排序方式: 共有808条查询结果,搜索用时 15 毫秒
761.
Blanc-Delmas E Lebegue N Wallez V Leclerc V Yous S Carato P Farce A Bennejean C Renard P Caignard DH Audinot-Bouchez V Chomarat P Boutin J Hennuyer N Louche K Carmona MC Staels B Pénicaud L Casteilla L Lonchampt M Dacquet C Chavatte P Berthelot P Lesieur D 《Bioorganic & medicinal chemistry》2006,14(22):7377-7391
A series of 1,3-dicarbonyl compounds having 2(3H)-benzazolonic heterocycles has been synthesized and tested for PPARgamma agonist activity. SAR were developed and revealed that 6-acyl-2(3H)-benzothiazolone derivatives with 1,3-dicarbonyl group were the most potent. IP administration of compound 22 exhibited comparable levels of glucose and triglyceride correction to PO administration of rosiglitazone in the ob/ob mouse studies. 相似文献
762.
Prospects for exosomes in immunotherapy of cancer 总被引:8,自引:0,他引:8
Mignot G Roux S Thery C Ségura E Zitvogel L 《Journal of cellular and molecular medicine》2006,10(2):376-388
Exosomes are nanometer sized membrane vesicles invaginating from multivesicular bodies and secreted from epithelial and hematopoietic cells. They were first described "in vitro" but vesicles with the hallmarks of exosomes are present in vivo in germinal centers and biological fluids. Their protein and lipid composition are unique and could account for their expanding functions such as eradication of obsolete proteins, antigen presentation or "Trojan horses" for viruses or prions. Exosome secretion could be a regulated process participating in the transfer of molecules inbetween immune cells. Despite numerous questions pertaining to their biological relevance, the potential of dendritic cell derived-exosomes as cell-free cancer vaccines is currently being assessed. This review will summarize the composition and formation of exosomes, preclinical data, Phase I trials and optimization protocols for improving their immunogenicity in tumor bearing patients. 相似文献
763.
Stéphane P Dufour Elodie Ponsot Joffrey Zoll Stéphane Doutreleau Evelyne Lonsdorfer-Wolf Bernard Geny Eliane Lampert Martin Flück Hans Hoppeler Véronique Billat Bertrand Mettauer Ruddy Richard Jean Lonsdorfer 《Journal of applied physiology》2006,100(4):1238-1248
This study investigates whether a 6-wk intermittent hypoxia training (IHT), designed to avoid reductions in training loads and intensities, improves the endurance performance capacity of competitive distance runners. Eighteen athletes were randomly assigned to train in normoxia [Nor group; n = 9; maximal oxygen uptake (VO2 max) = 61.5 +/- 1.1 ml x kg(-1) x min(-1)] or intermittently in hypoxia (Hyp group; n = 9; VO2 max = 64.2 +/- 1.2 ml x kg(-1) x min(-1)). Into their usual normoxic training schedule, athletes included two weekly high-intensity (second ventilatory threshold) and moderate-duration (24-40 min) training sessions, performed either in normoxia [inspired O2 fraction (FiO2) = 20.9%] or in normobaric hypoxia (FiO2) = 14.5%). Before and after training, all athletes realized 1) a normoxic and hypoxic incremental test to determine VO2 max and ventilatory thresholds (first and second ventilatory threshold), and 2) an all-out test at the pretraining minimal velocity eliciting VO2 max to determine their time to exhaustion (T(lim)) and the parameters of O2 uptake (VO2) kinetics. Only the Hyp group significantly improved VO2 max (+5% at both FiO2, P < 0.05), without changes in blood O2-carrying capacity. Moreover, T(lim) lengthened in the Hyp group only (+35%, P < 0.001), without significant modifications of VO2 kinetics. Despite similar training load, the Nor group displayed no such improvements, with unchanged VO2 max (+1%, nonsignificant), T(lim) (+10%, nonsignificant), and VO2 kinetics. In addition, T(lim) improvements in the Hyp group were not correlated with concomitant modifications of other parameters, including VO2 max or VO2 kinetics. The present IHT model, involving specific high-intensity and moderate-duration hypoxic sessions, may potentialize the metabolic stimuli of training in already trained athletes and elicit peripheral muscle adaptations, resulting in increased endurance performance capacity. 相似文献
764.
