Abstract |
Studies were performed in female Sprague-Dawley rats to determine the efficacy of a new RXR specific retinoid ( 9cUAB30) when combined with tamoxifen in the prevention of mammary cancers and to determine various pharmacokinetic parameters of the retinoid. When administered by gavage, 9cUAB30 was rapidly absorbed and had a serum t(1/2) of 13.5 h. Since the retinoid was administered in the diet for the chemoprevention study, a 28-day study in which 9cUAB30 was given at dose levels of 200, 400, and 600 mg/kg diet revealed fairly constant serum levels regardless of dose or length of treatment; possibly accounting for the observed low toxicity of this compound. When suboptimal doses of 9cUAB30 were given in the methylnitrosourea (MNU)-induced mammary cancer model, the following average number of mammary cancers were observed: 9cUAB30 (150 mg/kg diet), 4.3; tamoxifen (0.4 mg/kg diet), 4.6; 9cUAB30 (150 mg/kg diet)+ tamoxifen (0.4 mg/kg diet), 2.6; and controls, 6.0. Thus, the combination of the agents resulted in an increased effect in preventing mammary cancers; suggesting that cancer cell proliferation was inhibited by the compounds blocking different pathways.
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Authors | Clinton J Grubbs, Donald L Hill, Kirby I Bland, Samuel W Beenken, Tsu-Han Lin, Isao Eto, Venkatram R Atigadda, Kimberly K Vines, Wayne J Brouillette, Donald D Muccio |
Journal | Cancer letters
(Cancer Lett)
Vol. 201
Issue 1
Pg. 17-24
(Nov 10 2003)
ISSN: 0304-3835 [Print] Ireland |
PMID | 14580682
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Alkylating Agents
- Antineoplastic Agents, Hormonal
- Fatty Acids, Unsaturated
- Naphthalenes
- Receptors, Retinoic Acid
- Retinoid X Receptors
- Retinoids
- Transcription Factors
- Tamoxifen
- Methylnitrosourea
- UAB 30
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Topics |
- Administration, Oral
- Alkylating Agents
(toxicity)
- Animals
- Antineoplastic Agents, Hormonal
(pharmacology)
- Antineoplastic Combined Chemotherapy Protocols
(pharmacology)
- Body Weight
(drug effects)
- Chromatography, High Pressure Liquid
- Diet
- Dose-Response Relationship, Drug
- Fatty Acids, Unsaturated
(administration & dosage, blood, pharmacology)
- Female
- Mammary Neoplasms, Experimental
(chemically induced, drug therapy, prevention & control)
- Methylnitrosourea
(toxicity)
- Naphthalenes
(administration & dosage, blood, pharmacology)
- Rats
- Rats, Sprague-Dawley
- Receptors, Retinoic Acid
- Retinoid X Receptors
- Retinoids
(pharmacology)
- Tamoxifen
(pharmacology)
- Transcription Factors
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