Adenoviruses
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Cyclophosphamide enhances antitumor efficacy of oncolytic adenovirus expressing uracil phosphoribosyltransferase (UPRT) in immunocompetent Syrian hamsters
Abstract
Oncolytic viruses (OVs) are novel cancer therapeutics with great promise, but host antiviral immunity represents the hurdle for their efficacy. Immunosuppression by cyclophosphamide (CP) has thus been shown to enhance the oncolytic efficacy of many OVs, but its effects on OVs armed with therapeutic genes remain unknown. We have previously reported on the efficacy of AxE1CAUP, an oncolytic adenovirus (OAd) expressing uracil phosphoribosyltransferase (UPRT), an enzyme that markedly enhanced the toxicity of 5‐fluorouracil (5‐FU), in immunodeficient, Ad‐nonpermissive nude mice. Here we explored the efficacy and ...
Source: International Journal of Cancer - February 27, 2013 Category: Cancer & Oncology Authors: Naoyuki Hasegawa, Masato Abei, Kazunari K. Yokoyama, Kuniaki Fukuda, Emiko Seo, Rei Kawashima, Yuri Nakano, Takeshi Yamada, Koji Nakade, Hirofumi Hamada, Yuichi Obata, Ichinosuke Hyodo Tags: Cancer Therapy Source Type: research
microRNA response elements-regulated TRAIL expression shows specific survival-suppressing activity on bladder cancer
Conclusions:
Collectively, we demonstrated that MREs-based TRAIL delivery into bladder cancer cells was feasible and efficient for cancer gene therapy. (Source: Journal of Experimental and Clinical Cancer Research)
Source: Journal of Experimental and Clinical Cancer Research - February 26, 2013 Category: Cancer & Oncology Authors: Youguang ZhaoYing LiLiang WangHang YangQingtang WangHaiyan QiShadan LiPeng ZhouPing LiangQiwu WangXiaowei Li Source Type: research
Polymerase‐Chain‐Reaction‐Based Diagnosis of Viral Pulmonary Infections in Immunocompromised Children
ConclusionPCR‐based diagnosis from BAL may increase the rate of pathogen detection in immunocompromised children, decrease the time to diagnosis and spare patients unnecessary antimicrobial treatment.©2013 The Author(s)/Acta Pædiatrica ©2013 Foundation Acta Pædiatrica (Source: Acta Paediatrica)
Source: Acta Paediatrica - February 20, 2013 Category: Pediatrics Authors: Gili Kadmon, Itzhak Levy, Michal Mandelboim, Elhanan Nahum, Jerry Stein, Sara Dovrat, Tommy Schonfeld Tags: Regular Article Source Type: research
High prevalence of myocarditis in patients with hypertensive heart disease and cardiac deterioration
Conclusion
Myocarditis is a major cause of cardiac deterioration in patients with HHD; its recognition may improve patient treatment and outcome. (Source: European Journal of Heart Failure)
Source: European Journal of Heart Failure - February 20, 2013 Category: Cardiology Authors: Frustaci, A., Francone, M., Petrosillo, N., Chimenti, C. Tags: HISTOPATHOLOGY Source Type: research
[Articles] Safety and immunogenicity of an oral, replicating adenovirus serotype 4 vector vaccine for H5N1 influenza: a randomised, double-blind, placebo-controlled, phase 1 study
Oral Ad4 vector priming might enhance the efficacy of poorly immunogenic vaccines such as H5N1. (Source: The Lancet Infectious Diseases)
Source: The Lancet Infectious Diseases - February 19, 2013 Category: Infectious Diseases Authors: Marc Gurwith, Michael Lock, Eve M Taylor, Glenn Ishioka, Jeff Alexander, Tim Mayall, John E Ervin, Richard N Greenberg, Cynthia Strout, John J Treanor, Richard Webby, Peter F Wright Tags: Articles Source Type: research
Evaluation of the FilmArray® Respiratory Panel for Clinical Use in a Large Children's Hospital
ConclusionFARP overall performed better than DFA with the exception of Adenovirus, making the FARP an attractive alternative to laboratories looking to replace DFA with a rapid, user‐friendly, multiplex molecular assay. (Source: Journal of Clinical Laboratory Analysis)
Source: Journal of Clinical Laboratory Analysis - February 19, 2013 Category: Laboratory Medicine Authors: Marc Roger Couturier, Trenda Barney, Garrison Alger, Weston C. Hymas, Jeffery B. Stevenson, David Hillyard, Judy A. Daly Tags: Original Article Source Type: research
Long‐Range Quantitative PCR for Determining Inactivation of Adenovirus 2 by Ultraviolet Light
ConclusionThe LR‐qPCR can be used as a tool for estimating DNA damage caused by UV in adenovirus. The LR‐qPCR results were related to reduction in viral infectivity.
