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https://www.readbyqxmd.com/read/28745271/nuclear-domain-10-components-upregulated-via-interferon-during-human-cytomegalovirus-infection-potently-regulate-viral-infection
#1
Caroline L Ashley, Mandy S Glass, Allison Abendroth, Brian P McSharry, Barry Slobedman
Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus that causes life-threatening disease in immunocompromised and immunonaïve individuals. Type I interferons (IFNs) are crucial molecules in the innate immune response to HCMV and are also known to upregulate several components of the interchromosomal multiprotein aggregates collectively referred to as nuclear domain 10 (ND10). In the context of herpesvirus infection, ND10 components are known to restrict gene expression. This raises the question as to whether key ND10 components (PML, Sp100 and hDaxx) act as anti-viral IFN-stimulated genes (ISGs) during HCMV infection...
July 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28744813/inhibition-of-protein-kinase-ck2-sensitizes-non-small-cell-lung-cancer-cells-to-cisplatin-via-upregulation-of-pml
#2
Bo Yang, Jinhong Yao, Bai Li, Guoguang Shao, Yongsheng Cui
Non-small cell lung carcinoma (NSCLC), a malignancy of lungs, is very aggressive and usually ends up with a dismal prognosis. Cisplatin (CDDP)-based systemic chemotherapy is the main pharmaceutical approach for treating NSCLC, but its effect is discounted by some hitherto unknown reasons. Thus, this study is dedicated to improving the efficacy of CDDP. Our results show that combining use of CDDP with CK2 siRNA or inhibitor is more efficient in suppressing cancer cell growth and promoting apoptosis than use of CDDP alone...
July 25, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28743050/pml-rar%C3%AE-stabilized-by-zinc-in-human-acute-promyelocytic-leukemia-nb4-cells
#3
Bo Zhu, Jia-Yu Wang, Jun-Jie Zhou, Feng Zhou, Wei Cheng, Ying-Ting Liu, Jie Wang, Xiao Chen, Dian-Hua Chen, Lan Luo, Zi-Chun Hua
Acute promyelocytic leukemia (APL) is characterized and driven by the promyelocytic leukemia protein-retinoic acid receptor alpha (PML-RARα) fusion gene. Previous studies have highlighted the importance of PML-RARα degradation in the treatment against APL. Considering the presence of two zinc fingers in the PML-RARα fusion protein, we explored the function of zinc homeostasis in maintaining PML-RARα stability. We demonstrated for the first time that zinc depletion by its chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) triggered PML-RARα degradation in NB4 APL cells via the proteasome pathway rather than the autophagy-lysosomal pathway...
July 19, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28740552/npm1-mutant-mediated-pml-delocalization-and-stabilization-enhances-autophagy-and-cell-survival-in-leukemic-cells
#4
Qin Zou, Shi Tan, Zailin Yang, Qian Zhan, Hongjun Jin, Jingrong Xian, Shuaishuai Zhang, Liyuan Yang, Lu Wang, Ling Zhang
Accumulating evidence has defined nucleophosmin 1 (NPM1) mutation as a driver genetic event in acute myeloid leukemia (AML), whereas the pathogenesis of NPM1-mutated AML remains to be fully elucidated. In this study, we showed that mutant NPM1 elevated autophagic activity and autophagic activation contributed to leukemic cell survival in vitro. Meanwhile, we also found high expression of promyelocytic leukemia gene (PML) and its cytoplasmic dislocation in primary NPM1-mutated AML blasts and NPM1-mA positive OCI-AML3 cells...
2017: Theranostics
https://www.readbyqxmd.com/read/28735486/detection-and-quantification-of-acute-myeloid-leukemia-associated-fusion-transcripts
#5
Jonathan Schumacher, Philippe Szankasi, Todd W Kelley
Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR)-based detection of abnormal fusion transcripts is an important strategy for the diagnosis and monitoring of patients with acute myeloid leukemia (AML) with t(8;21)(q22;q22); RUNX1-RUNX1T1, inv(16)(p13.1;q22); CBFB-MYH11 or t(15;17)(q22;q12); PML-RARA. In RT-qPCR assays, patient-derived cDNA is subjected to amplification using PCR primers directed against the fusion transcript of interest as well as a reference gene for normalization...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28731850/the-diagnostic-accuracy-of-biomarkers-for-diagnosis-of-primary-biliary-cholangitis-pbc-in-anti-mitochondrial-antibody-ama-negative-pbc-patients-a-review-of-literature
#6
Federica de Liso, Caterina Matinato, Mariangela Ronchi, Rita Maiavacca
Primary biliary cholangitis (PBC), also known as primary biliary cirrhosis, is an autoimmune disease of the liver characterized by anti-mitochondrial antibodies (AMA) in 90%-95% of patients. The aim of this study was to evaluate the diagnostic value of several serum biomarkers in patients with PBC but negative for AMA. Some antinuclear antibodies (ANA) pattern, detected by indirect immunofluorescence (IIF), such as multiple nuclear dot (MND) and rim-like patterns are well-known to be specific for PBC. The corresponding nuclear antigens are the components of the nuclear pore complex (Gp210 for rim-like pattern) and Sp100, PML proteins (for MND pattern) detectable by immunoblotting and ELISA methods...
