidence that asbestos exposure to mesothelial cells causes cytotoxicity or apoptosis rather than malignant transformation. Although it has been shown that the iron associated with asbestos participates in the cell toxicity and probably MM pathogenesis via generation of reactive oxygen species (ROS), the molecular mechanisms largely remain unknown. Here, we demonstrate that ferritin heavy chain (FHC), a core subunit of iron-binding protein ferritin, works as an anti-apoptotic protein against toxic asbestos and oxidative stress in human mesothelial cells and MM cells. We found that FHC was induced in asbestos-exposed MeT-5A human mesothelial cells. The mesothelial cell line stably expressing FHC generated less amount of hydrogen peroxide (H2O2), one of the main ROS, after asbestos exposure and was more resistant to apoptosis induced by H2O2 compared with the cells transfected with the empty vector. Next, we investigated biological roles of FHC in human MM cell. We found that NCI-H2052, a human MM cell line, had a higher expression of endogenous FHC than MeT-5A and used the cell to address FHC function in MM. NCI-H2052 showed reduced H2O2 production and an apoptosis-resistant phenotype compared with MeT-5A. Suppression of the over-expressed FHC by using FHC small interfering RNA rendered the MM cells sensitive to apoptosis, suggesting the contribution of FHC to apoptosis resistance of the MM cells. Our findings highlight the potential role of FHC in the pathogenesis of asbestos-induced mesothelioma.
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PMID:Potential role of ferritin heavy chain in oxidative stress and apoptosis in human mesothelial and mesothelioma cells: implications for asbestos-induced oncogenesis. 1743 31

The role of asbestos bodies (and associated proteinacious coating) in asbestos associated diseases is not well understood. Currently employed methods of isolation of these bodies employ harsh chemicals that lead to destruction of their proteinacious coating. In this work a method was developed that enabled the purification of whole, integral, unmodified asbestos bodies (AB) by exploiting their magnetic properties. Albumin and ferritin were found to be the major proteins associated with AB isolated from lung tissue of mesothelioma patients. Magnetically isolated AB were shown to be cytotoxic and to activate free radical production from inflammatory cells at a higher extent than that induced by bodies obtained by chemical digestion. The finding that hypochlorite-treated AB induce DNA damage, while AB obtained by the method described in this article failed to do so, together with the differential behavior of these bodies toward inflammatory cells, suggests that native asbestos bodies should be used to investigate the pathogenetic role of these structures.
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PMID:A procedure for the isolation of asbestos bodies from lung tissue by exploiting their magnetic properties: a new approach to asbestos body study. 1757 37

While exposure to fibers and particles has been proposed to be associated with several different lung malignancies including mesothelioma, the mechanism for the carcinogenesis is not fully understood. Along with mineralogical observation, we have analyzed forty-four major and trace elements in extracted asbestos bodies (fibers and proteins attached to them) with coexisting fiber-free ferruginous protein bodies from extirpative lungs of individuals with malignant mesothelioma. These observations together with patients' characteristics suggest that inhaled iron-rich asbestos fibers and dust particles, and excess iron deposited by continuous cigarette smoking would induce ferruginous protein body formation resulting in ferritin aggregates in lung tissue. Chemical analysis of ferruginous protein bodies extracted from lung tissues reveals anomalously high concentrations of radioactive radium, reaching millions of times higher concentration than that of seawater. Continuous and prolonged internal exposure to hotspot ionizing radiation from radium and its daughter nuclides could cause strong and frequent DNA damage in lung tissue, initiate different types of tumour cells, including malignant mesothelioma cells, and may cause cancers.
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PMID:Accumulation of radium in ferruginous protein bodies formed in lung tissue: association of resulting radiation hotspots with malignant mesothelioma and other malignancies. 1964 23

Exposure to asbestos is a risk for malignant mesothelioma (MM) in humans. Among the commercially used types of asbestos (chrysotile, crocidolite, and amosite), the carcinogenicity of chrysotile is not fully appreciated. Here, we show that all three asbestos types similarly induced MM in the rat peritoneal cavity and that chrysotile caused the earliest mesothelioma development with a high fraction of sarcomatoid histology. The pathogenesis of chrysotile-induced mesothelial carcinogenesis was closely associated with iron overload: repeated administration of an iron chelator, nitrilotriacetic acid, which promotes the Fenton reaction, significantly reduced the period required for carcinogenesis; massive iron deposition was found in the peritoneal organs with high serum ferritin; and homozygous deletion of the CDKN2A/2B/ARF tumour suppressor genes, the most frequent genomic alteration in human MM and in iron-induced rodent carcinogenesis, was observed in 92.6% of the cases studied with array-based comparative genomic hybridization. The induced rat MM cells revealed high expression of mesoderm-specific transcription factors, Dlx5 and Hand1, and showed an iron regulatory profile of active iron uptake and utilization. These data indicate that chrysotile is a strong carcinogen when exposed to mesothelia, acting through the induction of local iron overload. Therefore, an intervention to remove local excess iron might be a strategy to prevent MM after asbestos exposure.
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PMID:Iron overload signature in chrysotile-induced malignant mesothelioma. 2286 72

Malignant pleural mesothelioma (MPM) is an aggressive cancer with poor prognosis. The development of MPM is frequently linked to inhalation of asbestos fibers. A genetic component of susceptibility to this disease is suggested by the observation that some individuals develop MPM following lower doses of asbestos exposure, whereas others exposed to higher quantities do not seem to be affected. This hypothesis is supported also by frequent reports of MPM familial clustering. Despite the widely recognized role of iron (Fe) in cellular asbestos-induced pulmonary toxicity, the role of the related gene polymorphisms in the etiology of MPM has apparently not been evaluated. Eighty-six single-nucleotide polymorphisms (SNPs) of 10 Fe-metabolism genes were examined by exploiting formalin-fixed paraffin-embedded postmortem samples from 77 patients who died due to MPM (designated AEM) and compared with 48 who were exposed to asbestos but from died in old age of cause other than asbestos (designated AENM). All subjects showed objective signs of asbestos exposure. Three SNPs, localized in the ferritin heavy polypeptide, transferrin, and hephaestin genes, whose frequencies were distributed differently in AEM and AENM populations, were identified. For ferritin and transferrin the C/C and the G/G genotypes, respectively, representing intronic polymorphisms, were significantly associated with protection against MPM and need to be considered as possible genetic markers of protection. Similarly, the C/C hephaestin SNP, a missense variation of this multicopper ferroxidase encoding gene, may be related, also functionally, with protection against MPM. In conclusion, it is proposed that three Fe metabolism-associated genes, significantly associated with protection against development of MPM, may serve as protective markers for this aggressive tumor.
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PMID:Iron signature in asbestos-induced malignant pleural mesothelioma: A population-based autopsy study. 2681 92


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