Clioquinol: To harm or heal
Publication date: Available online 18 March 2019Source: Pharmacology & TherapeuticsAuthor(s): Dominique R. Perez, Larry A. Sklar, Alexandre ChigaevAbstractClioquinol, one of the first mass-produced drugs, was considered safe and efficacious for many years. It was used as an antifungal and an antiprotozoal drug until it was linked to an outbreak of subacute myelo-optic neuropathy (SMON), a debilitating disease almost exclusively confined to Japan. Today, new information regarding clioquinol targets and its mechanism of action, as well as genetic variation (SNPs) in efflux transporters in the Japanese population, provide...
Source: Pharmacology and Therapeutics - March 19, 2019 Category: Drugs & Pharmacology Source Type: research

Super-enhancers in cancer
This article reviews the current understanding of super-enhancer assembly and activation, the different mechanisms by which cancer cells acquire oncogenic super-enhancers and, finally, the potential of targeting super-enhancers as future therapeutics. (Source: Pharmacology and Therapeutics)
Source: Pharmacology and Therapeutics - March 16, 2019 Category: Drugs & Pharmacology Source Type: research

Mast cell tryptase – marker and maker of cardiovascular diseases
Publication date: Available online 12 March 2019Source: Pharmacology & TherapeuticsAuthor(s): Mohammad Mohajeri, Petri T. Kovanen, Vanessa Bianconi, Matteo Pirro, Arrigo F.G. Cicero, Amirhossein SahebkarAbstractMast cells are tissue-resident cells, which have been proposed to participate in various inflammatory diseases, among them the cardiovascular diseases (CVDs). For mast cells to be able to contribute to an inflammatory process, they need to be activated to exocytose their cytoplasmic secretory granules. The granules contain a vast array of highly bioactive effector molecules, the neutral protease tryptase being t...
Source: Pharmacology and Therapeutics - March 13, 2019 Category: Drugs & Pharmacology Source Type: research

Gene-environment interactions in Alzheimer's Disease: A potential path to precision medicine
Publication date: Available online 12 March 2019Source: Pharmacology & TherapeuticsAuthor(s): Aseel Eid, Isha Mhatre, Jason R. RichardsonAbstractAlzheimer’s disease (AD) is the leading cause of dementia in the United States and afflicts greater than 5.7 million Americans in 2018. Therapeutic options remain extremely limited to those that are symptom targeting, while no drugs have been approved for the modification or reversal of the disease itself. Risk factors for AD including aging, the female sex, as well as carrying an APOE4 genotype. These risk factors have been extensively examined in the literature, while ...
Source: Pharmacology and Therapeutics - March 13, 2019 Category: Drugs & Pharmacology Source Type: research

The emerging concept of “individualized cholesterol-lowering therapy”: A change in paradigm
Publication date: Available online 12 March 2019Source: Pharmacology & TherapeuticsAuthor(s): Dieter Lütjohann, Frans Stellaard, Monique T. Mulder, Eric J.G. Sijbrands, Oliver WeingärtnerAbstractHigh LDL-cholesterol concentrations constitute a risk for atherosclerotic cardiovascular disease. By consensus, cholesterol-lowering therapy is initiated with a statin that reduces endogenous cholesterol synthesis, upregulates hepatic LDL receptor activity, increases LDL clearance and lowers LDL-cholesterol concentrations in the bloodstream. The efficacy of statin treatment is dose dependent and achieves a risk reduct...
Source: Pharmacology and Therapeutics - March 13, 2019 Category: Drugs & Pharmacology Source Type: research

Limiting tumor seeding as a therapeutic approach for metastatic disease
Publication date: Available online 12 March 2019Source: Pharmacology & TherapeuticsAuthor(s): Asurayya Worrede-Mahdi, Olimpia Meucci, Alessandro FatatisAbstractHere we propose that therapeutic targeting of circulating tumor cells (CTCs), which are widely understood to be the seeds of metastasis, would represent an effective strategy towards limiting numerical expansion of secondary lesions and containing overall tumor burden in cancer patients. However, the molecular mediators of tumor seeding have not been well characterized. This is in part due to the limited number of pre-clinical in vivo approaches that appropriate...
Source: Pharmacology and Therapeutics - March 13, 2019 Category: Drugs & Pharmacology Source Type: research

