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https://www.readbyqxmd.com/read/28107358/modeling-an-excitable-biosynthetic-tissue-with-inherent-variability-for-paired-computational-experimental-studies
#1
Tanmay A Gokhale, Jong M Kim, Robert D Kirkton, Nenad Bursac, Craig S Henriquez
To understand how excitable tissues give rise to arrhythmias, it is crucially necessary to understand the electrical dynamics of cells in the context of their environment. Multicellular monolayer cultures have proven useful for investigating arrhythmias and other conduction anomalies, and because of their relatively simple structure, these constructs lend themselves to paired computational studies that often help elucidate mechanisms of the observed behavior. However, tissue cultures of cardiomyocyte monolayers currently require the use of neonatal cells with ionic properties that change rapidly during development and have thus been poorly characterized and modeled to date...
January 20, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28056084/sbds-deficient-cells-have-an-altered-homeostatic-equilibrium-due-to-translational-inefficiency-which-explains-their-reduced-fitness-and-provides-a-logical-framework-for-intervention
#2
Piera Calamita, Annarita Miluzio, Arianna Russo, Elisa Pesce, Sara Ricciardi, Farhat Khanim, Cristina Cheroni, Roberta Alfieri, Marilena Mancino, Chiara Gorrini, Grazisa Rossetti, Ivana Peluso, Massimiliano Pagani, Diego L Medina, Johanna Rommens, Stefano Biffo
Ribosomopathies are a family of inherited disorders caused by mutations in genes necessary for ribosomal function. Shwachman-Diamond Bodian Syndrome (SDS) is an autosomal recessive disease caused, in most patients, by mutations of the SBDS gene. SBDS is a protein required for the maturation of 60S ribosomes. SDS patients present exocrine pancreatic insufficiency, neutropenia, chronic infections, and skeletal abnormalities. Later in life, patients are prone to myelodisplastic syndrome and acute myeloid leukemia (AML)...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28039467/targeting-cancer-stem-cell-propagation-with-palbociclib-a-cdk4-6-inhibitor-telomerase-drives-tumor-cell-heterogeneity
#3
Gloria Bonuccelli, Maria Peiris-Pages, Bela Ozsvari, Ubaldo E Martinez-Outschoorn, Federica Sotgia, Michael P Lisanti
In this report, we systematically examined the role of telomerase activity in lung and ovarian cancer stem cell (CSC) propagation. For this purpose, we indirectly gauged telomerase activity, by linking the hTERT-promoter to eGFP. Using lung (A549) and ovarian (SKOV3) cancer cells, transduced with the hTERT-GFP reporter, we then employed GFP-expression levels to fractionate these cell lines into GFP-high and GFP-low populations. We functionally compared the phenotype of these GFP-high and GFP-low populations...
December 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/28035326/the-new-immortalized-uroepithelial-cell-line-hblak-contains-defined-genetic-aberrations-typical-of-early-stage-urothelial-tumors
#4
Michèle J Hoffmann, Evangelia Koutsogiannouli, Margaretha A Skowron, Maria Pinkerneil, Günter Niegisch, Artur Brandt, Stefanie Stepanow, Harald Rieder, Wolfgang A Schulz
Background: Cell culture models of normal urothelial cells are important for studying differentiation, disease mechanisms and anticancer drug development. Beyond primary cultures with their limitations in lifespan, interindividual heterogeneity and supply, few conditionally immortalized cell lines with limited applicability due to partial transformation or impaired differentiation capacity are available. We describe characteristics of the new spontaneously immortalized cell line HBLAK derived from a primary culture of uroepithelial cells...
