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https://www.readbyqxmd.com/read/29156743/hepatitis-c-virus-core-overcomes-all-trans-retinoic-acid-induced-apoptosis-in-human-hepatoma-cells-by-inhibiting-p14-expression-via-dna-methylation
#1
Juri Kwak, Jung-Hye Choi, Kyung Lib Jang
All-trans retinoic acid (ATRA), the most biologically active metabolite of vitamin A, is known to induce p14 expression via promoter hypomethylation to activate the p14-MDM2-p53 pathway, which leads to activation of the p53-dependent apoptotic pathway and subsequent induction of apoptosis in human hepatoma cells. In the present study, we found that hepatitis C virus (HCV) Core derived from ectopic expression or HCV infection overcomes ATRA-induced apoptosis in p53-positive hepatoma cells. For this effect, HCV Core upregulated both protein levels and enzyme activities of DNA methyltransferase 1 (DNMT1), DNMT3a, and DNMT3b and thereby repressed p14 expression via promoter hypermethylation, resulting in inactivation of the pathway leading to p53 accumulation in the presence of ATRA...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155646/combination-treatment-of-docosahexaenoic-acid-dha-and-all-trans-retinoic-acid-atra-inhibit-il-17-and-ror%C3%AE-t-gene-expression-in-pbmcs-of-patients-with-relapsing-remitting-multiple-sclerosis
#2
Ateke Mousavi Nasl-Khameneh, Abbas Mirshafiey, Abdorreza Naser Moghadasi, Reza Chahardoli, Maryam Mahmoudi, Karim Parastouei, Mir Saeed Yekaninejad, Ali Akbar Saboor-Yaraghi
OBJECTIVES: Multiple sclerosis (MS) is a demyelinating disorder with a complex autoimmune pathophysiology. Its initiation and progression correlate with IL-17 and the related transcription factor, RORγt. All-trans retinoic acid (ATRA) is a bioactive derivative of vitamin A, and docosahexaenoic acid (DHA) is an active metabolite of omega-3 fatty acid; both have immunomodulatory effects in many immune disorders. This study investigated the effects of DHA and ATRA individually and in combination on IL-17 and RORγt gene expression in peripheral blood mononuclear cells (PBMCs) of relapsing-remitting MS (RRMS) patients who were receiving interferon beta (IFN-β)...
November 18, 2017: Neurological Research
https://www.readbyqxmd.com/read/29154838/tp-0903-inhibits-neuroblastoma-cell-growth-and-enhances-the-sensitivity-to-conventional-chemotherapy
#3
Sanja Aveic, Diana Corallo, Elena Porcù, Marcella Pantile, Daniele Boso, Carlo Zanon, Giampietro Viola, Viktoryia Sidarovich, Elena Mariotto, Alessandro Quattrone, Giuseppe Basso, Gian Paolo Tonini
Neuroblastoma (NB) is an embryonal tumor with low cure rate for patients classified as high-risk. This class of NB tumors shows a very complex genomic background and requires aggressive treatment strategies. In this work we evaluated the efficacy of the novel multi-kinase inhibitor TP-0903 in impairing NB cells' growth, proliferation and motility. In vitro studies were performed using cell lines with different molecular background, and in vivo studies were done using the zebrafish experimental model. Our results confirmed a strong cytotoxicity of TP-0903 already at the sub-micro molar concentrations...
November 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29150592/the-influence-of-genetic-stability-on-aspergillus-fumigatus-virulence-and-azole-resistance
#4
Thaila Fernanda Dos Reis, Lilian Pereira Silva, Patrícia Alves de Castro, Pollyne Borborema Almeida de Lima, Rafaela Andrade do Carmo, Marjorie Mendes Marini, José Franco da Silveira, Beatriz Henriques Ferreira, Fernando Rodrigues, Iran Malavazi, Gustavo H Goldman
Genetic stability is extremely important for the survival of every living organism and a very complex set of genes have evolved to cope with DNA repair upon DNA damage. Here, we investigated the Aspergillus fumigatus AtmA (Ataxia-telangiectasia mutated) and AtrA kinases and how they impact virulence and the evolution of azole resistance. We demonstrated that A. fumigatus atmA and atrA null mutants are haploid and have a discrete chromosomal polymorphism. The ΔatmA and ΔatrA strains are sensitive to several DNA damaging agents but surprisingly both strains were more resistant than the wild-type strain to paraquat, menadione, and hydrogen peroxide...
