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https://www.readbyqxmd.com/read/28434229/the-cell-cycle-dependent-kinase-cdk9-is-a-post-exposure-drug-target-against-human-adenoviruses
#1
Vibhu Prasad, Maarit Suomalainen, Silvio Hemmi, Urs F Greber
Human adenoviruses (HAdVs) infect respiratory, gastrointestinal and urinary tracts, and give rise to eye infections and epidemic keratoconjunctivitis (EKC). They persist in lymphoid tissue, and cause morbidity and mortality in immunocompromised people. Treatments with significant post-exposure efficacy are not available. Here, we report that inhibition of the cell cycle-dependent kinase 9 (Cdk9) by RNA-interference, or the compound Flavopiridol blocked infections with HAdV-C2/5, EKC-causing HAdV-D8/37, and progeny formation in human corneal epithelial and cancer cells...
April 24, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28432301/ampk-signaling-in-the-nucleus-accumbens-core-mediates-cue-induced-reinstatement-of-cocaine-seeking
#2
Xue-Jiao Gao, Kai Yuan, Lu Cao, Wei Yan, Yi-Xiao Luo, Min Jian, Jian-Feng Liu, Qin Fang, Ji-Shi Wang, Ying Han, Jie Shi, Lin Lu
Relapse to drug seeking can be caused by exposure to drug-associated cues, provoking drug craving even after prolonged abstinence. Recent studies demonstrated that AMP-activated protein kinase (AMPK) regulates neuronal morphology and membrane excitability in neurons. Here, we investigated the role of AMPK activity in the nucleus accumbens (NAc) in relapse to cocaine seeking. We found that exposure to drug-related cues reinstated cocaine-seeking behavior and increased AMPK and p70s6k phosphorylation in the NAc core but not shell...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432274/sensitive-detection-of-viable-circulating-tumor-cells-using-a-novel-conditionally-telomerase-selective-replicating-adenovirus-in-non-small-cell-lung-cancer-patients
#3
Shinsaku Togo, Nobuyoshi Katagiri, Yukiko Namba, Miniwan Tulafu, Kumi Nagahama, Kotarou Kadoya, Kazuya Takamochi, Siaki Oh, Kenji Suzuki, Fuminori Sakurai, Hiroyuki Mizuguchi, Yasuo Urata, Kazuhisa Takahashi
Circulating tumor cells (CTCs) have a crucial role in the clinical outcome of cancer patients. Detection of non-small cell lung cancer (NSCLC) using an antibody against epithelial cell adhesion molecule (EpCAM) in captured CTCs has low sensitivity; the loss of epithelial markers leads to underestimation of CTCs with mesenchymal phenotype. We propose a new approach for detection of viable CTCs, including those with epithelial-mesenchymal transition status (EMT-CTCs), using the new telomerase-specific replication-selective adenovirus (OBP-1101), TelomeScan F35...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429670/expression-of-dominant-negative-k6w-ubiquitin-in-the-lens-epithelium-via-an-adenoviral-vector-delays-posterior-capsule-opacification-in-a-rabbit-model
#4
Xuan Bao, Min Hou, Ruiping Peng, Furong Luo, Mingxing Wu
PURPOSE: Ubiquitin is involved in cell proliferation and differentiation, and the objective of this study is to investigate the potential of dominant negative Ubiquitin (Ub) with a lysine to tryptophan mutation at the 6 position (K6W) through an adenoviral expression vector in the prevention of posterior capsule opacification (PCO) in a rabbit PCO model. METHODS: Recombinant dominant negative K6W-Ub adenovirus (RAd-K6W-Ub) with green fluorescent protein (RAd-K6W-Ub/GFP) and RAd-GFP viruses (control) were generated with QBI-HEK 293A cells...
