Associations phytoplanctoniques indicatrices de la pollution par le zinc

Quatre bioessais in vitro ont été réalisés pour évaluer la réponse des communautés phytoplanctoniques naturelles à différentes concentrations de zinc (2,5; 10; 20 - 25 et 40 - 50 mg.l-1). Les essais réalisés au cours des quatre saisons , ont été menés en conditions contrôlées pendant un mois avec des échantillonnages tous les 2-3 jours.La réponse algale fut variable selon la saison et dépendante des concentrations en Zinc, des espèces algales, de la densité de l' inoculum et de la température. 2,5 et 10 mg Zinc.l-1 dans le milieu de culture ont stimulé la croissance de certaines diatomées; à une concentration de Zinc de 20-25 mg.l-1Chlorella vulgaris (Chlorophyceae) s'est particulièrement développée, et, dans des systèmes contenant 40-50 mg Zinc.l-1 une mortalité importante a été généralement trouvée, à l'exception de Chlorella vulgaris et de quelques espèces de diatomées qui se sont montrées tolérantes au zinc: Cyclotella meneghiniana, Gomphonema parvulum, Navicula sp., Nitzschia palea, Nitzschia sp., Pinnularia biceps, Synedra acus et Synedra ulna var. amphirrhynchus. Les Cyanophyceae, les Euglenophyceae, les Tribophyceae, les Chrysophyceae, les Zygophyceae et les Dinophyceae ont été particulièrement sensibles. En présence d' inoculums abondants, la sensibilité au Zinc a été observée à partir de 25 mg.l-1 (automne-20°C, printemps-20°C et été-25°C); par contre, en présence d'inoculums peu denses, elle est apparue dès 10 mg.l-1 (hiver-15°C). De manière générale, à mesure que la concentration de Zinc augmentait, Chlorella vulgaris Biej. est devenue graduellement, le taxon dominant; ce qui a eu pour conséquence une diminution de la diversité du système algal testé. Des communautés plus simples se sont alors développées, dominées presque toutes par des espèces tolérantes au Zinc.In order to study the response of native phytoplanktonic communities to different zinc concentrations (2.5, 10, 20 - 25 and 40 - 50 mg.l-1), four bioassays in vitro were carried out. They were conducted in autumn, winter, spring and summer under controlled conditions during a month and the samplings were performed each 2-3 days.The algal responses were variable according to the season and zinc-concentration, species, inoculum density and temperature dependent. 2.5 and 10 mg.l-1 of Zinc in the test medium caused a stimulatory effect on the growth rate of certain diatoms; with 20-25 mg.l-1 of Zinc the development of Chlorella vulgaris (Chlorophyceae) was stimulated, and with 40-50 mg.l-1 of Zinc it was generally found important mortality rates except for Chlorella vulgaris and for some tolerant diatom species: Cyclotella meneghiniana, Gomphonema parvulum, Navicula sp., Nitzschia palea, Nitzschia sp., Pinnularia biceps, Synedra acus and Synedra ulna var. amphirrhynchus. The Cyanophyceae, Euglenophyceae, Tribophyceae, Chrysophyceae, Zygophyceae and Dinophyceae were particularly sensitive to Zinc. In presence of abundant inoculums, the sensivity to Zinc was observed up to 25 mg.l-1 (autumn-20°C, spring-20°C and summer-25°C) while in presence of smaller inoculums the sensivity manifested up to 10 mg.l-1 (winter-15°C). In general, as Zinc concentration increased, Chlorella vulgaris gradually became the dominant taxon and thus, a decrease in the specific diversity of the assayed algal system made of Zinc-tolerant species was observed

Alterations of immune response of non-small lung cancer with azacytidine

Innovative therapies are needed for advanced Non-Small Cell Lung Cancer (NSCLC). We have undertaken a genomics based, hypothesis driving, approach to query an emerging potential that epigenetic therapy may sensitize to immune checkpoint therapy targeting PD-L1/PD-1 interaction. NSCLC cell lines were treated with the DNA hypomethylating agent azacytidine (AZA - Vidaza) and genes and pathways altered were mapped by genome-wide expression and DNA methylation analyses. AZA-induced pathways were analyzed in The Cancer Genome Atlas (TCGA) project by mapping the derived gene signatures in hundreds of lung adeno (LUAD) and squamous cell carcinoma (LUSC) samples. AZA up-regulates genes and pathways related to both innate and adaptive immunity and genes related to immune evasion in a several NSCLC lines. DNA hypermethylation and low expression of IRF7, an interferon transcription factor, tracks with this signature particularly in LUSC. In concert with these events, AZA up-regulates PD-L1 transcripts and protein, a key ligand-mediator of immune tolerance. Analysis of TCGA samples demonstrates that a significant proportion of primary NSCLC have low expression of AZA-induced immune genes, including PD-L1. We hypothesize that epigenetic therapy combined with blockade of immune checkpoints - in particular the PD-1/PD-L1 pathway - may augment response of NSCLC by shifting the balance between immune activation and immune inhibition, particularly in a subset of NSCLC with low expression of these pathways. Our studies define a biomarker strategy for response in a recently initiated trial to examine the potential of epigenetic therapy to sensitize patients with NSCLC to PD-1 immune checkpoint blockade

