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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Giant cell carcinoma of the lung (GCCL) is an uncommon and extremely aggressive variant of lung cancer. Characteristic microscopic findings include marked pleomorphism, aggregates of mononucleated or multinucleated giant cells (or both), a general lack of architectural cohesiveness, extensive necrosis, and endocytosis by the giant cells. Although the epithelial character of GCCL has been confirmed by a number of studies, controversy persists as to whether it represents a variant of poorly differentiated adenocarcinoma or of squamous carcinoma. Histochemical studies for mucosubstances have yielded variable and conflicting results. This report describes conventionally fixed and processed samples from 10 cases of GCCL studied with a panel of monoclonal antibodies (Mabs) recognizing different cytokeratin polypeptides (AE1, AE3, AE1/AE3 cocktail, and CAM 5.2), vimentin, and Mab A-80, the last of which binds to a mucinous glycoprotein associated with exocrine differentiation. All 10 cases of GCCL reacted with all cytokeratin Mabs; the extent and intensity of the reaction varied notably. All cases stained strongly and diffusely with Mab AE1 and AE1/AE3, the reaction was less extensive and weaker with CAM 5.2. Significantly, 2 cases reacted focally with Mab AE3. Nine cases reacted extensively and intensely with the vimentin Mab, often showing prominent paranuclear globular profiles. All cases reacted with Mab A-80; the reaction was often strong, but the extent was variable. Findings indicate that all GCCL are indeed cytokeratin positive but that most express polypeptides toward the low-molecular weight end of the spectrum; a small subset also expresses heavier polypeptides.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunohistochemical features of giant cell carcinoma of the lung: patterns of expression of cytokeratins, vimentin, and the mucinous glycoprotein recognized by monoclonal antibody A-80. 171 80

Alpha 2-macroglobulin, a major glycoprotein component of plasma, is unique in its capacity to bind and inhibit the proteolytic activities of all classes of proteinases. Since proteinases implicated in cancer dissemination (type-IV collagenase, plasminogen activator, cathepsins B) are normal constitutents of blood, we have explored the hypothesis that elevated tissue levels of activated proteinases bound to alpha 2M might be detected in plasma of patients with cancer. To test this premise, blood was collected from 149 subjects (33 healthy controls, 31 patients with infections and non-malignant diseases, 16 with myeloproliferative disease, 10 with gastrointestinal cancer, 7 with genito-urinary cancer, 16 with lung cancer, 14 with lymphoma, 11 with miscellaneous cancers and 11 with chronic lymphocytic leukemia and myeloma). Plasma was assayed for alpha 2M-proteinase complexes using a sandwich ELISA which employs a mouse monoclonal antibody (MAb) that binds to a neo-antigenic determinant on complexed alpha 2M and a rabbit polyclonal anti-native human alpha 2M antibody. The concentration of complexed alpha 2M in healthy controls was 14.2 +/- 9.8 micrograms/ml (mean +/- standard deviation). No significant differences in complexed alpha 2M were noted between normal and cancer groups (range 7.4-14.6 micrograms/ml). On the basis of these data, we propose that, in patients with cancer, activated proteinases are bound locally to inhibitors in the tissues and are not available to form complexes with plasma alpha 2M. An alternative explanation is that proteinases are not secreted in excess by cancer cells in vivo.
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PMID:Proteinase-alpha 2 macroglobulin complexes are not increased in plasma of patients with cancer. 171 Feb 7