March 31, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28429344/up-regulation-of-microrna-367-promotes-liver-steatosis-through-repressing-tbl1-in-obese-mice
#5
D-D Li, Y Liu, L Xue, D-Y Su, W-Y Pang
OBJECTIVE: Increasing evidence has demonstrated that microRNAs (miRNAs) play a critical role in the progression of metabolic disorders, including obesity-induced non-alcoholic fatty liver disease (NAFLD). In the present study, the expression and function of miR-367 were investigated. MATERIALS AND METHODS: C57BL/6 male mice aged 8 weeks were fed with a normal diet (ND) or high-fat-diet (HFD). The expression levels of miR-367 were analyzed in livers from two groups of mice by quantitative real-time PCR...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28428308/genome-sequence-of-canine-adenovirus-type-1-isolated-from-a-wolf-canis%C3%A2-lupus-in-southern-italy
#6
Federica Pizzurro, Maurilia Marcacci, Guendalina Zaccaria, Massimiliano Orsini, Francesca Cito, Alfonso Rosamilia, Ludovica Di Renzo, Daniela Malatesta, Daria Di Sabatino, Alessio Lorusso
Canine adenovirus type 1 (CAdV-1), a DNA virus of the family Adenoviridae, causes infectious canine hepatitis, a highly contagious disease primarily affecting canids. In this report, we describe the isolation and whole-genome sequence of a CAdV-1 isolate from the liver of a free-ranging wolf (Canis lupus).
April 20, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28428220/cmtm3-cklf-like-marvel-transmembrane-domain-3-mediates-angiogenesis-by-regulating-cell-surface-availability-of-ve-cadherin-in-endothelial-adherens-junctions
#7
Ihsan Chrifi, Laura Louzao-Martinez, Maarten Brandt, Christian G M van Dijk, Petra Burgisser, Changbin Zhu, Johan M Kros, Dirk J Duncker, Caroline Cheng
OBJECTIVE: Decrease in VE-cadherin adherens junctions reduces vascular stability, whereas disruption of adherens junctions is a requirement for neovessel sprouting during angiogenesis. Endocytosis plays a key role in regulating junctional strength by altering bioavailability of cell surface proteins, including VE-cadherin. Identification of new mediators of endothelial endocytosis could enhance our understanding of angiogenesis. Here, we assessed the function of CMTM3 (CKLF-like MARVEL transmembrane domain 3), which we have previously identified as highly expressed in Flk1(+) endothelial progenitor cells during embryonic development...
April 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28428179/adamts13-controls-vascular-remodeling-by-modifying-vwf-reactivity-during-stroke-recovery
#8
Haochen Xu, Yongliang Cao, Xing Yang, Ping Cai, Lijing Kang, Ximin Zhu, Haiyu Luo, Lu Lu, Lixiang Wei, Xiaofei Bai, Yuanbo Zhu, Bing-Qiao Zhao, Wenying Fan
Angiogenic response is essential for ischemic brain repair. However, the mechanisms leading to postischemic neovascularization have not been established, and no therapies have been identified. The VWF-cleaving protease ADAMTS13 is required for endothelial tube formation in vitro However, there is currently no in vivo evidence supporting a function of ADAMTS13 in angiogenesis. Here we show that mice deficient in ADAMTS13 exhibited significantly reduced neovascularization, brain capillary perfusion, pericyte and smooth muscle cell coverage on microvessels, expression of the tight junction and basement membrane proteins, and accelerated blood-brain barrier (BBB) breakdown and extravascular deposits of serum proteins in the peri-infarct cortex at 14 days after stroke...
April 20, 2017: Blood
https://www.readbyqxmd.com/read/28427886/identification-of-excipients-for-stabilizing-fiberless-adenovirus-as-biopharmaceuticals
#9
Grit Kupgan, Shyamal P Choudhari, Nicholas H Flynn, Adane Nigatu, Sravanthi Vupputuri, William D Picking, Wendy L Picking, Joshua D Ramsey
Reducing the promiscuous tropism of native adenovirus by using fiberless adenovirus is advantageous towards its use as a gene therapy vector or vaccine component. The removal of the fiber protein on native adenovirus abrogates several undesirable interactions; however, this approach decreases the particle's physical stability. In order to create stable fiberless adenovirus for pharmaceutical use, the effects of temperature and pH on the particle's stability profile must be addressed. Our results indicate that the stability of fiberless adenovirus is increased when it is stored in mildly acidic conditions around pH 6...
April 17, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28427434/adenovirus-mediated-cd40l-gene-transfer-increases-teffector-tregulatory-cell-ratio-and-upregulates-death-receptors-in-metastatic-melanoma-patients
#10
A Schiza, J Wenthe, S Mangsbo, E Eriksson, Anders Nilsson, T H Tötterman, A Loskog, G Ullenhag
BACKGROUND AND AIMS: Malignant melanoma is an aggressive tumor sensitive for immunotherapy such as checkpoint blockade antibodies. Still, most patients with late stage disease do not respond, and the side effects can be severe. Stimulation of the CD40 pathway to initiate anti-tumor immunity is a promising alternative. Herein, we demonstrate immune profiling data from melanoma patients treated with an adenovirus-based CD40 ligand gene therapy (AdCD40L). METHODS: Peripheral blood mononuclear cells and plasma were collected from malignant melanoma patients (n = 15) enrolled in a phase I/IIa study investigating intratumoral delivery of AdCD40L with or without low dose cyclophosphamide...
