Traitement de maintenance par des doses alternées de dasatinib dans la leucémie myéloïde chronique

Tyrosine kinase inhibitors (TKIs) induce deep lasting molecular responses in patients with chronic myeloid leukemia (CML). However, 60% of patients eligible to TKIs discontinuation will experience loss of major molecular response (MMR). We evaluated maintenance therapy with dasatinib administrated every other day as an alternative to discontinuation. The main goal of the study was to assess survival without MMR loss (BCR-ABL1IS>0.1%) in maintenance in a retrospective cohort R and then in a prospective trial P. A cohort of 100 patients was studied, including 64 in the R cohort and 36 in the P cohort (inclusion criteria were similar to those of the EUROSKI discontinuation trial that is to say at least 3 years of treatment with TKIs and 1 year of MR4). Median duration of dasatinib was 44.8 (5.6 – 116) and 47.8 (32.7 – 88.4) months with a median daily dose before maintenance of 50 and 100 mg in R and P respectively. With a median follow-up of 24 and 30.7 months in both R and P, the 2-year survival without MMR loss was 80.8% (95% CI, 70.7 – 92.3) and 95.5% (95% CI, 87.1 – 100) respectively. Among the R patients fulfilling the EUROSKI criteria (N=24), this 2-year survival was up to 95% (95% CI, 91 – 100). Patients who lost MMR (N=14) recovered it in 71% cases without detection of resistance mutation. No pleural effusion was recorded in maintenance and patients reported improved quality of life with lower side effects. Maintenance is a feasible alternative to dasatinib discontinuation for patients in 1st or 2nd line treatment with duration of TKIs > or = 3 years and duration of MR4 > or = 1 year.Les inhibiteurs de tyrosine kinase (ITKs) induisent des réponses durables chez les patients atteints de leucémie myéloïde chronique (LMC). Malgré cela, 60% des patients éligibles à un arrêt de traitement perdent la réponse moléculaire majeure (RMM) au décours. Nous avons évalué comme alternative un schéma de maintenance par le dasatinib avec une prise toutes les 48 h. L’objectif principal de notre étude était de déterminer la survie sans perte de la RMM (BCR-ABL1IS>0.1%) en maintenance dans une cohorte rétrospective R puis par un essai prospectif P. Une cohorte de 100 patients a été étudiée dont 64 dans la cohorte R et 36 dans la cohorte P (critères d’inclusion identiques à ceux de l’étude d’arrêt EUROSKI soit au moins 3 ans de traitement et 1 an de RM4). La durée médiane d’administration du dasatinib était de 44.8 (5.6 – 116) et 47.8 (32.7 – 88.4) mois et la dose médiane quotidienne de 50 et 100 mg dans les cohortes R et P respectivement. Avec un suivi médian de 24 et 30.7 mois dans les cohortes R et P, la survie sans perte de la RMM à 2 ans était de 80.8% (IC 95%, 70.7 – 92.3) et 95.5% (IC 95%, 87.1 – 100) respectivement. Chez les patients de la cohorte R répondant aux critères EUROSKI (N=24) elle augmentait à 95% (IC 95%, 91 – 100). Les patients ayant perdu la RMM (N=14) l’ont retrouvée dans 71% des cas, sans mutation de résistance. Aucun épanchement pleural n’a été signalé en maintenance. Une réduction des effets secondaires ainsi qu’une amélioration de la qualité de vie ont été observées. La maintenance apparait comme une alternative à l’arrêt du dasatinib chez les patients en 1ère ou seconde ligne ayant au moins 1 an de RM4 et 3 ans de recul sur leur traitement

Valeur des différentes techniques de diagnostic de la toxoplasmose congénitale (Etude rétrospective au CHU d'Angers de 1995 à 2004)

ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Highlighting the Potency of Biosurfactants Produced by Pseudomonas Strains as Anti-Legionella Agents

