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https://www.readbyqxmd.com/read/29765526/esophageal-cancer-cells-resistant-to-t-dm1-display-alterations-in-cell-adhesion-and-the-prostaglandin-pathway
#1
Juliette Sauveur, Eva-Laure Matera, Kamel Chettab, Philippe Valet, Jerome Guitton, Ariel Savina, Charles Dumontet
Trastuzumab-emtansine (T-DM1) is an antibody-drug conjugate that specifically targets HER2 thanks to its antibody component trastuzumab. In spite of responses to this novel agent, acquired resistance to treatment remains a major obstacle. Prolonged in vitro exposure of the gastroesophageal junction cancer cell line OE-19 to T-DM1, in the absence or presence of ciclosporin A resulted in the selection of two resistant cell lines to T-DM1. T-DM1-resistant cells presented an increased expression of adhesion genes, altered spreading and higher sensitivity to anoikis than parental cells...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29763833/%C3%AE-2-adrenoceptor-signalling-bias-in-asthma-and-copd-and-the-potential-impact-on-the-comorbidities-associated-with-these-diseases
#2
REVIEW
Maria Gabriella Matera, Clive Page, Barbara Rinaldi
Inhaled selective β2-agonists are the most widely used treatment for obstructive airway diseases. The classical mechanism of action of these drugs is considered as their ability to activate β2-adrenergic receptors (β2-AR) on airway smooth muscle leading to G-protein activation and subsequent generation of c-AMP causing bronchodilation. However, there is now growing evidence to suggest that binding of β2-agonists to β2-AR is pleotropically coupled to many intracellular pathways whereby depending on the state of the β2-AR when activated, a subset of different intracellular responses can be triggered...
May 12, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29735047/brazilian-cheeses-a-survey-covering-physicochemical-characteristics-mineral-content-fatty-acid-profile-and-volatile-compounds
#3
Juliana Matera, Aderval S Luna, Diego B Batista, Tatiana C Pimentel, Jeremias Moraes, Bruna A Kamimura, Marcus Vinicius S Ferreira, Hugo L A Silva, Simone P Mathias, Erick A Esmerino, Monica Q Freitas, Renata S L Raices, Simone L Quitério, Anderson S Sant'Ana, Marcia C Silva, Adriano G Cruz
Chemical characteristics, mineral levels (Ca, Fe, K, Mg, Na, Zn, Cr, Cu, and Mn), fatty acid profile and volatile compounds of typically Brazilian cheeses (Minas Frescal, Minas Padrão, Prato and Coalho, n = 200, equally distributed) were investigated. The cheeses have proven to be a source of Ca, Cu and Zn (>15% RDI/30 g), with low atherogenic and thrombogenic indices, with ethanol as the main alcohol and butanoic acid as the main acid, and moderate to high sodium content. Minas Frescal cheese presented lower nutritional value (proteins, lipids, and minerals), while Prato cheese had a higher fatty acids concentration, including conjugated linoleic acid (0...
June 2018: Food Research International
https://www.readbyqxmd.com/read/29720510/efficacy-and-safety-profile-of-xanthines-in-copd-a-network-meta-analysis
#4
REVIEW
Mario Cazzola, Luigino Calzetta, Peter J Barnes, Gerard J Criner, Fernando J Martinez, Alberto Papi, Maria Gabriella Matera
Theophylline can still have a role in the management of stable chronic obstructive pulmonary disease (COPD), but its use remains controversial, mainly due to its narrow therapeutic window. Doxofylline, another xanthine, is an effective bronchodilator and displays a better safety profile than theophylline. Therefore, we performed a quantitative synthesis to compare the efficacy and safety profile of different xanthines in COPD.The primary end-point of this meta-analysis was the impact of xanthines on lung function...
June 30, 2018: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/29716427/the-safety-of-dual-bronchodilation-on-cardiovascular-serious-adverse-events-in-copd
#5
Paola Rogliani, Josuel Ora, Maria Gabriella Matera, Mario Cazzola, Luigino Calzetta
Introduction Long-acting β2 -adrenoceptor (β2 -AR) agonists (LABAs) plus long-acting muscarinic antagonists (LAMAs) is the cornerstone for treating chronic obstructive pulmonary disease (COPD). LABA/LAMA combinations elicit clinical and functional synergistic interaction, and such an interaction should permit to reduce the dose of each monocomponent in the drug mixture to minimize the risk of adverse events (AEs). Overall, currently available LABA/LAMA fixed-dose combinations (FDCs) combine the drugs at the same doses of formulations designed for a single drug...
