32 research outputs found
Hybrid catalysis for enantioselective Baeyer-Villiger oxidation and stereoselective epoxidation: a Cp*Ir complex to fuel FMN and FAD reduction for flavoprotein monooxygenase modules
Taking advantage of the unique properties of two-component flavo-monooxygenases and the ability of [Cp*Ir(bpy-OMe)H]+ to transfer hydrides to reduce flavins, we extended the scope of the pH- and oxygen-robust iridium(iii)-complex to drive the enzymatic reaction of a FMN-dependent Baeyer-Villiger monooxygenase and a FAD-dependent styrene monooxygenase (respectively FPMO Group C and E), using formic acid as H-donor for NADH recycling
The Protein Environment Drives Selectivity for Sulfide Oxidation by an Artificial Metalloenzyme
International audienc
Dasatinib induces lung vascular toxicity and predisposes to pulmonary hypertension
International audienc
A randomized study of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in elderly patients with acute lymphoblastic leukemia: the GRAALL-SA1 study
International audienceBACKGROUND: The prognosis of acute lymphoblastic leukemia in the elderly is poor. The GRAALL-SA1 phase II, randomized trial compared the efficacy and toxicity of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in patients 55 years or older with Philadelphia chromosome-negative acute lymphoblastic leukemia. DESIGN AND METHODS: Sixty patients received either continuous-infusion doxorubicin (12 mg/m(2)/day) and continuous-infusion vincristine (0.4 mg/day) on days 1-4 or pegylated liposomal doxorubicin (40 mg/m(2)) and standard vincristine (2 mg) on day 1, accompanied by dexamethasone, followed at day 28 by a second cycle, reinforced by cyclophosphamide. End-points were safety, outcome and prognostic factors. RESULTS: Myelosuppression was reduced in the pegylated liposomal doxorubicin arm with shorter severe neutropenia (P=0.05), shorter severe thrombocytopenia (P=0.03), and fewer red blood cell transfusions (P=0.04). Grade 3/4 infections and Gram-negative bacteremia were reduced in the pegylated liposomal doxorubicin arm (P=0.04 and P=0.02, respectively). There was a trend towards fewer cardiac events among the patients who received pegylated liposomal doxorubicin (1/29 versus 6/31). The complete remission rate was 82% and, with a median follow-up of 4 years, median event-free survival and overall survival were 9 and 10 months, respectively. Despite the better tolerance of pegylated liposomal doxorubicin, no differences in survival were observed between the two arms, due to trends towards more induction refractoriness (17 versus 3%, P=0.10) and a higher cumulative incidence of relapse (52% versus 32% at 2 years, P=0.20) in the pegylated liposomal doxorubicin arm. CONCLUSIONS: With the drug schedules used in this study, pegylated liposomal doxorubicin did not improve the outcome of elderly patients with acute lymphoblastic leukemia despite reduced toxicities
Formes et dispositions du texte théâtral du symbolisme à aujourd’hui
Comment écrit-on pour le théâtre ? Ou, plus précisément, comment le texte de théâtre investit-il l’espace de la page ? Comment se dispose-t-il sur le papier ? Quelle forme emprunte-t-il ? L’objectif de ce volume collectif est d’étudier la question de la disposition du texte dramatique sur un large empan, de la fin du xixe siècle à aujourd’hui, dans ses multiples enjeux. Cette perspective paraît essentielle pour aborder une période extraordinairement riche du théâtre. En dépassant à ses débuts la traditionnelle opposition du vers et de la prose, elle a permis de définir de nouveaux horizons d’écriture - et donc de lecture et de représentation. Actuellement, comme en écho, on ne compte plus les exemples d’auteurs dramatiques qui exploitent, dans l’édition de leurs œuvres, les possibilités typographiques disponibles avec la généralisation des traitements de texte. L’ouvrage, principalement composé d’études monographiques centrées sur des exemples français, propose un parcours problématisé sur cette riche matière jusque-là peu explorée
Dasatinib dose optimisation based on therapeutic drug monitoring reduces pleural effusion rates in chronic myeloid leukaemia patients
Dasatinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor approved for patients with chronic myeloid leukaemia (CML). Dasatinib 100 mg per day is associated with an increased risk of pleural effusion (PlEff). We randomly evaluated whether therapeutic drug monitoring (TDM) may reduce dasatinib-associated significant adverse events (AEs) by 12 months (primary endpoint). Eligible patients started dasatinib at 100 mg per day followed by dasatinib (C)min assessment. Patients considered overdosed [(C)min ≥ 3 nmol/l) were randomised between a dose-reduction strategy (TDM arm) and standard of care (control arm). Out of 287 evaluable patients, 80 patients were randomised. The primary endpoint was not met due to early haematological AEs occurring before effective dose reduction. However, a major reduction in the cumulative incidence of PlEff was observed in the TDM arm compared to the control arm (4% vs. 15%; 11% vs. 35% and 12% vs. 39% at one, two and three years, respectively (P = 0·0094)). Molecular responses were superimposable in all arms. Dasatinib TDM during treatment initiation was feasible and resulted in a significant reduction of the incidence of PlEff in the long run, without impairing molecular responses. (NCT01916785; https://clinicaltrials.gov)
Regulation of Interleukin‑6 in Head and Neck Squamous Cell Carcinoma Is Related to Papillomavirus Infection
The prevalence of head and neck squamous
cell carcinoma (HNSCC)
related to human papillomavirus (HPV) is increasing, unlike tobacco-
and alcohol-associated cancers. To gain a clearer understanding of
the molecular mechanisms implicated in HNSCC, depending on the presence
or not of a viral sequence, we investigated the expression of proteins
detected in the tumor regions of HNSCC patients. Twenty-two untreated
HNSCC patients were selected according to the presence of HPV-16.
For six patients, tumor and controlateral healthy tissues were tested
for viral detection before quantitative proteomic analysis. After
confirmation by Western blot, proteins were connected into a network,
leading to investigate interleukin-6 (IL-6) by immunocytochemistry
and ELISA. 41 ± 5% of proteins quantified by proteomics were
differentially expressed in tumor compared with healthy regions. Among
them, 36 proteins were retained as modulated in HPV-16 positive or
negative tumors, including cytokeratins, tubulins, annexin A1, and
serpin B1. Network analysis suggested a central role of IL-6, confirmed
by
overexpression of IL-6 in tumor tissues as in sera of HPV-negative
HNSCC compared with HPV-16-positive tumors. This modulation may contribute
to the survival and proliferation of cancer cells, although it was
not related to tumor stage or to the level of HPV-16 DNA