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)

Sialyl Lewis antigens (sLe(x/a)) are cancer-associated carbohydrate determinants, serve as ligands of the selectin family and are associated with hematogenous metastasis of cancer. So far, the clinicopathologic values of sialyl Lewis x (sLe(x)) and sialyl Lewis a (sLe(a)) in lung cancer have remained controversial. Using immunohistochemistry, the expressions of sLe(x) and sLe(a) antigens, and an airway mucin (MUC5AC) protein, which was supposed to be the major carrying protein of sialyl Lewis moieties, were studied in surgically resected tumor tissues of 61 patients with stages I or II NSCLC. Thirty-two (52.5%) of the 61 studied subjects were found to be positive for expression of sLe(a), 40 (65.6%) were positive for expression of sLe(x), and 16 (26.2%) were positive for MUC5AC protein. Both the expression of sLe(x) and MUC5AC were associated with adenocarcinoma subtype. Patients bearing tumors with MUC5AC and/or sLe(x) expression had a higher probability of post-operative distant metastasis. Survival analysis demonstrated that patients bearing tumors with expression of sLe(x) antigen or MUC5AC had shorter overall survival. The multivariate logistic regression showed that age >65 years old (OR = 0.207, 95% CI = 0.075-0.569, P = 0.002), nodal status (OR = 6.575, 95% CI = 2.459-17.583, P < 0.001), and MUC5AC (OR = 5.545, 95% CI = 1.998-15.386, P = 0.001) were independent factors affecting survival. We concluded that the expression of sLe(x) was related to MUC5AC protein, while patients with tumors co-expressing both MUC5AC and sLe(x) antigen had the worst survival.
Lung Cancer 2005 Jan
PMID:Sialyl Lewis antigens: association with MUC5AC protein and correlation with post-operative recurrence of non-small cell lung cancer. 1560 55

Metastatic lymph nodes (LNs) are the major prognostic factor in resected non small cell lung carcinoma (NSCLC). However, almost 50% of pN0 patients relapse, suggesting metastatic cells undetected by current staging procedures. A combination of markers [cytokeratins 19 and 7 (CK19, CK7) and mucin type 1 (MUC1) mRNAs] was therefore evaluated by real-time RT-PCR in order to detect occult cancer cells. Forty-three NSCLC tumor samples, 4 micrometastatic, 6 metastatic and 84 histologically negative mediastinal LNs from 19 patients with NSCLC were evaluated as well as blood mononuclear cells from 29 healthy volunteers and 17 benign LNs. When tested on cell lines, RT-PCR was particularly efficient for evaluation of CK19, CK7 and MUC1 mRNA expression. All tumor samples were positive for at least 1 marker and 74% of samples were positive for all 3 markers. CK7 and CK19 mRNA were not detected in benign LN and blood cells from healthy donors in contrast with MUC1 mRNA. Only CK7 and CK19 mRNA were therefore used for evaluation of mediastinal LNs: the 6 histologically metastatic and the 4 micrometastatic LNs were positive for at least one marker. Among the 84 histologically negative LNs, 6 (7%) were positive for at least one marker, potentially changing the stage of 2 out of 19 patients. In conclusion, in our feasibility study, parallel molecular detection of CK19 and CK7 mRNA can be considered a specific diagnostic tool for the assessment of microscopic lymphatic spread. Its prognostic impact remains to be evaluated in a prospective study.
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PMID:Real-time RT-PCR detection of CK19, CK7 and MUC1 mRNA for diagnosis of lymph node micrometastases in non small cell lung carcinoma. 1572 95