July 21, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28721050/the-use-of-natalizumab-for-multiple-sclerosis
#7
REVIEW
Rachel Brandstadter, Ilana Katz Sand
Natalizumab is a monoclonal antibody that acts as an α4 integrin antagonist to prevent leukocyte trafficking into the central nervous system. It is US Food and Drug Administration (FDA) approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Natalizumab demonstrated high efficacy in Phase III trials by reducing the annualized relapse rate, preventing multiple sclerosis (MS) lesion accumulation on magnetic resonance imaging, and decreasing the probability of sustained progression of disability...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28712407/-detection-and-clinical-significance-of-pml-protein-expression-of-acute-promyelocytic-leukemia-cells
#8
Mei Song, Xiumei Wu, Mei Zhang, Pengcheng He
Objective To study the expression patterns of promyelocytic leukemia (PML) protein at different stages of acute promyelocytic leukemia (APL) and investigate the effects that the arsenical, all-trans retinoic acid (ATRA) and chemotherapeutic drugs on PML protein expression patterns. Methods The bone marrow cells of 42 APL patients, NB4 cells and MR2 cells were collected and treated separately with 1 μmol/L arsenic trioxide (As2O3), 1 μmol/L tetra-arsenic tetra-sulfide (As4S4), 1 μmol/L ATRA, 10 mg/L cytosine arabinoside, and 1 mg/L homoharringtonine...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28700942/a-pml-slit-axis-controls-physiological-cell-migration-and-cancer-invasion-in-the-cns
#9
Valeria Amodeo, Deli A, Joanne Betts, Stefano Bartesaghi, Ying Zhang, Angela Richard-Londt, Matthew Ellis, Rozita Roshani, Mikaella Vouri, Sara Galavotti, Sarah Oberndorfer, Ana Paula Leite, Alan Mackay, Aikaterini Lampada, Eva Wessel Stratford, Ningning Li, David Dinsdale, David Grimwade, Chris Jones, Pierluigi Nicotera, David Michod, Sebastian Brandner, Paolo Salomoni
Cell migration through the brain parenchyma underpins neurogenesis and glioblastoma (GBM) development. Since GBM cells and neuroblasts use the same migratory routes, mechanisms underlying migration during neurogenesis and brain cancer pathogenesis may be similar. Here, we identify a common pathway controlling cell migration in normal and neoplastic cells in the CNS. The nuclear scaffold protein promyelocytic leukemia (PML), a regulator of forebrain development, promotes neural progenitor/stem cell (NPC) and neuroblast migration in the adult mouse brain...
July 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28698405/novel-function-of-the-tumor-suppressor-pml-at-er-mitochondria-sites-in-the-control-of-autophagy
#10
EDITORIAL
Sonia Missiroli, Massimo Bonora, Simone Patergnani, Carlotta Giorgi
No abstract text is available yet for this article.
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28695742/the-human-regulatory-protein-ki-1-57-is-a-target-of-sumoylation-and-affects-pml-nuclear-body-formation
#11
Ângela Saito, Edmarcia E de Souza, Fernanda C Costa, Gabriela V Meirelles, Kaliandra de Almeida Gonçalves, Marcos T Santos, Gustavo C Bressan, Mark E McComb, Catherine E Costello, Stephen A Whelan, Jörg Kobarg
Ki-1/57 is a nuclear and cytoplasmic regulatory protein first identified in malignant cells from Hodgkin's lymphoma. It is involved in gene expression regulation on both transcriptional and mRNA metabolism levels. Ki-1/57 belongs to the family of intrinsically unstructured proteins, undergoes phosphorylation by PKC and methylation by PRMT1. Previous characterization of its protein interaction profile by yeast two-hybrid screening showed that Ki- 1/57 interacts with proteins of the SUMOylation machinery: the SUMO E2 conjugating enzyme UBC9 and the SUMO E3 ligase PIAS3, which suggested that Ki-1/57 could be involved with this process...
