Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A solid-phase, enzyme-linked immunosorbent assay (ELISA) for a human lung tumor-associated antigen (LTA) was based on immobilized LTA that was detected with the use of an antiserum raised in a goat against a highly purified antigen preparation. Bound goat antibodies were detected in a series of steps that included incubation with a) biotinylated rabbit antibodies to goat immunoglobulins, b) glucose oxidase conjugated to avidin, and c) peroxidase and the substrates glucose and 2,2'-azino-di-(3-ethylbenzthiazoline sulfonic acid). The absorbance of the final product was measured at 405 nm, and its formation was dependent on substrate incubation time and antibody concentration. The antigen was immobilized and highly purified, and the goat antiserum was bound to and eluted from an immobilized crude antigen column before use. The ELISA could detect less than 1 ng antigen and was able to discriminate extracts of normal lung tissue from those of lung tumor. As was found earlier with a radioimmunoassay for the same antigen, normal human serum could inhibit in the ELISA but only when used at high concentration, indicating levels of antigen or antigen-like activity in the 100-200 ng/ml range. With the use of this assay, 3 lung cancer patients were monitored 6-12 months prior to death. In all 3 patients, LTA levels rose dramatically 2-4 months before the patients died; in 2 patients the levels exceeded 3,000 ng/ml just before death. In contrast, in 2 of these patients, carcinoembryonic antigen levels remained essentially unchanged, with no more than a twofold increase prior to death.
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PMID:A solid-phase, enzyme-linked immunosorbent assay for a human lung tumor-associated antigen. 636 40

The highly sensitive peroxidase-antiperoxidase immunocytochemical method was used to demonstrate the presence of the beta-subunit of human chorionic gonadotropin (HCG) within paraffin sections of human lung tumors of diverse histologic patterns. Of the 61 tumors studied, 51 (84%) displayed HCG-like immunoreactivity. This is a much higher incidence than was expected considering studies by other investigators in which serum samples from patients with lung cancer were assayed for HCG. Our results are, however, consistent with data from studies by other investigators in which tumor extracts were assayed for HCG. In addition, it was found that HCG production was often linked with glycogen storage within tumor cells. This may explain the association of HCG production with large-cell carcinomas of the lung, because these tumors often contain copious quantities of glycogen.
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PMID:Elaboration of human chorionic gonadotropin by lung tumors: an immunocytochemical study. 701 Dec 52

A pancreas cancer-associated antigen (PCAA) was identified and isolated from ascites fluid of human pancreatic cancer. Purified PCAA was homogeneous as determined by polyacrylamide gel electrophoresis. PCAA was a glycoprotein with a molecular weight of approximately 1,000,000 and consisted of 20% carbohydrates and 80% peptides, had an isoelectric point of 4.7, and migrated to alpha 2-beta region. It possessed a sedimentation coefficient of 14S and appeared to be a fibrous or fibroglobular protein. Immunoreactivity of PCAA was sensitive to proteolytic enzymes, perchloric acid, KSCN, glycine-HCl at pH 2.5, urea and lithium diiodosalicylate; and insensitive to neuraminidase or beta-glucosidase. Immunohistochemical technique revealed that PCAA was located in the cytoplasm of ductal epithelial cells of malignant pancreas. Using heteroantiserum raised against purified PCAA, horseradish peroxidase and CNBr-activated Sepharose 4B, an enzyme-immunoassay (EIA) for circulating PCAA has been developed. From a group of 40 healthy blood donors, an upper limit of 16.2 micrograms of PCAA/ml of serum has been tentatively determined. An elevated PCAA was shown in 67% (29/43) of patients with pancreas cancer, as well as in 30% (11/36) of lung cancer patients, 27% (10/37) of colonic cancer patients, and in 16% (6/36) of breast cancer patients. The reactive antigen in sera of these cancers was shown to be immunologically identical. PCAA also was detected in extracts of various human tissues, particularly pancreatic tumors, colonic tumors, and in a normal colon. Further, PCAA exhibited heterogeneity in molecular weight, isoelectric point, and electrophoretic mobility.
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PMID:Isolation, characterization and clinical evaluation of a pancreas cancer-associated antigen. 702 47

