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Clinic pharmacology

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https://www.readbyqxmd.com/read/28922779/targeting-the-myofibroblastic-cancer-associated-fibroblast-phenotype-through-inhibition-of-nox4
#1
Christopher J Hanley, Massimiliano Mellone, Kirsty Ford, Steve M Thirdborough, Toby Mellows, Steven J Frampton, David M Smith, Elena Harden, Cedric Szyndralewiez, Marc Bullock, Fergus Noble, Karwan A Moutasim, Emma V King, Pandurangan Vijayanand, Alex H Mirnezami, Timothy J Underwood, Christian H Ottensmeier, Gareth J Thomas
Background: Cancer-associated fibroblasts (CAFs) are tumor-promoting and correlate with poor survival in many cancers, which has led to their emergence as potential therapeutic targets. However, effective methods to manipulate these cells clinically have yet to be developed. Methods: CAF accumulation and prognostic significance in head and neck cancer (oral, n = 260; oropharyngeal, n = 271), and colorectal cancer (n = 56) was analyzed using immunohistochemistry...
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28922421/effects-of-acute-administration-of-donepezil-or-memantine-on-sleep-deprivation-induced-spatial-memory-deficit-in-young-and-aged-non-human-primate-grey-mouse-lemurs-microcebus-murinus
#2
Anisur Rahman, Yves Lamberty, Esther Schenker, Massimo Cella, Solène Languille, Régis Bordet, Jill Richardson, Fabien Pifferi, Fabienne Aujard
The development of novel therapeutics to prevent cognitive decline of Alzheimer's disease (AD) is facing paramount difficulties since the translational efficacy of rodent models did not resulted in better clinical results. Currently approved treatments, including the acetylcholinesterase inhibitor donepezil (DON) and the N-methyl-D-aspartate antagonist memantine (MEM) provide marginal therapeutic benefits to AD patients. There is an urgent need to develop a predictive animal model that is phylogenetically proximal to humans to achieve better translation...
2017: PloS One
https://www.readbyqxmd.com/read/28921650/antibody-drug-conjugates-as-cancer-therapeutics-past-present-and-future
#3
Heather E Vezina, Monette Cotreau, Tae H Han, Manish Gupta
Antibody-drug conjugates (ADCs) represent an innovative therapeutic approach that provides novel treatment options and hope for patients with cancer. By coupling monoclonal antibodies (mAbs) to cytotoxic small-molecule payloads with a plasma-stable linker, ADCs offer the potential for increased drug specificity and fewer off-target effects than systemic chemotherapy. As evidence for the potential of these therapies, many new ADCs are in various stages of clinical development. Because their structure poses unique challenges to pharmacokinetic and pharmacodynamic characterization, it is critical to recognize the differences between ADCs and conventional chemotherapy in the design of ADC clinical development strategies...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921644/clinical-pharmacology-considerations-for-the-development-of-immune-checkpoint-inhibitors
#4
Jennifer Sheng, Shivani Srivastava, Kinjal Sanghavi, Zheng Lu, Brian J Schmidt, Akintunde Bello, Manish Gupta
Immuno-oncology works through activation of the patient's immune system against cancer, with several advantages over other treatment approaches, including cytotoxic agents and molecular-targeted therapies. The most notable feature of immuno-oncology treatments is the nature of the patient responses achieved, which can be more durable and sustained than with other modalities. Increased understanding of immune system complexity has provided a number of opportunities to advance several strategies for the development of immuno-oncology therapies...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921642/clinical-pharmacology-tools-and-evaluations-to-facilitate-comprehensive-dose-finding-in-oncology-a-continuous-risk-benefit-approach
#5
Julie M Bullock, Tiffany Lin, Sanela Bilic
Targeted therapies are now considered an integral component in the treatment armamentarium for many malignancies, and the approach to developing these drugs needs to be refined from the previous cytotoxic paradigm of toxicity-guided dose finding and identification of maximum tolerated dose to a paradigm driven by target activity. Moving away from the toxicity-driven dose finding and justification model requires an integrated approach in order to adequately characterize the risk-benefit of a drug. This approach starts with understanding the importance of collecting samples for pharmacokinetic and pharmacodynamic assessments in all phases of clinical development to fully characterize the pharmacokinetics and identify covariates and then correlating exposure to key markers of safety and efficacy in pharmacometric analyses to perform a robust risk-benefit assessment and establish the right dose...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921641/pharmacokinetic-guided-dosing-of-new-oral-cancer-agents
#6
Catherine J Lucas, Jennifer H Martin
Generally, licensed drug-dosing recommendations for chemotherapy are based on results from clinical trials in which subjects are usually of relatively normal body size, middle-aged, and are relatively racially homogeneous, with minimal comorbidity and specific tumor characteristics. Very few nontrial patients meet these characteristics, resulting in clinical practice having to extrapolate dosing recommendations to the specific patient. There is insufficient research on the impact of obesity-associated physiological changes prevalent in patients with common cancers on standard pharmacokinetic and pharmacodynamic parameters...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921640/the-role-of-clinical-pharmacology-in-oncology-dose-selection-advances-and-opportunities-in-personalized-medicine
#7
Stacy S Shord
No abstract text is available yet for this article.
