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https://www.readbyqxmd.com/read/28645482/proton-pump-inhibitors-and-survival-outcomes-in-patients-with-metastatic-renal-cell-carcinoma
#1
Aly-Khan A Lalani, Rana R McKay, Xun Lin, Ronit Simantov, Marina D Kaymakcalan, Toni K Choueiri
INTRODUCTION: Proton pump inhibitors (PPIs) are potent inhibitors of gastric acid secretion and can affect the optimal absorption of concomitant oral medications, such as vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKIs). The purpose of this study was to investigate the effect of PPI use on survival in metastatic renal cell carcinoma (mRCC) patients treated in the targeted therapy era. MATERIALS AND METHODS: We conducted a pooled analysis of mRCC patients treated in phase II and III clinical trials...
May 31, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28644196/cebranopadol-a-novel-first-in-class-analgesic-drug-candidate-first-experience-in-patients-with-chronic-low-back-pain-in-a-randomized-clinical-trial
#2
Annette Christoph, Marie-Henriette Eerdekens, Maurits Kok, Gisela Volkers, Rainer Freynhagen
Chronic low back pain (LBP) is a common condition, usually with involvement of nociceptive and neuropathic pain components, high economic burden and impact on quality of life. Cebranopadol is a potent, first-in-class drug candidate with a novel mechanistic approach, combining nociceptin/orphanin FQ peptide and opioid peptide receptor agonism. We conducted the first Phase II, randomized, doubleblind, placebo- and active-controlled trial, evaluating the analgesic efficacy, safety, and tolerability of cebranopadol in patients with moderate to severe chronic LBP with and without neuropathic pain component...
June 21, 2017: Pain
https://www.readbyqxmd.com/read/28642139/clinical-characteristics-and-epidemiology-of-sepsis-in-the-neonatal-intensive-care-unit-in-the-era-of-multi-drug-resistant-organisms-a-retrospective-review
#3
Dawood Yusef, Tala Shalakhti, Samah Awad, Hana'a Algharaibeh, Wasim Khasawneh
BACKGROUND: Sepsis in the neonatal intensive care unit (NICU) remains one of the most significant causes of morbidity and mortality, especially for preterm newborns. Multi-drug resistant organisms (MDROs) are emerging as important pathogens that cause neonatal sepsis in NICU. Therefore, studying the epidemiology, clinical features, and outcome caused by MDROs vs. non-MDROs, and identifying risk factors that may predispose patients to sepsis by MDROs are important. METHODS: Episodes of blood culture-proven sepsis (age: 0-90 days) in the NICU at our institution from January 2012 to December 2015 were retrospectively reviewed...
June 9, 2017: Pediatrics and Neonatology
https://www.readbyqxmd.com/read/28635172/doxorubicin-kinetics-and-effects-on-lung-cancer-cell-lines-using-in-vitro-raman-micro-spectroscopy-binding-signatures-drug-resistance-and-dna-repair
#4
Zeineb Farhane, Franck Bonnier, Orla Howe, Alan Casey, Hugh J Byrne
Raman micro-spectroscopy is a non-invasive analytical tool, whose potential in cellular analysis and monitoring drug mechanisms of action has already been demonstrated, and which can potentially be used in pre-clinical and clinical applications for the prediction of chemotherapeutic efficacy. To further investigate such potential clinical application, it is important to demonstrate its capability to differentiate drug mechanisms of action and cellular resistances. Using the example of Doxorubicin (DOX), in this study, it was used to probe the cellular uptake, signatures of chemical binding and subsequent cellular responses, of the chemotherapeutic drug in two lung cancer cell lines, A549 and Calu-1...
June 21, 2017: Journal of Biophotonics
https://www.readbyqxmd.com/read/28634759/current-applications-of-high-resolution-mass-spectrometry-for-the-analysis-of-new-psychoactive-substances-a-critical-review
#5
REVIEW
Daniel Pasin, Adam Cawley, Sergei Bidny, Shanlin Fu
The proliferation of new psychoactive substances (NPS) in recent years has resulted in the development of numerous analytical methods for the detection and identification of known and unknown NPS derivatives. High-resolution mass spectrometry (HRMS) has been identified as the method of choice for broad screening of NPS in a wide range of analytical contexts because of its ability to measure accurate masses using data-independent acquisition (DIA) techniques. Additionally, it has shown promise for non-targeted screening strategies that have been developed in order to detect and identify novel analogues without the need for certified reference materials (CRMs) or comprehensive mass spectral libraries...
