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https://www.readbyqxmd.com/read/28214218/implication-of-downregulation-and-prospective-pathway-signaling-of-microrna-375-in-lung-squamous-cell-carcinoma
#1
Wen-Jie Chen, Ting-Qing Gan, Hui Qin, Su-Ning Huang, Li-Hua Yang, Ye-Ying Fang, Zu-Yun Li, Lin-Jiang Pan, Gang Chen
BACKGROUND: Lung cancer is one of the most typical cancers in the world. Altered expression profiles of microRNA-375(miR-375) are linked to many diseases including lung cancer. However, the relationship between miR-375 and lung squamous cell carcinoma (LUSC) is controversial. METHODS: We first evaluated the 23 LUSCs and the paired normal lung tissues by qRT-PCR. Then we analyzed the LUSC samples with miR-375 expression based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO)...
January 22, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28214179/mixture-toxicity-of-flubendazole-and-fenbendazole-to-daphnia-magna
#2
Alan Puckowski, Stefan Stolte, Marta Wagil, Marta Markiewicz, Paulina Łukaszewicz, Piotr Stepnowski, Anna Białk-Bielińska
Nowadays, residual amounts of many pharmaceuticals can be found in various environmental compartments including surface and ground waters, soils and sediments as well as biota. Even though they undergo degradability, their environmental discharge is relatively continuous, thus they may be regarded as quasi-persistent contaminants, and are also frequently regarded as emerging organic pollutants. Benzimidazoles, especially flubendazole (FLU) and fenbendazole (FEN), represent two anthelmintic drugs belonging to this group...
February 3, 2017: International Journal of Hygiene and Environmental Health
https://www.readbyqxmd.com/read/28214087/targeting-the-pd-1-pd-l1-axis-in-non-small-cell-lung-cancer
#3
REVIEW
Rajiv Kumar, Dearbhaile Collins, Saoirse Dolly, Fiona McDonald, Mary E R O'Brien, Timothy A Yap
The last decade has witnessed rapid advances in the discovery and development of immune checkpoint inhibitors in cancer medicine, particularly drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). The proven antitumor efficacy coupled with low rates of drug-related toxicities observed, albeit idiosyncratic, with these novel immunotherapeutics have led to the registration of multiple PD-1 and PD-L1 inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, in second-line advanced NSCLC, whereas durvalumab and avelumab are in late-phase clinical testing...
December 23, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28214006/-conduct-of-epidemiologic-studies-in-french-cancer-survivors-methods-difficulties-encountered-and-solutions-provided-lessons-learned-from-the-simonal-study-on-long-term-toxicities-after-non-hodgkin-lymphoma-treatment
#4
Sabine Anthony, Pierre Hebel, André Garrel, Vanina Oliveri, Catherine Thieblemont, Vincent Ribrag, Hervé Tilly, Corinne Haioun, René-Olivier Casasnovas, Franck Morschhauser, Pierre Feugier, Richard Delarue, Loic Ysebaert, Catherine Sebban, Florence Broussais, Gandhi Damaj, Virginie Nerich, Jean-Philippe Jais, Gilles Salles, Michel Henry-Amar, Nicolas Mounier
INTRODUCTION: Since the introduction of targeted therapies, specific lymphoma mortality has decreased. Possible long-term toxicities, however, are not known yet. This article describes the implementation of the SIMONAL study that investigates the hypothesis of an overconsumption of care after lymphoma treatment with a 10-year follow-up. METHODS: After the mandatory regulatory steps (CCTIRS and CNIL) the vital status and address of 5247 patients treated in 131 French centers were retrieved using a secure web portal, in order to send a quality of life after lymphoma questionnaire...
