Abstract：
:A major focus of contemporary drug screening strategies is the identification of novel anticancer compounds, which often results in underutilization of resources. Current drug evaluation involves in vivo tumor (xenograft) regression as proof-of-principle for cytotoxicity (POC). However, this end-point lacks any assessment of drug resistance of the residual tumor and its capability to establish refractory and/or recurrent disease, which would represent more appropriate indicators of therapeutic failure. We have recently developed a flow cytometry-based approach for the analyses of intra-tumor cellular heterogeneity across stem cell hierarchies, genetic instability and differential cell cycling fractions, which can potentially be predictive of refractory disease and tumor relapse. Iterating this approach after initial POC screening in the drug discovery pipeline would have a great impact in terms of precision of drug evaluation, design of optimal drug combinations and/or drug repositioning. In this perspective, we highlight how through embracing of a comprehensive, informative and analytical assessment of the cellular content of residual tumors, the fidelity and statistical robustness of preclinical drug discovery can be greatly improved.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Naik RR,Luo T,Kohandel M,Bapat SAdoi
10.1016/j.phrs.2016.07.018subject
Has Abstractpub_date
2016-09-01 00:00:00pages
815-819eissn
1043-6618issn
1096-1186pii
S1043-6618(16)30667-3journal_volume
111pub_type
杂志文章abstract：:The pharmacological physiological effects of the endogenous cannabinomimetic (endocannabinoid) anandamide have been well characterized. Another endocannabinoid, 2-arachidonoyl-glycerol (2-AG), has been less-widely studied. 2-AG occurs in vertebrate and invertebrate tissues and binds to both cannabinoid receptors (CB1 ...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.2000.0702
更新日期：2000-10-01 00:00:00
abstract：:Proton pump inhibitors (PPIs) are used widely for the treatment of acid-related disorders. Despite their excellent efficacy and tolerance, the pharmacodynamics and pharmacokinetics of PPIs are affected by each patient's CYP2C19 and gastric H+,K+-ATPase genotype. The aim of this review was to analyze the effect of gene...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2019.104606
更新日期：2020-02-01 00:00:00
abstract：:The effect of the inhalation of vaporized ethanol on injected [1-14C]pyruvate kinetics was studied in mice. The [1-14C]pyruvate kinetics were modelled by means of a four-compartment closed model, i.e. injected site, blood, periphery and expired 14CO2. The results show that the inhalation of vaporized ethanol can stimu...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1997.0261
更新日期：1998-01-01 00:00:00
abstract：:The blood-brain barrier (BBB) keeps the central nervous system (CNS) safe from various brain diseases, while the BBB makes it difficult for effective drugs to enter the CNS. Mfsd2a is specifically expressed on the cell membrane of brain-microvascular endothelial cell (BMEC) and is implicated in the delivery of some su...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2015.12.024
更新日期：2016-02-01 00:00:00
abstract：:New quick-acting blood schizontocides are needed to contain the spread of multiple drug resistant strains of P. falciparum and for the treatment of the cerebral malaria cases. A multiple drug resistant strain of P. yoelii nigeriensis resistant to mefloquine (128 mg/kg x 6 days), quinine (300 mg/kg x 7 days) and chloro...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/1043-6618(89)90159-x
更新日期：1989-07-01 00:00:00
abstract：:The cytoprotective activity of alpha-lipoic acid against free radical toxicity, manifested during experimental hyperoxaluria, has been investigated. Glycollate was used as the inducer of oxalate hyperoxaluria in rats. The increase in lipid peroxidation and superoxide dismutase (SOD) activity, associated with a decreas...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1993.1031
更新日期：1993-05-01 00:00:00
abstract：:Duchenne muscular dystrophy (DMD) is a severe muscle disease of known etiology without effective, or generally applicable therapy. Mitochondria are affected by the disease in animal models but whether mitochondrial dysfunction is part of the pathogenesis in patients remains unclear. We show that primary cultures obtai...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2017.09.001
更新日期：2017-11-01 00:00:00
abstract：:In this lipopolysaccharide (LPS)-induced endotoxemia model, the effects of 3-aminobenzamide (3-AB), a poly(ADP-ribose) synthetase (PARS) inhibitor, on ileal apoptosis were evaluated by light microscopy and M30 cell death staining. Moreover, the relationship between Bcl-2, iNOS expression, and serum nitrate (NO(3)(-)) ...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(02)00075-0
