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Marcy, France
Marcy, France
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Gay F.,ERYtech Pharma | Aguera K.,ERYtech Pharma | Senechal K.,ERYtech Pharma | Tainturier A.,Voxcan | And 9 more authors.
Cancer Medicine | Year: 2017

Erymet is a new therapy resulting from the encapsulation of a methionine gamma-lyase (MGL; EC number 4.4.1.11) in red blood cells (RBC). The aim of this study was to evaluate erymet potential efficacy in methionine (Met)-dependent cancers. We produced a highly purified MGL using a cGMP process, determined the pharmacokinetics/pharmacodynamics (PK/PD) properties of erymet in mice, and assessed its efficacy on tumor growth prevention. Cytotoxicity of purified MGL was tested in six cancer cell lines. CD1 mice were injected with single erymet product supplemented or not with vitamin B6 vitamer pyridoxine (PN; a precursor of PLP cofactor). NMRI nude mice were xenografted in the flank with U-87 MG-luc2 glioblastoma cells for tumor growth study following five intravenous (IV) injections of erymet with daily PN oral administration. Endpoints included efficacy and event-free survival (EFS). Finally, a repeated dose toxicity study of erymet combined with PN cofactor was conducted in CD1 mice. Recombinant MGL was cytotoxic on 4/6 cell lines tested. MGL half-life was increased from <24 h to 9–12 days when encapsulated in RBC. Conversion of PN into PLP by RBC was demonstrated. Combined erymet + PN treatment led to a sustained Met depletion in plasma for several days with a 85% reduction of tumor volume after 45 days following cells implantation, and a significant EFS prolongation for treated mice. Repeated injections in mice exhibited a very good tolerability with only minor impact on clinical state (piloerection, lean aspect) and a slight decrease in hemoglobin and triglyceride concentrations. This study demonstrated that encapsulation of methioninase inside erythrocyte greatly enhanced pharmacokinetics properties of the enzyme and is efficacy against tumor growth. The perspective on these results is the clinical evaluation of the erymet product in patients with Met starvation-sensitive tumors. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.


Khoshnevis M.,VetAgro Sup | Carozzo C.,VetAgro Sup | Bonnefont-Rebeix C.,VetAgro Sup | Belluco S.,VetAgro Sup | And 7 more authors.
Journal of Neuroscience Methods | Year: 2017

Background Glioblastoma is the most common and deadliest primary brain tumor for humans. Despite many efforts toward the improvement of therapeutic methods, prognosis is poor and the disease remains incurable with a median survival of 12–14.5 months after an optimal treatment. To develop novel treatment modalities for this fatal disease, new devices must be tested on an ideal animal model before performing clinical trials in humans. New method A new model of induced glioblastoma in Yucatan minipigs was developed. Nine immunosuppressed minipigs were implanted with the U87 human glioblastoma cell line in both the left and right hemispheres. Computed tomography (CT) acquisitions were performed once a week to monitor tumor growth. Results Among the 9 implanted animals, 8 minipigs showed significant macroscopic tumors on CT acquisitions. Histological examination of the brain after euthanasia confirmed the CT imaging findings with the presence of an undifferentiated glioma. Comparison with existing method Yucatan minipig, given its brain size and anatomy (gyrencephalic structure) which are comparable to humans, provides a reliable brain tumor model for preclinical studies of different therapeutic Methods in realistic conditions. Moreover, the short development time, the lower cyclosporine and caring cost and the compatibility with the size of commercialized stereotactic frames make it an affordable and practical animal model, especially in comparison with large breed pigs. Conclusion This reproducible glioma model could simulate human anatomical conditions in preclinical studies and facilitate the improvement of novel therapeutic devices, designed at the human scale from the outset. © 2017 Elsevier B.V.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-11-2015 | Award Amount: 6.44M | Year: 2016