SignificanceThe use of LR‐qPCR to determine DNA damage and estimate inactivation of adenovirus 2 from UV disinfection allows for same‐day results compared to >7 days required for cell culture. This accelerates adenovirus inactivation results for the water industry where adenovirus is used as a representative virus for crediting UV systems. This PCR approach provides a framework that can be used for other viral viability assays using the inhibition o...
Source: Journal of Applied Microbiology - February 16, 2013 Category: Microbiology Authors: Roberto A. Rodríguez, Sarah H. Bounty, Karl G. Linden Tags: Original Article Source Type: research
A phase I dose escalation study of Ad GV.EGR.TNF.11D (TNFerade™ Biologic) with concurrent chemoradiotherapy in patients with recurrent head and neck cancer undergoing reirradiation
Conclusions
TNFerade™ Biologic can be safely integrated with FHX chemoradiotherapy at an MTD of 4 x 1010 PU. Monitoring for thrombotic events is indicated. (Source: Annals of Oncology)
Source: Annals of Oncology - February 16, 2013 Category: Cancer & Oncology Authors: Seiwert, T. Y., Darga, T., Haraf, D., Blair, E. A., Stenson, K., Cohen, E. E. W., Salama, J. K., Villaflor, V., Witt, M. E., Lingen, M. W., Weichselbaum, R. R., Vokes, E. E. Tags: head and neck cancer Source Type: research
LY294002 Enhances Expression
of Proteins Encoded by
Recombinant Replication-Defective Adenoviruses via mTOR- and Non-mTOR-Dependent
Mechanisms
Molecular PharmaceuticsDOI: 10.1021/mp3003122 (Source: Molecular Pharmaceutics)
Source: Molecular Pharmaceutics - February 15, 2013 Category: Drugs & Pharmacology Authors: Mikhail V. Shepelev, Elena V. Korobko, Tatiana V. Vinogradova, Eugene P. Kopantsev and Igor V. Korobko Source Type: research
PGC-1{beta} Inhibits Neointimal Lesion Formation [Gene Regulation]
Proliferation of vascular smooth muscle cells (VSMCs) in response to vascular injury plays a critical role in vascular lesion formation. Emerging data suggest that peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1) is a key regulator of energy metabolism and other biological processes. However, the physiological role of PGC-1β in VSMCs remains unknown. A decrease in PGC-1β expression was observed in balloon-injured rat carotid arteries. PGC-1β overexpression substantially inhibited neointima formation in vivo and markedly inhibited VSMC proliferation and induced cell cycle arrest at the G1/S transition ...
Source: Journal of Biological Chemistry - February 15, 2013 Category: Chemistry Authors: Guo, Y., Fan, Y., Zhang, J., Chang, L., Lin, J. D., Chen, Y. E. Tags: Molecular Bases of Disease Source Type: research
Effect of increased viral replication and infectivity enhancement on radioiodide uptake and oncolytic activity of adenovirus vectors expressing the sodium iodide symporter
& J C Morris (Source: Cancer Gene Therapy)
Source: Cancer Gene Therapy - February 15, 2013 Category: Cancer & Oncology Authors: M J OnealM A TrujilloJ DavydovaS McDonoughM YamamotoJ C Morris Tags: adenovirus ADP hybrid fiber NIS oncolytics radiovirotherapy Source Type: research
Case report: Severe disseminated adenovirus infection in a neonate following water birth delivery
We present a case of infant who developed severe pneumonia and disseminated adenoviral infection following water birth delivery to a mother with gastroenteritis. The infant's infection was due to an adenovirus strain that has not been previously reported in neonates. J. Med. Virol. 85:667–669, 2013. © 2013 Wiley Periodicals, Inc. (Source: Journal of Medical Virology)
Source: Journal of Medical Virology - February 15, 2013 Category: Virology Authors: Stacey L. Soileau, Eileen Schneider, Dean D. Erdman, Xiaoyan Lu, William D. Ryan, Ryan M. McAdams Tags: Case Report Source Type: research
Genetic blockade of IGF‐1R via recombinant adenovirus in lung cancer can be enhanced by histone deacetylase inhibitor, vorinostat
ConclusionVorinostat enhanced the blocking capability of ad‐shIGF‐1R. The combined treatment of vorinostat and ad‐sh‐IGF‐1R appears to be a promising potential as a new therapeutic approach for lung cancer. Copyright © 2013 John Wiley & Sons, Ltd. (Source: The Journal of Gene Medicine)
Source: The Journal of Gene Medicine - February 14, 2013 Category: Genetics & Stem Cells Authors: Mi‐Young Park, Dal Rae Kim, Eun Young Eo, Hyo Jeong Lim, Jong Sun Park, Young‐Jae Cho, Ho‐Il Yoon, Jae Ho Lee, Choon‐Taek Lee Tags: Research Article Source Type: research
Molecular Mechanisms Responsible for the Differential Effects of ApoE3 and ApoE4 on Plasma Lipoprotein-Cholesterol Levels.
