Biomedical subjects

J Desreux

Publications and source records attributed to J Desreux.

9 recordsLinked to original sources

PubMed2003

Effects of a progestogen on normal human breast epithelial cell apoptosis in vitro and in vivo.

Many investigators have reported cyclic proliferation of normal human breast epithelial cells. A delicate balance between proliferation and apoptosis (programmed cell death) ensures breast homeostasis. Both the follicular and luteal phases of the menstrual cycle are characterized by proliferation, whereas apoptosis occurs only at the end of the latter phase. In this study, we observed that the withdrawal of a synthetic progestin (nomegestrol acetate or NOMAC), but not continuous treatment with it, induced apoptosis of normal human breast epithelial cells in vitro and in women who applied NOMAC gel to their breasts. Furthermore, this apoptotic response was specific to normal breast cells, since withdrawal of NOMAC did not induce apoptosis of tumoral T47D cells in vitro or of fibroadenoma cells in women. These observations open up new perspectives in the prevention of hyperplasia and breast cancer.

Adolescent↗

PubMed2003

[Hormone replacement therapy after breast cancer. Yes...or no?].

Clinical and experimental studies indicate that combined unique conjugated estrogens and medroxyprogesterone acetate moderately increase the risk of breast cancer in postmenopausal women. Classically, hormone replacement therapy is contra-indicated in women with a past history of breast cancer due to the fear of recurrence. However, these postmenopausal patients complain about hot flushes and adjuvant hormonal therapies (such as aromatase inhibitors, SERMs and Tamoxifen...) aggravate their symptoms. Observational studies and their meta-analyses do not show a deleterious effect but rather a beneficial impact of hormone replacement therapy among women with a past history of breast cancer. We summarise all these studies and their biological, clinical and epidemiological interpretations. We conclude that short term hormone replacement therapy is safe among those women requesting a replacement therapy after complete information. It is however advisable to conclude definitely only when prospective randomised trials with estradiol or tibolone (a promising alternative) will be available. Such ongoing studies will allow to conclude definitely the possible benefits and risks of hormone replacement therapy among patients with a past history of breast cancer.

Breast Neoplasms↗

PubMed2003

[Benefits and limitations of mammography].

The literature on screening mammography provides ample opportunity for doubt (the sceptics) and dogma (the screening zealots), and can be interpreted to prove both benefit and harm. The benefit of mammography screening, if any, is modest and the balance between beneficial (potentially, a 20% relative reduction in breast cancer mortality with no significant benefit on all-cause mortality) and harmful (physical and psychological morbidity related to the 15-40% missed cancers and the 80-90% false-positive diagnoses) effects is still delicate. The mammogram alone is a modest weapon. Concurrent clinical breast examination is mandatory. Women that are concerned about breast cancer should be fully informed of the potential benefits and risks of screening mammography. These women should benefit from mammography with concurrent clinical breast examination, and possible whole-breast ultrasound in heterogeneously dense and extremely dense breast patterns.

Age Factors↗

PubMed2000

Progesterone receptor activation. an alternative to SERMs in breast cancer.

Data regarding the effects of progesterone and a progestagen on human normal breast epithelial cell proliferation and apoptosis are presented here. In postmenopausal women, adding progesterone to percutaneously administrated oestradiol significantly reduces the proliferation induced by oestradiol. In vitro and in premenopausal women, stopping the administration of nomegestrol acetate triggers a peak of apoptosis. Fibro-adenoma and cancerous cells do not show this regulation of apoptosis. Progesterone seems to be important in normal breast homeostasis.

Apoptosis↗

PubMed2000

[Revised postmenopausal treatments? A new polemic!].

The study by Schairer et al. aims to determine whether increases in risk of breast cancer associated with the estrogen-progestin regimen are greater than those associated with estrogen alone. This study is a cohort of follow-up data for 1980-1995 from the Breast Cancer Detection Demonstration Project, a nationwide breast cancer screening program that involved 29 screening centers throughout the United States. A total of 46,355 postmenopausal women were followed. During follow up, 2,082 cases of breast cancer were identified. Increases in risk with estrogen only and estrogen-progestin only were restricted to use within the previous 4 years. The relative risk increased by 0.01 with each year of estrogen-only use and by 0.08 with each year of estrogen-progestin-only use among recent users. Among women with a Body Mass Index of 24.4 kg/m2 or less, increases in relative risk with each year of estrogen-only use and estrogen-progestin-only use among recent users were 0.03 and 0.12, respectively. The authors conclude that the estrogen-progestin regimen increases breast cancer risk beyond that associated with estrogen alone. This study was largely commented in the lay media. Unfortunately the Belgian media introduced the confusion between the relative risk and the risk attributable to estrogen and estrogen-progestin. The aim of this manuscript is to precisely inform our colleagues, to analyze the Schairer study and to present the actual figures of risk associated with the use of estrogen and estrogen-progestin replacement therapy. Finally, we formulate some suggestions for the physician to whom the patient declares: "Did you read the negative effects of hormones?". What should we advice?

