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Sanchez C.J.,Laboratoire Of Biochimie Et Of Biologie Moleculaire | Sanchez C.J.,Aix - Marseille University | Sanchez C.J.,French Institute of Health and Medical Research | Sanchez C.J.,Laboratoire dHematologie | And 10 more authors.
Cancer Immunology, Immunotherapy | Year: 2011

Despite recent progress in the therapeutic approach of malignant haemopathies, their prognoses remain frequently poor. Immunotherapy offers an alternative of great interest in this context but defect or abnormal expression of human leukocyte antigens (HLA), frequently observed in cancer cells, limits its efficiency. Natural killer (NK) cells, which are able to kill target cells in a HLA-independent way, represent a novel tool in the treatment of haematological malignancies. Abnormal NK cytolytic function is observed in all the haematological malignancies studied, such as acute leukaemia, myelodysplastic syndromes or chronic myeloid/lymphoid leukaemia. Several mechanisms are involved in the alterations of NK cytotoxicity: decreased expression of activating receptors, increased expression of inhibitory receptors or defective expression of NK ligands on target cells. Further studies are needed to identify how each type of haematological malignancy escapes from the innate immune response. Attempts to increase the expression of activating receptors, to counteract inhibitory receptors expression, or to increase NK cell cytotoxic capacities could overcome tumour escape from innate immunity. These therapies are based on monoclonal antibodies or culture of NK cells in presence of cytokines or dendritic cells. Moreover, many novel drugs used in haematological malignancies [tyrosine kinase inhibitors, IMIDs®, proteasome inhibitors, demethylating agents, histone deacetylase inhibitors (HDACis), histamine dihydrochloride] display interesting immunomodulatory properties that affect NK cells. These data suggest that combined modalities associating cytotoxic drugs with innate immunity modulators may represent a major breakthrough in tumour eradication. © Springer-Verlag 2010. Source

Vieira T.,Paris-Sorbonne University | Antoine M.,Paris-Sorbonne University | Ruppert A.-M.,Paris-Sorbonne University | Fallet V.,Paris-Sorbonne University | And 10 more authors.
Lung Cancer | Year: 2014

Objectives: Pulmonary sarcomatoid carcinomas (SC) are highly disseminated types of non-small-cell lung carcinoma. Their prognosis is poor. New therapeutic targets are needed to improve disease management. Materials and methods: From 1995 to 2013, clinical and survival data from all consecutive patients with surgically treated SC were collected. Pathological and biomarker analyses were performed: TTF1, P63, c-MET and ALK expression (immunohistochemistry), PAS staining, ALK rearrangement (FISH), and EGFR, KRAS, HER2, BRAF, PIK3CA, and MET genes mutations (PCR). Results: Seventy-seven patients were included. Median age was 61 years (53-69). Histological subtypes were pleomorphic carcinoma (78%), carcinosarcoma (12%), and giant-cell and/or spindle-cell carcinoma (10%). Blood vessel invasion (BVI) was present in 90% of cases. Morphology and immunohistochemistry were indicative of an adenocarcinoma, squamous, and adenosquamous origin in 41.5%, 17% and 11.5%, respectively, 30% remained not-otherwise-specified. KRAS, PIK3CA, EGFR, and MET mutations were found in 31%, 8%, 3%, and 3%, respectively. No tumors had HER2 or BRAF mutations, or ALK rearrangement, whereas 34% had a c-MET positive score. Five-year overall survival (OS) was 29% for the whole population. At multivariate analysis, tumor size <50. mm (HR = 1.96 [1.04-3.73], p= 0.011), no lymph-node metastasis (HR = 3.25 [1.68-6.31], p< 0.0001), no parietal pleural invasion (HR = 1.16 [1.06-1.28], p= 0.002), no BVI (HR = 1.22 [1.06-1.40], p= 0.005), and no squamous component (HR = 3.17 [1.48-6.79], p= 0.01) were associated with longer OS. Biomarkers did not influence OS. Conclusion: Dedifferentiation in NSCLC could lead to SC and an epithelial subtype component could influence outcome. BVI was present in almost all SCs and was an independent factor of poor prognosis. © 2014 Elsevier Ireland Ltd. Source