October 27, 2016: Bladder Cancer
https://www.readbyqxmd.com/read/28035072/%C3%AE-np73-overexpression-promotes-resistance-to-apoptosis-but-does-not-cooperate-with-pml-rara-in-the-induction-of-an-apl-leukemic-phenotype
#5
Antonio R Lucena-Araujo, Juan L Coelho-Silva, Diego A Pereira-Martins, Carolina Thomé, Priscila S Scheucher, Ana P Lange, Helder H Paiva, Benjamin T Hemmelgarn, Mariana C Morais-Sobral, Elisa A Azevedo, Pedro L Franca-Neto, Rafael F Franca, Cleide L Silva, Alexandre Krause, Eduardo M Rego
Here, we evaluated whether the overexpression of transcriptionally inactive ΔNp73 cooperates with PML/RARA fusion protein in the induction of an APL-leukemic phenotype, as well as its role in vitro in proliferation, myeloid differentiation, and drug-induced apoptosis. Using lentiviral gene transfer, we showed in vitro that ΔNp73 overexpression resulted in increased proliferation in murine bone marrow (BM) cells from hCG-PML/RARA transgenic mice and their wild-type (WT) counterpart, with no accumulation of cells at G2/M or S phases; instead, ΔNp73-expressing cells had a lower rate of induced apoptosis...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28033682/the-effect-of-two-drug-delivery-systems-in-ropivacaine-cytotoxicity-and-cytokine-release-by-human-keratinocytes-and-fibroblasts
#6
Luiz Eduardo Nunes Ferreira, Bruno Vilela Muniz, Jonny Burga-Sánchez, Maria Cristina Volpato, Eneida de Paula, Edvaldo Antonio Ribeiro Rosa, Francisco Carlos Groppo
OBJECTIVES: Modified drug delivery systems have been developed to improve pharmacological properties of local anaesthetics. However, the inflammatory potential of these formulations was not investigated. This study compared the in-vitro effects of ropivacaine (ropi) in plain, liposomal (MLV) or 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) formulations on cell viability, apoptosis and cytokine (IL-1α, TNF-α, IL-6 and IL-10) release. METHODS: Human immortalized keratinocytes (HaCaT) and human immortalized gingival fibroblasts (HGF) were exposed to 1-100 μm ropi concentrations...
February 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/27979915/neural-stem-cell-based-anti-cancer-gene-therapy-a-first-in-human-study-in-recurrent-high-grade-glioma-patients
#7
Jana Portnow, Timothy W Synold, Behnam Badie, Revathiswari Tirughana, Simon F Lacey, Massimo D'Apuzzo, Marianne Z Metz, Joseph Najbauer, Victoria Bedell, Tien Vo, Margarita Gutova, Paul Frankel, Mike Y Chen, Karen S Aboody
PURPOSE: Human neural stem cells (NSCs) are inherently tumor-tropic, making them attractive drug delivery vehicles. Toward this goal, we retrovirally transduced an immortalized, clonal NSC line to stably express cytosine deaminase (HB1.F3.CD.C21; CD-NSCs), which converts the prodrug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU). EXPERIMENTAL DESIGN: Recurrent high grade glioma patients underwent intracranial administration of CD-NSCs during tumor resection or biopsy...
December 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27975193/inhibition-of-glomerular-mesangial-cell-proliferation-by-sipdgf-b-and-sipdgfr-%C3%AE-containing-chitosan-nanoplexes
#8
Emine Salva, Suna Özbaş Turan, Jülide Akbuğa
Mesangioproliferative glomerulonephritis is a disease that has a high incidence in humans. In this disease, the proliferation of glomerular mesangial cells and the production of extracellular matrix are important. In recent years, the RNAi technology has been widely used in the treatment of various diseases due to its capability to inhibit the gene expression with high specificity and targeting. The objective of this study was to decrease mesangial cell proliferation by knocking down PDGF-B and its receptor, PDGFR-β...
December 14, 2016: AAPS PharmSciTech
https://www.readbyqxmd.com/read/27956139/characterization-of-stem-cell-derived-liver-and-intestinal-organoids-as-a-model-system-to-study-nuclear-receptor-biology
#9
Ingrid T G W Bijsmans, Alexandra Milona, Noortje Ijssennagger, Ellen C L Willemsen, José M Ramos Pittol, Johan W Jonker, Katja Lange, Guido J E J Hooiveld, Saskia W C van Mil
Nuclear receptors (NRs) are ligand-activated transcription factors regulating a large variety of processes involved in reproduction, development, and metabolism. NRs are ideal drug targets because they are activated by lipophilic ligands that easily pass cell membranes. Immortalized cell lines recapitulate NR biology poorly and generating primary cultures is laborious and requires a constant need for donor material. There is a clear need for development of novel preclinical model systems that better resemble human physiology...
December 10, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27928842/evaluating-beneficial-drug-effects-in-a-non-interventional-setting-a-review-of-effectiveness-studies-based-on-swedish-prescribed-drug-register-data
#10
Susanna M Wallerstedt, Mikael Hoffmann
AIMS: To describe and assess current effectiveness studies published up to 2014 using Swedish Prescribed Drug Register (SPDR) data. METHODS: Study characteristics were extracted. Each study was assessed concerning the clinical relevance of the research question, the risk of bias according to a structured checklist, and as to whether its findings contributed to new knowledge. The biases encountered and ways of handling these were retrieved. RESULTS: A total of 24 effectiveness studies were included in the review, the majority on cardiovascular and psychiatric disease (n = 17; 71%)...
