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https://www.readbyqxmd.com/read/28239030/metabolic-profiling-of-gemcitabine-and-paclitaxel-treated-immortalized-human-pancreatic-cell-lines-with-k-ras-g12d
#1
Akiko Todaka, Rina Umehara, Keiko Sasaki, Masakuni Serizawa, Kenichi Urakami, Masatoshi Kusuhara, Ken Yamaguchi, Hirofumi Yasui
The mechanisms of action of gemcitabine (GEM) and paclitaxel (PTX) have been well investigated, and shown to be the inhibition of DNA polymerase and polymerization of tubulin, respectively. Meanwhile, genomic research has revealed that mutations in the K-RAS oncogene occur in over 90% of pancreatic cancer. Oncogenic alteration rewires alternative metabolic pathways to satisfy the demands of growth. The K-RAS oncogene also has been shown to upregulate glycolysis and glutaminolysis. However, it is still unclear whether K-RAS independently plays a central role in controlling tumor metabolism...
2017: Biomedical Research
https://www.readbyqxmd.com/read/28238931/effect-of-interleukin-il-8-on-benzo-a-pyrene-metabolism-and-dna-damage-in-human-lung-epithelial-cells
#2
Q Shi, A W Boots, L Maas, C Veith, K van Kuijk, G R Haenen, R W Godschalk, F J Van Schooten
It has been well established that inflammation and concurrent mutagenic exposures drive the carcinogenic process in a synergistic way. To elucidate the role of the inflammatory cytokine IL-8 in this process, we studied its effect on the activation and deactivation of the chemical mutagen benzo[a]pyrene B[a]P in the immortalized pulmonary BEAS-2B cell line. After 24hours incubation with B[a]P in the presence or absence of IL-8, the B[a]P induced cytochrome P450 1A1 and 1B1 (CYP1A1 and CYP1B1) gene expression and CYP1A1 enzyme activity was significantly higher in the presence of the cytokine...
February 23, 2017: Toxicology
https://www.readbyqxmd.com/read/28235973/endothelin-signaling-regulates-mineralization-and-posttranscriptionally-regulates-sost-in-tmob-cells-via-mir-126-3p
#3
Michael G Johnson, Kathryn Konicke, Jasmin Kristianto, Anne Gustavson, Rachel Garbo, Xiaohu Wang, Baozhi Yuan, Robert D Blank
Previously, our laboratory identified ECE-1, encoding endothelin-converting enzyme-1 (ECE-1), as a positional candidate for a pleiotropic quantitative trait locus affecting femoral size, shape, and biomechanical performance. We hypothesized that endothelin-1 (ET-1) signaling promotes osteogenesis. Exposure of immortalized mouse osteoblast (TMOb) cells to big ET-1 increased mineralization. Following big ET-1 treatment, we measured the secretion of insulin-like-growth factor-1 (IGF1), dickkopf-homolog-1 protein 1 (DKK1), and sclerostin (SOST)...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28230862/inactivation-of-lsd1-triggers-senescence-in-trophoblast-stem-cells-by-induction-of-sirt4
#4
Josefina Castex, Dominica Willmann, Toufike Kanouni, Laura Arrigoni, Yan Li, Marcel Friedrich, Michael Schleicher, Simon Wöhrle, Mark Pearson, Norbert Kraut, Michaël Méret, Thomas Manke, Eric Metzger, Roland Schüle, Thomas Günther
Coordination of energy metabolism is essential for homeostasis of stem cells, whereas an imbalance in energy homeostasis causes disease and accelerated aging. Here we show that deletion or enzymatic inactivation of lysine-specific demethylase 1 (Lsd1) triggers senescence in trophoblast stem cells (TSCs). Genome-wide transcriptional profiling of TSCs following Lsd1 inhibition shows gene set enrichment of aging and metabolic pathways. Consistently, global metabolomic and phenotypic analyses disclose an unbalanced redox status, decreased glutamine anaplerosis and mitochondrial function...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230642/strategies-to-obtain-diverse-and-specific-human-monoclonal-antibodies-from-transgenic-animals
#5
Marianne Brüggemann, Michael J Osborn, Biao Ma, Roland Buelow
Techniques to obtain large quantities of antigen-specific monoclonal antibodies, mAbs, were first established in the 1970s when Georges Köhler and César Milstein immortalized antibody-producing mouse B-lymphocytes by fusion with myeloma cells (http://www.whatisbiotechnology.org/exhibitions/milstein). Combined with the expression of human antibodies in transgenic animals, this technique allowed upon immunization the generation of highly specific fully human mAbs for therapeutic applications. Apart from being extremely beneficial, mAbs are a huge success commercially...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28228480/a-stable-but-reversible-integrated-surrogate-reporter-for-assaying-crispr-cas9-stimulated-homology-directed-repair
#6
Yahong Wen, Grace Liao, Thomas Pritchard, Ting-Ting Zhao, Jon P Connelly, Shondra M Pruett-Miller, Valerie Blanc, Nicholas O Davidson, Blair B Madison
The discovery and application of CRISPR/Cas9 technology for genome editing has greatly accelerated targeted mutagenesis in a variety of organisms. CRISPR/Cas9-mediated site-specific cleavage is typically exploited for the generation of insertions or deletions (indels) following aberrant dsDNA repair via the endogenous non-homology end-joining (NHEJ) pathway, or alternatively, for enhancing homology directed repair (HDR) to facilitate the generation of a specific mutation (or knock-in). However, there is a need for efficient cellular assays that can measure Cas9/guide RNA (gRNA) activity...
