Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumors H-59 and M-27, two stable metastatic variants of the Lewis lung carcinoma, differ in their ability to disseminate lymphatically. Tumor H-59 metastasizes to the regional lymph nodes regardless of the local site of growth and gives rise to widespread lymphatic dissemination, whereas tumor M-27 disseminates hematogenously without involvement of the regional nodes (P. Brodt, Cancer Res., 46: 2442-2448, 1986). In a previous paper we reported that this divergent potential to disseminate lymphatically correlated well with adhesion to frozen sections of syngeneic lymph nodes and spleens (P. Brodt, Clin. Exp. Metastasis, 7: 343-352, 1989). A monoclonal antibody (12/50) specific for tumor H-59 was subsequently generated. This antibody (an IgG1) but not three control antibodies, which reacted with tumor H-59, significantly reduced tumor cell binding to the frozen sections. Western blot analysis revealed that it recognized a plasma membrane protein of Mr 37,000 on tumor H-59 cells. No antibody binding was detected when solubilized plasma membrane preparations of tumor M-27 were used. Subsequent enzymatic assays indicated that the binding of monoclonal antibody 12/50 was insensitive to cell treatment with exoglycosidases but could be significantly reduced by pretreatment of the tumor cells with Pronase. Together these results suggest that monoclonal antibody 12/50 recognizes a cell surface adhesion protein relevant to lymphatic dissemination of this tumor.
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PMID:A monoclonal antibody to Lewis lung carcinoma variant H-59 identifies a plasma membrane protein with apparent relevance to lymph node adhesion and metastasis. 240 49

Two monoclonal antibodies (LN-1, LN-2) reactive with B lymphocytes in B5 formalin-fixed, paraffin-embedded tissue sections have been produced by utilizing cell extracts from pokeweed mitogen-stimulated peripheral blood lymphocytes and diffuse histiocytic lymphoma SU-DHL-4 cells, respectively. Both monoclonal antibodies were initially identified by indirect immunofluorescence screening techniques on paraformaldehyde-acetone-fixed cell preparations. Specificity screens with 36 well-characterized human lymphoma and leukemia cell lines showed that both LN-1 and LN-2 stained cell lines of B cell lineage but were unreactive with those of T cell or, with one exception, myeloid derivation. Null cell acute lymphoblastic leukemia cell lines were found to be LN-2+ but LN-1-. The B cell specificity of these reagents was confirmed on 15 lymphoma and 17 leukemia biopsy specimens by using indirect immunofluorescence techniques. Immunoperoxidase staining of sections from B5-fixed, paraffin-embedded human lymphoid tissues showed that LN-1 bound to the cell membrane and cytoplasm of germinal center cells whereas LN-2 stained the nuclear membrane and cytoplasm of germinal center and mantle zone B lymphocytes as well as interfollicular histiocytes and thymic medullary dendritic cells. Both monoclonal antibodies failed to stain cortical thymocytes, lymph node T cells, and peripheral blood T and myeloid cells. Immunoperoxidase staining of 20 nonlymphoid human organs and tissues revealed that LN-1 reacted positively with red blood cell precursors of the bone marrow, ciliated epithelial cells of the bronchus, distal tubular cells of the kidney, and ductal cells from several organs including the breast and prostate. In contrast, LN-2 was unreactive with all human nonlymphoid organs and tissues including the bone marrow. Indirect immunofluorescence staining of a panel of 26 solid tumor cells lines showed that LN-1 was reactive with the majority of epithelium-derived cell lines, glioblastomas, and astrocytomas but was unreactive with neuroblastomas, small cell carcinoma of the lung, and sarcomas. LN-2 was unreactive with 25 of 26 of the solid tumor cell lines by these techniques. Immunobiochemical studies have shown that LN-1 recognizes a cell surface sialoantigen whereas LN-2 is directed against a 35,000 dalton nuclear membrane protein. Because of their high specificity for B cell tumors and their ability to stain B5-fixed, paraffin-embedded tissues, LN-1 and LN-2 are useful reagents for the diagnosis and classification of the human lymphomas and leukemias.
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PMID:Two new monoclonal antibodies (LN-1, LN-2) reactive in B5 formalin-fixed, paraffin-embedded tissues with follicular center and mantle zone human B lymphocytes and derived tumors. 637 28