February 14, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28213937/targeting-phosphodiesterase-5-as-a-therapeutic-option-against-myocardial-ischemia-reperfusion-injury-and-in-treating-heart-failure
#5
REVIEW
Sevil Korkmaz-Icöz, Tamás Radovits, Gábor Szabó
Phosphodiesterase type 5 (PDE5) selectively hydrolyses the second messenger cyclic 3´-5´guanosine monophosphate (cGMP) into 5'-GMP, thereby regulating its intracellular concentrations. Dysregulation of the cGMP-dependent pathway plays a significant role in various cardiovascular diseases. Therefore, its modulation by drugs, such as PDE5 inhibitors, may represent an effective therapeutic approach. There are currently four PDE5 inhibitors available for the treatment of erectile dysfunction: sildenafil, vardenafil, tadalafil, and avanafil...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28213776/the-importance-of-drug-induced-sedation-endoscopy-d-i-s-e-techniques-in-surgical-decision-making-conventional-versus-target-controlled-infusion-techniques-a-prospective-randomized-controlled-study-and-a-retrospective-surgical-outcomes-analysis
#6
Andrea De Vito, Vanni Agnoletti, Gianluca Zani, Ruggero Massimo Corso, Giovanni D'Agostino, Elisabetta Firinu, Chiara Marchi, Ying-Shuo Hsu, Stefano Maitan, Claudio Vicini
Drug-Induced Sedation Endoscopy (DISE) consists of the direct observation of the upper airways during sedative-induced sleep, allowing the identification of the sites of pharyngeal collapse, which is the main pathological event in Obstructive Sleep Apnea (OSA). The Authors have compared Target Controlled Infusion (TCI) sedation endoscopy (TCI-DISE) technique to conventional DISE (CDISE), performed by a manual bolus injection of sedative agent, to recreate accurately and safely snoring and apnea patterns comparable to natural sleep...
February 17, 2017: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/28213771/a-novel-spiroindoline-targets-cell-cycle-and-migration-via-modulation-of-microtubule-cytoskeleton
#7
Naveen Kumar, Santanu Hati, Parthapratim Munshi, Subhabrata Sen, Seema Sehrawat, Shailja Singh
Natural product-inspired libraries of molecules with diverse architectures have evolved as one of the most useful tools for discovering lead molecules for drug discovery. In comparison to conventional combinatorial libraries, these molecules have been inferred to perform better in phenotypic screening against complicated targets. Diversity-oriented synthesis (DOS) is a forward directional strategy to access such multifaceted library of molecules. From a successful DOS campaign of a natural product-inspired library, recently a small molecule with spiroindoline motif was identified as a potent anti-breast cancer compound...
February 17, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28213714/-current-biomarkers-for-gastric-cancer
#8
G B Baretton, D E Aust
Gastric cancer is still a relevant malignant disease with high morbidity and mortality. Current molecular genetic data show that gastric cancer, as other solid tumors as well, is not a single entity but consists of several molecular subtypes of gastric cancer with diverse biology. The increasing understanding of molecular pathways is the basis for innovative therapies. These either directly target altered signaling pathways or genes in tumor cells or as in immune checkpoint inhibitors, indirectly target tumor cells by blocking tumor-induced immune inhibition leading to improvement in the prognosis...
February 17, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28213566/a-randomised-phase-iib-study-of-mavrilimumab-a-novel-gm-csf-receptor-alpha-monoclonal-antibody-in-the-treatment-of-rheumatoid-arthritis
#9
Gerd R Burmester, Iain B McInnes, Joel Kremer, Pedro Miranda, Mariusz Korkosz, Jiri Vencovsky, Andrea Rubbert-Roth, Eduardo Mysler, Matthew A Sleeman, Alex Godwood, Dominic Sinibaldi, Xiang Guo, Wendy I White, Bing Wang, Chi-Yuan Wu, Patricia C Ryan, David Close, Michael E Weinblatt
OBJECTIVES: Despite the therapeutic value of current rheumatoid arthritis (RA) treatments, agents with alternative modes of action are required. Mavrilimumab, a fully human monoclonal antibody targeting the granulocyte-macrophage colony-stimulating factor receptor-α, was evaluated in patients with moderate-to-severe RA. METHODS: In a phase IIb study (NCT01706926), patients with inadequate response to ≥1 synthetic disease-modifying antirheumatic drug(s), Disease Activity Score 28 (DAS28)-C reactive protein (CRP)/erythrocyte sedimentation rate ≥3...
February 17, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28213527/advancing-viral-rna-structure-prediction-measuring-the-thermodynamics-of-pyrimidine-rich-internal-loops
#10
Andy Phan, Katherine Mailey, Jessica Sakai, Xiaobo Gu, Susan J Schroeder
Accurate thermodynamic parameters improve RNA structure predictions and thus accelerate understanding of RNA function and the identification of RNA drug binding sites. Many viral RNA structures, such as internal ribosome entry sites, have internal loops and bulges that are potential drug target sites. Current models used to predict internal loops are biased towards small, symmetric purine loops, and thus poorly predict asymmetric, pyrimidine-rich loops with more than 6 nucleotides that occur frequently in viral RNA...
