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https://www.readbyqxmd.com/read/28815320/inhibitory-growth-evaluation-and-apoptosis-induction-in-mcf-7-cancer-cells-by-new-5-aryl-2-butylthio-1-3-4-oxadiazole-derivatives
#1
Rashmin Khanam, Kamal Ahmad, Iram I Hejazi, Ibrar A Siddique, Vikash Kumar, Abdul Roouf Bhat, Amir Azam, Fareeda Athar
BACKGROUND: Cancer has become one of the global health issues and it is the life-threatening disease characterized by unrestrained growth of cells. Despite various advances being adopted by chemotherapeutic management, the use of the current anticancer drugs such as Doxorubicin, Asparginase, Methotrexate, Vincristine remains limited due to high toxicity, side effects and developing drug resistance. Apoptosis is a crucial cellular process and improper regulation of apoptotic signaling pathways may lead to cancer formation...
August 16, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28811125/pharmacokinetics-and-pharmacodynamics-of-thiopurines-in-an-in-vitro-model-of-human-hepatocytes-insights-from-an-innovative-mass-spectrometry-assay
#2
Marco Pelin, Elena Genova, Laura Fusco, Monzer Marisat, Ute Hofmann, Diego Favretto, Marianna Lucafò, Andrea Taddio, Stefano Martelossi, Alessandro Ventura, Gabriele Stocco, Matthias Schwab, Giuliana Decorti
AIM: To apply an innovative LC-MS/MS method to quantify thiopurine metabolites in human hepatocytes and to associate them to cytotoxicity. METHODS: Immortalized human hepatocytes (IHH cells) were treated for 48 and 96 h, with 1.4 × 10(-4) M azathioprine and 1.1 × 10(-3) M mercaptopurine, concentrations corresponding to the IC50 values calculated after 96 h exposure in previous cytotoxicity analysis. After treatments, cells were collected for LC-MS/MS analysis to quantify 11 thiopurine metabolites with different level of phosphorylation and viable cells were counted by Trypan blue exclusion assay to determine thiopurines in vitro effect on cell growth and survival...
August 12, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28800587/highly-efficient-gene-inactivation-by-adenoviral-crispr-cas9-in-human-primary-cells
#3
Olaf Voets, Frans Tielen, Edo Elstak, Julian Benschop, Max Grimbergen, Jan Stallen, Richard Janssen, Andre van Marle, Christian Essrich
Phenotypic assays using human primary cells are highly valuable tools for target discovery and validation in drug discovery. Expression knockdown (KD) of such targets in these assays allows the investigation of their role in models of disease processes. Therefore, efficient and fast modes of protein KD in phenotypic assays are required. The CRISPR/Cas9 system has been shown to be a versatile and efficient means of gene inactivation in immortalized cell lines. Here we describe the use of adenoviral (AdV) CRISPR/Cas9 vectors for efficient gene inactivation in two human primary cell types, normal human lung fibroblasts and human bronchial epithelial cells...
2017: PloS One
https://www.readbyqxmd.com/read/28799948/anticancer-drugs-and-the-regulation-of-hedgehog-genes-gli1-and-ptch1-a-comparative-study-in-nonmelanoma-skin-cancer-cell-lines
#4
Uffe H Olesen, Sophie Bojesen, Julie Gehl, Merete Haedersdal
Nonmelanoma skin cancer is the most common cancer in humans, comprising mainly basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BCC proliferation is highly dependent on the Hedgehog signaling pathway. We aimed to investigate a panel of anticancer drugs with known activity against skin cancer for their therapeutic potential in localized, enhanced topical treatment of SCC and BCC. Cytotoxicity profiles for vismodegib, 5-fluorouracil (5-FU), methotrexate (MTX), cisplatin, bleomycin, and vorinostat were established in terms of half maximal inhibitory concentration values in a panel of immortalized keratinocytes (HaCaT), BCC (UWBCC1 and BCC77015), and SCC (A431 and SCC25) cell lines...
August 9, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28797103/effects-of-cancer-testis-antigen-tfdp3-on-cell-cycle-regulation-and-its-mechanism-in-l-02-and-hepg2-cell-lines-in-vitro
#5
Yunshen Jiao, Lingyu Ding, Ming Chu, Tieshan Wang, Jiarui Kang, Xiaofan Zhao, Huanhuan Li, Xi Chen, Zirui Gao, Likai Gao, Yuedan Wang
TFDP3, also be known as HCA661, was one of the cancer-testis antigens, which only expressed in human tissues. The recent researches about TFDP3 mostly focused on its ability to control the drug resistance and apoptosis of tumor cells. However, the role of TFDP3 in the progress of the cell cycle is rarely involved. In this study, we examined the expression of TFDP3 in human liver tissues firstly. After that, we detect the expression of TFDP3 at the RNA level and protein level in L-02 cell line and HepG2 cell line, and the location of TFDP3 was defined by immunofluorescence technique...
