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https://www.readbyqxmd.com/read/30545064/mitochondrial-hyperactivation-and-enhanced-ros-production-are-involved-in-toxicity-induced-by-oncogenic-kinases-over-signaling
#1
Monica Ceccon, Mario Mauri, Luca Massimino, Giovanni Giudici, Rocco Piazza, Carlo Gambacorti-Passerini, Luca Mologni
Targeted therapy is an effective, rational, and safe approach to solid and hematological tumors treatment. Unfortunately, a significant fraction of patients treated with tyrosine kinase inhibitors (TKI) relapses mainly because of gene amplification, mutations, or other bypass mechanisms. Recently a growing number of papers showed how, in some cases, resistance due to oncogene overexpression may be associated with drug addiction: cells able to proliferate in the presence of high TKI doses become also TKI dependent, undergoing cellular stress, and apoptosis/death upon drug withdrawal...
December 12, 2018: Cancers
https://www.readbyqxmd.com/read/30510251/wiskott-aldrich-syndrome-protein-wasp-is-a-tumor-suppressor-in-t-cell-lymphoma
#2
Matteo Menotti, Chiara Ambrogio, Taek-Chin Cheong, Chiara Pighi, Ines Mota, Seth H Cassel, Mara Compagno, Qi Wang, Riccardo Dall'Olio, Valerio G Minero, Teresa Poggio, Geeta Geeta Sharma, Enrico Patrucco, Cristina Mastini, Ramesh Choudhari, Achille Pich, Alberto Zamo, Roberto Piva, Silvia Giliani, Luca Mologni, Clayton K Collings, Cigall Kadoch, Carlo Gambacorti-Passerini, Luigi D Notarangelo, Ines M Anton, Claudia Voena, Roberto Chiarle
In T lymphocytes, the Wiskott-Aldrich Syndrome protein (WASP) and WASP-interacting-protein (WIP) regulate T cell antigen receptor (TCR) signaling, but their role in lymphoma is largely unknown. Here we show that the expression of WASP and WIP is frequently low or absent in anaplastic large cell lymphoma (ALCL) compared to other T cell lymphomas. In anaplastic lymphoma kinase-positive (ALK+) ALCL, WASP and WIP expression is regulated by ALK oncogenic activity via its downstream mediators STAT3 and C/EBP-β. ALK+ lymphomas were accelerated in WASP- and WIP-deficient mice...
December 3, 2018: Nature Medicine
https://www.readbyqxmd.com/read/30471673/homologation-of-ugi-and-passerini-reactions-using-ynamides
#3
REVIEW
Bo Huang, Sunliang Cui
Being important biological and pharmacological units, β-amino amides and β-acyloxy amides have a privileged position in both academia and industry. Developing a methods to prepare them has gained attention. Ynamides, which possess dual nucleophilic and electrophilic properties, are similar to isonitriles. In this review, usage of ynamides in the single reactant replacement approach of Ugi and Passerini reactions to develop two new multicomponent reactions to get various β-amino amides and β-acyloxy amides is reported...
November 2018: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/30462552/downregulation-of-gata6-in-mtor-inhibited-human-aortic-endothelial-cells-effects-on-tnf%C3%AE-induced-vcam-1-expression-and-monocytic-cell-adhesion
#4
Xing Fan, Xiaolin Chen, Qi Feng, Kai Peng, Qianqian Wu, Anthony G Passerini, Scott I Simon, ChongXiu Sun
Increased expression of vascular cell adhesion molecule-1 (VCAM-1) on aortic endothelium is an early marker of atherogenesis, promoted in part by elevated inflammatory cytokines such as TNFα. Mammalian target of rapamycin (mTOR) is a ubiquitous signaling molecule that has been considered to contribute to diverse cellular processes through mTOR complex 1 (mTORC1) or complex 2 (mTORC2). This study aimed to elucidate the role of mTOR signaling in TNFα-induced VCAM-1 expression by arterial endothelium. Primary human aortic endothelial cells (HAEC) were treated with low-dose (0...
November 21, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/30446494/genomic-alterations-important-for-the-prognosis-in-patients-with-follicular-lymphoma-treated-on-swog-study-s0016
#5
Xiaoyu Qu, Hongli Li, Rita M Braziel, Verena Passerini, Lisa M Rimsza, Eric D Hsi, John P Leonard, Sonali M Smith, Robert Kridel, Oliver Press, Oliver Weigert, Michael LeBlanc, Jonathan W Friedberg, Min Fang
Although recent advances in molecular genetics have enabled improved risk classification of follicular lymphoma (FL) using, for example, the m7-FLIPI score, the impact on treatment has been limited. We aimed to assess the prognostic significance of copy number aberrations (CNAs) and copy neutral loss of heterozygosity (cnLOH) identified by chromosome genomic array testing (CGAT) at FL diagnosis using prospectively collected clinical trial specimens from 255 patients enrolled in SWOG S0016. The impact of genomic aberrations was assessed for early progression (progressed or died within 2 years after registration), progression free survival (PFS), and overall survival (OS)...
