Effect of asoprisnil on uterine proliferation markers and endometrial expression of the tumour suppressor gene, PTEN  

Oleh:

Wilkens, J. ; Williams, A.R.W. ; Chwalisz, K. ; Han, C. ; Cameron, I.T.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Human Reproduction vol. 24 no. 05 (May 2009), page 1036.
Topik: asoprisnil/uterine tissues/proliferation/phosphatase and tensin homologue

Ketersediaan

Perpustakaan FK Nomor Panggil: H07.K.2009.02 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

BACKGROUND: The selective progesterone receptor modulator asoprisnil suppresses uterine bleeding and decreases leiomyoma volume while maintaining follicular phase estrogen concentrations. For safety of potential clinical applications, any proliferative effect of asoprisnil on uterine tissues, particularly endometrium, needs to be established. METHODS: In a double-blind, randomized, placebo-controlled study (continuation of previously published trial No. NCT00150644 [ClinicalTrials.gov] (Williams et al., 2007 and Wilkens et al., 2008)), 33 patients with symptomatic uterine leiomyomata received placebo, 10 or 25 mg asoprisnil daily for 12 weeks before hysterectomy. Proliferation markers Ki-67 and anti-phospho-histone H3 (PH3) were immunolocalized in endometrium, myometrium and leiomyoma tissue. Endometrial PTEN (phosphatase and tensin homologue, a tumour suppressor gene) expression was also assessed by immunohistochemistry. PH3-positive glandular and stromal cells were counted per measured endometrial area. Endometrial Ki-67 expression was assessed using stereological methods. Stained myometrial and leiomyoma cells were counted per 10 fields (x250). PTEN immunostaining was quantified using a histoscore. Each asoprisnil group was compared with placebo (secretory phase) with significance at 0.05 level. RESULTS: Endometrial epithelial proliferation and PTEN expression were not significantly different between placebo and asoprisnil groups. Decreased stromal Ki-67 expression (P < 0.05) suggested any effect of asoprisnil on endometrial proliferation to be inhibitory. Immunolocalization of PTEN expression was not different between treatment groups in any tissue compartments. Myometrial Ki-67 expression decreased following asoprisnil 25 mg (P < 0.05). CONCLUSIONS: Asoprisnil does not induce proliferation of uterine tissues and does not suppress endometrial PTEN expression.

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