2017: PloS One
https://www.readbyqxmd.com/read/28780319/cdk1-mediated-mitotic-phosphorylation-of-pbk-is-involved-in-cytokinesis-and-inhibits-its-oncogenic-activity
#6
Seth Stauffer, Yongji Zeng, Jiuli Zhou, Xingcheng Chen, Yuanhong Chen, Jixin Dong
PDZ-binding kinase (PBK) plays a major role in proliferation and in safeguarding mitotic fidelity in cancer cells. Frequently upregulated in many cancers, PBK drives tumorigenesis and metastasis. PBK has been shown to be phosphorylated in mitosis by cyclin-dependent kinase 1 (CDK1)/cyclin B, however, no studies have been done examining PBK mitotic phosphorylation in oncogenesis. Additionally to the previously identified Threonine-9 phosphorylation, we found that Threonine-24, Serine-32, and Serine-59 of PBK are also phosphorylated...
August 3, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28776259/increased-egfr-expression-induced-by-a-novel-oncogene-cug2-confers-resistance-to-doxorubicin-through-stat1-hdac4-signaling
#7
Sirichat Kaowinn, Seung Won Jun, Chang Seok Kim, Dong-Myeong Shin, Yoon-Hwae Hwang, Kyujung Kim, Bosung Shin, Chutima Kaewpiboon, Hyeon Hee Jeong, Sang Seok Koh, Oliver H Krämer, Randal N Johnston, Young-Hwa Chung
BACKGROUND: Previously, it has been found that the cancer upregulated gene 2 (CUG2) and the epidermal growth factor receptor (EGFR) both contribute to drug resistance of cancer cells. Here, we explored whether CUG2 may exert its anticancer drug resistance by increasing the expression of EGFR. METHODS: EGFR expression was assessed using Western blotting, immunofluorescence and capacitance assays in A549 lung cancer and immortalized bronchial BEAS-2B cells, respectively, stably transfected with a CUG2 expression vector (A549-CUG2; BEAS-CUG2) or an empty control vector (A549-Vec; BEAS-Vec)...
August 3, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28768817/cxcr4-specific-nanobodies-as-potential-therapeutics-for-whim-syndrome
#8
Raymond H de Wit, Raimond Heukers, Hendrik Brink, Angela Arsova, David Maussang, Pasquale Cutolo, Beatrijs Strubbe, Henry Vischer, Francoise Bachelerie, Martine J Smit
WHIM syndrome is a rare congenital immunodeficiency disease, named after its main clinical manifestations: Warts, Hypogammaglobulinemia, Infections and Myelokathexis. The disease is primarily caused by C-terminal truncation mutations of the chemokine receptor CXCR4. Consequently, these CXCR4-WHIM mutants have a gain of function in response to its ligand CXCL12, which results in abnormal leukocyte migration and thereby immune system dysfunctions. Treatment of WHIM patients currently consists of symptom relief, leading to unsatisfactory clinical responses...
August 2, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28757458/a-computational-integrative-approach-based-on-alternative-splicing-analysis-to-compare-immortalized-and-primary-cancer-cells
#9
Kumar Parijat Tripathi, Ilaria Granata, Mario Rosario Guarracino
Immortalized cell lines are widely used to study the effectiveness and toxicity of anti cancer drugs as well as to assess the phenotypic characteristics of cancer cells, such as proliferation and migration ability. Unfortunately, cell lines often show extremely different properties than tumor tissues. Also the primary cells, that are deprived of the in vivo environment, might adapt to artificial conditions, and differ from the tissue they should represent. Despite these considerations, cell lines are still one of the most used cancer models due to their availability and capability to expand without limitation, but the clinical relevance of their use is still a big issue in cancer research...