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921612/systematic-review-and-meta-analysis-of-non-pharmacological-interventions-to-reduce-the-symptoms-of-mild-to-moderate-anxiety-in-pregnant-women
#8
REVIEW
Kerry Evans, C Jane Morrell, Helen Spiby
AIM: To assess the effectiveness of non-pharmacological interventions for pregnant women with symptoms of mild to moderate anxiety. BACKGROUND: Many pregnant women experience mild to moderate symptoms of anxiety and could benefit from additional support. Non-pharmacological interventions have been suggested for use during pregnancy. DESIGN: A systematic review of randomised controlled trials. DATA SOURCES: Randomised controlled trials published since 1990, identified from electronic databases: Medline; CINAHL; Maternity and Infant Care; PsycINFO; Cochrane Database of Systematic Reviews; CENTRAL; EMBASE; Centre for Reviews and Dissemination; Social Sciences Citation Index; ASSIA; HTA Library; Joanna Briggs Institute Evidence-Based Practice database; Allied and Complementary Medicine...
September 16, 2017: Journal of Advanced Nursing
https://www.readbyqxmd.com/read/28921504/g%C3%AE-12-facilitates-carbachol-induced-shortening-in-human-airway-smooth-muscle-by-modulating-phosphoinositide-3-kinase-mediated-activation-in-a-rhoa-dependent-manner
#9
Edwin J Yoo, Gaoyuan Cao, Cynthia J Koziol-White, Christie A Ojiaku, Krishna Sunder, Joseph A Jude, James V Michael, Hong Lam, Ivan Pushkarsky, Robert Damoiseaux, Dino Di Carlo, Kwangmi Ahn, Steven S An, Raymond B Penn, Reynold A Panettieri
BACKGROUND AND PURPOSE: Phosphoinositide 3-kinase (PI3K)-dependent activation of Rho kinase (ROCK) is necessary for agonist-induced human airway smooth muscle cell (HASMC) contraction, and inhibition of PI3K promotes bronchodilation of human small airways. The upstream mechanisms driving agonist-mediated PI3K/ROCK axis activation, however, remain unclear. Given the capacity of G12 family proteins to activate ROCK pathways in other cell types (Riobo and Manning, 2005), the role of G12 proteins in modulating M3 muscarinic acetylcholine receptor (M3R)-stimulated PI3K/ROCK activation and HASMC contraction was examined...
September 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28921125/exogenous-cannabinoid-efficacy-merely-a-pharmacokinetic-interaction
#10
Jennifer H Martin, Jennifer Schneider, Catherine J Lucas, Peter Galettis
Endocannabinoid pharmacology is now relatively well understood with a number of endocannabinoids and endogenous cannabinoid neurotransmitters identified and the pharmacokinetics relatively well ascertained. Further, the cannabinoid receptors are now molecularly and pharmacologically characterised and the cell processes involved in endocannabinoid transcription, synthesis, post-translational modification and protein expression are reported. Endogenous cannabinoids have been shown to have key roles in immune and pain pathways and neuro-behavioural signalling including appetite regulation...
