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Efficacy of Selective Estrogen Receptor Modulators in Nude Mice Bearing Human Transitional Cell Carcinoma

Authors
Journal
Urology
0090-4295
Publisher
Elsevier
Publication Date
Volume
69
Issue
6
Identifiers
DOI: 10.1016/j.urology.2007.02.041
Keywords
  • Basic Science
Disciplines
  • Medicine

Abstract

Objectives To evaluate estrogen receptors as a therapeutic target for human bladder cancer. Methods The ability of the selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene to inhibit 5637 human transitional cell carcinoma cell proliferation was determined in vitro and in xenograft studies using 5637 cells in female athymic BALB/c nu/nu mice. Results Treatment with tamoxifen, raloxifene, or the pure antiestrogen ICI 182,780 inhibited proliferation of 5637 cells in vitro. In the first xenograft study, raloxifene (10, 100, or 1000 μg/day) administered by oral gavage inhibited the growth of tumors compared with placebo or untreated controls ( P <0.05). In a second experiment, tamoxifen (8.3, 125, or 1250 μg/day) delivered by time-release pellet inhibited tumor growth compared with placebo-treated controls ( P <0.01). A comparison study in which tamoxifen (8.3 or 125 μg/day) or raloxifene (100 μg/day) was administered by slow-release pellet demonstrated that both SERMs reduced growth compared to placebo-treated controls ( P <0.05), with comparable effectiveness. There was no detectable tumor in 17 of 30 treated mice. In all studies, average tumor volumes in SERM-treated animals declined over the course of treatment. Conclusions Selective estrogen receptor modulators inhibit the growth of 5637 transitional cell carcinoma cell xenografts, supporting the rationale to evaluate these agents as targeted therapeutics for patients with urothelial carcinoma.

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