CONCLUSIONS: ApoE4 possesses enhanced lipid and VLDL-binding ability relative to apoE3, which gives rise to impaired lipolytic processing of VLDL in apoE4-expressing mice. These effects reduce VLDL remnant clearance from the plasma compartment and decrease the amount of VLDL surface components available for incorporation into the high-density lipoprotein pool, accounting for the more proatherogenic lipoprotein profile (higher VLDL-C/high-density lipoprotein-cholesterol ratio) occurring in apoE4-expressing animals compared with their apoE3 counterparts.
PMID: 23413428 [PubMed - as supplied by publisher] (Source: Arterio...
Source: Arteriosclerosis, Thrombosis and Vascular Biology - February 14, 2013 Category: Cardiology Authors: Li H, Dhanasekaran P, Alexander ET, Rader DJ, Phillips MC, Lund-Katz S Tags: Arterioscler Thromb Vasc Biol Source Type: research
Nucleus of the Solitary Tract (Pro)Renin Receptor-Mediated Antihypertensive Effect Involves Nuclear Factor-{kappa}B-Cytokine Signaling in the Spontaneously Hypertensive Rat [Nervous System]
In this study, we tested the hypothesis that altered activity of PRR in the NTS is linked to hypertension. Eight weeks of chronic knockdown of the NTS PRR, using recombinant adeno-associated virus type 2 (AAV2)-PRR-small hairpain RNA (shRNA)–mediated gene transduction, caused a significant increase in mean arterial pressure (MAP) in the SHR (shRNA, 173±5; Control, 151±6 mm Hg) but not in Wistar Kyoto rats (shRNA, 108±7; Control, 106±6 mm Hg). The MAP elevation in the SHR was associated with decreased inflammatory markers tumor necrosis factor-α, interleukin-6, C-C motif ligand 5, and...
Source: Hypertension - February 13, 2013 Category: Cardiology Authors: Zubcevic, J., Jun, J. Y., Lamont, G., Murca, T. M., Shi, P., Yuan, W., Lin, F., Carvajal, J. M., Li, Q., Sumners, C., Raizada, M. K., Shan, Z. Tags: Nervous System Source Type: research
Angiotensin Type 1a Receptors in the Subfornical Organ Are Required for Deoxycorticosterone Acetate-Salt Hypertension [Original Articles Part 2]
Although elevated renin–angiotensin system activity and angiotensinergic signaling within the brain are required for hypertension, polydipsia, and increased metabolic rate induced by deoxycorticosterone acetate (DOCA)-salt, the contribution of specific receptor subtypes and brain nuclei mediating these responses remains poorly defined. We hypothesized that angiotensin type 1a receptors (AT1aR) within the subfornical organ (SFO) mediate these responses. Transgenic mice carrying a conditional allele of the endogenous AT1aR (AT1aRflox) were administered an adenovirus encoding Cre-recombinase and enhanced green fluoresce...
Source: Hypertension - February 13, 2013 Category: Cardiology Authors: Hilzendeger, A. M., Cassell, M. D., Davis, D. R., Stauss, H. M., Mark, A. L., Grobe, J. L., Sigmund, C. D. Tags: Animal models of human disease, Other hypertension Original Articles Part 2 Source Type: research
The Brain Subfornical Organ Mediates Leptin-induced Increases in Renal Sympathetic Activity but not its Metabolic Effects [Original Articles Part 2]
The adipocyte-derived hormone leptin acts within the central nervous system to decrease food intake and body weight and to increase renal and thermogenic brown adipose tissue sympathetic nerve activity (SNA). Previous studies have focused on hypothalamic brain regions, although recent findings have identified leptin receptors (ObR) in a distributed brain network, including the circumventricular subfornical organ (SFO), a forebrain region devoid of a blood–brain barrier. We tested the hypothesis that ObR in the SFO are functionally linked to leptin-induced decreases in food intake and body weight and increases in SNA....
