La Tour-du-Pin, France
La Tour-du-Pin, France

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Gressette M.,University Paris - Sud | Verillaud B.,University Paris - Sud | Jimenez-Pailhes A.-S.,University Paris - Sud | Lelievre H.,Institute Of Recherches Internationales Servier | And 7 more authors.
PLoS ONE | Year: 2014

EBV-related nasopharyngeal carcinomas (NPCs) still raise serious therapeutic problems. The therapeutic potential of the histone-deacetylase (HDAC) inhibitor Abexinostat was investigated using 5 preclinical NPC models including 2 patient-derived xenografts (C15 and C17). The cytotoxicity of Abexinostat used either alone or in combination with cis-platin or irradiation was assessed in vitro by MTT and clonogenic assays using 2 EBV-negative (CNE1 and HONE1) and 3 EBV-positive NPC models (C15, C17 and C666-1). Subsequently, the 3 EBV-positive models were used under the form of xenografts to assess the impact of systemic treatments by Abexinostat or combinations of Abexinostat with cis-platin or irradiation. Several cell proteins known to be affected by HDAC inhibitors and the small viral non-coding RNA EBER1 were investigated in the treated tumors. Synergistic cytotoxic effects of Abexinostat combined with cis-platin or irradiation were demonstrated in vitro for each NPC model. When using xenografts, Abexinostat by itself (12.5 mg/kg, BID, 4 days a week for 3 weeks) had significant anti-tumor effects against C17. Cooperative effects with cis-platin (2 mg/kg, IP, at days 3, 10 and 17) and irradiation (1Gy) were observed for the C15 and C17 xenografts. Simultaneously two types of biological alterations were induced in the tumor tissue, especially in the C17 model: a depletion of the DNA-repair protein RAD51 and a stronger in situ detection of the small viral RNA EBER1. Overall, these results support implementation of phase I/II clinical trials of Abexinostat for the treatment of NPC. A depletion of RAD51 is likely to contribute to the cooperation of Abexinostat with DNA damaging agents. Reduction of RAD51 combined to enhanced detection of EBER 1 might be helpful for early assessment of tumor response. © 2014 Gressette et al.


Sevestre M.-A.,Service de medecine vasculaire | Belizna C.,CHU de Rouen | Durant C.,Nantes University Hospital Center | Bosson J.-L.,Grenoble University Hospital Center | And 4 more authors.
Journal des Maladies Vasculaires | Year: 2014

Cancer is associated with venous thromboembolism in 20% of patients. In such patients, thrombosis is difficult to treat, associated with bleeding, recurrence, and death. Specific treatments for venous thromboembolism in cancer are recommended. Guidelines have been implemented in many countries and international guidelines have been recently developed. We evaluated the adhesion to national French guidelines via a survey of cancer patients treated for venous thromboembolism. Methods: A national cross-sectional observational study evaluated the adhesion to guidelines in hospitalized patients. Good clinical practice was defined as initial 10-day treatment with injectable molecules followed by long-term treatment with low molecular weight heparin for at least 3 months. Demographic data, cancer type, stage, treatment, risk factors and type of thrombosis, were recorded. Results: Five patients were included in 47 centers. Overall adhesion to guidelines was present in 59% (55-63%) of patients (295/500). During initial treatment, adhesion was high (487/496; 98%) but dropped (296/486; 62%) during the long-term maintenance. In patients with renal insufficiency, only a fourth of them received the adequate treatment. A majority of patients had metastatic disease (64%). Cancer sites were gastro-intestinal (25%), gynecologic (23%), pulmonary (21%), hematological (14%), urologic (10%), or other (8%). Lung and hematological malignancies were significantly associated with the highest and lowest rates of adhesion. Conclusion: Adhesion to national guidelines for treatment of venous thromboembolism in cancer is not optimal. Good compliance is observed during initial treatment, but drops after 10 days, underlying the need for further education to achieve a better implementation on a national level. © 2014 Elsevier Masson SAS.


PubMed | Hopital Saint Louis, Hopital du Val de Grace, GH Pitie Salpetriere, Nantes University Hospital Center and 4 more.
Type: Journal Article | Journal: Journal des maladies vasculaires | Year: 2014

