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 mechanisms such as overexpression of drug-detoxifying enzymes and alterations in pro-survival or pro-death signaling pathways are also responsible for MDR. Inflammatory mediators including interleukin-6 (IL-6) play important roles in various events during inflammation and are also involved in development and progression of several types of cancers. Mounting evidence has suggested a crosstalk between IL-6 and MDR in cancer, highlighting the role of IL-6 in chemotherapy response, and the potential opportunity to control MDR through modulation of IL-6 expression. Upregulation of IL-6 has been shown to promote MDR through activation of Janus kinases (JAK)/signal transducer and activator of transcription 3 (STAT3), phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt), and Ras-MAPK (mitogen-activated protein kinase) pathways. Activation of the aforementioned pathways changes the expression pattern of several genes involved in proliferation, survival and cell cycle regulation, thus facilitating MDR. Conversely, IL-6 inhibition using different strategies (antibodies, siRNA, and antisense transfection) has been shown to improve tumor responsiveness and mitigate MDR in different cancer cell lines. This review focuses on the in vitro, experimental and clinical findings on the role of IL-6 in MDR, and potential therapeutic opportunities arising from this role of IL-6.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Ghandadi M,Sahebkar Adoi
10.2174/1381612822666151124234417subject
Has Abstractpub_date
2016-01-01 00:00:00pages
518-26issue
5eissn
1381-6128issn
1873-4286pii
CPD-EPUB-72076journal_volume
22pub_type
杂志文章,评审abstract:BACKGROUND:Plants have been used to treat health disorders and prevent diseases since antiquity in all civilizations including the Indian and Chinse civilizations. Giloy (Tinospora cordifolia L.) is one of the most important medicinal plants in Indian folk medicine and is commonly known as the "Heart-leaved Moonseed" o...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200625111530
更新日期:2020-06-25 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::Molecular Mechanics (MM) force fields are the methods of choice for protein simulations, which are essential in the study of conformational flexibility. Given the importance of protein flexibility in drug binding, MM is involved in most if not all Computational Structure-Based Drug Discovery (CSBDD) projects. This pap...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990600
更新日期:2014-01-01 00:00:00
abstract::Over the last several years, it has become increasingly clear that dendritic cells (DC) are not only critical for the initiation of T cell immunity, but these cells also determine the course of the subsequent immune response (i.e. tolerance vs. immunity, Th1 vs. Th2). However, the mechanisms by which DC can influence ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612013397627
更新日期:2001-07-01 00:00:00
abstract:BACKGROUND:Multi-drug resistant infections are a growing worldwide health concern. There is an urgent need to produce alternative antimicrobial agents. OBJECTIVE:The study aimed to design a new hybrid antimicrobial peptide, and to evaluate its antimicrobial activity alone and in combination with traditional antibiotic...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200128090700
更新日期:2020-01-01 00:00:00
abstract::Chronic pain is a widespread healthcare problem affecting not only the patient but in many ways all the society. Chronic pain is a disease itself that endures for a long period of time and it is resistant to the majority of medical treatments that provide modest improvements in pain and minimum improvements in physica...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140314150634
更新日期:2014-01-01 00:00:00
abstract::Free energy perturbation (FEP) theory coupled to molecular dynamics (MD) or Monte Carlo (MC) statistical mechanics offers a theoretically precise method for determining the free energy differences of related biological inhibitors. Traditionally requiring extensive computational resources and expertise, it is only rece...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212799436421
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Enhancing a compound's biological activity is the central task for lead optimization in small molecules drug discovery. However, it is laborious to perform many iterative rounds of compound synthesis and bioactivity tests. To address the issue, it is highly demanding to develop high quality in silico bioacti...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200427111309
更新日期:2020-01-01 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::Supraventricular tachycardias (SVTs) are observed in 0,1-0,4% of the paediatric population and represent an important clinical problem with related significant health and social issues. Most tachycardias are paroxysmal, being associated with sudden onset and termination, and only a relatively small number of them is p...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784007761
更新日期:2008-01-01 00:00:00
abstract::First generation drug-eluting stents (DES) have significantly improved the treatment options for patients with symptomatic coronary artery disease by decreasing rates of acute vessel closure and restenosis after percutaneous coronary revascularization procedures. However, early enthusiasm was temperd by reports of lat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210794454879
更新日期:2010-01-01 00:00:00
abstract::Emerging evidence has shown that microRNAs (miRNAs) can act as oncogenes in the initiation and progression of leukemia and lymphoma. Aberrant expression of oncogenic miRNAs, including miR-155, miR-17-92, miR-21, miR-125b, miR-93, miR-143-p3, miR-196b, and miR-223 promotes leukemogenesis through increasing the leukemic...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140128211724
更新日期:2014-01-01 00:00:00
abstract::Helicobacter pylori infection causes progressive damage to gastric mucosa and results in serious disease such as peptic ulcer disease, MALT lymphoma, or gastric adenocarcinoma in 20% to 30% of patients. The current approach is to make a firm diagnosis, give combination antibiotic and antisecretory therapy, and confirm...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003399077
更新日期:2000-10-01 00:00:00
abstract::The recent developments in the field of recombinant DNA, protein engineering and cancer biology, have let us gain insight into many cancer-related mechanisms. Moreover, novel techniques have facilitated tools allowing unique distinction between malignantly transformed cells, to regular ones. This understanding has pav...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206775201983