Source: Hypertension - February 13, 2013 Category: Cardiology Authors: Young, C. N., Morgan, D. A., Butler, S. D., Mark, A. L., Davisson, R. L. Tags: Animal models of human disease Original Articles Part 2 Source Type: research
HeLa cell heterogeneity and coxsackievirus B3 cytopathic effect: Implications for inter‐laboratory reproducibility of results
Abstract
Concerns over cell line identities and contamination have led investigators to acquire fresh stocks of HeLa CCL‐2 cells, but results with the HeLa CCL‐2 cells do not always reproduce results with HeLa cells that have long history in the laboratory. When used for TCID50 assays of Coxsackievirus B3/28 (CVB3/28), HeLa CCL‐2 cells returned titers for CVB3/28 that were more than ten‐fold lower than titers obtained using laboratory HeLa cells. The viral cytopathic effect was less distinct in the HeLa CCL‐2 cultures, suggestive of a mixed population of cells with varied susceptibility to viral cytopathic effect...
Source: Journal of Medical Virology - February 13, 2013 Category: Virology Authors: Steven D. Carson, Samuel J. Pirruccello Tags: Research Article Source Type: research
Pasteurella multocida toxin (PMT) upregulates CTGF which leads to mTORC1 activation in Swiss 3T3 cells.
Abstract
Pasteurella multocida toxin (PMT) is a mitogenic protein that hijacks cellular signal transduction pathways via deamidation of heterotrimeric G proteins. We previously showed that rPMT activates mTOR signaling via a Gα(q/11)/PLCβ/PKC mediated pathway, leading in part to cell proliferation and migration. Herein, we show that mTOR and MAPK, but not membrane-associated tyrosine kinases, are activated in serum-starved 3T3 cells by an autocrine/paracrine substance(s) secreted into the conditioned medium following rPMT treatment. Surprisingly, this diffusible factor(s) is capable of activating mTOR and MAPK pa...
Source: Cellular Signalling - February 13, 2013 Category: Cytology Authors: Oubrahim H, Wong A, Wilson BA, Chock PB Tags: Cell Signal Source Type: research
Creation of a cardiotropic adeno-associated virus: the story of viral directed evolution
Adeno-associated virus (AAV) is an important vector system for human gene therapy. Although use of AAV serotypes can result in efficient myocardial gene transfer, improvements in the transduction efficiency and specificity are still required. As a method for artificial modification and selection of gene function, directed evolution has been used for diverse applications in genetic engineering of enzymes and proteins. Since 2000, pioneering work has been performed on directed evolution of viral vectors. We further attempted to evolve the AAV using DNA shuffling and in vivo biopanning in a mouse model. An AAVM41 mutant was c...
Source: Virology Journal - February 11, 2013 Category: Virology Authors: Lin YangXiao Xiao Source Type: research
Collect, Boil and Amplify - A Simple Approach for the Detection of Three Common Viruses Associated with Epidemic Keratoconjunctivitis, Conjunctivitis and Dendritic Ulcers.
Abstract
During 2011' an outbreak of epidemic keratoconjunctivitis led to increased clinical requests for molecular screening of viruses from conjunctival swabs. To maximise throughput with minimal cost, a simple boil extraction on dry swabs followed by amplification and real-time detection using 'in-house' assays for herpes simplex viruses (HSV) and adenoviruses with RNaseP as an internal control was validated and introduced. Data from 541 patients who were tested for one or more viral targets was analysed. Adenovirus was most frequently detected accounting for 30% of all cases including the community outbreak. Ge...
Source: Journal of Virological Methods - February 11, 2013 Category: Virology Authors: Moore C, Gatica L, Jones T, Matthews P, Watkins J, Tyson L, Keelan P, Corden S, Phillips I, Jones R Tags: J Virol Methods Source Type: research
A Novel Selective LSD1/KDM1A Inhibitor Epigenetically Blocks Herpes Simplex Virus Lytic Replication and Reactivation from Latency.
In this study, a novel specific LSD1 inhibitor was identified that potently repressed HSV IE gene expression, genome replication, and reactivation from latency. Importantly, the inhibitor also suppressed primary infection of HSV in vivo in a mouse model. Based on common control of a number of DNA viruses by epigenetic modulation, it was also demonstrated that this LSD1 inhibitor blocks initial gene expression of the human cytomegalovirus and adenovirus type 5. IMPORTANCE Epigenetic mechanisms, including histone modification and chromatin remodeling, play important regulatory roles in all cellular processes requiring acce...
