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https://www.readbyqxmd.com/read/29716920/cd20-tcb-with-obinutuzumab-pretreatment-as-next-generation-treatment-of-hematological-malignancies
#1
Marina Bacac, Sara Colombetti, Sylvia Herter, Johannes Sam, Mario Perro, Stanford Chen, Roberta Bianchi, Sarah Diggelmann, Florian Limani, Ramona Schlenker, Tamara Hüsser, Wolfgang F Richter, Katharine Bray-French, Heather J Hinton, Anna Maria F Giusti, Anne Freimoser-Grundschober, Laurent Larivière, Christiane Neumann, Christian Klein, Pablo Umana
PURPOSE: Despite promising clinical activity, T cell engaging therapies including T cell bispecific antibodies (TCBs) are associated with severe side effects requiring the use of step-up-dosing (SUD) regimens to mitigate safety. Here, we present a next generation CD20-targeting TCB (CD20-TCB) with significantly higher potency and a novel approach enabling safer administration of such potent drug. EXPERIMENTAL DESIGN: We developed CD20-TCB based on the 2:1 TCB molecular format and characterized its activity pre-clinically...
May 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29650691/predictive-score-for-the-development-or-progression-of-graves-orbitopathy-in-patients-with-newly-diagnosed-graves-hyperthyroidism
#2
Wilmar M Wiersinga, Miloš Žarković, Luigi Bartalena, Simone Donati, Petros Perros, Onyebuchi Okosieme, Daniel Morris, Nicole Fichter, Juerg Lareida, Georg von Arx, Chantal Daumerie, Maria-Cristina Burlacu, George J Kahaly, Susanne Pitz, Biljana Beleslin, Jasmina Ćirić, Goksun Ayvaz, Onur Konuk, Fusun Balos Toruner, Mario Salvi, Danila Covelli, Nicola Currò, Laszlo Hegedüs, Thomas Heiberg Brix
Objective: To construct a predictive score for the development or progression of Graves' orbitopathy (GO) in Graves' hyperthyroidism (GH). Design: Prospective observational study in patients with newly diagnosed GH, treated with antithyroid drugs (ATD) for 18 months at ten participating centers from EUGOGO in 8 European countries. Methods: 348 patients were included with untreated GH but without obvious GO. Mixeded effects logistic regression was used to determine best predictors. A predictive score (called PREDIGO) was constructed...
April 12, 2018: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29499378/the-integrated-stress-response-system-in-cardiovascular-disease
#3
REVIEW
Diana Santos-Ribeiro, Laurent Godinas, Charles Pilette, Frédéric Perros
The integrated stress response system represents an ancillary, extremely conserved signalling pathway present in virtually all eukaryotic cells, which plays an important part in the pathophysiology of several disorders such as cancer and neurodegeneration. However, its role in the cardiovascular system remains largely elusive. Hence, this review aims to acknowledge recent findings regarding the action of the eIF2α kinases in the cardiovascular system and their role in the pathophysiology of related disorders...
April 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29444988/nmda-type-glutamate-receptor-activation-promotes-vascular-remodeling-and-pulmonary-arterial-hypertension
#4
Sébastien J Dumas, Gilles Bru-Mercier, Audrey Courboulin, Marceau Quatredeniers, Catherine Rücker-Martin, Fabrice Antigny, Morad K Nakhleh, Benoit Ranchoux, Elodie Gouadon, Maria-Candida Vinhas, Matthieu Vocelle, Nicolas Raymond, Peter Dorfmüller, Elie Fadel, Frédéric Perros, Marc Humbert, Sylvia Cohen-Kaminsky
Background -Excessive proliferation and apoptosis resistance in pulmonary vascular cells underlie vascular remodeling in pulmonary arterial hypertension (PAH). Specific treatments for PAH exist, mostly targeting endothelial dysfunction, but high pulmonary arterial pressure still causes heart failure and death. Pulmonary vascular remodeling may be driven by metabolic reprogramming of vascular cells to increase glutaminolysis and glutamate production. The N-methyl-D-aspartate receptor (NMDAR), a major neuronal glutamate receptor, is also expressed on vascular cells, but its role in PAH is unknown...
February 14, 2018: Circulation
https://www.readbyqxmd.com/read/29413507/respiratory-effects-of-trichloroethylene
#5
REVIEW
Orianne Dumas, Thomas Despreaux, Frédéric Perros, Edmund Lau, Pascal Andujar, Marc Humbert, David Montani, Alexis Descatha
Trichloroethylene (TCE) is a chlorinated solvent that has been used widely around the world in the twentieth century for metal degreasing and dry cleaning. Although TCE displays general toxicity and is classified as a human carcinogen, the association between TCE exposure and respiratory disorders are conflicting. In this review we aimed to systematically evaluate the current evidence for the respiratory effects of TCE exposure and the implications for the practicing clinician. There is limited evidence of an increased risk of lung cancer associated with TCE exposure based on animal and human data...
