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

This study evaluates the cell surface expression of urokinase-type plasminogen activator (u-PA) and the capacity to bind exogenous urokinase as possible parameters for the distinction of various types of human lung tumours. Twelve different tumour cell lines including four small cell carcinoma, two large cell carcinoma, three squamous cell carcinoma, one adenocarcinoma and two mesothelioma cell lines of lung origin were investigated. Surface expression of endogenous u-PA was determined in a cellular radioimmunoassay (CRIA) using the u-PA-specific monoclonal antibody 98/6. To estimate additional u-PA binding capacity, exogenous two-chain, 54 kDa u-PA was employed in the CRIA. The influence of phorbol ester (PMA) treatment on expression and binding of these molecules was studied. Three different groups of lung tumour cell lines could be distinguished according to their expression of u-PA and u-PA-binding ability: (i) non small cell lung carcinoma (NSCLC) cell lines of squamous cell carcinoma/adenocarcinoma origin expressed small amounts of u-PA and bound little u-PA. Large cell carcinoma cell lines expressed high amounts of u-PA and bound large amounts of u-PA. In general, expression of u-PA and u-PA binding was enhanced after PMA treatment. (ii) Mesothelioma cell lines did not express u-PA, but were able to bind u-PA. (iii) Small cell carcinoma (SCLC) lines were devoid of surface-expressed u-PA and could not bind u-PA, both under untreated and PMA-treated conditions. It could thus be demonstrated that these three groups of lung tumour cell lines differ in their ability to express u-PA and to bind external u-PA. This may reflect the different in vivo growth behaviour and origin of the respective tumour groups.
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PMID:Three types of human lung tumour cell lines can be distinguished according to surface expression of endogenous urokinase and their capacity to bind exogenous urokinase. 131 Feb 52

Occupationally induced lung cancer and mesothelioma have long been attributed to asbestos and moreover, several epidemiological studies have indicated a co-carcinogenic effect of cigarette smoking on the incidence of lung cancer in asbestos workers. The aim of the present study was to investigate the co-carcinogenic effects of asbestos and other carcinogens with emphasis placed on determining the effects of cigarette smoking on the incidence of asbestos induced carcinomas. Doses of 15 mg of chrysotile asbestos were administered intratracheally to Wistar rats alone and in conjunction with N-bis(hydroxypropyl)nitrosamine (DHPN) and/or cigarette smoking. DHPN at dose of 1 g/kg/B.W. was injected three times intraperitoneally, and the subject animals were exposed to smoke from 10 cigarettes per day, six days a week, for their entire life span. As a result, lung carcinomas were induced in one out of the 31 rats receiving only asbestos. Lung tumors were induced at a much higher incidence in the groups receiving DHPN alone and in conjunction with asbestos: of the 37 rats treated with DHPN alone 19 (51.4%) developed lung tumors, whereas those receiving asbestos as well showed an incidence of 68.4% (23/38) of carcinomas. The development of lung carcinomas (including adenocarcinomas, epidermoid carcinomas, anaplastic carcinomas, and combined carcinomas) was seen in 8 (21.6%) out of the 37 rats receiving DHPN alone and in 23 (60.5%) out of the 38 rats receiving asbestos as well. The incidence of lung carcinoma was significantly increased in combined treatment with asbestos than DHPN alone. In the group receiving asbestos in combination with cigarette smoke, 4 (13.8%) out of the 29 rats developed lung carcinomas, but these carcinomas were more common than in the group receiving only asbestos. Moreover, in the group administered asbestos, DHPN and smoking combined, lung tumors developed in 18 (62.1%) out of the 29, 15 (51.7%) of which proved to be malignant. Mesothelioma (pleura) was induced in three groups in the following combinations: DHPN plus asbestos, 8/38 (21.1%); smoking plus asbestos, 2/29 (6.9%); and smoking, DHPN and asbestos, 4/29 (13.8%). These tumors were extensively located, that is, on the parietal pleura, visceral pleura, epicardium and diaphragm surface. However, mesothelioma was not induced by asbestos alone nor by DHPN alone. Carcinogenicity of asbestos for pleural tumors was significantly promoted by combined treatment with DHPN to an extent greater than DHPN alone. It should be noted that asbestos plus smoking resulted in a higher incidence of mesothelioma than asbestos alone.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Effect of cigarette smoking and/or N-bis(2-hydroxypropyl)nitrosamine (DHPN) on the development of lung and pleural tumors in rats induced by administration of asbestos]. 206 37