Cellulose binding domains of a Phytophthora cell wall protein are novel pathogen-associated molecular patterns 总被引:5,自引:0,他引:5 下载免费PDF全文
Gaulin E Dramé N Lafitte C Torto-Alalibo T Martinez Y Ameline-Torregrosa C Khatib M Mazarguil H Villalba-Mateos F Kamoun S Mazars C Dumas B Bottin A Esquerré-Tugayé MT Rickauer M 《The Plant cell》2006,18(7):1766-1777
The cellulose binding elicitor lectin (CBEL) from Phytophthora parasitica nicotianae contains two cellulose binding domains (CBDs) belonging to the Carbohydrate Binding Module1 family, which is found almost exclusively in fungi. The mechanism by which CBEL is perceived by the host plant remains unknown. The role of CBDs in eliciting activity was investigated using modified versions of the protein produced in Escherichia coli or synthesized in planta through the potato virus X expression system. Recombinant CBEL produced by E. coli elicited necrotic lesions and defense gene expression when injected into tobacco (Nicotiana tabacum) leaves. CBEL production in planta induced necrosis. Site-directed mutagenesis on aromatic amino acid residues located within the CBDs as well as leaf infiltration assays using mutated and truncated recombinant proteins confirmed the importance of intact CBDs to induce defense responses. Tobacco and Arabidopsis thaliana leaf infiltration assays using synthetic peptides showed that the CBDs of CBEL are essential and sufficient to stimulate defense responses. Moreover, CBEL elicits a transient variation of cytosolic calcium levels in tobacco cells but not in protoplasts. These results define CBDs as a novel class of molecular patterns in oomycetes that are targeted by the innate immune system of plants and might act through interaction with the cell wall. 相似文献
765.
Elodie Loum Stephanie Giraud Barbara Bessette Serge Battu Muriel Mathonnet Christophe Lautrette 《Cytotechnology》2010,62(5):381-388
Colon cancer is the second leading cause of cancer-related death in industrialized countries. Many anti-cancer researches
are consequently performed and individualized tumor response testing (ITRT) methods are now used to individualize patient
chemotherapeutic administrations. Then, a new ITRT method, Oncogramme, was developed for colon cancer. Colon tumor fragments
from different patients were dissociated and seeded in a defined culture medium. Cell preparation process as well as culture
medium allowed high cell viability and a good primary culture success rate. After treatment of isolated tumoral cells by chemotherapeutics
alone or in combination, cytotoxicity was determined by cell death assay allowing the Oncogramme establishment, which was
validated by statistical analysis. Indeed, significant results were obtained such as different profile for each patient’s
cells with various drugs, and variability between patient’s cells in the response to each drug. Procedure described here to
obtain the Oncogramme is a new, fast and technically reliable ITRT method applied to colon cancer. For an individualized cancer
treatment use, this test should be further validated by a phase I clinical trial. 相似文献
766.
767.
Bousquet C Guillermet-Guibert J Saint-Laurent N Archer-Lahlou E Lopez F Fanjul M Ferrand A Fourmy D Pichereaux C Monsarrat B Pradayrol L Estève JP Susini C 《The EMBO journal》2006,25(17):3943-3954
Phosphatidylinositol 3-kinase (PI3K) regulates many cellular functions including growth and survival, and its excessive activation is a hallmark of cancer. Somatostatin, acting through its G protein-coupled receptor (GPCR) sst2, has potent proapoptotic and anti-invasive activities on normal and cancer cells. Here, we report a novel mechanism for inhibiting PI3K activity. Somatostatin, acting through sst2, inhibits PI3K activity by disrupting a pre-existing complex comprising the sst2 receptor and the p85 PI3K regulatory subunit. Surface plasmon resonance and molecular modeling identified the phosphorylated-Y71 residue of a p85-binding pYXXM motif in the first sst2 intracellular loop, and p85 COOH-terminal SH2 as direct interacting domains. Somatostatin-mediated dissociation of this complex as well as p85 tyrosine dephosphorylation correlates with sst2 tyrosine dephosphorylation on the Y71 residue. Mutating sst2-Y71 disabled sst2 to interact with p85 and somatostatin to inhibit PI3K, consequently abrogating sst2's ability to suppress cell survival and tumor growth. These results provide the first demonstration of a physical interaction between a GPCR and p85, revealing a novel mechanism for negative regulation by ligand-activated GPCR of PI3K-dependent survival pathways, which may be an important molecular target for antineoplastic therapy. 相似文献
768.