Intestinal microbiome as a novel therapeutic target for local and systemic inflammation
Publication date: Available online 12 March 2019Source: Pharmacology & TherapeuticsAuthor(s): Kazuhiko Uchiyama, Yuji Naito, Tomohisa TakagiAbstractRecently, the pathogenesis of systemic inflammatory disease such as inflammatory bowel disease (IBD), multiple sclerosis (MS), systemic inflammatory arthritis, asthma, and non-alcoholic fatty liver disease has been reported to be related to the dysbiosis of gut microbiota. The contribution of special bacteria for the development of those diseases has been elucidated by disease animal models such as germ-free mice. Besides, the contribution by several bacteria for the pathog...
Source: Pharmacology and Therapeutics - March 13, 2019 Category: Drugs & Pharmacology Source Type: research

Emerging drug development technologies targeting Ubiquitination for Cancer therapeutics
Publication date: Available online 7 March 2019Source: Pharmacology & TherapeuticsAuthor(s): Gianluca Veggiani, María Carla Rosales Gerpe, Sachdev S. Sidhu, Wei ZhangAbstractDevelopment of effective cancer therapeutic strategies relies on our ability to interfere with cellular processes that are dysregulated in tumors. Given the essential role of the ubiquitin proteasome system (UPS) in regulating a myriad of cellular processes, it is not surprising that malfunction of UPS components is implicated in numerous human diseases, including many types of cancer. The clinical success of proteasome inhibitors in treatin...
Source: Pharmacology and Therapeutics - March 7, 2019 Category: Drugs & Pharmacology Source Type: research

Fast-acting antidepressant activity of ketamine: highlights on brain serotonin, glutamate, and GABA neurotransmission in preclinical studies
Publication date: Available online 7 March 2019Source: Pharmacology & TherapeuticsAuthor(s): Thu Ha PHAM, Alain M. GARDIERAbstract:Ketamine, a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptor, displays a fast antidepressant activity in treatment-resistant depression and in rodent models of anxiety/depression. A large body of evidence concerning the cellular and molecular mechanisms underlying its fast antidepressant-like activity comes from animal studies. Although structural remodeling of frontocortical/hippocampal neurons has been proposed as critical, the role of excitatory/inhibitory neurotransmit...
Source: Pharmacology and Therapeutics - March 7, 2019 Category: Drugs & Pharmacology Source Type: research

Intestinal bacterial β-glucuronidase as a possible predictive biomarker of irinotecan-induced diarrhea severity
Publication date: Available online 1 March 2019Source: Pharmacology & TherapeuticsAuthor(s): Ali N. Chamseddine, Michel Ducreux, Jean-Pierre Armand, Xavier Paoletti, Tuvana Satar, Angelo Paci, Olivier MirAbstractIrinotecan is an anticancer drug with a broad spectrum of activity, characterized by multistep and complex pharmacology. Regardless of its schedule of administration, neutropenia and delayed-type diarrhea are the most common side effects. The latter was the dose-limiting toxicity in phase I trials, and its prediction by pharmacogenetic (UGT1A1*28/*28) testing remains sub-optimal. Recent studies have highlighted...
Source: Pharmacology and Therapeutics - March 4, 2019 Category: Drugs & Pharmacology Source Type: research

Alcohol Abuse and Disorder of Granulopoiesis
This article reviews the recent development in understanding alcohol-induced disruption of marrow granulopoiesis and the granulopoietic response with the focus on progress in delineating cell signaling mechanisms underlying the alcohol-induced injury to hematopoietic tissue. Efforts in exploring effective therapy to improve patient care in this field will also be discussed. (Source: Pharmacology and Therapeutics)
Source: Pharmacology and Therapeutics - March 4, 2019 Category: Drugs & Pharmacology Source Type: research

What doesn't kill you makes you stranger: Dipeptidyl peptidase-4 (CD26) proteolysis differentially modulates the activity of many peptide hormones and cytokines generating novel cryptic bioactive ligands
Publication date: Available online 10 February 2019Source: Pharmacology & TherapeuticsAuthor(s): Ahmed M. Elmansi, Mohamed E. Awad, Nada H. Eisa, Dmitry Kondrikov, Khaled A. Hussein, Alexandra Aguilar-Pérez, Samuel Herberg, Sudharsan Periyasamy-Thandavan, Sadanand Fulzele, Mark W. Hamrick, Meghan E. McGee-Lawrence, Carlos M. Isales, Brian F. Volkman, William D. HillAbstractDipeptidyl peptidase 4 (DPP4) is an exopeptidase found either on cell surfaces where it is highly regulated in terms of its expression and surface availability (CD26) or in a free/circulating soluble constitutively available and intrinsically ...
Source: Pharmacology and Therapeutics - March 1, 2019 Category: Drugs & Pharmacology Source Type: research

