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)

Alterations in mucin expression have been detected in many clinically relevant cancers and, in particular, the polymorphic epithelial mucin, encoded by the MUC1 gene, has attracted considerable attention. We investigated its expression in human breast, colon, ovarian, lung, and skin cancer cells and their metastases grown in severe combined immunodeficient (scid) mice using three different monoclonal antibodies (HMFG-1, HMFG-2, and SM3). Four of five breast cancer cell lines, three of five colon cancer cell lines, two of three small-cell carcinoma of the lung cell lines, and A 431 cells all expressed the MUC1 gene product. Neuraminidase predigestion often enhanced HMFG-1 immunoreactivity, which was more widespread and stronger than SM3 immunoreactivity. A considerable heterogeneity of MUC1 gene product expression was observed in the same tumors grown in different mice. The binding pattern between single-cell/small-cell clusters (up to 10 cells) and larger cell number aggregates varied. The results indicate that the MUC1 gene expression both in primary tumors and metastases is not tightly controlled within a particular tumor cell line. Because of this heterogeneous antigen expression in vivo, it appears impossible to target all metastatic deposits by a single monoclonal antibody directed against the MUC1 gene product. (J Histochem Cytochem 46:127-134, 1998)
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PMID:Immunohistochemical detection of the MUC1 gene product in human cancers grown in scid mice. 940 2

Lung carcinoma cell lines are being used in many laboratories to study various airway epithelial functions, including mucin gene expression. To identify model systems for investigating regulation of MUC5/5AC gene expression and secretion of MUC5/5AC mucins in airway epithelial cells, we evaluated the expression of several mucin genes in six carcinoma cell lines of respiratory tract origin. RNA was extracted from A549, Calu-3, NCI H292, Calu-6, RPMI 2650, and A-427 cells; MUC1, MUC2, MUC4, MUC5/5AC, and MUC5B messenger RNA (mRNA) expression was determined. By Northern analyses, all cell lines expressed MUC1 mRNA, whereas MUC2 mRNA was not detectable in any of the cell lines. RPMI 2650 cell lines expressed only MUC1 mRNA. NCI-H292 cells expressed MUC4 and low levels of MUC5/5AC mRNA. Calu-3 and A549 cells expressed MUC5/5AC mRNA; A549 cells also expressed MUC5B mRNA. Glycoconjugates secreted by lung carcinoma cells were also examined. By wheat germ lectin analysis, Calu-3, H292, and A549 cells secreted high molecular weight glycoproteins having N-acetylglucosamine and/or sialic acid moieties. Western blot analyses with an anti-MUC5:TR-3A antibody demonstrated that Calu-3 and A549 cells secreted MUC5/5AC mucins. All six carcinoma cell lines secreted large, radiolabeled, sulfated macromolecules; the majority were proteoglycans that were digested by hyaluronidase. However, Calu-3 cells also secreted sulfated high molecular-weight glycoproteins that were immunoprecipitated by anti-MUC5:TR-3A antibody. These studies demonstrated that Calu-3 and A549 cell lines expressed high and moderate amounts of MUC5/5AC mRNA and MUC5/5AC mucins, whereas H292 cells expressed lesser amounts. These cell lines should prove useful for studies of MUC5/5AC gene expression and MUC5/5AC biosynthesis, trafficking, and secretions in airway epithelial cells.
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PMID:Respiratory carcinoma cell lines. MUC genes and glycoconjugates. 1003 Aug 49

A number of cancer vaccine and gene therapy approaches are being evaluated in patients with lung cancer. Cancer vaccine strategies include GM-CSF gene-modified cancer cells, liposomal MUC1 peptide, anti-idiotype antibody targeting GD3, Mage-3 peptide, and mutant p53 pulsed dendritic cells among others. Preliminary human trials have demonstrated immune responses as well as tumor regression in late stage disease. The largest human gene therapy experience in lung cancer is with intratumoral gene replacement therapy, predominantly with p53, but such approaches are limited to locoregional disease control. Earlier stage gene therapy programs targeting the immune system or tumor vasculature hold promise as systemic therapies for treatment of advanced, disseminated disease.
Lung Cancer 2003 Aug
PMID:Lung cancer vaccines and gene therapy. 1286 69