September 18, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28920461/discovery-and-development-of-tramadol-for-the-treatment-of-pain
#11
Lidia Bravo, Juan Antonio Mico, Esther Berrocoso
Tramadol is an opioid drug that, unlike classic opioids, also modulates the monoaminergic system by inhibiting noradrenergic and serotoninergic reuptake. For this reason, tramadol is considered an atypical opioid. These special pharmacological characteristics have made tramadol one of the most commonly prescribed analgesic drugs to treat moderate to severe pain. Areas covered: The aim of this review is to provide a historical description of the biochemistry, pharmacokinetics and particularly, the mechanisms of action of tramadol...
September 17, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28920153/optimizing-somatostatin-analog-use-in-well-or-moderately-differentiated-gastroenteropancreatic-neuroendocrine-tumors
#12
REVIEW
Alberto Carmona-Bayonas, Paula Jiménez-Fonseca, Ana Custodio, Enrique Grande, Jaume Capdevila, Carlos López, Alex Teule, Rocío Garcia-Carbonero
BACKGROUND: Somatostatin analogues, aiming to control tumor secretion or growth, constitute the most attractive therapeutic option for patients with well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The objective of this article is to provide a comprehensive review of the current state-of-the-art knowledge gaps and potential opportunities for future development and optimization of this therapeutic modality. METHOD: A contextualized systematic review with a narrative component was conducted using PubMed, The Cochrane Library, EMBASE, and Google Scholar...
September 18, 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28920044/effect-of-multisensory-stimulation-on-pain-of-eye-examination-in-preterm-infants
#13
Hossein Zeraati, Javad Shahinfar, Hamidreza Behnam Vashani, Tayebeh Reyhani
BACKGROUND: Eye examination as one of the painful procedures for retinopathy of prematurity screening can cause some pain-related physiological and behavioral changes in preterm infants. Multisensory stimulation is an analgesic non-pharmacological method that has analgesic effects on infants during painful procedures. OBJECTIVES: This study aimed to determine the effect of multisensory stimulation on induced pain during eye examination for retinopathy of prematurity screening in preterm infants...
February 2017: Anesthesiology and Pain Medicine
https://www.readbyqxmd.com/read/28920007/towards-treatment-of-stargardt-disease-workshop-organized-and-sponsored-by-the-foundation-fighting-blindness
#14
REVIEW
Avery E Sears, Paul S Bernstein, Artur V Cideciyan, Carel Hoyng, Peter Charbel Issa, Krzysztof Palczewski, Philip J Rosenfeld, SriniVas Sadda, Ulrich Schraermeyer, Janet R Sparrow, Ilyas Washington, Hendrik P N Scholl
Accumulation of fluorescent metabolic byproducts of the visual (retinoid) cycle is associated with photoreceptor and retinal pigment epithelial cell death in both Stargardt disease and atrophic (nonneovascular) age-related macular degeneration (AMD). As a consequence of this observation, small molecular inhibitors of enzymes in the visual cycle were recently tested in clinical trials as a strategy to protect the retina and retinal pigment epithelium in patients with atrophic AMD. To address the clinical translational needs for therapies aimed at both diseases, a workshop organized by the Foundation Fighting Blindness was hosted by the Department of Pharmacology at Case Western Reserve University on February 17, 2017, at the Tinkham Veale University Center, Cleveland, OH, USA...