The occurrence of inflammatory processes and of cancer in the human respiratory tract is intimately associated. One of the major factors in this is probably the recruitment of and stimulated activity of polymorphonuclear leukocytes (PML) in conjunction with the ability of these cells to convert various carcinogens to their ultimate active metabolites. In this study, we demonstrate that nitrite and sulfite, the major dissolution products of the environmental pollutants nitrogen dioxide and sulfur dioxide in water enhance the metabolic activation of trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-dihydrodiol), the proximal carcinogen of benzo[a]pyrene, to trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and tetraols, the corresponding hydrolysis products, in human PML prestimulated with 12-O-tetradecanoylphorbol-13-acetate. Nitrite was more efficient than sulfite in stimulating the formation of reactive intermediates of BP-7,8-dihydrodiol in PML that covalently bind to extracellular DNA and, in particular, to intracellular proteins. The mechanism by which sulfite stimulates the metabolism of BP-7,8-dihydrodiol most probably involves the intermediate formation of a sulfur trioxide radical anion (SO3.-) the subsequent formation of the corresponding sulfur peroxyl radical anion (.OOSO3-) in the presence of oxygen. The mechanism underlying the stimulatory action of nitrite is less clear but the major pathway seems to involve myeloperoxidase. These results offer an explanation for the increased incidence of lung cancer in cigarette smokers living in urban areas. The major glutathione transferase (GST) isoenzyme in human PML is GST P1-1, a Pi-class form. The GST activity of PML was found to be inversely correlated with the extent of binding of BP-7,8-dihydrodiol products to exogenous DNA. These results suggest that individuals exhibiting high GST-activity in the PML may be better protected against the type of carcinogenic dealt with in this study.
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PMID:Stimulatory effects of sulfur and nitrogen oxides on carcinogen activation in human polymorphonuclear leukocytes. 782 Dec 91

KL-6, a circulating mucin-like glycoprotein, is a pulmonary adenocarcinoma-associated antigen and is also regarded as an indicator of disease activity of interstitial pneumonitis. KL-6 has extensive heterogeneous antigenic determinants and consists of multiple heterogeneous antigen molecules. We have searched for circulating KL-6-associated glycoproteins with superior diagnostic value to KL-6 as a tumor marker for pulmonary adenocarcinoma. A new murine monoclonal antibody EH-123 reacting with an asialosugar chain on KL-6 was established. A new KL-6-associated molecule detected by a bimonoclonal bideterminant sandwich assay using the EH-123 antibody as a catcher and horseradish peroxidase-labeled KL-6 as a tracer was designated as CAM 123-6. In 59% (22 of 37) of patients with pulmonary adenocarcinoma, serum levels of CAM 123-6 were abnormally elevated and the positive rate increased with the progression of clinical stage. Elevated levels were not detected in normal individuals or in patients with benign lung diseases, other histologic types of lung cancer, gastric cancer, colon cancer or breast cancer. CAM 123-6 was more specific to pulmonary adenocarcinoma than carcinoembryonic antigen (CEA), but the sensitivity of CAM 123-6 for pulmonary adenocarcinoma was similar to that of CEA. CAM 123-6 is a promising candidate as a serum tumor marker for pulmonary adenocarcinoma.
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PMID:A new serum tumor marker, CAM 123-6, highly specific to pulmonary adenocarcinoma. 814 2