A panel of murine monoclonal antibodies was generated against a high-molecular-weight glycoprotein produced by human lung cancer cells. This lung cancer-associated protein (LCAP) has been shown to circulate in the plasma of patients with lung cancer. Various combinations of MAbs were used in solid-phase enzyme-linked sandwich immunoassays to optimize the detection of LCAP in the plasma of these patients. One of these monoclonal antibodies, designated DF-L1, used both in the solid phase as well as the tracer, was selected to evaluate circulating levels of LCAP in normal subjects and in patients with lung cancer. In 341 normal subjects, the mean LCAP level was 7 units/ml, with 47 (13.8%) and 18 (5.3%) subjects having levels greater than or equal to 15 units/ml and 23 units/ml, respectively. In contrast, 27 of 35 (77.1%) patients with lung cancer had LCAP levels greater than or equal to 23 units/ml. A total of 16 of 19 (84.2%) patients with adenocarcinoma, four of seven (57.1%) patients with squamous cell carcinoma, and four of six (66.7%) patients with small cell carcinoma had levels greater than or equal to 23 units/ml. Moreover, in a small group of patients, serial LCAP levels correlated with clinical course during therapy. The LCAP assay is technically reproducible and unaffected by interfering substances in the blood or by variations in the handling of samples. These results indicate that LCAP is a new and potentially useful marker for the evaluation of patients with lung cancer.
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PMID:Lung cancer-associated protein: development and characterization of a new assay that detects a circulating lung cancer marker. 185 1

In an earlier publication (Harvey, et al. (1982) J. Biol. Chem., 257, 5645-5651) the discovery of a family of unusually large molecules with plasminogen activator activity in the conditioned medium of a human lung cancer cell line was reported. These molecules are related to urokinase (uPA) by functional and immunological criteria. We have now purified two representatives of this glycoprotein family of Mr 900,000 (PA900) and Mr 660,000 (PA660). While these could be fractionated into subspecies exhibiting size and charge differences, reduction yielded in all cases two predominant chains of 70 and 40 kDa, respectively. Since the amino acid composition of the subfractions was identical, we conclude that the heterogeneity is due to demonstrated differences in glycosylation. The amino acid composition of the unreduced species and of the major reduced chains differed from that of 55 kDa uPA. These enzymes are active toward the substrate, plasminogen, as well as toward the uPA-specific synthetic substrate, Spectrozyme UK, and these activities are inhibitable by diisopropylphosphorofluoridate (DFP). Treatment of PA660 with [3H]DFP resulted in the incorporation of 1.4 mol of DFP into 1 mol of enzyme, suggesting the presence of a single active site. The label was quantitatively recovered in a 21 kDa fragment in a reduction experiment. This fragment also demonstrated immunological reactivity with antiurokinase. It is postulated that PA660 is composed of five or six pairs of the 70 and 40 kDa chains, and of a single uPA-like entity. All of these chains are linked by disfulfide bonds. Whether larger portions of uPA are also present in this molecule, is not yet clear. By electron microscopy, PA900 shows a filamentous structure, while PA660 is predominantly globular. The occurrence of large uPA-like activators in extracts of human colon carcinomas that crossreact with monospecific antibody against uPA, is discussed.
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PMID:Characterization of a family of high-molecular-weight plasminogen activators secreted by a lung tumor cell line. 185 26

Several studies have been performed in the last ten-years on the biochemical and physiopathologic properties of angiotensin-converting enzyme (ACE). Human lung and kidney are a rich source of ACE and the enzyme is bound to the plasma-membrane of vascular endothelial cells; however, the small intestine and the choroid plexus are also particularly rich in ACE, where it is concentrated on the surface of cuboidal epithelial cells facing the cerebrospinal fluid. The ACE is a glycoprotein with a molecular weight of 150,000 daltons and it cleaves C-terminal dipeptides of several oligo-peptides, including angiotensin I and bradykinin. It catalyzes conversion of angiotensin I to angiotensin II and induces inactivation of bradykinin. Synthetic acylated tripeptides such as radiolabelled hippuryl-histidyl-leucine and hippuryl-glycyl-glycine have been found to be the most suitable substrates for determining the activity of ACE with radiochemical assays. The mean-normal values for ACE activity is 25 U/ml; there are no significant differences in ACE activity between different sexes and races, but there is significant decrease in adults. The measurement of ACE activity in sarcoidosis suggests the following results: 1) There is a relationship between the increased SACE and LACE activity and active disease and between normal ACE activity and inactive disease. 2) Normal or decreased ACE activity is useful for therapeutic evaluation of sarcoidosis. 3) Increased SACE activity can be a sensitive parameter for predicting clinical relapse of the disease. An increased SACE activity is found in a wide variety of non-sarcoid granulomatous diseases and non-granulomatous systemic diseases. A decreased SACE and LACE activity is found in non-granulomatous pulmonary diseases such as "Adult Respiratory Distress Syndrome", lung cancer and lung toxicity caused by antineoplastic drugs. Moreover, a low preoperative SACE is associated with poor prognosis in lung cancer and its levels may be useful for predicting clinical relapse of this disorder after operation. Finally, a low SACE activity is found in malignant lymphomas, leukemia and multiple myeloma. A relationship is also found between decreased enzyme activity and a poor prognosis and clinical relapse of these diseases.
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PMID:[ACE: physiopathology and role in the diagnosis and prognosis of systemic granulomatosis, neoplasms and lung toxicity caused by antineoplastic agents]. 217 27

