Adenomyosis is an oestrogen-dependent disease caused by a downward extension of the endometrium into the uterine myometrium. Epithelial-mesenchymal transition (EMT) endows cells with migratory and invasive properties and can be induced by oestrogen. We hypothesized that oestrogen-induced EMT is critical in the pathogenesis of adenomyosis. We first investigated whether EMT occurred in adenomyotic lesions and whether it correlated with serum 17β-oestradiol (E2) levels. Immunohistochemistry was performed on adenomyotic lesions and corresponding eutopic endometrium samples from women with adenomyosis. Endometria from women without endometrial disorders were used as a control. In the epithelial component of adenomyotic lesions, vimentin expression was up-regulated and E-cadherin expression was down-regulated compared to the eutopic endometrium, suggesting that EMT occurs in adenomyosis. In adenomyosis, the serum E2 level was negatively correlated with E-cadherin expression in the epithelial components of the eutopic endometrium and adenomyotic lesions, suggesting the involvement of oestrogen-induced EMT in endometrial cells. In oestrogen receptor-positive Ishikawa endometrial epithelial cells, oestrogen induced a morphological change to a fibroblast-like phenotype, a shift from epithelial marker expression to mesenchymal marker expression, increased migration and invasion, and up-regulation of the EMT regulator Slug. Raloxifene, a selective oestrogen receptor modulator, abrogated these effects. To determine the role of oestrogen-induced EMT in the implantation of ectopic endometrium, we xenotransplanted eutopic endometrium or adenomyotic lesions from adenomyosis patients into ovariectomized SCID mice. The implantation of endometrium was oestrogen-dependent and was suppressed by raloxifene. Collectively, these data highlight the crucial role of oestrogen-induced EMT in the development of adenomyosis and suggest that raloxifene may be a potential therapeutic agent for adenomyosis patients.

Objective To evaluate the risk of preterm delivery in patients with adenomyosis.Design A 1:2 nested case-control study.Setting Tertiary-care institution.Population A base cohort population of 2138 pregnant women who attended routine prenatal check-up between July 1999 and June 2005.Methods From this base cohort population, gravid women with singleton pregnancy who delivered prior to the completion of 37 weeks of gestation were identified and formed the study group. Singleton gravid women who had term delivery and who matched with age, body mass index, smoking, and status of previous preterm delivery were recruited concurrently and served as control group. Preterm delivery cases were further divided into spontaneous preterm delivery and preterm premature rupture of membranes (PPROM) cases.Main outcome measures Risk analysis of preterm delivery between gravid women with and without adenomyosis.Results One-hundred and four preterm delivery case subjects and 208 control subjects were assessed. Overall, gravid women with adenomyosis were associated with significantly increased risk of preterm delivery (adjusted odds ratio 1.96, 95% CI 1.23-4.47, P = 0.022). For subgroup analysis, gravid women with adenomyosis had an adjusted 1.84-fold risk of spontaneous preterm delivery (95% CI 1.32-4.31, P = 0.012) and an adjusted 1.98-fold risk of PPROM (95% CI 1.39-3.15, P = 0.017).Conclusions Gravid women with adenomyosis were associated with increased risk of both spontaneous preterm delivery and PPROM. A common pathophysiological pathway may exist in these two disorders. Further in-depth biochemical and molecular studies are necessary to explore this phenomenon.

Intravenous and intraperitoneal chemotherapy are associated with equivalent survival in patients with minimal residual stage III epithelial ovarian cancer after optimal cytoreductive surgery.

The interplay between tumor microenvironment and cancer that causes chemoresistance remains unclear. By analyzing public available microarray datasets, we identified that periostin (POSTN) was overexpressed in cancer stroma in epithelial ovarian cancer (EOC) patients. Immunohistochemistry analysis showed overexpression of stromal POSTN is a powerful independent poor prognostic predictor for EOC patients. Furthermore, patients with high levels of stromal POSTN tend to have higher percentage of cisplatin resistance compared to those with low levels of stromal POSTN. Moreover, we found POSTN treatment can induce cisplatin resistant and activate AKT pathway in A2780 cells in vitro. Inhibition of AKT activity by AKT inhibitor MK-2206 abolished POSTN-induced AKT activation and cisplatin resistance in vitro. Taken together, we found high POSTN expression in cancer microenvironment is correlated with poor prognosis in EOC patients and associated with platinum resistance. The effect of POSTN in cancer stroma cells may activate AKT pathway in tumor and AKT inhibitor can be beneficial to augment the efficacy of existing cancer therapeutics.

Primary chemotherapy with epirubicin and cisplatin, although resulting in tumor response in a significant proportion of patients, is accompanied by an inferior local control rate and survival compared with standard pelvic radiotherapy alone.