July 11, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28691927/ubiquitination-of-tumor-suppressor-pml-regulates-prometastatic-and-immunosuppressive-tumor-microenvironment
#12
Ya-Ting Wang, Jocelyn Chen, Chou-Wei Chang, Jayu Jen, Tzu-Yu Huang, Chun-Ming Chen, Roger Shen, Suh-Yuen Liang, I-Cheng Cheng, Shuenn-Chen Yang, Wu-Wei Lai, Kuang-Hung Cheng, Tao-Shih Hsieh, Ming-Zong Lai, Hung-Chi Cheng, Yi-Ching Wang, Ruey-Hwa Chen
The tumor microenvironment plays an important role in tumor growth and metastasis. However, the mechanism by which tumor cells regulate the cell and non-cell constituents of surrounding stroma remains incompletely understood. Promyelocytic leukemia (PML) is a pleiotropic tumor suppressor, but its role in tumor microenvironment regulation is poorly characterized. PML is frequently downregulated in many cancer types, including lung cancer. Here, we identify a PML ubiquitination pathway that is mediated by WD repeat 4-containing cullin-RING ubiquitin ligase 4 (CRL4WDR4)...
July 10, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28690845/diagnostic-autoantibodies-for-autoimmune-liver-diseases
#13
REVIEW
Ban-Hock Toh
Autoimmune liver diseases are conditions of low prevalence that comprise the triad of autoimmune hepatitis, primary biliary cholangitis (cirrhosis) and primary sclerosing cholangitis and their poorly characterised overlapping syndromes. Diagnostic autoantibodies are associated with autoimmune hepatitis and primary biliary cholangitis but not with primary sclerosing cholangitis. Autoantibodies are useful disease markers that facilitate early diagnosis of autoimmune hepatitis and primary biliary cholangitis and allow for therapeutic intervention to prevent progression to liver cirrhosis and associated complications...
May 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28688535/caballeronia-mineralivorans-sp-nov-isolated-from-oak-scleroderma-citrinum-mycorrhizosphere
#14
S Uroz, P Oger
Six bacterial strains were isolated from the oak-Scleroderma citrinum ectomycorrhizosphere in acidic and nutrient-poor forest soil for their high efficacy to weather minerals. Four of the six isolates, PML1(12)(T) and PML1(4), PML1(14) and PML1(16), were further characterized extensively. They were Gram negative, obligate aerobic, motile, non spore forming and rod-shaped. The major fatty acids of strain PML1(12)(T) were cyclo-C17:0, cyclo-C19:0-ω8c, C16:0 and C18:1-ω7c. The GC content of the DNA was 60.8%...
June 7, 2017: Systematic and Applied Microbiology
https://www.readbyqxmd.com/read/28687976/annexin-a2-s100a10-heterotetramer-is-upregulated-by-pml-rar%C3%AE-fusion-protein-and-promotes-plasminogen-dependent-fibrinolysis-and-matrix-invasion-in-acute-promyelocytic-leukemia
#15
Dan Huang, Yan Yang, Jian Sun, Xiaorong Dong, Jiao Wang, Hongchen Liu, Chengquan Lu, Xueyu Chen, Jing Shao, Jinsong Yan
Aberrant expression of annexin A2-S100A10 heterotetramer (AIIt) associated with PML/RARα fusion protein causes lethal hyperfibrinolysis in acute promyelocytic leukemia (APL), but the mechanism is unclear. To facilitate the investigation of regulatory association between ANXA2 and promyelocytic leukemia/retinoic acid receptor α (PML/RARα) fusion protein, this work was performed to determine the transcription start site of ANXA2 promoter with rapid amplification of 5'-cDNA ends analysis. Zinc-induced U937/PR9 cells expressed PML/RARα fusion protein, and resultant increases in ANXA2 transcripts and translational expressions of both ANXA2 and S100A10, while S100A10 transcripts remained constitutive...
July 8, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28685056/pml-silencing-inhibits-cell-proliferation-and-induces-dna-damage-in-cultured-ovarian-cancer-cells
#16
Sheng-Bing Liu, Zhong-Fei Shen, Yan-Jun Guo, Li-Xian Cao, Ying Xu
The promyelocytic leukemia (PML) gene is a tumor suppressor gene. It was first identified in acute promyelocytic leukemia, in which it is fused to retinoic acid receptor α by the (15;17) chromosomal translocation. The function of the PML protein is frequently lost or aberrant in human solid tumors. In human ovarian carcinoma tissue, PML detected by immunohistochemistry was highly expressed. A PML-silencing vector, pSRG-shPml, was constructed and used to transfect human ovarian cancer cells. Cells were cultured and selected with puromycin for 10-15 days, and then the PML mRNA expression levels were detected by RT-qPCR and immunofluorescence...