December 8, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27908660/targeting-of-multiple-senescence-promoting-genes-and-signaling-pathways-by-triptonide-induces-complete-senescence-of-acute-myeloid-leukemia-cells
#11
Yanyan Pan, Mei Meng, Nana Zheng, Zhifei Cao, Ping Yang, Xiaodong Xi, Quansheng Zhou
Leukemia cells aberrantly overexpress senescence-suppression telomerase reverse transcriptase (TERT) and down-regulate key senescence-promoting genes to escape complete senescence, resulting in immortalization and malignant progression. Accordingly, induction of complete senescence is a sensible strategy for anti-leukemia therapy. However, effective senescence-based anti-leukemia drugs with low toxicity are currently lacking. In this study, we found that triptonide (chemical name diterpene triepoxide), a small molecule derived from the herb Tripterygium wilfordii Hook, strongly induced complete senescence in cultured acute myeloid leukemia (AML) cell lines, and potently inhibited growth and colony formation of U937 and HL-60 AML cell line with IC50 values of 7...
November 28, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27894093/new-use-of-an-old-drug-inhibition-of-breast-cancer-stem-cells-by-benztropine-mesylate
#12
Jihong Cui, Maija Hollmén, Lina Li, Yong Chen, Steven T Proulx, Daniel Reker, Gisbert Schneider, Michael Detmar
Cancer stem cells (CSCs) play major roles in cancer initiation, metastasis, recurrence and therapeutic resistance. Targeting CSCs represents a promising strategy for cancer treatment. The purpose of this study was to identify selective inhibitors of breast CSCs (BCSCs). We carried out a cell-based phenotypic screening with cell viability as a primary endpoint, using a collection of 2,546 FDA-approved drugs and drug-like molecules in spheres formed by malignant human breast gland-derived cells (HMLER-shEcad cells, representing BCSCs) and control immortalized non-tumorigenic human mammary cells (HMLE cells, representing normal stem cells)...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27892610/beside-to-bench-jak-inhibitor-ruxolitinib-inhibits-the-expression-of-cytokines-characteristic-of-cutaneous-lupus-erythematosus
#13
Anna Sophie Klaeschen, Dominik Wolf, Peter Brossart, Thomas Bieber, Joerg Wenzel
This study was stimulated by the clinical observation of a rapid response of a chilblain lupus patient to treatment with JAK1/2-kinase inhibitor ruxolitinib. We investigated the in-vivo expression of phospho-JAK2 in CLE skin samples as well as the immunomodulatory in-vitro effect of ruxolitinib in cultured immortalized keratinocytes and in a 3D human epidermis model (epiCS). Our results demonstrate that ruxolitinib significantly decreases the production of CLE-typical cytokines (CXCL10, CXCL9, MxA) and might be a promising drug for future clinical studies in patients with CLE and related autoimmune skin diseases...
November 28, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27872579/simultaneous-dual-targeting-of-par-4-and-g6pd-a-promising-new-approach-in-cancer-therapy-quintessence-of-a-literature-review-on-survival-requirements-of-tumor-cells
#14
Ingeborg Elisabeth Cernaj
: The aim of this hypothesis is to propose a new approach in targeted therapy of cancer: The simultaneous, dual targeting of two single molecules, Par-4 and G6PD, rather than inhibition of full-length signaling pathways. RATIONALE: Targeted inhibition of especially two survival signaling pathways (PI3K/AKT/mTOR and MAPK/ERK) is frequently tried, however, a major breakthrough has not yet been reported. Inhibition of complete pathways naturally goes along with a variety of dose-limiting side effects thus contributing to poor efficacy of the administered drugs...
2016: Cancer Cell International
https://www.readbyqxmd.com/read/27842930/the-effect-of-poly-ethylene-glycol-coating-and-monomer-type-on-poly-alkyl-cyanoacrylate-nanoparticle-interactions-with-lipid-monolayers-and-cells
#15
Habib Baghirov, Sopio Melikishvili, Yrr Mørch, Einar Sulheim, Andreas K O Åslund, Tibor Hianik, Catharina de Lange Davies
The interaction of the promising drug carriers poly(alkyl cyanoacrylate) nanoparticles (PACA NPs) with lipid monolayers modeling the cell membrane and with RBE4 immortalized rat brain endothelial cells was compared to assess the relevance of lipid monolayer-based cell membrane models for PACA NP cellular uptake. NP properties such as size and charge of NPs and density of poly(ethylene glycol) coating (PEG) were kept in a narrow range to assess whether the type of PEG coating and the PACA monomer affected NP-monolayer and NP-cell interactions...
