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Biomedical subjects

A Gompel

Publications and source records attributed to A Gompel.

At least 37 records · Page 2Linked to original sources
PubMed1997

Fibrinogen and plasminogen modifications during oral estradiol replacement therapy.

OBJECTIVE: To assess the effects of oral E2 replacement therapy on various hemostatic parameters and cardiovascular risk factors in healthy, postmenopausal women. DESIGN: A double-blind, randomized, prospective study comparing the effect of a placebo and of oral micronized E2 (2 mg daily) during a 6-month period. Evaluations were performed before treatment and after 3 and 6 months. SETTING: Departments of Gynecology, Hemostasis, and Nutrition, Hôtel-Dieu, Paris, France. PATIENT(S): Thirty-six healthy women with natural or surgical menopause. RESULT(S): Compared with placebo, oral E2 replacement therapy resulted in a significant decrease in fibrinogen and apo B and a significant increase in plasminogen. CONCLUSION(S): Besides the effects on lipoproteins, oral estrogen replacement therapy modifies parameters involved in coagulation and fibrinolysis.

Administration, Oral↗
PubMed1996

Antagonism between estradiol and progestin on Bcl-2 expression in breast-cancer cells.

Bcl-2 is a key protein involved in the control of apoptosis. Our previous studies on breast and endometrium indicated hormonal regulation of bcl-2 in these tissues. In the present work we have analyzed Bcl-2 and Bax protein expressions in MCF-7 and T47-D, 2 hormone-dependent breast-cancer cell lines, by immunoblots. Estradiol markedly increased Bcl-2 protein content, both in short- and in long-term treatments of MCF-7 cells. Two types of anti-estrogens (4-hydroxytamoxifen and RU 58668) were able to reverse this effect. Also, a synthetic progestin (ORG 2058) was able to decrease the Bcl-2 level in T47-D cells. The level of Bax protein, however, was not affected in the same conditions of hormonal treatments. The level of Bcl-2 expression was 4.5-fold higher in MCF-7 than in MDA-MB 231 (an estradiol-independent cell line). From these results, we infer the existence of hormonal regulation of Bcl-2 expression and evoke a novel role for estradiol and progestin in the genesis of breast cancer.

Blotting, Western↗
PubMed1996

Epidermal growth factor receptor and c-erbB-2 expression in normal breast tissue during the menstrual cycle.

EGF receptor (EGF-R) and c-erbB-2 are homologous tyrosine kinase transmembrane receptors. They are involved in controlling proliferation, and probably differentiation, of normal breast epithelial cells, and their expression has been linked to the prognosis of breast cancer. Their physiological roles in normal breast tissue remain to be elucidated, as most studies to date have involved breast cancer cell lines. We studied the location of EGF-R and c-erbB-2 in 100 samples of normal breast with standard immunohistochemical methods and double-labelling techniques. EGF-R was mainly expressed on the stroma and myoepithelial cells, whereas c-erbB-2 expression was exclusively epithelial. An image analyser was used to quantitate variations in their expression during the menstrual cycle. EGF-R and c-erbB-2 expression on epithelial cells was stronger during the luteal phase than the follicular phase (p < 0.01 for EGF-R). The pattern of expression was also compared with that in 28 breast cancers and 7 fibroadenomas.

Breast↗
PubMed1995

[Contraceptions in women with contra-indication to estrogen-progestins].

Estrogen-progestin pill contra-indications can be related to a metabolic or vascular risk or to an estrogen-dependent disease. In the first case, a pregnane progestin (chlormadinone acetate or cyproterone acetate) can be used as a first choice, because of its good tolerance and absence of deleterious effects on these diseases. IUD use is limited due to the risk of infection and a decreased efficiency with corticosteroids. Diaphragm plus spermicides or condoms can be used in any case and are the only possibilities during the course or just after a deep vein thrombosis. In case of estrogen-dependent diseases, high-dose progestin is the treatment of the diseases in most of the cases and normethyl-testosterone derivatives or other progestin can be used.

Contraception↗
PubMed1995

Estradiol stimulates c-myc proto-oncogene expression in normal human breast epithelial cells in culture.