更新日期:2006-01-01 00:00:00
abstract::Adenosine A(2A)-dopamine D(2) receptor interactions play a very important role in striatal function. A(2A)-D(2) receptor interactions provide an example of the capabilities of information processing by just two different G protein-coupled receptors. Thus, there is evidence for the coexistence of two reciprocal antagon...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784480108
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:On a tide of big data, machine learning is coming to its day. Referring to huge amounts of epigenetic data coming from biological experiments and clinic, machine learning can help in detecting epigenetic features in genome, finding correlations between phenotypes and modifications in histone or genes, accele...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666181112114228
更新日期:2018-01-01 00:00:00
abstract::Naoxintong (NXT), a Chinese Materia Medica standardized product, extracted from 16 various kinds of Chinese traditional herbal medicines including Salvia miltiorrhiza, Angelica sinennsis, Astragali Radix, is clinically effective in treating atherosclerosisrelated diseases. Here, we tested the hypothesis that the anti-...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612811319330008
更新日期:2013-01-01 00:00:00
abstract::microRNAs (miRNAs) comprise a recently discovered class of non-coding RNAs with regulatory functions in post-transcriptional gene expression control. Many miRNAs are located in genomic regions that are frequently deleted in cancer, or are subject to epigenetic and transcriptional deregulation in cancer cells. The miRN...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161213804805649
更新日期:2013-01-01 00:00:00
abstract::Anxiety disorders are common and disabling conditions. Current drug treatment methods have limitations including resistance, delayed efficacy and side effects. The advent of sophisticated imaging techniques and the production of highly selective receptor ligands have increased our knowledge of the biological mechanism...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208786848775
更新日期:2008-01-01 00:00:00
abstract::Carcinogenesis results from the long-term accumulation of genetic and epigenetic aberrations at the molecular level, which are under constant selection pressure for growth advantage. Recognizing that cancer is the result of this long-term, multi-step process provides opportunities for molecularly targeted cancer preve...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023394935
更新日期:2002-01-01 00:00:00
abstract::The pivotal therapeutic role of myocardial metabolic modulation in ischemic heart disease (IHD) is increasingly recognized. Among the others, inhibitors of free fatty acids (FFA) oxidation have been consistently shown to play an important role in the therapeutic strategy of IHD patients. Additionally, abnormalities of...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787582093
更新日期:2009-01-01 00:00:00
abstract::Gestational diabetes mellitus is a common metabolic complication of pregnancy. Universal guidelines on gestational diabetes have been impeded by the long-term controversies on its definition and screening strategies. The prevalence of gestational diabetes is rising all over the world, is significantly influenced by et...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666201106092423
更新日期:2020-01-01 00:00:00
abstract::Dengue is one of the most important arboviral infections worldwide, infecting up to 390 million people and causing 25,000 deaths annually. Although a licensed dengue vaccine is available, it is not efficacious against dengue serotypes that infect people living in South East Asia, where dengue is an endemic disease. He...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170913163904
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Erectile dysfunction (ED) is an evolving health problem in the aging male population. Chronic low-grade inflammation is a critical component of ED pathogenesis and a probable intermediate stage of endothelial dysfunction, especially in metabolic diseases, with the inclusion of obesity, metabolic syndrome, an...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200424161018
更新日期:2020-01-01 00:00:00
abstract::Age-associated cognitive decline and dementia are conditions in which there is deterioration in memory, thinking, and behavior, with profound effects on the ability to perform everyday activities and well-being. Even if dementia mainly affects older persons, it is not a normal part of aging. Alzheimer's disease accoun...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612822666151204000733
更新日期:2016-01-01 00:00:00
abstract::Natural product drugs that target the tubulin/microtubule system remain an important component in the therapeutic arsenal to treat many types of malignancies. Agents such as the taxanes and vinca alkaloids bind to beta-tubulin and disrupt microtubule dynamics by inducing a potent mitotic block and subsequent cell deat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612053764706
更新日期:2005-01-01 00:00:00
abstract::Abnormal regulation of the ubiquitin-proteasome system (UPS) has been known to be involved in the pathogenesis of a variety of human diseases. A number of studies have focused on the identification of small modifiers for the UPS. Even though the proteasome inhibitor Bortezomib (Velcade®) has been approved for the ther...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319220013
更新日期:2013-01-01 00:00:00
abstract::Opioid peptides showing selectivity for delta receptor have been isolated from enzymatic digests of plant proteins. Five peptides were derived from wheat gluten, and named gluten exorphins A5, A4, B5, B4 and C. Two opioid peptides were also released from spinach ribulose-bisphosphate-carboxylase/oxygenase (Rubisco), a...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033454838
更新日期:2003-01-01 00:00:00
abstract::Kv7.x channels are a family of six transmembrane domain, single pore-loop, voltage-gated K(+) channels. Five members of the family have been identified to date, including the cardiac channel Kv7.1 (formerly known as KvLQT1) and four neuronal Kv7.x channels, Kv7.2-5. Heteromeric channels containing Kv7.3 and either Kv7...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788186326
更新日期:2009-01-01 00:00:00
abstract::The rapid advancement of computer architectures and development of mathematical algorithms offer a unique opportunity to leverage the simulation of macromolecular systems at physiologically relevant timescales. Herein, we discuss the impact of diverse structure-based and ligand-based molecular modeling techniques in d...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190304123545
更新日期:2019-01-01 00:00:00