Adhesion G-protein coupled receptors: Implications for metabolic function
Publication date: Available online 27 February 2019Source: Pharmacology & TherapeuticsAuthor(s): Oladapo E. Olaniru, Shanta J. PersaudAbstractAdhesion G-protein coupled receptors (aGPCRs) are emerging as important actors in energy homeostasis. Recent biochemical and functional studies using transgenic mice indicate that aGPCRs play important roles in endocrine and metabolic functions including β-cell differentiation, insulin secretion, adipogenesis and whole body fuel homeostasis. Most aGPCRs are orphans, for which endogenous ligands have not yet been identified, and many of the endogenous ligands of the already d...
Source: Pharmacology and Therapeutics - February 28, 2019 Category: Drugs & Pharmacology Source Type: research

Recent therapeutic trends and promising targets in triple negative breast cancer
Publication date: Available online 28 February 2019Source: Pharmacology & TherapeuticsAuthor(s): Soo-Yeon Hwang, Seojeong Park, Youngjoo KwonAbstractBreast cancer accounts for 25% of all types of cancer in women, and triple negative breast cancer (TNBC) comprises around 15~20% of breast cancers. Conventional chemotherapy and radiation are the primary systemic therapeutic strategies; no other FDA-approved targeted therapies are yet available as for TNBC. TNBC is generally characterized by a poor prognosis and high rates of proliferation and metastases. Due to these aggressive features and lack of targeted therapies, num...
Source: Pharmacology and Therapeutics - February 28, 2019 Category: Drugs & Pharmacology Source Type: research

CD26/DPP4 - a potential biomarker and target for cancer therapy
Publication date: Available online 26 February 2019Source: Pharmacology & TherapeuticsAuthor(s): Njanja Enz, Gwendolyn Vliegen, Ingrid De Meester, Wolfgang JungraithmayrAbstractCD26/dipeptidyl peptidase (DPP)4 is a membrane-bound protein found in many cell types of the body, and a soluble form is present in body fluids. There is longstanding evidence that various primary tumors and also metastases express CD26/DPP4 to a variable extent. By cleaving dipeptides from peptides with a proline or alanine in the penultimate position at the N-terminus, it regulates the activity of incretin hormones, chemokines and many other p...
Source: Pharmacology and Therapeutics - February 27, 2019 Category: Drugs & Pharmacology Source Type: research

Pathobiological mechanisms underlying metabolic syndrome (MetS) in chronic obstructive pulmonary disease (COPD): clinical significance and therapeutic strategies
Publication date: Available online 26 February 2019Source: Pharmacology & TherapeuticsAuthor(s): Stanley M.H. Chan, Stavros Selemidis, Steven Bozinovski, Ross VlahosABSTRACTChronic obstructive pulmonary disease (COPD) is a major incurable global health burden and is currently the 4th largest cause of death in the world. Importantly, much of the disease burden and health care utilisation in COPD is associated with the management of its comorbidities (e.g. skeletal muscle wasting, ischemic heart disease, cognitive dysfunction) and infective viral and bacterial acute exacerbations (AECOPD). Current pharmacological treatme...
Source: Pharmacology and Therapeutics - February 27, 2019 Category: Drugs & Pharmacology Source Type: research

Animal models of closed-skull, repetitive mild traumatic brain injury
Publication date: Available online 26 February 2019Source: Pharmacology & TherapeuticsAuthor(s): Wouter S. Hoogenboom, Craig A. Branch, Michael L. LiptonAbstractThe underlying mechanisms that result in neurophysiological changes and cognitive sequelae in the context of repetitive mild traumatic brain injury (rmTBI) remain poorly understood. Animal models provide a unique opportunity to examine cellular and molecular responses using histological assessment, which can give important insights on the neurophysiological changes associated with the evolution of brain injury. To better understand the potential cumulative effe...
Source: Pharmacology and Therapeutics - February 27, 2019 Category: Drugs & Pharmacology Source Type: research

Editorial Board
Publication date: March 2019Source: Pharmacology & Therapeutics, Volume 195Author(s): (Source: Pharmacology and Therapeutics)
Source: Pharmacology and Therapeutics - February 27, 2019 Category: Drugs & Pharmacology Source Type: research

Nanotechnology in the diagnosis and treatment of lung cancer
Publication date: Available online 21 February 2019Source: Pharmacology & TherapeuticsAuthor(s): Alexander M. Cryer, Andrew J. ThorleyAbstractLung cancer is an umbrella term for a subset of heterogeneous diseases that are collectively responsible for the most cancer-related deaths worldwide. Despite the tremendous progress made in understanding lung tumour biology, advances in early diagnosis, multimodal therapy and deciphering molecular mechanisms of drug resistance, overall curative outcomes remain low, especially in metastatic disease. Nanotechnology, in particular nanoparticles (NPs), continue to progressively impa...
Source: Pharmacology and Therapeutics - February 22, 2019 Category: Drugs & Pharmacology Source Type: research

