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)

We assessed the usefulness of several immunohistochemical stains in distinguishing these two neoplasms, including cytokeratin 7, cytokeratin 20 (CK20), neuron-specific enolase, chromogranin, synaptophysin, neurofilaments (NF), thyroid-transcription factor-1 (TTF-1), CD56 antigen, S-100 protein, vimentin, c-erbB-2 oncoprotein, and CD117 antigen. All 13 cases of Merkel cell carcinoma evaluated were positive for CK20, and negative for TTF-1. Twelve of 13 Merkel cell carcinoma cases were positive for NF. Eleven of 13 cases of small cell lung carcinoma were positive for TTF-1. All small cell lung carcinoma cases were negative for NF, and all but one were negative for CK20. In terms of the remaining antigens, there were no differences of significance between the two neoplasms. These findings suggest that a set of three immunohistochemical stains, including CK20, NF, and TTF-1, is useful in affording a distinction between Merkel cell carcinoma and small cell lung carcinoma.
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PMID:Immunohistochemical distinction between merkel cell carcinoma and small cell carcinoma of the lung. 1662 69

Mevalonate metabolites play an essential role in transducing epidermal growth factor (EGF) receptor (EGFR)-mediated signaling, as several of these metabolites are required for the function of this receptor and the components of its signaling cascades. Thus, the depletion of mevalonate metabolites may have a significant effect on EGFR function. Lovastatin is a specific and potent inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme of the mevalonate pathway. Targeting 3-hydroxy-3-methylglutaryl CoA reductase using lovastatin induces a potent tumor-specific apoptotic response in a variety of tumor types at therapeutically achievable levels of this drug. The effects of lovastatin on EGFR function and the potential combination effects with EGFR tyrosine kinase inhibitors, such as gefitinib, were evaluated. Lovastatin treatment inhibited EGF-induced EGFR autophosphorylation and its downstream signaling cascades by 24 hours. Combining lovastatin and gefitinib showed enhanced inhibition and cooperative cytotoxicity in a variety of cell lines that included all eight squamous cell carcinomas, four non-small cell lung carcinoma, and four colon carcinoma cell lines tested. Isobologram analyses confirmed that this combination was synergistic, inducing a potent apoptotic response. A phase I study has shown the safety and potential clinical benefit of high-dose lovastatin in patients with recurrent squamous cell carcinoma. The use of lovastatin, which is metabolized by CYP3A4, is contraindicated with drugs, such as gefitinib and erlotinib, which are also metabolized by CYP3A4 due to greatly enhanced toxicity. Rosuvastatin, a relatively novel potent mevalonate pathway inhibitor that is not metabolized significantly by CYP3A4, is a more appropriate statin to combine with either erlotinib or gefitinib. The combination of erlotinib and rosuvastatin has been proposed for a phase I/II study in advanced non-small cell lung carcinoma.
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PMID:Strategies to enhance epidermal growth factor inhibition: targeting the mevalonate pathway. 1685 22

The aim of this study was to determine the incidence and role of c-erbB-2 overexpression as a predictive/prognostic marker in small-cell lung carcinoma (SCLC). We performed a retrospective study on subjects with a biopsy-proven diagnosis of SCLC. A chart review for demographic and clinical data was performed on patients with SCLC diagnosed between 1998 and 2004. c-erbB-2 overexpression was evaluated using immunohistochemistry performed on archival paraffin-embedded specimens. Sixty-seven patients with SCLC were identified (6 females, 61 males; median age- 56.5 yr, range-34-75) all of whom had adequate tissue specimens available for c-erB-2 testing. Of the 67 specimens, 12 (17.9%) showed c-erbB-2 overexpression. Seventy-five of the cases were positive for c-erbB-2, had extensive disease. The median overall survival of patients with SCLC whose tumors were positive and negative for c-erbB-2 were 8 +/- 0.9 months (95%CI 6.3-9.7) and 11 +/- 1.5 months (95%CI 8.0-14.0), respectively. c-erbB-2 overexpression detected using immunohistochemistry is observed in 17.9% of patients with SCLC and has statistically significant prognostic value. Our findings suggest that c-erbB-2 may be a potential target for site-specific immunotherapy in SCLC. Considering one technique examined, further molecular investigation is needed to confirm these preliminary findings.
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PMID:The role of c-erbB-2 expression on the survival of patients with small-cell lung cancer. 1723 26