Source: Herpes - February 10, 2013 Category: Infectious Diseases Authors: Liang Y, Quenelle D, Vogel JL, Mascaro C, Ortega A, Kristie TM Tags: MBio Source Type: research
Inactivation of Pathogenic Viruses by Plant-Derived Tannins: Strong Effects of Extracts from Persimmon (Diospyros kaki) on a Broad Range of Viruses.
In this study, we investigated the anti-viral effects of tannins on 12 different viruses including both enveloped viruses (influenza virus H3N2, H5N3, herpes simplex virus-1, vesicular stomatitis virus, Sendai virus and Newcastle disease virus) and non-enveloped viruses (poliovirus, coxsachievirus, adenovirus, rotavirus, feline calicivirus and mouse norovirus). We found that extracts from persimmon (Diospyros kaki), which contains ca. 22% of persimmon tannin, reduced viral infectivity in more than 4-log scale against all of the viruses tested, showing strong anti-viral effects against a broad range of viruses. Other tannin...
Source: Herpes - February 10, 2013 Category: Infectious Diseases Authors: Ueda K, Kawabata R, Irie T, Nakai Y, Tohya Y, Sakaguchi T Tags: PLoS One Source Type: research
Adenovirus‐mediated Interferon‐γ Gene Therapy Induced Human Pancreatic Carcinoma Capan‐2 Cell Apoptosis In Vitro and In Vivo
In this study, we examined the potential therapeutic effects of an adenovirus encoding human interferon gamma (Ad‐IFNγ) on pancreatic carcinoma cells Capan‐2 in vitro and in vivo. The results indicated that Ad‐IFNγ could significantly inhibit tumor cell growth via inducing cell apoptosis. After infection, IFNγ expressed durably and stably in xenografts, predominantly in tumor tissue, while much less in blood and liver. Thus, adenovirus‐mediated intratumoral injection of human IFNγ gene could be an effective gene therapeutic system for the treatment of pancreatic carcinoma. Anat Rec, 00:000–000, 2013. © 2013 ...
Source: The Anatomical Record Part B: The New Anatomist - February 9, 2013 Category: Anatomy Authors: Fa‐Jun Xie, Peng Zhao, Yi‐Ping Zhang, Fei‐Ye Liu, Xi‐Lin Nie, Ying‐Hui Zhu, Xin‐Min Yu, Qiu‐Qing Zheng, Wei‐Min Mao, Hong‐Yang Lu, Hong Wei, WenLin Huang Tags: Full Length Article Source Type: research
Safety Profile, Efficacy, and Biodistribution of a Bicistronic High-Capacity Adenovirus Vector Encoding a Combined Immunostimulation and Cytotoxic Gene Therapy as a Prelude to a Phase I Clinical Trial for Glioblastoma.
We reported the efficacy of a gene therapy approach for glioma consisting of intratumoral injection of Ads encoding conditionally cytotoxic herpes simplex type 1 thymidine kinase (Ad-TK) and the immunostimulatory cytokine fms-like tyrosine kinase ligand 3 (Ad-Flt3L). Herein, we report the biodistribution, efficacy, and neurological and systemic effects of a bicistronic high-capacity Ad, i.e., HC-Ad-TK/TetOn-Flt3L. HC-Ads elicit sustained transgene expression, even in the presence of anti-Ad immunity, and can encode large therapeutic cassettes, including regulatory elements to enable turning gene expression "on" or "off" ac...
Source: Toxicology and Applied Pharmacology - February 9, 2013 Category: Toxicology Authors: Puntel M, A K M GM, Farrokhi C, Vanderveen N, Paran C, Appelhans A, Kroeger KM, Salem A, Lacayo L, Pechnick RN, Kelson KR, Kaur S, Kennedy S, Palmer D, Ng P, Liu C, Krasinkiewicz J, Lowenstein PR, Castro MG Tags: Toxicol Appl Pharmacol Source Type: research
Adenovirus-mediated Interferon-γ Gene Therapy Induced Human Pancreatic Carcinoma Capan-2 Cell Apoptosis In Vitro and In Vivo.
In this study, we examined the potential therapeutic effects of an adenovirus encoding human interferon gamma (Ad-IFNγ) on pancreatic carcinoma cells Capan-2 in vitro and in vivo. The results indicated that Ad-IFNγ could significantly inhibit tumor cell growth via inducing cell apoptosis. After infection, IFNγ expressed durably and stably in xenografts, predominantly in tumor tissue, while much less in blood and liver. Thus, adenovirus-mediated intratumoral injection of human IFNγ gene could be an effective gene therapeutic system for the treatment of pancreatic carcinoma. Anat Rec, 00:000-000, 2013. © 2013 Wiley Peri...