April 20, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28426845/her2-specific-chimeric-antigen-receptor-modified-virus-specific-t-cells-for-progressive-glioblastoma-a-phase-1-dose-escalation-trial
#11
Nabil Ahmed, Vita Brawley, Meenakshi Hegde, Kevin Bielamowicz, Mamta Kalra, Daniel Landi, Catherine Robertson, Tara L Gray, Oumar Diouf, Amanda Wakefield, Alexia Ghazi, Claudia Gerken, Zhongzhen Yi, Aidin Ashoori, Meng-Fen Wu, Hao Liu, Cliona Rooney, Gianpietro Dotti, Adrian Gee, Jack Su, Yvonne Kew, David Baskin, Yi Jonathan Zhang, Pamela New, Bambi Grilley, Milica Stojakovic, John Hicks, Suzanne Z Powell, Malcolm K Brenner, Helen E Heslop, Robert Grossman, Winfried S Wels, Stephen Gottschalk
Importance: Glioblastoma is an incurable tumor, and the therapeutic options for patients are limited. Objective: To determine whether the systemic administration of HER2-specific chimeric antigen receptor (CAR)-modified virus-specific T cells (VSTs) is safe and whether these cells have antiglioblastoma activity. Design, Setting, and Participants: In this open-label phase 1 dose-escalation study conducted at Baylor College of Medicine, Houston Methodist Hospital, and Texas Children's Hospital, patients with progressive HER2-positive glioblastoma were enrolled between July 25, 2011, and April 21, 2014...
April 20, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28426340/a-novel-recombinant-canine-adenovirus-type-1-detected-from-acute-lethal-cases-of-infectious-canine-hepatitis
#12
Magdelene Wong, Lucy Woolford, Noor Haliza Hasan, Farhid Hemmatzadeh
In this study, canine adenoviruses (CAdVs) from two acute fatal cases of infectious canine hepatitis (ICH) were analyzed using molecular detection and sequencing of the pVIII, E3, and fiber protein genes. Pathological findings in affected dogs were typical for CAdV-1 associated disease, characterized by severe centrilobular to panlobular necrohemorrhagic hepatitis and the development of disseminated intravascular coagulation in the terminal stages of disease. Comparison of partial genome sequences revealed that although these newly detected viruses mainly had CAdV-1 genome characteristics, their pVIII gene was more similar to that of CAdV-2...
April 20, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28423586/the-role-of-ros-and-subsequent-dna-damage-response-in-puma-induced-apoptosis-of-ovarian-cancer-cells
#13
Jun Yang, Xinyu Zhao, Mei Tang, Lei Li, Yi Lei, Ping Cheng, Wenhao Guo, Yu Zheng, Wei Wang, Na Luo, Yong Peng, Aiping Tong, Yuquan Wei, Chunlai Nie, Zhu Yuan
PUMA is a member of the "BH3-only" branch of the BCL-2 family. Our previous study suggests a therapeutic potential of PUMA in treating ovarian cancer, however, the action mechanism of PUMA remains elusive. In this work, we found that in PUMA adenovirus-infected A2780s ovarian cancer cells, exogenous PUMA was partially accumulated in the cytosol and mainly located to the mitochondria. We further showed that PUMA induces mitochondrial dysfunction-mediated apoptosis and ROS generation through functional BAX in a ROS generating enzyme- and caspase-independent manner irrespective of their p53 status, and results in activation of Nrf2/HO-1 pathway...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420553/incidence-of-respiratory-viral-infections-and-associated-factors-among-children-attending-a-public-kindergarten-in-taipei-city
#14
Chun-Yi Lu, Li-Min Huang, Tsui-Yien Fan, A-Ling Cheng, Luan-Yin Chang
BACKGROUND: Kindergarteners frequently encounter various infectious diseases, so surveillance of viral infectious diseases would provide information for their health promotion. METHODS: We enrolled kindergarten attendees, age 2-5 years, during the academic years of 2006 and 2007 in a Taipei City kindergarten. Daily monitoring of illness and regular biweekly physical examinations were undertaken. Multiple infections were defined as one child having two or more laboratory-confirmed viral infections with different viruses or different serotypes during one academic year...