Diaw M.,Laboratoire Of Physiologie Et Explorations Fonctionnelles | Samb A.,Laboratoire Of Physiologie Et Explorations Fonctionnelles | Diop S.,Laboratoire dHematoimmunologie | Sall N.D.,Laboratoire Of Biochimie Et Of Biologie Moleculaire | And 3 more authors.
British Journal of Sports Medicine | Year: 2014

The present study compared the changes in blood viscosity, hydration status, body temperature and heart rate between a group of sickle cell trait (SCT) carriers and a control (Cont) group before and after a soccer game performed in two conditions: one with water offered ad libitum (hydration condition; Hyd) and the other one without water (dehydration condition; Dehyd). Blood viscosity and haematocrit per blood viscosity ratio (HVR; an index of red blood cell oxygen transport effectiveness) were measured before and at the end of each game. Resting blood viscosity was greater in the SCT carriers than in the Cont group. The increase of blood viscosity over baseline at the end of the game in the Cont group was similar in the two conditions. In contrast, the change in blood viscosity occurring in SCT carriers during soccer games was dependant on the experimental condition: (1) in Dehyd condition, blood viscosity rose over baseline; (2) in Hyd condition, blood viscosity decreased below resting level reaching Cont values. The Cont group had higher HVR than SCT carriers at rest. HVR remained unchanged in the Cont group at the end of the games, whatever the experimental condition. Although HVR of SCT carriers decreased below baseline at the end of the game performed in Dehyd condition, it increased over resting level in Hyd condition reaching the values of the Cont group. Our study demonstrated that ad libitum hydration in exercising SCT carriers normalises the blood hyperviscosity. Source

Ben Lassoued A.,Laboratoire Of Biochimie Et Of Biologie Moleculaire | Nivaggioni V.,Laboratoire dHematologie | Gabert J.,Laboratoire Of Biochimie Et Of Biologie Moleculaire | Gabert J.,French Institute of Health and Medical Research
Expert Review of Molecular Diagnostics | Year: 2014

Minimal residual disease (MRD) assays are of a great value to assess treatment efficacy and may provide prognostic information. This is particularly relevant in the era of targeted therapy where the introduction of MRD monitoring has fundamentally transformed the way in which cancer patients are managed. While MRD guidelines are well-established for chronic myeloid leukemia, acute promyelocytic leukemia and acute lymphoblastic leukemia, areas for continuing development are available. High level of standardization and regular external quality control rounds and recommendations for data interpretation remain essential to improve MRD monitoring. In this review, we describe the different applications of MRD assays in most frequent hematologic malignancies and solid cancer and provide an overview of the strengths and potential weaknesses of each method. © 2014 Informa UK, Ltd. Source

Veyrat-Durebex C.,University of Tours | Veyrat-Durebex C.,Laboratoire Of Biochimie Et Of Biologie Moleculaire | Corcia P.,University of Tours | Dangoumau A.,University of Tours | And 9 more authors.
Molecular Neurobiology | Year: 2014

Amyotrophic lateral sclerosis (ALS), the most common adult-onset motor neuron disorder, is fatal for most patients less than 3 years from when the first symptoms appear. The aetiologies for sporadic and most familial forms of ALS are unknown, but genetic factors are increasingly recognized as causal in a subset of patients. Studies of disease physiology suggest roles for oxidative stress, glutamate-mediated excitotoxicity or protein aggregation; how these pathways interact in the complex pathophysiology of ALS awaits elucidation. Cellular models are being used to examine disease mechanisms. Recent advances include the availability of expanded cell types, from neuronal or glial cell culture to motoneuron-astrocyte co-culture genetically or environmentally modified. Cell culture experiments confirmed the central role of glial cells in ALS. The recent adaptation of induced pluripotent stem cells (iPSC) for ALS modeling could allow a broader perspective and is expected to generate new hypotheses, related particularly to mechanisms underlying genetic factors. Cellular models have provided meaningful advances in the understanding of ALS, but, to date, complete characterization of in vitro models is only partially described. Consensus on methodological approaches, strategies for validation and techniques that allow rapid adaptation to new genetic or environmental influences is needed. In this article, we review the principal cellular models being employed in ALS and highlight their contribution to the understanding of disease mechanisms. We conclude with recommendations on means to enhance the robustness and generalizability of the different concepts for experimental ALS. © 2013 Springer Science+Business Media. Source

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