June 20, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28629035/sodium-alginate-polyvinyl-alcohol-bovin-serum-albumin-coated-fe3o4-nanoparticles-as-anticancer-drug-delivery-vehicle-doxorubicin-loading-and-in-vitro-release-study-and-cytotoxicity-to-hepg2-and-l02-cells
#6
G Prabha, V Raj
The challenging part of this work was to research the potential aspects of sodium alginate (SA)-polyvinyl alcohol (PVA)-bovin serum albumin (BSA) coated Fe3O4 nanoparticles (Fe3O4-SA-PVA-BSA) as a drug delivery system for doxorubicin (DOX). The anticancer drug doxorubicin was selected as a model drug which is powerful for numerous cancer treatments. Superparamagnetic Fe3O4 nanoparticles were prepared by co-precipitation method. The mixture solution of Fe3O4-sodium alginate (SA) - doxorubicin (DOX) was crosslinked with Ca(2+) to form (Fe3O4-SA-DOX) nanoparticles and addition of PVA and BSA with (Fe3O4-SA-DOX) nanoparticles was prepared by coating procedure...
October 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28627970/genome-wide-codon-usage-profiling-of-ocular-infective-chlamydia-trachomatis-serovars-and-drug-target-identification
#7
Anupriya Sadhasivam, Umashankar Vetrivel
Chlamydia trachomatis (C.t) is a gram-negative obligate intracellular bacteria and is a major causative of infectious blindness and sexually transmitted diseases. Among the varied serovars of this organism, A, B & C are reported as prominent ocular pathogens. Genomic studies of these strains shall aid in deciphering potential drug targets and genomic influence on pathogenesis. Hence, in this study we performed deep statistical profiling of codon usage in these serovars. The overall base composition analysis reveals that these serovars are over biased to AU than GC...
June 19, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28626016/the-mtor-substrate-s6-kinase-1-s6k1-is-a-negative-regulator-of-axon-regeneration-and-a-potential-drug-target-for-central-nervous-system-injury
#8
Hassan Al-Ali, Ying Ding, Tatiana Slepak, Wei Wu, Yan Sun, Yania Martinez, Xiao-Ming Xu, V P Lemmon, J L Bixby
The mammalian target of Rapamycin (mTOR) positively regulates axon growth in the mammalian central nervous system (CNS). Though axon regeneration and functional recovery from CNS injuries are typically limited, knockdown or deletion of PTEN, a negative regulator of mTOR, increases mTOR activity and induces robust axon growth and regeneration. It has been suggested that inhibition of S6 Kinase 1 (S6K1, gene symbol: RPS6KB1), a prominent mTOR target, would blunt mTOR's positive effect on axon growth. In contrast to this expectation, we demonstrate that inhibition of S6K1 in CNS neurons promotes neurite outgrowth in vitro by 2-3 fold...
June 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28624659/surface-engineering-of-solid-lipid-nanoparticle-assemblies-by-methyl-%C3%AE-d-mannopyranoside-for-the-active-targeting-to-macrophages-in-anti-tuberculosis-inhalation-therapy
#9
Eleonora Maretti, Luca Costantino, Cecilia Rustichelli, Eliana Leo, Maria Antonietta Croce, Francesca Buttini, Eleonora Truzzi, Valentina Iannuccelli
This study describes the development of new mannosylated Solid Lipid Nanoparticle assemblies (SLNas) delivering rifampicin for an inhaled treatment of tuberculosis. SLNas were surface engineered with mannose residues to recognize mannose receptors located on infected alveolar macrophages and facilitate cell internalization. Two sets of SLNas were produced by the melt emulsifying technique using biocompatible lipid components, i.e. cholesteryl myristate combined with palmitic acid (PA set) or tripalmitin (TP set), in the presence of the targeting moiety, methyl α-d-mannopyranoside...
June 15, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28623668/impact-of-pci-appropriateness-in-the-long-term-outcomes-of-consecutive-patients-treated-with-second-generation-drug-eluting-stents
#10
Ana Cristina Seixas, Amanda Sousa, Jose de Ribamar Costa, Adriana Costa Moreira, Ricardo Costa, Lucas Damiani, Cantídio Campos Neto, Galo Maldonado, Manuel Cano, J Eduardo Sousa
BACKGROUND: Appropriate use criteria (AUC) for coronary revascularization were developed to deliver high-quality care; however, the prognostic impact of these criteria remains unclear. We sought to assess the outcomes of patients treated with second-generation drug-eluting stent (DES) classified according to the updated American College of Cardiology Foundation/American Heart Association/Society for Cardiac Angiography and Intervention AUC for percutaneous coronary intervention (PCI)...