Regulation of the Phosphoprotein Phosphatase 2A System and its Modulation during Oxidative Stress: A Potential Therapeutic Target?
Publication date: Available online 22 February 2019Source: Pharmacology & TherapeuticsAuthor(s): I. Elgenaidi, J.P. SpiersAbstractPhosphoprotein phosphatases are of growing interest in the pathophysiology of many diseases and are often the neglected partner of protein kinases. One family member, PP2A, accounts for dephosphorylation of ~55-70% of all serine/threonine phosphosites. Interestingly, dysregulation of kinase signalling is a hallmark of many diseases in which an increase in oxidative stress is also noted. With this in mind, we assess the evidence to support oxidative stress-mediated regulation of the PP2A syst...
Source: Pharmacology and Therapeutics - February 22, 2019 Category: Drugs & Pharmacology Source Type: research

Growth differentiation factor 15 (GDF15): A survival protein with therapeutic potential in metabolic diseases
Publication date: Available online 18 February 2019Source: Pharmacology & TherapeuticsAuthor(s): Seung Joon Baek, Thomas ElingAbstractGrowth Differentiation Factor 15 (GDF15), also known as NSAID activated gene-1 (NAG-1), is associated with a large number of biological processes and diseases, including cancer and obesity. GDF15 is synthesized as pro-GDF15, is dimerized, and is cleaved and secreted into the circulation as a mature dimer GDF15. Both the intracellular GDF15 and the circulating mature GDF15 are implicated in biological processes, such as energy homeostasis and body weight regulation. Although there have be...
Source: Pharmacology and Therapeutics - February 19, 2019 Category: Drugs & Pharmacology Source Type: research

Modulating Wnt signaling at the root: Porcupine and Wnt acylation
Publication date: Available online 18 February 2019Source: Pharmacology & TherapeuticsAuthor(s): Viviana I. Torres, Juan A. Godoy, Nibaldo C. InestrosaAbstractCommunication between cells occurs through secreted molecules, among which Wnt ligands play a critical role in balancing cell proliferation, differentiation and cellular homeostasis. The action of Wnt signaling can be modulated at several levels, including posttranslational modification of the Wnt ligands, whose acylation is critical for biological activity. At least three enzymes are necessary for Wnt acylation/deacylation: stearoyl CoA desaturase (SCD), porcupi...
Source: Pharmacology and Therapeutics - February 19, 2019 Category: Drugs & Pharmacology Source Type: research

Recent advances in the development of Mcl-1 inhibitors for cancer therapy
Publication date: Available online 18 February 2019Source: Pharmacology & TherapeuticsAuthor(s): Alexander W. Hird, Adriana E. TronAbstractDysregulation of the mitochondrial apoptotic pathway controlled by members of the Bcl-2 protein family plays a central role in cancer development and resistance to conventional cytotoxic as well as targeted therapies. Hence, selective inhibition of pro-survival Bcl-2 family of proteins to activate apoptosis in malignant cells represents an exciting anti-cancer strategy. The remarkable clinical performance of the selective Bcl-2 antagonist venetoclax has highlighted the potential for...
Source: Pharmacology and Therapeutics - February 19, 2019 Category: Drugs & Pharmacology Source Type: research

Cathepsins: Potent regulators in carcinogenesis
Publication date: Available online 11 February 2019Source: Pharmacology & TherapeuticsAuthor(s): Tejinder Pal Khaket, Taeg Kyu Kwon, Sun Chul KangAbstractCathepsins (CTS) are mainly lysosomal acid hydrolases extensively involved in the prognosis of different diseases, and having a distinct role in tumor progression by regulating cell proliferation, autophagy, angiogenesis, invasion, and metastasis. As all these processes conjunctively lead to cancer progression, their site-specific regulation might be beneficial for cancer treatment. CTS regulate activation of the proteolytic cascade and protein turnover, while extrace...
Source: Pharmacology and Therapeutics - February 12, 2019 Category: Drugs & Pharmacology Source Type: research

Quenching the fires: Pro-resolving mediators, air pollution, and smoking
Publication date: Available online 10 February 2019Source: Pharmacology & TherapeuticsAuthor(s): Thomas H. Thatcher, Collynn F. Woeller, Claire E. McCarthy, Patricia J. SimeAbstractExposure to air pollution and other environmental inhalation hazards, such as occupational exposures to dusts and fumes, aeroallergens, and tobacco smoke, is a significant cause of chronic lung inflammation leading to respiratory disease. It is now recognized that resolution of inflammation is an active process controlled by a novel family of small lipid mediators termed “specialized pro-resolving mediators” or SPMs, derived main...
Source: Pharmacology and Therapeutics - February 11, 2019 Category: Drugs & Pharmacology Source Type: research

