Evaluation of the quality of the management of cancer of the corpus uteri-Selection of relevant quality indicators and implementation in Belgium

Objective Describe the methodology and selection of quality indicators (QI) to be implemented in the EFFECT (EFFectiveness of Endometrial Cancer Treatment) project. EFFECT aims to monitor the variability in Quality of Care (QoC) of uterine cancer in Belgium, to compare the effectiveness of different treatment strategies to improve the QoC and to check the internal validity of the QI to validate the impact of process indicators on outcome. Methods A QI list was retrieved from literature, recent guidelines and QI databases. The Belgian Healthcare Knowledge Center methodology was used for the selection process and involved an expert's panel rating the QI on 4 criteria. The resulting scores and further discussion resulted in a final QI list. An online EFFECT module was developed by the Belgian Cancer Registry including the list of variables required for measuring the QI. Three test phases were performed to evaluate the relevance, feasibility and understanding of the variables and to test the compatibility of the dataset. Results 138 QI were considered for further discussion and 82 QI were eligible for rating. Based on the rating scores and consensus among the expert's panel, 41 QI were considered measurable and relevant. Testing of the data collection enabled optimization of the content and the user-friendliness of the dataset and online module. Conclusions This first Belgian initiative for monitoring the QoC of uterine cancer indicates that the previously used QI selection methodology is reproducible for uterine cancer. The QI list could be applied by other research groups for comparison. © 2013 Elsevier Inc.

Negative hormonal control by the androgen DHT and antiestrogen EM-139 on cell cycle kinetics and proliferation in human breast cancer ZR-75-1 cells

info:eu-repo/semantics/submittedForPublication

Characteristics of the biphasic action of androgens and of the potent antiproliferative effects of the new pure antiestrogen EM-139 on cell cycle kinetic parameters in LNCaP human prostatic cancer cells

The most potent steroid in human prostatic carcinoma LNCaP cells, i.e. dihydrotestosterone (DHT), has a biphasic stimulatory effect on cell proliferation. At the maximal stimulatory concentration of 0.1 nM DHT, analysis of cell kinetic parameters shows a decrease of the G0-G1 fraction with a corresponding increase of the S and G2 + M fractions. In contrast, concentrations of 1 nM DHT or higher induce a return of cell proliferation to control levels, reflected by an increase in the G0-G1 fraction at the expense of the S and especially the G2 + M fractions. Continuous labeling for 144 h with the nucleotide analogue 5'-bromodeoxyuridine shows that the percentage of cycling LNCaP cells rises more than 90% after treatment with stimulatory concentrations of DHT, whereas in control cells as well as in cells treated with high concentrations of the androgen, this value remains below 50%. Although LNCaP cells do not contain detectable estrogen receptors, the new pure steroidal antiestrogen EM-139 not only reversed the stimulation of cell proliferation and cell kinetics induced by stimulatory doses of DHT but also inhibited basal cell proliferation.

Stimulation of apolipoprotein D secretion by steroids coincides with inhibition of cell proliferation in human LNCaP prostate cancer cells

Although steroid hormones are known to play a predominant role in the regulation of cell growth in hormone-sensitive cancers, their mechanisms of action, especially their interaction with growth factors and/or growth inhibitors, is poorly understood. We have recently observed that the effects of androgens and estrogens on the expression of the major protein found in human breast gross cystic disease fluid, protein-24, are opposite to their respective action on cell proliferation in human breast cancer cell lines. Somewhat surprisingly, the recent elucidation of the amino acid sequence of this progesterone binding protein reveals that this tumor marker is apolipoprotein D (apo D), a member of a superfamily of lipophilic ligand carrier proteins. The present study was designed to determine whether apo D is secreted by human prostate cancer cells and could thus be a new marker of steroid action in these cancer cells, and whether the sex steroid-induced stimulation of apo D secretion coincides with inhibition of cell proliferation. We took advantage of the biphasic pattern of the effect of steroids on the proliferation of the human prostate cancer LNCaP cell line, which offers the opportunity to discriminate between positive and negative steroid receptor-regulated cell growth processes. A 10-day exposure to low concentrations of dihydrotestosterone and testosterone caused a potent stimulation of LNCaP cell proliferation, whereas incubation with higher concentrations of these androgens led to a progressive decrease in cell proliferation towards basal levels. The biphasic action of androgens was also observed on apo D secretion, the effects on apo D secretion being inversely related to their action on LNCaP cell proliferation. Similar opposite biphasic effects were also observed with 9 other steroids, thus indicating that the stimulation of secretion of this new biochemical marker coincides with inhibition of cell proliferation in LNCaP human prostatic cancer cells.