The quantitative changes of glycosaminoglycans in tumor tissue of human lung cancers (6 squamous cell carcinomas, 7 small cell carcinomas and 10 adenocarcinomas) were studied. Normal lung tissues contained of 3.38 mumol uronic acid/g dry weight glycosaminoglycans which consisted of hyaluronic acid, chondroitin sulfates, dermatan sulfate and heparan sulfate. The total amount of glycosaminoglycans in human lung cancer tissues increased 1.7 to 3.5 times in comparison with that in normal lung tissues. The increase in tissue content of glycosaminoglycans was accompanied by an increase in the chondroitin sulfate level in every histologic type of lung cancer, as well as marked increase in hyaluronic acid level in squamous cell carcinomas, and a moderate increase in small cell carcinomas. The concentrations of dermatan sulfate and heparan sulfate in lung cancer tissues did not show any significant changes compared with those in normal lung tissues. The increase in total amount and changes in the composition of glycosaminoglycans in human lung cancer tissue were closely related to the histologic type of the tumor. In adenocarcinomas, some acid glycoprotein with sialic acid was simultaneously detected during the separating course of glycosaminoglycans, which was considered to be derived from mucinous substances related to adenocarcinoma cells.
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PMID:[Glycosaminoglycans in human normal lung tissues and lung cancer tissues]. 229 Feb 28

Flow cytometry was used to detect fibrinogen (platelet associated fibrinogen: PAFbg) and fibronectin (PAFn) on the surface membrane of platelets in leukemia (9 cases), lung cancer (15 cases) and hepatoma (8 cases) patients (by one color analysis method), and simultaneously to investigate the binding of monoclonal anti-glycoprotein (GP) IIb/IIIa and anti-GP Ib antibodies (by two color analysis). All patient groups showed higher Fbg values than the normal control group, but no differences were found between patient groups. The values of Fbg and Fn showed a correlation, but the pattern of binding did not show a regular tendency in any patient group. There also was no significant correlation between Fbg values and the positive percentage of monoclonal anti-GPIIb/IIIa and anti-GPIb antibodies, and the binding of Fbg did not inhibit that of monoclonal antibody. The results suggest the following. 1. There are no differences in platelet activation in leukemia, lung cancer and hepatoma patients, and the degree of platelet activation is decided by the degree and the kind of stimulation. 2. The increase of both PAFbg and PAFn prove to the existence of activated platelet.
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PMID:[Analysis of adhesive proteins on the surface membrane of platelet in malignant neoplasm]. 232 78