Potential biomarkers for persistent and neuropathic pain therapy
Publication date: Available online 10 February 2019Source: Pharmacology & TherapeuticsAuthor(s): Marco Sisignano, Jörn Lötsch, Michael J. Parnham, Gerd GeisslingerAbstractPersistent, in particular neuropathic pain affects millions of people worldwide. However, the response rate of patients to existing analgesic drugs is less than 50%. There are several possibilities to increase this response rate, such as optimization of the pharmacokinetic and pharmacodynamic properties of analgesics. Another promising approach is to use prognostic biomarkers in patients to determine the optimal pharmacological therapy for e...
Source: Pharmacology and Therapeutics - February 11, 2019 Category: Drugs & Pharmacology Source Type: research

What doesn’t kill you makes you stranger: Dipeptidyl peptidase-4 (CD26) proteolysis differentially modulates the activity of many peptide hormones and cytokines generating novel cryptic bioactive ligands
Publication date: Available online 10 February 2019Source: Pharmacology & TherapeuticsAuthor(s): Ahmed M. Elmansi, Mohamed E. Awad, Nada H. Eisa, Dmitry Kondrikov, Khaled A. Hussein, Alexandra Aguilar-Pérez, Samuel Herberg, Sudharsan Periyasamy-Thandavan, Sadanand Fulzele, Mark W. Hamrick, Meghan E. McGee-Lawrence, Carlos M. Isales, Brian F. Volkman, William D. HillAbstractDipeptidyl peptidase 4 (DPP4) is an exopeptidase found either on cell surfaces where it is highly regulated in terms of its expression and surface availability (CD26) or in a free/circulating soluble constitutively available and intrinsically ...
Source: Pharmacology and Therapeutics - February 11, 2019 Category: Drugs & Pharmacology Source Type: research

Phosphodiesterases As Therapeutic Targets for Respiratory Diseases
Publication date: Available online 10 February 2019Source: Pharmacology & TherapeuticsAuthor(s): Haoxiao Zuo, Isabella Cattani-Cavalieri, Nshunge Musheshe, Viacheslav O. Nikolaev, Martina SchmidtAbstractChronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and asthma, affect millions of people all over the world. Cyclic adenosine monophosphate (cAMP) which is one of the most important second messengers, plays a vital role in relaxing airway smooth muscles and suppressing inflammation. Given its vast role in regulating intracellular responses, cAMP provides an attractive pharmaceutical targe...
Source: Pharmacology and Therapeutics - February 11, 2019 Category: Drugs & Pharmacology Source Type: research

Novel genetic an epigenetic factors of importance for inter-individual differences in drug disposition, response and toxicity
Publication date: Available online 22 January 2019Source: Pharmacology & TherapeuticsAuthor(s): Volker M. Lauschke, Yitian Zhou, Magnus Ingelman-SundbergAbstractIndividuals differ substantially in their response to pharmacological treatment. Personalized medicine aspires to embrace these inter-individual differences and customize therapy by taking a wealth of patient-specific data into account. Pharmacogenomic constitutes a cornerstone of personalized medicine that provides therapeutic guidance based on the genomic profile of a given patient. Pharmacogenomics already has applications in the clinics, particularly in onc...
Source: Pharmacology and Therapeutics - February 2, 2019 Category: Drugs & Pharmacology Source Type: research

Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function
Publication date: Available online 4 December 2018Source: Pharmacology & TherapeuticsAuthor(s): Matthew W. Johnson, Peter S. Hendricks, Frederick S. Barrett, Roland R. GriffithsAbstractThe purpose of this paper is to provide an integrative review and offer novel insights regarding human research with classic psychedelics (classic hallucinogens), which are serotonin 2A receptor (5-HT2AR) agonists such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Classic psychedelics have been administered as sacraments since ancient times. They were of prominent interest within psychiatry and neuroscience in the 1950s...
Source: Pharmacology and Therapeutics - January 30, 2019 Category: Drugs & Pharmacology Source Type: research

Sarcolemmal α2-adrenoceptors in feedback control of myocardial response to sympathetic challenge
Publication date: Available online 28 January 2019Source: Pharmacology & TherapeuticsAuthor(s): Alexey E. Alekseev, Sungjo Park, Oleg Yu Pimenov, Santiago Reyes, Andre TerzicAbstractα2-adrenoceptor (α2-AR) isoforms, abundant in sympathetic synapses and noradrenergic neurons of the central nervous system, are integral in the presynaptic feed-back loop mechanism that moderates norepinephrine surges. We recently identified that postsynaptic α2-AR, found in the myocellular sarcolemma, also contribute to a muscle-delimited feedback control capable of attenuating mobilization of intracellular Ca2+ and myoca...
Source: Pharmacology and Therapeutics - January 29, 2019 Category: Drugs & Pharmacology Source Type: research