November 17, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29138846/itr%C3%A2-284-modulates-cell-differentiation-in-human-chronic-myelogenous-leukemia-k562-cells
#5
Jai-Sing Yang, Chao-Ying Lee, Hsin-Chung Cho, Chi-Cheng Lu, Sheng-Chu Kuo, Yen-Fang Wen, Fuu-Jen Tsai, Miau-Rong Lee, Shih-Chang Tsai
ITR‑284 is a carboxamide analog that can inhibit proliferation in human promyelocytic leukemia HL-60 cells. To understand the effects and molecular mechanisms of ITR‑284 in human erythromyeloblastoid leukemia, we treated K562 cells with different concentrations of ITR‑284 (0, 2, 4, 6, 8 and 10 nM) and all-trans retinoic acid (ATRA) (0, 0.1, 0.5, 1, 5 and 10 µM) for 24 h. The IC50 of ITR‑284 was ~10 nM in K562 cells treated for 24 h as determined by MTT assay. May-Grünwald-Giemsa staining and nitro blue tetrazolium (NBT) assays were used to determine cell morphology changes and differentiation after ITR‑284 and ATRA treatment...
November 9, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29137406/the-forkhead-box-c1-foxc1-transcription-factor-is-downregulated-in-acute-promyelocytic-leukemia
#6
Emiliano Fabiani, Giulia Falconi, Nélida Inés Noguera, Ernestina Saulle, Laura Cicconi, Mariadomenica Divona, Cristina Banella, Alessandra Picardi, Anna Maria Cerio, Letizia Boe, Massimo Sanchez, Elvira Pelosi, Ugo Testa, Francesco Lo-Coco, Maria Teresa Voso
Forkhead box (FOX) genes encode transcription factors, which regulate embryogenesis and play an important role in hematopoietic differentiation and in mesenchymal niche maintenance. Overexpression of the family member FOXC1 has been reported in solid tumors and acute myeloid leukemia (AML). We studied FOXC1 expression and function in acute promyelocytic leukemia (APL) and normal hematopoietic progenitors. FOXC1 mRNA and protein levels were significantly lower in primary marrow samples from 27 APL patients, as compared to samples obtained from 27 patients with other AML subtypes, and 5 normal CD34+ hematopoietic cells...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29131833/mek-inhibitors-enhance-therapeutic-response-towards-atra-in-nf1-associated-malignant-peripheral-nerve-sheath-tumors-mpnst-in-vitro
#7
Susan Fischer-Huchzermeyer, Anna Dombrowski, Gordon Wilke, Verena Stahn, Anna Streubel, Victor Felix Mautner, Anja Harder
OBJECTIVE: Neurofibromatosis type 1 (NF1) is a hereditary tumor syndrome characterized by an increased risk of malignant peripheral nerve sheath tumors (MPNST). Chemotherapy of MPNST is still insufficient. In this study, we investigated whether human tumor Schwann cells derived from NF1 associated MPNST respond to all-trans retinoic acid (ATRA). We analyzed effects of ATRA and MEK inhibitor (MEKi) combination therapy. METHODS: MPNST cell lines S462, T265, NSF1 were treated with ATRA and MEKi U0126 and PD0325901...
