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https://www.readbyqxmd.com/read/28528510/immunogenomics-using-genomics-to-personalize-cancer-immunotherapy
#1
Rance C Siniard, Shuko Harada
While the use of genomic data has the potential to revolutionize patient care, there is still much work to be done with regard to the transformation of host-tumor interactions into favorable clinical outcomes for our patients. High-throughput technologies, such as next-generation sequencing (NGS), have rapidly advanced our understanding of oncology, and we are learning that most tumors do not simply possess consistently mutated genes that are responsible for tumorigenesis, facilitating the need for personalized cancer therapy...
May 20, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28528286/assessing-the-stable-conformations-of-ibuprofen-in-solution-by-means-of-residual-dipolar-couplings
#2
Maria Enrica Di Pietro, Giorgio Celebre, Christie Aroulanda, Denis Merlet, Giuseppina De Luca
Detailing the conformational equilibria between global and local minimum energy structures of anti-inflammatory α-arylpropionic acids directly in solution is of the utmost importance for a better understanding of the structure-activity relationships, hence providing valuable clues for rational structure-based drug design studies. Here the conformational preferences of the widely used pharmaceutical ibuprofen were investigated in solution by NMR spectroscopy in weakly ordering phases. A thorough theoretical treatment of the anisotropic interactions that are relevant for NMR spectra led to a conformational model characterized by six pairs of symmetry-related conformers, in particular four couples of gauche structures, with a total probability of 93%, and 2 couples of trans structures, counting for the remaining 7%...
May 17, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28528283/poly-vinyl-alcohol-hydroxyapatite-monolithic-in-needle-extraction-mine-device-preparation-and-examination-of-drug-affinity
#3
Monika Pietrzyńska, Michał Czerwiński, Adam Voelkel
Polymer-ceramic materials based on poly(vinyl alcohol) (PVA) and hydroxyapatite were applied as sorption material in Monolithic In-Needle Extraction (MINE) device. The presented device provides new possibilities for the examination of bisphosphonates affinity for bone and will be a helpful tool in evaluation of potential antiresorptive drugs suitability. A ceramic part of monoliths was prepared by incorporation of hydroxyapatite (HA) into the reaction mixture or by using a soaking method (mineralization of HA on the PVA)...
May 17, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28527735/advances-in-combination-therapy-of-lung-cancer-rationales-delivery-technologies-and-dosage-regimens
#4
REVIEW
Lan Wu, Donglei Leng, Dongmei Cun, Camilla Foged, Mingshi Yang
Lung cancer is a complex disease caused by a multitude of genetic and environmental factors. The progression of lung cancer involves dynamic changes in the genome and a complex network of interactions between cancer cells with multiple, distinct cell types that form tumors. Combination therapy using different pharmaceuticals has been proven highly effective due to the ability to affect multiple cellular pathways involved in the disease progression. However, the currently used drug combination designs are primarily based on empirical clinical studies, and little attention has been given to dosage regimens, i...
May 17, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28527708/cortical-cytoskeleton-dynamics-regulates-plasma-membrane-calcium-atpase-isoform-2-pmca2-activity
#5
Marianela G Dalghi, Mariela Ferreira-Gomes, Nicolás Montalbetti, Alexandre Simonin, Emanuel E Strehler, Matthias A Hediger, Juan Pablo Rossi
We have previously shown that purified actin can directly bind to human plasma membrane Ca(2+) ATPase 4b (hPMCA4b) and exert a dual modulation on its Ca(2+)-ATPase activity: F-actin inhibits PMCA while short actin oligomers may contribute to PMCA activation. These studies had to be performed with purified proteins given the nature of the biophysical and biochemical approaches used. To assess whether a functional interaction between the PMCAs and the cortical cytoskeleton is of physiological relevance, we characterized this phenomenon in the context of a living cell by monitoring in real-time the changes in the cytosolic calcium levels ([Ca(2+)]CYT)...