The proto-oncogene c-myc is involved in the stimulation of cell proliferation, and its expression is known to be stimulated by estradiol (E2) in human breast cancer cell lines and various non-cancerous E2-dependent tissues. However, little information is currently available concerning its expression and regulation in normal human breast tissue. We therefore studied c-myc expression and hormone modulation in normal human breast epithelial (HBE) cells in culture, routinely obtained in our laboratory and which remain hormone-dependent. On these normal HBE cells, E2 induced a biphasic increase in c-myc mRNA level, with a first peak as early as 30 min, and a secondary increase after 2 h of treatment; this stimulation was dose-dependent, with an optimal concentration of 10 nM E2. Its primary action is probably at the transcriptional level since the half-life of c-myc mRNA measured in the presence of actinomycin D (12 +/- 3 min) was not modified by E2 treatment. In addition, E2 stimulation of c-myc mRNA does not require protein synthesis since it was not suppressed by cycloheximide treatment. Western blot studies of c-myc protein in HBE cells revealed the same biphasic pattern of stimulation, with a first peak after 60 min and a second one after 2 h of E2 treatment. In conclusion, the c-myc proto-oncogene is expressed in normal HBE cells, as in breast cancer cells. Moreover, E2 stimulates c-myc expression which, therefore, may partly mediate the growth-promoting effect of E2.

Breast↗
PubMed1995

[Pulmonary lymphangiomyomatosis. Long-term benefit of anti-estrogen treatments remains uncertain].

Lymphangiomyomatosis is a rare disease which affects young women of childbearing age. Ten women with pulmonary lymphangiomyomatosis were treated with antiestrogen therapy from 3 to 9 years (mean time of treatment: 5.3 years). Efficacy of treatment was evaluated by clinical, radiological, pulmonary function testing response as well as the overall long-term outcome. Four patients died of respiratory failure after 3, 5, 5 and 9 years of treatment. Of the 6 patients remaining alive, respiratory function deteriorated in 4 cases after a transient period of mild improvement lasting 3 years in 2 cases. Two patients appeared stable after 3 and 7 years of treatment. Without a control group, although a longer time of survival along these last years, it seems difficult to impute this benefit to the sole antiestrogen treatment and the overall long term prognosis of the disease remains really uncertain.

Adult↗
PubMed1994

bcl-2 expression in normal breast tissue during the menstrual cycle.

bcl-2 is a proto-oncogene discovered through the t(14;18) translocation occurring in most human follicular lymphomas. The function so far attributed to bcl-2 is to counteract the occurrence of apoptosis and to prolong cell survival without affecting the cycling cells. Apoptosis has been described in normal breast tissue epithelial cells, and it peaks at the end of the luteal phase. We have studied bcl-2 expression by an immunohistochemical method in 50 samples of normal breast tissue distributed throughout the menstrual cycle. bcl-2 staining predominated in the lobular epithelial cells. It displayed a striking cyclic variation, with maximal expression at the mid-cycle period and a sharp decrease at the end of the cycle. These results strongly suggest that the regulation of bcl-2 expression in breast tissue is hormone-dependent. This could be of significance in tumorigenesis.

Adolescent↗
PubMed1994

Bcl-2 expression in normal endometrium during the menstrual cycle.

Bcl-2 is a proto-oncogene initially described in the (14;18) translocation in follicular lymphoma. It has been shown to prolong cell survival by preventing apoptosis. Endometrium undergoes rapid proliferation and differentiation under hormone control and is thus an excellent model to study the hormone dependency of Bcl-2 expression. We studied Bcl-2 expression by an immunohistochemical method in 53 samples of normal endometrium randomly distributed throughout the menstrual cycle, as well as five samples of hyperplastic endometrium. Bcl-2 staining predominated in glandular cells and peaked at the end of the follicular phase. Bcl-2 expression disappeared at the onset of secretory activity. The stroma, surface lining epithelium and arterial vessels also displayed cyclic variations in Bcl-2 expression. These results strongly suggest hormone-dependent regulation of Bcl-2 expression, which could play an important role in tumorigenesis.

Adult↗
PubMed1993

[Progestin treatments of menopause].

