Abstract:
:One of the crucial challenges in the clinical management of cancer is resistance to chemotherapeutics. Multidrug resistance (MDR) has been intensively studied, and one of the most prominent mechanisms underlying MDR is overexpression of adenosine triphosphate (ATP)-binding cassette (ABC) transporters. Despite research efforts to develop compounds that inhibit the efflux activity of ABC transporters and thereby increase classical chemotherapy efficacy, to date, the Food and Drug Administration (FDA) has not approved the use of any ABC transporter inhibitors due to toxicity issues. Hedgehog signaling is aberrantly activated in many cancers, and has been shown to be involved in chemotherapy resistance. Recent studies showed that the Hedgehog receptor Ptch1, which is over-expressed in many recurrent and metastatic cancers, is a multidrug transporter and it contributes to the efflux of chemotherapeutic agents such as doxorubicin, and to chemotherapy resistance. Remarkably, Ptch1 uses the proton motive force to efflux drugs, in contrast to ABC transporters, which use ATP hydrolysis. Indeed, the "reversed pH gradient" that characterizes cancer cells, allows Ptch1 to function as an efflux pump specifically in cancer cells. This makes Ptch1 a particularly attractive therapeutic target for cancers expressing Ptch1, such as lung, breast, prostate, ovary, colon, brain, adrenocortical carcinoma, and melanoma. Screening of chemical libraries have identified several molecules that are able to enhance the cytotoxic effect of different chemotherapeutic agents by inhibiting Ptch1 drug efflux activity in different cancer cell lines that endogenously over-express Ptch1. In vivo proof of concept has been performed in mice where combining one of these compounds with doxorubicin prevented the development of xenografted adrenocortical carcinoma tumors more efficiently than doxorubicin alone, and without obvious undesirable side effects. Therefore, the use of a Ptch1 drug efflux inhibitor in combination with classical or targeted therapy could be a promising therapeutic option for Ptch1-expressing cancers.
journal_name
Cellsjournal_title
Cellsauthors
Hasanovic A,Mus-Veteau Idoi
10.3390/cells7080107subject
Has Abstractpub_date
2018-08-14 00:00:00issue
8issn
2073-4409pii
cells7080107journal_volume
7pub_type
杂志文章,评审相关文献
Cells文献大全abstract::Lysosomal function has a central role in maintaining neuronal homeostasis, and, accordingly, lysosomal dysfunction has been linked to neurodegeneration and particularly to Parkinson's disease (PD). Lysosomes are the converging step where the substrates delivered by autophagy and endocytosis are degraded in order to re...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells9112399
更新日期:2020-11-02 00:00:00
abstract::The third isotype of beta-adrenoreceptors (β3-AR) has recently come (back) into focus after the observation of its expression in white and beige human adipocytes and its implication in metabolic regulation. This coincides with the recent development and marketing of agonists at the human receptor with superior specifi...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells9122584
更新日期:2020-12-02 00:00:00
abstract:BACKGROUND:The search for an effective therapy for local radiation injuries (LRI) is urgent; one option is mesenchymal stem cells (MSC) derived from the placenta and their conditioned medium for the regenerative processes of the skin. METHODS:We used 80 animals, randomly assigned to four groups: control (C) animals th...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells9122558
更新日期:2020-11-29 00:00:00
abstract::Respiratory syncytial virus (RSV) infection affects the lives of neonates throughout the globe, causing a high rate of mortality upon hospital admission. Yet, therapeutic options to deal with this pulmonary pathogen are currently limited. Helminth therapy has been well received for its immunomodulatory role in hosts, ...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells9051314
更新日期:2020-05-25 00:00:00
abstract::Osteoarthritis (OA) is a degenerative and inflammatory joint disorder with cartilage loss. Dental pulp stem cells (DPSCs) can undergo chondrogenic differentiation and secrete growth factors associated with tissue repair and immunomodulation. Leukocyte- and platelet-rich fibrin (L-PRF) emerges in regenerative medicine ...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells9040980
更新日期:2020-04-15 00:00:00
abstract::Microalgae have emerged as a promising platform for production of carbon- and energy- rich molecules, notably starch and oil. Establishing an economically viable algal biotechnology sector requires a holistic understanding of algal photosynthesis, physiology, cell cycle and metabolism. Starch/oil productivity is a com...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells8101154
更新日期:2019-09-26 00:00:00
abstract::Tissue inhibitor of metalloproteinase-3 (TIMP-3) is a component of the extracellular environment, where it mediates diverse processes including matrix regulation/turnover, inflammation and angiogenesis. Rare TIMP-3 risk alleles and mutations are directly linked with retinopathies such as age-related macular degenerati...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells9010039
更新日期:2019-12-21 00:00:00
abstract::The Hippo pathway is a cellular signalling network, which plays major roles in organ homeostasis and development[...]. ...