Human lung tumor cell lines established from the major histological types of lung cancer were examined by immunofluorescent staining techniques for their patterns of intermediate filament (keratin, vimentin, and neurofilament triplet protein) expression. All cell lines examined, both small cell lung carcinoma (SCLC) and non-SCLC (squamous cell carcinoma, adenocarcinoma, large cell carcinoma, and mesothelioma) contained keratin, consistent with their epithelial derivation. These lung carcinoma cell lines also expressed vimentin, the characteristic intermediate filament of mesenchymal cells in vivo. In light of the proposed neuroectodermal origin of SCLC, cell lines were also studied for neurofilament expression. Two of four SCLC tumor cell lines, as well as non-SCLC cell lines, showed no reactivity with antibodies to neurofilament triplet protein. Two of the SCLC cell lines stained weakly with anti-neurofilament antibody. Examination of specific keratin patterns in human lung tumor cell lines by selective immunoprecipitation with keratin antiserum and sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that small-sized keratin proteins (Mr 44,000 to 52,000) were present in cell lines derived from SCLC and non-SCLC types of lung cancer. Tumor cell lines exhibiting squamous differentiation by light microscopic criteria (i.e., intracellular keratin, intercellular bridging, "pearl" formation, and/or individual cell keratinization) also displayed a preponderance of intermediate-sized keratins (Mr 57,000 and 59,000) and exhibited another feature of terminal keratinocyte differentiation (cross-linked envelope formation). Mesothelioma cell lines had varying keratin profiles. The presence of keratin proteins in all SCLC cell lines examined argues against a neuroectodermal origin for these tumors and is consistent with the notion that these tumors arise from a common bronchial "stem cell," similar to that from which other types of bronchogenic carcinomas arise.
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PMID:Intermediate filament and cross-linked envelope expression in human lung tumor cell lines. 257 76

The diagnostic value of a recently developed polyclonal antibody to mesothelial cells has been tested by means of an immunoperoxidase technique to differentiate mesothelioma from lung carcinoma. All 16 unequivocal mesotheliomas reacted with the antibody, whereas none of the 31 lung carcinomas did, thus confirming the high specificity and the high sensitivity of the antibody. Furthermore, 20 cases of serous membranes tumor, in which major diagnostic disagreement was present when reviewed by the members of the Commission of the European Communities Mesothelioma Panel, were examined. Sixteen of the 20 cases were immunoreactive to the antimesothelial cell antibody, thus establishing their mesothelial origin. Given conventionally fixed and processed tissues, it appears that this antibody may be used as an appropriate diagnostic adjunct to increase the accuracy of the diagnosis of mesothelioma.
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PMID:Verification of the histologic diagnosis of malignant mesothelioma in relation to the binding of an antimesothelial cell antibody. 264 6

Asbestos-associated malignancies have received significant attention in the lay and medical literature because of the increasing frequency of two asbestos-associated tumors, lung carcinoma and mesothelioma; the wide distribution of asbestos; its status as a prototype environmental carcinogen; and the many recent legal compensation proceedings, for which medical testimony has been required. The understanding of asbestos-associated carcinogenesis has increased through study of animal models, human epidemiology, and, recently, the application of modern molecular biological techniques. However, the detailed mechanisms of carcinogenesis remain unknown. A wide variety of malignancies have been associated with asbestos, although the strongest evidence for a causal association is confined to lung cancer and mesothelioma. Epidemiological studies have provided evidence that both the type of asbestos fiber and the industry in which the exposure occurs may affect the rates of asbestos-associated cancers. It has been shown that asbestos exerts a carcinogenic effect independent of exposure to cigarette smoking that, for lung cancers, is synergistically enhanced by smoking. Other questions remain controversial, such as whether pulmonary fibrosis necessarily precedes asbestos-associated lung cancer and whether some threshold level of exposure to asbestos (including low-dose exposures that may occur in asbestos-associated public buildings) may be safe. Mesothelioma, the most closely asbestos-associated malignancy, has a dismal natural history and has been highly resistant to therapy. However, investigational multi-modality therapy may offer benefit to some patients. A description of the processes through which compensation claims for asbestos-associated malignancies are evaluated illustrates for physicians the legal system's approach to possible injury from toxic substances. The differences between scientific and legal reasoning about the causes of diseases with long latency, especially when they are imputed to toxic exposures are substantial, and may impede the application of toxicological evidence to legal disputes.
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PMID:Asbestos-related malignancy. 306 83