May 1, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29705620/impact-of-doxofylline-in-copd-a-pair-wise-meta-analysis
#6
Mario Cazzola, Luigino Calzetta, Paola Rogliani, Clive Page, Maria Gabriella Matera
Doxofylline is an effective bronchodilator for relieving airway obstruction in patients with asthma or chronic obstructive pulmonary disease (COPD), and displays a better safety profile with respect to theophylline. Herein, we performed a pair-wise meta-analysis of the currently available data to provide consistent and homogeneous findings on the impact of this xanthine in COPD patients. Results obtained from 820 patients were selected from 20 clinical trials. Meta-regression was performed to examine the source of heterogeneity between-studies and identify potential confounder covariates...
April 26, 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29702145/activation-of-m2-muscarinic-acetylcholine-receptors-by-a-hybrid-agonist-enhances-cytotoxic-effects-in-gb7-glioblastoma-cancer-stem-cells
#7
Ilaria Cristofaro, Zaira Spinello, Carlo Matera, Mario Fiore, Luciano Conti, Marco De Amici, Clelia Dallanoce, Ada Maria Tata
In previous studies, we found that the orthosteric muscarinic agonist arecaidine propargyl ester (APE) (100 μM) induced a decreased cell proliferation and severe apoptosis in glioblastoma cancer stem cells (GSCs). In this report, we have investigated the effects mediated by hybrid (orthosteric/allosteric) muscarinic agonists P-6-Iper and N-8-Iper on GSCs survival. At variance with APE, the agonist N-8-Iper inhibited cell growth in a dose dependent manner and also impaired cell survival at low doses. The inhibitory effects of the N-8-Iper action appear to be mediated by M2 receptor activation, since they were strongly reduced by co-administration of the selective M2 receptor antagonist methoctramine as well as upon M2 receptor silencing...
April 24, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29700359/quantitative-correlation-between-the-void-morphology-of-niobium-tin-wires-and-their-irreversible-critical-current-degradation-upon-mechanical-loading
#8
C Barth, B Seeber, A Rack, C Calzolaio, Y Zhai, D Matera, C Senatore
Understanding the critical current performance variation of Nb3 Sn superconducting wires under mechanical loading is a crucial issue for the design of next generation accelerator and fusion magnets. In these applications, the mechanical properties of the conductors may become a limiting factor due to the strong electro-magnetic forces resulting from the combination of large magnets and intense magnetic fields. In particular, the presence of voids in the superconducting filament structure, which are formed during the fabrication and the reaction heat treatment, determines localized stress concentrations and possibly the formation of cracks...
April 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29664355/fibulin-3-immunoexpression-in-malignant-mesothelioma-due-to-fluoro-edenite-a-preliminary-report
#9
Rosario Caltabiano, Carla Loreto, Ermanno Vitale, Serena Matera, Edoardo Miozzi, Marcello Migliore, Giuseppe Angelico, Rosario Tumino, Caterina Ledda, Venerando Rapisarda
An increased standardized incidence and mortality rate were reported due to malignant mesothelioma (MM) in Biancavilla. Environmental investigations showed the presence of an asbestiform fiber: fluoro-edenite (FE). MM develops with a latency of 20-60 years from exposure and specific and sensitive biomarkers are urgently needed. For this purpose, we evaluated Fibulin-3 (Fb-3) immunoexpression in human cases of MM related to FE exposure and its prognostic role. Immunohistochemical analysis of Fb-3 was carried out in eight MM patients resident in Biancavilla and the analysis showed evidence of environmental exposure to FE fibers...
March 2018: Future Oncology
https://www.readbyqxmd.com/read/29650006/beclomethasone-dipropionate-and-formoterol-fumarate-synergistically-interact-in-hyperresponsive-medium-bronchi-and-small-airways
#10
Luigino Calzetta, Maria Gabriella Matera, Francesco Facciolo, Mario Cazzola, Paola Rogliani
BACKGROUND: Corticosteroids increase the expression of β2 -adrenoceptors (β2 -ARs) and protect them against down-regulation. Conversely, β2 -AR agonists improve the anti-inflammatory action of corticosteroids. Nevertheless, it is still uncertain whether adding a long-acting β2 -AR agonist (LABA) to an inhaled corticosteroid (ICS) results in an additive effect, or there is true synergy. Therefore, the aim of this study was to pharmacologically characterize the interaction between the ICS beclomethasone diproprionate (BDP) and the LABA formoterol fumarate (FF) in a validated human ex vivo model of bronchial asthma...