Source: Anatomical Record - February 9, 2013 Category: Anatomy Authors: Xie FJ, Zhao P, Zhang YP, Liu FY, Nie XL, Zhu YH, Yu XM, Zheng QQ, Mao WM, Lu HY, Wei H, Huang W Tags: Anat Rec (Hoboken) Source Type: research
Immunotherapeutic effects of recombinant adenovirus encoding granulocyte-macrophage colony-stimulating factor in experimental pulmonary tuberculosis.
Abstract
BALB/c mice with pulmonary tuberculosis (TB) develop a T helper cell type 1 that temporarily controls bacterial growth. Bacterial proliferation increases, accompanied by decreasing expression of interferon (IFN)-γ, tumour necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS). Activation of dendritic cells (DCs) is delayed. Intratracheal administration of only one dose of recombinant adenoviruses encoding granulocyte-macrophage colony-stimulating factor (AdGM-CSF) 1 day before Mycobacterium tuberculosis (Mtb) infection produced a significant decrease of pulmonary bacterial loads, higher act...
Source: Clinical and Developmental Immunology - February 8, 2013 Category: Allergy & Immunology Authors: Francisco-Cruz A, Mata-Espinosa D, Estrada-Parra S, Xing Z, Hernández-Pando R Tags: Clin Exp Immunol Source Type: research
Predictors of severity and mortality in children hospitalized with respiratory syncytial virus infection in a tropical region
ConclusionsRSV is an important cause of ALRI in infants and young children living in tropical regions, especially during the rainy season. The identified predictors of severe disease and mortality should be taken into account when planning interventions to reduce the burden of ALRI in young children living in these regions. Pediatr Pulmonol. © 2013 Wiley Periodicals, Inc. (Source: Pediatric Pulmonology)
Source: Pediatric Pulmonology - February 8, 2013 Category: Respiratory Medicine Authors: Diego Andrés Rodríguez, Carlos E. Rodriguez‐Martinez, Andrea Constanza Cárdenas, Ivonne Emilce Quilaguy, Leydy Yasmin Mayorga, Luz Marlesvy Falla, Gustavo Nino Tags: Original Article: Respiratory Infections Source Type: research
Gene therapy for malignant mesothelioma: Current prospects and challenges
& K Hiroshima (Source: Cancer Gene Therapy)
Source: Cancer Gene Therapy - February 8, 2013 Category: Cancer & Oncology Authors: M TagawaY TadaH ShimadaK Hiroshima Tags: malignant mesothelioma adenovirus clinical trials p53 Source Type: research
Virus-induced hepatocellular carcinomas cause antigen-specific local tolerance
T cell surveillance is often effective against virus-associated tumors because of their high immunogenicity. It is not clear why surveillance occasionally fails, particularly against hepatitis B virus– or hepatitis C virus–associated hepatocellular carcinoma (HCC). We established a transgenic murine model of virus-induced HCC by hepatocyte-specific adenovirus-induced activation of the oncogenic SV40 large T antigen (TAg). Adenovirus infection induced cytotoxic T lymphocytes (CTLs) targeted against the virus and TAg, leading to clearance of the infected cells. Despite the presence of functional, antigen-specif...
Source: Journal of Clinical Investigation - February 7, 2013 Category: Biomedical Science Authors: Gerald Willimsky, Karin Schmidt, Christoph Loddenkemper, Johanna Gellermann, Thomas Blankenstein Source Type: research
Adeno-associated virus capsid antigen presentation is dependent on endosomal escape
In this study, we used traditional pharmacological agents and AAV mutants to elucidate the pathway of capsid cross-presentation in AAV-permissive cells. Endosomal acidification inhibitors blocked AAV2 antigen presentation by over 90%, while proteasome inhibitors completely abrogated antigen presentation. Using mutant viruses that are defective for nuclear entry, we observed a 90% decrease in capsid antigen presentation. Different antigen presentation efficiencies were achieved by selectively mutating virion nuclear localization signals. Low antigen presentation was demonstrated with basic region 1 (BR1) mutants, despite re...
