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Mona Dawood, Sami Hamdoun, Thomas Efferth
Arsenic trioxide is a traditional remedy in Chinese Medicine since ages. Nowadays, it is clinically used to treat acute promyelocytic leukemia (APL) by targeting PML/RARA. However, the drug's activity is broader and the mechanisms of action in other tumor types remain unclear. In this study, we investigated molecular modes of action by classical and network pharmacological approaches. CEM/ADR5000 resistance leukemic cells were similar sensitive to As2 O3 as their wild-type counterpart CCRF-CEM (resistance ratio: 1...
2018: Frontiers in Pharmacology
Mohamed Ali Maroui, Ghizlane Maarifi, Francis P McManus, Frederic Lamoliatte, Pierre Thibault, Mounira K Chelbi-Alix
We report that interferon (IFN) a treatment at short and long periods increases the global cellular SUMOylation and requires the presence of the SUMO E3 ligase promyelocytic leukemia protein (PML), the organizer of PML nuclear bodies (NBs). Several PML isoforms (PMLI-PMLVII) derived from a single PML gene by alternative splicing, share the same N-terminal region but differ in their C-terminal sequences. Introducing each of the human PML isoform in PML-negative cells revealed that enhanced SUMOylation in response to IFN is orchestrated by PMLIII and PMLIV...
March 13, 2018: Molecular & Cellular Proteomics: MCP
Jian-An Li, Jinghong Zhou, Zhu Mao, Zongliang Xie, Zhan Yang, Bingjia Xu, Cong Liu, Xin Chen, Dingyang Ren, Hui Pan, Guang Shi, Yi Zhang, Zhenguo Chi
Persistent luminescence from purely organic materials is basically triggered by light and electricity, which largely confines its practical applications. Herein, we present a purely organic AIEgen that exhibited not only persistent photoluminescence, but also transient and persistent room-temperature mechanoluminescence. By simply turning on and off the UV lamp, tricolor emission switching between blue, white and yellow was also achieved. The data from single-crystal structure analysis and theoretical calculation suggest that mechanism of the observed persistent mechanoluminescence (pML) is correlated with the strong spin-orbit coupling of bromine atom, as well as the formation of H-aggregates and restriction of intramolecular motions in noncentrosymmetric crystal structure...
March 13, 2018: Angewandte Chemie
Shinji Aoyama, Masahiro Mori, Akiyuki Uzawa, Tomohiko Uchida, Hiroki Masuda, Ryohei Ohtani, Satoshi Kuwabara
BACKGROUND: The risk of developing progressive multifocal leukoencephalopathy in natalizumab-treated multiple sclerosis (MS) patients is related to serum anti-JCV antibody (JCVAb) index. However, the correlation of JCVAb index with other disease-modifying treatments (DMTs) is not well understood. OBJECTIVE: In this study, we investigated the JCVAb seropositivity rate/JCVAb indexes and its correlation with clinical profiles in Japanese MS patients, and the relationship between JCVAb indexes and DMTs...
March 12, 2018: Journal of Neurology
Martijn T Wijburg, Iris Kleerekooper, Birgit I Lissenberg-Witte, Marlieke de Vos, Clemens Warnke, Bernard M J Uitdehaag, Frederik Barkhof, Joep Killestein, Mike P Wattjes
Importance: The JC virus (JCV) was named after the first patient to be described with progressive multifocal leukoencephalopathy (PML), John Cunningham. Detection of JC virus DNA in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR), and of specific lesions by brain magnetic resonance imaging (MRI), are both considered essential for the diagnosis of natalizumab-associated PML (NTZ-PML) in patients with multiple sclerosis. However, strict pharmacovigilance by MRI can result in detection of patients with small lesions and undetectable JCV DNA in CSF...
March 12, 2018: JAMA Neurology
Nicoletta Coccaro, Antonella Zagaria, Paola Orsini, Luisa Anelli, Giuseppina Tota, Paola Casieri, Luciana Impera, Angela Minervini, Crescenzio F Minervini, Cosimo Cumbo, Elisa Parciante, Anna Mestice, Mario Delia, Claudia Brunetti, Giorgina Specchia, Francesco Albano
Most Acute Promyelocytic Leukemia (APL) patients express PML-RARA fusion; in rare cases RARA is rearranged with partner genes other than PML. To date, only two patients presenting features similar to APL showing the RARG gene rearrangement have been described. We report an Acute Myeloid Leukemia (AML) patient with morphology resembling APL without involvement of the RARA gene. Molecular and Fluorescent In Situ Hybridization (FISH) analyses excluded PML-RARA fusion and variant rearrangements involving RARA and RARG loci...