Cancer is associated with venous thromboembolism in 20% of patients. In such patients, thrombosis is difficult to treat, associated with bleeding, recurrence, and death. Specific treatments for venous thromboembolism in cancer are recommended. Guidelines have been implemented in many countries and international guidelines have been recently developed. We evaluated the adhesion to national French guidelines via a survey of cancer patients treated for venous thromboembolism.A national cross-sectional observational study evaluated the adhesion to guidelines in hospitalized patients. Good clinical practice was defined as initial 10-day treatment with injectable molecules followed by long-term treatment with low molecular weight heparin for at least 3 months. Demographic data, cancer type, stage, treatment, risk factors and type of thrombosis, were recorded.Five patients were included in 47 centers. Overall adhesion to guidelines was present in 59% (55-63%) of patients (295/500). During initial treatment, adhesion was high (487/496; 98%) but dropped (296/486; 62%) during the long-term maintenance. In patients with renal insufficiency, only a fourth of them received the adequate treatment. A majority of patients had metastatic disease (64%). Cancer sites were gastro-intestinal (25%), gynecologic (23%), pulmonary (21%), hematological (14%), urologic (10%), or other (8%). Lung and hematological malignancies were significantly associated with the highest and lowest rates of adhesion.Adhesion to national guidelines for treatment of venous thromboembolism in cancer is not optimal. Good compliance is observed during initial treatment, but drops after 10 days, underlying the need for further education to achieve a better implementation on a national level.


PubMed | Hopital Desgenettes, Institute Gustave Roussy, Hopital du Val de Grace, Institute National dOncologie and University Pierre and Marie Curie
Type: Journal Article | Journal: Bulletin du cancer | Year: 2014

Disseminated intravascular coagulation (DIC) is a complex abnormality of hemostasis with dramatic consequences and long described as associated with tumors. Yet the diagnosis and management of paraneoplastic DIC are poorly defined. The purpose of this paper is to review DIC associated with solid tumors, at the pathophysiological and therapeutic levels in particular. We also report data from a recent retrospective series of patients with DIC in the context of a solid tumor, to illustrate the epidemiological, clinical and prognostic.


Ducray F.,Rockefeller University | Dutertre G.,Hopital du Val de Grace | Ricard D.,Hopital du Val de Grace | Gontier E.,Hopital du Val de Grace | And 2 more authors.
Bulletin du Cancer | Year: 2010

A better understanding of gliomas biology is now leading to a combined histo-molecular classification of these tumors. In anaplastic gliomas ongoing studies depend on 1p/19q codeletion status and in glioblastomas on MGMT methylation status. Advanced brain tumor imaging elicits a better identification of gliomas evolutive potential of. In lowgrade gliomas, the importance of maximal resection and the role of chemotherapy are being increasingly recognized. In anaplastic gliomas, phase III studies have clarified the respective roles of chemotherapy and radiotherapy. In glioblastomas concomitant chemoradiotherapy is the standard. Most targeted therapies, namely anti-EGFR therapies have failed to demonstrate efficacy but anti-angiogenics are promising. The aim of this review is to discuss the main advances in adults' gliomas biology, imaging and treatment. ©John Libbey Eurotext.


Culine S.,CRLC Val dAurelle | Flechon A.,Center Leon Berard | Guillot A.,Institute Of Cancerologie Of La Loire | Le Moulec S.,Hopital du Val de Grace | And 8 more authors.
European Urology | Year: 2011

Background: The optimal chemotherapy for patients with advanced transitional cell carcinoma of the urothelium who are not eligible for cisplatin remains to be defined. Objective: To assess the activity of gemcitabine alone (GEM) or in combination with oxaliplatin (GEMOX) in a randomized phase 2 trial. Design, setting, and participants: The primary end point was the objective response rate according to Response Evaluation Criteria in Solid Tumors criteria. The sample size was based on a two-stage Fleming design with p0 = 35% and p1 = 55%. At the end of the first stage designed to register 20 patients on each treatment arm, the observation of seven or more objective responses would have led to the inclusion of 30 more patients in each arm. Results and limitations: From July 2004 to March 2009, 44 patients in 10 centers were randomly assigned into the GEM or the GEMOX arm, 22 on each treatment arm. The median age was 76 yr. Seven patients were included for a performance status (PS) of 2 only. The remaining 37 patients had an impaired renal function, 11 of whom also had a PS of 2. The median creatinine clearance was 45 ml/min (range: 30-80 ml/min). The trial was closed after the first part because the GEMOX arm did not reach the targeted objective response rate to proceed further. Conclusions: Oxaliplatin does not add any significant activity (in terms of response rates) compared with gemcitabine alone in patients with advanced transitional cell carcinoma of the urothelium who are ineligible for cisplatin. © 2011 European Association of Urology.


Auxemery Y.,Service medical de psychologie clinique appliquee a laeronautique | Lahutte B.,Hopital du Val de Grace
Annales Medico-Psychologiques | Year: 2015

We present the learned lessons from clinical practice of French military psychiatrists in Afghanistan between 2009 and 2013. The main tasks of these psychiatrists were: medical and psychological debriefing closer to the wounded soldiers, outpatient activity marked by psychotraumatology and liaison psychiatry, forensic activities and technical advice to the command. The psychiatrist at the Medical Surgical Hospital supports the health care team as much as he is benefiting to supervision by a more experienced practitioner. On his return, the practitioner transmits his experience, which will give us the opportunity to discuss the "Afghan syndrome" and mental disorders resulting from a double "psychic and brain" trauma. We conclude on this clinic and practice in exceptional conditions. © 2015 Elsevier Masson SAS.


