Ecrins Therapeutics

La Tronche, France

Ecrins Therapeutics

La Tronche, France
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Stephanou A.,CNRS Complex Medical Engineering Laboratory | Lesart A.C.,CNRS Complex Medical Engineering Laboratory | Deverchere J.,Ecrins Therapeutics | Juhem A.,Ecrins Therapeutics | And 2 more authors.
Journal of Theoretical Biology | Year: 2017

A computational model was developed to describe experimentally observed vascular changes induced by the introduction of a tumour on a mouse equipped with a dorsal skinfold chamber. The vascular structure of the host tissue was segmented from in vivo images and transposed into the computational framework. Simulations of tumour-induced vascular changes were performed and include the destabilizing effects of the growth factor VEGF on the integrity of the vessels walls. The integration of those effects, that include alteration of the vessel wall elasticity and wall breaching, were required to realistically reproduce the experimental observations. The model was then used to investigate the importance of the vascular changes for oxygen delivery and tumour development. To that end, we compared simulations obtained with a dynamic vasculature with those obtained with a static one. The results showed that the tumour growth was strongly impeded by the constant vascular changes. More precisely, it is the angiogenic process itself that was affected by vascular changes occurring in bigger upstream vessels and resulting in a less efficient angiogenic network for oxygen delivery. As a consequence, tumour cells are mostly kept in a non-proliferative hypoxic state. Tumour dormancy thus appears as one potential consequence of the intense vascular changes in the host tissue. © 2017 Elsevier Ltd

Zaccaria A.,French Institute of Health and Medical Research | Bouamrani A.,CEA Grenoble | Selek L.,French Institute of Health and Medical Research | Selek L.,Center Hospitalier University | And 18 more authors.
ACS Chemical Neuroscience | Year: 2013

Access to cerebral tissue is essential to better understand the molecular mechanisms associated with neurodegenerative diseases. In this study, we present, for the first time, a new tool designed to obtain molecular and cellular cerebral imprints in the striatum of anesthetized monkeys. The imprint is obtained during a spatially controlled interaction of a chemically modified micro-silicon chip with the brain tissue. Scanning electron and immunofluorescence microscopies showed homogeneous capture of cerebral tissue. Nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) analysis of proteins harvested on the chip allowed the identification of 1158 different species of proteins. The gene expression profiles of mRNA extracted from the imprint tool showed great similarity to those obtained via the gold standard approach, which is based on post-mortem sections of the same nucleus. Functional analysis of the harvested molecules confirmed the spatially controlled capture of striatal proteins implicated in dopaminergic regulation. Finally, the behavioral monitoring and histological results establish the safety of obtaining repeated cerebral imprints in striatal regions. These results demonstrate the ability of our imprint tool to explore the molecular content of deep brain regions in vivo. They open the way to the molecular exploration of brain in animal models of neurological diseases and will provide complementary information to current data mainly restricted to post-mortem samples. © 2012 American Chemical Society.

Boca-Farcau S.,Babes - Bolyai University | Boca-Farcau S.,CNRS Physics Laboratory | Potara M.,Babes - Bolyai University | Simon T.,Babes - Bolyai University | And 4 more authors.
Molecular Pharmaceutics | Year: 2014

The effectiveness of a therapeutic agent for cancer stands in its ability to reduce and eliminate tumors without harming the healthy tissue nearby. Nanoparticles peripherally conjugated with targeting moieties offer major improvements in therapeutics through site specificity. In this study we demonstrate this approach by targeting the folate receptor of NIH:OVCAR-3 human ovary cancer cell line. Herein we used silver nanotriangles which were biocompatibilized with chitosan (bio)polymer, labeled with para-aminothiophenol (pATP) Raman reporter molecule, and conjugated with folic acid. The nanoparticles conjugation and efficient labeling was investigated by localized surface plasmon resonance (LSPR), zeta potential, and surface-enhanced Raman scattering (SERS) measurements. Conjugated particles were proven to be highly stable in aqueous and cellular medium. The targeted uptake of conjugated nanoparticles by human ovary cancer cells was confirmed by dark field microscopy and scattering spectra of the particles inside cells. Comparative studies revealed specific internalization of the conjugated nanoparticles in comparison with similar bare nanoparticles. Moreover, the SERS identity of the particles was proven to be highly conserved inside cells. Targeted cancer cell treatment conducted by irradiating the nanoparticle-treated cells with a continuous wave-nearinfrared (cw-NIR) laser in resonance with their plasmonic band proved an efficient therapeutic response. By integrating the advantages of multimodal optical imaging and SERS detection with hyperthermia capabilities through site specificity, these nanoparticles can represent a real candidate for personalized medicine. © 2013 American Chemical Society.

Juhem A.,Ecrins Therapeutics | Boumendjel A.,CNRS Molecular Pharmacochemistry Department | Touquet B.,French National Center for Scientific Research | Guillot A.,Altran GmbH | And 3 more authors.
Anticancer Research | Year: 2013

Background: New chemotherapy drugs should be investigated to improve survival of patients with advanced bladder cancer. Here, we report the synthesis and evaluation of AG11, a new flavanone derivative obtained through cyclization of its chalcone precursor CB11. Materials and Methods: The effect of AG11 on cell viability was evaluated by 3-(4,5-dimethylthiazol-2yl)-2,5- diphenyltetrazolium bromide assay and apoptotic cell death was analyzed by flow cytometry. Finally, the effect of AG11 on tubulin polymerization in vitro and microtubule distribution across the cells was investigated. Results: AG11 was found to have an IC50 (half-maximal inhibitory concentration) of 4.6 ìM and its inhibitory effect on RT4 cells proliferation is associated with a cell-cycle arrest in G2+ M phases followed by apoptosis after a 48 h treatment. AG11 prevented polymerization of purified tubulin in a concentration-dependent manner in vitro and disrupted mitotic spindle formation in cells. Conclusion: AG11 appears to be an attractive scaffold for further development of a structurally simpler new anti-microtubule agents.

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