Source: Journal of Clinical Investigation - February 7, 2013 Category: Biomedical Science Authors: Chengwen Li, Yi He, Sarah Nicolson, Matt Hirsch, Marc S. Weinberg, Ping Zhang, Tal Kafri, R. Jude Samulski Source Type: research
Inhibitory Effect of Adenoviral Vector-Mediated Delivery of p21(WAF1/CIP1) on Retinal Vascular Endothelial Cell Proliferation and Tube Formation in Cultured Rhesus Monkey Cells (RF/6A).
Conclusions: Ad-p21 inhibits RF/6A cell proliferation and tube formation. The underlying mechanism to account for this may be that overexpression of p21 arrests the cell-cycle transition from the G1- to the S-phase via inhibition of CDK2 activity.
PMID: 23383964 [PubMed - as supplied by publisher] (Source: Current Eye Research)
Source: Current Eye Research - February 5, 2013 Category: Opthalmology Authors: Han J, Yuan Z, Yan H Tags: Curr Eye Res Source Type: research
RelB/p50 regulates TNF production in LPS-stimulated dendritic cells and macrophages.
Abstract
Dendritic cells (DCs) and macrophages are effective antigen-presenting cells, and DCs, once matured, have the ability to potently activate naïve T cells. While the canonical p65/p50 NF-κB pathway seems to have an important role during LPS-stimulation of these cells, the specific contribution of the non-canonical RelB/p50 subunits is not clear yet. We aimed to investigate the relevance of this pathway in DCs and macrophages by using replication-deficient adenoviruses overexpressing RelB and p50 subunits to test their effect on cytokine production. In both cells, after LPS treatment, overexpression of RelB...
Source: Cytokine - February 5, 2013 Category: Molecular Biology Authors: Gasparini C, Foxwell BM, Feldmann M Tags: Cytokine Source Type: research
Immunotherapeutic effects of recombinant adenovirus encoding granulocyte–macrophage colony‐stimulating factor in experimental pulmonary tuberculosis
Summary
BALB/c mice with pulmonary tuberculosis (TB) develop a T helper cell type 1 that temporarily controls bacterial growth. Bacterial proliferation increases, accompanied by decreasing expression of interferon (IFN)‐γ, tumour necrosis factor (TNF)‐α and inducible nitric oxide synthase (iNOS). Activation of dendritic cells (DCs) is delayed. Intratracheal administration of only one dose of recombinant adenoviruses encoding granulocyte–macrophage colony‐stimulating factor (AdGM‐CSF) 1 day before Mycobacterium tuberculosis (Mtb) infection produced a significant decrease of pulmonary bacterial loads, higher ac...
Source: Clinical and Experimental Immunology - February 4, 2013 Category: Allergy & Immunology Authors: A. Francisco‐Cruz, D. Mata‐Espinosa, S. Estrada‐Parra, Z. Xing, R. Hernández‐Pando Tags: Original Article Source Type: research
Epicardial HIF signaling regulates vascular precursor cell invasion into the myocardium.
In conclusion, our studies demonstrate that HIF signaling potentially regulates the degree of epicardial EMT and the extent of EPDC migration into the myocardium, both of which are likely critical in patterning the coronary vasculature during early cardiac vasculogenesis. These signals could explain why the larger coronaries appear and remain on the epicardial surface.
PMID: 23384563 [PubMed - as supplied by publisher] (Source: Developmental Biology)
Source: Developmental Biology - February 2, 2013 Category: Biology Authors: Tao J, Doughman Y, Yang K, Ramirez-Bergeron D, Watanabe M Tags: Dev Biol Source Type: research
Profilin-1 promotes the development of hypertension-induced cardiac hypertrophy
Conclusion: Profilin-1 promotes cardiac hypertrophy partly through interfering with the formation of sarcolemmal caveolae and attenuating the eNOS/NO pathway. These results demonstrate a crucial role for profilin-1 in hypertensive cardiac hypertrophy. (Source: Journal of Hypertension)
Source: Journal of Hypertension - February 1, 2013 Category: Cardiology Tags: ORIGINAL PAPERS: Heart Source Type: research
Nampt secreted from cardiomyocytes promotes development of cardiac hypertrophy and adverse ventricular remodeling
This study was designed to examine the role of Nampt in the development of cardiac hypertrophy and ventricular remodeling. We studied the hypertrophic response in Nampt heterozygous (+/–) knockout and cardiac-specific overexpressing Nampt transgenic mice. Whereas Nampt+/– mice were protected against agonist (isoproterenol and angiotensin II)-induced hypertrophy, Nampt transgenic mice spontaneously developed cardiac hypertrophy at 6 mo of age. Experiments conducted to gain insight into the mechanism revealed that treatment of cardiomyocytes with recombinant (eNampt) or overexpression with Nampt-synthesizing aden...