DF3 is an IgG1 monoclonal antibody (MAb) generated against a Mr 350,000-400,000 glycoprotein expressed by approximately 80% of human breast cancers. We have coupled MAb DF3 to ricin. Purification of the immunotoxin (DF3-IT) was obtained by affinity and size exclusion chromatography. DF3 antigen-positive breast cancer cell lines (ZR-75-1, BT-20, and MCF-7) and DF3 antigen-negative lung cancer cell lines (A549 and CALU6) were tested for cytotoxicity with metabolic labeling and clonogenic assays. The cells were exposed for 3 h to different concentrations of DF3-IT, MAb DF3, ricin, and a combination of unconjugated MAb DF3 and ricin. In the presence of 100 mM lactose, DF3-IT specifically inhibited protein synthesis of lines expressing DF3 antigen on their cell surface. Moreover, clonogenic survival experiments demonstrated that DF3-IT at a concentration of 1 x 10(-9) M specifically kills 2.6-2.8 log of ZR-75-1 and BT-20 cells and 1.6 log of MCF-7 cells. At the same concentration, nonspecific toxicity of DF3-IT resulted in a 30% reduction of bone marrow granulocyte and macrophage colony formation. In bone marrow-purging experiments, tumor cells were mixed with an excess of bone marrow cells and treated with DF3-IT or ricin. Tumor cell clonogenic survival assays demonstrated that the presence of bone marrow cells had no detectable effect on activity or specificity of the DF3-IT. These results thus indicate that MAb DF3 is an effective vehicle to specifically deliver toxins to cancer cells which express DF3 antigen on their surface and that DF3-IT may be useful for in vitro purging of bone marrow.
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PMID:Evaluation of monoclonal antibody DF3 conjugated with ricin as a specific immunotoxin for in vitro purging of human bone marrow. 240 89

Two monoclonal antibodies, NCC-LU-35 and NCC-LU-81, have been established after immunization of mice with membrane preparations of human lung cancer Lu65 tumor xenograft cells grown in vivo and intact cells cultured in vitro, respectively. These two antibodies react specifically with a majority of human adenocarcinomas, irrespective of the host's blood group ABO status, as well as with normal tissues and erythrocytes of blood group A individuals. The antigenicity is associated with a high molecular weight mucin-like glycoprotein separated by gel filtration of Lu65 tumor extracts. The epitope of the mucin-like glycoprotein has been identified as alpha-N-acetylgalactosaminyl residue directly linked O-glycosidically to serine or threonine residues of polypeptides. This epitope was serologically detected several years ago and given the name Tn. Our identification of the epitope is based on the following results: The antigen is sensitive to alpha-N-acetylgalactosaminidase, but not to sialidase or alpha-fucosidase. Various mono- and difucosyl A determinants, either type 1 or type 2 chain, cross-react with both antibodies. The reactivity with both antibodies can be created by treatment of glycophorin A of normal erythrocytes with sialidase followed by beta-galactosidase. N-[3H]acetylgalactosamine can be released by galactose oxidase/NaB3H4 treatment from the Lu65 mucin-like glycoprotein but not from the mucin-like glycoprotein of normal colonic mucosa upon reductive beta-elimination (alkaline borohydride treatment). The antigen may be one of the tumor-associated A cross-reacting antigens occurring in a wide variety of human adenocarcinomas of hosts belonging to all ABO blood groups.
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PMID:Blood group A cross-reacting epitope defined by monoclonal antibodies NCC-LU-35 and -81 expressed in cancer of blood group O or B individuals: its identification as Tn antigen. 241 56

One hundred and one cases of lung cancer were immunohistochemically studied for stainability with Leu-7 (anti-myelin fiber associated glycoprotein) and OKT-9 (anti-transferrin receptor) monoclonal antibodies. All small cell carcinomas and carcinoid tumors were positively stained by Leu-7, and 22 of 41 differentiated adenocarcinomas were also positively stained, especially well-differentiated Clara cell-type adenocarcinoma, (11/14 cases). However, only one of 26 squamous cell carcinomas, one of six large cell carcinomas, one of six adenosquamous carcinomas and none of 16 poorly differentiated adenocarcinomas were stained by Leu-7. On the other hand, all squamous cell carcinomas (26/26 cases), 10 of the 16 poorly differentiated adenocarcinomas, four of the six large cell carcinomas showed positive membranous staining with OKT-9. However, only one of 41 differentiated adenocarcinomas and no small cell carcinomas nor carcinoid tumors were stained by OKT-9. The stainability of lung cancer by these antibodies is discussed.
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PMID:Stainability of lung cancer cells with Leu-7 and OKT-9 monoclonal antibodies. 241 90


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