February 17, 2017: RNA
https://www.readbyqxmd.com/read/28213505/revealing-the-concealed-nature-of-long-qt-type-3-syndrome
#11
Amara Greer-Short, Sharon A George, Steven Poelzing, Seth H Weinberg
BACKGROUND: Gain-of-function mutations in the voltage-gated sodium channel (Nav1.5) are associated with the long-QT-3 (LQT3) syndrome. Nav1.5 is densely expressed at the intercalated disk, and narrow intercellular separation can modulate cell-to-cell coupling via extracellular electric fields and depletion of local sodium ion nanodomains. Models predict that significantly decreasing intercellular cleft widths slows conduction because of reduced sodium current driving force, termed "self-attenuation...
February 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28213330/drug-discovery-strategies-in-the-field-of-tumor-energy-metabolism-limitations-by-metabolic-flexibility-and-metabolic-resistance-to-chemotherapy
#12
REVIEW
N D Amoedo, E Obre, R Rossignol
The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28213274/differentially-cleaving-peptides-as-a-strategy-for-controlled-drug-release-in-human-retinal-pigment-epithelial-cells
#13
Madhushree Bhattacharya, Sanjay Sarkhel, Jonne Peltoniemi, Robert Broadbridge, Marjo Tuomainen, Seppo Auriola, Arto Urtti
Currently, drug delivery to the posterior eye segment relies on intravitreal injections of therapeutics. This approach requires frequent injections and does not guarantee drug delivery to intracellular targets. Controlled release systems and nanoparticles are being investigated to mitigate these challenges but most of these approaches lack translational success to the clinics. In our present study, we report a peptide based delivery system that utilizes enzyme assisted cleavable linkers to release conjugated cargo within the retinal pigment epithelial (RPE) cells...
February 14, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28213177/tiered-analytics-for-purity-assessment-of-macrocyclic-peptides-in-drug-discovery-analytical-consideration-and-method-development
#14
Jingfang Jenny Qian Cutrone, Xiaohua Stella Huang, Edward S Kozlowski, Ye Bao, Yingzi Wang, Christopher S Poronsky, Dieter M Drexler, Adrienne A Tymiak
Synthetic macrocyclic peptides with natural and unnatural amino acids have gained considerable attention from a number of pharmaceutical/biopharmaceutical companies in recent years as a promising approach to drug discovery, particularly for targets involving protein-protein or protein-peptide interactions. Analytical scientists charged with characterizing these leads face multiple challenges including dealing with a class of complex molecules with the potential for multiple isomers and variable charge states and no established standards for acceptable analytical characterization of materials used in drug discovery...
February 3, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28213174/evidence-of-the-presence-of-a-calmodulin-sensitive-plasma-membrane-ca-2-atpase-in-trypanosoma-equiperdum
#15
María Carolina Pérez-Gordones, José Rubén Ramírez-Iglesias, Vincenza Cervino, Graciela L Uzcanga, Gustavo Benaim, Marta Mendoza
Trypanosoma equiperdum belongs to the subgenus Trypanozoon, which has a significant socio-economic impact by limiting animal protein productivity worldwide. Proteins involved in the intracellular Ca(2+) regulation are prospective chemotherapeutic targets since several drugs used in experimental treatment against trypanosomatids exert their action through the disruption of the parasite intracellular Ca(2+) homeostasis. Therefore, the plasma membrane Ca(2+)-ATPase (PMCA) is considered as a potential drug target...
February 14, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28213089/monoglyceride-lipase-as-a-drug-target-at-the-crossroads-of-arachidonic-acid-metabolism-and-endocannabinoid-signaling
#16
REVIEW
Gernot F Grabner, Robert Zimmermann, Rudolf Schicho, Ulrike Taschler
Monoglyerides (MGs) are short-lived, intermediary lipids deriving from the degradation of phospho- and neutral lipids, and monoglyceride lipase (MGL), also designated as monoacylglycerol lipase (MAGL), is the major enzyme catalyzing the hydrolysis of MGs into glycerol and fatty acids. This distinct function enables MGL to regulate a number of physiological and pathophysiological processes since both MGs and fatty acids can act as signaling lipids or precursors thereof. The most prominent MG species acting as signaling lipid is 2-arachidonoylglycerol (2-AG) which is the most abundant endogenous agonist of cannabinoid receptors in the body...