Cytokine Production but Lack of Proliferation in Peripheral Blood Mononuclear Cells from Chronic Chagas' Disease Cardiomyopathy Patients in Response to T. cruzi Ribosomal P Proteins

Background:Trypanosoma cruzi ribosomal P proteins, P2β and P0, induce high levels of antibodies in patients with chronic Chagas' disease Cardiomyopathy (CCC). It is well known that these antibodies alter the beating rate of cardiomyocytes and provoke apoptosis by their interaction with β1-adrenergic and M2-muscarinic cardiac receptors. Based on these findings, we decided to study the cellular immune response to these proteins in CCC patients compared to non-infected individuals.Methodology/Principal findings:We evaluated proliferation, presence of surface activation markers and cytokine production in peripheral blood mononuclear cells (PBMC) stimulated with P2β, the C-terminal portion of P0 (CP0) proteins and T. cruzi lysate from CCC patients predominantly infected with TcVI lineage. PBMC from CCC patients cultured with P2β or CP0 proteins, failed to proliferate and express CD25 and HLA-DR on T cell populations. However, multiplex cytokine assays showed that these antigens triggered higher secretion of IL-10, TNF-α and GM-CSF by PBMC as well as both CD4+ and CD8+ T cells subsets of CCC subjects. Upon T. cruzi lysate stimulation, PBMC from CCC patients not only proliferated but also became activated within the context of Th1 response. Interestingly, T. cruzi lysate was also able to induce the secretion of GM-CSF by CD4+ or CD8+ T cells.Conclusions/Significance:Our results showed that although the lack of PBMC proliferation in CCC patients in response to ribosomal P proteins, the detection of IL-10, TNF-α and GM-CSF suggests that specific T cells could have both immunoregulatory and pro-inflammatory potential, which might modulate the immune response in Chagas' disease. Furthermore, it was possible to demonstrate for the first time that GM-CSF was produced by PBMC of CCC patients in response not only to recombinant ribosomal P proteins but also to parasite lysate, suggesting the value of this cytokine to evaluate T cells responses in T. cruzi infection.Fil: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Atienza, Augusto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Perez Prados, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Buying, Alcinette. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Balouz, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Buscaglia, Carlos Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Santos, Radleigh. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Tasso, Laura Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Bonato, Ricardo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Chiale, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Pinilla, Clemencia. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Judkowski, Valeria A.. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Analogue peptides for the immunotherapy of human acute myeloid leukemia

Accepted manuscript. The final publication is available at: http://link.springer.com/article/10.1007%2Fs00262-015-1762-9The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies

Intrathoracic solitary fibrous tumor - an international multicenter study on clinical outcome and novel circulating biomarkers

Intrathoracic solitary fibrous tumor (SFT) is a rare disease. Radical resection is the standard of care. However, estimating prognosis and planning follow-up and treatment strategies remains challenging. Data were retrospectively collected by five international centers to explore outcome and biomarkers for predicting event-free-survival (EFS). 125 histological proven SFT patients (74 female; 59.2%; 104 benign; 83.2%) were analyzed. The one-, three-, five- and ten-year EFS after curative-intent surgery was 98%, 90%, 77% and 67%, respectively. Patients age (>/=59 vs. 10 cm vs. 5 vs. < 5 HR 3.91, CI 1.40-10.89, p = 0.009) were prognostic after univariate analyses. After multivariate analyses tumor-dignity and fibrinogen remained as independent prognosticators. Besides validating the role of age, tumor-dignity, tumor-size, stage and resection margins, we identified for the first time inflammatory markers as prognosticators in SFT

Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial

PURPOSE: Talimogene laherparepvec (T-VEC) is an oncolytic immunotherapy designed to induce tumor regression of injected lesions through direct lytic effects, and of uninjected lesions through induction of systemic antitumor immunity. In this study, we describe the patterns and time course of response to T-VEC from the phase III OPTiM trial of 436 patients with unresected stages IIIB–IV melanoma. METHODS: Lesion-level response analyses were performed based on the type of lesion (injected or uninjected cutaneous, subcutaneous, or nodal lesions; or visceral lesions [uninjected]), and the best percentage change from baseline of the sum of products of the longest diameters was calculated. Patients randomized to T-VEC (n = 295) who experienced a durable response (continuous partial or complete response for ≥6 months) were evaluated for progression prior to response (PPR), defined as the appearance of a new lesion or >25 % increase in total baseline tumor area. RESULTS: T-VEC resulted in a decrease in size by ≥50 % in 64 % of injected lesions (N = 2116), 34 % of uninjected non-visceral lesions (N = 981), and 15 % of visceral lesions (N = 177). Complete resolution of lesions occurred in 47 % of injected lesions, 22 % of uninjected non-visceral lesions, and 9 % of visceral lesions. Of 48 patients with durable responses, 23 (48 %) experienced PPR, including 14 who developed new lesions only. No difference in overall survival was observed, and median duration of response was not reached in patients with PPR versus those without PPR. CONCLUSIONS: Responses in uninjected lesions provide validation of T-VEC-induced systemic immunotherapeutic effects against melanoma. PPR did not negatively impact the clinical effectiveness of T-VEC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1245/s10434-016-5286-0) contains supplementary material, which is available to authorized users