Abstract: In accordance with the present invention, there are provided novel receptor interacting factors, referred to herein as “SMRT”, i.e., a silencing mediator (co-repressor) for retinoic acid receptor (RAR) and thyroid hormone receptor (TR). SMRT is a novel protein whose association with RAR and TR both in solution and on DNA response elements is destabilized by ligand. The interaction of SMRT with mutant receptors correlates with the transcriptional silencing activities of receptors. In vivo, SMRT functions as a potent co-repressor. A GAL4 DNA binding domain (DBD) fusion of SMRT behaves as a frank repressor of a GAL4-dependent reporter. Together, these data identify a novel class of cofactor which is believed to represent an important mediator of hormone action.

Abstract: A novel gamma retinoic acid receptor is disclosed. The novel receptor is encoded for by cDNA carried on plasmid pGEM-hRAR&ggr;, which has been deposited with the American Type Culture Collection for patent purposes. Chimeric receptor proteins are also disclosed. The chimera contain at least one functional domain from the new gamma retinoic acid receptor.

Abstract: In accordance with the present invention, it has been discovered that monocyte conditioned medium (MCM) obtained from patients with liver disease stimulates the proliferation of fibroblasts. Platelet derived growth factor (PDGF) has also been found to stimulate fibroproliferation of fibroblasts, and to be at least partially responsible for the fibroproliferative effect of the MCM. Further in accordance with the present invention, the effect of MCM and PDGF on the expression of c-fos and c-jun has been investigated, because c-fos and c-jun form AP-1 complexes which can stimulate genes involved in proliferation. It has recently been reported that pentoxifylline inhibits platelet derived growth factor-stimulated proliferation. The mechanism of this action of pentoxifylline is unclear. Thus, in the course of the work undertaken as part of the present invention, studies were conducted to determine whether pentoxifylline altered the expression of c-fos and c-jun.

Abstract: The present invention provides novel cryptophycin compounds having the following structure: ##STR1## The present invention also provides methods for producing cryptophycins from the Nostoc sp. of blue-green algae (cyanobacteria). Pharmaceutical compositions comprising novel cryptophycins are also provided by the present invention, as are methods for using cryptophycins to inhibit the proliferation of hyperproliferative cells. The present invention further provides methods for using cryptophycins to inhibit the proliferation of hyperproliferative cells with drug resistant phenotypes, and to treat pathological conditions, such as neoplasia.

Abstract: In accordance with the present invention, novel retroviral vectors containing modified long terminal repeats (LTRS) which enable high level and ligand-modulatable expression of a desired gene product, even after prolonged periods of cellular quiescence, have been designed and constructed. Invention vectors overcome proviral transcriptional inactivation which occurs in cultured primary cells that are growth arrested due to environmental constraints such as contact inhibition and/or nutrient starvation. Invention vectors represent a class of retroviral vectors in which LTR-promoted proviral expression in infected cells may be maintained or increased, even in situations generally considered to be non-permissive for retroviral vectors.