Legionella pneumophila, the causative agent of Legionnaires’ disease, is a waterborne bacterium mainly found in man-made water systems in close association with free-living amoebae and multispecies biofilms. Pseudomonas strains, originating from various environments including freshwater systems or isolated from hospitalized patients, were tested for their antagonistic activity towards L. pneumophila. A high amount of tested strains was thus found to be active. This antibacterial activity was correlated to the presence of tensioactive agents in culture supernatants. As Pseudomonas strains were known to produce biosurfactants, these compounds were specifically extracted and purified from active strains and further characterized using reverse-phase HPLC and mass spectrometry methods. Finally, all biosurfactants tested (lipopeptides and rhamnolipids) were found active and this activity was shown to be higher towards Legionella strains compared to various other bacteria. Therefore, described biosurfactants are potent anti-Legionella agents that could be used in the water treatment industry although tests are needed to evaluate how effective they would be under field conditions

Legionella pneumophila: The Paradox of a Highly Sensitive Opportunistic Waterborne Pathogen Able to Persist in the Environment

International audienceLegionella pneumophila, the major causative agent of Legionnaires' disease, is found in freshwater environments in close association with free-living amoebae and multispecies biofilms, leading to persistence, spread, biocide resistance, and elevated virulence of the bacterium. Indeed, legionellosis outbreaks are mainly due to the ability of this bacterium to colonize and persist in water facilities, despite harsh physical and chemical treatments. However, these treatments are not totally efficient and, after a lag period, L. pneumophila may be able to quickly re-colonize these systems. Several natural compounds (biosurfactants, antimicrobial peptides…) with anti-Legionella properties have recently been described in the literature, highlighting their specific activities against this pathogen. In this review, we first consider this hallmark of Legionella to resist killing, in regard to its biofilm or host-associated life style. Then, we focus more accurately on natural anti-Legionella molecules described so far, which could provide new eco-friendly and alternative ways to struggle against this important pathogen in plumbing

Monitoring Insect Transposable Elements in Large Double-Stranded DNA Viruses Reveals Host-to-Virus and Virus-to-Virus Transposition

International audienceAbstract The mechanisms by which transposable elements (TEs) can be horizontally transferred between animals are unknown, but viruses are possible candidate vectors. Here, we surveyed the presence of host-derived TEs in viral genomes in 35 deep sequencing data sets produced from 11 host–virus systems, encompassing nine arthropod host species (five lepidopterans, two dipterans, and two crustaceans) and six different double-stranded (ds) DNA viruses (four baculoviruses and two iridoviruses). We found evidence of viral-borne TEs in 14 data sets, with frequencies of viral genomes carrying a TE ranging from 0.01% to 26.33% for baculoviruses and from 0.45% to 7.36% for iridoviruses. The analysis of viral populations separated by a single replication cycle revealed that viral-borne TEs originating from an initial host species can be retrieved after viral replication in another host species, sometimes at higher frequencies. Furthermore, we detected a strong increase in the number of integrations in a viral population for a TE absent from the hosts’ genomes, indicating that this TE has undergone intense transposition within the viral population. Finally, we provide evidence that many TEs found integrated in viral genomes (15/41) have been horizontally transferred in insects. Altogether, our results indicate that multiple large dsDNA viruses have the capacity to shuttle TEs in insects and they underline the potential of viruses to act as vectors of horizontal transfer of TEs. Furthermore, the finding that TEs can transpose between viral genomes of a viral species sets viruses as possible new niches in which TEs can persist and evolve

Skador inom dam- och herrishockeyn

<p><b>(A)</b> Light microscopy image of Jurkat cell. The straights line reveals the contrast due to the nucleus. <b>(B)</b> Cluster average spectra from HCA results. <b>(C)</b> Chemical image of Jurkat cell building from the HCA results. The colors correspond to the Raman spectra generated by HCA methods (see B) and characteristic of the different cell compartments (see description in the text). Arrows allow to highlight the differences between cells treated and untreated by the peptides.</p

Median lethal dose (LD₅₀) of WRK on cancer cell lines tested.

<p>Median lethal dose (LD₅₀) of WRK on cancer cell lines tested.</p