Mechanisms involved in the evolution of @entity1871 resistance in XXXX @entity1869 --precursor of endometrial cancer.

@entity1 @entity1420 @entity5072 @entity7828 @entity1871 @entity12 @entity982 @entity98 @entity1869
BACKGROUND: Successful treatment of @entity1869 with @entity7828 is commonly accompanied by the finding of an inactive or suppressed endometrium after therapy. However, approximately 30% of the @entity1869 cases do not respond to @entity7828 and @entity5072 glands persist. The Fas/ @entity12 system is known to play a role in tissue remodeling as a result of changes in menstrual hormone levels. The aims of this study are to examine Fas/ @entity12 expression in @entity1869 of pre- and postprogestin treatment samples and to study the Fas/ @entity12 regulation in vitro with Ishikawa cells after @entity1871 stimulation. DESIGN: Pre- and posttreatment @entity982 -embedded @entity1869 tissue samples from 26 @entity1 were examined by immunohistochemistry for changes in Fas/ @entity12 expression related to the administration of @entity7828 . Among 26 @entity1 , 18 were successfully treated with @entity7828 and 8 failed treatment. Fas/ @entity12 positivity was defined by the presence of 10% or more immunoreactive epithelial cells in each specimen. In positive cases, a percentage or an immunoscore of immunoreactive cells was given by counting 500 cells. Cell viability was evaluated by the @entity98 assay. The in vitro effects of @entity1420 on Fas/ @entity12 expression and apoptosis in Ishikawa cells were examined by using Western blot and TUNEL assays, respectively. RESULTS: Fas immunoreactivity was present in 4/26 (15%) preprogestin cases with an average of 16% of the epithelial cells expressing Fas. @entity12 was expressed in 21/26 (80%) pretreatment cases with an average of 42% of the @entity5072 glandular cells being positive. In postprogestin cases, an increase of Fas expression (14/18, 77%) with an average of 47% stained cells was seen in responders (P < 0.001), while @entity12 was found in 16/18 (89%) responders with an average of 65% of cells positive (P = 0.587). In nonresponders, no significant changes in Fas/ @entity12 expression were detected compared to pretreatment samples. With in vitro Ishikawa cells, a slight increase (10-20%) of Fas and @entity12 protein expression was detected after 24 h of @entity1420 treatment, but a more significant increase (220-343%) of both Fas and @entity12 expression was found after 48 h of withdrawing @entity1420 , which parallels apoptotic activity. CONCLUSIONS: The Fas/ @entity12 system may be involved in the development of @entity1869 . Part of the molecular mechanisms of @entity1871 therapy for @entity1869 is through upregulation of Fas/ @entity12 expression. Dysregulation of Fas/ @entity12 expression in @entity5072 endometrium may be part of the molecular mechanisms for nonresponders to @entity1871 treatment. Intermittent, rather than continuous, @entity1871 treatment may be more effective clinically for the treatment of @entity1869 .
