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1.
Emeline Colomba Patricia Pautier Fanny Pommeret Alexandra Leary 《Expert review of anticancer therapy》2019,19(6):437-446
Introduction: The landscape of poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer is rapidly evolving and becoming increasingly complex. Ovarian cancer is leading therapeutic innovation by providing the proof of concept for DNA repair as a target. Three different PARP inhibitors have now received approvals in the US and Europe in different indications. Subtle but crucial differences can be found among the licensed indications for each PARP inhibitor in terms of histology, type of BRCA mutation (germline and/or somatic), number of prior lines of chemotherapy and whether the indication is in the treatment or maintenance settings.
Areas covered: We review the latest clinical data regarding the PARP inhibitor rucaparib in ovarian cancer, provide an update on the evolving landscape of PARP inhibition in ovarian cancer, and summarize avenues of ongoing and future research.
Expert opinion: All eligible patients should be offered a PARP inhibitor. SOLO1 trial results demonstrated an unprecedented benefit maintenance with PARP inhibitors in first line. Results from trials evaluating PARP inhibitors as maintenance in first line regardless of BRCA status and from trials evaluating combinatorial strategies are eagerly awaited. 相似文献
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Transection of an optic nerve (ON) is followed by slow removal of myelin. We studied microglia for the expression of molecules that characterize activated myelin phagocytosing macrophages: MAC-1, FcγII/III receptor (FcR), MAC-2, and F4/80. In-vitro, microglia expressed all molecules and phagocytosed myelin. In-vivo, intact ON displayed high levels of MAC-1, little FcR and F4/80, and no MAC-2. The expression of these molecules was upregulated differentially in in-vivo degenerating ON: MAC-1 uniformly, FcR and F4/80 variably, and MAC-2 sporadically. The distribution of MAC-2 expression correlated best with a pattern of sporadic structural degeneration. Thus in-vivo, ON injury is followed by deficient microglia activation, which we suggest contributes significantly to the slow clearance of myelin. 相似文献
4.
Upregulation of TGF-beta, FOXP3, and CD4+CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection 总被引:8,自引:0,他引:8
Walther M Tongren JE Andrews L Korbel D King E Fletcher H Andersen RF Bejon P Thompson F Dunachie SJ Edele F de Souza JB Sinden RE Gilbert SC Riley EM Hill AV 《Immunity》2005,23(3):287-296
Understanding the regulation of immune responses is central for control of autoimmune and infectious disease. In murine models of autoimmunity and chronic inflammatory disease, potent regulatory T lymphocytes have recently been characterized. Despite an explosion of interest in these cells, their relevance to human disease has been uncertain. In a longitudinal study of malaria sporozoite infection via the natural route, we provide evidence that regulatory T cells have modifying effects on blood-stage infection in vivo in humans. Cells with the characteristics of regulatory T cells are rapidly induced following blood-stage infection and are associated with a burst of TGF-beta production, decreased proinflammatory cytokine production, and decreased antigen-specific immune responses. Both the production of TGF-beta and the presence of CD4+CD25+FOXP3+ regulatory T cells are associated with higher rates of parasite growth in vivo. P. falciparum-mediated induction of regulatory T cells may represent a parasite-specific virulence factor. 相似文献
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Camille Granger Paul Guedeney Camille Arnaud Soulef Guendouz Claire Cimadevilla Mathieu Kerneis Caroline Kerneis Michel Zeitouni Constance Verdonk Camille Legeai Guillaume Lebreton Pascal Leprince Eva Désiré Sabato Sorrentino Johanne Silvain Gilles Montalescot Fanny Hazan Shaida Varnous Richard Dorent 《Transplant international》2021,34(4):721-731
Available data on clinical presentation and mortality of coronavirus disease-2019 (COVID-19) in heart transplant (HT) recipients remain limited. We report a case series of laboratory-confirmed COVID-19 in 39 HT recipients from 3 French heart transplant centres (mean age 54.4 ± 14.8 years; 66.7% males). Hospital admission was required for 35 (89.7%) cases including 14/39 (35.9%) cases being admitted in intensive care unit. Immunosuppressive medications were reduced or discontinued in 74.4% of the patients. After a median follow-up of 54 (19–80) days, death and death or need for mechanical ventilation occurred in 25.6% and 33.3% of patients, respectively. Elevated C-reactive protein and lung involvement ≥50% on chest computed tomography (CT) at admission were associated with an increased risk of death or need for mechanical ventilation. Mortality rate from March to June in the entire 3-centre HT recipient cohort was 56% higher in 2020 compared to the time-matched 2019 cohort (2% vs. 1.28%, P = 0.15). In a meta-analysis including 4 studies, pre-existing diabetes mellitus (OR 3.60, 95% CI 1.43–9.06, I2 = 0%, P = 0.006) and chronic kidney disease stage III or higher (OR 3.79, 95% CI 1.39–10.31, I2 = 0%, P = 0.009) were associated with increased mortality. These findings highlight the aggressive clinical course of COVID-19 in HT recipients. 相似文献
7.