June 15, 2017: Journal of Invasive Cardiology
https://www.readbyqxmd.com/read/28622592/second-generation-h1-antihistamines-interaction-with-food-and-alcohol-a-systematic-review
#11
REVIEW
Paweł Paśko, Tomasz Rodacki, Renata Domagała-Rodacka, Krzysztof Palimonka, Monika Marcinkowska, Danuta Owczarek
Histamine is a mediator of many physiological processes. It plays an important role in modulating allergy reactions and immune system responses. H1 receptor is a therapeutic target for drugs applied in allergic diseases such as allergic rhinoconjunctivitis, urticarial, or atopic dermatitis. H1-antihistamines display different chemical structures, pharmacokinetics and a potential for drug-drug and drug-food interactions. Drug-food interactions are known to reduce therapeutic effects of the medicine, as well as to induce a potent adverse drug reactions...
June 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28618197/analysis-of-mutant-allele-fractions-in-driver-genes-in-colorectal-cancer-biological-and-clinical-insights
#12
Rodrigo Dienstmann, Elena Elez, Guillem Argiles, Ignacio Matos, Enrique Sanz-Garcia, Carolina Ortiz, Teresa Macarulla, Jaume Capdevila, Maria Alsina, Tamara Sauri, Helena Verdaguer, Marta Vilaro, Fiorella Ruiz-Pace, Cristina Viaplana, Ariadna Garcia, Stefania Landolfi, Hector G Palmer, Paolo Nuciforo, Jordi Rodon, Ana Vivancos, Josep Tabernero
Sequencing of tumors is now routine and guides personalized cancer therapy. Mutant allele fractions (MAFs, or the 'mutation dose') of a driver gene may reveal the genomic structure of tumors and influence response to targeted therapies. We performed a comprehensive analysis of MAFs of driver alterations in unpaired primary and metastatic colorectal cancer (CRC) at our institution from 2010 to 2015 and studied their potential clinical relevance. Out of 763 CRC samples, 622 had detailed annotation on overall survival in the metastatic setting (OSmet) and 89 received targeted agents matched to KRAS (MEK inhibitors), BRAF (BRAF inhibitors) or PIK3CA mutations (PI3K pathway inhibitors)...
June 15, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28617920/milestone-analyses-of-immune-checkpoint-inhibitors-targeted-therapy-and-conventional-therapy-in-metastatic-non-small-cell-lung-cancer-trials-a-meta-analysis
#13
Gideon M Blumenthal, Lijun Zhang, Hui Zhang, Dickran Kazandjian, Sean Khozin, Shenghui Tang, Kirsten Goldberg, Rajeshwari Sridhara, Patricia Keegan, Richard Pazdur
Importance: Novel intermediate end points may be useful to detect signals of early activity and prioritize new therapies to treat patients with advanced malignant neoplasms, including metastatic non-small cell lung cancer (mNSCLC). Objective: To explore milestone rate, a proposed intermediate end point for immunotherapy trials. Data Sources: Trials submitted to the US Food and Drug Administration with more than 150 patients and in which the intention-to-treat population was assessed were identified...
June 15, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28617226/contextualization-of-drug-mediator-relations-using-evidence-networks
#14
Hai Joey Tran, Gil Speyer, Jeff Kiefer, Seungchan Kim
BACKGROUND: Genomic analysis of drug response can provide unique insights into therapies that can be used to match the "right drug to the right patient." However, the process of discovering such therapeutic insights using genomic data is not straightforward and represents an area of active investigation. EDDY (Evaluation of Differential DependencY), a statistical test to detect differential statistical dependencies, is one method that leverages genomic data to identify differential genetic dependencies...