November 16, 2018: Blood
https://www.readbyqxmd.com/read/30444462/spray-congealing-a-versatile-technology-for-advanced-drug-delivery-systems
#6
Serena Bertoni, Luisa S Dolci, Beatrice Albertini, Nadia Passerini
Spray congealing is a low cost, simple and versatile method to produce microparticles without the use of organic or aqueous solvent. This review provides a detailed picture of the pharmaceutical applications of this technology, with an overview of the spray-congealed-based drug-delivery systems. First, the basic principles and equipment of spray congealing technology are presented. Then, representative examples of the drug-delivery systems are examined and critically discussed. Emphasis is given on the role of formulation variables, together with practical considerations for formulation design...
November 2018: Therapeutic Delivery
https://www.readbyqxmd.com/read/30423416/modulation-of-alendronate-release-from-a-calcium-phosphate-bone-cement-an-in-vitro-osteoblast-osteoclast-co-culture-study
#7
Luisa Stella Dolci, Silvia Panzavolta, Paola Torricelli, Beatrice Albertini, Laura Sicuro, Milena Fini, Adriana Bigi, Nadia Passerini
In this study, we loaded a biomimetic calcium phosphate bone cement (CPC) with relatively high amounts of a bisphosphonate through the use of Solid Lipid Microparticles (MPs) and investigated bone cells response to the composite cements. 10, 20 and 30% w/w of Alendronate (AL) were successfully introduced into microparticles of Cutina HR and Precirol, which were prepared by means of spray-congealing technique. Addition of AL-loaded MPs to the cement composition provoked a lengthening of the setting and of the hardening processes...
November 10, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/30371554/onclarity-human-papillomavirus-extended-genotyping-in-the-management-of-cervical-intraepithelial-neoplasia-2-lesions
#8
Fabio Bottari, Anna Daniela Iacobone, Sara Boveri, Eleonora Petra Preti, Dorella Franchi, Luciano Mariani, Mario Preti, Fabio Landoni, Rita Passerini, Maria Teresa Sandri
OBJECTIVE: Many methods are available today for human papillomavirus (HPV) testing; they differ for technology, targets, and information on the genotypes detected. In this study, we evaluated the performance of the Onclarity HPV assay in detection and follow-up of cervical preneoplastic lesions. MATERIALS AND METHODS: One hundred sixty-seven women referred to the European Institute of Oncology, Milan, for treatment of cervical lesions were enrolled. We investigated the utility of Onclarity extended genotyping HPV test in the management of cervical intraepithelial neoplasia (CIN) 2+ preneoplastic lesion...
October 26, 2018: Journal of Lower Genital Tract Disease
https://www.readbyqxmd.com/read/30354943/reply-to-liu-et-al
#9
Lucian Itu, Saikiran Rapaka, Tiziano Passerini, Bogdan Georgescu, Chris Schwemmer, Max Schoebinger, Thomas Flohr, Puneet Sharma, Dorin Comaniciu
No abstract text is available yet for this article.
October 1, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/30354108/synthesis-of-glycomimetics-by-diastereoselective-passerini-reaction
#10
Kristina Vlahoviček-Kahlina, Mario Vazdar, Andreja Jakas, Vilko Smrečki, Ivanka Jerić
We describe the utilization of bis-isopropylidene-protected d-fructose-derived aldehyde in the Passerini reaction with various acids and isocyanides. A library of densely functionalized glycomimetics bearing up to 3 carbohydrate units was obtained in high yields and diastereoselectivities. The configuration of the newly formed stereocenter was determined and the diastereoselectivity was rationalized by DFT calculations.
November 2, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/30324420/novel-clinical-findings-in-autosomal-recessive-nr2e3-related-retinal-dystrophy
#11
Vittoria Murro, Dario Pasquale Mucciolo, Andrea Sodi, Ilaria Passerini, Dario Giorgio, Gianni Virgili, Stanislao Rizzo
PURPOSE: To evaluate the clinical phenotype of autosomal recessive NR2E3-related retinal dystrophy. METHODS: We retrospectively studied 11 patients carrying out at least 2 NR2E3 mutations; they had undergone comprehensive ophthalmological examination, fundus photography, optical coherence tomography, electrophysiological testing, and visual field at the Regional Reference Center for Hereditary Retinal Degenerations of the Eye Clinic in Florence. RESULTS: Five females and six males with a diagnosis of NR2E3-related retinal dystrophy were included in the study...