March 9, 2018: Human Pathology
Elaine J Lin, Shivani Reddy, Vidhi V Shah, Jashin J Wu
The use of biologic medications has represented a great advancement in the treatment of moderate to severe plaque psoriasis and has improved patients' quality of life. Despite the increasing popularity of biologics, their neurological side effects have been a constant concern. Reports of demyelinating diseases associated with tumor necrosis factor α (TNF-α) inhibitors continue to accumulate. Additionally, efalizumab was withdrawn from the market in 2009 for causing progressive multifocal leukoencephalopathy (PML)...
January 2018: Cutis; Cutaneous Medicine for the Practitioner
Kuo-Sheng Hsu, Hung-Ying Kao
[This corrects the article DOI: 10.1186/s13578-018-0204-8.].
2018: Cell & Bioscience
Fang Qiu, Changjiang Dong, Yanxin Liu, Xiaoqi Shao, Di Huang, Yanna Han, Bing Wang, Yanli Liu, Rong Huo, Petro Paulo, Zhiren Zhang, Dan Zhao, Wen-Feng Chu
BACKGROUND AND PURPOSE: Protein modification by small ubiquitin-like modifier (SUMO) plays a critical role in the pathogenesis of heart diseases. The present study was designed to determine whether ginkgolic acid (GA) as a SUMO-1 inhibitor exerts an inhibitory effect on cardiac fibrosis induced by myocardial infarction (MI). EXPERIMENTAL APPROACH: GA was delivered by osmotic pumps in MI mice. Masson staining, electron microscopy (EM) and echocardiography were used to assess cardiac fibrosis, ultrastructure and function...
March 7, 2018: Toxicology and Applied Pharmacology
Cai Yuan, Candace Deberardinis, Rushang Patel, Seema M Shroff, Steven A Messina, Steven Goldstein, Shahram Mori
Progressive multifocal leukoencephalopathy (PML) is a rare, yet typically fatal complication of allogeneic stem cell transplantation. It is caused by reactivation of the John Cunningham (JC) virus in an immunocompromised host. This report describes an unfortunate case of PML in a recipient of an allogeneic stem cell transplant for acute myelogenous leukemia. The JC virus was undetectable in the patient's cerebrospinal fluid by PCR; however, a positive diagnosis was made after a brain biopsy. This and other published cases demonstrate that recipients of allogeneic stem cells can develop PML...
March 7, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Joseph R Berger, Vineeta Malik, Stuart Lacey, Paul Brunetta, Patricia B Lehane
This report assesses the observed risk of PML in patients treated with the anti-CD20 monoclonal antibody rituximab in the regulatory authority-approved autoimmune indications rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA). This was a cumulative analysis of confirmed PML cases in patients receiving rituximab for RA or GPA/MPA from both spontaneous reports and clinical trial sources, as captured in the manufacturer global company safety and clinical databases...
March 5, 2018: Journal of Neurovirology
C P Sawicki, S A Climans, C C Hsia, J A Fraser
Progressive multifocal leukoencephalopathy (pml) is a rare demyelinating disease of the central nervous system that most often affects immunocompromised individuals. It is caused by the reactivation of the John Cunningham virus (jcv), which is found in latent form in the majority of adults. We describe a 59-year-old man with multiple myeloma who developed severe neurological deficits during treatment with ixazomib-based chemotherapy. A diagnosis of pml was established with gadolinium-enhanced magnetic resonance imaging (mri) and by detection of jcv in the cerebrospinal fluid...
February 2018: Current Oncology
Louise Dubuisson, Florence Lormières, Stefania Fochi, Jocelyn Turpin, Amandine Pasquier, Estelle Douceron, Anaïs Oliva, Ali Bazarbachi, Valérie Lallemand-Breitenbach, Hugues De Thé, Chloé Journo, Renaud Mahieux
Since the identification of the antisense protein of HTLV-2 (APH-2) and the demonstration that APH-2 mRNA is expressed in vivo in most HTLV-2 carriers, much effort has been dedicated to the elucidation of similarities and/or differences between APH-2 and HBZ, the antisense protein of HTLV-1. Similar to HBZ, APH-2 negatively regulates HTLV-2 transcription. However, it does not promote cell proliferation. In contrast to HBZ, APH-2 half-life is very short. Here, we show that APH-2 is addressed to PML nuclear bodies in T-cells, as well as in different cell types...