Active specific immunotherapy with liposomal vaccines targeted to the mucinous carcinoma-associated glycoprotein MUC1 have shown promising results in animal models. The aim of this phase I study was to evaluate the safety and immunogenicity of 2 dose levels of the MUC1 liposomal vaccine preparation BLP25. Patients with stage IIIB or IV non-small-cell lung cancer received either 20 microg or 200 microg of the liposomal BLP25 vaccine preparation. Injections were administered subcutaneously at weeks 0, 2, 5, and 9. Immunological responses to vaccination were measured by antibody production, cytotoxic T lymphocytes (CTL), and proliferative T-helper cells. Seventeen patients were entered on study; 12 patients completed the vaccination protocol. Two patients, 1 in each dose group, developed clinically insignificant grade 3 lymphopenia during the study. Nonhematologic toxicities were mild and self-limiting, and there were no significant long-term injection site reactions. Immunological assays revealed the generation of CTLs against MUC1-positive tumor cell lines in 5 of 12 evaluable patients. These patients did not have CTLs prior to receiving the vaccine. No significant humoral response to the vaccination was observed. No objective antitumor responses were observed. Of the 12 patients completing all the vaccinations, 4 had stable disease. Median survival time was 5.4 months in the 20 microg group and 14.6 months in the 200 microg group. In summary, the BLP25 liposomal vaccine was well tolerated and elicited a primarily cellular immune response in these lung cancer patients. This study forms the basis for further clinical exploration of the MUC1 liposomal vaccine, BLP25.
Clin Lung Cancer 2001 Aug
PMID:Phase I study of the BLP25 (MUC1 peptide) liposomal vaccine for active specific immunotherapy in stage IIIB/IV non-small-cell lung cancer. 1465 92

We previously reported MUC1 was a cell surface receptor for Pseudomonas aeruginosa, and binding of bacteria to cells was significantly reduced by pretreatment with neutrophil elastase (NE) (Lillehoj EP, Hyun SW, Kim BT, Zhang XG, Lee DI, Rowland S, and Kim KC. Am J Physiol Lung Cell Mol Physiol 280: L181-L187, 2001). The current study was conducted to ascertain NE effects on MUC1 gene transcription, and MUC1 protein synthesis and degradation. A549 human lung carcinoma cells treated with NE exhibited significantly higher MUC1 protein levels in detergent lysates compared with cells treated with vehicle alone. Also, MUC1 protein shed into cell-conditioned medium was rapidly and completely degraded by NE. Actinomycin D blocked NE-stimulated increase in MUC1 protein expression, suggesting a mechanism of increased gene transcription that was confirmed by measurement of quantitatively greater MUC1 mRNA levels in NE-treated cells compared with controls. However, NE did not alter MUC1 mRNA stability, implying increased de novo transcription induced by the protease. NE increased promoter activity in A549 cells transfected with MUC1 gene promoter-luciferase reporter plasmid. This effect of NE was completely blocked by mithramycin A, an inhibitor of Sp1, as well as mutation of one of the putative Sp1 binding sites in MUC1 promoter located at -99/-90 relative to transcription initiation site. EMSA revealed NE enhanced binding of Sp1 to this 10-bp segment in a time-dependent manner. These results indicate the increase in MUC1 gene transcription by NE is mediated through increase in Sp1 binding to -99/-90 segment of MUC1 promoter.
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PMID:Neutrophil elastase stimulates MUC1 gene expression through increased Sp1 binding to the MUC1 promoter. 1584 14