To examine how fiber type, fiber concentration, and fiber size correlate with the presence of asbestos-related disease in workers with heavy chrysotile exposure, we used analytic electron microscopy to determine the fiber content of the lungs of 94 long-term chrysotile miners and millers from the region of Thetford Mines, Quebec. Mesothelioma, airway fibrosis, and asbestosis were strongly associated with a high tremolite fiber concentration, whereas pleural plaques and carcinoma of the lung showed no relationship to tremolite burden. Similar patterns were seen for chrysotile concentration, but further analysis suggested that the apparent effect of chrysotile probably was due to the high correlation (r = 0.70) between chrysotile and tremolite concentration rather than to an independent effect of chrysotile. Increased tremolite-chrysotile ratio was marginally associated with the presence of pleural plaques but not with any other disease. Very high correlations (r > 0.90) between the concentrations of fibers longer or shorter than 8 microns prevented assessment of the effects of long compared with short fibers. Pleural plaques were very strongly associated with higher mean tremolite fiber aspect ratios, but no differences in mean fiber size (length, width, aspect ratio, surface area, and mass) were seen for any other disease. Total fiber size measures (total fiber length/g and others) showed differences similar to fiber concentration for mesothelioma, airways fibrosis, and asbestosis, but no one measure was clearly better than another or better than fiber concentration. We conclude that, in this population of heavily exposed chrysotile miners and millers, the presence of airways fibrosis and asbestosis and, probably, mesothelioma reflects high tremolite burden.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fiber burden and patterns of asbestos-related disease in chrysotile miners and millers. 839 Dec 35

The treatment of diffuse malignant pleural mesothelioma (DMPM) remains grim. Neither surgery, radiotherapy nor chemotherapy can be considered as a standard therapy. Immunotherapy with interferon (IFN) in combination with chemotherapy may be an interesting new approach. In 13 consecutive patients with DMPM, we used a weekly combination of cisplatin (CDDP) (60 mg/m2; day 2) and IFN alpha 2a (6 MU/day; days 1-4) in a protocol of two cycles of 4 weeks on/4 weeks off followed by 3 weeks on/3 weeks off. Total treatment duration was thus 25 weeks. In responders, IFN as maintenance monotherapy was continued for a further 6 months. There were nine males and four females with an average age of 65.3 years (range 51-72 years). Eleven had epithelial, one had mixed and one had a sarcomatoid form of DMPM. Five patients were classified as stage II, six as stage III and two as stage IV, as per the International Mesothelioma Interest Group. Thirty-five cycles were administered with a median of three cycles/patient (range 0.75-4). The median total cumulative dose of CDDP was 596 mg/m2 (range 114-861) and that of IFN alpha 2a was 264 MU (range 72-336). Four patients received IFN maintenance therapy, one for 3 months and three for 6 months. One patient had a complete response, four had a partial response, six had a stable disease and the disease progressed in one. One patient was non evaluable for response. All patients were assessable for toxicity. Hematological toxicity was the most frequently observed but was manageable (grade 3 anemia in five patients, grade 3 thrombocytopenia in three patients, grade 3 neutropenia in five patients). Grade 1 renal toxicity was observed in six patients, grade 2-3 asthenia in six patients and an average 5-kg weight loss was noted in nine patients. In conclusion, systemic combination of CDDP and IFN alpha 2a in large doses is effective at the expense of non-negligible toxicity.
Lung Cancer 1998 Nov
PMID:Weekly systemic combination of cisplatin and interferon alpha 2a in diffuse malignant pleural mesothelioma. 1002 19