January 2018: Respiratory Medicine
https://www.readbyqxmd.com/read/29396246/mycophenolate-plus-methylprednisolone-versus-methylprednisolone-alone-in-active-moderate-to-severe-graves-orbitopathy-mingo-a-randomised-observer-masked-multicentre-trial
#6
George J Kahaly, Michaela Riedl, Jochem König, Susanne Pitz, Katharina Ponto, Tanja Diana, Elena Kampmann, Elisa Kolbe, Anja Eckstein, Lars C Moeller, Dagmar Führer, Mario Salvi, Nicola Curro, Irene Campi, Danila Covelli, Marenza Leo, Michele Marinò, Francesca Menconi, Claudio Marcocci, Luigi Bartalena, Petros Perros, Wilmar M Wiersinga
BACKGROUND: European guidelines recommend intravenous methylprednisolone as first-line treatment for active and severe Graves' orbitopathy; however, it is common for patients to have no response or have relapse after discontinuation of treatment. We aimed to compare the efficacy and safety of add-on mycophenolate to methylprednisolone in comparison with methylprednisolone alone in patients with moderate-to-severe Graves' orbitopathy. METHODS: MINGO was an observer-masked, multicentre, block-randomised, centre-stratified trial done in two centres in Germany and two in Italy...
April 2018: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/29369849/sirtuin-1-regulates-pulmonary-artery-smooth-muscle-cell-proliferation-role-in-pulmonary-arterial-hypertension
#7
Giada Zurlo, Jérôme Piquereau, Maryline Moulin, Julie Pires Da Silva, Mélanie Gressette, Benoît Ranchoux, Anne Garnier, Renée Ventura-Clapier, Elie Fadel, Marc Humbert, Christophe Lemaire, Frédéric Perros, Vladimir Veksler
OBJECTIVE: Energy metabolism shift from oxidative phosphorylation toward glycolysis in pulmonary artery smooth muscle cells (PASMCs) is suggested to be involved in their hyperproliferation in pulmonary arterial hypertension (PAH). Here, we studied the role of the deacetylase sirtuin1 (SIRT1) in energy metabolism regulation in PASMCs via various pathways including activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), master regulator of mitochondrial biogenesis...
May 2018: Journal of Hypertension
https://www.readbyqxmd.com/read/29360952/loss-of-kcnk3-is-a-hallmark-of-rv-hypertrophy-dysfunction-associated-with-pulmonary-hypertension
#8
Mélanie Lambert, Angèle Boet, Catherine Rucker-Martin, Pedro Mendes-Ferreira, Véronique Capuano, Stéphane Hatem, Rui Adão, Carmen Brás-Silva, Aurélie Hautefort, Jean-Baptiste Michel, Peter Dorfmuller, Elie Fadel, Tom Kotsimbos, Laura Price, Philippe Jourdon, David Montani, Marc Humbert, Frédéric Perros, Fabrice Antigny
Aims: Mutations in the KCNK3 gene, which encodes for an outward-rectifier K+ channel, have been identified in patients suffering from pulmonary arterial hypertension (PAH), and constitute the first described channelopathy in PAH. In human PAH and experimental pulmonary hypertension (PH), we demonstrated that KCNK3 expression and function are severely reduced in pulmonary vascular cells, promoting PH-like phenotype at the morphologic and hemodynamic levels. Since KCNK3 channel is also expressed in both the human and rodent heart, we aimed to elucidate the pathophysiological role of KCNK3 channel in right ventricular (RV) hypertrophy (RVH) related to PH...
January 19, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29330194/telotristat-ethyl-in-carcinoid-syndrome-safety-and-efficacy-in-the-telecast-phase-3-trial
#9
Marianne Pavel, David J Gross, Marta Benavent, Petros Perros, Raj Srirajaskanthan, Richard R P Warner, Matthew H Kulke, Lowell B Anthony, Pamela L Kunz, Dieter Hörsch, Martin O Weickert, Pablo Lapuerta, Wenjun Jiang, Kenneth Kassler-Taub, Suman Wason, Rosanna Fleming, Douglas Fleming, Rocio Garcia-Carbonero
Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing ≥4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a phase 3 companion study, assessed the safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea or elevated urinary 5-hydroxyindoleacetic acid (u5-HIAA)) with <4 BMs/day on SSAs (or ≥1 symptom or ≥4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE)...