The multidrug-resistance associated protein MRP is a 180- to 195-kDa membrane protein associated with resistance of human tumor cells to cytotoxic drugs. We have investigated how MRP confers drug resistance in SW-1573 human lung carcinoma cells by generating a subline stably transfected with an expression vector containing MRP cDNA. MRP-overexpressing SW-1573 cells are resistant to doxorubicin, daunorubicin, vincristine, VP-16, colchicine, and rhodamine 123, but not to 4'-(9-acridinylamino)methanesulfon-m-anisidide or taxol. The intracellular accumulation of drug (daunorubicin, vincristine, and VP-16) is decreased and the efflux of drug (daunorubicin) is increased in the transfectant. The decreased accumulation of daunorubicin is abolished by permeabilization of the plasma membrane with digitonin, showing that MRP can lower the intracellular daunorubicin level against a concentration gradient. Anti-MRP antisera predominantly stain the plasma membrane of MRP-overexpressing cells. We conclude that MRP is a plasma membrane drug-efflux pump.
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PMID:The human multidrug resistance-associated protein MRP is a plasma membrane drug-efflux pump. 791 58

Cluster 13 was defined by 2 independently derived murine monoclonal antibodies (MAbs), RS7 (IgG1) and MR54 (IgG2a), which were raised against human squamous-cell carcinoma of the lung and a human ovarian-carcinoma cell line, respectively. Immunologic and biochemical evidence demonstrated that RS7 and MR54, as well as 2 additional MAbs, MR6 (IgG2a) and MR23 (IgG1), generated in the same fusion as MR54, recognize the same antigen, a 46- to 48-kDa glycoprotein. Evaluation of the expression of antigen on the surface of tumor cell lines, Western blotting analyses, competitive binding studies, and double-determinant ELISA assays, support this conclusion. Two distinct epitopes are defined by these MAbs. In order to further characterize this antigen, amino-acid-sequence analyses were performed on peptides derived from antigen purified by affinity chromatography with MAb RS7. The sequence data obtained from 2 peptides, which were independently generated by CNBr cleavage and trypsin digestion respectively indicated identity to GA733-1. The GA733-1 genomic DNA sequence predicted a type-1 membrane protein of 35 kDa, with 4 potential N-linked glycosylation sites. The GA733-1 protein product has not been identified previously, and MAbs to this tumor-associated antigen were not previously known.
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PMID:Characterization of cluster 13: the epithelial/carcinoma antigen recognized by MAb RS7. 819 3

Epstein-Barr virus (EBV) is strongly associated with nasopharyngeal carcinoma and lymphoepithelioma-like carcinomas (LELC) of foregut-derived organs. Recently this group of EBV-associated carcinomas has been expanded by the identification of the virus in conventional adenocarcinomas of the stomach. In situ hybridization (ISH) using a sensitive digoxigenin-labelled EBER RNA probe was performed on 167 consecutive unselected primary non-small cell lung carcinomas, to determine the frequency of EBV association in these tumours. Nine cases (5.4 per cent) showed strong EBER signals in the tumour cell nuclei. By immunohistochemistry, four of the EBER-positive tumours showed patchy expression of the viral latent membrane protein (LMP-1) and none showed any expression of the EBV nuclear antigen 2 (EBNA2). Morphologically, all the positive tumours were LELC, whereas no conventional type of non-small cell lung carcinoma showed EBV association. The LELC presented a morphological spectrum from undifferentiated to squamoid or glandular differentiation. The patients showed a male to female ratio of 8:1. The mean age at presentation was 48 years. Smoking was not a risk factor. All patients were alive at follow-up periods of 23-52 months. Southern blot analysis performed on eight of the nine positive tumours showed a clonal episomal form of EBV, suggesting the clonal expansion of an infected tumour cell early in oncogenesis. These characteristics of the EBV-associated lung tumours justify their consideration as a distinct clinicopathological entity.
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PMID:In situ detection of Epstein-Barr virus in non-small cell lung carcinomas. 855 84