The expression of c-erbB receptors was immunohistochemically examined in paraffin embedded specimens from non-small-cell lung carcinomas. A total of 209 patients were enrolled [squamous-cell carcinomas (n=59), adenocarcinomas (n=130), large-cell carcinomas (n=15) and giant-cell carcinomas (n=5)]. The HercepTest kit scoring guidelines were used for the interpretation of positivity. C-erbB-1 was overexpressed in older patients, in squamous-cell carcinomas and in poorly-differentiated tumours, whereas c-erbB-2 overexpression with adenocarcinomas and poorly-differentiated tumours. C-erbB-4 overexpression correlated with advanced disease stage. The c-erbB-1/4 pair was the most commonly overexpressed and significantly correlated with female gender, while the c-erbB-1/2 pair with older age. Response to chemotherapy was significantly reduced in patients with tumours overexpressing c-erbB-1 receptor as well as the c-erbB-1/2 and c-erbB-3/4 receptor pairs. Patients' overall survival was significantly correlated with the co-expression of c-erbB-1 and c-erbB-4 receptors. These findings clearly suggest that specific receptors overexpression or co-overexpression is correlated with patients' disease control rate and outcome. A better understanding of the overexpression of the heterodimerized partners of c-erbB family receptors may provide a useful predictive indicator of response to molecular targeted therapies with c-erbB inhibitors.
Lung Cancer 2007 Aug
PMID:Simultaneous expression of c-erbB-1, c-erbB-2, c-erbB-3 and c-erbB-4 receptors in non-small-cell lung carcinomas: correlation with clinical outcome. 1744 48

Matrix metalloproteinases (MMPs) are proteolytic enzymes that are implicated in multiple stages of cancer progression including invasion and metastasis. MMPs exert these effects by cleaving a diverse group of substrates, which include not only structural components of the extracellular matrix, but also growth factor receptors. By gelatin zymography we verified MMP activity in the pleural effusions of patients with benign and malignant disease. Of these patients, 32 had malignant pleural effusion, consisting of 20 breast cancer, 6 non-small cell lung carcinoma, 4 ovarian carcinoma, and 2 colonic adenocarcinoma, and 10 had benign pleural effusion (5 pleurisy and 5 cirrhosis). Zymography showed the constant presence of a substantial amount of MMP-2 in all samples analyzed, whereas MMP-9 was present to lesser quantities. MMP-2 activity was enhanced in pleural effusions from patients with benign diseases compared with cancer patients. MMP-9 was present in 59% of cancer patients and the lytic activity was enhanced in pleurisy and absent in cirrhosis. Furthermore, we determined the pleural effusion levels of the soluble extracellular domain of HER-2/neu. The levels of HER-2/neu ECD were above the cut-off value in breast cancer patients. No correlation between gelatinolytic activities and high HER-2/neu ECD values was found.
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PMID:Gelatinolytic activities (matrix metalloproteinase-2 and -9) and soluble extracellular domain of Her-2/neu in pleural effusions. 1761 66

Clinical efficacy of gefitinib (ZD1839, Iressa), which is an inhibitor specific for epidermal growth factor (EGF) receptor tyrosine kinase, has been shown in non-small-cell lung carcinoma patients with EGF receptor mutations, so these mutations are useful marker(s) to find a responder for the drug. Recent studies have shown that the EGF receptor gene mutation is rare in squamous cell carcinoma in the esophageal and head and neck regions. We previously reported that the expression of the chemokine BRAK/CXCL14 in head and neck squamous cell carcinoma (HNSCC) cells was down-regulated by EGF treatment, and that forced expression of BRAK in tumor cells decreased the tumorigenicity of the cells in xenografts. Thus, we investigated the relationship between restoration of BRAK expression by gefitinib and the efficacy of the drug for tumor suppression. We found that EGF down-regulated BRAK expression through the MEK-extracellular signal regulated kinase pathway and that this down-regulated expression was restored by gefitinib in vitro. Oral administration of gefitinib significantly (P < 0.001) reduced tumor growth of xenografts of three HNSCC cell lines (HSC-2, HSC-3, and HSC-4), in female athymic nude mice, accompanied by an increase in BRAK expression specifically in tumor tissue. This tumor-suppressing effect of the drug was not observed in the case of BRAK non-expressing cells. Furthermore introduction of BRAK shRNA vector reduced both the expression levels of BRAK in HSC-3 cells and the antitumor efficacy of gefitinib in vivo. Our data showing an inverse relationship between BRAK expression levels in tumor cells and the tumor growth rate indicate that the gefitinib-induced increase in BRAK expression is beneficial for tumor suppression in vivo.
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PMID:Restoration of BRAK / CXCL14 gene expression by gefitinib is associated with antitumor efficacy of the drug in head and neck squamous cell carcinoma. 1967 87

Lung cancer is the leading cause of death from cancer in Western countries. For improved diagnosis and refined therapeutical approaches it is of major importance to understand by what mechanisms carcinoma of the lung develop. The analysis of primary lung cancer revealed specific chromosomal alterations and allelic losses of the short arm of chromosome 3. Genetic aberrations have been observed in proto-oncogenes such as H-ras, K-ras, C-myc and raf-1 as well as in the tumor suppressor genes Rb and p53. Rearrangement of rlf and elevated expression in certain lung tumors have also been reported. The development of lung cancer also involves the altered activation of genes coding for growth factors such as TGF beta 2 and certain growth factor receptor genes such as c-erbB-2, HEK2 and FGFR-4.
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PMID:Oncogenic alterations in primary human lung-tumors (review). 2160 36


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