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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
October 26, 2016: 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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/27761819/assessing-the-histone-deacetylase-activity-of-sirt6-in-primary-murine-hepatocytes-via-proximity-ligation-assay
#11
Katharina Wolf, Susanne Strand
Generation of primary cell culture of hepatocytes by mouse liver perfusion (MLP) combines the advantages of in vivo and in vitro models. It provides hepatocytes that grow under physiological conditions in mice, with the genotype of the whole organism or a specific gene knockout. In contrast to immortalized cell cultures, primary murine hepatocytes (pmHep) are non-cancerous cells with a limited lifespan but still amenable to classical in vitro methods such as treatment with drugs, small molecule inhibitors, and agonistic/antagonistic antibodies of surface receptors as well as transfection...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27756242/hepatocellular-carcinoma-targeted-drug-discovery-through-image-based-phenotypic-screening-in-co-cultures-of-hcc-cells-with-hepatocytes
#12
Jae-Woo Jang, Yeonhwa Song, Kang Mo Kim, Jin-Sun Kim, Eun Kyung Choi, Joon Kim, Haengran Seo
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide and is associated with substantial mortality. Because HCCs have strong resistance to conventional chemotherapeutic agents, novel therapeutic strategies are needed to improve survival in HCC patients. METHODS: Here, we developed a fluorescence image-based phenotypic screening system in vitro to identify HCC-specific drugs in co-cultures of HCC cells with hepatocytes. To this end, we identified two distinctive markers of HCC, CHALV1 and AFP, which are highly expressed in HCC cell lines and liver cancer patient-derived materials...
October 18, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27750367/novel-mouse-model-recapitulates-genome-and-transcriptome-alterations-in-human-colorectal-carcinomas
#13
Nicole E McNeil, Hesed M Padilla-Nash, Floryne O Buishand, Yue Hue, Thomas Ried
Human colorectal carcinomas are defined by a non-random distribution of genomic imbalances that are characteristic for this disease. Often, these imbalances affect entire chromosomes. Understanding the role of these aneuploidies for carcinogenesis is of utmost importance. Currently, established transgenic mice do not recapitulate the pathognonomic genome aberration profile of human colorectal carcinomas. We have developed a novel model based on the spontaneous transformation of murine colon epithelial cells...
October 17, 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27716287/modeling-neurological-diseases-with-induced-pluripotent-cells-reprogrammed-from-immortalized-lymphoblastoid-cell-lines
#14
Koki Fujimori, Toshiki Tezuka, Hiroyuki Ishiura, Jun Mitsui, Koichiro Doi, Jun Yoshimura, Hirobumi Tada, Takuya Matsumoto, Miho Isoda, Ryota Hashimoto, Nubutaka Hattori, Takuya Takahashi, Shinichi Morishita, Shoji Tsuji, Wado Akamatsu, Hideyuki Okano
Patient-specific induced pluripotent stem cells (iPSCs) facilitate understanding of the etiology of diseases, discovery of new drugs and development of novel therapeutic interventions. A frequently used starting source of cells for generating iPSCs has been dermal fibroblasts (DFs) isolated from skin biopsies. However, there are also numerous repositories containing lymphoblastoid B-cell lines (LCLs) generated from a variety of patients. To date, this rich bioresource of LCLs has been underused for generating iPSCs, and its use would greatly expand the range of targeted diseases that could be studied by using patient-specific iPSCs...
October 3, 2016: Molecular Brain
https://www.readbyqxmd.com/read/27694896/an-in-vivo-screening-system-to-identify-tumorigenic-genes
#15
T Ihara, Y Hosokawa, K Kumazawa, K Ishikawa, J Fujimoto, M Yamamoto, T Muramkami, N Goshima, E Ito, S Watanabe, K Semba
Screening for oncogenes has mostly been performed by in vitro transformation assays. However, some oncogenes might not exhibit their transforming activities in vitro unless putative essential factors from in vivo microenvironments are adequately supplied. Here, we have developed an in vivo screening system that evaluates the tumorigenicity of target genes. This system uses a retroviral high-efficiency gene transfer technique, a large collection of human cDNA clones corresponding to ~70% of human genes and a luciferase-expressing immortalized mouse mammary epithelial cell line (NMuMG-luc)...