Vitamin A Signaling and Homeostasis in Obesity, Diabetes, and Metabolic Disorders
Publication date: Available online 29 January 2019Source: Pharmacology & TherapeuticsAuthor(s): William S. BlanerABSTRACTMuch evidence has accumulated in the literature over the last fifteen years that indicates vitamin A has a role in metabolic disease prevention and causation. This literature proposes that vitamin A can affect obesity development and the development of obesity-related diseases including insulin resistance, type 2 diabetes, hepatic steatosis and steatohepatitis, and cardiovascular disease. Retinoic acid, the transcriptionally active form of vitamin A, accounts for many of the reported associations. Ho...
Source: Pharmacology and Therapeutics - January 29, 2019 Category: Drugs & Pharmacology Source Type: research

Editorial Board
Publication date: February 2019Source: Pharmacology & Therapeutics, Volume 194Author(s): (Source: Pharmacology and Therapeutics)
Source: Pharmacology and Therapeutics - January 23, 2019 Category: Drugs & Pharmacology Source Type: research

The eye as a novel imaging site in diabetes research
Publication date: Available online 22 January 2019Source: Pharmacology & TherapeuticsAuthor(s): Shao-Nian Yang, Per-Olof BerggrenABSTRACTDiabetes develops due to deficient functional β cell mass, insulin resistance, or both. Yet, various challenges in understanding the mechanisms underlying diabetes development in vivo remain to be overcome owing to the lack of appropriate intravital imaging technologies. To meet these challenges, we have exploited the anterior chamber of the eye (ACE) as a novel imaging site to understand diabetes basics and clinics in vivo. We have developed a technology platform transplanting p...
Source: Pharmacology and Therapeutics - January 22, 2019 Category: Drugs & Pharmacology Source Type: research

The Adenosine A2B G Protein-Coupled Receptor: Recent Advances and Therapeutic Implications
Publication date: Available online 22 January 2019Source: Pharmacology & TherapeuticsAuthor(s): Elizabeth A. Vecchio, Paul J. White, Lauren T. MayAbstractThe adenosine A2B receptor (A2BAR) is one of four adenosine receptor subtypes belonging to the Class A family of G protein-coupled receptors (GPCRs). Until recently, the A2BAR remained poorly characterised, in part due to its relatively low affinity for the endogenous agonist adenosine and therefore presumed minor physiological significance. However, the substantial increase in extracellular adenosine concentration, the sensitisation of the receptor and the upregulati...
Source: Pharmacology and Therapeutics - January 22, 2019 Category: Drugs & Pharmacology Source Type: research

Are cell-based therapies for kidney disease safe? A systematic review of preclinical evidence
In conclusion, for benign cell-based therapies, well-designed pre-clinical studies, including all control groups required and good manufacturing processes securing safety, need to be done early in development. Preferably, this should be performed side by side with efficacy evaluation and according to the official guidelines of leading health organizations. (Source: Pharmacology and Therapeutics)
Source: Pharmacology and Therapeutics - January 22, 2019 Category: Drugs & Pharmacology Source Type: research

Environmental neurotoxicant-induced dopaminergic neurodegeneration: a potential link to impaired neuroinflammatory mechanisms
Publication date: Available online 22 January 2019Source: Pharmacology & TherapeuticsAuthor(s): Arthi Kanthasamy, Huajun Jin, Adhithiya Charli, Anantharam Vellareddy, Anumantha KanthasamyAbstractWith the increased incidence of neurodegenerative diseases worldwide, Parkinson’s disease (PD) represents the second-most common neurodegenerative disease. PD is a progressive multisystem neurodegenerative disorder characterized by a marked loss of nigrostriatal dopaminergic neurons and the formation of Lewy pathology in diverse brain regions. Although the mechanisms underlying dopaminergic neurodegeneration remain poorly...
Source: Pharmacology and Therapeutics - January 22, 2019 Category: Drugs & Pharmacology Source Type: research

Novel genetic and epigenetic factors of importance for inter-individual differences in drug disposition, response and toxicity
Publication date: Available online 22 January 2019Source: Pharmacology & TherapeuticsAuthor(s): Volker M. Lauschke, Yitian Zhou, Magnus Ingelman-SundbergAbstractIndividuals differ substantially in their response to pharmacological treatment. Personalized medicine aspires to embrace these inter-individual differences and customize therapy by taking a wealth of patient-specific data into account. Pharmacogenomic constitutes a cornerstone of personalized medicine that provides therapeutic guidance based on the genomic profile of a given patient. Pharmacogenomics already has applications in the clinics, particularly in onc...
Source: Pharmacology and Therapeutics - January 22, 2019 Category: Drugs & Pharmacology Source Type: research