2017: PloS One
https://www.readbyqxmd.com/read/29118638/new-records-of-the-soldier-flies-of-morocco-with-a-bibliographical-inventory-of-the-north-african-fauna-diptera-stratiomyidae
#8
Driss Yimlahi, Turgay Üstüner, Sanae Zinebi, Boutaïna Belqat
A checklist of soldier flies species recorded from the North African countries of Morocco, Algeria, Tunisia, Libya, and Egypt is based on both literature records and material newly collected in Morocco. Four subfamilies (Stratiomyinae, Sarginae, Nemotelinae, and Pachygasterinae), and twelve species from five genera have been collected and are recognized in Morocco. Pachygaster atra (Panzer, 1798), Oxycera pardalina (Meigen, 1822), Nemotelus danielssoni (Mason, 1989), and Oxycera terminata (Meigen, 1822) are newly recorded to the North African fauna...
2017: ZooKeys
https://www.readbyqxmd.com/read/29114972/frontline-therapy-of-acute-promyelocytic-leukemia-randomized-comparison-of-atra-and-intensified-chemotherapy-versus-atra-and-anthracyclines
#9
Eva Lengfelder, Dennis Görlich, Daniel Nowak, Karsten Spiekermann, Claudia Haferlach, Utz Krug, Karl-Anton Kreuzer, Jan Braess, Christoph Schliemann, Hans-Walter Lindemann, Heinz A Horst, Xaver Schiel, Michael Flasshove, Anna Hecht, Susanne Schnittger, Stephanie Schneider, Bernhard Wörmann, Wolf-Karsten Hofmann, Wolfgang E Berdel, Eike Bormann, Cristina Sauerland, Thomas Büchner, Wolfgang Hiddemann
OBJECTIVES: Randomized comparison of two treatment strategies in frontline therapy of acute promyelocytic leukemia (APL): all-trans retinoic acid (ATRA) and double induction intensified by high dose cytosine arabinoside (HD ara-C) (German AMLCG) and therapy with ATRA and anthracyclines (Spanish PETHEMA, LPA99). PATIENTS AND RESULTS: Eighty of 87 adult patients with genetically confirmed APL of all risk groups were eligible. The outcome of both arms was similar: AMLCG vs PETHEMA: hematological complete remission 87% vs 83%, early death 13% vs 17% (p=0...
November 7, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29111326/c-ebp%C3%AE-contributes-to-transcriptional-activation-of-long-non-coding-rna-neat1-during-apl-cell-differentiation
#10
Yewei Wang, Lei Fu, Ailian Sun, Doudou Tang, Yunxiao Xu, Zheyuan Li, Mingjie Chen, Guangsen Zhang
Emerging evidences have shown that long non-coding RNAs (lncRNAs) play critical roles in cancer development and cancer therapy. LncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) is indispensable during acute promyelocytic leukemia (APL) cell differentiation induced by all-trans retinoic acid (ATRA). However, the precise mechanism of NEAT1 upregulation has not been fully understood. In this study, we performed chromatin immunoprecipitation and luciferase reporter assays to demonstrate that C/EBP family transcription factor C/EBPβ bind to and transactivate the promoter of lncRNA NEAT1 through the C/EBPβ binding sites both around -54 bp and -1453 bp upstream of the transcription start site...
October 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29110117/successful-treatment-of-acute-promyelocytic-leukemia-in-pregnancy-with-single-agent-all-trans-retinoic-acid
#11
REVIEW
Cordula M Nellessen, Viktor Janzen, Karin Mayer, Giulia Giovannini, Ulrich Gembruch, Peter Brossart, Waltraut M Merz
PURPOSE: The diagnosis of acute promyelocytic leukemia (APL) in pregnancy is an uncommon, life-threatening emergency. Choice of treatment and management of complications are challenging. METHODS: We report the case of a patient with diagnosis of APL at gestational age (GA) 24 + 4. We describe the interdisciplinary management during pregnancy and delivery and provide a 2-year follow-up. Existing reports on APL in pregnancy are summarized. RESULTS: Single-agent induction therapy with all-trans retinoic acid (ATRA) was started and resulted in normalization of blood cell counts after 32 days...