October 3, 2016: Oncogene
https://www.readbyqxmd.com/read/27668559/the-grace-checklist-a-validated-assessment-tool-for-high-quality-observational-studies-of-comparative-effectiveness
#16
Nancy A Dreyer, Allison Bryant, Priscilla Velentgas
BACKGROUND: Recognizing the growing need for robust evidence about treatment effectiveness in real-world populations, the Good Research for Comparative Effectiveness (GRACE) guidelines have been developed for noninterventional studies of comparative effectiveness to determine which studies are sufficiently rigorous to be reliable enough for use in health technology assessments. OBJECTIVE: To evaluate which aspects of the GRACE Checklist contribute most strongly to recognition of quality...
October 2016: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/27667770/novel-celecoxib-analogues-inhibit-glial-production-of-prostaglandin-e2-nitric-oxide-and-oxygen-radicals-reverting-the-neuroinflammatory-responses-induced-by-misfolded-prion-protein-fragment-90-231-or-lipopolysaccharide
#17
Valentina Villa, Stefano Thellung, Adriana Bajetto, Elena Gatta, Mauro Robello, Federica Novelli, Bruno Tasso, Michele Tonelli, Tullio Florio
We tested the efficacy of novel cyclooxygenase 2 (COX-2) inhibitors in counteracting glia-driven neuroinflammation induced by the amyloidogenic prion protein fragment PrP90-231 or lipopolysaccharide (LPS). In search for molecules with higher efficacy than celecoxib, we focused our study on its 2,3-diaryl-1,3-thiazolidin-4-one analogues. As experimental models, we used the immortalized microglial cell line N9, rat purified microglial primary cultures, and mixed cultures of astrocytes and microglia. Microglia activation in response to PrP90-231 or LPS was characterized by growth arrest, morphology changes and the production of reactive oxygen species (ROS)...
September 22, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27663735/neurotensin-stimulates-sortilin-and-mtor-in-human-microglia-inhibitable-by-methoxyluteolin-a-potential-therapeutic-target-for-autism
#18
Arti B Patel, Irene Tsilioni, Susan E Leeman, Theoharis C Theoharides
We had reported elevated serum levels of the peptide neurotensin (NT) in children with autism spectrum disorders (ASD). Here, we show that NT stimulates primary human microglia, the resident immune cells of the brain, and the immortalized cell line of human microglia-SV40. NT (10 nM) increases the gene expression and release (P < 0.001) of the proinflammatory cytokine IL-1β and chemokine (C-X-C motif) ligand 8 (CXCL8), chemokine (C-C motif) ligand 2 (CCL2), and CCL5 from human microglia. NT also stimulates proliferation (P < 0...
September 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27649700/herg1-potassium-channel-in-cancer-cells-a-tool-to-reprogram-immortality
#19
Saverio Gentile
It has been well established that changes in ion fluxes across cellular membranes as a function of time is fundamental in maintaining cellular homeostasis of every living cell. Consequently, dysregulation of ion channels activity is a critical event in pathological conditions of several tissues, including cancer. Nevertheless, the role of ion channels in cancer biology is still not well understood and very little is known about the possible therapeutic opportunities offered by the use of the vast collection of drugs that target ion channels...
October 2016: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/27640198/clinical-and-prognostic-role-of-annexin-a2-in-adamantinomatous-craniopharyngioma
#20
Yuelong Wang, Jiaojiao Deng, Gang Guo, Aiping Tong, Xirui Peng, Haifeng Chen, Jianguo Xu, Yi Liu, Chao You, Liangxue Zhou
Annexin A2 (AnxA2) is a highly conserved Ca2(+)-regulated membrane binding protein, which affects cell mobility and tumor progression. Adamantinomatous craniopharyngioma (AdaCP) are a kind of epithelial tumors of the sellar region with high tendency to recur. Robust biomarkers are required to predict tumor behavior and to establish follow-up individualized treatment approaches. In this study, we firstly compared four surgical AdaCP samples with normal brain by two-dimensional gel electrophoresis (2DE) proteomic analysis...
September 17, 2016: Journal of Neuro-oncology
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