journal_title:Cells
pub_type: 社论
doi:10.3390/cells8101179
更新日期:2019-09-30 00:00:00
abstract::Cell division cycle 42 (CDC42), a small Rho GTPase, plays a critical role in many cellular processes, including cell proliferation and survival. CDC42 interacts with the CRIB (Cdc42- and Rac-interactive binding) domain of CDC42SE1, a small effector protein of 9 kDa. We found that the expression of CDC42SE1 was reduced...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells8020117
更新日期:2019-02-02 00:00:00
abstract::Second-generation antipsychotics (SGAs) are the cornerstone of treatment for schizophrenia because of their high clinical efficacy. However, SGA treatment is associated with severe metabolic alterations and body weight gain, which can increase the risk of type 2 diabetes and cardiovascular disease, and greatly acceler...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells8111336
更新日期:2019-10-29 00:00:00
abstract::The endoplasmic reticulum (ER) stress response and autophagy are important cellular responses that determine cell fate and whose dysregulation is implicated in the perturbation of homeostasis and diseases. Tonicity-responsive enhancer-binding protein (TonEBP, also called NFAT5) is a pleiotropic stress protein that med...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells9091928
更新日期:2020-08-20 00:00:00
abstract::Meiosis is required to reduce to haploid the diploid genome content of a cell, generating gametes-oocytes and sperm-with the correct number of chromosomes. To achieve this goal, two specialized cell divisions without intermediate S-phase are executed in a time-controlled manner. In mammalian female meiosis, these divi...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells9020390
更新日期:2020-02-07 00:00:00
abstract::Nile tilapia is the third most cultivated fish worldwide and a novel model species for evolutionary studies. Aiming to improve productivity and contribute to the selection of traits of economic impact, biotechnological approaches have been intensively applied to species enhancement. In this sense, recent studies have ...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells9081752
更新日期:2020-07-22 00:00:00
abstract::Rab proteins compose the largest family of small GTPases and control the different steps of intracellular membrane traffic. More recently, they have been shown to also regulate cell signaling, division, survival, and migration. The regulation of these processes generally occurs through recruitment of effectors and reg...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells8080909
更新日期:2019-08-16 00:00:00
abstract::Skin models with efficient skin barrier function are required for percutaneous absorption studies. The contribution of media supplementation with n-3 and n-6 polyunsaturated fatty acids (PUFAs) to the development of the skin barrier function of in vitro skin models remains incompletely understood. To investigate wheth...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells8101142
更新日期:2019-09-25 00:00:00
abstract::All eukaryotes rely on the ubiquitin-proteasome system (UPS) and autophagy to control the abundance of key regulatory proteins and maintain a healthy intracellular environment. In the UPS, damaged or superfluous proteins are ubiquitinated and degraded in the proteasome, mediated by three types of ubiquitin enzymes: E1...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells9102219
更新日期:2020-10-01 00:00:00
abstract::The primary cilium is an organelle involved in cellular signalling. Mutations affecting proteins involved in cilia assembly or function result in diseases known as ciliopathies, which cause a wide variety of phenotypes across multiple tissues. These mutations disrupt various cellular processes, including regulation of...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells9020278
更新日期:2020-01-23 00:00:00
abstract:BACKGROUND:The current approaches to distinguish follicular adenomas (FA) and follicular thyroid cancer (FTC) at the pre-operative stage have low predictive value. Liquid biopsy-based analysis of circulating extracellular vesicles (EVs) presents a promising diagnostic method. However, the extreme heterogeneity of plasm...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells9081917
更新日期:2020-08-18 00:00:00
abstract::Autophagy is an intracellular catabolic system that delivers cytoplasmic constituents and organelles in the vacuole. This degradative process is mediated by a group of proteins coded by autophagy-related (ATG) genes that are widely conserved from yeasts to plants and mammals. Homologs of ATG genes have been also ident...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells6040036
