Rôle des calpaïnes extracellulaires dans la progression des adénocarcinomes lépidiques

Calpain 1 is pro inflammatory calcium-activated cysteine proteases, which can be partly externalized. Extracellular calpains limit inflammatory processes and promote tissue repair, through cell proliferation and migration. Toll like receptor (TLR) 2 has been identified as a target of extracellular calpains in lymphocytes. The aim was to investigate the role of extracellular calpain 1 in tumor progression of lepidic pulmonary adenocarcinoma (LPA). Extracellular calpain 1, soluble fragment of TLR2 and cytokines were analyzed by ELISA in bronchoalveolar lavage fluid (BALF) supernatants from patients with LPA (n=68). Source of calpain was analyzed by immunohistochemistry. TLR2 as target of extracellular calpain was studied by flow cytometry on polymorphonuclear neutrophils (PMN) and human lung cancer cell lines. Extracellular Calpain 1, secreted by tumor cells, was associated to tumor progression, neutrophilic inflammation, with a poor prognostic factor on survival (p=0,003). TLR2 was expressed on PMN or tumor cells and decreased after calpain treatment. The soluble fragment of TLR2 was correlated to the extracellular calpain 1 concentration in the BALF supernatants (r=0.624; p<0.001). High soluble fragment of TLR2 was associated with tumor progression and a pro-inflammatory environment. Extracellular Calpain 1 secreted by tumor cell, promotes inflammatory microenvironment and tumor progression through TLR2 in LPA.La calpaïne 1 est une protéase à cystéine activée par le calcium, qui peut être partiellement externalisée. Les calpaines extracellulaires favorisent la résolution de l'inflammation et la réparation des tissus, à travers la prolifération et la migration cellulaire. Le récepteur Toll like (TLR) 2 a été identifié comme une cible des calpaïnes extracellulaires dans les lymphocytes. L'objectif est d'étudier le rôle de la calpaïne extracellulaire 1 dans la progression tumorale de l'adénocarcinome pulmonaire lepidique (ADL). La calpaïne extracellulaire, le fragment soluble de TLR2, le versican et les cytokines étaient analysés par ELISA dans des surnageants de lavage bronchoalvéolaire (LBA) de patients atteints d'ADL (n = 68). La source de calpaïne était analysée par immunohistochimie. TLR2, cible de la calpaïne extracellulaire était étudiée par cytométrie de flux sur les polynucléaires neutrophiles (PNN) et des lignées humaines de cancer bronchiques. Calpain 1 extracellulaire, sécrété par les cellules tumorales, était associée à la progression tumorale, l'inflammation à neutrophiles, avec un facteur de mauvais pronostic de survie (p = 0,003). TLR2 était exprimé sur les cellules tumorales ou les PNN avec une diminution d¿expression après traitement par calpaïne. Le fragment soluble de TLR2 était corrélée à la concentration extracellulaire de calpaïne 1 dans les surnageants de LBA (r = 0,624; p <0,001). Le fragment soluble de TLR2 élevé était associé à la progression tumorale et un environnement pro-inflammatoire La calpain extracellulaire sécrétée par la cellule tumorale, favorise un microenvironnement inflammatoire et la progression tumorale médiée par TLR2 dans ADL

Byzantine agreement with homonyms

So far, the distributed computing community has either assumed that all the processes of a distributed system have distinct identifiers or, more rarely, that the processes are anonymous and have no identifiers. These are two extremes of the same general model: namely, n processes use l different authenticated identifiers, where 1 ≤ l ≤ n. In this paper, we ask how many identifiers are actually needed to reach agreement in a distributed system with t Byzantine processes. We show that having 3t+1 identifiers is necessary and sufficient for agreement in the synchronous case but, more surprisingly, the number of identifiers must be greater than n+3t/2 in the partially synchronous case. This demonstrates two differences from the classical model (which has l=n): there are situations where relaxing synchrony to partial synchrony renders agreement impossible; and, in the partially synchronous case, increasing the number of correct processes can actually make it harder to reach agreement. The impossibility proofs use the fact that a Byzantine process can send multiple messages to the same recipient in a round. We show that removing this ability makes agreement easier: then, t+1 identifiers are sufficient for agreement, even in the partially synchronous model

