Abstract:
:The activities of individual cells must be tightly coordinated in order to build and maintain complex 3- dimensional body structures during embryogenesis and regeneration. Thus, one way to view cancer is within systems biology as a network disorder affecting the ability of cells to properly interact with a morphodynamic field of instructive signals that keeps proliferation and migration orchestrated toward the anatomical needs of the host organism. One layer of this set of instructive microenvironmental cues is bioelectrical. Voltage gradients among all somatic cells (not just excitable nerve and muscle) control cell behavior, and the ionic coupling of cells into networks via electrochemical synapses allows them to implement tissue-level patterning decisions. These gradients have been increasingly implicated in the induction and suppression of tumorigenesis and metastasis, in the emerging links between developmental bioelectricity to the cancer problem. Consistent with the well-known role of neurotransmitter molecules in transducing electrical activity to downstream cascades in the brain, serotonergic signaling has likewise been implicated in cancer. Here, we review these recent data and propose new approaches for manipulating bioelectric and neurotransmitter pathways in cancer biology based on a bioelectric view of cancer. To support this methodology, we present new data on the effects of the SSRI Prozac and its analog (ZINC ID = ZINC06811610) on survival of both cancer (MCF7) and normal (MCF10A) breast cells exposed to these compounds. We found an IC50 concentration (25 µM for Prozac and 100 µM for the Prozac analog) at which these compounds inhibited tumor cell survival and proliferation. Additionally, at these concentrations, we did not observe alterations in a non-tumoral cell line. This constitutes a proof-of-concept demonstration for our hypothesis that the use of both existing and novel drugs as electroceuticals could serve as an alternative to highly toxic chemotherapy strategies replacing or augmenting them with less toxic alternatives. We believe this new approach forms an exciting roadmap for future biomedical advances.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Tuszynski J,Tilli TM,Levin Mdoi
10.2174/1381612823666170530105837subject
Has Abstractpub_date
2017-01-01 00:00:00pages
4827-4841issue
32eissn
1381-6128issn
1873-4286pii
CPD-EPUB-83760journal_volume
23pub_type
杂志文章,评审abstract::Hepatitis C virus (HCV) infections are a serious viral health problem globally, causing liver cirrhosis and inflammation that can develop to hepatocellular carcinoma and death. Since the HCV NS3/4A protease complex cleaves the scissile peptide bond in the viral encoded polypeptide to release the non-structural protein...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990632
更新日期:2014-01-01 00:00:00
abstract::Melanoma is the deadliest type of skin cancers, accounting for more than 80% of skin cancer mortality. Although melanoma was known very early in the history of medicine, treatment for this disease had remained largely the same until very recently. Previous treatment options, including removal surgery and systemic chem...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200130091318
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Origanum vulgare is used in Armenian cuisine as well as in folk medicine. The aim of this investigation was to determine the peculiarities of the chemical composition of Armenian flora's oregano essential oil (EO) and ethanol extract (EE) and to characterize mainly antioxidant and antibacterial properties in...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612825666190702095612
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Bacterial cellulose (BC) has recently attained greater interest in various research fields, including drug delivery for biomedical applications. BC has been studied in the field of drug delivery, such as tablet coating, controlled release systems and prodrug design. OBJECTIVE:In the current work, we tested ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612825666191011103851
更新日期:2019-01-01 00:00:00
abstract::The comorbid prevalence of major depressive disorder (MDD) with obesity and type II diabetes mellitus reflects the existence of a subset of individuals with a complex common pathophysiology and overlapping risk factors. Such comorbid disease presentations imply a number of difficulties, including: decreased treatment ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160922165706
更新日期:2016-01-01 00:00:00
abstract::Angiogenic eye disease is among the most common causes of blindness worldwide. Current treatment approaches are insufficiently effective and partially associated with significant adverse effects. From an investigational view, the eye provides an ideal setting to observe real-time and serial observations of angiogenesi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054367292