September 2017: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/28919990/pharmacological-targeting-of-peptidylarginine-deiminase-4-prevents-cancer-associated-kidney-injury-in-mice
#15
Jessica Cedervall, Anca Dragomir, Falk Saupe, Yanyu Zhang, Johan Ärnlöv, Erik Larsson, Anna Dimberg, Anders Larsson, Anna-Karin Olsson
Renal insufficiency is a frequent cancer-associated problem affecting more than half of all cancer patients at the time of diagnosis. To minimize nephrotoxic effects the dosage of anticancer drugs are reduced in these patients, leading to sub-optimal treatment efficacy. Despite the severity of this cancer-associated pathology, the molecular mechanisms, as well as therapeutic options, are still largely lacking. We here show that formation of intravascular tumor-induced neutrophil extracellular traps (NETs) is a cause of kidney injury in tumor-bearing mice...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919721/profile-of-sodium-phenylbutyrate-granules-for-the-treatment-of-urea-cycle-disorders-patient-perspectives
#16
REVIEW
Luis Peña-Quintana, Marta Llarena, Desiderio Reyes-Suárez, Luis Aldámiz-Echevarria
Urea-cycle disorders are a group of rare hereditary metabolic diseases characterized by deficiencies of one of the enzymes and transporters involved in the urea cycle, which is necessary for the removal of nitrogen produced from protein breakdown. These hereditary metabolic diseases are characterized by hyperammonemia and life-threatening hyperammonemic crises. Pharmacological treatment of urea-cycle disorders involves alternative nitrogen-scavenging pathways. Sodium benzoate combines with glycine and phenylacetate/phenylbutyrate with glutamine, forming, respectively, hippuric acid and phenylacetylglutamine, which are eliminated in the urine...
2017: Patient Preference and Adherence
https://www.readbyqxmd.com/read/28919712/recent-developments-in-the-clinical-pharmacology-of-rolapitant-subanalyses-in-specific-populations
#17
REVIEW
Bernardo Leon Rapoport, Matti Aapro, Martin R Chasen, Karin Jordan, Rudolph M Navari, Ian Schnadig, Lee Schwartzberg
Knowledge of the involvement of the neurokinin substance P in emesis has led to the development of the neurokinin-1 receptor antagonists (NK-1 RAs) for control of chemotherapy-induced nausea and vomiting (CINV), in combination with serotonin type 3 receptor antagonists and corticosteroids. The NK-1 RA rolapitant, recently approved in oral formulation, has nanomolar affinity for the NK-1 receptor, as do the other commercially available NK-1 RAs, aprepitant and netupitant. Rolapitant is rapidly absorbed and has a long half-life in comparison to aprepitant and netupitant...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28919704/secondary-prevention-of-major-cerebrovascular-events-with-seven-different-statins-a-multi-treatment-meta-analysis
#18
Ping Zhong, Danhong Wu, Xiaofei Ye, Ying Wu, Tuming Li, Shuwen Tong, Xueyuan Liu
BACKGROUND: Statins have been recommended for the use in atherosclerotic cardiovascular diseases, but different statins have distinct pharmacological characteristics. This multi-treatment meta-analysis aimed to evaluate the efficacy of seven statins in the secondary prevention of major cerebrovascular events (CVEs). METHODS AND ANALYSES: The PubMed, Embase, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials were searched to identify studies published between January 1, 2011, and June 30, 2016...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28919375/the-association-between-leukotriene-modifying-agents-and-suicidality-a-review-of-literature
#19
REVIEW
Faiza Khalid, Awais Aftab, Sumita Khatri
BACKGROUND: In 2008 Food and Drug Administration issued a warning regarding a possible association between leukotriene-modifying agents and suicidality. OBJECTIVE: The warning remains controversial and this review of literature is an attempt to examine the evidence on the matter. METHODS: Literature search on PubMed. RESULTS: The data supporting a relationship between leukotriene-modifying agents and suicidality comes primarily from reviews of individual safety reports in adverse event databases; it is subject to considerable reporting bias and does not control for confounding factors...
August 9, 2017: Psychosomatics
https://www.readbyqxmd.com/read/28919335/the-effect-of-resistance-exercise-on-sleep-a-systematic-review-of-randomized-controlled-trials
#20
REVIEW
Ana Kovacevic, Yorgi Mavros, Jennifer J Heisz, Maria A Fiatarone Singh
Impaired sleep quality and quantity are associated with future morbidity and mortality. Exercise may be an effective non-pharmacological intervention to improve sleep, however, little is known on the effect of resistance exercise. Thus, we performed a systematic review of the literature to determine the acute and chronic effects of resistance exercise on sleep quantity and quality. Thirteen studies were included. Chronic resistance exercise improves all aspects of sleep, with the greatest benefit for sleep quality...
July 19, 2017: Sleep Medicine Reviews
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