更新日期：2002-08-01 00:00:00
abstract：:Alzheimer's is the neurodegenerative disease affecting the largest number of patients in the world. In spite of the intense research of the last decades, progress about its knowledge and therapy was limited. In particular, various cytotoxic processes remained debated, while the few drugs approved for therapy were of o...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2019.104316
更新日期：2019-08-01 00:00:00
abstract：:Cysteamine, a potent somatostatin depletor, was used in the present study to investigate the role of endogenous somatostatin in acute peripheral inflammation. The acute inflammation was induced by intraplantar injection of carrageenan (1%), histamine (5 micromol), or formalin (2.5%) in the rat hind paw. The induced in...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.2002.0955
更新日期：2002-04-01 00:00:00
abstract：:The metabolism of arachidonic acid by cytochrome P450 (CYP) epoxygenases generates epoxyeicosatrienoic acids (EETs) which affect numerous cellular process including Ca(2+) signaling and the activity of Ca(2+)-dependent K(+) channels. The expression of the CYP epoxygenase(s) that generate EETs in endothelial cells is n...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2003.11.016
更新日期：2004-06-01 00:00:00
abstract：PURPOSE OF THE REVIEW:This review article discusses recent advances in the mechanism of dipeptidyl peptidase-4 (DPP-4) actions in renal diseases, especially diabetic kidney fibrosis, and summarizes anti-fibrotic functions of various DPP-4 inhibitors in diabetic nephropathy (DN). RECENT FINDINGS:DN is a common complica...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2019.104391
更新日期：2019-09-01 00:00:00
abstract：:In the field of kinase inhibitors for applications in cancer research, tubulin is emerging as a targeted cellular protein that can significantly contribute to their activities. However, investigation of kinase inhibitors beyond the kinome is an area often neglected. Herein, we describe the results of pharmacological s...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2018.06.023
更新日期：2018-08-01 00:00:00
abstract：:In China, child and adolescent pediatricians often face challenges in treating children with the appropriate medications. Within the last 8 years, the Chinese government has already initiated a series of policies to promote development of age-appropriate medicines for children. In this study,we introduced the current ...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2019.104412
更新日期：2019-10-01 00:00:00
abstract：:Fatty-acid amide hydrolase (FAAH) catalyzes the intracellular hydrolysis of the endocannabinoid anandamide and other bioactive lipid amides. In the present study, we conducted a comparative characterization of the effects of the newly identified brain-impermeant FAAH inhibitor, URB937 ([3-(3-carbamoylphenyl)-4-hydroxy...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2012.02.012
更新日期：2012-05-01 00:00:00
abstract：:The interaction of mianserin with ethanol in central nervous system (CNS) was investigated. Mianserin was administered at a single dose of 5 or 20 mgkg(-1) i.p. or as daily injections in a dose of 2.5 mgkg(-1) given for 14 days. The influence of mianserin on acute ethanol toxicity (LD(50)), on ED(50) of ethanol in rot...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(02)00031-2
更新日期：2002-07-01 00:00:00
abstract：:Epidemiological studies suggest that diets with a high intake of vegetables and fruits may reduce the incidence of degenerative disorders including Alzheimer's disease. Berries are some of the popular fruits consumed worldwide. They are considered to be rich in anthocyanin pigments, a group belonging to the flavonoids...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2005.07.003
更新日期：2005-12-01 00:00:00
abstract：:Hydrogen sulfide (H2S) is an endogenously produced signaling molecule synthesized by cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST). Given that H2S exerts significant effects on bioenergetics and metabolism, the goal of the current study was to determine th...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2017.09.023
更新日期：2018-02-01 00:00:00
abstract：:Cardiovascular disease (CVD) is the leading cause of death worldwide and the prevalence of obesity and diabetes are increasing. In obesity, adipose tissue increases the secretion of bioactive mediators (adipokines) that may represent a key mechanism linking obesity to CVD. Adiponectin, extensively studied in metabolic...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2014.03.003