November 6, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/29097117/dasatinib-synergizes-with-atra-to-trigger-granulocytic-differentiation-in-atra-resistant-acute-promyelocytic-leukemia-cell-lines-via-lyn-inhibition-mediated-activation-of-raf-1-mek-erk
#12
Ming Ding, Xiang-Qin Weng, Yan Sheng, Jing Wu, Cui Liang, Xun Cai
All-trans retinoic acid (ATRA) resistance has been a critical problem in acute promyelocytic leukemia (APL) relapsed patients. In this study, dasatinib synergized with ATRA to trigger differentiation in ATRA-resistant APL cell lines. The combined treatment activated RAF-1, MEK and ERK as well as enhanced ATRA-promoted up-regulation of the protein level of PU.1, C/EBPβ and C/EBPε. U0126 (MEK specific inhibitor) and sorafenib tosylate (RAF-1 specific inhibitor) suppressed the combined treatment-induced differentiation, ERK phosphorylation and the up-regulation of C/EBPs and PU...
October 30, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29096331/nucleostemin-silencing-induces-differentiation-and-potentiates-all-trans-retinoic-acid-effects-in-human-acute-promyelocytic-leukemia-nb4-cells-via-autophagy
#13
Aila Fakhimahmadi, Farinaz Nazmi, Marveh Rahmati, Nazila Moghtaran Bonab, Mehrdad Hashemi, Mohammad Amin Moosavi
Here, we report that targeting Nucleostemin (NS), a recently discovered stem cells-enriched gene, by a specific small interference RNA (siNS), decreases the rate of proliferation of acute promyelocytic leukemia (APL) NB4 cells and induces differentiation and autophagy. In addition, NS silencing promotes the effects of all-trans-retinoic acid (ATRA)-based differentiation therapy in NB4 cells. Autophagy inhibitors 3-methyladenine and bafilomycin block the effect of NS targeting on differentiation, indicating a new functional link between NS and autophagy as an important regulator of differentiation in NB4 cells...
October 26, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29095919/raldh1-promotes-adiposity-during-adolescence-independently-of-retinal-signaling
#14
Di Yang, Charles R Krois, Priscilla Huang, Jinshan Wang, Jin Min, Hong Sik Yoo, Yinghua Deng, Joseph L Napoli
All-trans-retinoic acid (RA) inhibits adipogenesis in established preadipocyte cell lines. Dosing pharmacological amounts of RA reduces weight gain in mice fed a high-fat diet, i.e. counteracts diet-induced obesity (DIO). The aldehyde dehydrogenase Raldh1 (Aldh1a1) functions as one of three enzymes that converts the retinol metabolite retinal into RA, and one of many proteins that contribute to RA homeostasis. Female Raldh1-ablated mice resist DIO. This phenotype contrasts with ablations of other enzymes and binding-proteins that maintain RA homeostasis, which gain adiposity...
2017: PloS One
https://www.readbyqxmd.com/read/29081694/recurrent-fusion-genes-in-leukemia-an-attractive-target-for-diagnosis-and-treatment
#15
REVIEW
Yuhui Wang, Nan Wu, Duo Liu, Yan Jin
INTRODUCTION: Since the first fusion gene was discovered decades ago, a considerable number of fusion genes have been detected in leukemia. The majority of them are generated through chromosomal rearrangement or abnormal transcription. With the development of techniques, high-throughput sequencing method makes it possible to detect fusion genes systematically in multiple human cancers. Owing to their biological significance and tumor-specific expression, some of the fusion genes are attractive diagnostic tools and therapeutic targets...
