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Corinne Bouvier, Nicolas Macagno, Quy Nguyen, Anderson Loundou, Carine Jiguet-Jiglaire, Jean-Claude Gentet, Jean-Luc Jouve, Alexandre Rochwerger, Jean-Camille Mattei, Daniel Bouvard, Sébastien Salas
INTRODUCTION: Currently, very few studies are available concerning the mammalian Hippo pathway in bone sarcomas. YAP/TAZ transcription co-activators are key downstream effectors of this pathway and may also have oncogenic properties. Additionally, recent in-vitro experiments showed that expression of β1-integrin promoted metastasis in osteosarcomas. This study investigated the expression of YAP/TAZ and β1-integrin in human osteosarcomas. MATERIALS AND METHODS: We performed automated immunohistochemistry on tissue-microarrays (TMA) in which 69 conventional osteosarcomas biopsies performed prior to chemotherapy were embedded...
September 2, 2016: Oncotarget
Sophie Piperno-Neumann, Marie-Cécile Le Deley, Françoise Rédini, Hélène Pacquement, Perrine Marec-Bérard, Philippe Petit, Hervé Brisse, Cyril Lervat, Jean-Claude Gentet, Natacha Entz-Werlé, Antoine Italiano, Nadège Corradini, Emmanuelle Bompas, Nicolas Penel, Marie-Dominique Tabone, Anne Gomez-Brouchet, Jean-Marc Guinebretière, Eric Mascard, François Gouin, Aurélie Chevance, Naïma Bonnet, Jean-Yves Blay, Laurence Brugières
BACKGROUND: Based on preclinical data for the antitumour effect of zoledronate in osteosarcoma, we assessed whether zoledronate combined with chemotherapy and surgery improved event-free survival in children and adults with osteosarcoma. METHODS: In this randomised, multicentre, open-label, phase 3 trial (OS2006), patients aged between 5 years and 50 years with newly diagnosed high-grade osteosarcoma were randomly assigned to receive standard chemotherapy with or without ten zoledronate intravenous infusions (four preoperative and six postoperative)...
August 2016: Lancet Oncology
Marie Amélie Heng, Laetitia Padovani, Philippe Dory-Lautrec, Jean Claude Gentet, Arnaud Verschuur, Eddy Pasquier, Dominique Figarella-Branger, Didier Scavarda, Nicolas André
The association of bevacizumab and irinotecan has been shown to display a quick efficacy in low-grade glioma (LGG), but most patients relapse within months after cessation of therapy. From October 2012 to March 2014, four patients have been treated with irinotecan-bevacizumab followed by a metronomic maintenance with weekly vinblastine to try to prevent relapses. After a median follow-up of 23 months after the end of the bevacizumab-irinotecan induction, no patient relapsed. These observations suggest that maintenance chemotherapy with weekly vinblastine after an induction by irinotecan-bevacizumab can improve progression-free survival in children with LGG...
July 2016: Cancer Medicine
Quentin Perrenoud, Cyriel M A Pennartz, Luc J Gentet
Cortical gamma activity (30-80 Hz) is believed to play important functions in neural computation and arises from the interplay of parvalbumin-expressing interneurons (PV) and pyramidal cells (PYRs). However, the subthreshold dynamics underlying its emergence in the cortex of awake animals remain unclear. Here, we characterized the intracellular dynamics of PVs and PYRs during spontaneous and visually evoked gamma activity in layers 2/3 of V1 of awake mice using targeted patch-clamp recordings and synchronous local field potentials (LFPs)...
February 2016: PLoS Biology
Martin Vinck, Jeroen J Bos, Laura A Van Mourik-Donga, Krista T Oplaat, Gerbrand A Klein, Jadin C Jackson, Luc J Gentet, Cyriel M A Pennartz
Beta and gamma rhythms have been hypothesized to be involved in global and local coordination of neuronal activity, respectively. Here, we investigated how cells in rodent area S1BF are entrained by rhythmic fluctuations at various frequencies within the local area and in connected areas, and how this depends on behavioral state and cell type. We performed simultaneous extracellular field and unit recordings in four connected areas of the freely moving rat (S1BF, V1M, perirhinal cortex, CA1). S1BF spiking activity was strongly entrained by both beta and gamma S1BF oscillations, which were associated with deactivations and activations, respectively...
