Abstract:
:P-Glycoprotein (P-gp) is a 170-kDa transmembrane glycoprotein that works as an efflux pump and confers multidrug resistance (MDR) in normal tissues and tumors, including nervous tissues and brain tumors. In the developing telencephalon, the endothelial expression of P-gp, and the subcellular localization of the transporter at the luminal endothelial cell (EC) plasma membrane are early hallmarks of blood-brain barrier (BBB) differentiation and suggest a functional BBB activity that may complement the placental barrier function and the expression of P-gp at the blood-placental interface. In early fetal ages, P-gp has also been immunolocalized on radial glia cells (RGCs), located in the proliferative ventricular zone (VZ) of the dorsal telencephalon and now considered to be neural progenitor cells (NPCs). RG-like NPCs have been found in many regions of the developing brain and have been suggested to give rise to neural stem cells (NSCs) of adult subventricular (SVZ) neurogenic niches. The P-gp immunosignal, associated with RG-like NPCs during cortical histogenesis, progressively decreases in parallel with the last waves of neuroblast migrations, while 'outer' RGCs and the deriving astrocytes do not stain for the efflux transporter. These data suggest that in human glioblastoma (GBM), P-gp expressed by ECs may be a negligible component of tumor MDR. Instead, tumor perivascular astrocytes may dedifferentiate and resume a progenitor-like P-gp activity, becoming MDR cells and contribute, together with perivascular P-gpexpressing glioma stem-like cells (GSCs), to the MDR profile of GBM vessels. In conclusion, the analysis of Pgp immunolocalization during brain development may contribute to identify the multiple cellular sources in the GBM vessels that may be involved in P-gp-mediated chemoresistance and can be responsible for GBM therapy failure and tumor recurrence.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
de Trizio I,Errede M,d'Amati A,Girolamo F,Virgintino Ddoi
10.2174/1381612826666200318130625subject
Has Abstractpub_date
2020-01-01 00:00:00pages
1428-1437issue
13eissn
1381-6128issn
1873-4286pii
CPD-EPUB-105348journal_volume
26pub_type
杂志文章abstract::Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic relapsing conditions resulting from immune system activity in a genetically predisposed individual. IBD is based on progressive damage to the inflamed gut tissue. As its pathogenesis remains unknown, recent accumu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200406081920
更新日期:2020-01-01 00:00:00
abstract::Effective blood pressure control with a large arsenal of conventional antihypertensive drugs, such as diuretics, beta-adrenergic blockers, and calcium channel blockers, significantly reduce the morbidity and mortality associated with cardiovascular disease. However, blood pressure control with these drugs does not red...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207780618876
更新日期:2007-01-01 00:00:00
abstract::The intestinal epithelium forms a barrier against the intestinal contents and the wider environment, allowing entry of selected molecules for nutrition and programming of the mucosal immune system, but excluding toxins and most microorganisms. Many receptors and signalling pathways are coupled and implicated in the ep...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612819666131119110835
更新日期:2014-01-01 00:00:00
abstract::The discovery of the delicate role of endogenous nitric oxide in the homeostasis of various cellular functions and the dynamic behaviour of the airways, has led to a new, rapidly progressing area of physiological science, that has direct bearing for our understanding of multiple airway diseases. The potentially protec...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206778194141
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel category of oral antidiabetic drugs that inhibit renal glucose reabsorption and increase renal glucose excretion, thus lowering plasma glucose levels. This unique mechanism of SGLT2i action is insulin independent, thus improving glycemic control ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170113152742
更新日期:2017-01-01 00:00:00
abstract::Pulmonary arterial hypertension (PAH) is a severe vascular complication of connective tissue diseases. In the context of systemic sclerosis (SSc), PAH is a devastating disease with a dramatic impact on prognosis and survival. Despite advances in early diagnosis and the development of new targeted treatments, SSc-relat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212799504704
更新日期:2012-01-01 00:00:00
abstract::The use of systematic approach for the analysis of mechanism of action of drugs at different levels of biological organization of organisms is an important task in experimental and clinical pharmacology for drug designing and increasing the efficacy and safety of drugs. The analysis of published data on pharmacologica...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170829135115
更新日期:2018-01-01 00:00:00
abstract::Ever since pure molecular entities have been adapted as drug, varied manifestations other than elimination of infections are frequently been acknowledged as side effects. Contemporary drug research focuses on these issues besides developing new molecules for the restoration of unnatural functional deviations in variou...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207780249119
更新日期:2007-01-01 00:00:00
abstract:AIMS:To compare the efficacy of pemafibrate (PF) and fenofibrate (FF) in treating dyslipidemia. METHODS:A comprehensive search was performed on the public database to identify relevant randomized controlled trials (RCTs), which compared the effects of PF and FF treatment in lipid parameters among patients with dyslipi...
