Composition pour retarder l'initiation tumorale de cellules cancereuses chez un mammifère à risque

La présente invention concerne une composition préventive antitumorale comprenant une quantité pharmaceutiquement efficace d\u27au moins un antagoniste du récepteur AT2 de l\u27angiotensine II pour son application comme médicament afin de prévenir le développement de cancers chez un mammifère à risque. La présente invention concerne également un procédé de prévention du développement de cancer chez un mammifère à risque, ainsi qu\u27un kit de prévention du développement de cancers

Effects of organochlorine pesticides on endothelial cell adhesion, proliferation, nitric oxide and superoxide anion productions

National audienc

Paradoxical effects of the topoisomerase inhibitor, ethoxidine, in the cellular processes leading to angiogenesis on EaHy.926 endothelial cells

Topoisomerase I generates transient single-stranded breaks in DNA and have the capacity to fragment the genome. Thus, this enzyme is the target for some of the most successful anticancer drugs. Ethoxidine, a benzo[c]phenanthridines derivative, was identified as a potent inhibitor of topoisomerase I. As angiogenesis is a critical step in tumorigenesis, this study was designed to test the potential effect of ethoxidine on different processes leading to neovascularisation on EaHy endothelial cells including adhesion, migration and proliferation. Ethoxidine was tested at two concentrations, 100 μM and 10 μM . VEGF (20 ng/mL) was used as control. Adherent cells were evaluated using crystal violet staining, migration using a model of wound healing. Proliferation was analyzed using CyQUANT Cell Proliferation Assay Kit. Both O2- and NO productions were assessed using electronic paramagnetic resonance technique. All the effects of ethoxidine were evaluated at 24 h treatment. Low concentration of ethoxidine promoted migration to the same extent as that produced by VEGF whereas high concentration inhibited this process. Ethoxidine significantly enhanced adhesion at similar level than VEGF at low concentration. It was without effect at high concentration. Although ethoxidine had no effect at low concentration, it significantly reduced cell proliferation at high concentration. At any concentration tested, ethoxidine did not modify basal O2- production. Interestingly, ethoxidine significantly increase NO production at low concentration but it was without effect at high concentration. As control experiment, VEGF enhanced Eahy cells NO production under the same experimental conditions. Altogether, the present study highlights paradoxical effects of ethoxidine depending on the concentration used. At low concentration, it promotes both Eahy cells migration and adhesion without any effect on proliferation. Importantly, these effects were associated with an increase of NO production. In contrast at high concentration, ethoxidine reduced Eahy cells migration and proliferation but had no effect neither on adhesion nor NO release. Of note is the fact that ethoxidine did not alter endothelial cells oxidative stress at any concentration tested. Thus, these data underscore the potential anti-tumoral property of ethoxidine at high concentration and endothelial cells in the present study. The property of ethoxidine in inhibiting proliferation in both cell type probably account for its high antitumor activity

Pleiotropic beneficial effects of epigallocatechin gallate, quercetin and delphinidin on cardiovascular diseases associated with endothelial dysfunction

Cardiovascular diseases are an important public health problem because they represent a major cause of death worldwide. The pathophysiology of these chronic diseases is defined, among others, by an excess of reactive oxygen species production, a defect of endothelium-dependent vasodilation, a high blood pressure or a modification of platelet function. Epidemiological studies suggest that the beneficial cardiovascular health effects of diets rich in fruits and vegetables are, in part, mediated by their flavonoid content, with particular benefits provided by members of this family such as epigallocatechin gallate, quercetin or delphinidin. Many studies show that these phytochemicals are promising natural compounds to prevent cardiovascular diseases associated with endothelial dysfunction. Mechanistically, shortterm effects on endothelium-dependent vasodilation following the consumption of these flavonoids have been linked to an increased nitric oxide bioactivity. Moreover, besides their well-described antioxidant properties, these flavonoids are able to prevent endothelial cell apoptosis and to modulate various signaling pathways leading to inflammation. Therefore, this review attempts to outline our understanding about the pleiotropic beneficial effects of epigallocathecin gallate, quercetin or delphinidin on cardiovascular diseases associated with endothelial dysfunction. Furthermore, this review aims to identify the potential protective vascular effects of these flavonoids and their therapeutic value in cardiovascular medicine