Aged↗

PubMed1998

Induction of endothelial cell apoptosis by solid tumor cells.

The mechanisms by which tumor cells extravasate to form metastasis remain controversial. Previous studies performed in vivo and in vitro demonstrate that the contact between tumor cells and the vascular wall impairs endothelium integrity. Here, we investigated the effect of breast adenocarcinoma MCF-7 cells on the apoptosis of human umbilical vein endothelial cells (HUVEC). TUNEL labeling, nuclear morphology, and DNA electrophoresis indicated that MCF-7 cells induced a two- to fourfold increase in HUVEC apoptosis. Caspase-3 activity was significantly enhanced. Neither normal cells tested (mammary epithelial cells, fibroblasts, leukocytes) nor transformed hematopoietic cells tested (HL60, Jurkat) induced HUVEC apoptosis. On the contrary, cells derived from solid tumors (breast adenocarcinoma, MDA-MB-231 and T47D; fibrosarcoma, HT 1080) had an effect similar to that of MCF-7 cells. The induction of apoptosis requires cell-to-cell contact, since it could not be reproduced by media conditioned by MCF-7 cells cultured alone or cocultured with HUVEC. Our results suggest that cells derived from solid tumors may alter the endothelium integrity by inducing endothelial cell apoptosis. On the contrary, normal or malignant leukocytes appear to extravasate by distinct mechanisms and do not damage the endothelium. Our data may lead to a better understanding of the steps involved in tumor cell extravasation.

Adenocarcinoma↗

PubMed1998

Estradiol and progesterone regulate the proliferation of human breast epithelial cells.

OBJECTIVE: To study the effects of estradiol and progesterone on the proliferation of normal human breast epithelial cells in vivo. DESIGN: Double-blind randomized study. SETTING: Departments of gynecology and of cell biology at a university hospital. PATIENT(S): Forty postmenopausal women with untreated menopause and documented plasma FSH levels of >30 mIU/mL and estradiol levels of <20 pg/mL. INTERVENTION(S): Daily topical application to both breasts of a gel containing a placebo, estradiol, progesterone, or a combination of estradiol and progesterone during the 14 days preceding esthetic breast surgery or excision of a benign lesion. MAIN OUTCOME MEASURE(S): Plasma and breast tissue concentrations of estradiol and progesterone. Epithelial cell cycles were evaluated in normal breast tissue by counting mitoses and performing quantitative proliferating cell nuclear antigen immunolabeling analyses. RESULT(S): Increasing the estradiol concentration enhanced the number of cycling epithelial cells, whereas increasing the progesterone concentration significantly limited the number of cycling epithelial cells. CONCLUSION(S): Exposure to progesterone for 14 days reduced the estradiol-induced proliferation of normal breast epithelial cells in vivo.

Aged↗

PubMed1998

[Transdermal replacement hormone therapy: a trend or an advantage?].

This review describes the clinical usefulness of transdermal hormone replacement therapy. This route of administration is particularly important in women with hypertriglyceridemia, in hypertensive postmenopausal women, in women who smoke or have an increased risk of biliary or liver disorder, for those who display a reduced glucose tolerance or in women who are at risk of thrombotic disorders. The avoidance of the "first passage effect" is ensured by the transdermal application of estrogen and probably explains the superiority of this route of steroid administration.

Administration, Cutaneous↗

PubMed1997

Alteration of interendothelial adherens junctions following tumor cell-endothelial cell interaction in vitro.

The integrity of the vascular endothelium is mainly dependent upon the organization of interendothelial adherens junctions (AJ). These junctions are formed by the homotypic interaction of a transmembrane protein, vascular endothelial cadherin (VE-cadherin), which is complexed to an intracellular protein network including alpha-, beta-, and gamma-catenin. Additional proteins such as vinculin and alpha-actinin have been suggested to link the VE-cadherin/catenin complex to the actin-based cytoskeleton. During the process of hematogenous metastasis, circulating tumor cells must disrupt these intercellular junctions in order to extravasate. In the present study, we have investigated the influence of tumor cell-endothelial cell interaction upon interendothelial AJ. We show that human breast adenocarcinoma cells (MCF-7), but not normal human mammary epithelial cells, induce a rapid endothelial cell (EC) dissociation which correlates with the loss of VE-cadherin expression at the site of tumor cell-EC contact and with profound changes in vinculin distribution and organization. This process could not be inhibited by metalloproteinase nor serine protease inhibitors. Immunoprecipitations and Western blot analysis demonstrate that the overall expression of VE-cadherin and vinculin as well as the composition of the VE-cadherin/catenins complex are not affected by tumor cells while the tyrosine phosphorylation status of proteins within the complex is significantly altered. Our data suggest that tumor cells modulate AJ protein distribution and phosphorylation in EC and may, thereby, facilitate EC dissociation.

Adenocarcinoma↗