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https://www.readbyqxmd.com/read/28216661/mir-194-5p-bclaf1-deregulation-in-aml-tumorigenesis
#1
C Dell'Aversana, C Giorgio, L D'Amato, G Lania, F Matarese, S Saeed, A Di Costanzo, V B Petrizzi, C Ingenito, J H A Martens, I Pallavicini, S Minucci, A Carissimo, H G Stunnenberg, L Altucci
Deregulation of epigenetic mechanisms, including miRNA, contributes to leukaemogenesis and drug resistance by interfering with cancer-specific molecular pathways. Here, we show that the balance between miR-194-5p and its newly discovered target BCL2-associated transcription factor 1 (BCLAF1) regulates differentiation and survival of normal haematopoietic progenitors. In acute myeloid leukaemias (AMLs) this balance is perturbed, locking cells into an immature, potentially 'immortal' state. Enhanced expression of miR-194-5p by treatment with the HDAC inhibitor SAHA or by exogenous miR-194-5p expression re-sensitizes cells to differentiation and apoptosis by inducing BCLAF1 to shuttle between nucleus and cytosol...
February 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28197378/identification-of-inhibitors-of-myeloid-derived-suppressor-cells-activity-through-phenotypic-chemical-screening
#2
Matthias Schröder, Simone Loos, Svenja Kerstin Naumann, Christopher Bachran, Marit Krötschel, Viktor Umansky, Laura Helming, Lee Kim Swee
Tumors are infiltrated by cells of the immune system that interact through complex regulatory networks. Although tumor-specific CD8(+) T cells can be found in peripheral blood and tumor samples from cancer patients, their function is inhibited by immunosuppressive cells such as regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells (MDSC). Recent clinical successes have demonstrated that alleviating immunosuppression and T cell exhaustion translates into long-term clinical benefits...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28191273/oxidative-stress-triggered-by-apigenin-induces-apoptosis-in-a-comprehensive-panel-of-human-cervical-cancer-derived-cell-lines
#3
Raquel P Souza, Patrícia de S Bonfim-Mendonça, Fabrícia Gimenes, Bianca A Ratti, Vanessa Kaplum, Marcos L Bruschi, Celso V Nakamura, Sueli O Silva, Silvya S Maria-Engler, Marcia E L Consolaro
Recently, the cytotoxic effects of apigenin (4',5,7-trihydroxyflavone), particularly its marked inhibition of cancer cell viability both in vitro and in vivo, have attracted the attention of the anticancer drug discovery field. Despite this, there are few studies of apigenin in cervical cancer, and these studies have mostly been conducted using HeLa cells. To evaluate the possibility of apigenin as a new therapeutic candidate for cervical cancer, we evaluated its cytotoxic effects in a comprehensive panel of human cervical cancer-derived cell lines including HeLa (human papillomavirus/HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and HPV 18-positive), and C33A (HPV-negative) cells in comparison to a nontumorigenic spontaneously immortalized human epithelial cell line (HaCaT)...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28178655/chl1-hypermethylation-as-a-potential-biomarker-of-poor-prognosis-in-breast-cancer
#4
Esperanza Martín-Sánchez, Saioa Mendaza, Ane Ulazia-Garmendia, Iñaki Monreal-Santesteban, Idoia Blanco-Luquin, Alicia Córdoba, Francisco Vicente-García, Noemí Pérez-Janices, David Escors, Diego Megías, Paula López-Serra, Manel Esteller, José Juan Illarramendi, David Guerrero-Setas
The CHL1 gene encodes a cell-adhesion molecule proposed as being a putative tumour-suppressor gene in breast cancer (BC). However, neither the underlying molecular mechanisms nor the clinical value of CHL1 downregulation in BC has been explored. The methylation status of three CpG sites in the CHL1 promoter was analysed by pyrosequencing in neoplastic biopsies from 142 patients with invasive BC and compared with that of non-neoplastic tissues. We found higher CHL1 methylation levels in breast tumours than in non-neoplastic tissues, either from mammoplasties or adjacent-to-tumour, which correlated with lower levels of protein expression in tumours measured by immunohistochemistry...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28177527/effects-of-linagliptin-on-human-immortalized-podocytes-a-cellular-system-to-study-dipeptidyl-peptidase-4-inhibition
#5
Gianluca Miglio, Giovanna Vitarelli, Thomas Klein, Elisa Benetti
BACKGROUND AND PURPOSE: Dipeptidyl-peptidase (DPP)4 is expressed by resident renal cells, including glomerular cells. Dipeptidyl-peptidase 4 inhibitors (gliptins) exert albuminuria lowering effects, but the role of renal DPP4 as a pharmacological target has not been elucidated. To better understand the actions of gliptins, the effects of linagliptin on behaviour of immortalized human podocytes and mesangial cells have been evaluated. EXPERIMENTAL APPROACH: Expression of DPP4 was measured at both the mRNA and protein levels...
