Paris Descartes University

About: Paris Descartes University is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Transplantation. The organization has 20987 authors who have published 37456 publications receiving 1206222 citations. The organization is also known as: Université Paris V-Descartes & Université de Paris V.

Treg depletion with a low-dose metronomic temozolomide regimen in a rat glioma model

Abstract: CD4+CD25+ regulatory T cells (Treg), which constitute about 2–3% of CD4+ human T cells, are the main contributors to the maintenance of immune tolerance. Cancer patients, including glioblastoma patients, bear increased number of circulating and tumor infiltrating Treg that exert functional inhibition on tumor-specific T cells. Temozolomide (TMZ) is one of the most effective chemotherapeutic agents in glioblastoma (GBM). Lymphopenia is a common side effect of TMZ treatment, but to what extent the Treg compartment is affected by this chemotherapy has been poorly investigated. We therefore studied the impact of various TMZ regimens on Treg cell population in a TMZ-resistant rat model of glioma. RG2 glioma cells were implanted s.c. in Fischer rats. Twelve days after tumor implantation, TMZ was administered orally with schedules designed to mimic the TMZ regimens currently used in humans: 30 mg/kg per day for 5 days, or 10 mg/kg per day for 21 days. In addition, two metronomic regimens with low-dose TMZ (2 and 0.5 mg/kg per day for 21 days) were evaluated. Splenocytes and tumor infiltrating lymphocytes were analysed by flow cytometry using CD3, CD4, CD25, and Foxp3 mAbs. Statistical significance was determined by the Mann–Whitney U test, the Student’s t test or the ANOVA test. In the spleen of tumor-bearing animals, low-dose TMZ metronomic regimens (0.5 and 2 mg/kg for 21 days) induced a significant decrease of Treg/CD4+ ratios (13 ± 2; p < 0.01, 14 ± 3; p < 0.05, respectively, vs. 19 ± 5 for controls). On the contrary, high-dose TMZ regimen (10 mg/kg per day for 21 days or 30 mg/kg for 5 days) did not significantly modify the percentage of Treg/CD4+. Within tumors, treatment with the 0.5 mg/kg TMZ regimen induced a slight and nearly significant decrease in the percentage of Treg/CD4+ after a 2 to 3-week treatment (24 ± 9 vs. 35 ± 11; p = 0.06). Treg depletion induced by the low-dose metronomic TMZ regimen was accompanied by a decreased suppressive function of the remaining Treg cells as assessed by an in vitro functional test. Treatment with 0.5 mg/kg metronomic TMZ reduced tumor progression when compared to untreated animals but the effect did not reach statistical significance, indicating that Treg depletion alone is not sufficient to significantly impact tumor growth in our model of fully established tumor. A low-dose metronomic TMZ regimen, but not a standard TMZ regimen, reduced the number of circulating Tregs. These results can have clinical applications for immunotherapeutic approaches in GBM.

Postmenopausal Hormone Therapy and Risk of Idiopathic Venous Thromboembolism. Results From the E3N Cohort Study

Abstract: Oral estrogen therapy increases venous thromboembolism risk among postmenopausal women. Although recent data showed transdermal estrogens may be safe with respect to thrombotic risk, the impact of the route of estrogen administration and concomitant progestogens is not fully established. We used data from the E3N French prospective cohort of women born between 1925 and 1950 and biennially followed by questionnaires from 1990. Study population consisted of 80 308 postmenopausal women (average follow-up: 10.1 years) including 549 documented idiopathic first venous thromboembolism. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional models. Compared to never-users, past-users of hormone therapy had no increased thrombotic risk (HR=1.1; 95% CI: 0.8 to 1.5). Oral not transdermal estrogens were associated with increased thrombotic risk (HR=1.7; 95% CI: 1.1 to 2.8 and HR=1.1; 95% CI: 0.8 to 1.8; homogeneity: P=0.01). The thrombotic risk significantly differed by concomitant progestogens type (homogeneity: P<0.01): there was no significant association with progesterone, pregnanes, and nortestosterones (HR=0.9; 95% CI: 0.6 to 1.5, HR=1.3; 95% CI: 0.9 to 2.0 and HR=1.4; 95% CI: 0.7 to 2.4). However, norpregnanes were associated with increased thrombotic risk (HR=1.8; 95% CI: 1.2 to 2.7). In this large study, we found that route of estrogen administration and concomitant progestogens type are 2 important determinants of thrombotic risk among postmenopausal women using hormone therapy. Transdermal estrogens alone or combined with progesterone might be safe with respect to thrombotic risk.

Pregnancy and Birth Cohort Resources in Europe: a Large Opportunity for Aetiological Child Health Research

Abstract: BACKGROUND During the past 25 years, many pregnancy and birth cohorts have been established. Each cohort provides unique opportunities for examining associations of early-life exposures with child development and health. However, to fully exploit the large amount of available resources and to facilitate cross-cohort collaboration, it is necessary to have accessible information on each cohort and its individual characteristics. The aim of this work was to provide an overview of European pregnancy and birth cohorts registered in a freely accessible database located at http://www.birthcohorts.net. METHODS European pregnancy and birth cohorts initiated in 1980 or later with at least 300 mother-child pairs enrolled during pregnancy or at birth, and with postnatal data, were eligible for inclusion. Eligible cohorts were invited to provide information on the data and biological samples collected, as well as the timing of data collection. RESULTS In total, 70 cohorts were identified. Of these, 56 fulfilled the inclusion criteria encompassing a total of more than 500,000 live-born European children. The cohorts represented 19 countries with the majority of cohorts located in Northern and Western Europe. Some cohorts were general with multiple aims, whilst others focused on specific health or exposure-related research questions. CONCLUSION This work demonstrates a great potential for cross-cohort collaboration addressing important aspects of child health. The web site, http://www.birthcohorts.net, proved to be a useful tool for accessing information on European pregnancy and birth cohorts and their characteristics.