May 31, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28615203/phosphorylation-of-serine-225-in-hepatitis-c-virus-ns5a-regulates-protein-protein-interactions
#15
Niluka Goonawardane, Anna Gebhardt, Christopher Bartlett, Andreas Pichlmair, Mark Harris
Hepatitis C virus (HCV) non-structural protein 5A (NS5A) is a phosphoprotein that plays key, yet poorly defined, roles in both virus genome replication and virion assembly/release. It has been proposed that differential phosphorylation could act as a switch to regulate the various functions of NS5A, however the mechanistic details of the role of this post-translational modification in the virus life cycle remains obscure. We previously reported (Ross-Thriepland et al, 2015) a role for phosphorylation at serine 225 (S225) of NS5A in the regulation of JFH-1 (genotype 2a) genome replication...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28611957/genetic-virulence-profile-of-enteroaggregative-escherichia-coli-strains-isolated-from-danish-children-with-either-acute-or-persistent-diarrhea
#16
Betina Hebbelstrup Jensen, Anja Poulsen, Stig Hebbelstrup Rye Rasmussen, Carsten Struve, Jørgen H Engberg, Alice Friis-Møller, Nadia Boisen, Rie Jønsson, Randi F Petersen, Andreas M Petersen, Karen A Krogfelt
Enteroaggregative Escherichia coli (EAEC) is frequently found in diarrheal stools worldwide. It has been associated with persistent diarrhea, weight loss, and failure to thrive in children living in developing countries. A number of important EAEC virulence genes are identified; however, their roles in acute and persistent diarrhea have not been previously investigated. The aim of this study was to identify specific EAEC virulence genes associated with duration and type of diarrhea in Danish children. We aimed to improve the current diagnostics of EAEC and enable targeting of strains with an expected severe disease course...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28611939/selective-targeting-of-the-l858r-mutation-egfr-in-non-small-cell-lung-cancer-a-mechanism-for-advancing-targeted-chemotherapy
#17
Rohan Arora, Venkat Krishnan
Lung cancer remains one of today's most deadly and intractable cancers. Non-small cell lung cancer (NSCLC) accounts for roughly 85% of lung cancers, with an extremely poor survival rate. To ensure patient comfort and survival, the development of a selective therapy is imperative. However, lung cancer does not display surface proteins associated uniquely with tumor cells; thus, it is very difficult to develop a tumor-specific drug. Current techniques that target overexpression of proteins or inhibit growth pathways are either non-specific or prone to rapid drug resistance...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28599476/identification-of-gene-markers-associated-with-metastasis-in-clear-cell-renal-cell-carcinoma
#18
Hailing Yang, Pengfei Huo, Guozhang Hu, Bo Wei, Dalian Kong, Hongjun Li
The present study aimed to screen potential target genes for the early diagnosis and treatment of early metastatic clear cell renal cell carcinoma (ccRCC) using the microarray data of early metastatic and non-metastatic ccRCC samples. The DNA microarray dataset GSE47352 was downloaded from Gene Expression Omnibus and included 4 early metastatic and 5 non-metastatic ccRCC samples. Differentially expressed genes (DEGs) were screened using the limma package. Then, pheatmap package was used to conduct two-way clustering for the DEGs...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28597356/structural-insight-into-the-role-of-gln293met-mutation-on-the-peloruside-a-laulimalide-association-with-%C3%AE-%C3%AE-tubulin-from-molecular-dynamics-simulations-binding-free-energy-calculations-and-weak-interactions-analysis
#19
Matías A Zúñiga, Joel B Alderete, Gonzalo A Jaña, Verónica A Jiménez
Peloruside A (PLA) and Laulimalide (LAU) are novel microtubule-stabilizing agents with promising properties against different cancer types. These ligands share a non-taxoid binding site at the outer surface of β-tubulin and promote microtubule stabilization by bridging two adjacent αβ-tubulin dimers from parallel protofilaments. Recent site-directed mutagenesis experiments confirmed the existence of a unique β-tubulin site mutation (Gln293Met) that specifically increased the activity of PLA and caused resistance to LAU, without affecting the stability of microtubules in the absence of the ligands...
June 9, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28595540/apicoplast-import-protein-tic20-a-promising-therapeutic-molecular-target-for-plasmodium-falciparum-an-insilico-approach-for-therapeutic-intervention
#20
Pavan C P K Srimath-Tirumala-Peddinti, Sandeep Solmon Kusuma, Deepthi Nammi, Nageswara Rao Reddy Neelapu
Malaria is a lethal disease causing mortality to over millions each year. Drug resistance in the malarial parasite encouraged to discover effective antimalarial drug targets and drugs. An objective of this current study is to identify drug targets for malarial parasite. Genes unique, non-homologous to humans and essential for parasite are identified using BLASTn by comparing genomes between parasite and host. Further open BLASTp was used to filter the targets specific to Plasmodium species and later were subjected to gene property analysis to identify 65 potential targets...
June 5, 2017: Infectious Disorders Drug Targets
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