Fanny Varenne Ali Makky Mireille Gaucher-Delmas Frédéric Violleau Christine Vauthier 《Pharmaceutical research》2016,33(5):1220-1234
Purpose
Evaluation of particle size distribution (PSD) of multimodal dispersion of nanoparticles is a difficult task due to inherent limitations of size measurement methods. The present work reports the evaluation of PSD of a dispersion of poly(isobutylcyanoacrylate) nanoparticles decorated with dextran known as multimodal and developed as nanomedecine.Methods
The nine methods used were classified as batch particle i.e. Static Light Scattering (SLS) and Dynamic Light Scattering (DLS), single particle i.e. Electron Microscopy (EM), Atomic Force Microscopy (AFM), Tunable Resistive Pulse Sensing (TRPS) and Nanoparticle Tracking Analysis (NTA) and separative particle i.e. Asymmetrical Flow Field-Flow Fractionation coupled with DLS (AsFlFFF) size measurement methods.Results
The multimodal dispersion was identified using AFM, TRPS and NTA and results were consistent with those provided with the method based on a separation step prior to on-line size measurements. None of the light scattering batch methods could reveal the complexity of the PSD of the dispersion.Conclusions
Difference between PSD obtained from all size measurement methods tested suggested that study of the PSD of multimodal dispersion required to analyze samples by at least one of the single size particle measurement method or a method that uses a separation step prior PSD measurement.8.
9.
Adama Dnou Adiaratou Togola Kari Tvete Inngjerdingen Nastaran Moussavi Frode Rise Yuan Feng Zou Dalen G. Dafam Elijah I. Nep Abubakar Ahmed Taiwo E. Alemika Drissa Diallo Rokia Sanogo Berit Smestad Paulsen 《Pharmaceutical biology》2022,60(1):1278
ContextGlobal studies on Argemone mexicana L. (Papaveraceae) traditionally used against malaria in Mali are limited to its low-mass compounds activities, and little information on its bioactive polysaccharides is available.ObjectiveThis study determines the structure and the immunomodulatory activity of polysaccharides from aerial parts of A. mexicana.Materials and methodsAcidic polysaccharides from this plant material named HMAmA1 and HMAmA2 were isolated from water extracts. Their monosaccharide composition was determined by gas chromatography. Glycosidic linkages were determined using GC-MS. NMR was also applied. The polymers were tested for effects on the human complement system in vitro at different doses.ResultsThe monosaccharide composition showed that the two polysaccharides contained in different amounts the following monomers: arabinose, rhamnose, galactose, and galacturonic acid. Overall structural analysis showed the presence of a low ratio of 1,2-linked rhamnose compared to 1,4-linked galacturonic acid with arabinogalactans substituted on position 4 of rhamnose. NMR data showed the presence of galacturonans alternated by rhamnogalacturonans bearing arabinose and galactose units. α-Linkages were found for l-arabinose, l-rhamnose and d-galacturonic acid, while β-linkages were found for d-galactose. The two polysaccharides exhibited strong complement fixation activities, with HMAmA1 being the highest potent fraction. ICH50 value of HMAmA1 was 5 µg/mL, compared to the control BPII being 15.9 µg/mL.Discussion and conclusionsPolysaccharides form A. mexicana presented a complement fixation effect. The complement system is an important part of the immune defense, and compounds acting on the cascade are of interest. Therefore, these polymers may be useful as immunodulatory agents. 相似文献
10.
Jim Secka Arpan Pal Francis A. Acquah Blaine H. M. Mooers Anand B. Karki Dania Mahjoub Mohamed K. Fakhr David R. Wallace Takuya Okada Naoki Toyooka Adama Kuta Naga Koduri Deacon Herndon Kenneth P. Roberts Zhiguo Wang Bethany Hileman Nisha Rajagopal Syed R. Hussaini 《RSC advances》2022,12(30):19431
This paper describes the synthesis of enamino carbonyl compounds by the copper(i)-catalyzed coupling of acceptor-substituted diazo compounds and tertiary thioamides. We plan to use this method to synthesize indolizidine (−)-237D analogs to find α6-selective antismoking agents. Therefore, we also performed in silico α6-nAchRs binding studies of selected products. Compounds with low root-mean-square deviation values showed more favorable binding free energies. We also report preliminary pharmacokinetic data on indolizidine (−)-237D and found it to have weak activity at CYP3A4. In addition, as enamino carbonyl compounds are also known for antimicrobial properties, we screened previously reported and new enamino carbonyl compounds for antibacterial, antimicrobial, and antifungal properties. Eleven compounds showed significant antimicrobial activities.This paper describes the synthesis of enamino carbonyl compounds by the copper(i)-catalyzed coupling of acceptor-substituted diazo compounds and tertiary thioamides. 相似文献