February 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28220954/is-god-just-a-big-person-children-s-conceptions-of-god-across-cultures-and-religious-traditions
#7
Melanie A Nyhof, Carl N Johnson
The present research examines the influence of intuitive cognitive domain and religion on the God concepts of children growing up in religious traditions that present God in ways varying from abstract to concrete. In Study 1, we compared children from a Latter-Day Saints (LDS) background with those from mainstream Christian (MC) backgrounds in the United States. In contrast to MC theology that holds that God is all-knowing, all-powerful, and disembodied, LDS theology depicts God as embodied. In Study 1, 3- to 7-year-olds from LDS and MC backgrounds were asked about supernatural mental and immaterial attributes of God, a ghost, a dad, and a bug...
March 2017: British Journal of Developmental Psychology
https://www.readbyqxmd.com/read/28218725/treating-cancer-by-targeting-telomeres-and-telomerase
#8
REVIEW
Marko Ivancich, Zachary Schrank, Luke Wojdyla, Brandon Leviskas, Adijan Kuckovic, Ankita Sanjali, Neelu Puri
Telomerase is expressed in more than 85% of cancer cells. Tumor cells with metastatic potential may have a high telomerase activity, allowing cells to escape from the inhibition of cell proliferation due to shortened telomeres. Human telomerase primarily consists of two main components: hTERT, a catalytic subunit, and hTR, an RNA template whose sequence is complimentary to the telomeric 5'-dTTAGGG-3' repeat. In humans, telomerase activity is typically restricted to renewing tissues, such as germ cells and stem cells, and is generally absent in normal cells...
February 19, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28216661/mir-194-5p-bclaf1-deregulation-in-aml-tumorigenesis
#9
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/28214865/inhibition-of-trpc6-signal-pathway-alleviates-podocyte-injury-induced-by-tgf-%C3%AE-1
#10
Haiting Huang, Yanwu You, Xu Lin, Chunrong Tang, Xiangjun Gu, Meiying Huang, Youling Qin, Junhua Tan, Feifan Huang
BACKGROUND/AIMS: Transforming growth factor beta 1 (TGF-β1) plays a critical role in the pathogenesis of glomerulosclerosis. The purpose of this study was to examine the effects of inhibition of transient receptor potential cation channel C6 (TRPC6) on podocyte injury induced by TGF-β1 via nephrin and desmin mechanisms. METHODS: A rat model of nephropathy was first induced by intravenous injections of adriamycin to determine TRPC6 signal pathway engaged in glomerulosclerosis in vivo...
January 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28210005/mll-is-essential-for-nup98-hoxa9-induced-leukemia
#11
Y Shima, M Yumoto, T Katsumoto, I Kitabayashi
Rearrangements involving the NUP98 gene resulting in fusions to several partner genes occur in acute myeloid leukemia and myelodysplastic syndromes. This study demonstrates that the second FG repeat domain of the NUP98 moiety of the NUP98-HOXA9 fusion protein is important for its cell immortalization and leukemogenesis activities. We demonstrate that NUP98-HOXA9 interacts with MLL via this FG repeat domain and that, in the absence of MLL, NUP98-HOXA9-induced cell immortalization and leukemogenesis are severely inhibited...
February 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28209158/gene-regulatory-network-underlying-the-immortalization-of-epithelial-cells
#12
Luis Fernando Méndez-López, Jose Davila-Velderrain, Elisa Domínguez-Hüttinger, Christian Enríquez-Olguín, Juan Carlos Martínez-García, Elena R Alvarez-Buylla
BACKGROUND: Tumorigenic transformation of human epithelial cells in vitro has been described experimentally as the potential result of spontaneous immortalization. This process is characterized by a series of cell-state transitions, in which normal epithelial cells acquire first a senescent state which is later surpassed to attain a mesenchymal stem-like phenotype with a potentially tumorigenic behavior. In this paper we aim to provide a system-level mechanistic explanation to the emergence of these cell types, and to the time-ordered transition patterns that are common to neoplasias of epithelial origin...
February 16, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28208427/growing-complex-network-of-citations-of-scientific-papers-modeling-and-measurements
#13
Michael Golosovsky, Sorin Solomon
We consider the network of citations of scientific papers and use a combination of the theoretical and experimental tools to uncover microscopic details of this network growth. Namely, we develop a stochastic model of citation dynamics based on the copying-redirection-triadic closure mechanism. In a complementary and coherent way, the model accounts both for statistics of references of scientific papers and for their citation dynamics. Originating in empirical measurements, the model is cast in such a way that it can be verified quantitatively in every aspect...