April 12, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29626716/pharmacological-mechanisms-leading-to-synergy-in-fixed-dose-dual-bronchodilator-therapy
#11
REVIEW
Luigino Calzetta, Maria Gabriella Matera, Mario Cazzola
Long-acting β2 adrenoceptor agonists (LABAs) in combination with long-acting muscarinic antagonists (LAMAs) can elicit functional and clinical benefits in chronic obstructive pulmonary disease (COPD). LABA/LAMA combinations synergistically relax human isolated airways at the level of the medium and small bronchi. LABAs and LAMAs both modulate the bronchial tone via different pathways localized at the level of presynaptic parasympathetic fibers and airway smooth muscle cells. The exact nature of the interactions between these pathways is not completely understood, but there is cross-talk at many levels in airway smooth muscle cells that is also regulated by the activity of calcium-activated potassium channels and protein tyrosine kinases...
April 4, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29609004/emerging-biological-therapies-for-treating-chronic-obstructive-pulmonary-disease-a-pairwise-and-network-meta-analysis
#12
Paola Rogliani, Maria Gabriella Matera, Ermanno Puxeddu, Marco Mantero, Francesco Blasi, Mario Cazzola, Luigino Calzetta
Inflammation in chronic obstructive pulmonary disease (COPD) is often corticosteroid resistant and, thus, alternative anti-inflammatory approaches are needed. Since it is still not clear whether blocking specific pro-inflammatory factors may provide clinical benefit in COPD, we have performed a meta-analysis to quantify the impact of monoclonal antibodies (mABs) targeting the cytokine/chemokine-mediated inflammation in COPD. A pairwise and network meta-analyses were performed by extracting data from randomized clicnial trials on COPD concerning the impact of mABs vs...
March 30, 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29582435/combining-long-acting-bronchodilators-with-different-mechanisms-of-action-a-pharmacological-approach-to-optimize-bronchodilation-of-equine-airways
#13
L Calzetta, P Rogliani, E Pistocchini, M Mattei, G Cito, P Alfonsi, C Page, M G Matera
The ultra long-acting β2 -adrenoceptor agonist olodaterol plus the ultra long-acting muscarinic antagonist tiotropium bromide are known to relax equine airways. In human bronchi combining these drugs elicits a positive interaction, thus we aimed to characterize this information further in equine isolated airways stimulated by electrical field stimulation (EFS) and using the Concentration-Reduction Index (CRI) and Combination Index (CI) equations. The drugs were administered alone and together by reproducing ex vivo the concentration-ratio delivered by the currently available fixed-dose combination (1:1)...
March 26, 2018: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29535593/increase-of-vascular-endothelial-growth-factor-and-decrease-of-mcp-1-and-some-updated-epidemiology-aspects-of-cystic-echinococcosis-human-cases-in-calabria-region
#14
Giovanni Matera, Maria Teresa Loria, Cinzia Peronace, Tatiana Catanzariti, Pio Settembre, Aida Giancotti, Angelo G Lamberti, Giorgio S Barreca, Luisa Galati, Gessica Dodaro, Maria Mazzitelli, Alessio Strazzulla, Carlo Torti, Angela Quirino, Maria Carla Liberto, Alfredo Focà
We aim to investigate some of the pathogenetic mediators of the human echinococcosis and to obtain updated epidemiological findings on cases of echinococcosis in Calabria, Southern Italy. Echinococcosis diagnosis was based on imaging, serological investigations, and molecular assay. Indeed, real-time PCR indicated the presence of G2/G3 genotypes of Echinococcus granulosus complex. Regarding pathogenesis, a relevant novel tool of immune depression should be deemed the reduced level of serum MCP-1. Also, we found a previously unreported VEGF, possibly associated with neovascularization requested by the parasite cyst metabolism...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29528249/how-does-race-ethnicity-influence-pharmacological-response-to-asthma-therapies
#15
Mario Cazzola, Luigino Calzetta, Maria Gabriella Matera, Nicola A Hanania, Paola Rogliani
Our understanding of whether and/or how ethnicity influences pharmacological response to asthma therapies is still very scarce. A possible explanation for the increased asthma treatment failures observed in ethnic and racial minorities receiving asthma therapies is that some of these groups may have a pharmacogenomic predisposition to either nonresponse or to adverse response with a specific class of drugs. However, the effects of ethnicity on pharmacological response to asthma therapies are also, and mainly, determined by socioeconomic and environmental factors to a varying extent, depending on the ethnic groups...