Composition Containing an Angiotensin Ii at2 Receptor Antagonist, Intended for Slowing Cancer Cell Tumor Initiation in a High-Risk Mammal

The present invention relates to a preventive anti-tumor composition containing a pharmaceutically effective amount of at least one angiotensin II AT2 receptor antagonist for the use thereof as a drug to prevent cancer development in a high-risk mammal. The present invention also relates to a method for preventing cancer development in a high-risk mammal, as well as to a cancer development prevention kit., La présente invention concerne une composition préventive antitumorale comprenant une quantité pharmaceutiquement efficace d\u27au moins un antagoniste du récepteur AT2 de l\u27angiotensine II pour son application comme médicament afin de prévenir le développement de cancers chez un mammifère à risque. La présente invention concerne également un procédé de prévention du développement de cancer chez un mammifère à risque, ainsi qu\u27un kit de prévention du développement de cancers

Two dechlorinated chlordecone derivatives formed by in situ chemical reduction are devoid of genotoxicity and mutagenicity and have lower proangiogenic properties compared to the parent compound

Chlordecone (CLD) is a chlorinated hydrocarbon insecticide, now classified as a persistent organic pollutant. Several studies have previously reported that chronic exposure to CLD leads to hepatotoxicity, neurotoxicity, raises early child development and pregnancy complications, and increases the risk of liver and prostate cancer. In situ chemical reduction (ISCR) has been identified as a possible way for the remediation of soils contaminated by CLD. In the present study, the objectives were (i) to evaluate the genotoxicity and the mutagenicity of two CLD metabolites formed by ISCR, CLD-5a-hydro, or CLD-5-hydro (5a- or 5- according to CAS nomenclature; CLD-1Cl) and tri-hydroCLD (CLD-3Cl), and (ii) to explore the angiogenic properties of these molecules. Mutagenicity and genotoxicity were investigated using the Ames\u27s technique on Salmonella typhimurium and the in vitro micronucleus micromethod with TK6 human lymphoblastoid cells. The proangiogenic properties were evaluated on the in vitro capillary network formation of human primary endothelial cells. Like CLD, the dechlorinated derivatives of CLD studied were devoid of genotoxic and mutagenic activity. In the assay targeting angiogenic properties, significantly lower microvessel lengths formed by endothelial cells were observed for the CLD-3Cl-treated cells compared to the CLD-treated cells for two of the three tested concentrations. These results suggest that dechlorinated CLD derivatives are devoid of mutagenicity and genotoxicity and have lower proangiogenic properties than CLD

Effects of N,N-diethyl-m-toluamide (DEET) in the cellular processes leading to angiogenesis

National audienc

Pro-angiogenic effet of N,N-diethyl-m-toluamide (DEET) mediated by M3 receptors

National audienc

Plasma cells release membrane microparticles in a mouse model of multiple myeloma.

Microparticles (MPs) released from the plasma membrane play a role in tumor progression. Involvement of MPs in myeloma (MM) has been poorly investigated. Because of the strong interaction of MM cells with bone microenvironment, we hypothesized an implication of MPs in MM using a murine model. Forty-four mice were injected with 5THL-MM cells and compared with 14 non-injected mice. Blood was collected at the early and end stages of MM development (EMM and LMM) to characterize the circulating MPs. At LMM, MPs were isolated from bone marrow (BM) of long bones of 22 mice, after centrifugation. Electron microscopy immunohistochemistry and Western blotting using CD138 were performed on BM-derived MPs. At EMM, MPs circulating level was significantly lower versus controls. In LMM, a significant increase of the total MP number from plasma was observed versus controls. Characterization of circulating MPs showed an increase of leukocyte- and erythrocyte-derived MPs. In LMM, serum M-protein was correlated with circulating MP number. BM-derived MPs increased in LMM and expressed CD138. Anti-CD138 coupled with nanobeads localized at the MP surface. There is evidence of an association between increase of MPs and MM development; the results underscore the participation of plasma cell-derived MPs originating from BM