2015: Frontiers in Systems Neuroscience
Mathilde Penel-Page, Isabelle Ray-Coquard, Julie Larcade, Magali Girodet, Laure Bouclier, Muriel Rogasik, Nadège Corradini, Natacha Entz-Werle, Laurence Brugieres, Julien Domont, Cyril Lervat, Sophie Piperno-Neumann, Helène Pacquement, Jacques-Olivier Bay, Jean-Claude Gentet, Antoine Thyss, Loic Chaigneau, Bérangère Narciso, Helène Cornille, Jean-Yves Blay, Perrine Marec-Bérard
BACKGROUND: The objective of this study is to explore the off-label use of targeted therapies (TTs) for patients with osteosarcoma registered within the French Sarcoma Group--Bone Tumor Study Group (GSF-GETO) national registry. METHODS: All patients with an osteosarcoma, registered between January 1, 2009 and July 15, 2013 were analyzed. RESULTS: Twenty-nine patients with refractory relapsed osteosarcomas received 33 treatment lines of TTs...
2015: BMC Cancer
Nadia Urbain, Paul A Salin, Paul-Antoine Libourel, Jean-Christophe Comte, Luc J Gentet, Carl C H Petersen
The thalamus transmits sensory information to the neocortex and receives neocortical, subcortical, and neuromodulatory inputs. Despite its obvious importance, surprisingly little is known about thalamic function in awake animals. Here, using intracellular and extracellular recordings in awake head-restrained mice, we investigate membrane potential dynamics and action potential firing in the two major thalamic nuclei related to whisker sensation, the ventral posterior medial nucleus (VPM) and the posterior medial group (Pom), which receive distinct inputs from brainstem and neocortex...
October 27, 2015: Cell Reports
Clothilde Vallet, Nicolas André, Jean-Claude Gentet, Arnauld Verschuur, Gérard Michel, Frédéric Sotteau, Cécile Martha, Laurent Grélot
AIM OF THE STUDY: To evaluate the feasibility and to measure the effects of a six-week-long adapted physical activity programme (APAP), including 5 days of intense dog sledding, on the physical and psychological health of children and adolescents treated for cancer. METHODS: Eleven children and teenagers (4 girls, 7 boys; mean age 14.3 ± 2.9 years) participated in this monocentric pilot programme of adapted physical activities from February 2013 to March 2013. Seven were still on treatment...
2015: Ecancermedicalscience
Pascal Chastagner, Bénédicte Devictor, Birgit Geoerger, Isabelle Aerts, Pierre Leblond, Didier Frappaz, Jean-Claude Gentet, Serge Bracard, Nicolas André
PURPOSE: To determine the maximum recommended dose (RD) and pharmacokinetics of Myocet®, a non-pegylated liposomal doxorubicin, in children. METHODS: Eligible patients were children with refractory high-grade glioma who had received prior chemotherapy and radiotherapy but no anthracyclines. Cohorts of at least three patients each received escalating doses of Myocet® starting at 60 mg/m(2) at 3-week intervals, administered intravenously over 1 h, and then doses were escalated to 75 mg/m(2) corresponding to the adult RD...
August 2015: Cancer Chemotherapy and Pharmacology
J-C Gentet, C Vallet, G Michel, N André, A Verschuur, M-N Bonfanti, S Faure, F Sotteau
No abstract text is available yet for this article.