July 27, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28750799/mouse-neuroblastoma-cb1-cannabinoid-receptor-stimulated-35-s-gtp%C3%A9-s-binding-total-and-antibody-targeted-g%C3%AE-protein-specific-scintillation-proximity-assays
#10
Khalil Eldeeb, Sandra Leone-Kabler, Allyn C Howlett
G protein-coupled receptors (GPCRs) are important regulators of cellular signaling functions and therefore are a major target for drug discovery. The CB1 cannabinoid receptor is among the most highly expressed GPCRs in neurons, where it regulates many differentiated neuronal functions. One model system for studying the biochemistry of neuronal responses is the use of neuroblastoma cells originating from the C1300 tumor in the A/J mouse, including cloned cell lines NS20, N2A, N18TG2, N4TG1, and N1E-115, and various immortalized hybrids of neurons with N18TG2 cells...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28747712/2-oxoadenosine-induces-cytotoxicity-through-intracellular-accumulation-of-2-oxo-atp-and-depletion-of-atp-but-not-via-the-p38-mapk-pathway
#11
Shinji Asada, Eiko Ohta, Yoriko Akimoto, Nona Abolhassani, Daisuke Tsuchimoto, Yusaku Nakabeppu
2-Oxoadenosine (2-oxo-Ado), an oxidized form of adenosine, is cytotoxic and induces growth arrest and cell death, which has potential as an anti-cancer drug. However, it is not well understood how 2-oxo-Ado exerts its cytotoxicity. We examined the effects of 2-oxo-Ado on non-tumour cells, namely immortalized mouse embryonic fibroblast lines, and investigated mechanisms by which 2-oxo-Ado exerts its cytotoxicity. We found that cell death induced by 2-oxo-Ado is classical caspase-dependent apoptosis, and requires its sequential intracellular phosphorylation catalysed by adenosine kinase (ADK) and adenylate kinase 2, resulting in intracellular accumulation of 2-oxo-ATP accompanied by accumulation of 2-oxo-Ado in RNA and depletion of ATP...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28736828/genomic-and-metabolic-characterization-of-a-chromophobe-renal-cell-carcinoma-cell-line-model-uok276
#12
Youfeng Yang, Cathy D Vocke, Christopher J Ricketts, Darmood Wei, Hesed M Padilla-Nash, Martin Lang, Carole Sourbier, J Keith Killian, Shawna L Boyle, Robert Worrell, Paul S Meltzer, Thomas Ried, Maria J Merino, Adam R Metwalli, W Marston Linehan
Chromophobe renal cell carcinoma (ChRCC) represents 5% of all RCC cases and frequently demonstrates multiple chromosomal losses and an indolent pattern of local growth, but can demonstrate aggressive features and resistance to treatment in a metastatic setting. Cell line models are an important tool for the investigation of tumor biology and therapeutic drug efficacy. Currently, there are few ChRCC-derived cell lines and none is well characterized. This study characterizes a novel ChRCC-derived cell line model, UOK276...
October 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28728108/new-tacrine-dimers-with-antioxidant-linkers-as-dual-drugs-anti-alzheimer-s-and-antiproliferative-agents
#13
Jesús M Roldán-Peña, Daniel Alejandre-Ramos, Óscar López, Inés Maya, Irene Lagunes, José M Padrón, Luis Emiliano Peña-Altamira, Manuela Bartolini, Barbara Monti, Maria L Bolognesi, José G Fernández-Bolaños
We have designed a series of tacrine-based homo- and heterodimers that incorporate an antioxidant tether (selenoureido, chalcogenide) as new dual compounds: for the treatment of Alzheimer's disease and as antiproliferative agents. Symmetrical homodimers bearing a dichalcogenide or selenide-based tether, the best compounds in the series, were found to be strong and highly selective electric eel AChE inhibitors, with inhibition constants within the low nanomolar range. This high inhibitory activity was confirmed on recombinant human AChE for the most interesting derivatives...
June 27, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28728086/nanostructured-lipid-systems-modified-with-waste-material-of-propolis-for-wound-healing-design-in-vitro-and-in-vivo-evaluation
#14
Hélen Cássia Rosseto, Lucas de Alcântara Sica de Toledo, Lizziane Maria Belloto de Francisco, Elisabetta Esposito, Yunsook Lim, Giuseppe Valacchi, Rita Cortesi, Marcos Luciano Bruschi
Propolis, a natural compound that can accelerate the wound healing process, is mainly used as ethanolic extract. The extractive solution may also be obtained from the propolis by-product (BP), transforming this waste material into a pharmaceutical active ingredient. Even if propolis does not show toxicity, when used as an extract over harmed skin or mucosa, the present ethanol content may be harmful to the tissue recovering, besides hindering the drug release. This study describes the development of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) as topical propolis delivery systems and the investigation of their in vitro and in vivo activities...