March 6, 2018: Oncogene
Farhoud Faraji, Stephanie F Coquia, Meghan B Wenderoth, Ericka S Padilla, Dana Blitz, M Robert DeJong, Nafi Aygun, Ulrike M Hamper, Carole Fakhry
OBJECTIVE: To compare transcervical ultrasonography (US) to standard cross-sectional imaging for the visualization of human papillomavirus-related oropharyngeal cancer (HPV-OPC). MATERIALS AND METHODS: Patients with HPV-OPC and available standard imaging (CT and/or MRI) were identified in clinic and prospectively enrolled. US was performed to visualize the oropharynx and lymph nodes. Tumor characteristics across imaging modalities were evaluated (CT versus MRI, and US versus standard imaging (SI))...
March 2018: Oral Oncology
Philipp E Merkl, Megan Orzalli, David M Knipe
The initial events after DNA virus infection involve a race between epigenetic silencing of the incoming viral DNA by host cell factors and expression of viral genes. Several host gene products, including the nuclear domain 10 (ND10) components PML (promyelocytic leukemia) and Daxx (death domain-associated protein 6), as well as IFI16 (interferon-inducible protein 16), have been shown to restrict herpes simplex virus 1 (HSV-1) replication. Whether IFI16 and ND10 components work together or separately to restrict HSV-1 replication is not known...
February 28, 2018: Journal of Virology
Rossella Avagliano Trezza, Janny van den Burg, Nico van den Oever, Ben Distel
Ubiquitination is a posttranslational protein modification that regulates most aspects of cellular life. The sheer number of ubiquitination enzymes that are present in a mammalian cell, over 700 in total, has thus far hampered the analysis of distinct protein ubiquitination cascades in a cellular context. To overcome this complexity we have developed a versatile vector system that allows the reconstitution of specific ubiquitination cascades in the model eukaryote Saccharomyces cerevisae (baker's yeast). The vector system consists of 32 modular yeast shuttle plasmids allowing inducible or constitutive expression of up to four proteins of interest in a single cell...
December 5, 2017: Microbial Cell
José Carlos Jaime-Pérez, José Ramón Padilla-Medina, Lucía Teresa Fernández, José Luis Herrera-Garza, César Homero Gutiérrez-Aguirre, Luz Tarín-Arzaga, David Gómez-Almaguer
INTRODUCTION: The outcomes for adolescents and young adults (AYAs) with acute myeloid leukemia (AML) have been poorly characterized in Hispanics in low- to middle-income countries. The results are influenced by biologic and socioeconomic factors. The clinical paths for AYA patients with AML are reported. PATIENTS AND METHODS: A retrospective analysis of AYA and pediatric AML patients aged 1 to 39 years during 2003 to 2016 from a single reference center in Northeast Mexico treated with a 7+3 standard protocol was performed...
February 8, 2018: Clinical Lymphoma, Myeloma & Leukemia
Dejan Pavlovic, Mayur A Patel, Andriani C Patera, Ilse Peterson
Progressive multifocal leukoencephalopathy (PML) is a disease of the central nervous system caused by neuropathogenic prototypes of ubiquitous community-acquired JC virus (JCV). The disease became of particular concern following its association with certain therapies that modulate immune system function without heavy immunosuppression. Due to lack of prophylactic/treatment options and poor outcomes, which often include severe disability or death, PML is a considerable concern for development of new drugs that interfere with immune system functions...
February 2, 2018: Immunobiology
Thamir Alandijany, Ashley P E Roberts, Kristen L Conn, Colin Loney, Steven McFarlane, Anne Orr, Chris Boutell
[This corrects the article DOI: 10.1371/journal.ppat.1006769.].
February 2018: PLoS Pathogens
Elodie Collinge, Isabelle Tigaud, Brigitte Balme, Luc-Marie Gerland, Pierre Sujobert, Violette Carlioz, Gilles Salles, Xavier Thomas, Etienne Paubelle
RATIONALE: Acute promyelocytic leukemia (APL) is a curable subtype of acute myeloid leukemia. APL is currently treated with combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) resulting in the induction of apoptosis and differentiation of the leukemic cells. Differentiation syndrome (so-called ATRA syndrome) is the main life-threatening complication of induction therapy with these differentiating agents. PATIENT CONCERNS: Herein, we report the case of a 49-year-old woman diagnosed with APL with, concomitantly, a bulky cutaneous lesion of 10 cm diameter with a red-to-purple background and a necrotic center, localized on her abdomen...
February 2018: Medicine (Baltimore)
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