PubMed | Hopital du Val de Grace and Gustave Roussy Campus Cancer
Type: Journal Article | Journal: Bulletin du cancer | Year: 2013

The combination of paclitaxel and bevacizumab was EMA-approved as first-line therapy in metastatic breast cancer. Moreover, in vitro studies showed a potential antiangiogenic synergistic effect of paclitaxel and bevacizumab.Between November 2008 and March 2010, this case series study included 15 patients with metastatic non squamous-cell lung carcinoma (NSCLC). Those were bevacizumab eligible and received the same regimen used in metastatic breast cancer with weekly paclitaxel (80 mg/m(2), days 1, 8 and 15) and bevacizumab (10 mg/kg at days 1 and 15) after at least one prior line of chemotherapy. Efficacy was evaluated by CT-scan and PET-FDG every two months. Circulating endothelial progenitor cells (CEP) and circulating endothelial cells (CEC) levels were explored in a subset of patients.Median age 56 (36-75), female: 47%, never smokers: 27%, adenocarcinoma: 100%, PS 0-1: 87% and PS 3: 13%. All patients were treated with a first-line platinum-based doublet with or without bevacizumab and 70% of them with erlotinib in the second-line. No major toxicity was observed. Partial response (PR) rate was 44% (31-63%) using RECIST criteria on CT-scan, and 65% (29-88%) with PET FDG. PS improved in 33% of the cases. Median progression free survival was 4.6 months. An increase of CEC and CEP was observed in patients with NSCLC treated with paclitaxel and bevacizumab.In this retrospective series, our results suggest efficacy signal in pre-treated metastatic NSCLC and warrant further assessment in a randomized clinical trial.


Pons Y.,Hopital du Val de Grace | Clement P.,Hopital du Val de Grace | Crambert A.,Hopital du Val de Grace | Conessa C.,Hopital du Val de Grace
Revue de Laryngologie Otologie Rhinologie | Year: 2010

Introduction: Facial palsy (FP) is a feared complication of parotidectomy. Facial nerve monitoring (FNM) has been poorly evaluated since it was created at the beginning of the 90's. The authors described a retrospective series and discussed it reviewing the literature data. Subjects et method: From January 2002 to January 2009, 75 parotidectomies were performed in 72 patients (34 males, 38 females), without FNM in 28 cases (group 1) and with FNM in 47 cases (group 2). Results: In group 1, 9 FP were noted, 5 were transient and 4 were definitive. In group 2, 12 FP were noted, 9 were transient and 3 were definitive. Both one month and six months after parotidectomy, the FP rate was significatively higher in group 1 than in group 2 for the reoperations. Conclusions: Facial nerve monitoring is an adjunctive method available to a surgeon during parotid surgery to assist with the functional preservation of the facial nerve. It did not allow to improve the facial prognosis in benign tumours removal but it improved the facial prognosis in reoperations. Its interest should be tested for malignant tumour removal.


Pons Y.,Hopital du Val de Grace | De Ballivet Regloix S.,Hopital du Val de Grace | Maurin O.,Hopital du Val de Grace | Conessa C.,Hopital du Val de Grace
Revue de Laryngologie Otologie Rhinologie | Year: 2011

Introduction: Obstructive Sleep Apnea Syndrome (OSAS) is becoming an important public health problem because of its frequency and adverse health consequences. The objective of this prospective study was to evaluate the prevalence of and risk factors for OSA in a cohort of subjects working for the french Army. Subjects and methods: This prospective study was carried out on a sample of volunteers working for the French army. The subjects were recruited at their annual work visit between November 2008 and September 2009. Subjects were asked to complete 2 screening questionnaires (Epworth and Berlin) and were given a medical examination. Subjects suspected of having OSAS (based on high questionnaire scores) were monitored by nocturnal ventilatory polygraphy. OSAS was diagnosed if the subject was found to have an apnea/hypopnea index (AHI) greater than or equal to 5. Results: In this healthy, young and active population (n= 1054), 4.20% of subjects were diagnosed with OSA. Comparing our two groups of subjects (OSA and non-OSA), several statistically significant (p< .05) differences emerged that may be associated with OSA: the individuals with OSA were older by an average of 7 years, they presented with an average BMI greater than 4.5 kg/m 2, an average abdominal girth greater than 12.2 cm and an average cervical circumference greater than 2.6 cm. In addition, they consumed more tobacco when they were smokers and were more likely to present with permanent nasal obstruction. They were also more likely to suffer from gastroesophageal reflux and present with skeletal class II. Finally, they presented with a longer average soft palate as determined by the Mallampati scoring system. Conclusion: We found that the major risk factors for OSAS were age, BMI, abdominal girth and cervical circumference (linear correlations determined by bi-variate analysis).

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