March 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29206084/identity-crisis-in-pulmonary-arterial-hypertension
#10
G Ruffenach, S Bonnet, S Rousseaux, S Khochbin, S Provencher, F Perros
Pulmonary arterial hypertension (PAH) shares many hallmarks with cancer. Cancer cells acquire their hallmarks by a pathological Darwinian evolution process built on the so-called cancer cell "identity crisis." Here we demonstrate that PAH shares the most striking features of the cancer identity crisis: the ectopic expression of normally silent tissue-specific genes.
January 2018: Pulmonary Circulation
https://www.readbyqxmd.com/read/29108819/pulmonary-vascular-remodeling-patterns-and-expression-of-general-control-nonderepressible-2-gcn2-in-pulmonary-veno-occlusive-disease
#11
Esther J Nossent, Fabrice Antigny, David Montani, Harm Jan Bogaard, Maria Rosa Ghigna, Mélanie Lambert, Vincent Thomas de Montpréville, Barbara Girerd, Xavier Jaïs, Laurent Savale, Olaf Mercier, Elie Fadel, Florent Soubrier, Olivier Sitbon, Gérald Simonneau, Anton Vonk Noordegraaf, Marc Humbert, Frédéric Perros, Peter Dorfmüller
BACKGROUND: Heritable pulmonary veno-occlusive disease (PVOD) is linked to mutations in the eukaryotic initiation factor 2 alpha kinase 4 (EIF2AK4) gene, leading to a loss of general control nonderepressible 2 (GCN2). The role of GCN2 expression in pulmonary vascular remodeling remains obscure. We sought to identify specific histologic and biologic features in heritable PVOD. METHODS: Clinical data and lung histology of 24 PVOD patients (12 EIF2AK4 mutation carriers, 12 non-carriers) were submitted to systematic histologic analysis and semiautomated morphometry...
October 4, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28931663/targeting-fatty-acid-amide-hydrolase-as-a-therapeutic-strategy-for-antitussive-therapy
#12
Michael A Wortley, John J Adcock, Eric D Dubuis, Sarah A Maher, Sara J Bonvini, Isabelle Delescluse, Ross Kinloch, Gordon McMurray, Christelle Perros-Huguet, Marianthi Papakosta, Mark A Birrell, Maria G Belvisi
Cough is the most common reason to visit a primary care physician, yet it remains an unmet medical need. Fatty acid amide hydrolase (FAAH) is an enzyme that breaks down endocannabinoids, and inhibition of FAAH produces analgesic and anti-inflammatory effects. Cannabinoids inhibit vagal sensory nerve activation and the cough reflex, so it was hypothesised that FAAH inhibition would produce antitussive activity via elevation of endocannabinoids.Primary vagal ganglia neurons, tissue bioassay, in vivo electrophysiology and a conscious guinea pig cough model were utilised to investigate a role for fatty acid amides in modulating sensory nerve activation in vagal afferents...
September 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28900641/core-shell-colloidal-particles-with-dynamically-tunable-scattering-properties
#13
Guangnan Meng, Vinothan N Manoharan, Adeline Perro
We design polystyrene-poly(N'-isopropylacrylamide-co-acrylic acid) core-shell particles that exhibit dynamically tunable scattering. We show that under normal solvent conditions the shell is nearly index-matched to pure water, and the particle scattering is dominated by Rayleigh scattering from the core. As the temperature or salt concentration increases, both the scattering cross-section and the forward scattering increase, characteristic of Mie scatterers. The magnitude of the change in the scattering cross-section and scattering anisotropy can be controlled through the solvent conditions and the size of the core...
September 27, 2017: Soft Matter
https://www.readbyqxmd.com/read/28881789/pulmonary-endothelial-cell-dna-methylation-signature-in-pulmonary-arterial-hypertension
#14
Aurélie Hautefort, Julie Chesné, Jens Preussner, Soni S Pullamsetti, Jorg Tost, Mario Looso, Fabrice Antigny, Barbara Girerd, Marianne Riou, Saadia Eddahibi, Jean-François Deleuze, Werner Seeger, Elie Fadel, Gerald Simonneau, David Montani, Marc Humbert, Frédéric Perros
Pulmonary arterial hypertension (PAH) is a severe and incurable pulmonary vascular disease. One of the primary origins of PAH is pulmonary endothelial dysfunction leading to vasoconstriction, aberrant angiogenesis and smooth muscle cell proliferation, endothelial-to-mesenchymal transition, thrombosis and inflammation. Our objective was to study the epigenetic variations in pulmonary endothelial cells (PEC) through a specific pattern of DNA methylation. DNA was extracted from cultured PEC from idiopathic PAH (n = 11), heritable PAH (n = 10) and controls (n = 18)...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28834559/improving-the-prehospital-safety-of-steroid-dependent-patients-in-northern-england-a-hospital-initiated-ambulance-service-registration-pathway
#15
LETTER
Anna L Mitchell, Kerri Devine, Vikram Lal, Paul Galloway, Matthew House, Katherine White, Julie Watson, Steve Parry, Margaret Miller, Margaret Morris, R Andy James, Petros Perros, Simon H S Pearce, Richard Quinton
No abstract text is available yet for this article.