July 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28681388/matrix-metalloproteinase-9-is-decreased-in-natalizumab-treated-multiple-sclerosis-patients-at-risk-for-progressive-multifocal-leukoencephalopathy
#17
Nicolas Fissolo, Béatrice Pignolet, Clara Matute-Blanch, Juan Carlos Triviño, Berta Miró, Miriam Mota, Santiago Perez-Hoyos, Alex Sanchez, Patrick Vermersch, Aurélie Ruet, Jérôme de Sèze, Pierre Labauge, Sandra Vukusic, Caroline Papeix, Laurent Almoyna, Ayman Tourbah, Pierre Clavelou, Thibault Moreau, Jean Pelletier, Christine Lebrun-Frenay, Xavier Montalban, David Brassat, Manuel Comabella
OBJECTIVE: To identify biomarkers associated with the development of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients treated with natalizumab (NTZ). METHODS: Relapsing-remitting MS patients who developed PML under NTZ therapy (pre-PML) and non-PML NTZ-treated patients (NTZ-ctr) were included in the study. Cryopreserved peripheral blood mononuclear cells and serum samples collected at baseline, at 1- and 2-year treated time points, and during PML were analyzed for gene expression by RNA sequencing and for serum protein levels by Luminex and enzyme-linked immunosorbent assays, respectively...
July 6, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28681343/detectable-cerebrospinal-fluid-jcv-dna-in-late-presenting-hiv-positive-patients-beyond-progressive-multifocal-leukoencephalopathy
#18
S Mornese Pinna, E Scarvaglieri, M G Milia, D Imperiale, V Ghisetti, S Audagnotto, A Prochet, F Lipani, S Bonora, G Di Perri, A Calcagno
In the absence of effective prophylaxis and treatment, therapeutic options in HIV-positive patients with progressive multifocal leukoencephalopathy (PML) are limited to antiretroviral therapy: nevertheless, outcome is poor. We conducted a retrospective study (2009-2015) describing the outcome of 25 HIV-positive patients with detectable cerebrospinal fluid JC virus DNA: 14 had a probable PML while the others had evidence of other inflammatory central nervous system (CNS) affecting disorders. In the former group, 6-month mortality was 45...
July 5, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28674518/brain-susceptibility-changes-in-a-patient-with-natalizumab-related-progressive-multifocal-leukoencephalopathy-a-longitudinal-quantitative-susceptibility-mapping-and-relaxometry-study
#19
Giuseppe Pontillo, Sirio Cocozza, Roberta Lanzillo, Pasquale Borrelli, Anna De Rosa, Vincenzo Brescia Morra, Enrico Tedeschi, Giuseppe Palma
BACKGROUND: Brain MRI plays an essential role in both diagnosis and follow-up of the JC virus infection of the brain. Recently, MR studies with susceptibility-weighted imaging (SWI) sequences have shown hypointensities in U-fibers adjacent to white matter (WM) lesions of progressive multifocal leukoencephalopathy (PML). This finding has been confirmed with the use of quantitative susceptibility mapping (QSM), allowing to hypothesize a paramagnetic effect in these regions. Here, we report the first longitudinal assessment of QSM and R2* maps in natalizumab-associated PML to evaluate serial changes in susceptibility contrast images and their role in PML diagnosis and follow-up...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28665088/a-role-for-susceptibility-weighted-imaging-in-progressive-multifocal-leukoencephalopathy
#20
S M Yap, B Murray, T Lynch, E Kavanagh, P MacMahon
We report a radiologic finding on magnetic resonance imaging (MRI) of the brain of two cases of progressive multifocal leukoencephalopathy (PML) of hypointense signal of subcortical U-fibres on susceptibility weighted (SW) sequence. The first case is a 50-year-old man recently treated with chemotherapy including rituximab for non-Hodgkin's lymphoma. The second case is a 64-year-old woman with human immunodeficiency virus (HIV) infection. Iron deposition is a likely causative factor. We propose that SWI may be especially useful in the assessment of indeterminate cases to reduce the likelihood of a missed diagnosis of PML...
April 10, 2017: Irish Medical Journal
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