Role of extracellular calpains in progression of lepidic adenocarcinoma

La calpaïne 1 est une protéase à cystéine activée par le calcium, qui peut être partiellement externalisée. Les calpaines extracellulaires favorisent la résolution de l'inflammation et la réparation des tissus, à travers la prolifération et la migration cellulaire. Le récepteur Toll like (TLR) 2 a été identifié comme une cible des calpaïnes extracellulaires dans les lymphocytes. L'objectif est d'étudier le rôle de la calpaïne extracellulaire 1 dans la progression tumorale de l'adénocarcinome pulmonaire lepidique (ADL). La calpaïne extracellulaire, le fragment soluble de TLR2, le versican et les cytokines étaient analysés par ELISA dans des surnageants de lavage bronchoalvéolaire (LBA) de patients atteints d'ADL (n = 68). La source de calpaïne était analysée par immunohistochimie. TLR2, cible de la calpaïne extracellulaire était étudiée par cytométrie de flux sur les polynucléaires neutrophiles (PNN) et des lignées humaines de cancer bronchiques. Calpain 1 extracellulaire, sécrété par les cellules tumorales, était associée à la progression tumorale, l'inflammation à neutrophiles, avec un facteur de mauvais pronostic de survie (p = 0,003). TLR2 était exprimé sur les cellules tumorales ou les PNN avec une diminution d¿expression après traitement par calpaïne. Le fragment soluble de TLR2 était corrélée à la concentration extracellulaire de calpaïne 1 dans les surnageants de LBA (r = 0,624; p <0,001). Le fragment soluble de TLR2 élevé était associé à la progression tumorale et un environnement pro-inflammatoire La calpain extracellulaire sécrétée par la cellule tumorale, favorise un microenvironnement inflammatoire et la progression tumorale médiée par TLR2 dans ADL.Calpain 1 is pro inflammatory calcium-activated cysteine proteases, which can be partly externalized. Extracellular calpains limit inflammatory processes and promote tissue repair, through cell proliferation and migration. Toll like receptor (TLR) 2 has been identified as a target of extracellular calpains in lymphocytes. The aim was to investigate the role of extracellular calpain 1 in tumor progression of lepidic pulmonary adenocarcinoma (LPA). Extracellular calpain 1, soluble fragment of TLR2 and cytokines were analyzed by ELISA in bronchoalveolar lavage fluid (BALF) supernatants from patients with LPA (n=68). Source of calpain was analyzed by immunohistochemistry. TLR2 as target of extracellular calpain was studied by flow cytometry on polymorphonuclear neutrophils (PMN) and human lung cancer cell lines. Extracellular Calpain 1, secreted by tumor cells, was associated to tumor progression, neutrophilic inflammation, with a poor prognostic factor on survival (p=0,003). TLR2 was expressed on PMN or tumor cells and decreased after calpain treatment. The soluble fragment of TLR2 was correlated to the extracellular calpain 1 concentration in the BALF supernatants (r=0.624; p<0.001). High soluble fragment of TLR2 was associated with tumor progression and a pro-inflammatory environment. Extracellular Calpain 1 secreted by tumor cell, promotes inflammatory microenvironment and tumor progression through TLR2 in LPA

Epidémiologie moléculaire d'une série de 115 cancers bronchiques non à petites cellules (Implication de deux voies de signalisation passant par les récepteurs membranaires tyrosine kinase (c-Met, EGFR) et les récepteurs nucléaires (récepteurs aux oestrogènes alpha et béta).)

STRASBOURG-Medecine (674822101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Mise en forme à chaud d'intermétalliques à base gamma-TiAl

PARIS-MINES ParisTech (751062310) / SudocSOPHIA ANTIPOLIS-Mines ParisTech (061522302) / SudocSudocFranceF

La réintroduction de chimiothérapie est-elle faisable au cours du traitement du cancer pulmonaire non à petites cellules de stade avancé ?