May 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28527265/-profile-of-lithium-carbonate-use-in-patients-with-bipolar-disorder-in-colombia
#6
Manuel Enrique Machado-Duque, Catalina Alzate-Carvajal, Kevin Zapata-Castañeda, Jorge Enrique Machado-Alba
INTRODUCTION: Lithium is the drug of choice for the treatment of bipolar affective disorder. OBJECTIVE: To define lithium therapeutic profile and adverse reactions to its use in patients with bipolar affective disorder in Colombia. MATERIALS AND METHODS: We conducted an observational retrospective cohort study between January 1 and December 31, 2013, which included patients with a diagnosis of bipolar disorder treated with lithium carbonate in 25 Colombian cities; we evaluated socio-demographic variables, lithium dose, co-medication, drug interactions and adverse reactions...
April 1, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28527154/structure-based-classification-for-bile-salt-export-pump-bsep-inhibitors-using-comparative-structural-modeling-of-human-bsep
#7
Sankalp Jain, Melanie Grandits, Lars Richter, Gerhard F Ecker
The bile salt export pump (BSEP) actively transports conjugated monovalent bile acids from the hepatocytes into the bile. This facilitates the formation of micelles and promotes digestion and absorption of dietary fat. Inhibition of BSEP leads to decreased bile flow and accumulation of cytotoxic bile salts in the liver. A number of compounds have been identified to interact with BSEP, which results in drug-induced cholestasis or liver injury. Therefore, in silico approaches for flagging compounds as potential BSEP inhibitors would be of high value in the early stage of the drug discovery pipeline...
May 19, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28527149/characterisation-of-drug-related-problems-and-associated-factors-at-a-clinical-pharmacist-service-na%C3%A3-ve-hospital-in-northern-sweden
#8
Cecilia Peterson, Maria Gustafsson
BACKGROUND: Polypharmacy and increased sensitivity to side effects cause adverse drug events, drug-drug interactions and medication errors in the elderly. OBJECTIVE: The objective of this study was to investigate the prevalence and type of drug-related problems and associated factors among patients admitted to a clinical pharmacist service-naïve medical ward in an inland hospital in northern Sweden. METHODS: During September-November 2015 and February-April 2016, clinical pharmacists working as part of a ward team on the medical ward conducted 103 medication reviews...
May 19, 2017: Drugs—Real World Outcomes
https://www.readbyqxmd.com/read/28527127/evaluation-of-heparg-cells-for-the-assessment-of-indirect-drug-induced-hepatotoxicity-using-inh-as-a-model-substance
#9
Anika Mann, Thomas Pelz, Knut Rennert, Alexander Mosig, Michael Decker, Amelie Lupp
HepaRG cells are widely used as an in vitro model to assess drug-induced hepatotoxicity. However, only few studies exist so far regarding their suitability to detect the effects of drugs requiring a preceding activation via the cytochrome P450 (CYP) system. A prototypic substance is the anti-tuberculosis agent INH, which is metabolized into N-acetylhydrazine, which then triggers hepatotoxicity. Therefore, the aim of the present study was to test if this effect can also be detected in HepaRG cells and if it can be counteracted by the known hepatoprotectant silibinin...
May 19, 2017: Human Cell
https://www.readbyqxmd.com/read/28527109/erratum-to-clinical-pharmacokinetics-of-sacubitril-valsartan-lcz696-a-novel-angiotensin-receptor-neprilysin-inhibitor
#10
Surya Ayalasomayajula, Thomas Langenickel, Parasar Pal, Sreedevi Boggarapu, Gangadhar Sunkara
Sacubitril/valsartan (LCZ696) is indicated for the treatment of heart failure with reduced ejection fraction. Absorption of sacubitril/valsartan and conversion of sacubitril (prodrug) to sacubitrilat (neprilysin inhibitor) was rapid with maximum plasma concentrations of sacubitril, sacubitrilat, and valsartan (angiotensin receptor blocker) reaching within 0.5, 1.5-2.0, and 2.0-3.0 h, respectively. With a twofold increase in dose, an increase in the area under the plasma concentration-time curve was proportional for sacubitril, ~1...
