TREATMENT OF DISEASE STATES WHICH RESULT FROM NEOPLASTIC CELL PROLIFERATION USING PPAR-GAMMA ACTIVATORS AND COMPOSITIONS USEFUL THEREFOR

摘要

In accordance with the present invention, it has been discovered that PPAR gamma is expressed consistently in tissues associated with each of a variety of disease states which result from neoplastic cell proliferation. It has further been discovered that maximal activation of PPAR gamma with exogenous ligand promotes terminal differentiation of primary cells which are otherwise subject to neoplastic cell proliferation. In accordance with another aspect of the invention, it has been discovered that RXR-specific ligands are also potent agents for induction of differentiation of cells expressing the PPAR gamma /RXR alpha heterodimer, and that simultaneous treatment of cells subject to neoplastic cell proliferation with a PPAR gamma -selective ligand, in combination with an RXR-specific ligand, results in an additive stimulation of differentiation. Thus, the effect of neoplastic cell proliferation can be ameliorated by treatment of cells undergoing neoplastic cell proliferation with PPAR gamma agonists, optionally in the further presence of RXR agonists, thereby blocking further proliferation thereof. Accordingly, compounds and compositions which are useful for the treatment of a variety of disease states which result from neoplastic cell proliferation have been identified and are described herein.