journal_title:Current pharmaceutical design
pub_type: meta分析
doi:10.2174/1381612825666191126102943
更新日期:2019-01-01 00:00:00
abstract::Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle and RNA polymerase II transcription. Several pharmacological CDK inhibitors (PCIs) are currently in clinical trials as potential cancer therapeutics since CDK hyperactivation is detected in the majority of neoplasias. Within the last few years, the a...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777442083
更新日期:2006-01-01 00:00:00
abstract::Chemotherapy is one of the most frequently employed and reliable treatment options for the management of a variety of cancers. Taxanes (paclitaxel, docetaxel and cabazitaxel) are frequently prescribed to treat breast cancer, hormone refractory prostate cancer, non-small cell lung cancer and ovarian cancer. Most of the...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160524144926
更新日期:2016-01-01 00:00:00
abstract::The endocannabinoid system (ECS) is now recognised as an important modulator of various central nervous system processes. More recently, an increasing body of evidence has accumulated to suggest antioxidant, anti-inflammatory and neuroprotective roles of ECS. In this review we discuss the role and therapeutic potentia...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990434
更新日期:2014-01-01 00:00:00
abstract::Curcumin is a natural polyphenol product derived from the rhizome of the Curcuma longa. In vivo and in vitro studies have uncovered many important bioactivities of curcumin, such as antioxidant activity, inducing cell apoptosis, inhibiting cell proliferation, anti-cell adhesion and motility, anti-angiogenesis and anti...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:2013-01-01 00:00:00
abstract::Extracellular matrix (ECM) is composed of large collagen fibrils. Glycoproteins, such as fibronectin, can bind to collagen or form their own networks. Collagen fibrils are also decorated by proteoglycans, proteins that have large glycosaminoglycan sidechains. In addition, extracellular space often contains hyaluronan,...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787846720
更新日期:2009-01-01 00:00:00
abstract::Stability of a dosage form is its ability to preserve its quality attributes within preset limits. The time span over which these attributes remain within specifications is the shelf-life of the drug product. Stability is a very complex feature and is influenced not only by the stability of the drug substance but also...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160726094236
更新日期:2016-01-01 00:00:00
abstract::Multidrug resistance (MDR) is a phenomenon through which tumor cells develop resistance against the cytotoxic effects of various structurally and mechanistically unrelated chemotherapeutic agents. The most consistent feature in MDR is overexpression and/or overactivity of ATP-dependent drug efflux transporters. Other ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151124234417
更新日期:2016-01-01 00:00:00
abstract::Membrane disrupting lytic peptides are abundant in nature and serve insects, invertebrates, vertebrates and humans as defense molecules. Initially, these peptides attracted attention as antimicrobial agents; later, the sensitivity of tumor cells to lytic peptides was discovered. In the last decade intensive research h...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043383971
更新日期:2004-01-01 00:00:00
abstract::Oncology remains an increasingly important focus of therapeutic development yet there remain many scientific and operational bottlenecks to deliver optimum treatments efficiently. Radiopharmaceuticals constitute a group of methodologies able to support the many stages of drug development. Methods such as [(18)F]-FDG-P...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787581977
更新日期:2009-01-01 00:00:00
abstract::MicroRNA-34a (miR-34a) promotes apoptosis via down-regulating many anti-apoptotic proteins. Aldehyde dehydrogenase 2 (ALDH2) is an anti-apoptotic enzyme whose activity decline associates with myocardial injury. We tested hypothesis that miR-34a might play a pro-apoptotic role in myocardial infarction (MI) by down-regu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990325
更新日期:2013-01-01 00:00:00
