Subject(s)
Argyria/diagnosis , Skin/pathology , Aged , Argyria/etiology , Argyria/pathology , Colloids/adverse effects , Color , Humans , Male , Silver Compounds/adverse effectsSubject(s)
Carcinoma, Non-Small-Cell Lung/metabolism , Dinoprostone/metabolism , Isoenzymes/metabolism , Lung Neoplasms/metabolism , Microtubule-Associated Proteins/metabolism , Neoplasm Proteins/metabolism , Prostaglandin-Endoperoxide Synthases/metabolism , Animals , Antisense Elements (Genetics) , Cell Line, Tumor , Cyclooxygenase 2 , Gene Expression , Humans , Inhibitor of Apoptosis Proteins , Membrane Proteins , Mice , Mice, SCID , SurvivinABSTRACT
Elevated tumor cyclooxygenase 2 (COX-2) expression is associated with increased angiogenesis, tumor invasion and promotion of tumor cell resistance to apoptosis. The mechanism(s) by which COX-2 exerts its cytoprotective effects are not completely understood but may be due to an imbalance of pro- and anti-apoptotic gene expression. To analyze COX-2-dependent gene expression and apoptosis, we created cell lines constitutively expressing COX-2 cDNA in sense and antisense orientations. Whereas COX-2 sense cells have significantly heightened resistance to radiation and drug-induced apoptosis, COX-2 antisense cells are highly sensitive to apoptosis induction. We found that the expression of the anti-apoptotic protein survivin correlated positively with COX-2 expression. A COX-2-dependent modulation of survivin ubiquitination led to its stabilization in COX-2 overexpressing cells, and this effect was replicated by exogenous PGE2 treatment of parental tumor cells. In contrast to previous studies in other cell types, in nonsmall cell lung cancer cells survivin was expressed in a cell cycle-independent manner. When established in SCID mice in vivo, COX-2 antisense-derived tumors had significantly decreased survivin levels while COX-2 sense-derived tumors demonstrated elevated levels compared with controls. In accord with these findings, survivin and COX-2 were frequently upregulated and co-expressed in human lung cancers in situ.
Subject(s)
Carcinoma, Non-Small-Cell Lung/enzymology , Isoenzymes/metabolism , Lung Neoplasms/enzymology , Microtubule-Associated Proteins/metabolism , Prostaglandin-Endoperoxide Synthases/metabolism , Animals , Antisense Elements (Genetics) , Apoptosis , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Cell Cycle , Cell Line, Tumor , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Cyclooxygenase Inhibitors/pharmacology , Dinoprostone/pharmacology , Humans , Inhibitor of Apoptosis Proteins , Isoenzymes/antagonists & inhibitors , Isoenzymes/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Membrane Proteins , Mice , Neoplasm Proteins , Prostaglandin-Endoperoxide Synthases/genetics , Survivin , Ubiquitins/metabolism , Up-RegulationABSTRACT
BACKGROUND: Fine needle aspiration (FNA) diagnosis of simultaneous medullary and papillary thyroid carcinoma in independent thyroid lobes is exceedingly rare. CASE: A 36-year-old female presented with a one-month history of dysphagia. Thyroid ultrasound revealed a multinodular goiter. She was clinically and biochemically euthyroid. FNA of the right thyroid nodule was consistent with medullary carcinoma, and FNA of the left thyroid lobe was consistent with papillary carcinoma. Immunohistochemistry revealed strong calcitonin and CEA positivity in the right lobe and lack of staining in the left lobe. Conversely, staining for thyroglobulin was negative on the right lobe and positive on the left lobe. CONCLUSION: The patient developed tumors in separate lobes of the thyroid. Immunoreactivity of calcitonin, CEA and thyroglobulin made a sharp distinction between the two tumors. Therefore, we conclude that these tumors were not linked by either embryology or genetics.