One-hundred and twenty-one cases of malignant pleural mesothelioma (MPM) seen between 1986 and 1999 at the authors' Institution were reviewed. Histotype was epithelial in 88 patients (73%), sarcomatous in 21 (17%) and mixed in 12 (10%). Ninety-one patients received a treatment (38 palliative pleurectomy and no further therapy, 16 palliative pleurectomy followed by chemotherapy, 37 chemotherapy alone), while 30 were referred to supportive care only. Median survival of the whole population was 10.5 months. The 1-, 2- and 3-year survival were 40, 17 and 8%, respectively. Univariate analysis of subgroups showed that poor performance status (PS), non-epithelial histotype, Butchart stage>I and International Mesothelioma Interest Group (IMIG) stage>I were individually associated with lower survival. Patients receiving any therapy survived longer than patients treated with supportive care only (P=0.0004). Treatment modality had an independent prognostic value (P=0.00005), with a survival advantage for patients receiving surgery and adjuvant chemotherapy. Multivariate analysis confirmed the independent prognostic value of PS (P=0.001; HR=2.48) and treatment modality (P=0.003; HR=1.38). The prognostic role of PS (P=0.02) and treatment modality (P=0.01) was confirmed in the subset of patients with epithelial histology. On the contrary, therapy had no impact on survival in patients with sarcomatoid MPM (P=0.74). Despite the predicted bias of a retrospective non-randomized evaluation of treatment-related factors, patients with good PS and epithelial histology seemed to have a survival benefit from surgery or multimodality therapy, as opposite to patients with poor PS or non-epithelial histotype. However, these results must be confirmed in a larger prospective trial with uniform treatment.
Lung Cancer 2001 Nov
PMID:Therapeutic outcome according to histologic subtype in 121 patients with malignant pleural mesothelioma. 1167 87

The incidence of malignant mesothelioma (MM) in Italy is increasing and is assumed to be a consequence of high levels of asbestos exposure. Establishment of the National Mesothelioma Registry (ReNaM) and the co-operation of five regional centers has allowed the estimation of the incidence of malignant mesothelioma in major parts of Italy and the definition of exposure to asbestos.
Lung Cancer 2004 Aug
PMID:Epidemiology of pleural mesothelioma in Italy. 1526 29

The incidence of malignant mesotheliomas in Germany has increased since about the mid 1980s, and a further increase is expected until about 2020 due to the peak in asbestos processing in Germany between 1965 and 1980. About 90% of the mesotheliomas recorded in the files of the German Mesothelioma Registry in Bochum are asbestos-related and therefore possibly due to an occupational exposure. In 2003, 717 mesotheliomas were newly diagnosed at the German Mesothelioma Registry. Mesotheliomas are very heterogeneous in terms of histological appearances and of prognosis. At present, the diagnostic gold standard is conventional histology in combination with additional immunohistochemical analysis. We were not able to confirm a promising report that described telomerase reverse transcriptase catalytic subunit (TERT) for the differentiation between reactive and neoplastic mesothelial lesions, which can be extremely difficult. DNA cytometric analysis may also help differentiate between reactive and neoplastic mesothelial lesions. There are some characteristic patterns of chromosomal imbalances as detectable by comparative genomic hybridization (CGH), but at present, specific chromosomal or genetic defects that give rise to a mesothelioma are not known. A reliable pathological diagnosis is the basis for therapeutic, prognostic, and medicolegal consequences. In general, it can be achieved by thoracoscopic inspection with specifically directed biopsy. Furthermore, a description of the peculiarities of each mesothelioma by the pathologist might be the key to a more individual therapy in the future.
Lung Cancer 2004 Aug
PMID:Pathological anatomy and molecular pathology. 1526 30


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