Here's one of the abstracts reporting Rexinoid synergizatiion with Takeda's second generation TZD (CNBC just announced that WLA was slated to open between 118 and 122):
Proc Natl Acad Sci U S A 1997 Jan 7;94(1):237-241
Terminal differentiation of human liposarcoma cells
induced by ligands for peroxisome proliferator-activated
receptor gamma and the retinoid X receptor.
Tontonoz P, Singer S, Forman BM, Sarraf P, Fletcher JA, Fletcher CD, Brun RP, Mueller
E, Altiok S, Oppenheim H, Evans RM, Spiegelman BM
Induction of terminal differentiation represents a promising therapeutic approach to certain human
malignancies. The peroxisome proliferator-activated receptor gamma (PPAR gamma) and the
retinoid X receptor alpha (RXR alpha) form a heterodimeric complex that functions as a central
regulator of adipocyte differentiation. Natural and synthetic ligands for both receptors have been
identified. We demonstrate here that PPAR gamma is expressed at high levels in each of the major
histologic types of human liposarcoma. Moreover, primary human liposarcoma cells can be induced
to undergo terminal differentiation by treatment with the PPAR gamma ligand pioglitazone,
suggesting that the differentiation block in these cells can be overcome by maximal activation of the
PPAR pathway. We further demonstrate that RXR-specific ligands are also potent adipogenic
agents in cells expressing the PPAR gamma/RXR alpha heterodimer, and that simultaneous
treatment of liposarcoma cells with both PPAR gamma- and RXR-specific ligands results in an
additive stimulation of differentiation. Liposarcoma cell differentiation is characterized by
accumulation of intracellular lipid, induction of adipocyte-specific genes, and withdrawal from the
cell cycle. These results suggest that PPAR gamma ligands such as thiazolidinediones and
RXR-specific retinoids may be useful therapeutic agents for the treatment of liposarcoma.
PMID: 8990192, UI: 97144425 |
