Search results for "Lipide A"
showing 5 items of 5 documents
Study of the antitumor effect of inducible nitric oxide synthase in a breast cancer model : analysis of molecular mechanisms
2013
The anti -tumor effect of a lipid A, OM -174 (lipid portion of LPS) was studied in a model of breast cancer in mice. In vivo, OM- 174 increases the survival of mice whereas in vitro it is not toxic to cancer cells. OM -174 binds to TLR4 immune cells inducing the production of cytokines such as IFNγ. In vitro, the combination of IFNγ to lipid A is cytotoxic. The objective of this thesis is to analyze those molecular mechanisms. We have shown both in vitro and in vivo that the cytotoxicity of the lipid A / IFNγ is dependent of TLR4 and of the receptor for IFNγ, and the NOS II expression. We also showed that the radical species, NO and superoxide anion forming peroxynitrite play a crucial role…
Study of mechanisms of action of an immunotherapy by triacyl lipid A in humans
2013
Immunotherapy acting at the primary tumor site and preventing the development of metastases is one of the strategies for treatment of patients with cancer. To improve the efficiency of the latter, it is necessary to understand how it induces tumor cell death. In the laboratory, it was observed the cure of PROb tumors in rats BDIX by the triacyl lipid A. It has been shown that this effect involved the immune system involving interactions with TLRs present in many tumor cells and innate immunity cells such as neutrophils.In this work, we investigated the possible involvement of neutrophils in the antitumor activity of triacyl lipid A in humans.In a Phase 1 study in patients with refractory so…
Etude des mécanismes d'action d'une immunothérapie par un lipide A, seul ou associé à l'oxaliplatine, dans des modèles de cancers coliques
2013
Colorectal cancer is a major public health concern in France. Resistance to standard chemotherapy requires development of novel therapeutic approaches. In the past decades, our team showed the immunotherapeutic properties of lipid A in a model of colon cancer in rats. 95% of rats bearing small carcinomas were cured following treatment by lipid A. The study of mechanisms underlying this immunotherapy allowed us to show that the antitumor effect of lipid A was dependent on cytotoxicity induced by granzyme B produced by intratumoral neutrophils. Indeed, we have shown that, in the tumor microenvironment, neutrophils produced granzyme B and had a pro-tumorigenic N2 phenotype. When rats were trea…
P073 L’obésité diminue, de manière réversible, la préférence pour les lipides alimentaires chez la souris
2013
International audience; Introduction et but de l’étude. – Au cours des dernières années, il a été suggéré l’existence d’un lien étroit entre la détection oro-sensorielle des lipides alimentaire, la régulation de la prise alimentaire et l’IMC. Toutefois, les mécanismes affectant la sensibilité aux lipides ainsi que l’éventuelle implication directe de l’obésité restent mal connus.
Physico-chimie des lipopolysaccharides et réponse inflammatoire : rôle des lipoprotéines
2014
LPS is a potent bacterial pro-inflammatory agent, consisting of hydrophilic, polysaccharide part and of a lipid A which is considered like active moiety. Nevertheless, the O chain of LPS influences their aggregation in aqueous media. Therefore, our goal has been to determine the role of O chain on the LPS biological and physiopathological effects. Our work was organized according to three main axes, and led to the following findings :- development of a new LPS assay by LC-MS/MS. The combination of this new technique with LAL test allowed us to calculate an inactivation ratio which reflects the ability of host organism to inactivate LPS, especially through their transfer to HDL by PLTP. The …