March 12, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29517082/benralizumab-for-the-treatment-of-asthma
#16
REVIEW
M G Matera, P Rogliani, L Calzetta, G W Canonica, M Cazzola
Benralizumab is a humanized monoclonal antibody directed at the a subunit of the interleukin-5 receptor (IL-5R) that is under clinical development. The binding of benralizumab with the alpha chain of IL-5R results in inhibition of hetero-oligomerization of alpha and beta subunits and thus no signal transduction occurs. Consequently, this inhibition prevents proliferation of eosinophils and basophils and the cascade of events following it. Several pivotal trials have documented that benralizumab reduces asthma exacerbation rates with a significant increase in time to the next exacerbation, statistically improves prebronchodilator forced expiratory volume in 1 second (FEV1) and disease-specific health-related quality of life, and is well tolerated in patients with severe asthma and blood eosinophil counts greater than or equal to 150 cells/mcL...
December 2017: Drugs of Today
https://www.readbyqxmd.com/read/29505318/a-safety-comparison-of-laba-lama-vs-laba-ics-combination-therapy-for-copd
#17
Maria Gabriella Matera, Luigino Calzetta, Ermanno Puxeddu, Paola Rogliani, Mario Cazzola
LABA+LAMA and LABA+ICS combinations are key pharmacological approaches to the treatment of COPD. However, both combination types can induce adverse events (AEs). Areas covered: Current literature on LABA+LAMA and LABA+ICS combinations has been reviewed with a specific focus on their safety profile in the treatment of COPD. Expert opinion: Several meta-analyses have compared the pooled safety data from randomized clinical trials (RCTs) of LABA+LAMA combinations with LABA+ICS combinations. LABA+LAMA caused significantly less AEs and SAEs...
May 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29504568/the-role-of-different-nonspecific-interactions-and-halogen-contacts-in-the-crystal-structure-organization-of-5-chloroisatoic-anhydride
#18
Dorota Pogoda, Agnieszka Matera-Witkiewicz, Marcin Listowski, Jan Janczak, Veneta Videnova-Adrabinska
The crystal structure of 6-chloro-2,4-dihydro-1H-3,1-benzoxazine-2,4-dione (5-chloroisatoic anhydride), C8 H4 ClNO3 , has been determined and analysed in terms of connectivity and packing patterns. The compound crystallizes in the noncentrosymmetric space group Pna21 with one molecule in the asymmetric unit. The role of different weak interactions is discussed with respect to three-dimensional network organization. Molecules are extended into one-dimensional helical arrangements, making use of N-H...O hydrogen bonds and π-π interactions...
March 1, 2018: Acta Crystallographica. Section C, Structural Chemistry
https://www.readbyqxmd.com/read/29486600/safety-of-humanized-monoclonal-antibodies-against-il-5-in-asthma-focus-on-reslizumab
#19
REVIEW
Mario Cazzola, Maria Gabriella Matera, Francesca Levi-Schaffer, Paola Rogliani
Reslizumab, a humanized mAb against IL-5, reduces the number of eosinophils in the blood and lungs. Based on efficacy and safety data from pivotal RCTs, reslizumab had been approved for use as an add-on maintenance treatment of severe asthma with an eosinophilic phenotype in adults who have a history of exacerbations despite receiving their current asthma medicines. Areas covered: Current literature on reslizumab has been reviewed with a specific focus on its safety profile in the treatment of severe asthma...
April 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29466941/transcription-start-site-profiling-uncovers-divergent-transcription-and-enhancer-associated-rnas-in-drosophila-melanogaster
#20
Michael P Meers, Karen Adelman, Robert J Duronio, Brian D Strahl, Daniel J McKay, A Gregory Matera
BACKGROUND: High-resolution transcription start site (TSS) mapping in D. melanogaster embryos and cell lines has revealed a rich and detailed landscape of both cis- and trans-regulatory elements and factors. However, TSS profiling has not been investigated in an orthogonal in vivo setting. Here, we present a comprehensive dataset that links TSS dynamics with nucleosome occupancy and gene expression in the wandering third instar larva, a developmental stage characterized by large-scale shifts in transcriptional programs in preparation for metamorphosis...
February 21, 2018: BMC Genomics
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