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J C Philippe

Publications and source records attributed to J C Philippe.

27 records · Page 2Linked to original sources
PubMedDate not supplied

Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues.

In the present study, the concentrations of estrone (E(1)), estradiol (E(2)) and their sulfates (E(1)S and E(2)S), as well as the sulfatase and aromatase activities, were evaluated in post-menopausal patients with breast cancer. Comparative studies of the evaluation of these parameters were carried out in (a) tumor tissue, (b) areas surrounding the tumor, and (c) areas distant from the tumor (glandular tissue) which were considered as normal tissue. The levels (in pm/g; mean +/- SEM) were: for E(1) in the (a) area: 320+/-95; in (b): 232+/-86; and in (c): 203+/-71; for E(2) in the (a) area: 388+/-106; in (b): 224+/-48; and in (c): 172+/-80; for E(1)S in the (a) area: 454+/-110; in (b): 259+/-90; and in (c): 237+/-65; for E(2)S in the (a) area:318+/-67; in (b): 261+/-72; and in (c): 232+/-75, respectively. The values of E(1)S and E(2) were significantly higher in the tumor tissue than in the area considered as normal. In all the tissues studied, the sulfatase activity was much higher than aromatase (130-200). In addition, the sulfatase levels were significantly higher in the peripheral and in the tumor tissue than in the area considered as normal. The levels of aromatase were significantly higher in tumoral than in normal tissue. The present data extend the "intracrine concept" for breast cancer tumors. The physiopathology and clinical significance as promoter parameters in breast cancer is to be explored.

Aged↗
PubMedDate not supplied

Effects of Org OD14 (Livial) and its metabolites on 17 beta-hydroxysteroid dehydrogenase activity in hormone-dependent MCF-7 and T-47D breast cancer cells.

It is well recognized that estradiol (E2) is one of the most important hormones supporting the growth and evolution of breast cancer. Consequently, to block this hormone before it enters the cancer cell, or in the cell itself, has been one of the main targets in recent years. In the present study we explored the effect of Org OD14 (active substance in Livial) and its metabolites (Org 30126, Org 4094, Org OM38) on the 17 beta-hydroxysteroid dehydrogenase (17 beta HSD) activity of MCF-7 and T-47D human breast cancer cells. Using physiological doses of estrone ([3H]-E1: 5 x 10(-9) M) this estrogen is converted in a great proportion to E2 in both cell lines. After 24 hours, Org OD14 significantly inhibits this transformation in a dose-dependent manner, by 32 and 73% at 5 x 10(-7) M and 5 x 10(-5) M respectively, in T-47D cells; the effect is similar in MCF-7 cells. Among the three Org OD14 metabolites tested, Org 4094 and Org 30126 (3 alpha- and 3 beta-hydroxy metabolites) are more potent than their precursor, and Org OM-38 (4-ene isomer) is the weakest of the three steroids. The IC50 values were 0.79, 1.98, 7.12, and 22.84 microM in MCF-7 cells for Org 4094, Org 30126, Org OD14, and Org OM-38, respectively, and 4.83, 1.44, 2.03, and 35.25 microM, respectively, in T-47D cells. As Org OD14 and two of its metabolites, Org 30126 and Org 4094, also strongly decrease the conversion of estrone sulphate to estradiol in the hormone-dependent MCF-7 and T-47D breast cancer cells, it is concluded that the inhibition provoked by these steroids on the enzymes (estrone sulphatase and 17 beta-HSD) involved in the local biosynthesis of the biologically active estrogen estradiol, may reduce the risk of breast cancer in postmenopausal women during long-term hormone replacement treatment with Livial.

17-Hydroxysteroid Dehydrogenases↗
PubMedDate not supplied

Effect of Org OD14 (LIVIAL) and its metabolites on human estrogen sulphotransferase activity in the hormone-dependent MCF-7 and T-47D, and the hormone-independent MDA-MB-231, breast cancer cell lines.

The concentration of estrogen sulphates (ES) is particularly high in tumoural breast tissues in post-menopausal women. It is well known that during the post-menopausal phase the levels of circulating estrogens are very low, suggesting the local production of these hormones in the breast cancer tissue itself. Breast cancer cells possess all the enzymes involved in the last steps of estradiol (E2) formation, as well as in its transformation (e.g.: sulphotransferase). As ES are not biologically active, the formation of this conjugate is an important transformation pathway in the control of E2. Consequently, it was interesting to investigate the factors which regulate the sulphotransferase activity. In the present study, we explored the effect of Org OD14; the active substance in Livial, and of its main metabolites (Org 4094, Org 30126, Org OM-38) on the estrogen sulphotransferase activity in the hormone-dependent: MCF-7, T-47D, and hormone-independent: MDA-MB-231, human breast cancer cell lines. After 24 hours incubation at 37 degrees C of physiological concentrations of estrone ([3H]-E1: 5 x 10(-9) mol/l), it was observed that the sulphotransferase activity is detectable in MCF-7 and T-47D cells, since the concentrations of ES found were 14.90 and 17.30 pmol/mg DNA, respectively, whereas in MDA-MB-231 cells the concentration of ES found was only 2.01 pmol/mg DNA. Sulphates are found exclusively in the culture medium, which suggests that as soon as the sulphate is biosynthesized it is secreted into the medium. Org OD14, Org 30126, and Org 4094 have a biphasic effect on sulphotransferase activity in the hormone-dependent cells only. At low doses (5 x 10(-8) mol/l) these compounds stimulate this enzyme by 63, 101, and 51%, respectively in the MCF-7 cells, and by 41, 102, and 80%, respectively in the T-47D cells. No stimulatory effect was detected with Org OM-38. At high concentrations (5 x 10(-5) mol/l) Org OD14 and its three metabolites inhibit the sulphotransferase activity in MCF-7 and T-47D cells by 50-70%. In conclusion, the stimulatory effect provoked at low doses by Org OD14 and its metabolites (Org 4094, Org 30126) on the estrogen sulphotransferase involved in the biosynthesis of the inactive estrogen sulphates in estrogen-dependent breast cancer cells, can contribute to the protection of breast tissue in postmenopausal women with hormone replacement therapy.

Antineoplastic Agents, Hormonal↗
PubMedDate not supplied

[Role of scanography in the diagnosis of parathyroid adenomas. Apropos of 27 cases].

Scanner imagine pre-operatively in 27 patients with hyperparathyroidism provided assessment of the sensitivity (92 p.cent) and diagnostic precision (92.5 p.cent) of this investigational method. The need for a strict methodology and the advantages gained by high resolution and angioscanning programmes are emphasized. After analyzing the results, a review of the published literature enables the advantages and the limits of the scanner X to be defined, and a strategy for exploration of parathyroid adenomas to be proposed.

Adenoma↗
PubMedDate not supplied

[Preventive treatment with theophylline of apnea in premature infants: clinical, pharmokinetic and neurophysiological study].

Apnoea is a major problem in the neonatal paediatrics and its prevention is as important as the prevention of neonatal anoxia. The present study has three aims: 1. The strict evaluation of the results of therapy with Theophylline. 2. The determination of the pharmacokinetics of Theophylline and the establishment of the therapeutic protocol. 3. The study of the relationship between blood theophylline levels, apnoea and the states of sleep using prolonged polygraphic recordings.

Apnea↗