May 19, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28527093/income-disparities-in-healthcare-use-remain-after-controlling-for-healthcare-need-evidence-from-swedish-register-data-on-psoriasis-and-psoriatic-arthritis
#11
Sofia Löfvendahl, Anna Jöud, Ingemar F Petersson, Elke Theander, Åke Svensson, Katarina Steen Carlsson
We used a southern Swedish cohort of psoriasis (PSO) and psoriatic arthritis (PsA) patients and population-based referents (N = 57,800) to investigate the influence of socioeconomic and demographic factors on the probability of healthcare use and on healthcare costs when controlling for need as measured by PSO/PsA and common additional morbidities such as diabetes, depression and myocardial infarction. People with PSO/PsA were identified by ICD-10 codes in the Skåne Healthcare Register 1998-2007. Resource use and costs for years 2008-2011 were retrieved from the Skåne Healthcare Register and the Swedish Prescribed Drug Register, and socioeconomic data were retrieved from Statistics Sweden...
May 19, 2017: European Journal of Health Economics: HEPAC: Health Economics in Prevention and Care
https://www.readbyqxmd.com/read/28527083/shared-mechanisms-of-epilepsy-migraine-and-affective-disorders
#12
Davide Zarcone, Simona Corbetta
Since the nineteenth century several clinical features have been observed in common between migraine and epilepsy (such as episodic attacks, triggering factors, presence of aura, frequent familiarity), but only in recent years researchers have really engaged in finding a common pathogenic mechanism. From studies of disease incidence, we understand how either migraine among patients with epilepsy or epilepsy among migraine patients are more frequent than in the general population. This association may result from a direct causality, by the same environmental risk factors and/or by a common genetic susceptibility...
May 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28527057/behavioral-therapy-emotion-and-pain-a-common-anatomical-background
#13
Lauren A-M Dahlke, Jeffrey J Sable, Frank Andrasik
Emotion and pain are closely intertwined in the brain, as the human experience of pain includes both affective and nociceptive components. Although each of these components relies on a different system in the brain, the two systems converge on the anterior cingulate and insular cortices, which interact with the prefrontal cortex and other frontal structures to influence behavior. Both emotional and physical pain elicit activity in these common areas, and conditions that affect one system (e.g., drugs, neural plasticity) may affect the function of the other-ultimately altering the experience of pain...
May 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28526744/combining-properties-of-different-classes-of-pi3k%C3%AE-inhibitors-to-understand-molecular-features-that-confer-selectivity
#14
Grace Q Gong, Jackie D Kendall, James Mj Dickson, Gordon W Rewcastle, Christina M Buchanan, William A Denny, Peter R Shepherd, Jack U Flanagan
Phosphoinositide 3-kinases (PI3K) are major regulators of many cellular functions, and hyperactivation of PI3K cell signalling pathways is a major target for anticancer drug discovery. PI3Kα is the isoform most implicated in cancer, and our aim is to selectively inhibit this isoform, which may be more beneficial than concurrent inhibition of all Class I PI3Ks. We have used structure-guided design to merge high selectivity and high affinity characteristics found in existing compounds. Molecular docking including the prediction of water-mediated interactions, was used to model interactions between the ligands and the PI3Kα affinity pocket...
May 19, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28526536/trastuzumab-emtansine-versus-capecitabine-plus-lapatinib-in-patients-with-previously-treated-her2-positive-advanced-breast-cancer-emilia-a-descriptive-analysis-of-final-overall-survival-results-from-a-randomised-open-label-phase-3-trial
#15
Véronique Diéras, David Miles, Sunil Verma, Mark Pegram, Manfred Welslau, José Baselga, Ian E Krop, Kim Blackwell, Silke Hoersch, Jin Xu, Marjorie Green, Luca Gianni
BACKGROUND: The antibody-drug conjugate trastuzumab emtansine is indicated for the treatment of patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. Approval of this drug was based on progression-free survival and interim overall survival data from the phase 3 EMILIA study. In this report, we present a descriptive analysis of the final overall survival data from that trial. METHODS: EMILIA was a randomised, international, open-label, phase 3 study of men and women aged 18 years or older with HER2-positive unresectable, locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane...