Editorial Board
Publication date: January 2019Source: Pharmacology & Therapeutics, Volume 193Author(s): (Source: Pharmacology and Therapeutics)
Source: Pharmacology and Therapeutics - December 22, 2018 Category: Drugs & Pharmacology Source Type: research

Cognitive neuropsychological theory: Reconciliation of psychological and biological approaches for depression
Publication date: Available online 19 December 2018Source: Pharmacology & TherapeuticsAuthor(s): Beata R. GodlewskaAbstractNew antidepressants and individualized approaches to treatment, matching specific therapies to individual patients, are urgently needed. For this, a better understanding of processes underpinning the development of depressive symptoms and response to medications are required. The cognitive neuropsychological model offers a novel approach uniquely combining biological and psychological approaches to explain how antidepressants exert their effect, why there is a delay in the onset of their clinical e...
Source: Pharmacology and Therapeutics - December 21, 2018 Category: Drugs & Pharmacology Source Type: research

Organic Anion Transporting Polypeptide 2B1 – More than a Glass-Full of Drug Interactions
Publication date: Available online 14 December 2018Source: Pharmacology & TherapeuticsAuthor(s): Savannah J. McFeely, Lanxiang Wu, Tasha K. Ritchie, Jashvant UnadkatAbstractThe importance of uptake transporters in determining drug disposition is increasingly appreciated. While the focus of regulatory agencies worldwide has been on the hepatic organic anion transporting polypeptides (OATPs) 1B1 and 1B3, there is another isoform of the OATP sub-family, OATP2B1, which should be considered equally relevant. Unlike the other members of the OATP sub-family, OATP2B1 is expressed in multiple organs in humans, including in the ...
Source: Pharmacology and Therapeutics - December 15, 2018 Category: Drugs & Pharmacology Source Type: research

KIT as a therapeutic target for non-oncological diseases
Publication date: Available online 14 December 2018Source: Pharmacology & TherapeuticsAuthor(s): Asuncion Martinez-Anton, Delphine Gras, Arnaud Bourdin, Patrice Dubreuil, Pascal ChanezAbstractKIT is a receptor tyrosine kinase that after binding to its ligand stem cell factor activates signaling cascades linked to biological processes such as proliferation, differentiation, migration and cell survival. Based on studies performed on SCF and/or KIT mutant animals that presented anemia, sterility, and/or pigmentation disorders, KIT signaling was mainly considered to be involved in the regulation of hematopoiesis, gametogen...
Source: Pharmacology and Therapeutics - December 15, 2018 Category: Drugs & Pharmacology Source Type: research

Mechanisms of cardiac ethanol toxicity and novel treatment options
Publication date: Available online 14 December 2018Source: Pharmacology & TherapeuticsAuthor(s): Julian Mustroph, Simon Lebek, Lars S. Maier, Stefan NeefAbstractEthanol can acutely and chronically alter cardiomyocyte and whole-organ function in the heart. Importantly, ethanol acutely and chronically predisposes to arrhythmias, while chronic abuse can induce heart failure. However, the molecular mechanisms of ethanol toxicity in the heart are incompletely understood.In this review, we summarize the current mechanistic knowledge on cardiac ethanol toxicity, with a focus on druggable pathways. Ethanol effects on excitatio...
Source: Pharmacology and Therapeutics - December 15, 2018 Category: Drugs & Pharmacology Source Type: research

Effective Effectors: How T cells Access and Infiltrate the Central nervous System
Publication date: Available online 14 December 2018Source: Pharmacology & TherapeuticsAuthor(s): Kendra L. Congdon, Luis A. Sanchez-Perez, John H. SampsonAbstractSeveral Phase II and III clinical trials have demonstrated that immunotherapy can induce objective responses in otherwise refractory malignancies in tumors outside the central nervous system. In large part, effector T cells mediate much of the antitumor efficacy in these trials, and potent antitumor T cells can be generated through vaccination, immune checkpoint blockade, adoptive transfer, and genetic manipulation. However, activated T cells must still traffi...
Source: Pharmacology and Therapeutics - December 15, 2018 Category: Drugs & Pharmacology Source Type: research