Antagonists of bombesin/gastrin-releasing peptide (BN/GRP) have been developed to inhibit the stimulatory effects of BN/GRP on the mitogenesis of tumor cells such as human small-cell lung carcinoma (SCLC). The mode of action of these antagonists is not completely understood. In this study, we evaluated the effect of BN/GRP antagonist RC-3095 on receptors for BN/GRP and epidermal growth factor (EGF) in H-128 human SCLC line xenografted into nude mice. Treatment with RC-3095, administered s.c. at a dose of 20 microg/day per animal for 4 weeks caused a 70% reduction in tumor volume and weight. Membrane receptors for BN/GRP and EGF were characterized in untreated and treated animals. In the control group, [125I-Tyr4]BN was bound to a single class of specific, high affinity binding sites with a dissociation constant (Kd) = 6.55 +/- 0.93 nM and maximal binding capacity (Bmax) = 512.8 +/- 34.8 fmol/mg membrane protein. Therapy with RC-3095 decreased the concentration of BN/GRP receptors on H-128 SCLC tumor membranes. Specific, high affinity binding sites for EGF with Kd = 1.78 +/- 0.26 nM and Bmax = 216.8 +/- 19.6 fmol/mg membrane protein were also found on the untreated H-128 SCLC tumors. Treatment with RC-3095 significantly decreased Bmax of receptors for EGF. Our results indicate that the suppression of growth of H-128 SCLC by BN antagonist RC-3095 is accompanied by a decrease in the number of receptors for both BN/GRP and EGF. These observations are in agreement with the results obtained in other experimental cancers. The findings on antagonist RC-3095 reinforce the view that both BN/GRP and EGF receptors participate in a cascade of events involved in the growth of SCLC and other cancers. Although the complete mechanisms of action of antagonist RC-3095 remain to be elucidated, the antitumor effect could be the result of the fall in the EGF receptor number, which might lead to a decrease in EGF receptor autophosphorylation.
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PMID:Reduction in receptors for bombesin and epidermal growth factor in xenografts of human small-cell lung cancer after treatment with bombesin antagonist RC-3095. 902 64

Having reviewed the data on 3,663 consecutive cases of primary lung carcinoma in southern China, we found that 32 cases could meet the criteria for lymphoepithelioma-like carcinoma (LELC) of the lung. To study the relationship between pulmonary LELC and Epstein-Barr virus (EBV) infection, we used in situ hybridization and immunohistochemistry techniques to detect the EBV-encoded small nonpolyadenylated RNA (EBER), latent membrane protein 1 (LMP1), and viral capsid antigen (VCA) in 32 cases of LELC and 19 cases of non-LELC lung carcinoma. Of the 32 cases, 30 (94%) showed EBER positivity. Of the 30 EBER-positive pulmonary LELC cases, 16 and 7 expressed LMP1 and VCA, respectively. In contrast with LELC, none of the 19 cases of non-LELC lung carcinoma showed EBER-, LMP1-, or VCA-positive signals in carcinoma cells. The results demonstrate that there is a close relationship between EBV infection and pulmonary LELC. EBV infection may have an essential role in the tumorigenesis of pulmonary LELC. EBV latent infection is the main status in pulmonary LELC except for individual EBV entering into a lytic cycle.
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PMID:Association of Epstein-Barr virus with lymphoepithelioma-like carcinoma of the lung in southern China. 1094 37