February 8, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28165853/biocompatibility-and-characterization-of-polyglycerol-based-thermoresponsive-nanogels-designed-as-novel-drug-delivery-systems-and-their-intracellular-localization-in-keratinocytes
#6
Christian Gerecke, Alexander Edlich, Michael Giulbudagian, Fabian Schumacher, Nan Zhang, Andre Said, Guy Yealland, Silke B Lohan, Falko Neumann, Martina C Meinke, Nan Ma, Marcelo Calderón, Sarah Hedtrich, Monika Schäfer-Korting, Burkhard Kleuser
Novel nanogels that possess the capacity to change their physico-chemical properties in response to external stimuli are promising drug delivery candidates for the treatment of severe skin diseases. As thermoresponsive nanogels (tNGs) are capable of enhancing penetration through biological barriers such as the stratum corneum and are taken up by keratinocytes of human skin, potential adverse consequences of their exposure must be elucidated. In this study, tNGs were synthesized from dendritic polyglycerol (dPG) and two thermoresponsive polymers...
February 6, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28161093/large-family-cohorts-of-lymphoblastoid-cells-provide-a-new-cellular-model-for-investigating-facioscapulohumeral-muscular-dystrophy
#7
Takako I Jones, Charis L Himeda, Daniel P Perez, Peter L Jones
Facioscapulohumeral muscular dystrophy (FSHD) is associated with aberrant epigenetic regulation of the chromosome 4q35 D4Z4 macrosatellite repeat. The resulting DNA hypomethylation and relaxation of epigenetic repression leads to increased expression of the deleterious DUX4-fl mRNA encoded within the distal D4Z4 repeat. With the typical late onset of muscle weakness, prevalence of asymptomatic individuals, and an autosomal dominant mode of inheritance, FSHD is often passed on from one generation to the next and affects multiple individuals within a family...
March 2017: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/28159976/screening-and-characterization-of-drugs-that-protect-corneal-endothelial-cells-against-unfolded-protein-response-and-oxidative-stress
#8
Eun Chul Kim, Tetsuya Toyono, Cynthia A Berlinicke, Donald J Zack, Ula Jurkunas, Tomohiko Usui, Albert S Jun
Purpose: To screen for and characterize compounds that protect corneal endothelial cells against unfolded protein response (UPR) and oxidative stress. Methods: Bovine corneal endothelial cells (BCECs) were treated for 48 hours with 640 compounds from a Food and Drug Administration (FDA)-approved drug library and then challenged with thapsigargin or H2O2 to induce UPR or oxidative stress, respectively. Cell viability was measured using the CellTiter-Glo survival assay...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28156159/cholesterol-peg-comodified-poly-n-butyl-cyanoacrylate-nanoparticles-for-brain-delivery-in-vitro-and-in-vivo-evaluations
#9
Xiao Hu, Feifei Yang, Yonghong Liao, Lin Li, Lan Zhang
This study investigated cholesterol-polyethylene glycol (PEG) comodified poly (ethyleneglycol)-poly (lactide) nanoparticles (CLS-PEG NPs) as a novel, biodegradable brain drug delivery system and included an evaluation of its in vitro and in vivo properties. To this end, coumarin-6 (C6), a fluorescent probe, was encapsulated into CLS-PEG NPs by an emulsion polymerization method. We reported that the use of CLS-PEG NPs led to a sustained drug release in vitro. Additionally, cell viability experiments confirmed their safety...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28137210/the-metabolism-of-methazolamide-in-immortalized-human-keratinocytes-hacat-cells
#10
Tetsuo Sasabe, Shinichiro Maeda, Kenichi Kishida, Mariko Yamano, Yoshihiro Miwa, Toshihiro Sugiyama
OBJECTIVE: Drug therapy is occasionally accompanied by an idiosyncratic severe toxicity, which occurs very rarely, but can lead to patient mortality. Methazolamide, an anti-glaucomatous agent, could cause severe skin eruptions called Stevens-Johnson syndrome/toxic epidermal necrolyis (SJS/TEN). Its precise etiology is still uncertain. In this study, the metabolism of methazolamide was investigated in immortalized human keratinocytes to reveal the possible mechanism which causes SJS/TEN...