January 2017: Physical Review. E
https://www.readbyqxmd.com/read/28203523/glutathione-peroxidase-4-plays-an-important-role-in-oxidative-homeostasis-and-wound-repair-in-corneal-epithelial-cells
#14
Osamu Sakai, Takatoshi Uchida, Hirotaka Imai, Takashi Ueta
Oxidative stress is involved in the pathologies of corneal epithelial cells. However, the importance of specific antioxidant enzymes in corneal epithelial cells is not fully understood. The purpose of this study is to elucidate the role of glutathione peroxidase 4 (GPx4) in corneal epithelial cells. For in vitro experiments, an immortalized human corneal epithelial cell line was used. Cytotoxicity measured through LDH activity, lipid peroxidation immunostained for 4-hydroxynonenal, cell viability, and cell death were compared between cells transfected with either GPx4 siRNA or scrambled control siRNA...
December 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/28202506/recurrent-patterns-of-dna-copy-number-alterations-in-tumors-reflect-metabolic-selection-pressures
#15
Nicholas A Graham, Aspram Minasyan, Anastasia Lomova, Ashley Cass, Nikolas G Balanis, Michael Friedman, Shawna Chan, Sophie Zhao, Adrian Delgado, James Go, Lillie Beck, Christian Hurtz, Carina Ng, Rong Qiao, Johanna Ten Hoeve, Nicolaos Palaskas, Hong Wu, Markus Müschen, Asha S Multani, Elisa Port, Steven M Larson, Nikolaus Schultz, Daniel Braas, Heather R Christofk, Ingo K Mellinghoff, Thomas G Graeber
Copy number alteration (CNA) profiling of human tumors has revealed recurrent patterns of DNA amplifications and deletions across diverse cancer types. These patterns are suggestive of conserved selection pressures during tumor evolution but cannot be fully explained by known oncogenes and tumor suppressor genes. Using a pan-cancer analysis of CNA data from patient tumors and experimental systems, here we show that principal component analysis-defined CNA signatures are predictive of glycolytic phenotypes, including (18)F-fluorodeoxy-glucose (FDG) avidity of patient tumors, and increased proliferation...
February 15, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28197657/gestational-diabetes-and-adverse-perinatal-outcomes-from-716-152-births-in-france-in-2012
#16
Cécile Billionnet, Delphine Mitanchez, Alain Weill, Jacky Nizard, François Alla, Agnès Hartemann, Sophie Jacqueminet
AIMS/HYPOTHESIS: The aim of this study was to assess the risk of adverse perinatal outcomes in gestational diabetes mellitus (GDM) in a large national cohort. METHODS: All deliveries taking place after 22 weeks in France in 2012 were included by extracting data from the hospital discharge database and the national health insurance system. The diabetic status of mothers was determined by the use of glucose-lowering agents and by hospital diagnosis. Outcomes were analysed according to the type of diabetes and, in the GDM group, whether or not diabetes was insulin-treated...
February 15, 2017: Diabetologia
https://www.readbyqxmd.com/read/28197378/identification-of-inhibitors-of-myeloid-derived-suppressor-cells-activity-through-phenotypic-chemical-screening
#17
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/28192959/a-spatial-dependent-fluorescent-probe-for-detecting-different-situations-of-mitochondrial-membrane-potential-conveniently-and-efficiently
#18
Xuechen Li, Minggang Tian, Ge Zhang, Ruoyao Zhang, Ruiqing Feng, Lifang Guo, Xiaoqiang Yu, Ning Zhao, Xiuquan He
The feedback from mitochondrial membrane potential (MMP) in different situations (normal, decreasing, and vanishing) can reflect different cellular status, which can be applied in biomedical research and diagnosis of the related diseases. Thus, the efficient and convenient detection for MMP in different situations is particularly important yet the operations of current fluorescent probes are complex. In order to address this concern, we presented herein a spatial-dependent fluorescent probe composed of organic cationic salt...
February 14, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28191273/oxidative-stress-triggered-by-apigenin-induces-apoptosis-in-a-comprehensive-panel-of-human-cervical-cancer-derived-cell-lines
#19
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/28188264/immortalized-human-myotonic-dystrophy-muscle-cell-lines-to-assess-therapeutic-compounds
#20
Arandel Ludovic, Polay-Espinosa Micaela, Matloka Magdalena, Bazinet Audrey, De Dea Diniz Damily, Naouar Naïra, Rau Frédérique, Jollet Arnaud, Edom-Vovard Frédérique, Mamchaoui Kamel, Tarnopolsky Mark, Puymirat Jack, Battail Christophe, Boland Anne, Deleuze Jean-Francois, Mouly Vincent, Klein F Arnaud, Furling Denis
Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA-aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared to control and DM2 cells...
February 10, 2017: Disease Models & Mechanisms
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