abstract::Synaptic plasticity is now known to occur at glutamate synapses throughout the brain, including the neocortex, and to play a role in neurodevelopment as well as in a broad spectrum of adult neural functions. Here the hypothesis that synaptic plasticity, specifically long term depression, is the neural substrate that m...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612819666140110122307
更新日期:2014-01-01 00:00:00
abstract::Stimulation of β-adrenergic receptors in the heart is the most effective endogenous way to increase the mechanical performance of cardiac tissues to meet the requirements of a fight-or-flight situation or stress. On the other hand, sustained activation of cardiac β-receptors initiates maladaptive remodeling of the myo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666141029111240
更新日期:2015-01-01 00:00:00
abstract::In the last two decades a tremendous development has been noticed in our understanding of the purinergic system, consisting of heterogeneously expressed purinoceptor subtypes and its classical agonists: e.g., adenosine triphosphate, uridine triphosphate or complex dinucleoside polyphosphates. These agonists exert mult...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212803582504
更新日期:2012-01-01 00:00:00
abstract::Since the first description of putative progenitor endothelial cells mobilized from bone marrow by stimuli like ischemia and cytokines, several studies in animals have confirmed their role in neovascularization of ischemic organs. In ischemic myocardium endothelial progenitor cells can prevent cardiomyocyte apoptosis,...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207780831329
更新日期:2007-01-01 00:00:00
abstract::Atherosclerosis is a multifactorial and long-lasting process in humans. Therefore, animal models where more rapid changes occur can be useful for the study of this process. Among such models are the apolipoprotein (apo) E knock out mice. Apo E deficient mice show impaired clearing of plasma lipoproteins and they devel...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208783497769
更新日期:2008-01-01 00:00:00
abstract::Although the obesity epidemic is constantly expanding at very high costs for health care systems, the currently available options for the pharmacotherapy of obesity are very limited. This is not due to lack of interest or research on the subject but rather to the poor efficacy and/or safety profile of the majority of ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990302
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:At sufficient sun exposure, humans can synthesize vitamin D3 endogenously in their skin, but today's lifestyle makes the secosteroid a true vitamin that needs to be taken up by diet or supplementation with pills. The vitamin D3 metabolite 1α,25-dihydroxyvitamin D3 acts as a nuclear hormone activating the tra...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190705193227
更新日期:2019-01-01 00:00:00
abstract::The pharmacophore concept is central to the rational drug design and discovery process. Traditionally, a pharmacophore is defined as a specific three-dimensional (3D) arrangement of chemical functional groups found in active molecules, which are characteristic of a certain pharmacological class of compounds. Herein, b...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612013397834
更新日期:2001-05-01 00:00:00
abstract::The deregulated proteolysis is associated with various diseases in humans. Proteases are commonly regarded as the therapeutic targets. Almost one-third of all proteolytic enzymes in humans are serine proteases. This work provides a brief characteristic of the proteinaceous natural inhibitors, mostly of serine protease...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:2013-01-01 00:00:00
abstract::A growing body of evidence shows that gamma-hydroxybutyric acid (GHB) is an addictive substance. Its precursors gammabutyrolactone (GBL) and 1,4-butanediol (1,4-BD) show the same properties and may pose even more risks due to different pharmacokinetics. There are indications that problematic GHB use is increasing in t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990624
更新日期:2014-01-01 00:00:00
abstract::Stimulant use disorders are an unrelenting public health concern worldwide. Agonist replacement therapy is among the most effective strategies for managing substance use disorders including nicotine and opioid dependence. The present paper reviewed clinical data from human laboratory self-administration studies and cl...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161281940131209142843
更新日期:2013-01-01 00:00:00