PMID- 9458093
OWN - NLM
STAT- MEDLINE
DCOM- 19980224
LR  - 20181201
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 58
IP  - 3
DP  - 1998 Feb 1
TI  - Beyond tamoxifen: the retinoid X receptor-selective ligand LGD1069 (TARGRETIN) 
      causes complete regression of mammary carcinoma.
PG  - 479-84
AB  - Recently, we reported that LGD1069, a high-affinity ligand for the retinoid X 
      receptors (RXRs), was shown to have an efficacy equivalent to that of tamoxifen 
      (TAM) as a chemopreventive agent in the N-nitroso-N-methylurea-induced rat 
      mammary carcinoma model. Furthermore, LGD1069 was very well tolerated during 13 
      weeks of chronic therapy with no classic signs of "retinoid-associated" 
      toxicities. Due to the high efficacy and benign profile of this RXR agonist as a 
      suppressor of carcinogenesis, we examined its role as a therapeutic agent on 
      established mammary carcinomas. In the rat mammary carcinoma model, 
      N-nitroso-N-methylurea was used to induce tumors, and the tumors were allowed to 
      grow to an established size prior to initiation of treatment. LGD1069-treated 
      animals showed complete regression in 72% of treated tumors and had a reduced 
      tumor load compared to control. In addition, the combination of LGD1069 and TAM 
      showed increased efficacy over either agent alone. Histopathological analysis 
      showed a reduction of LGD1069-treated tumor malignancy, an increase in 
      differentiation, and a sharp decrease in cellular proliferation compared to 
      vehicle-treated control tumors. These data demonstrate that the RXR-selective 
      ligand LGD1069 is a highly efficacious therapeutic agent for mammary carcinoma 
      and enhances the activity of TAM.
FAU - Bischoff, E D
AU  - Bischoff ED
AD  - Department of Retinoid Research, Ligand Pharmaceuticals, Inc., San Diego, 
      California 92121, USA.
FAU - Gottardis, M M
AU  - Gottardis MM
FAU - Moon, T E
AU  - Moon TE
FAU - Heyman, R A
AU  - Heyman RA
FAU - Lamph, W W
AU  - Lamph WW
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Anticarcinogenic Agents)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Tetrahydronaphthalenes)
RN  - 0 (Transcription Factors)
RN  - 094ZI81Y45 (Tamoxifen)
RN  - 684-93-5 (Methylnitrosourea)
RN  - A61RXM4375 (Bexarotene)
SB  - IM
MH  - Animals
MH  - Anticarcinogenic Agents/therapeutic use
MH  - Antineoplastic Agents/*therapeutic use
MH  - Antineoplastic Agents, Hormonal/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Bexarotene
MH  - Cell Division/drug effects
MH  - Drug Screening Assays, Antitumor
MH  - Drug Synergism
MH  - Female
MH  - Mammary Neoplasms, Experimental/chemically induced/*drug therapy/pathology
MH  - Methylnitrosourea
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Retinoic Acid/*agonists
MH  - Retinoid X Receptors
MH  - Tamoxifen/administration & dosage
MH  - Tetrahydronaphthalenes/administration & dosage/*therapeutic use
MH  - Transcription Factors/*agonists
EDAT- 1998/02/11 00:00
MHDA- 1998/02/11 00:01
CRDT- 1998/02/11 00:00
PHST- 1998/02/11 00:00 [pubmed]
PHST- 1998/02/11 00:01 [medline]
PHST- 1998/02/11 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1998 Feb 1;58(3):479-84.