The Epstein-Barr virus (EBV) is directly implicated in the pathogenesis of a variety of undifferentiated carcinomas and has also been identified in conventional adenocarcinomas of the stomach. To date, the association of EBV with non-small cell lung carcinoma is restricted to Asian patients. To evaluate the presence of EBV in lung cancers from Europeans, we investigated primary lung adenocarcinomas with a similar morphological tumour pattern to those of the stomach, specifically rare tumours with components of signet-ring cells. Three tumours of signet-ring cell type were examined by means of polymerase chain reaction (PCR). To localise the virus to the neoplastic cells, in situ hybridisation (ISH) was performed using an antisense Epstein-Barr virus encoded RNA probe. Immunohistochemistry was performed to evaluate the expression of latent membrane protein-1 (LMP-1) and EBV nuclear antigen 2 (EBNA-2). PCR investigation confirmed the presence of EBV in one case. Positive signals confined to tumour cells were present on ISH. None of the tumours showed expression of LMP-1 and EBNA-2. To our knowledge, this is the first report on the presence of EBV in primary adenocarcinoma of the lung in a Caucasian patient. The present study indicates that EBV may infect some lung cancers with a specific tumour pattern.
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PMID:Detection of the Epstein-Barr virus in primary adenocarcinoma of the lung with Signet-ring cells. 1211 Nov 97

During the last five years there has been interest in developing non-cytotoxic, targeted cancer treatments. This phenomenon has occurred as a result of increased information regarding factors which regulate tumor proliferation, survival, angiogenesis, invasiveness, and metastatic potential. In non-small cell lung cancer many investigators have focused their attention on the epidermal growth factor receptor (EGFR) because this membrane protein, which has an extracellular ligand binding domain, as well as, tyrosine kinase activity on the intracellular portion of the molecule, is expressed in a relatively high proportion of non-small cell lung cancers. Gefitinib which was the first EGFR specific tyrosine kinase inhibitor to be extensively tested in non-small cell lung cancer has shown single agent activity in non-small cell lung cancer. Subsequently, erlotinib, another EGFR specific tyrosine inhibitor, has also demonstrated single agent activity in non-small cell lung cancer. Phase III trials of erlotinib alone or in combination with chemotherapy have been completed, and data are being analyzed. Several dual inhibitors of erb B1 and erb B2 (PKI 166, GW 572016, EKB 569) have been or are being tested in phase I trials. In addition, CI 1033, a pan-erb inhibitor, is also being tested in phase I studies. Diarrhea and rash have been the predominant side effects of these agents. Life threatening toxicity has been rare. Although the erb tyrosine kinase inhibitors are attrative agents to use in treating non-small cell lung cancer because of their relatively benign toxicity profile, more data are needed to define the role of these agents in non-small cell lung cancer.
Lung Cancer 2003 Aug
PMID:Clinical studies with non-iressa EGFR tyrosine kinase inhibitors. 1286 61

Cell surface retention sequence binding protein-1 (CRSBP-1) is a cell surface binding protein for the cell surface retention sequence (CRS) motif of the v-sis gene product (platelet-derived growth factor-BB). It has been shown to be responsible for cell surface retention of the v-sis gene product in v-sis-transformed cells (fibroblasts) and has been hypothesized to play a role in autocrine growth and transformation of these cells. Here we demonstrate that the CRSBP-1 cDNA cloned from bovine liver libraries encodes a 322-residue type I membrane protein containing a 23-residue signal peptide, a 215-residue cell surface domain, a 21-residue transmembrane domain, and a 63-residue cytoplasmic domain. CRSBP-1 expressed in transfected cells is an approximately 120-kDa disulfide-linked homodimeric glycoprotein and exhibits dual ligand (CRS-containing growth regulators (v-sis gene product and insulin-like growth factor binding protein-3, IGFBP-3) and hyaluronic acid) binding activity. CRSBP-1 overexpression (by stable transfection of cells with CRSBP-1 cDNA) enhances autocrine loop signaling, cell growth, and tumorigenicity (in mice) of v-sis-transformed cells. CRSBP-1 expression also enhances autocrine cell growth mediated by IGFBP-3 in human lung carcinoma cells (H1299 cells), which express very little, if any, endogenous CRSBP-1 and exhibits a mitogenic response to exogenous IGFBP-3, stably transfected with IGFBP-3 cDNA. However, CRSBP-1 overexpression does not affect growth of normal and transformed cells that do not produce these CRS-containing growth regulators. These results suggest that CRSBP-1 plays a role in autocrine regulation of cell growth mediated by growth regulators containing CRS.
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PMID:Cloning, expression, characterization, and role in autocrine cell growth of cell surface retention sequence binding protein-1. 1291 78


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