August 23, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28801076/early-development-of-right-ventricular-ischemic-lesions-in-a-novel-large-animal-model-of-acute-right-heart-failure-in-chronic-thromboembolic-pulmonary-hypertension
#16
David Boulate, Jennifer Arthur Ataam, Andrew J Connolly, Genevieve Giraldeau, Myriam Amsallem, Benoit Decante, Lilia Lamrani, Elie Fadel, Peter Dorfmuller, Frederic Perros, Francois Haddad, Olaf Mercier
BACKGROUND: Our aim was to develop a model of acute right heart failure (ARHF) in the setting of pulmonary hypertension and to characterize acute right ventricular lesions that develop early after hemodynamic restoration. METHODS AND RESULTS: We used a described piglet model of chronic pulmonary hypertension (cPH) induced by pulmonary artery occlusions. We induced ARHF in animals with cPH (ARHF-cPH group, n = 9) by volume loading and iterative acute pulmonary embolism until hemodynamic compromise followed by dobutamine infusion for hemodynamic restoration before sacrifice for right ventricular tissue evaluation...
December 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28755510/raising-awareness-of-graves-orbitopathy-with-early-warning-cards
#17
Anna L Mitchell, Janis Hickey, Bijay Vaidya, Rhianne Mason, Ramzi Ajjan, Nicola Zammitt, Petros Perros, Colin Dayan
BACKGROUND: Clinically significant Graves' orbitopathy (GO) develops in about 25% of those with Graves' disease (GD); most cases of GD in the UK are managed by endocrinologists. Despite this, patients report significant delays before a diagnosis of GO is made. Measures to increase awareness of the early signs of GO and establishing a fast-track referral pathway to specialist care should overcome these delays and potentially improve outcomes. AIMS: We aimed to determine whether issuing a "GO early warning card" to all GD patients raises awareness of GO and facilitates early diagnosis, what percentage of cards result in a telephone contact, the number of "false reports" from card carriers and patient perceptions of the cards...
December 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28725652/rescuing-bmpr2-driven-endothelial-dysfunction-in-pah-a-novel-treatment-strategy-for-the-future
#18
EDITORIAL
Rozenn Quarck, Fréderic Perros
No abstract text is available yet for this article.
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28655554/t-type-ca-2-channels-elicit-pro-proliferative-and-anti-apoptotic-responses-through-impaired-pp2a-akt1-signaling-in-pasmcs-from-patients-with-pulmonary-arterial-hypertension
#19
Safietou Sankhe, Sevasti Manousakidi, Fabrice Antigny, Jennifer Arthur Ataam, Sana Bentebbal, Yann Ruchon, Florence Lecerf, Jessica Sabourin, Laura Price, Elie Fadel, Peter Dorfmüller, Saadia Eddahibi, Marc Humbert, Frédéric Perros, Véronique Capuano
Idiopathic pulmonary arterial hypertension (iPAH) is characterized by obstructive hyperproliferation and apoptosis resistance of distal pulmonary artery smooth muscle cells (PASMCs). T-type Ca2+ channel blockers have been shown to reduce experimental pulmonary hypertension, although the impact of T-type channel inhibition remains unexplored in PASMCs from iPAH patients. Here we show that T-type channels Cav3.1 and Cav3.2 are present in the lung and PASMCs from iPAH patients and control subjects. The blockade of T-type channels by the specific blocker, TTA-A2, prevents cell cycle progression and PASMCs growth...
October 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28572541/pulmonary-endothelial-cell-dna-methylation-signature-in-pulmonary-arterial-hypertension
#20
Aurélie Hautefort, Julie Chesné, Jens Preussner, Soni S Pullamsetti, Jorg Tost, Mario Looso, Fabrice Antigny, Barbara Girerd, Marianne Riou, Saadia Eddahibi, Jean-François Deleuze, Werner Seeger, Elie Fadel, Gerald Simonneau, David Montani, Marc Humbert, Frédéric Perros
Pulmonary arterial hypertension (PAH) is a severe and incurable pulmonary vascular disease. One of the primary origins of PAH is pulmonary endothelial dysfunction leading to vasoconstriction, aberrant angiogenesis and smooth muscle cell proliferation, endothelial-to-mesenchymal transition, thrombosis and inflammation. Our objective was to study the epigenetic variations in pulmonary endothelial cells (PEC) through a specific pattern of DNA methylation.DNA was extracted from cultured PEC from idiopathic PAH (n = 11), heritable PAH (n = 10) and controls (n = 18)...
May 19, 2017: Oncotarget
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