Sialyl-Lewis x epitopes and MUC5AC protein are known to be overexpressed in mucins secreted by patients suffering from various respiratory diseases. To investigate the mechanisms by which airway inflammatory agents mediate the expression of sialyl-Lewis x epitopes and MUC5AC mucin, we examined the effects of tumor necrosis factor (TNF)-alpha and epidermal growth factor (EGF) in the human lung carcinoma cell line, NCI-H292. Basal expression levels of hST3GalIV, FUT3 and C2/4GnT mRNA, involved in the biosynthesis of sialyl-Lewis x, were higher than those of other glycosyltransferases in NCI-H292 cells. TNF-alpha induced expression of hST3GalIV, FUT3, C2/4GnT and MUC5AC mRNAs in NCI-H292 cells. When cells were pretreated with U73122, a phosphatidylinositol-phospholipase C (PI-PLC) inhibitor, the expression of these glycosyltransferase mRNAs was suppressed. Treating cells with EGF induced the down-regulation of these glycosyltransferase mRNAs and sialyl-Lewis x epitopes, while inducing an increase in expression of MUC5AC mRNA. These EGF-mediated effects on the glycosyltransferase and MUC5AC mRNAs were blocked when cells were first exposed to AG1478, an EGF receptor tyrosine kinase inhibitor. These findings suggest that the expression of sialyl-Lewis x epitopes, which is regulated separately from the expression of MUC5AC protein, may be controlled through pathways such as the EGF receptor tyrosine kinase and PI-PLC signaling cascades in NCI-H292 cells.
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PMID:Regulation of sialyl-Lewis x epitope expression by TNF-alpha and EGF in an airway carcinoma cell line. 1586 35

The cutaneous mucinoses are a heterogeneous group of diseases in which mucin accumulates in the skin. Reticular erythematous mucinosis (REM) is an infrequent variant. We present a 48-year-old man with essential thrombocytosis and REM lesions with atypical telangiectasias on his chest, who developed a non-small cell lung carcinoma. We discuss the unusual clinical finding of telangiectasias over REM lesions and the association with essential thrombocytosis and lung carcinoma.
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PMID:Reticular erythematous mucinosis (REM) with telangiectasias associated with essential thrombocytosis and lung carcinoma. 1590 3

Two Japanese females complained of cough and bronchorrhea for which chest radiographs showed infiltrate in the lungs. The patients were subsequently diagnosed as having bronchioloalveolar carcinoma by transbronchial lung biopsy. After receiving systemic chemotherapy, their symptoms were slightly improved. A few months later, their bronchorrhea and dyspnea worsened, and they were then treated with gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor. Bronchorrhea and dyspnea were improved within 24 h after treatment with gefitinib where the improvement was evident after 6 h for one patient and 24 h for the other patient. Thereafter, their radiological findings showed gradual improvement. Rapid relief of bronchorrhea preceded the improvement seen by the radiological findings. These observations suggest that gefitinib may inhibit mucin production as well as exert anti-proliferative activity against bronchioloalveolar carcinoma.
Lung Cancer 2005 Jul
PMID:Novel effects of gefitinib on mucin production in bronchioloalveolar carcinoma; two case reports. 1594 98

Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is an active agent in non-small cell lung cancer, and rapidly relieves bronchorrhea in patients with bronchioloalveolar carcinoma before the improvement of radiological findings. In addition, epidermal growth factor regulates mucin secretion in normal airway goblet cells. The present study was designed to clarify whether gefitinib modifies mucin production in lung cancer cell lines apart from its anti-proliferative effects, using A549 adenocarcinoma and NCI-H292 mucoepidermoid carcinoma cells expressing EGFR and MUC5AC mRNA. Mucin synthesis was measured by RT-PCR and ELISA, and MAPK and Akt, the downstream targets of EGFR, were examined by Western blotting assay. The clinically-achievable concentration of 1muM gefitinib inhibited the growth of both cells by only 10%, but gefitinib suppressed MUC5AC mRNA levels subsequent to a decrease in intracellular and secreted MUC5AC protein. Gefitinib also inhibited the phosphorylation of MAPK and Akt, and the selective inhibitors PD98059 and LY294002 also suppressed MUC5AC protein synthesis. These findings suggest that gefitinib may inhibits MUC5AC synthesis, at least in part, through MAPK and Akt signaling pathways. Thus, gefitinib inhibits mucin production, which is encouraging for trials involving its use against bronchorrhea in patients with lung cancer.
Lung Cancer 2005 Oct
PMID:Gefitinib inhibits MUC5AC synthesis in mucin-secreting non-small cell lung cancer cells. 1600 52

