Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0037116 (silicosis)
 1,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Levels of 9 different oncoproteins and growth factors were assayed by immunoblotting with monoclonal antibodies in 91 serum samples collected between March 1983 and August 1987 from 46 pneumoconiosis patients (36 asbestosis, 10 silicosis) at high risk for the development of cancer. Follow-up of these patients through June 1991 showed that 18 had developed cancer (11 lung, 2 pleural mesothelioma, 2 transitional-cell carcinomas of the urinary bladder, 1 osteosarcoma, 1 non-Hodgkin's lymphoma, 1 adenocarcinoma of the gallbladder). Increased serum levels of ras oncogene-related protein (p21) were found in 7 of the 18 patients who developed cancer (5 lung, 2 pleural mesothelioma) versus 2 of the 28 patients without cancer, a statistically significant difference (p = 0.012). In addition, 6 of the 7 p21-positive cancer cases had positive serum samples prior to clinical diagnosis of disease (average = 16.3 months, range = 3-26 months prior to diagnosis), suggesting that elevated serum p21 levels may be a useful marker for earlier detection in a significant percentage of respiratory malignancies. Finally, elevated serum levels of PDGF-related protein were detected significantly more frequently in advanced pneumoconiosis cases (ILO radiographic classification of 2/1 or greater) than in less advanced cases (80% vs. 41.9%; p = 0.016), and there was a tendency for these PDGF-positive patients to have progression of their disease (68.2% vs. 41.7%; p = 0.065), suggesting that elevated serum PDGF levels may be a marker for the development of severe and progressive pneumoconioses.
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PMID:Serum oncoproteins and growth factors in asbestosis and silicosis patients. 131 98

Crystalline silica (quartz) induces silicosis and associated peripheral lung carcinomas in rats. The role and pattern of expression of transforming growth factor (TGF)-beta1/beta2 mRNA transcripts were investigated in the fetal rat lung epithelial cell line FRLE, its neoplastic transformants and derived tumors in athymic nude mice. FRLE cells, treated with 100 microgram/cm2 of quartz in serum-free medium, gave rise to phenotypically altered, tumorigenic cells. Quartz-treated, transformed and tumorigenic cells, subcultured directly (QTT-C1) or after growth in soft agar (QTT-C2), formed tumors in athymic nude mice (QTT-T1). Cells subcultured from the tumors (QTT-T1C) were also tumorigenic in nude mice (QTT-T2). QTT-T1 and QTT-T2 tumors were poorly differentiated carcinomas with variable amounts of extracellular matrix-associated TGF-beta1 and desmoplasia. For comparison, a tumorigenic cell line derived from FRLE cells transformed with a mutated K-ras plasmid (RT-C1) and cells subcultured from a corresponding nude mouse tumor (RT-T1) and designated RT-T1C were used. Whereas TGF-beta1 and TGF-beta2 inhibited the growth of QTT-T1C and FRLE cells in a dose-dependent fashion, RT-T1C cells, containing an activated ras gene, were relatively unaffected. TGF-beta1 and TGF-beta2 mRNAs were expressed at higher levels in QTT-T1C cells than in FRLE and TR-T1C cells, and there was an increase in TGF-beta type II receptor (TGR-betaR) mRNA expression in QTT-T1C and RT-T1C cells compared to FRLE cells. Carcinomas in nude mice derived from QTT and RT cells and silicosis-associated lung carcinomas induced in rats by intra-tracheal quartz did not express either active or latent forms of TGF-beta1 protein on immunohistochemistry. The disparity between TGF-beta1 mRNA and TGF-beta1 protein expression in QTT tumors may be due to post-transcriptional regulation of TGF-beta1.
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PMID:Transforming growth factor beta expression and transformation of rat lung epithelial cells by crystalline silica (quartz). 859 16

The pathogenesis of mesenchymal and epithelial lung reactions was studied after a single intratracheal instillation of quartz into rats. Relationships between transforming growth factor beta1 (TGF-beta1) and the ras and p53 genes were investigated in silicosis and associated lung cancer. Immunohistochemical reactivity to mature TGF-beta1 was localized intracellularly in fibroblasts and macrophages at the periphery of silicotic granulomas and in stroma adjacent to hyperplastic alveolar type II cells and extracellularly in connective tissue matrix adjacent to hyperplastic alveolar type II cells. TGF-beta1 precursor was localized intracellularly in hyperplastic alveolar type II cells adjacent to granulomas and in the cells of adenomas, but not in carcinomas. Hematite-treated controls showed no reactivity to TGF-beta1. Immunohistochemical localization of pan-reactive p21 ras protein in quartz-treated rat lungs was increased in hyperplastic alveolar type II cells adjacent to granulomas, but not in adenomas and carcinomas. Foci of nuclear immunoreactivity to p53 protein were observed in 25% of the carcinomas.
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PMID:Transforming growth factor beta1, ras and p53 in silica-induced fibrogenesis and carcinogenesis. 892 85

It is well established that patients with silicosis are at high risk for lung cancer; however, it is difficult to detect lung cancer by chest radiography during follow-up treatment of patients with silicosis because of preexisting diffuse pulmonary shadows. The purpose of this study is to evaluate the usefulness of detection of serum DNA methylation for early detection of lung cancer in silicosis. Serum samples from healthy controls (n = 20) and silicosis patients with (n = 11) and without (n = 67) lung cancer were tested for aberrant hypermethylation at the promoters of the DNA repair gene O(6)-methylguanine-DNA methyltransferase (MGMT), p16(INK4a), ras association domain family 1A (RASSF1A), the apoptosis-related gene death-associated protein kinase (DAPK) and retinoic acid receptor beta (RARbeta) by methylation-specific polymerase chain reaction. Aberrant promoter methylation in at least one of five tumor suppressor genes was detected more frequently in the serum DNA of silicosis patients with lung cancer than in that of patients without it (P = 0.006). Furthermore, the odds ratio of having lung cancer was 9.77 (P = 0.009) for those silicosis patients with methylation of at least one gene. Extended exposure to silica (>30 years) was correlated with an increased methylation frequency (P = 0.017); however, methylation status did not correlate with age, smoking history or radiographic findings of silicosis. These results suggest that testing for aberrant promoter methylation of tumor suppressor genes using serum DNA may facilitate early detection of lung cancer in patients with silicosis.
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PMID:Aberrant promoter hypermethylation in serum DNA from patients with silicosis. 1863 57