Caulobacter crescentus is a gram negative, non-pathogenic bacterium, common in aquatic and soil environments. One feature of note is a protein surface layer (S-layer) composed of a single protein, organized as a self-assembled crystalline array that coats the bacterium. In the course of efforts to express cancer-associated peptides as genetic insertions into the S-layer, we noted a tumor suppressive effect of the unmodified bacterium. C. crescentus was examined for anti-tumor activity against three transplantable tumor mouse models: Lewis lung carcinoma cells transfected with the MUC1 gene in C57BL/6, murine mammary carcinoma (EMT-6) in BALB/c (both in prophylactic and therapeutic mode) and murine leukemia cells (L1210) in DBA2. Mice were immunized three times i.p. with C. crescentus (2 x 10(7) cells/mouse). In prophylactic mode, the mice were challenged with tumor cells two weeks after the last immunization. Immunization with live C. crescentus resulted in anti-tumor activity in all three transplantable tumor models, as measured by prolonged survival, reduced tumor mass or reduced number of lung nodules, compared to saline control groups. In the Lewis lung and the EMT-6 mammary carcinoma murine models the number of lung nodules as well as the tumor weight was lower in mice treated with C. crescentus, compared to the control group; for EMT-6, this was observed in prophylactic and therapeutic modes. In the murine leukemia and Lewis lung carcinoma models prolonged survival was observed in the groups of mice immunized with Caulobacters. In most cases the live C. crescentus cells were markedly more efficacious than heat killed or formalin fixed cells, despite the fact that they do not grow or persist in mice. The results suggest that C. crescentus may be a safe, bacterial immunomodulator for the treatment of tumors.
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PMID:Anti-tumor effects of the bacterium Caulobacter crescentus in murine tumor models. 1658 92

A new competitive enzyme linked immunosorbent assay was developed in this study. Monoclonal antibody (PR81) against the tandem repeat of the core protein was prepared, characterized, purified, and conjugated to HRP. This antibody exhibited no cross reactions with proteins such as bovine serum albumin, keyhole limpet homocyanin, human serum albumin, casein, human milk fat globin (HMFG), and peptone. The native cancerous MUC1 protein was purified from ascites fluid of a patient suffering from small cell lung carcinoma by immunoaffinity chromatography and used as a standard preparation in the assay buffer. The standard curve was constructed following a competitive procedure in the range of 0-200 U/mL. The level of MUC1 in normal and cancerous samples was compared following this procedure and using available CA15-3 EIA (Can Ag), as well as LIAISON CA15-3 commercial kits. The correlation coefficient between the procedure reported in this work (MRP83-CA15-3) and CA15-3 EIA (Can Ag) was 0.68 and was 0.95 with the LIAISON CA15-3 kit. We concluded that the present assay can detect MUC1 in breast cancer patients with great sensitivity and accuracy.
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PMID:A new competitive enzyme linked immunosorbent assay (MRP83-CA15-3) for MUC1 measurement in breast cancer. 1671 Dec 52

The mortality of lung cancer remains high, despite improved diagnostic techniques that allow small lung tumors to be detected. In this study, we evaluated the prognostic significance of the tracheal mucin MUC4 by immunohistochemical investigation of the expression profiles of MUC4, ErbB2, p27 and MUC1 in lung adenocarcinoma specimens (non-bronchiolo-alveolar type, < or =3cm) from 185 patients. MUC4 is a membrane mucin, similarly to MUC1, and in addition MUC4 functions as an intra-membrane ligand for receptor tyrosine kinase ErbB2 and is associated with regulation of p27. However, MUC4 expression was found to be unrelated to expression of MUC1, ErbB2 and p27 in small-sized lung adenocarcinomas. The disease-free interval (DFI) and survival rate of 25 patients with high MUC4 expression (> or =25% of neoplastic cells stained) were significantly lower than those of 160 patients with low MUC4 expression (<25% of neoplastic cells stained) (P<0.05), whereas ErbB2 and p27 expression showed no significant correlation with DFI and survival. Univariate analysis showed that high MUC4 and p27 expression correlated with blood vessel invasion (P=0.0004), and MUC4 expression was frequently detected in regions of stromal invasion. In addition, the survival rate of stage IA patients with high MUC4 expression was significantly lower than that of stage IA patients with low MUC4 expression (P<0.05). In conclusion, high MUC4 expression in small-sized lung adenocarcinomas correlates with a short DFI and a poor survival rate. Therefore, MUC4 expression might be a new independent factor for prediction of outcome and indication of poor prognosis in lung adenocarcinoma.
Lung Cancer 2007 Feb
PMID:MUC4 expression correlates with poor prognosis in small-sized lung adenocarcinoma. 1712 50