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:New Oral Anticoagulants (NOACs) are effective and widely used to prevent and treat thromboembolic diseases, but the response to NOACs differs according to ABCB1 genotypes. OBJECTIVE:We investigated the effects of ABCB1 genotypes on the pharmacokinetics and clinical outcomes of NOACs. METHODS:We searched Pu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,meta分析,评审
doi:10.2174/1381612824666181018153641
更新日期:2018-01-01 00:00:00
abstract::Pyrimidine nucleotides, including UTP, UDP and UDP-glucose, are important signaling molecules which activate G protein-coupled membrane receptors of the P2Y family. Four distinct pyrimidine nucleotide-sensitive P2Y receptor subtypes have been cloned, P2Y(2), P2Y(4), P2Y(6) and P2Y(14). Pharmacological experiments indi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023392937
更新日期:2002-01-01 00:00:00
abstract::The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a cAMP-regulated Cl- channel whose major function is to facilitate epithelial fluid secretion. Loss-of-function mutations in CFTR cause the genetic disease cystic fibrosis. CFTR is required for transepithelial fluid transport in certain secretor...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990321
更新日期:2013-01-01 00:00:00
abstract::Single-agent therapy with molecularly targeted agents has shown limited success in tumor growth control, mainly because escape or resistance mechanisms are activated once a signalling molecule is inhibited. Rational combinations of target-specific agents could counteract this response providing a useful strategy in ca...
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::The diatomic molecule of oxygen contains two uncoupled electrons and can therefore undergo reduction, yielding several different oxygen metabolites, which are collectively called Reactive Oxygen Species or ROS. They are invariably produced in aerobic environments through a variety of mechanisms, which include electron...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043384664
更新日期:2004-01-01 00:00:00
abstract::This review is based on carriers of natural origin such as polysaccharides, proteins, and cell derived entities which have been used for delivery of siRNA. To realize the therapeutic potential of a delivery system, the role of the carrier is of utmost importance. Historical aspects of viral vectors, the first carriers...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161282131151013185528
更新日期:2015-01-01 00:00:00
abstract::Ras is a 21 kDa membrane-localized G protein that is coupled to receptor and non-receptor tyrosine kinase activation of downstream cytoplasmic and nuclear events. Mutated ras genes are common, and occur in a wide variety of human malignancies. These activating mutations result in constitutive signaling, thereby stimul...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612013397258
更新日期:2001-11-01 00:00:00
abstract::Risk reduction and the attainment of good outcomes in contemporary cataract surgery depend in part on patient compliance with a postoperative regimen of topical eye drops. Topical drops are expensive and challenging to instill properly for patients. The consequences of noncompliance or poor compliance can be significa...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666161129150628
更新日期:2017-01-01 00:00:00
abstract::The Hereditary Spastic Paraparesis (HSP) or Strumpell-Lorrain disease is a heterogeneous neurodegenerative disease of the spinal cord. It is genetically transmitted and characterized by a progressive muscle weakness, spasticity of the lower limbs and awkward gain. There is no specific pharmacological treatment. The ph...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612822666151204001830
更新日期:2016-01-01 00:00:00
abstract::The liver acts as a host to many functions hence raising the possibility that any one may be compromised by a single gene defect. Inherited or de novo mutations in these genes may result in relatively mild diseases or be so devastating that death within the first weeks or months of life is inevitable. Some diseases ca...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211797247541
更新日期:2011-01-01 00:00:00
abstract::Colchicine is a lipophilic alkaloid drug, which exhibits ant-inflammatory and anti-fibrotic properties. Cardinal mechanisms of action of colchicine are the disruption of the microtubule system and the inhibition of neutrophil adhesion and recruitment. Colchicine is indicated in the prevention and treatment of gouty ar...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180123101313
更新日期:2018-01-01 00:00:00
abstract::Commonly, the angiogenic growth factors signify healing. However, gastrointestinal ulceration is still poorly understood particularly with respect to a general pharmacological/pathophysiological role of various angiogenic growth factors implemented in growth factors wound healing concept. Thereby, we focused on the st...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180712110447
