Here is the abstract:
[OR28-4] TARGRETIN CAUSES COMPLETE REGRESSION OF MAMMARY CARCINOMA BY INDUCING ADIPOCYTE DIFFERENTIATION IN MAMMARY GLANDS. V R Agarwal, E D Bischoff, R Prudente, T A Cooke, D L Love, R A Heyman, W W Lamph,. 1Retinoid Research, Ligand Pharmaceuticals, Inc., San Diego, CA.
Previously we have shown the chemotherapeutic and chemopreventive activity of a rexinoid, LGD1069 (Targretin), a high affinity ligand for the retinoid X receptors (RXRs) in the N-nitroso-N-methylurea(NMU)-induced rat mammary carcinoma model. To further explore the activity of LGD1069, we have developed a TAM-resistant model employing the NMU-mammary carcinoma model. We have observed that LGD1069 also caused complete regression of TAM-resistant tumors. To evaluate the mechanism of action of Targretin we are using NMU-induced rat mammary tumors. LGD1069 completely regressed 72% of tumors. To further elucidate the molecular mechanism of action of Targretin, we are evaluating the expression of various genes in control tumors, tumors undergoing regression and non-responding tumors.
We observe induction of adipsin, aP2 (fatty acid binding protein adipocyte P2) and LPL (lipoprotein lipase)in the tumors regressing with the LGD1069 treatment. But there was no induction of these genes in tumors which were not responding to the treatment. The adipsin and aP2 induction was rapid and seen even in 6 hrs after the administration of LGD1069. Significant induction of adipogenic markers implies that adipocyte differentiation may be involved with the regression of tumors treated with LGD1069. These modulated genes will also be good surrogate markers in future clinical trials.
Basic Oral Session: Hormones & Cancer II
(1:00 PM - 2:30 PM)
Presentation Date: Monday, June 14, 1999, Time: 1:00P, Room: 5B
L=Special Session, M=Meet the Professor, N=Nurse Symposium, OR=Oral, P=Poster, S=Symposium |