MUC1 (CD227), an established tumor marker, is expressed on glandular epithelia and on epithelial tumors. Tumor MUC1 differs from normal MUC1 by modified glycan side chains. Recently, a novel carbohydrate-induced conformational tumor-associated MUC1 epitope (TA-MUC1) was described, whose clinical relevance in lung cancer is not known. Eighty-five paraffin embedded tissue sections of non-small cell lung cancer (NSCLC) patients (73% male; mean age 64+/-9 years) were stained with the monoclonal antibody PankoMab (against TA-MUC1) and compared with the established antibodies E29 and 214D4 regarding prognostic relevance. TA-MUC1 is virtually absent in bronchial epithelium. As shown by multivariate analysis, only staining with PankoMab, but not with E29 or 214D4, was correlated with patients' survival (p=0.029). Moreover, when regarding interactions of MUC1 antibody staining results and clinico-pathological parameters, patients with lymph node metastasis lacking PankoMab staining were attributed the highest risk by far (Hazard ratio=4.6, 95% CI: 2.1-9.7, p=0.000). In summary, the presence of TA-MUC1 is a favorable prognostic factor in this cohort of NSCLC patients, in particular if lymph node metastases are present. This is in contrast to the results for E29 and 214D4, which recognize less or not glycosylation dependent epitopes. As this is the first report on a well-defined MUC1 epitope associated with improved survival in NSCLC, a more differentiated view on MUC1 may be mandatory.
Lung Cancer 2009 Jan
PMID:TA-MUC1 epitope in non-small cell lung cancer. 1853 57

Malignant epithelial lung carcinoma can be subclassified by histology into several tumor types, including adenocarcinoma and squamous cell carcinoma. The need for a uniform method of classifying lung carcinomas is growing as clinical trials reveal treatment and side effect differences associated with histological subtypes. Diagnosis is primarily performed by morphological assessment. However, the increased use of needle biopsy has diminished the amount of tissue available for interpretation. These changes in how lung carcinomas are diagnosed and treated suggest that the development of improved molecular-based classification tools could improve patient management. We used a 551-patient surgical specimen lung carcinoma retrospective cohort from a regional hospital to assess the association of a large number of proteins with histological type by immunohistochemistry. Five of these antibodies, targeting the proteins TRIM29, CEACAM5, SLC7A5, MUC1, and CK5/6, were combined into one test using a weighted algorithm trained to discriminate adenocarcinoma from squamous cell carcinoma. Antibody-based classification on 600 muM tissue array cores with the five-antibody test was compared to standard histological evaluation on surgical specimens in three independent lung carcinoma cohorts (combined population of 1111 patients). In addition, the five-antibody test was tested against the two-marker panel thyroid transcription factor-1 (TTF-1) and TP63. Both the five-antibody test and TTF-1/TP63 panel had similarly low misclassification rates on the validation cohorts compared to morphological-based diagnosis (4.1 vs 3.5%). However the percentage of patients remaining unclassifiable by TTF-1/TP63 (22%, 95% CI: 20-25%) was twice that of the five-antibody test (11%, 95% CI: 8-13%). The results of this study suggest the five-antibody test may have an immediate function in the clinic for helping pathologists distinguish lung carcinoma histological types. The results also suggest that if validated in prospectively defined clinical trials this classifier might identify candidates for targeted therapy that are overlooked with current diagnostic approaches.
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PMID:A novel five-antibody immunohistochemical test for subclassification of lung carcinoma. 1943 Apr 19


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