May 2015: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
Lauriane Eberst, Claire Cropet, Axel Le Cesne, Patricia Pautier, Nicolas Penel, Antoine Adenis, Christine Chevreau, Jacques-Olivier Bay, Olivier Collard, Didier Cupissol, Florence Duffaud, Jean-Claude Gentet, Sophie Piperno-Neumann, Perrine Marec-Berard, Emmanuelle Bompas, Antoine Thyss, Loic Chaigneau, Philippe Cassier, François Bertucci, Jean-Yves Blay, Isabelle Ray-Coquard
BACKGROUND: Few targeted therapies (TTs) are registered for sarcoma treatment despite numerous phase II studies and yet there are potential treatment options for patients after standard treatment escape. The French Sarcoma Group - Bone Tumor Study Group (GSF-GETO) created a national registry to evaluate the outcome of patients treated with off-label TTs. METHODS: Every consecutive sarcoma-patient receiving an off-label TT outside a clinical trial was included. The objective was to describe this patient efficacy and safety data in routine practice...
2014: BMC Cancer
Sébastien Salas, Carine Jiguet-Jiglaire, Loic Campion, Catherine Bartoli, Frédéric Frassineti, Jean-Laurent Deville, André Maues De Paula, Fabien Forest, Pascal Jézéquel, Jean-Claude Gentet, Corinne Bouvier
BACKGROUND: The standard therapy regimen of conventional osteosarcoma includes neoadjuvant chemotherapy followed by surgical resection and postoperative chemotherapy. The percentage of necrotic tissue following induction chemotherapy is assessed by using the Huvos grading system, which classifies patients as "poor responders" (PR) and "good responders" (GR). The aim of this study was to identify molecular markers expressed differentially between good and poor responders to neoadjuvant chemotherapy in order to predict the response to chemotherapy in conventional osteosarcomas before beginning treatment...
2014: BMC Cancer
Perrine Marec-Berard, Céline Segura-Ferlay, Marie-Dominique Tabone, Helene Pacquement, Cyril Lervat, Jean-Claude Gentet, Claudine Schmitt, Nathalie Gaspar, Laurence Brugières
Introduction. Osteosarcoma relapse has a poor prognosis, with less than 25% survival at 5 years. We describe the experience of the French Society of Paediatric Oncology (SFCE) with high dose (HD) thiotepa and autologous stem cell transplantation (ASCT) in 45 children with relapsed osteosarcoma. Patients and Methods. Between 1992 and 2004, 53 patients received HD thiotepa (900 mg/m(2)) followed by ASCT in 6 centres. Eight patients were excluded from analysis, and we retrospectively reviewed the clinical radiological and anatomopathological patterns of the 45 remaining patients...
2014: Sarcoma
David Meyronet, Karen Silva, Dominique Figarella-Branger, Catherine Godfraind, Marie-Bernadette Delisle, Claude-Alain Maurage, Catherine Miquel, Pascale Varlet, Jean-Claude Gentet, Anne-Isabelle-Bertozzi Salamon, Alexandre Vasiljevic, Anne Jouvet
Diagnosis of paediatric tumours of the central nervous system is often difficult because WHO classification criteria are mainly defined for adults tumours and do not always apply to their paediatric counterparts. These tumours are rare (400 cases/year among more than 50 pathological subtypes per year in France). Pathological diagnosis may be a challenge for a general pathologist with a too low number of paediatric cases in his recruitment. Hence, a reference group of paediatric neuropathologists was formed (GENOP) on the behalf of the comité "Tumeurs Cérébrales" de la Société Française de lutte contre les Cancers de l'Enfant...
February 2014: Annales de Pathologie
Nathalie Gaspar, Angela Di Giannatale, Birgit Geoerger, Françoise Redini, Nadège Corradini, Natacha Enz-Werle, Franck Tirode, Perrine Marec-Berard, Jean-Claude Gentet, Valérie Laurence, Sophie Piperno-Neumann, Odile Oberlin, Laurence Brugieres
Primary malignant bone tumours, osteosarcomas, and Ewing sarcomas are rare diseases which occur mainly in adolescents and young adults. With the current therapies, some patients remain very difficult to treat, such as tumour with poor histological response to preoperative CT (or large initial tumour volume for Ewing sarcomas not operated), patients with multiple metastases at or those who relapsed. In order to develop new therapies against these rare tumours, we need to unveil the key driving factors and molecular abnormalities behind the malignant characteristics and to broaden our understanding of the phenomena sustaining the metastatic phenotype and treatment resistance in these tumours...