International audienceBackground: Despite recent progress, non-small cell lung cancer (NSCLC) first-line treatment remains a platinum-based doublet in most cases. No guidelines exist beyond third line. Chemotherapy rechallenge is an option, but little data is available in NSCLC. Our study aims to describe patients who underwent chemotherapy rechallenge while assessing its efficacy and safety.Methods: Consecutive patients with advanced-stage NSCLC receiving first-line treatment in Tenon hospital in 2011 were included, with a 5-year follow-up. Patients were analyzed according to chemotherapy rechallenge or not. Chemotherapy rechallenge was defined as re-initiation of a previously administered chemotherapy agent at any point in the treatment sequence, with at least one treatment regimen between first use and rechallenge.Results: Of 149 patients, 18 underwent chemotherapy rechallenge (12%). They were younger (56 vs. 61 years, P = 0.04), mostly women (61% vs. 30%, P = 0.02), with lepidic adenocarcinoma (23% vs. 3.5%, P = 0.03), a better general state of health (100% performance status 0–1 vs. 74%, P = 0.04), and fewer cardiovascular comorbidities (16% vs. 42%, P = 0.04). They were more likely to have received a receptor tyrosine kinase inhibitor treatment (89% vs. 43%, P = 0.0003). Progression-free survival was longer at first use than at rechallenge (median 9.2 vs. 2.7 months, P = 0.002). No increased toxicity was observed at rechallenge compared to first use. Finally, a subsequent line of treatment was given after rechallenge in 61% of the patients.Conclusion: Patients eligible for chemotherapy rechallenge were those with good prognostic factors. Chemotherapy rechallenge may provide a well-tolerated additional line of treatment, with decreased efficacy compared to its first application.Introduction: Malgré des progrès récents, le traitement de première ligne des cancers bronchopulmonaires non à petites cellules (CBNPC) reste majoritairement un doublet à base de platine. Il n’existe pas de recommandations après la troisième ligne. La réintroduction de chimiothérapie est une option, mais peu de données sont disponibles. Notre étude vise à décrire les patients ayant eu une réintroduction de chimiothérapie, ainsi que sa faisabilité et sa tolérance.Méthodes: Les patients consécutifs avec un CBNPC de stade avancé ayant reçu un traitement de première ligne à l’hôpital Tenon en 2011 ont été inclus. Ceux ayant eu une réintroduction de chimiothérapie ont été comparés aux autres. Celle-ci était définie par la réutilisation d’un agent de chimiothérapie utilisé antérieurement, avec au moins une ligne entre la primo-utilisation et la réutilisation.Résultats: Parmi 149 patients, 18 ont eu une réintroduction de chimiothérapie (12 %). Ils étaient plus jeunes (56 ans vs 61 ans, p = 0,04), de sexe féminin (61 % vs 30 %, p = 0,02), avec un adénocarcinome lépidique (23 % vs 35 %, p = 0,03), un meilleur état général (PS 0–1 : 100 % vs 74 %, p = 0,04) et moins de comorbidités cardiovasculaires (16 % vs 42 %, p = 0,04). La survie sans progression était plus longue à la primo-utilisation qu’à la réintroduction (médiane 9,2 mois vs 2,7, p = 0,002). Il n’y avait pas de surcroît de toxicité à la réintroduction. Enfin, une ligne supplémentaire était possible après réintroduction chez 61 % des patients.Conclusion: La réintroduction de chimiothérapie fournit une ligne supplémentaire de traitement bien tolérée, avec une efficacité moindre par rapport à la primo-utilisation

Byzantine Agreement with Homonyms

International audienceSo far, the distributed computing community has either assumed that all the processes of a distributed system have distinct identifiers or, more rarely, that the processes are anonymous and have no identifiers. These are two extremes of the same general model: namely, n processes use l different authenticated identifiers, where 1 <= l <= n. In this paper, we ask how many identifiers are actually needed to reach agreement in a distributed system with $t$ Byzantine processes. We show that having 3t+1 identifiers is necessary and sufficient for agreement in the synchronous case but, more surprisingly, the number of identifiers must be greater than (n+3t)/2 in the partially synchronous case. This demonstrates two differences from the classical model (which has l=n): there are situations where relaxing synchrony to partial synchrony renders agreement impossible; and, in the partially synchronous case, increasing the number of correct processes can actually make it harder to reach agreement. The impossibility proofs use the fact that a Byzantine process can send multiple messages to the same recipient in a round. We show that removing this ability makes agreement easier: then, t+1 identifiers are sufficient for agreement, even in the partially synchronous model

Byzantine Agreement with Homonyms (Accord Byzantin avec des Homonymes)

International audienceSo far, the distributed computing community has either assumed that all the processes of a distributed system have distinct identifiers or, more rarely, that the processes are anonymous and have no identifiers. These are two extremes of the same general model: namely, n processes use l different authenticated identifiers, where 1 <= l <=n. In this paper, we ask how many identifiers are actually needed to reach agreement in a distributed system with $t$ Byzantine processes. We show that having 3t+1 identifiers is necessary and sufficient for agreement in the synchronous case but, more surprisingly, the number of identifiers must be greater than (n+3t)/2 in the partially synchronous case. This demonstrates two differences from the classical model (which has l=n):there are situations where relaxing synchrony to partial synchrony renders agreement impossible; and, in the partially synchronous case, increasing the number of correct processes can actually make it harder to reach agreement. The impossibility proofs use the fact that a Byzantine process can send multiple messages to the same recipient in a round. We show that removing this ability makes agreement easier: then, identifiers are sufficient for agreement, even in the partially synchronous model

Byzantine agreement with homonyms

International audienceSo far, the distributed computing community has either assumed that all the processes of a distributed system have distinct identifiers or, more rarely, that the processes are anonymous and have no identifiers. These are two extremes of the same general model: namely, n processes use ℓ different identifiers, where 1≤ℓ≤n. In this paper, we ask how many identifiers are actually needed to reach agreement in a distributed system with t Byzantine processes. We show that having 3t+1 identifiers is necessary and sufficient for agreement in the synchronous case but, more surprisingly, the number of identifiers must be greater than n+3t2 in the partially synchronous case. This demonstrates two differences from the classical model (which has ℓ=n): there are situations where relaxing synchrony to partial synchrony renders agreement impossible; and, in the partially synchronous case, increasing the number of correct processes can actually make it harder to reach agreement. The impossibility proofs use the fact that a Byzantine process can send multiple messages to the same recipient in a round. We show that removing this ability makes agreement easier: then, t+1 identifiers are sufficient for agreement, even in the partially synchronous model, assuming processes can count the number of messages with the same identifier they receive in a round