New insights on the regulation of cancer cachexia by N-3 polyunsaturated fatty acids
Publication date: Available online 4 December 2018Source: Pharmacology & TherapeuticsAuthor(s): Renata Gorjao, Cesar Miguel Momesso dos Santos, Tamires Duarte Afonso Serdan, Vinicius Leonardo Sousa Diniz, Tatiana Carolina Alba-Loureiro, Maria Fernanda Cury-Boaventura, Elaine Hatanaka, Adriana Cristina Levada-Pires, Fábio Takeo Sato, Tania Cristina Pithon-Curi, Luiz Claudio Fernandes, Rui Curi, Sandro Massao HirabaraAbstractCancer cachexia is a multifactorial syndrome that develops during malignant tumor growth. Changes in plasma levels of several hormones and inflammatory factors result in an intense catabolic s...
Source: Pharmacology and Therapeutics - December 14, 2018 Category: Drugs & Pharmacology Source Type: research

Immune mechanisms mediating abscopal effects in radioimmunotherapy
Publication date: Available online 5 December 2018Source: Pharmacology & TherapeuticsAuthor(s): María E. Rodriguez-Ruiz, I. Rodriguez, Olwen Leaman, Fernando López Campos, Angel Montero, Antonio J. Conde, J.J. Aristu, Pedro Lara, Manuel Calvo Felipe, Ignacio MeleroAbstractRadiotherapy of cancer has been traditionally considered as a local therapy without noticeable effects outside the irradiated fields. However, ionizing radiation exerts multiple biological effects on both malignant and stromal cells that account for a complex spectrum of mechanisms beyond simple termination of cancer cells. In the era of...
Source: Pharmacology and Therapeutics - December 6, 2018 Category: Drugs & Pharmacology Source Type: research

HMGB1 and repair: focus on the heart
Publication date: Available online 6 December 2018Source: Pharmacology & TherapeuticsAuthor(s): Laura Pellegrini, Eleonora Foglio, Elena Pontemezzo, Antonia Germani, Matteo Antonio Russo, Federica LimanaABSTRACTHigh-mobility group box 1 (HMGB1) is one of the most abundant proteins in eukaryotes and the best characterized damage-associated molecular pattern (DAMP).The biological activities of HMGB1 depend on its subcellular location, context and post-translational modifications. Inside the nucleus, HMGB1 is engaged in many DNA events such as DNA repair, transcription regulation and genome stability; in the cytoplasm, it...
Source: Pharmacology and Therapeutics - December 6, 2018 Category: Drugs & Pharmacology Source Type: research

Cytochrome P450 epoxygenases and cancer: A genetic and a molecular perspective
Publication date: Available online 3 December 2018Source: Pharmacology & TherapeuticsAuthor(s): Lindsay N. Sausville, Scott M. Williams, Ambra PozziAbstractCytochrome CYP450 epoxygenases catalyze the epoxidation of polyunsaturated fatty acids including arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid. The arachidonic acid-derived products are potent pro-angiogenic lipids and promote tumor development and growth. On the other hand, eicosapentaenoic acid- and docosahexaenoic acid-derived products inhibit angiogenesis and play a protective role in certain pathological conditions including cancer. Increase...
Source: Pharmacology and Therapeutics - December 4, 2018 Category: Drugs & Pharmacology Source Type: research

Classic Psychedelics: An integrative review of epidemiology, mystical experience, brain network function, and therapeutics
Publication date: Available online 4 December 2018Source: Pharmacology & TherapeuticsAuthor(s): Matthew W. Johnson, Peter S. Hendricks, Frederick S. Barrett, Roland R. GriffithsAbstractThe purpose of this paper is to provide an integrative review and offer novel insights regarding human research with classic psychedelics (classic hallucinogens), which are 5HT2AR agonists such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Classic psychedelics have been administered as sacraments since ancient times. They were of prominent interest within psychiatry and neuroscience in the 1950s to 1960s, and during thi...
Source: Pharmacology and Therapeutics - December 4, 2018 Category: Drugs & Pharmacology Source Type: research

Targeting indoleamine-2,3-dioxygenase in cancer: Scientific rationale and clinical evidence
Publication date: Available online 4 December 2018Source: Pharmacology & TherapeuticsAuthor(s): Biagio Ricciuti, Giulia Costanza Leonardi, Paolo Puccetti, Francesca Fallarino, Vanessa Bianconi, Amirhossein Sahebkar, Sara Baglivo, Rita Chiari, Matteo PirroAbstractImmunotherapy through immune checkpoint blockers (ICBs) is quickly transforming cancer treatment by improving patients' outcomes. However, innate and acquired resistance to ICBs remain a major challenge in clinical settings. Indoleamine 2,3-dioxygenases (IDOs) are enzymes involved in tryptophan catabolism with a central immunosuppressive function within the tum...
Source: Pharmacology and Therapeutics - December 4, 2018 Category: Drugs & Pharmacology Source Type: research