Analysis of cell surface glycosylation not only provides information about cell properties such as their state of differentiation or histogenetic lineage. The carbohydrate chains also provide potentially functional binding sites to endogenous carbohydrate-binding proteins. This interaction can elicit consequent signalling processes. Because of the importance of neutrophils in the host defence system, we monitored the effect of the binding of such sugar receptors to their cell surface on the release of the enzymatic activities of lysozyme, elastase, and myeloperoxidase. Besides the mannose-binding lectin concanavalin A and the immunomodulatory alpha/beta-galactoside-binding lectin from Viscum album L., three preparations of human sugar receptors - beta-galactoside-binding lectin (M(r) 14 kDa) and two affinity-purified polyclonal IgG fractions from serum with the capacity to recognize alpha- or beta-galactosides, respectively - were used. Two animal lectins from chicken liver and intestine that bind beta-galactosides, as well as the lectin-like human serum amyloid P component, were included in order to assess the importance of slight differences in ligand recognition. Cytochalasin B-enhanced enzyme release was invariably seen with the two plant lectins and the chicken liver beta-galactoside-binding lectin, but the related intestinal lectin did not increase enzyme release. The mammalian homologue of these avian lectins triggered lysozyme secretion, and the lactoside-binding IgG fraction enhanced the amount of extracellular elastase activity slightly but significantly. Thus, the actual lectin, not the nominal specificity of sugar receptors, is crucial for elucidation of responses. Due to the highly stimulatory activity of the two plant lectins, neutrophils from patients with non-cancerous diseases and from patients with lung cancer were monitored for the extent of lectin-mediated enzyme release. Only the concanavalin A-mediated reactivity of the neutrophils was associated with the type of disease.
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PMID:Carbohydrate-binding proteins (plant/human lectins and autoantibodies from human serum) as mediators of release of lysozyme, elastase, and myeloperoxidase from human neutrophils. 857 Sep 10

Occupational exposure to asbestos, a recognised carcinogen, poses a risk for such diseases as asbestosis, lung cancer and mesothelioma. It is thought that asbestos fibres may damage microphages which undergo neoplastic transformation as well as fibroblast, while partial phagocytosis may generate free oxygenic radicals which induce cellular peroxidase and damage macromolecules. A search for cellular changes or changes in cellular metabolism products, present in biological fluids, in order to detect early stages of a neoplastic process is an important factor in the prophylaxis of workers exposed to asbestos. Neoplastic biomarkers such as tissue polypeptide antigen (TPA) or carcinoembryonic antigen (CEA) are now used for this purpose. The aim of the work was to identify workers exposed to asbestos in the population, especially high risk groups neoplastic diseases and to evaluate the usefulness of TPA and CEA determinations. The study covered a group of asbestos exposed workers (n = 4000 and the control group of workers (n = 135) nonexposed to any toxic factor at work. Age, exposure time, smoking habits and workpost characteristics were taken into consideration in the analysis of the results. It was revealed that in 38 persons exposed to asbestos, TPA values were above the concentration limit set on the basis of studies carried out in the control group, and elevated CEA values applied to 13 persons. Significant differences between groups under study were found in the proportion of pathological TPA values. Such a relationship was not observed in regard to CEA values. In the exposed group the results also indicated an evident effect of age and exposure time on the number of persons with TPA values above concentration limit. There is a growing tendency in those changes but only in regard to TPA values. The effect of smoking on the frequency of pathological TPA values was also clear-cut in workers exposed to asbestos. Taking into account three types of employment: blue collar workers, white collar workers and other personnel, the analysis indicated significant differences in TPA values between blue collar workers and other personnel; and between white collar workers and other personnel. This means a similar percentage of pathological TPA values in the group of blue collar and white collar workers. The study carried out allowed to identify persons exposed to asbestos who should be covered with targeted medical care. They also proved that TPA biomarker is better than CEA one for this kind of studies.
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PMID:[Exposure to asbestos and levels of selected tumor biomarkers]. 865 7