October 15, 2018: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/30322862/lorlatinib-treatment-elicits-multiple-on-and-off-target-mechanisms-of-resistance-in-alk-driven-cancer
#12
Sara Redaelli, Monica Ceccon, Marina Zappa, Geeta G Sharma, Cristina Mastini, Mario Mauri, Marion Nigoghossian, Luca Massimino, Nicoletta Cordani, Francesca Farina, Rocco Piazza, Carlo Gambacorti-Passerini, Luca Mologni
Targeted therapy changed the standard of care in ALK-dependent tumors. However, resistance remains a major challenge. Lorlatinib is a third generation ALK inhibitor that inhibits most ALK mutants resistant to current ALK inhibitors. In this study, we utilize lorlatinib-resistant anaplastic large cell lymphoma (ALCL), non-small cell lung cancer (NSCLC), and neuroblastoma cell lines in vitro and in vivo to investigate the acquisition of resistance and its underlying mechanisms. ALCL cells acquired compound ALK mutations G1202R/G1269A and C1156F/L1198F in vitro at high drug concentrations...
October 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/30320074/portable-high-voltage-integrated-harvesting-storage-device-employing-dye-sensitized-solar-module-and-all-solid-state-electrochemical-double-layer-capacitor
#13
Alberto Scalia, Alberto Varzi, Andrea Lamberti, Timo Jacob, Stefano Passerini
A dye-sensitized solar module (DSSM) and a high voltage all-solid-state electrochemical double layer capacitor (EDLC) are, for the first time, implemented in a compact Harvesting-Storage (HS) device. Conductive glass is employed as current collecting substrate for both DSSM and EDLC, leading to a robust and portable final structure. The photovoltaic section is constituted by a 4 series cells W-type module, while in the storage section an EDLC employing an ionic liquid-based polymeric electrolyte (a mixture of polyethylene oxide and N-butyl-N-methylpyrrolidinium bis(trifluoromethanesulfonyl)imide, PEO-Pyr14 TFSI) and activated carbon electrodes is used...
2018: Frontiers in Chemistry
https://www.readbyqxmd.com/read/30300834/an-investigation-into-the-release-behavior-of-solid-lipid-microparticles-in-different-simulated-gastrointestinal-fluids
#14
Beatrice Albertini, Serena Bertoni, Beatrice Perissutti, Nadia Passerini
In recent years there has been a growing interest in solid lipid-based systems, particularly in solid lipid microparticles (SLMs); however, only very few studies deeply investigated the dissolution behaviour of orally delivered-SLMs. The present study provides new insights about the release performance in different gastrointestinal fluids of SLMs containing a freely water soluble drug (caffeine, as BCS class I drug). Three different formulations of SLMs were prepared by spray congealing using lipid excipients belonging to three chemical classes: fatty acids, triglycerides and waxes...
September 26, 2018: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/30290003/tyrosine-kinase-inhibitor-interruptions-discontinuations-and-switching-in-patients-with-chronic-phase-chronic-myeloid-leukemia-in-routine-clinical-practice-simplicity
#15
Rüdiger Hehlmann, Jorge E Cortes, Teresa Zyczynski, Carlo Gambacorti-Passerini, Stuart L Goldberg, Michael J Mauro, Mauricette Michallet, Bengt Simonsson, Loretta A Williams, Srikanth Gajavelli, Irene DeGutis, Ginny P Sen, Ron L Paquette
SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor (TKI) use and management patterns in patients with chronic phase-chronic myeloid leukemia in the US and Europe in routine clinical practice. Herein we describe interruptions, discontinuations and switching of TKI therapy during the initial 2 years of treatment among 1121 patients prospectively enrolled between October 1, 2010 and March 7, 2017. Patient characteristics were broadly similar between the imatinib (n = 370), dasatinib (n = 376), and nilotinib (n = 375) cohorts...