February 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28212935/dissecting-biochemical-peculiarities-of-the-atpase-activity-of-tcsub2-a-component-of-the-mrna-export-pathway-in-trypanosoma-cruzi
#17
Ize de Aguiar Bittencourt, Mariana Serpeloni, Priscila Mazzochi Hiraiwa, Tatiana de Arruda Campos Brasil de Souza, Andréa Rodrigues Ávila
The RNA helicase DEAD-box protein Sub2 (yeast)/UAP56 (mammals) is conserved across eukaryotes and is essential for mRNA export in trypanosomes. Despite the high conservation of Sub2 in lower eukaryotes such as Trypanosoma cruzi, the low conservation of other mRNA export factors raises questions regarding whether the mode of action of TcSub2 is similar to that of orthologs from other eukaryotes. Mutation of the conserved K87 residue of TcSub2 abolishes ATPase activity, showing that its ATPase domain is functional...
February 14, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28212930/molecular-recognition-between-pancreatic-lipase-and-natural-and-synthetic-inhibitors
#18
Martiniano Bello, Basilio-Antonio Lucia, Fragoso-Vázquez Jonathan, Avalos-Soriano Anaguiven, Correa-Basurto José
Pancreatic lipase (PL) is a primary lipase critical for triacylglyceride digestion in humans and is considered as a promising target for the treatment of obesity. Although the current synthetic drugs available for treating obesity have been demonstrated to be effective in inhibiting PL, their prolonged usage results in severe side effects. Based on this argument, in this study, we evaluated the structural and energetic features linked to molecular recognition between two well-known PL inhibitors, orlistat (ORL, synthetic inhibitor) and (-)-epigallocatechin gallate (EGCG, natural inhibitor) and PL through molecular dynamics simulations and free energy calculations of ORL and EGCG at the PL binding site when it is isolated (PL) from the heterodimer complex, forming the heterodimer complex with colipase (PLCL) and lacking structural calcium...
February 14, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28212901/the-dissociation-of-the-hsp60-pro-caspase-3-complex-by-bis-pyridyl-oxadiazole-copper-complex-cubipyoxa-leads-to-cell-death-in-nci-h292-cancer-cells
#19
Celeste Caruso Bavisotto, Dragana Nikolic, Antonella Marino Gammazza, Rosario Barone, Filippa Lo Cascio, Emanuele Mocciaro, Giovanni Zummo, Everly Conway de Macario, Alberto Jl Macario, Francesco Cappello, Valentina Giacalone, Andrea Pace, Giampaolo Barone, Antonio Palumbo Piccionello, Claudia Campanella
Cell survival and proliferation are central to carcinogenesis, involving various mechanisms among which those that impede apoptosis are important. In this, the role of the molecular chaperone Hsp60 is unclear since it has been reported that it can be both, pro- or anti-apoptotic. A solution to this riddle is crucial to the development of anti-cancer therapies targeting Hsp60. We addressed this question using a tumor cell line, NCI-H292, and [Cu(3,5-bis(2'-pyridyl)-1,2,4-oxadiazole)2(H2O)2](ClO4)2, CubipyOXA, a copper-containing compound with cytotoxic properties...
February 10, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28212750/conformational-rigidity-and-protein-dynamics-at-distinct-timescales-regulate-ptp1b-activity-and-allostery
#20
Meng S Choy, Yang Li, Luciana E S F Machado, Micha B A Kunze, Christopher R Connors, Xingyu Wei, Kresten Lindorff-Larsen, Rebecca Page, Wolfgang Peti
Protein function originates from a cooperation of structural rigidity, dynamics at different timescales, and allostery. However, how these three pillars of protein function are integrated is still only poorly understood. Here we show how these pillars are connected in Protein Tyrosine Phosphatase 1B (PTP1B), a drug target for diabetes and cancer that catalyzes the dephosphorylation of numerous substrates in essential signaling pathways. By combining new experimental and computational data on WT-PTP1B and ≥10 PTP1B variants in multiple states, we discovered a fundamental and evolutionarily conserved CH/π switch that is critical for positioning the catalytically important WPD loop...
February 16, 2017: Molecular Cell
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