The CD34 antigen is a glycosilated transmembrane protein with a molecular weight of 105-120 kDs, whose molecular function is still unknown. At present different epitopes of this antigen are recognized by more than 20 monoclonal antibodies. By flow cytometry is quite simple to identify and enumerate the CD34+ cells, present in physiological conditions on 1-3% of normal bone marrow, 0,1-0,5% of cord blood and 0,001-0,01% of peripheral blood cells. The concomitant expression of other monoclonal antibodies allows the identification of different subsets, lineage negative or already lineage "committed", so that CD34+ cells represent an heterogeneous population with only a small number of undifferentiated progenitors. The number of circulating progenitors has highly increased in peripheral blood for few hours during the fast hematopoietic recovery after high dose chemotherapy. Growth factors are able to mobilize CD34+ cells if used alone in a short treatment schedule and the effect is amplified by combining growth factors with chemotherapy. With this treatment CD34+ cells can increase in peripheral blood up to 100-1000 fold the baseline concentration. Collection of large scale of peripheral stem cells is now possible using different models of continuous-flow blood cell separators. The vast majority of the cells harvested by apheresis are constituted by "committed" elements, myeloid peroxidase positive cells (40%), T lymphocytes (30%), monocytes (20%), B lymphocytes (1-2%), the CD34+ representing not more than 3-4% of the total cells collected. The main biological characteristic of the CD34+ cells is the capacity to reconstitute the myelo and lymphopoietic system after a myeloablative treatment. For this reason in the last few years there has been an increasing interest in using these particular stem cells in many clinical settings. Peripheral blood autografting is widely used in a large number of trials for the treatment of chemosensitive tumors. At present peripheral blood allogeneic transplants have been done in a number of patients sufficient to conclude that it is safe and able to give rise to a sustained marrow engraftment. Moreover, due to the fact that circulating stem cells are a mixture of indifferentiated progenitors and "committed" cells, the hematopoietic recovery is significantly faster both in autologous and allogeneic transplant setting. The increasing use of peripheral blood stem cells for autografting has raised the problem of tumoral contamination. The role of reinfused tumoral cells in promoting the relapse had been proved in the past. Attempts to "purge" the bone marrow of patients affected by low-grade non-Hodgkin lymphoma were done several years ago at Dana Farber Institute, strongly suggesting the importance of tumor cells left in the inoculum in modifying the prognosis. In certain tumors, such as myeloma for example, using a PCR based method, the contamination was found in all the aphereses tested. Similar data were found in samples derived from advanced breast cancer or small-cell lung cancer patients. These findings have brought to the development of different systems of stem cell "purging" or CD34+ positive selection. At present at least two or three different methods are available on the market for small and large scale bone marrow or peripheral blood stem cell processing. The ongoing trials will clarify the clinical utility. In the end the availability of large amount of enriched CD34+ cells have suggested to several investigators a possible target for gene therapy. The first data seem to suggest this is a good way to pursue, even if a clinical application remains still far from being satisfying.
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PMID:[CD34+ cells: biological aspects]. 892 36

Myeloperoxidase is a lysosomal enzyme found in high concentrations in human lung due to recruitment of neutrophils. Myeloperoxidase activates benzo[a]pyrene as well as aromatic amines in tobacco smoke and generates carcinogen-free radicals. A single base substitution (G to A) in the promoter region of the myeloperoxidase gene has recently been demonstrated to markedly reduce transcription. We developed an RFLP/PCR assay to test the hypothesis that the allele favoring lower transcription (A allele) reduces the risk of lung cancer. Among population controls, 7.8% of 459 Caucasians and 9.4% of 244 African-Americans inherited two copies of the A allele. Caucasians with the A/A genotype were at 70% reduced risk of lung cancer (odds ratio, 0.30; 95% confidence interval, 0.10-0.93; P = 0.04; 182 cases). A lesser reduction in risk was observed for African-Americans with this genotype (odds ratio, 0.61; 95% confidence interval, 0.26-1.41; 157 cases). Individuals who inherit two copies of an allele that reduces transcription of the myeloperoxidase gene may be at decreased risk of lung cancer.
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PMID:Myeloperoxidase genetic polymorphism and lung cancer risk. 937 91

A 41-year old woman with lung cancer was admitted to our hospital with constipation, lumbago and paraplegia. Her serum calcium level was 13.9 mg/dl. She expired on the 33rd hospital day despite vigorous fluid and supportive therapy. An autopsy was performed 1 hour later. The cause of death was rupture of the sigmoid colon and panperitonitis. To evaluate the etiology underlying the symptomatic hypercalcemia in the autopsied lung, we measured serum and tumor tissue concentrations of PTH-related protein (PTHrP) by radioimmunoassay using a specific antibody against human PTHrP (1-34), and performed immunohistochemical staining by the peroxidase-anti-peroxidase method with the same PTHrP antiserum. Northern blot analysis was also performed to detect messenger RNA in cancer tissue. All of these tests were positive for PTHrP. To the best of our knowledge, this is the first reported autopsied case demonstrated to be a PTHrP-producing large cell lung cancer by molecular biological methods.
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PMID:[A case of PTH related protein-producing large cell carcinoma of the lung]. 961 51


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