Aquaporin 3 (AQP3) acts as the membrane channel of water and other small solutes and plays a major role in fluid homeostasis. To investigate the expression of AQP3 in normal and neoplastic lung tissues, we studied a series of 149 lung carcinoma tissues and 2 cell lines by immunohistochemistry, Western blotting, and reverse transcriptase-polymerase chain reaction. In normal lung tissues, immunohistochemical expression of AQP3 was demonstrated in bronchial basal cells, alveolar type II cells, bronchiolar epithelial cells, and secretory cells of submucosal glands. In lung carcinomas, AQP3 expression was observed in 59 (70.2%) of 84 adenocarcinomas. Squamous cell carcinoma and large cell carcinoma had rather low positive ratios (35.8% and 13.4%, respectively). No AQP3 expression was demonstrated in small cell carcinoma, pleomorphic carcinoma, or metastatic colon adenocarcinoma. In adenocarcinomas, AQP3 was detected in all tumors of bronchioloalveolar subtype. Papillary subtype also showed a higher positive ratio of AQP3 compared with that in acinar and solid with mucin subtypes. In addition, AQP3 expression was related to tumor differentiation and clinical stage in adenocarcinomas. Western blotting and reverse transcriptase-polymerase chain reaction analyses confirmed the expression of AQP3 protein and messenger RNA in cell lines and tissues of lung adenocarcinoma. We conclude that AQP3 is widely expressed in the normal respiratory tract and can play an important role in the maintenance of water homeostasis. In addition, lung carcinomas, especially adenocarcinomas, can produce AQP3, possibly in connection with their functional and/or biological nature, although the detailed mechanism of AQP3 expression in lung carcinomas remains to be clarified.
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PMID:Expression of aquaporin 3 (AQP3) in normal and neoplastic lung tissues. 1705 99

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

The initial diagnosis of lung carcinoma is frequently made by fine-needle aspiration biopsy. Novel therapeutic strategies of this disease include tyrosine kinase inhibitors (TKI), such as gefitinib (Iressa) or erlotinib (Tarceva), which target the kinase domain of epidermal growth factor receptor (EGFR). Somatic mutations of this region have been shown to predict a therapeutic response of lung carcinomas to TKI. EGFR mutations have been described in adenocarcinomas of the lung, especially the bronchioloalveolar subtype, which has both cytopathologic and histopathologic definitions. This study investigates whether tumors with EGFR mutations display a characteristic phenotype on fine-needle aspiration biopsy. We identified 37 fine-needle aspiration biopsy of lung masses on which molecular analysis for EGFR mutations was available. Molecular analysis was performed on DNA isolated from formalin-fixed, paraffin-embedded, or frozen tissue from the corresponding core biopsies/cell blocks or resection specimens followed by PCR with primers for the tyrosine kinase region exons 18-24 and nucleotide sequence analysis by gel electrophoresis. Two observers who were blinded to the mutational data assessed several cytomorphological parameters. A semiquantitative analysis included predominant tissue pattern (flat or overlapping), nuclear features (nucleoli, intranuclear inclusions, grooves), cytoplasmic qualities, and extracellular material. All cases were adenocarcinomas primary in the lung. Thirteen cases showed EGFR mutations in exons 18, 19, 20, or 21 of the tyrosine kinase domain. The 24 cases negative for the relevant mutation served as the control group. Tumors with EGFR mutations were statistically more likely to demonstrate a predominantly flat, monolayer architecture (P=0.04) with nuclear inclusions (P=0.014) and the absence of macronucleoli (P=0.001). The predominance of flat monolayers in conjunction with the absence of extracellular mucin and macronucleoli indicated the presence of EGFR mutations with a positive predictive value of 69% and a negative predictive value of 92%. All four cases with extracellular mucin were negative for the examined mutations. Some of the traditional cytomorphological features of bronchioloalveolar carcinoma, i.e., flat monolayers, intranuclear inclusions, and the absence of macronucleoli, statistically correlated with the presence of mutations within the tyrosine kinase region of EGFR. Cytomorphological features could serve as an adjunctive predictive marker of response to TKIs and possibly to other new therapies in development.
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PMID:Cytomorphological correlates of epidermal growth factor receptor mutations in lung carcinoma. 1742 21

