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Consistent with this protective effect of celecoxib, tumor multiplicity was similar in the two groups, despite the fact that the celecoxibtreated mice were generally older at the time of sacrifice.To ensure that this protective effect of celecoxib occurred at concentrations of drug that can be safely achieved in humans, serum celecoxib levels were measured.It was of interest, therefore, to determine amounts of PGE in mammary glands harvested from control versus celecoxibtreated mice.PGE elicits cellular responses via interaction with four Revefenacin cellsurface receptors, EP. Each of the four known EP receptors was expressed in the mammary glands of these mice. This finding provided a rationale for investigating the chemopreventive activity of celecoxib in this model.The fact that a clinically relevant concentration of celecoxib caused a significant delay in the onset of mammary tumors raises important issues.Observational studies show a clear correlation between NSAID use and reduced risk of colorectal cancer, the results are less clear than for colon cancer.Additionally, PGE was recently found to increase activity of the estrogen synthase aromatase. We showed that celecoxib caused nearly a reduction in amounts of PGE in mammary tissue.Four PGE receptor subtypes, EP, have been identified. In one recent study, homozygous deletion of EP caused a decrease in the number and size of intestinal polyps in a mouse model of human familial adenomatous polyposis. We show for the first time that all four EP receptors are expressed in mammary tissue.Notably, an EP receptor antagonist has been reported to decrease the incidence of chemically induced breast XY1 cancer in rats. It is also worth considering the potential implications of this study for the treatment of breast cancer.Celecoxib, a Selective Cyclooxygenase Inhibitor, Protects against Human Epidermal Growth Factor Receptor Louise R.Click on Request Permissions which will take you to the Copyright Clearance Centers Downloaded from cancerres.aacrjournals.org on April. American Association for Cancer Research. To optimize these treatment strategies, we have investigated whether tumor progression can be delayed by combining the pure antiestrogen fulvestrant with the nonsteroidal aromatase inhibitor letrozole.These studies were done in ovariectomized, athymic mice bearing tumors of estrogen receptorpositive human breast cancer cells stably transfected with the aromatase gene. All treatments were effective in suppressing tumor growth compared with controls. Tumor volumes of the fulvestranttreated group had doubled in weeks.After weeks of letrozole were assigned to secondline therapy with letrozole. However, tumors continued to increase in volume in these groups.Although the incidence of breast cancer increases with age, circulating levels of estrogen are low in postmenopausal women as the ovaries are no longer the major source of the estrogen synthesis.Production of estrogens in postmenopausal women occurs mainly via conversion of adrenal androgens mediated by aromatase in peripheral tissue, such as adipose tissue. Current treatments for postmenopausal hormonedependent breast cancer patients include two strategies to reduce the effects of estrogens on tumor growth.One method involves blocking estrogen from binding to estrogen receptors with antiestrogens and the other inhibits estrogen synthesis with aromatase inhibitors.The antiestrogen tamoxifen has been used since the s for the treatment of breast cancer and has been shown to delay recurrences and contralateral breast cancer.

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