更新日期：2014-04-01 00:00:00
abstract：:In hypothermic rats with acute hypertension induced by intravenous injection of adrenalin, regional changes in blood-brain barrier permeability to macromolecules were investigated using Evans blue as indication. Evans blue albumin extravasation was determined as a macroscopic finding and a quantitative estimation with...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：
更新日期：1992-07-01 00:00:00
abstract：:Implantable cardioverter-defibrillators (ICDs) have revolutionized the primary and secondary prevention of patients with ventricular arrhythmias. However, the adverse effects of appropriate or inappropriate shocks may require the adjunctive use of anti-arrhythmic drugs (AADs). Beta blockers are the cornerstone of phar...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2019.03.020
更新日期：2019-05-01 00:00:00
abstract：:The synergistic protective effect of nicorandil (KATP channel opener) and amlodipine (calcium channel blocker) on mitochondrial respiration and mitochondrial lipid contents were examined on isoproterenol-induced myocardial infarction in rats. The rats given isoproterenol (150 mg kg(-1) daily, i.p.) for 2 days showed s...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(03)00223-8
更新日期：2003-12-01 00:00:00
abstract：:Monoclonal antibodies (mAb) have revolutionised the way in which we treat disease. From cancer to autoimmunity, antibody therapy has been responsible for some of the most impressive clinical responses observed in the last 2 decades. A key component of this success has been their generally low levels of toxicity, and u...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2015.07.003
更新日期：2015-09-01 00:00:00
abstract：:The potential for modulating gene expression by the use of antisense oligonucleotides has become increasingly interesting in recent years. Antisense oligonucleotides are complementary nucleic acid fragments that hybridize to target sequences within RNA to form a DNA-RNA duplex, resulting in the block of translation of...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1006/phrs.1997.0227
更新日期：1997-09-01 00:00:00
abstract：:Our goal was to establish the requirement of β3 adrenoceptor (β3Adr) for green tea (GT) effects on the energy metabolism of obese mice. This study was carried out in wild-type (WT) and β3Adr knockout (KO) male mice fed with a standard diet or a high-fat diet (HFD/16 weeks) treated or not with GT (0.5 g/kg of body weig...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2020.104956
更新日期：2020-09-01 00:00:00
abstract：BACKGROUND:Oxidative stress plays an important role in the occurrence of chronic diseases. Zinc supplementation is also known to be an antioxidant agent. While, there is no review on the effects of zinc supplementation on oxidative stress, this study aimed to systematically summarize randomized clinical trials (RCTs) w...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2020.105166
更新日期：2020-11-01 00:00:00
abstract：:This paper discusses the discovery of ligands for orphan receptors and the identification of the natural endogenous ligands for those receptors in physiology. The central thesis is that orphan seven transmembrane receptors (7TMRs) are allosteric conduits of chemical information exchange from extracellular ligands to i...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2016.01.022
更新日期：2016-12-01 00:00:00
abstract：:Nebivolol is a new selective beta 1-adrenergic blocking agent, that possesses a peculiar pharmacodynamic profile and an original chemical structure, by which it differs from traditional beta 1-blockers. Nebivolol is a racemic mixture of two enantiomers in equal ratios. It is endowed with a highly selective beta 1-bloc...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1006/phrs.1998.0387
更新日期：1998-12-01 00:00:00
abstract：:Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most prevalent types of primary liver cancer. Compared with HCC, for which several drugs have been approved, ICC is associated with shorter survival, and no drug has been approved for this type. Previously, we reported that Bmi1 drives HC...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2020.105365
更新日期：2020-12-08 00:00:00
abstract：:Fecal microbiota transplant (FMT) has seen a historic emergence in last decade with its sojourn recently entering into a chequered path, due to a few reports of infection and subsequent mortality. Though FMT has been extensively reported, there is no comprehensive report on the delivery routes available for this non-p...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2020.104954
更新日期：2020-09-01 00:00:00