更新日期:2018-01-01 00:00:00
abstract::Current antiretroviral therapy has had a significant impact on HIV associated morbidity and mortality. Despite these positive outcomes current antiretroviral regimens have significant deficiencies which include multiple drug-drug interactions, high pill burdens, and considerable financial expense. Perhaps the greatest...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206776055868
更新日期:2006-01-01 00:00:00
abstract::Protein stability of hypoxia-inducible factor (HIF)alpha subunits is regulated by the oxygen-sensing prolyl-4-hydroxylase domain (PHD) enzymes. Under oxygen-limited conditions, HIFalpha subunits are stabilized and form active HIF transcription factors that induce a large number of genes involved in adaptation to hypox...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209789649411
更新日期:2009-01-01 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:BACKGROUND:Preterm birth is the major cause of perinatal mortality and morbidity worldwide. Attempts to reduce the burden may be proactive using biochemical or biophysical prediction and preventative measures. If these efforts fail, then the approach may have to be reactive using tocolytics to inhibit spontaneous prete...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190329124214
更新日期:2019-01-01 00:00:00
abstract::Advances in particle engineering techniques, such as spray drying, freeze drying and supercritical fluid precipitation, have greatly enhanced the ability to control the structure, morphology, and solid state phase of inhalable sized particles (1 - 5 µm) for formulation in pressurized metered dose inhalers (pMDI). To o...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150820110153
更新日期:2015-01-01 00:00:00
abstract::It is generally accepted that mitochondrial dysfunction and endoplasmic reticulum (ER) stress are related to insulin resistance and type 2 diabetes. Mitochondria use substrates from lipid and glucose metabolism in order to generate ATP, and when mitochondrial O2 consumption is decreased due to an altered metabolism th...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160209152033
更新日期:2016-01-01 00:00:00
abstract::Growth differentiation factor 5 (GDF5) is a member of the bone morphogenic protein (BMP) family and plays critical roles in organ development processes including bone, cartilage, ligament, and joint formation. GDF5 is expressed in the cartilage primordium in the early limb development, and in the interzone of joint fo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319190003
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Dietary supplements have been widely used among the United States of America (USA) and the European Union (EU) population not only as a form of nutrition but also for medicinal purposes. Still, the legislation regulating these supplements remains unclear due to the fact that they can be considered as foodstu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170117122801
更新日期:2017-01-01 00:00:00
abstract::A small but increasing number of gene expression based biomarkers are becoming available for routine clinical use, principally in oncology and transplantation. These underscore the potential of gene expression arrays and RNA sequencing for biomarker development, but this potential has not yet been fully realized and m...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150313130256
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Ulinastatin (UTI) plays the beneficial roles in modifying cerebral ischemic injury evoked by cardiac arrest (CA). XueBiJing (XBJ), comprised of extracts from Chinese herbals, has been used for the treatment of sepsis and ischemic disorders linked to multiple organ dysfunction syndromes. The current study was...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612825666190206224134
更新日期:2018-01-01 00:00:00
abstract::The development of radioligands to image beta-amyloid (A beta) plaques and neurofibrillary tangles (NFTs) in vivo in the aging human brain is an important and active area of radiopharmaceutical design. When used in combination with positron emission tomography (Pet) or single photon emission computed tomography (spect...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043384772
更新日期:2004-01-01 00:00:00
abstract::Pituitary adenylyl cyclase activating polypeptide (PACAP) is a neuropeptide with great neuroprotective effects and remarkable therapeutic potential. PACAP activates several cellular pathways to exert its protective effects. Emerging evidence shows that PACAP can modify the levels and activity of cell cycle components ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666181127102311
更新日期:2018-01-01 00:00:00