Chemopreventive efficacy of Targretin in rodent models of urinary bladder,             colon/intestine, head and neck and mammary cancers.
The chemopreventive efficacy of Targretin was evaluated in various rodent             cancer models. In the rat model of 4-hydroxybutyl(butyl)nitrosamine (OH-BBN)-induced             urinary bladder cancer, it was found that Targretin administered in the diet (beginning             one week after the last OH-BBN treatment) for 5.5 months increased the number             and size of urinary bladder cancers. In the azoxymethane (AOM)-induced model of             colon carcinogenesis (in which rats develop minimally invasive colonic cancers),             Targretin was ineffective as a chemopreventive agent, decreasing neither tumor             incidence nor multiplicity. Treatment of Min mice with Targretin for 45 days similarly             failed to decrease the multiplicity of small intestinal tumors. Similarly, no             preventive efficacy was noted for Targretin when the incidence of tumors in the             head and neck model (squamous cell tongue tumors) induced by 4-nitroquinoline             1-oxide (4-NQO) were examined. In contrast, use of even a suboptimal dose of Targretin             (40 ppm) in a sensitive breast cancer model [methylnitrosourea (MNU)-induced ER+             mammary cancers] reduced cancer multiplicity by 60%. Finally, based on the hypothesis             that Targretin may decrease the expression of COX‑2, the effects of Targretin             and COX inhibitors were compared in these models. There was minimal overlap of             efficacy. That is, models which were relatively susceptible to NSAIDs or COX-2             inhibitors tended not to be sensitive to Targretin and vice versa.
Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20852, USA. lubetr@mail.nih.gov
Ronald A
RA
Lubet
Margie L
ML
Clapper
David L
DL
McCormick
Michael A
MA
Pereira
W-C L
WC
Chang
Vernon E
VE
Steele
Susan M
SM
Fischer
M Margaret
MM
Juliana
Clinton J
CJ
Grubbs
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000077610:Bexarotene; D000068579:Celecoxib; D003110:Colonic Neoplasms / Q000517:prevention & control; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D006258:Head and Neck Neoplasms / Q000517:prevention & control; D007414:Intestinal Neoplasms / Q000517:prevention & control; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000517:prevention & control; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D011720:Pyrazoles / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000627:therapeutic use; D013764:Tetrahydronaphthalenes / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000517:prevention & control
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D013764:Tetrahydronaphthalenes; D000077610:Bexarotene; D000068579:Celecoxib