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Mol Cancer ; 13: 69, 2014 Mar 21.
Article in English | MEDLINE | ID: mdl-24655565

ABSTRACT

BACKGROUND: Recent evidence suggests that aromatase may be involved in the pathogenesis of malignant mesothelioma. Here, we evaluated the effect of exemestane, an inhibitor of aromatase, in the treatment of mesothelioma using in vitro and in vivo preclinical models. RESULTS: We show a significant reduction of cell proliferation, survival, migration and block of cells in S phase of cell cycle in mesothelioma cells upon exemestane treatment. Moreover, we find that CD44, which is involved in mesothelioma cells migration, was modulated by exemestane via cAMP and pCREB. Most importantly, in mice mesothelioma xenograft exemestane causes a significant decrease in tumor size and the association pemetrexed/exemestane is more effective than pemetrexed/cisplatin. CONCLUSION: The preclinical mesothelioma model suggests that exemestane might be beneficial in mesothelioma treatment.


Subject(s)
Androstadienes/administration & dosage , Cyclic AMP Response Element-Binding Protein/biosynthesis , Cyclic AMP/genetics , Hyaluronan Receptors/biosynthesis , Lung Neoplasms/drug therapy , Mesothelioma/drug therapy , Animals , Aromatase Inhibitors/administration & dosage , Cell Proliferation/drug effects , Cisplatin/administration & dosage , Cyclic AMP Response Element-Binding Protein/genetics , Gene Expression Regulation, Neoplastic/drug effects , Humans , Hyaluronan Receptors/genetics , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Mesothelioma/genetics , Mesothelioma/pathology , Mesothelioma, Malignant , Mice , Xenograft Model Antitumor Assays
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