Although small cell carcinoma of the gastrointestinal (GI) tract is well-recognized, nonsmall cell type high-grade neuroendocrine carcinoma (HGNEC) of this site remains undefined. At the current time, neither the World Health Organization nor American Joint Committee on Cancer includes this condition in the histologic classifications, and consequently it is being diagnosed and treated inconsistently. In this study, we aimed at delineating the histologic and immunophenotypical spectrum of HGNECs of the GI tract with emphasis on histologic subtypes. Guided primarily by the World Health Organization/International Association for the Study of Lung Cancer criteria for pulmonary neuroendocrine tumors, we were able to classify 87 high-grade GI tract tumors that initially carried a diagnosis of either poorly differentiated carcinoma with or without any neuroendocrine characteristics, small cell carcinoma, or combined adenocarcinoma-neuroendocrine carcinoma into the following 4 categories. The first was small cell carcinoma (n=23), which had features typical of pulmonary small cell carcinoma, although the cells tended to have a more round nuclear contour. The second was large cell neuroendocrine carcinoma (n=31), which had a morphology similar to its pulmonary counterpart and showed positive immunoreactivity for either chromogranin (71%) or synaptophysin (94%) or both. The third was mixed neuroendocrine carcinoma (n=11), which had intermediate histologic features (eg, cells with an increased nuclear/cytoplasmic ratio but with apparent nucleoli), and positive immunoreactivity for at least 1 neuroendocrine marker. The fourth was poorly differentiated adenocarcinoma (n=17). In addition, 5 of the 87 tumors showed either nonsmall cell type neuroendocrine morphology (n=3) or immunohistochemical reactivity for neuroendocrine markers (n=2), but not both. Further analysis showed that most HGNECs arising in the squamous lined parts (esophagus and anal canal) were small cell type (78%), whereas most involving the glandular mucosa were large cell (53%) or mixed (82%) type; associated adenocarcinomas were more frequent in large cell (61%) or mixed (36%) type than in small cell type (26%); and focal intracytoplasmic mucin was seen only in large cell or mixed type. As a group, the 2-year disease-specific survival for patients with HGNEC was 25.4% (median follow-up time, 11.3 mo). No significant survival difference was observed among the different histologic subtypes. In conclusion, our study demonstrates the existence of both small cell and nonsmall cell types of HGNEC in the GI tract, and provides a detailed illustration of their morphologic spectrum. There are differences in certain pathologic features between small cell and nonsmall cell types, whereas the differences between the subtypes of nonsmall cell category (large cell versus mixed) are less distinct. Given the current uncertainty as to whether large cell neuroendocrine carcinoma is as chemosensitive as small cell carcinoma even in the lung, our data provide further evidence in favor of a dichotomous classification scheme (small cell vs. nonsmall cell) for HGNEC of the GI tract. Separation of nonsmall cell type into large cell and mixed subtypes may not be necessary. These tumors are clinically aggressive. Prospective studies using defined diagnostic criteria are needed to determine their biologic characteristics and optimal management.
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PMID:Is nonsmall cell type high-grade neuroendocrine carcinoma of the tubular gastrointestinal tract a distinct disease entity? 1836 Feb 83


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