Hormone replacement therapy is prescribed to post-menopausal women in order to correct oestrogen deficiency and its short- or long-term consequences. Progestogens are combined with oestrogens to prevent the proliferative effect of the latter on the endometrium. There are three classes of progestogens: normethyl testosterone derivatives, pregnanes and norpregnanes, and natural progesterone. The usual choice is either natural progesterone or 17-hydroxyprogesterone derivatives which do not carry metabolic or vascular risks. The endometrium is protected by simple therapeutic rules: the doses of oestradiol must be minimal to prevent osteoporosis, and this product must not be administered alone for a sequence longer than 13 days. The progestogen sequence must last for 12 days. The wide range of progestogens available in France enables individual adjustments to be made. Using progestogens alone could be interesting in women from whom oestrogenic treatments are contraindicated, in view of their effect on sudden flush and on bone.

Animals↗
PubMed1993

[The role of calcium at different ages in women's life].

The present long life of women raises the problem of prevention against osteoporosis. Bone mass formation during adolescence is the first critical period, and it might condition the future bone mineral content. Eighty percent of the bone mass is of genetic origin, whereas 20 percent depends on the environment (diet, hormones, etc.). Menstrual disorders may be responsible for bone mineral loss. Pregnancy and breast-feeding are periods in which calcium requirements increase, yet in all but high risk women there are seldom responsible for osteopoenia. The first 10 years of menopause constitute a period of exponential bone mineral loss, and this is when oestrogen therapy is most effective against bone loss. The usefulness of calcium is still a matter of debate, with conflicting results concerning its preventive action on osteoporosis. There seems to be a threshold phenomenon: when normal diet provides a small amount of calcium, calcium supplementation is effective, but beyond a certain level supplementation is thought to be useless. The results found in the literature are presented, and the amounts of calcium intakes recommended at different ages are given.

Adolescent↗
PubMed1992

Pulmonary lymphangiomyomatosis. Follow-up and long-term outcome with antiestrogen therapy; a report of eight cases.

Lymphangiomyomatosis is a rare disease which affects young women of childbearing age. Eight women with pulmonary LAM were treated with antiestrogen therapy and were monitored by blood estrogen measurements along with clinical hypoestrogenic symptoms. Treatment ranged from three to nine years. The response to therapy was evaluated by the clinical course, chest x-ray films, pulmonary function tests and overall long-term outcome. Three patients died of respiratory failure after three, five and nine years of treatment. Of the five patients remaining alive, respiratory function deteriorated in four cases, after a transient period of mild improvement lasting three years in two cases. The last patient appeared stable after three years of follow-up. Time course ranged from 4 to 17 years. However, without a control group, we cannot determine whether or not the apparent improvement of the natural time course was due to the hormonal treatment.

Adult↗
PubMed1991

Estradiol and progesterone receptors in cultured normal human breast epithelial cells and fibroblasts: immunocytochemical studies.

The estradiol (E2) and progesterone (P) receptors (ER and PR) were studied in normal human breast epithelial (HBE) cells and fibroblasts cultured separately in our laboratory from surgical reductive mammoplasty samples. Immunocytochemical studies were performed on cytospun cells using the anti-ER antibody H222 Sp gamma and the anti-PR antibodies JZB39 and KD68. A specific immunostaining was observed for ER and PR in HBE cells. This immunostaining was nuclear, varying from cell to cell in positivity and intensity of staining. Moreover, ER and PR immunostaining was hormone-modulated: it increased in E2-treated cells and decreased after addition of the progestin R5020. In fibroblasts, a weak ER immunostaining and a stronger PR immunostaining could be observed; however it was not modified by either E2 or progestogen treatment. Thus, in normal breast epithelial cells, E2 stimulates both its own receptor and PR, whereas the progestin R5020 lowers ER and PR content. In contrast, ER and PR content in normal breast fibroblasts seem to be independent of E2 or P action.

Adolescent↗
PubMed1990

[Contraception and pregnancy in systemic lupus erythematosus].

In 1990 conflicting views are still being held concerning oral contraception and risks associated with pregnancy in women with systemic lupus erythematosus. As regards oral contraceptives, all authors agree that oestrogen-progestin combination pills are harmful, but the best alternative hormonal contraception remains to be determined. Protein-based "micropills" seem to be harmless; cyproterone acetate appears to be without side-effects, and its usefulness in preventing recurrences is being evaluated. As regards pregnancy, it would be wise not to contemplate having a child until 6 months have elapsed since the onset of remission. Blood pressure, platelet count and serum creatinine and uric acid levels must be closely monitored. Two types of antibodies may be present in the mother and are known to be responsible for foetal complications. These are antibodies to phospholipids (antiprothrombinase, anticardiolipin, antibodies responsible for dissociated treponema serology), which expose to spontaneous abortion or intrauterine death, and the antibody to SS-A (or anti-Ro), which exposes to foetal cardiomyopathy and congenital atrioventricular block.