July 10, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28691691/development-of-a-clay-based-bioink-for-3d-cell-printing-for-skeletal-application
#15
T Ahlfeld, G Cidonio, D Kilian, S Duin, A R Akkineni, J I Dawson, S Yang, A Lode, R O C Oreffo, M Gelinsky
Three-dimensional printing of cell-laden hydrogels has evolved as a promising approach on the route to patient-specific or complex tissue-engineered constructs. However, it is still challenging to print structures with both, high shape fidelity and cell vitality. Herein, we used a synthetic nanosilicate clay, called Laponite, to build up scaffolds utilising the extrusion-based method 3D plotting. By blending with alginate and methylcellulose, a bioink was developed which allowed easy extrusion, achieving scaffolds with high printing fidelity...
July 25, 2017: Biofabrication
https://www.readbyqxmd.com/read/28686713/transcriptome-wide-comparison-of-the-impact-of-atoh1-and-mir-183-family-on-pluripotent-stem-cells-and-multipotent-otic-progenitor-cells
#16
Michael Ebeid, Prashanth Sripal, Jason Pecka, Kirk W Beisel, Kelvin Kwan, Garrett A Soukup
Over 5% of the global population suffers from disabling hearing loss caused by multiple factors including aging, noise exposure, genetic predisposition, or use of ototoxic drugs. Sensorineural hearing loss is often caused by the loss of sensory hair cells (HCs) of the inner ear. A barrier to hearing restoration after HC loss is the limited ability of mammalian auditory HCs to spontaneously regenerate. Understanding the molecular mechanisms orchestrating HC development is expected to facilitate cell replacement therapies...
2017: PloS One
https://www.readbyqxmd.com/read/28674248/a-nanoparticle-based-ophthalmic-formulation-of-dexamethasone-enhances-corneal-permeability-of-the-drug-and-prolongs-its-corneal-residence-time
#17
Noriaki Nagai, Yosuke Nakazawa, Yoshimasa Ito, Kazutaka Kanai, Norio Okamoto, Yoshikazu Shimomura
We designed ophthalmic formulations containing dexamethasone-loaded solid nanoparticles (DEXnano dispersion), and investigated corneal permeability and toxicity. 0.1% dexamethasone (DEX) powder (DEX microparticles), 0.026% methyl p-hydroxybenzoate (MP), 0.014% propyl p-hydroxybenzoate (PP), and 0.5% methylcellulose were used, and the DEXnano dispersion was prepared by the bead mill method. The mean particle size of DEXnano dispersion was 78 nm. Antimicrobial activity of the DEXnano dispersion were measured by using Escherichia coli, and the corneal epithelium-debrided rat model and HCE-T cells (immortalized human corneal epithelial cell line) were used to estimate the corneal toxicity...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28660853/fluorescence-lifetime-based-bioassays
#18
Franz-Josef Meyer-Almes
Fluorescence lifetime (FLT) is a robust intrinsic property and material constant of fluorescent matter. Measuring this important physical indicator has evolved from a laboratory curiosity to a powerful and established technique for a variety of applications in drug discovery, medical diagnostics and basic biological research. This distinct trend was mainly driven by improved and meanwhile affordable laser and detection instrumentation on the one hand and the development of suitable FLT probes and biological assays on the other...
June 29, 2017: Methods and Applications in Fluorescence
https://www.readbyqxmd.com/read/28654058/in-vitro-assays-to-assess-blood-brain-barrier-mesh-like-vessel-formation-and-disruption
#19
Riya Thomas, Kazandra Diaz, Kevin P Koster, Leon M Tai
Blood-brain barrier (BBB) coverage plays a central role in the homeostasis of the central nervous system (CNS). The BBB is dynamically maintained by astrocytes, pericytes and brain endothelial cells (BECs). Here, we detail methods to assess BBB coverage using single cultures of immortalized human BECs, single cultures of primary mouse BECs, and a humanized triple culture model (BECs, astrocytes and pericytes) of the BBB. To highlight the applicability of the assays to disease states, we describe the effect of oligomeric amyloid-β (oAβ), which is an important contributor to Alzheimer's disease (AD) progression, on BBB coverage...
June 20, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28651607/the-long-non-coding-rna-bc200-bcyrn1-is-critical-for-cancer-cell-survival-and-proliferation
#20
Evan P Booy, Ewan Ks McRae, Amit Koul, Francis Lin, Sean A McKenna
BACKGROUND: BC200 is a long non-coding RNA expressed at high levels in the brain and elevated in a variety of tumour types. BC200 has a hypothesized role in translational regulation; however, to date the functional role of BC200 in both normal and diseased states remains poorly characterized. METHODS: Detailed BC200 expression analyses were performed in tumor cell lines, primary and non-tumorigenic cultured breast and lung cells, and a panel of normal human tissues by quantitative real-time PCR and confirmed by northern blot...
June 26, 2017: Molecular Cancer
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