October 2017: Current Genomics
https://www.readbyqxmd.com/read/29070519/the-mechanism-of-all-trans-retinoic-acid-in-the-regulation-of-apelin-expression-in-vascular-endothelial-cells
#16
Hongyun Shi, Lanhui Yuan, Huibing Yang, Aimin Zang
The apelin gene can promote vascular endothelial cell (VEC) proliferation, migration and angiogenesis. However, the molecular mechanism for regulation of the apelin gene is still unknown. Real-time PCR and Western blotting analysis were employed to detect the effect of all-trans retinoic acid (ATRA) in up-regulating apelin expression in human umbilical vein endothelial cells (HUVECs). Furthermore, the in vivo study also indicated that ATRA could increase apelin expression in balloon-injured arteries of rats, which is consistent with the results from the cultured HUVECs...
October 25, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29068287/hepatitis-b-virus-x-protein-suppresses-all-trans-retinoic-acid-induced-apoptosis-in-human-hepatocytes-by-repressing-p14-expression-via-dna-methylation
#17
Jung-Hye Choi, Hyerin Jeong, Kyung Lib Jang
All-trans retinoic acid (ATRA), the most biologically active metabolite of vitamin A, is known to activate p14 expression via promoter hypermethylation to induce p53-dependent apoptosis in human hepatocytes. In this study, we found that the oncogenic hepatitis B virus (HBV) X protein (HBx) of HBV, derived from both overexpression and 1.2-mer replicon systems, suppresses ATRA-induced apoptosis in p53-positive human hepatocytes. For this effect, HBx upregulated both protein and enzyme activity levels of DNA methyltransferase 1, 3a and 3b, in the presence of ATRA and thereby inhibited p14 expression via promoter hypermethylation, resulting in inactivation of the p14-mouse double minute 2 pathway and subsequent downregulation of p53 levels...
November 2017: Journal of General Virology
https://www.readbyqxmd.com/read/29055789/in-vitro-studies-on-the-role-of-recombinant-human-soluble-thrombomodulin-in-the-context-of-retinoic-acid-mediated-apl-differentiation-syndrome
#18
Shinsuke Kojima, Chie Nishioka, SungGi Chi, Akihito Yokoyama, Takayuki Ikezoe
Recombinant human soluble thrombomodulin (rTM) is a newly developed anti-coagulant approved for treatment of disseminated intravascular coagulation (DIC) in Japan. rTM exerts anti-inflammatory and cytoprotective functions via its lectin-like and epidermal growth factor-like domains, respectively. In this study, we retrospectively reviewed the treatment of 21 consecutive patients with coagulopathy, complicated by acute promyelocytic leukemia (APL), with all-trans retinoic acid (ATRA) with or without combination with rTM...
October 18, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29053272/cardiotoxins-functional-role-of-local-conformational-changes
#19
Anastasia G Konshina, Nikolay A Krylov, Roman G Efremov
Cardiotoxins (CTs) from snake venoms are a family of homologous highly basic proteins that have extended hydrophobic patterns on their molecular surfaces. CTs are folded into three β-structured loops stabilized by four disulfide bridges. Being well-structured in aqueous solution, most of these proteins are membrane-active, although the exact molecular mechanisms of CT-induced cell damage are still poorly understood. To elucidate the structure-function relationships in CTs, a detailed knowledge of their spatial organization and local conformational dynamics is required...
October 20, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29042924/inhibition-of-periderm-removal-in-all-trans-retinoic-acid-induced-cleft-palate-in-mice
#20
Ya-Dong Zhang, Shi-Yi Dong, Hong-Zhang Huang
Cleft palate is a common craniofacial birth defect. The aim of the present study was to investigate the effect of excess all-trans retinoic acid (atRA) on periderm removal and the disappearance of basal medial edge epithelial (MEE) cells during palatogenesis, particularly during the stage prior to contact. atRA (200 mg/kg) was administered to C57BL/6N mice at embryonic day (E) 12.0 by gavage. Fetal palates were processed and analyzed by histology and electron microscopy. Single palate shelf peridermal cells were removed and cultured in the presence of atRA (3 µM) only or in the presence of or the caspase inhibitor, Z-VAD (100 µM) only, for 48 h...
October 2017: Experimental and Therapeutic Medicine
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