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Hôpital-Camfrout, France

Clavreul A.,Angers University Hospital Center | Clavreul A.,French Institute of Health and Medical Research | Clavreul A.,University of Angers | Piard N.,Etablissement Francais du Sang EFS | And 7 more authors.
Journal of Clinical Neuroscience | Year: 2010

We report on the safety and feasibility of autologous tumor cell vaccination combined with infusion of granulocyte-macrophage colony-stimulating factor by a programmable pump in the treatment of recurrent malignant gliomas. The programmable pump is a promising tool used to infuse cytokines subcutaneously for vaccination. Our trial enrolled nine patients who had undergone surgery, radiation and had been successfully weaned off steroids. Unfortunately, only five patients completed the protocol and were monitored for side effects, local reactions, delayed-type hypersensitivity (DTH) responses and survival. The treatment was well tolerated. Two patients developed DTH reactions after vaccination and three patients had an unusually long survival without any other treatment. Despite the few patients treated, the results of this trial are encouraging. This study also highlights the specific difficulties encountered in vaccination programs for the treatment of glioma. © 2010 Elsevier Ltd. All rights reserved.

Etablissement Francais Du Sang Efs | Date: 2014-06-13

Isolated nucleic acid sequence encoding the CD20 gene comprising SEQ ID NO: 5, recombinant vector comprising a nucleic acid sequence placed under the control of one or a plurality of elements required for the expression thereof in a host cell, and method for improving the efficacy of a treatment comprising using a nucleic acid sequence comprising SEQ ID NO: 5.

Chen J.-M.,Etablissement Francais du Sang EFS | Chen J.-M.,French Institute of Health and Medical Research | Chen J.-M.,University of Western Brittany | Cooper D.N.,University of Cardiff | And 6 more authors.
Seminars in Cancer Biology | Year: 2010

Genomic rearrangements in inherited disease and cancer involve gross alterations of chromosomes or large chromosomal regions and can take the form of deletions, duplications, insertions, inversions or translocations. The characterization of a considerable number of rearrangement breakpoints has now been accomplished at the nucleotide sequence level, thereby providing an invaluable resource for the detailed study of the mutational mechanisms which underlie genomic recombination events. A better understanding of these mutational mechanisms is vital for improving the design of mutation detection strategies. At least five categories of mutational mechanism are known to give rise to genomic rearrangements: (i) homologous recombination including non-allelic homologous recombination (NAHR), gene conversion, single strand annealing (SSA) and break-induced replication (BIR), (ii) non-homologous end joining (NHEJ), (iii) microhomology-mediated replication-dependent recombination (MMRDR), (iv) long interspersed element-1 (LINE-1 or L1)-mediated retrotransposition and (v) telomere healing. Focussing on the first three of these general mechanisms, we compare and contrast their hallmark characteristics, and discuss the role of various local DNA sequence features (e.g. recombination-promoting motifs, repetitive sequences and sequences capable of non-B DNA formation) in mediating the recombination events that underlie gross genomic rearrangements. Finally, we explore how studies both at the level of the gene (using the neurofibromatosis type-1 gene as an example) and the whole genome (using data derived from cancer genome sequencing studies) are shaping our understanding of the impact of genomic rearrangements as a cause of human genetic disease. © 2010 Elsevier Ltd.

Gallot G.,French Institute of Health and Medical Research | Gallot G.,Nantes University Hospital Center | Vollant S.,French Institute of Health and Medical Research | Saiagh S.,French Institute of Health and Medical Research | And 17 more authors.
Journal of Immunotherapy | Year: 2014

We report herein the results we obtained and the limitations we experienced during the production and use of a bank of Epstein-Barr virus (EBV)-transformed human cytotoxic T lymphocytes (EBV-CTLs). To assess the feasibility and toxicity of this strategy, we selected and stored, in liquid nitrogen, 4 billion EBV-CTLs from each of the 13 selected donors. Subsequently, in a multicenter phase I/II study, 11 patients with EBV-associated lymphoma resistant to conventional treatments received 1-3 doses of 5 million EBV-CTLs/kg with 1-3 and 0-4 compatibilities for human leukocyte antigen (HLA)-I and HLA-II, respectively. Except for one event of fever after injection, no immediate or delayed toxicity, no graft versus host disease, and no graft rejection attributable to CTL infusion were observed. Three patients presented complete remission and 1 partial remission after treatment. Considering the clinical options currently available, and the constrains associated with CTL preparation and implementation, we conclude that CTL banks should consist of a reasonably small number of cell lines with documented specificities. This objective could be more easily achieved if the few homozygous donors for the most frequent HLA alleles of the targeted population could be made available for such a project. Copyright © 2014 by Lippincott Williams & Wilkins.

Leroux L.,French Institute of Health and Medical Research | Descamps B.,French Institute of Health and Medical Research | Tojais N.F.,French Institute of Health and Medical Research | Seguy B.,Pole Cardiothoracique | And 10 more authors.
Molecular Therapy | Year: 2010

Mesenchymal stem cells (MSC) are multipotent postnatal stem cells, involved in the treatment of ischemic vascular diseases. We investigate the ability of MSC, exposed to short-term hypoxic conditions, to participate in vascular and tissue regeneration in an in vivo model of hindlimb ischemia. Transplantation of hypoxic preconditioned murine MSC (HypMSC) enhanced skeletal muscle regeneration at day 7, improved blood flow and vascular formation compared to injected nonpreconditioned MSC (NormMSC). These observed effects were correlated with an increase in HypMSC engraftment and a putative role in necrotic skeletal muscle fiber clearance. Moreover, HypMSC transplantation resulted in a large increase in Wnt4 (wingless-related MMTV integration site 4) expression and we demonstrate its functional significance on MSC proliferation and migration, endothelial cell (EC) migration, as well as myoblast differentiation. Furthermore, suppression of Wnt4 expression in HypMSC, abrogated the hypoxia-induced vascular regenerative properties of these cells in the mouse hindlimb ischemia model. Our data suggest that hypoxic preconditioning plays a critical role in the functional capabilities of MSC, shifting MSC location in situ to enhance ischemic tissue recovery, facilitating vascular cell mobilization, and skeletal muscle fiber regeneration via a paracrine Wnt-dependent mechanism. © The American Society of Gene & Cell Therapy.

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