October 31, 2016: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/27808117/evaluation-of-uttroside-b-a-saponin-from-solanum-nigrum-linn-as-a-promising-chemotherapeutic-agent-against-hepatocellular-carcinoma
#16
Lekshmi R Nath, Jaggaiah N Gorantla, Arun Kumar T Thulasidasan, Vinod Vijayakurup, Shabna Shah, Shabna Anwer, Sophia M Joseph, Jayesh Antony, Kollery Suresh Veena, Sankar Sundaram, Udaya K Marelli, Ravi S Lankalapalli, Ruby John Anto
We report, for the first time, the remarkable efficacy of uttroside B, a potent saponin from Solanum nigrum Linn, against liver cancer. The compound has been isolated and characterized from the leaves of Solanum nigrum Linn, a plant widely used in traditional medicine and is a rich resource of several anticancer molecules. Uttroside B, that comprises of β-D-glucopyranosyl unit at C-26 of the furostanol and β-lycotetraosyl unit at C-3, is ten times more cytotoxic to the liver cancer cell line, HepG2 (IC50: 0...
November 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27794450/3d-engineered-in-vitro-hepatospheroids-for-studying-drug-toxicity-and-metabolism
#17
Swati Chitrangi, Prabha Nair, Aparna Khanna
Drug toxicity is one of the reasons for late stage drug attrition, because of hepatotoxicity. Various in vitro liver models like primary human hepatocytes, immortalized human hepatic cell lines, liver slices and microsomes have been used; but limited by viability, hepatic gene expression and function. The 3D-engineered construct of hepatocyte-like-cells (HLCs) differentiated from stem cells, may provide a limitless source of hepatocytes with improved reproducibility. Towards this end, we used hepatospheroids (diameter=50-80μm) differentiated from human-umbilical-cord-mesenchymal stem cells (hUC-MSCs) on 3D scaffold GEVAC (Gelatin-vinyl-acetate-copolymer) as in vitro model for studying drug metabolism/toxicity...
February 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27776169/hepatitis-c-virus-broadly-neutralizing-monoclonal-antibodies-isolated-25-years-after-spontaneous-clearance
#18
Sabrina J Merat, Richard Molenkamp, Koen Wagner, Sylvie M Koekkoek, Dorien van de Berg, Etsuko Yasuda, Martino Böhne, Yvonne B Claassen, Bart P Grady, Maria Prins, Arjen Q Bakker, Menno D de Jong, Hergen Spits, Janke Schinkel, Tim Beaumont
Hepatitis C virus (HCV) is world-wide a major cause of liver related morbidity and mortality. No vaccine is available to prevent HCV infection. To design an effective vaccine, understanding immunity against HCV is necessary. The memory B cell repertoire was characterized from an intravenous drug user who spontaneously cleared HCV infection 25 years ago. CD27+IgG+ memory B cells were immortalized using BCL6 and Bcl-xL. These immortalized B cells were used to study antibody-mediated immunity against the HCV E1E2 glycoproteins...
2016: PloS One
https://www.readbyqxmd.com/read/27770562/effect-of-matrix-metalloproteinase-mediated-matrix-degradation-on-glioblastoma-cell-behavior-in-3d-peg-based-hydrogels
#19
Christine Wang, Xinming Tong, Xinyi Jiang, Fan Yang
Glioblastoma (GBM) is the most common and aggressive form of primary brain tumor with median survival of 12 months. To improve clinical outcomes, it is critical to develop in vitro models that support GBM proliferation and invasion for deciphering tumor progression and screening drug candidates. A key hallmark of GBM cells is their extreme invasiveness, a process mediated by matrix metalloproteinase (MMP)-mediated degradation of the extracellular matrix. We recently reported the development of a MMP-degradable, poly(ethylene-glycol)-based hydrogel platform for culturing GBM cells...
October 22, 2016: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/27764131/generating-rho-0-cells-using-mesenchymal-stem-cell-lines
#20
Mercedes Fernández-Moreno, Tamara Hermida-Gómez, M Esther Gallardo, Andrea Dalmao-Fernández, Ignacio Rego-Pérez, Rafael Garesse, Francisco J Blanco
INTRODUCTION: The generation of Rho-0 cells requires the use of an immortalization process, or tumor cell selection, followed by culture in the presence of ethidium bromide (EtBr), incurring the drawbacks its use entails. The purpose of this work was to generate Rho-0 cells using human mesenchymal stem cells (hMSCs) with reagents having the ability to remove mitochondrial DNA (mtDNA) more safely than by using EtBr. METHODOLOGY: Two immortalized hMSC lines (3a6 and KP) were used; 143B...
2016: PloS One
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