May 16, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28526153/pharmacology-of-octreotide-clinical-implications-for-anesthesiologists-and-associated-risks
#16
REVIEW
Reza M Borna, Jonathan S Jahr, Susanna Kmiecik, Ken F Mancuso, Alan D Kaye
Many patients presenting with a history of foregut, midgut neuroendocrine tumors (NETs) or carcinoid syndrome can experience life-threatening carcinoid crises during anesthesia or surgery. Clinicians should understand the pharmacology of octreotide and appreciate the use of continuous infusions of high-dose octreotide, which can minimize intraoperative carcinoid crises. We administer a prophylactic 500-μg bolus of octreotide intravenously (IV) and begin a continuous infusion of 500 μg/h for all NET patients...
June 2017: Anesthesiology Clinics
https://www.readbyqxmd.com/read/28526123/-direct-mechanism-of-action-in-toxic-myopathies
#17
REVIEW
A Khelfi, M Azzouz, R Abtroun, M Reggabi, B Alamir
Toxic myopathies are a large group of disorders generated by surrounding agents and characterized by structural and/or functional disturbances of muscles. The most recurrent are those induced by commonly used medications. Illicit drugs, environmental toxins from animals, vegetables, or produced by micro-organisms as well as chemical products commonly used are significant causes of such disorders. The muscle toxicity results from multiple mechanisms at different biological levels. Many agents can induce myotoxicity through a direct mechanism in which statins, glucocorticoids and ethyl alcohol are the most representative...
May 16, 2017: Annales Pharmaceutiques Françaises
https://www.readbyqxmd.com/read/28526079/patient-needs-and-preferences-for-herb-drug-disease-interaction-alerts-a-structured-interview-study
#18
Carrie M Christensen, Rebecca S Morris, Seraphine Chepkemoi Kapsandoy, Melissa Archer, Jinqiu Kuang, Laura Shane-McWhorter, Bruce E Bray, Qing Zeng-Treitler
BACKGROUND: While complementary and alternative medicine (CAM) is commonly used in the United States and elsewhere, and hazardous interactions with prescription drugs can occur, patients do not regularly communicate with physicians about their CAM use. The objective of this study was to discover patient information needs and preferences for herb-drug-disease interaction alerts. METHODS: We recruited 50 people from several locations within the University of Utah Hospital to participate in this structured interview study...
May 19, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28525968/survivalgwas_sv-software-for-the-analysis-of-genome-wide-association-studies-of-imputed-genotypes-with-time-to-event-outcomes
#19
Hamzah Syed, Andrea L Jorgensen, Andrew P Morris
BACKGROUND: Analysis of genome-wide association studies (GWAS) with "time to event" outcomes have become increasingly popular, predominantly in the context of pharmacogenetics, where the survival endpoint could be death, disease remission or the occurrence of an adverse drug reaction. However, methodology and software that can efficiently handle the scale and complexity of genetic data from GWAS with time to event outcomes has not been extensively developed. RESULTS: SurvivalGWAS_SV is an easy to use software implemented using C# and run on Linux, Mac OS X & Windows operating systems...
May 19, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28525957/determining-dominant-driving-forces-affecting-controlled-protein-release-from-polymeric-nanoparticles
#20
Josh Smith, Kayla G Sprenger, Rick Liao, Andrea Joseph, Elizabeth Nance, Jim Pfaendtner
Enzymes play a critical role in many applications in biology and medicine as potential therapeutics. One specific area of interest is enzyme encapsulation in polymer nanostructures, which have applications in drug delivery and catalysis. A detailed understanding of the mechanisms governing protein/polymer interactions is crucial for optimizing the performance of these complex systems for different applications. Using a combined computational and experimental approach, this study aims to quantify the relative importance of molecular and mesoscale driving forces to protein release from polymeric nanoparticles...
May 19, 2017: Biointerphases
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