Franoise Maupas-Schwalm Aurlie Bedel Nathalie Aug Marie-Hlne Grazide Elodie Mucher Jean-Claude Thiers Robert Salvayre Anne Ngre-Salvayre 《Cellular signalling》2009,21(12):1925-1934
Plasminogen activators are implicated in the pathogenesis of several diseases such as inflammatory diseases and cancer. Beside their serine-protease activity, these agents trigger signaling pathways involved in cell migration, adhesion and proliferation. We previously reported a role for the sphingolipid pathway in the mitogenic effect of plasminogen activators, but the signaling mechanisms involved in neutral sphingomyelinase-2 (NSMase-2) activation (the first step of the sphingolipid pathway) are poorly known. This study was carried out to investigate how urokinase plasminogen activator (uPA) activates NSMase-2. We report that uPA, as well as its catalytically inactive N-amino fragment ATF, triggers the sequential activation of MMP-2, NSMase-2 and ERK1/2 in ECV304 cells that are required for uPA-induced ECV304 proliferation, as assessed by the inhibitory effect of Marimastat (a MMP inhibitor), MMP-2-specific siRNA, MMP-2 defect, and NSMase-specific siRNA. Moreover, upon uPA stimulation, uPAR, MT1-MMP, MMP-2 and NSMase-2 interacted with integrin αvβ3, evidenced by co-immunoprecipitation and immunocytochemistry experiments. Moreover, the αvβ3 blocking antibody inhibited the uPA-triggered MMPs/uPAR/integrin αvβ3 interaction, NSMase-2 activation, Ki67 expression and DNA synthesis in ECV304. In conclusion, uPA triggers interaction between integrin αvβ3, uPAR and MMPs that leads to NSMase-2 and ERK1/2 activation and cell proliferation. These findings highlight a new signaling mechanism for uPA, and suggest that, upon uPA stimulation, uPAR, MMPs, integrin αvβ3 and NSMase-2 form a signaling complex that take part in mitogenic signaling in ECV304 cells. 相似文献
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770.
Elodie Gauche Antoine Couturier Romuald Lepers Anne Michaut Giuseppe Rabita Christophe Hausswirth 《Journal of electromyography and kinesiology》2009,19(6):e481-e486
PurposeThis study investigated neuromuscular fatigue following high versus low-intensity eccentric exercise corresponding to the same amount of work.MethodsTen volunteers performed two eccentric exercises of the elbow flexors: a high-intensity versus a low-intensity exercise. Maximal voluntary contraction torque and surface electromyography of the biceps brachii muscle were recorded before, immediately and 48 h after exercises. Maximal voluntary activation level, neural (M-wave) and contractile (muscular twitch) properties of the biceps brachii muscle were analysed using electrical stimulation techniques.ResultsMaximal voluntary contraction torque was significantly (P < 0.01) reduced immediately and 48 h after exercise but the reduction was not different between the two conditions. Electromyography associated with maximal voluntary contraction significantly decreased (P < 0.05) immediately and 48 h after exercise for both conditions while maximal voluntary activation level was only significantly reduced immediately after the high-intensity exercise. Peak twitch alterations were observed immediately and 48 h after exercise for both conditions while M-wave did not change.ConclusionHigh and low-intensity eccentric exercises with the same amount of work induced the same reduction in maximal strength capacities of the biceps brachii muscles. The magnitude of peripheral and central fatigue was very similar in both conditions. 相似文献