2012: Sarcoma
Luc J Gentet
Although the neocortex forms a distributed system comprised of several functional areas, its vertical columnar organization is largely conserved across areas and species, suggesting the existence of a canonical neocortical microcircuit. In order to elucidate the principles governing the organization of such a cortical diagram, a detailed understanding of the dynamics binding different types of cortical neurons into a coherent algorithm is essential. Within this complex circuitry, GABAergic interneurons, while forming approximately only 15-20% of all cortical neurons, appear critical in maintaining a dynamic balance between excitation and inhibition...
2012: Frontiers in Neural Circuits
M Moutschen
We initiate this review article by a brief description of a few monogenic autoimmune diseases such as the APECED and the IPEX syndrome because they allow understand the fundamental mechanisms of self tolerance. Next we describe with more details the complex autoimmune diseases and discuss the recent data regarding the associated genetic and environmental factors and their modes of interaction. The conclusion of the article deals with the practical implications of this inherent complexity for the researcher and the clinician...
May 2012: Revue Médicale de Liège
Nathalie Gaspar, Annie Rey, Perrine Marec Bérard, Jean Michon, Jean Claude Gentet, Marie Dominique Tabone, Henri Roché, Anne Sophie Defachelles, Odile Lejars, Emmanuel Plouvier, Claudine Schmitt, Binh Bui, Patrick Boutard, Sophie Taque, Martine Munzer, Jean-Pierre Vannier, Dominique Plantaz, Natacha Entz-Werle, Natacha Enz-Werlé, Odile Oberlin
AIM OF THE STUDY: To determine whether a risk factor adapted chemotherapy would improve the outcome of non-metastatic bone Ewing's sarcoma. METHODS: Standard risk tumours (SR, good histological response to chemotherapy or small unresected tumours) received the previous EW88 chemotherapy. Ifosfamide/etoposide (IE) were introduced after 3 courses of cyclophosphamide/doxorubicine when tumour regression was <50% or during consolidation therapy for the intermediate risk tumours (IR, intermediate histological response 5-30% residual cells or large unresected tumours >100ml)...
June 2012: European Journal of Cancer
Luc J Gentet, Yves Kremer, Hiroki Taniguchi, Z Josh Huang, Jochen F Staiger, Carl C H Petersen
Neocortical GABAergic neurons have diverse molecular, structural and electrophysiological features, but the functional correlates of this diversity are largely unknown. We found unique membrane potential dynamics of somatostatin-expressing (SOM) neurons in layer 2/3 of the primary somatosensory barrel cortex of awake behaving mice. SOM neurons were spontaneously active during periods of quiet wakefulness. However, SOM neurons hyperpolarized and reduced action potential firing in response to both passive and active whisker sensing, in contrast with all other recorded types of nearby neurons, which were excited by sensory input...
April 2012: Nature Neuroscience
C Baunin, G Schmidt, K Baumstarck, C Bouvier, J C Gentet, A Aschero, A Ruocco, B Bourlière, G Gorincour, C Desvignes, N Colavolpe, G Bollini, P Auqier, P Petit
BACKGROUND: Preoperative diffusion-weighted MRI (DW-MRI) has been described as an efficient method to differentiate good and poor responders to chemotherapy in osteosarcoma patients. A DW-MRI performed earlier during treatment could be helpful in monitoring chemotherapy. OBJECTIVE: To assess the accuracy of DW-MRI in evaluating response to chemotherapy in the treatment of osteosarcoma, more specifically at mid-course of treatment. MATERIALS AND METHODS: This study was carried out on a prospective series of adolescents treated for long-bone osteosarcoma...
September 2012: Skeletal Radiology
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