17 research outputs found
Progestogenic effects of tibolone on human endometrial cancer cells
Tibolone, a synthetic steroid acting in a tissue-specific manner and used
in hormone replacement therapy, is converted into three active
metabolites: a Delta(4) isomer (exerting progestogenic and androgenic
effects) and two hydroxy metabolites, 3 alpha-hydroxytibolone (3
alpha-OH-tibolone) and 3beta-OH-tibolone (exerting estrogenic effects). In
the present study an endometrial carcinoma cell line (Ishikawa PRAB-36)
was used to investigate the progestogenic properties of tibolone and its
metabolites. This cell line contains progesterone receptors A and B, but
lacks estrogen and androgen receptors. When tibolone was added to the
cells, complete conversion into the progestogenic/androgenic Delta(4)
isomer was observed within 6 d. Furthermore, when cells were cultured with
tibolone or when the Delta(4) isomer or the established progestagen
medroxyprogesterone acetate was added to the medium, marked inhibition of
growth was observed. Interestingly, 3 beta-OH-tibolone also induces some
inhibition of growth. These growth inhibitions were not observed in
progesterone receptor-negative parental Ishikawa cells, and
progestagen-induced growth inhibition of PRAB-36 cells could readily be
reversed using the antiprogestagen Org-31489. Upon measuring the
expression of two progesterone-regulated genes (fibronectin and
IGF-binding protein-3), tibolone, the Delta(4) isomer and
medroxyprogesterone acetate showed similar gene expression regulation.
These results indicate that tibolone, the Delta(4) metabolite, and to some
extent 3 beta-OH-tibolone exert progestogenic effects. Tibolone and most
likely 3 beta-OH-tibolone are converted into the Delta(4) metabolite
Consequences of loss of progesterone receptor expression in development of invasive endometrial cancer
PURPOSE: In endometrial cancer, loss of progesterone receptors (PR) is
associated with more advanced disease. This study aimed to investigate the
mechanism of action of progesterone and the loss of its receptors (PRA and
PRB) in development of endometrial cancer. EXPERIMENTAL DESIGN: A
9600-cDNA microarray analysis was performed to study regulation of gene
expression in the human endometrial cancer subcell line Ishikawa PRAB-36
by the progestagen medroxy progesterone acetate (MPA). Five MPA-regulated
genes were selected for additional investigation. Expression of these
genes was studied by Northern blot and by immunohistochemistry in Ishikawa
subcell lines expressing different PR isoforms. Additionally, endometrial
cancer tissue samples were immunohistochemically stained to study the in
vivo protein expression of the selected genes. RESULTS: In the PRAB-36
cell line, MPA was found to regulate the expression of a number of
invasion- and metastasis-related genes. On additional investigation of
five of these genes (CD44, CSPG/Versican, Tenascin-C, Fibronectin-1, and
Integrin-beta 1), it was observed that expression and progesterone
regulation of expression of these genes varied in subcell lines expressing
different PR isoforms. Furthermore, in advanced endometrial cancer, it was
shown that loss of expression of both PR and E-cadherin was associated
with increased expression CD44 and CSPG/Versican. CONCLUSION: The present
study shows that progestagens exert a modulatory effect on the expression
of genes involved in tumor cell invasion. As a consequence, loss of PR
expression in human endometrial cancer may lead to development of a more
invasive phenotype of the respective tumor
Development and measurement of guidelines-based quality indicators of caesarean section care in the Netherlands: A RAND-modified delphi procedure and retrospective medical chart review
Background
There is an ongoing discussion on the rising CS rate worldwide. Suboptimal guideline adherence may be an important contributor to this rise. Before improvement of care can be established, optimal CS care in different settings has to be defined. This study aimed to develop and measure quality indicators to determine guideline adherence and identify target groups for improvement of care with direct effect on caesarean section (CS) rates.
Method
Eighteen obstetricians and midwives participated in an expert panel for systematic CS quality indicator development according to the RAND-modified Delphi method. A multi-center study was performed and medical charts of 1024 women with a CS and a stratified and weighted randomly selected group of 1036 women with a vaginal delivery were analysed. Quality indicator frequency and adherence were scored in 2060 women with a CS or vaginal delivery.
Results
The expert panel developed 16 indicators on planned CS and 11 indicators on unplanned CS. Indicator adherence was calculated, defined as the number of women in a specific obstetrical situation in which care was performed as recommended in both planned and unplanned CS settings. The most frequently occurring obstetrical situations with low indicator adherence were: 1) suspected fetal distress (frequency 17%, adh