October 5, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/30285522/cfh-y402h-polymorphism-in-italian-patients-with-age-related-macular-degeneration-retinitis-pigmentosa-and-stargardt-disease
#16
Andrea Sodi, Ilaria Passerini, Daniela Bacherini, Luca Boni, Simona Palchetti, Vittoria Murro, Orsola Caporossi, Dario Pasquale Mucciolo, Fabrizio Franco, Lorenzo Vannozzi, Francesca Torricelli, Elisabetta Pelo, Stanislao Rizzo, Gianni Virgili
BACKGROUND: The complement system has been implicated in the pathogenesis of age-related macular degeneration (AMD) and the CFH Y402H polymorphism has been suggested as a major risk factor for AMD. Recent evidences supported the role of inflammation in the pathogenesis of some retinal dystrophies. Aim of this study was to evaluate the prevalence of CFHY402H polymorphism in a group of Italian patients affected by atrophic AMD, Stargardt disease (STGD), or retinitis pigmentosa(RP). MATERIALS AND METHODS: Our case-control association study included 116 patients with atrophic AMD, 77 with RP, 86 with STGD, and 100 healthy controls...
October 4, 2018: Ophthalmic Genetics
https://www.readbyqxmd.com/read/30283963/constructing-reduction-sensitive-pegylated-nirf-mesoporous-silica-nanoparticles-via-a-one-pot-passerini-reaction-for-photothermal-chemo-therapy
#17
Yu Zhu, Wenhai Lin, Xin Wang, Wei Zhang, Li Chen, Zhigang Xie
In this work, we decorated the surface of MSNs by a one-pot Passerini reaction using near-infrared fluorescence BODIPY and poly(ethylene glycol) with an aldehyde group (PEG-CHO) for the first time. Doxorubicin (Dox) was loaded to demonstrate the reduction response. The formed MSNs neatly integrate chemotherapy, photothermal therapy and near-infrared fluorescence (NIRF) imaging.
October 28, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/30279743/biomarker-of-food-intake-for-assessing-the-consumption-of-dairy-and-egg-products
#18
REVIEW
Linda H Münger, Mar Garcia-Aloy, Rosa Vázquez-Fresno, Doreen Gille, Albert Remus R Rosana, Anna Passerini, María-Trinidad Soria-Florido, Grégory Pimentel, Tanvir Sajed, David S Wishart, Cristina Andres Lacueva, Guy Vergères, Giulia Praticò
Dairy and egg products constitute an important part of Western diets as they represent an excellent source of high-quality proteins, vitamins, minerals and fats. Dairy and egg products are highly diverse and their associations with a range of nutritional and health outcomes are therefore heterogeneous. Such associations are also often weak or debated due to the difficulty in establishing correct assessments of dietary intake. Therefore, in order to better characterize associations between the consumption of these foods and health outcomes, it is important to identify reliable biomarkers of their intake...
2018: Genes & Nutrition
https://www.readbyqxmd.com/read/30277019/enabling-reversible-de-lithiation-of-aluminum-via-the-use-of-bis-fluorosulfonyl-imide-based-electrolytes
#19
Bingsheng Qin, Sangsik Jeong, Huang Zhang, Ulderico Ulissi, Diogo Vieira Carvalho, Alberto Varzi, Stefano Passerini
Aluminum, a cost-effective and abundant metal capable of alloying with Li up to ~1000 mAh/g, is a very appealing anode material for high energy density lithium ion batteries (LIBs). However, despite the repeated efforts in the past three decades, reports presenting stable cycling performance are extremely rare. In this letter, we report our recent findings on the highly reversible (de-)lithiation of micro-sized Al anode (m-Al) enabled by the use of bis(fluorosulfonyl)imide (FSI)-based electrolytes. Using this kind of electrolytes, m-Al can deliver a specific capacity over 900 mAh/g and superior Coulombic efficiency (96...
October 1, 2018: ChemSusChem
https://www.readbyqxmd.com/read/30267834/conformational-polymorphic-changes-in-the-crystal-structure-of-the-chiral-antiparasitic-drug-praziquantel-and-interactions-with-calcium-carbonate
#20
Ana Borrego-Sánchez, Esperanza Carazo, Beatrice Albertini, Nadia Passerini, Beatrice Perissutti, Pilar Cerezo, César Viseras, A Hernández-Laguna, Carola Aguzzi, C Ignacio Sainz-Díaz
Praziquantel is an antiparasitic drug used for decades. Currently, the praziquantel commercial preparation is a racemic mixture, in which only the levo-enantiomer possesses anthelmintic activity. The knowledge of its properties in the solid state and other chemical-physical properties is necessary for improving its efficacy and applications. Drug solid dispersions were prepared with calcium carbonate at 1:5 drug to excipient weight ratio by solvent evaporation method. Then, the modification of the crystal structure of the racemic polymorph of praziquantel in presence of calcium carbonate has been studied by means of several analytical techniques (DSC, TGA, XRD, SEM, FTIR, Raman spectroscopy and chiral liquid chromatography)...
November 2018: European Journal of Pharmaceutics and Biopharmaceutics
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