更新日期:2017-10-22 00:00:00
abstract::Trichinella spiralis maintains chronic infections within its host, involving a variety of immunomodulatory properties, the mechanisms of which have not been completely elucidated. In this study, we found that T. spiralis infection induced strong regulatory T cell responses through parasite excretory-secretory (ES) pro...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells8111404
更新日期:2019-11-07 00:00:00
abstract::The nucleolus has emerged as a cellular stress sensor and key regulator of p53-dependent and -independent stress responses. A variety of abnormal metabolic conditions, cytotoxic compounds, and physical insults induce alterations in nucleolar structure and function, a situation known as nucleolar or ribosomal stress. R...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells1040774
更新日期:2012-10-15 00:00:00
abstract::The pathophysiology of diabetic nephropathy (DN), one of the most serious complications in diabetic patients and the leading cause of end-stage renal disease worldwide, is complex and not fully elucidated. A typical hallmark of DN is the excessive deposition of extracellular matrix (ECM) proteins in the glomerulus and...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells4040631
更新日期:2015-10-09 00:00:00
abstract::Specific nuclear sub-compartments that are regions of fundamental processes such as gene expression or DNA repair, contain phosphoinositides (PIPs). PIPs thus potentially represent signals for the localization of specific proteins into different nuclear functional domains. We performed limited proteolysis followed by ...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells10010068
更新日期:2021-01-04 00:00:00
abstract::Cannabidiol (CBD), as the only phytocannabinoid that has no psychoactive effect, has both antioxidant and anti-inflammatory effects, and thus might be suggested as a cytoprotective compound against UV-induced metabolic changes in skin cells. Therefore, the aim of this study was to investigate the level of protective C...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells8090995
更新日期:2019-08-28 00:00:00
abstract::Stromal immune cells constitute the tumor microenvironment. These immune cell subsets include myeloid cells, the so-called tumor-associated myeloid cells (TAMCs), which are of two types: tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). Breast tumors, particularly those in human epiderm...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells9081785
更新日期:2020-07-27 00:00:00
abstract::The proliferation of molds in domestic environments can lead to uncontrolled continuous exposure to mycotoxins. Even if not immediately symptomatic, this may result in chronic effects, such as, for instance, immunosuppression or allergenic promotion. Alternariol (AOH) is one of the most abundant mycotoxins produced by...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells9040847
更新日期:2020-03-31 00:00:00
abstract::An outbreak of the novel coronavirus (CoV) SARS-CoV-2, the causative agent of COVID-19 respiratory disease, infected millions of people since the end of 2019, led to high-level morbidity and mortality and caused worldwide social and economic disruption. There are currently no antiviral drugs available with proven effi...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells9091962
更新日期:2020-08-25 00:00:00
abstract::The MRE11-RAD50-NBS1 (MRN) protein complex is one of the primary vehicles for repairing DNA double strand breaks and maintaining the genomic stability within the cell. The role of the MRN complex to recognize and process DNA double-strand breaks as well as signal other damage response factors is critical for maintaini...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells9071678
更新日期:2020-07-13 00:00:00
abstract::The turnip Brassica rapa has important economic value and represents a good model system to study gene function in crop plants. ERF/AP2 transcription factors are a major group of proteins that are often involved in regulating stress-responses and developmental programs. Some ERF/AP2 proteins are targets of CULLIN3-bas...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells8040336
更新日期:2019-04-10 00:00:00
abstract::Successful RNAi applications depend on strategies allowing stable and persistent expression of minimal gene silencing triggers without perturbing endogenous gene expression. In this study, we proposed an endogenous microRNA (miRNA) cluster as a novel integration site for small hairpin RNAs (shRNAs). We successfully in...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells8020113
更新日期:2019-02-01 00:00:00