| 摘要 |
The present invention is based, in part, on our studies of molecular pathways that include the deubiquitinase CYLD. Accordingly, the present invention features, inter alia, nucleic acid constructs that express CYLD or a biologically active variant thereof (e.g., a variant including the catalytic domain), nucleic acids that inhibit the expression of a negative regulator of CYLD (e.g., PDE4B or LNK2), nucleic acids that modulate the expression of downstream CYLD targets (e.g., Akt, by inhibiting or promoting the expression of the downstream target), compositions including one or more of these types of constructs (e.g., pharmaceutical compositions), kits including one or more of the compositions described herein and instructions for use, screening methods to identify therapeutic agents {e.g., anti-inflammatory agents) that upregulate CYLD, downregulate a negative regulatory of CYLD, or modulate (e.g., inhibit) a downstream CYLD target (e.g., Akt), and various methods of treatment including the administration of the nucleic acids described above, protein biotherapeutics, and/or small molecules, alone or in combination, to address cancer, inflammation, and fibrosis. The compositions described herein can be used in the preparation of a medicament (e.g., used in the preparation of a medicament to treat cancer, inflammation, fibrosis, or one or more of the more specific conditions described herein). |
| 主权项 |
1. A method of treating a patient who is suffering from a medical condition associated with inflammation of the ears, nose, nasal passages, throat, the lung, the bronchial tree or a reproductive organ, the method comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising an agent that (a) upregulates the expression of the gene cylindromatosis (CYLD) or the activity of the encoded deubiquitinase or (b) downregulates the expression of the Akt gene or inhibits the activity of the encoded kinase. |