April 15, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28420073/future-prospects-for-the-development-of-cost-effective-adenovirus-vaccines
#15
REVIEW
Cyrielle Fougeroux, Peter J Holst
Vaccination is one of the most efficient tools for disease prevention, and a continuously growing field of research. However, despite progress, we still need more efficient and cost-effective vaccines that would improve access to those in need. In this review, we will describe the status of virus-vectored vaccine technology with a focus on adenoviral-based vaccines. Adenovirus (Ad) vaccines have proven to be efficient in military vaccinations against Ad4 and Ad7 and as highly efficient vectored vaccines against rabies...
March 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28419263/renal-toxicity-in-pediatric-patients-receiving-cidofovir-for-the-treatment-of-adenovirus-infection
#16
Surabhi B Vora, Adam W Brothers, Janet A Englund
Treatment options for adenovirus infection in immunocompromised children are limited. Nephrotoxicity has been associated with cidofovir use, but the rate of cidofovir-associated nephrotoxicity in pediatric patients is unclear. In a retrospective review of patients with adenovirus infection treated with cidofovir, neonates (n = 5) had higher viral loads and shorter times to renal insufficiency than older children (n = 24). Higher weekly doses of cidofovir were associated with greater increases in creatinine levels...
April 17, 2017: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/28418771/persistence-in-temporary-lung-niches-a-survival-strategy-of-lung-resident-memory-cd8-t-cells
#17
Shiki Takamura
Respiratory virus infections, such as those mediated by influenza virus, parainfluenza virus, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus (SARS-CoV), rhinovirus, and adenovirus, are responsible for substantial morbidity and mortality, especially in children and older adults. Furthermore, the potential emergence of highly pathogenic strains of influenza virus poses a significant public health threat. Thus, the development of vaccines capable of eliciting long-lasting protective immunity to those pathogens is a major public health priority...
April 18, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28418354/-clinical-and-morphological-signs-of-viral-damage-to-a-kidney-transplant
#18
S E Solovyeva, E M Paltseva, M M Morozova, M M Kaabak, N A Krainik, A V Matveev
AIM: Тo compare morphological changes and results of immunohistochemical (IHC) identification of viruses (polyomaviruses, adenoviruses, and herpesviruses) in the biopsy specimens with their clinical manifestations in recipients of renal transplants. MATERIAL AND METHODS: Morphological and IHC studies were conducted using 71 needle renal transplant biopsy specimens from patients in the study group and 10 renal biopsy specimens from those in the control group. A number of clinical indicators were estimated...
2017: Arkhiv Patologii
https://www.readbyqxmd.com/read/28417936/oncolytic-alphaviruses-in-cancer-immunotherapy
#19
REVIEW
Kenneth Lundstrom
Oncolytic viruses show specific targeting and killing of tumor cells and therefore provide attractive assets for cancer immunotherapy. In parallel to oncolytic viral vectors based on adenoviruses and herpes simplex viruses, oncolytic RNA viruses and particularly alphaviruses have been evaluated as delivery vehicles. Immunization studies in experimental rodent models for various cancers including glioblastoma, hematologic, hepatocellular, colon, cervix, and lung cancer as well as melanoma have been conducted with naturally occurring oncolytic alphavirus strains such as M1 and Sindbis AR339...
April 12, 2017: Vaccines
https://www.readbyqxmd.com/read/28417919/sumo-specific-cysteine-protease-1-promotes-epithelial-mesenchymal-transition-of-prostate-cancer-cells-via-regulating-smad4-desumoylation
#20
Xiaoyan Zhang, Hao Wang, Hua Wang, Fengjun Xiao, Prem Seth, Weidong Xu, Qinghua Jia, Chutse Wu, Yuefeng Yang, Lisheng Wang
In advanced prostate cancer, small ubiquitin-like modifier (SUMO)-specific cysteine protease 1 (SENP1) is up-regulated. However, the role of SENP1 in regulating deSUMOylation of TGF-β/SMADs signaling is unknown. In this study, we developed a lentiviral vector, PLKO.1-shSENP1, to silence SENP1 in prostate cancer cells with high metastatic characteristics (PC3M). Likewise, we also created an adenovirus vector, Ad5/F11p-SENP1 to over-express SENP1 in prostate cancer cells with low metastatic potential (LNCaP)...
April 12, 2017: International Journal of Molecular Sciences
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