January 27, 2017: Drug Metabolism Letters
https://www.readbyqxmd.com/read/28115366/adult-t-cell-leukemia-atl-molecular-basis-for-clonal-expansion-and-transformation-of-htlv-1-infected-t-cells
#11
Toshiki Watanabe
Adult T-cell leukemia (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1) that develops through a multistep carcinogenesis process involving five or more genetic events. In this review, we provided a comprehensive overview of recently uncovered information on the molecular basis of leukemogenesis in ATL. Broadly, the landscape of genetic abnormalities in ATL that include alterations highly enriched in genes for T cell receptor-NF-κB signaling such as PLCG1, PRKCB, and CARD11 and gain-of function mutations in CCR4 and CCR7 Conversely, the epigenetic landscape of ATL can be summarized as polycomb repressive complex 2 (PRC2) hyperactivation with genome-wide H3K27 me3 accumulation as the basis of the unique transcriptome of ATL cells...
January 23, 2017: Blood
https://www.readbyqxmd.com/read/28114822/ph-sensitive-niosomes-effects-on-cytotoxicity-and-on-inflammation-and-pain-in-murine-models
#12
Federica Rinaldi, Elena Del Favero, Valeria Rondelli, Stefano Pieretti, Alessia Bogni, Jessica Ponti, François Rossi, Luisa Di Marzio, Donatella Paolino, Carlotta Marianecci, Maria Carafa
pH-sensitive nonionic surfactant vesicles (niosomes) by polysorbate-20 (Tween-20) or polysorbate-20 derivatized by glycine (added as pH sensitive agent), were developed to deliver Ibuprofen (IBU) and Lidocaine (LID). For the physical-chemical characterization of vesicles (mean size, size distribution, zeta potential, vesicle morphology, bilayer properties and stability) dynamic light scattering (DLS), small angle X-ray scattering and fluorescence studies were performed. Potential cytotoxicity was evaluated on immortalized human keratinocyte cells (HaCaT) and on immortalized mouse fibroblasts Balb/3T3...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28112518/lc-ms-ms-based-quantitation-of-abc-and-slc-transporter-proteins-in-plasma-membranes-of-cultured-primary-human-retinal-pigment-epithelium-cells-and-immortalized-arpe19-cell-line
#13
Laura Pelkonen, Kazuki Sato, Mika Reinisalo, Heidi Kidron, Masanori Tachikawa, Michitoshi Watanabe, Yasuo Uchida, Arto Urtti, Tetsuya Terasaki
The retinal pigment epithelium (RPE) forms the outer blood-retinal barrier between neural retina and choroid. The RPE has several important vision supporting functions, such as transport mechanisms that may also modify pharmacokinetics in the posterior eye segment. Expression of plasma membrane transporters in the RPE cells has not been quantitated. The aim of this study was to characterize and compare transporter protein expression in the ARPE19 cell line and hfRPE (human fetal RPE) cells by using quantitative targeted absolute proteomics (QTAP)...
February 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28107358/modeling-an-excitable-biosynthetic-tissue-with-inherent-variability-for-paired-computational-experimental-studies
#14
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 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
#15
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
#16
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...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28035326/the-new-immortalized-uroepithelial-cell-line-hblak-contains-defined-genetic-aberrations-typical-of-early-stage-urothelial-tumors
#17
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
#18
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...
January 31, 2017: 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
#19
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
#20
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
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