Abortion, Spontaneous↗
PubMed1989

[Antiestrogens and normal human breast cell proliferation].

Steroidal (progestins) and non steroidal antiestrogens (tamoxifen and derivatives) are strong antiproliferative molecules when added to normal human breast cells in culture. The antiproliferative action of tamoxifen and 4-hydroxytamoxifen isomers is comparable to that observed in cultured breast cell lines. The progestin promegestone (R 5020) is a strong antiproliferative agent in the presence as well as in the absence of estradiol. Identically, at higher concentration the antiprogestin RU 486 slows down cell proliferation probably due to its progesterone agonist activity. Both progestins and antiprogestins stimulate 17 beta-hydroxysteroid dehydrogenase activity, a marker of progesterone receptor but only in estradiol primed cells.

17-Hydroxysteroid Dehydrogenases↗
PubMed1988

Tamoxifen and hydroxytamoxifen isomers versus estradiol effects on normal human breast cells in culture.

Estradiol and triphenylethylene antiestrogen actions have been studied extensively in breast cancer cell lines. However, their effects are still poorly understood on normal human breast cells. We have developed a culture system of normal human breast epithelial (HBE) cells. It has been shown previously that cultured HBE cells were hormone dependent and well adapted for the study of hormone/antihormone actions. However, until now, no data were available on estradiol receptor (ER) in HBE cells. In this study, the presence of ER was demonstrated by (a) whole-cell biochemical assay on breast cells after enzymatic tissue dissociation and (b) an immunocytochemical method using an anti-ER monoclonal antibody both on enzymatically dissociated cells and on 8-day cultured cells. Immunostaining was nuclear and cell positivity was heterogeneous. However, the percentage of positive cells and staining intensity were far greater in the presence of estradiol in the culture, indicating estradiol stimulation of ER. Moreover, HBE cells were used to study the action on cell growth of estradiol versus trans-tamoxifen (TAM), trans-4-hydroxytamoxifen (trans-4OHTAM), and cis-4-hydroxytamoxifen (cis-4OHTAM) alone or added to estradiol. Cell growth was estimated daily by a histometric method and by DNA assay at the end of the 7-day study. When the medium was minimally supplemented with human serum (1%), estradiol stimulated cell growth in a dose-dependent manner at concentrations varying from 10(-9) to 10(-7) M. TAM and trans-4OHTAM clearly inhibited mammary cell division when estradiol was added to the medium and, to a lesser extent, in the absence of estradiol. This inhibitory effect was dose dependent. trans-4OHTAM was 100 times more active than trans-TAM. cis-4OHTAM also clearly inhibited breast cell division at 10(-7) and 10(-6) M concentrations but was 3-fold less efficient than trans-4OHTAM. In conclusion, (a) the presence and estradiol dependence of ER have been demonstrated in HBE cells, which constitute a fruitful model for the study of hormone/antihormone actions, and (b) in these normal cells, estradiol stimulates growth, whereas TAM and the 4OHTAM isomers are potent inhibitors of cell multiplication, as they are in breast cancer cell lines in culture.

Breast↗
PubMed1988

Induction of ovulation with pulsatile GnRH in hypothalamic amenorrhoea.

Pulsatile administration of gonadotrophin releasing hormone (GnRH) is a very effective treatment for induction of ovulation in hypothalamic amenorrhoea (HA). Thirty-seven women have been treated for a total of 117 cycles which resulted in 42 pregnancies--four treatment failures occurred. If these cycles are excluded, the 42 pregnancies were obtained within 2.3 cycles. One twin pregnancy occurred and no hyperstimulation was observed. The treatment was administered intravenously with a dosage schedule based on the grading of HA. We concluded that pulsatile GnRH was safe and very successful in induction of pregnancy in HA. Other indications (polycystic ovary syndrome and luteal phase defect) remain much less suitable for this treatment.

Amenorrhea↗