The objective of the SPCCT project is to develop and validate a widely accessible, new quantitative and analytical in vivo imaging technology combining Spectral Photon Counting CT and contrast agents, to accurately and early detect, characterize and monitor neurovascular and cardiovascular disease. Spectral Photon Counting Computed Tomography (SPCCT) is a new imaging modality, currently in development, with a totally new type of detection chain designed to provide high count-rate capabilities while offering energy discrimination with high spatial resolution of 200m. Based on this discrimination, SPCCT can detect and quantify accurately a large variety of atoms (including Gadolinium, Gold, Bismuth) by using the K-edge technique. SPCCT, by a more accurate, less invasive (in comparison with IVUS and coronary angiography) and reliable evaluation of vascular inflammation will allow earlier disease diagnosis such as plaque inflammation before rupture, leading to improved clinical decisions and outcomes. This will be achievable with a high spatial resolution combined to the newly developed vascular inflammation specific contrast agent detected with high quality K-edge technique that can only be provided by a multi-spectral X-ray system. The project will therefore provide a complete tool (acquisition system and specific probes) dedicated to CV imaging. It will finally contribute to: Improved early diagnosis of atherosclerosis, prevention of acute event (MI, stroke) and personalized preventive treatment; Improved management of patient presenting with an acute CV event and clinical validation of treatment efficiency; Sustainability and harmonization of healthcare systems, as costly disorders of heart failure and stroke-related disability would be better prevented and efficiently treated; Economic growth in the EU diagnostics sector, through the development of new targeted contrast materials for SPCCT by SMEs.


Finck M.,University of Lyon | Finck M.,University of Glasgow | Ponce F.,University of Lyon | Guilbaud L.,University of Lyon | And 6 more authors.
Canadian Veterinary Journal | Year: 2015

There are no evidence-based guidelines as to whether computed tomography (CT) or endoscopy should be selected as the first-line procedure when a nasal tumor is suspected in a dog or a cat and only one examination can be performed. Computed tomography and rhinoscopic features of 17 dogs and 5 cats with a histopathologically or cytologically confirmed nasal tumor were retrospectively reviewed. The level of suspicion for nasal neoplasia after CT and/or rhinoscopy was compared to the definitive diagnosis. Twelve animals underwent CT, 14 underwent rhinoscopy, and 4 both examinations. Of the 12 CT examinations performed, 11 (92%) resulted in the conclusion that a nasal tumor was the most likely diagnosis compared with 9/14 (64%) for rhinoscopies. Computed tomography appeared to be more reliable than rhinoscopy for detecting nasal tumors and should therefore be considered as the first-line procedure. © 2015, Canadian Veterinary Medical Association. All rights reserved.


Chuzel T.,Voxcan | Sanchez V.,Sanofi S.A. | Vandamme M.,Voxcan | Martin S.,Voxcan | And 8 more authors.
PLoS ONE | Year: 2015

Infectious murine models greatly benefit from optical imaging using bioluminescent bacteria to non-invasively and repeatedly follow in vivo bacterial infection. In this context, one of the most critical parameters is the bioluminescence sensitivity to reliably detect the smallest number of bacteria. Another critical point is the anesthetic approaches that have been demonstrated to impact the bioluminescence flux emission in studies with luciferase-transfected tumor cells. However, this impact has never been assessed on bacteria bioluminescent models. To this end, we investigated the effects of four anesthesia protocols on the bioluminescence flux in a central venous catheter murine model (SKH1-hrhr mice) infected by a bioluminescent S. aureus Xen36 strain. Bioluminescence imaging was performed on mice anesthetized by either ketamine/xylazine (with or without oxygen supplementation), or isoflurane carried with air or oxygen. Total flux emission was determined in vivo daily for 3 days and ex vivo at the end of the study together with a CFU counting of the biofilm in the catheter. Bioluminescence flux differences appear between the different anesthetic protocols. Using a ketamine/xylazine anesthesia (with air), bacteria detection was impossible since the bioluminescence signal remains in the background signal. Mice anesthetized with isoflurane and oxygen led to a signal significantly higher to the background all along the kinetics. The use of isoflurane in air presents a bioluminescence signal similar to the use of ketamine/xylazine with oxygen. These data highlight the importance of oxygen to improve bioluminescence flux by bacteria with isoflurane as well as with ketamine/xylazine anesthetics. As a conclusion, we recommend the use of isoflurane anesthetic with oxygen to increase the bioluminescence sensitivity in this kind of study. © 2015 Chuzel et al.

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