Source: AJP: Heart and Circulatory Physiology - February 1, 2013 Category: Cardiology Authors: Pillai, V. B., Sundaresan, N. R., Kim, G., Samant, S., Moreno-Vinasco, L., Garcia, J. G. N., Gupta, M. P. Tags: SIGNALING AND STRESS RESPONSE Source Type: research
The regression effect of Hepatocyte Nuclear Factor 4α on liver cirrhosis in rats
ConclusionsOur findings broaden the knowledge on the reversibility of different stages of cirrhosis and HNF4α could present as a promising alternative for liver cirrhosis treatment. (Source: Chinese Journal of Digestive Diseases)
Source: Chinese Journal of Digestive Diseases - February 1, 2013 Category: Gastroenterology Authors: Ting Ting Fan, Ping Fang Hu, Jian Wang, Ji Wei, Qing Zhang, Bei Fang Ning, Chuan Yin, Xin Zhang, Wei Fen Xie, Yue Xiang Chen, Bin Shi Tags: Original Article Source Type: research
Coxsackievirus B transmission and possible new roles for extracellular vesicles.
Abstract
Coxsackievirus B1, a member of the Picornaviridae family is a non-enveloped single-stranded RNA virus associated with human diseases including myocarditis and pancreatitis. Infection of the intestinal mucosa, lined by polarized epithelial cells, requires interaction of coxsackievirus with apically located DAF (decay-accelerating factor) before transport to the basolaterally located CAR (coxsackie and adenovirus receptor), where entry is mediated by endocytosis. As with many other non-enveloped viruses, coxsackievirus has to induce lysis of host cells in order to perpetuate infection. However, recent eviden...
Source: Biochemical Society Transactions - February 1, 2013 Category: Biochemistry Authors: Inal JM, Jorfi S Tags: Biochem Soc Trans Source Type: research
Epidemiology of respiratory viral infection using multiplex rt-PCR in cheonan, Korea (2006-2010).
Abstract
Multiplex RT-PCR was used to detect respiratory viruses in 5,318 clinical samples referred to the laboratory of a tertiary teaching hospital from December 2006 to November 2010. The acquired data were analyzed with respect to types, ratio, and co-infection trends of infected respiratory viruses. Trends in respiratory viral infection according to sex, age, and period of infection were also analyzed. Of the 5,318 submitted clinical samples, 3,350 (63.0%) specimens were positive for at least one respiratory virus. The infection rates were 15.8% for human rhinovirus, 14.4% for human respiratory sync...
Source: Journal of Microbiology and Biotechnology - February 1, 2013 Category: Biotechnology Authors: Kim JK, Jeon JS, Kim JW, Rheem I Tags: J Microbiol Biotechnol Source Type: research
The efficiency of concentration methods used to detect enteric viruses in anaerobically digested sludge.
Abstract
The presence of enteric viruses in biosolids can be underestimated due to the inefficient methods (mainly molecular methods) used to recover the viruses from these matrices. Therefore, the goal of this study was to evaluate the different methods used to recover adenoviruses (AdV), rotavirus species A (RVA), norovirus genogroup II (NoV GII) and the hepatitis A virus (HAV) from biosolid samples at a large urban wastewater treatment plant in Brazil after they had been treated by mesophilic anaerobic digestion. Quantitative polymerase chain reaction (PCR) was used for spiking experiments to compare the detecti...
Source: Memorias do Instituto Oswaldo Cruz - February 1, 2013 Category: Infectious Diseases Authors: Prado T, Guilayn Wde C, Gaspar AM, Miagostovich MP Tags: Mem Inst Oswaldo Cruz Source Type: research
Potent growth-inhibitory effect of a dual cancer-specific oncolytic adenovirus expressing apoptin on prostate carcinoma.
Potent growth-inhibitory effect of a dual cancer-specific oncolytic adenovirus expressing apoptin on prostate carcinoma.
Int J Oncol. 2013 Mar;42(3):1052-60
Authors: Zhang M, Wang J, Li C, Hu N, Wang K, Ji H, He D, Quan C, Li X, Jin N, Li Y
Abstract
Apoptin is a chicken anemia virus-derived, p53-independent, bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis in various human tumor cells, but not in normal cells. To explore the use of apoptin in tumor gene therapy, we assessed a recombinant adenovirus expressing the apoptin protein (Ad-hTERTp-E...
Source: International Journal of Oncology - January 31, 2013 Category: Cancer & Oncology Authors: Zhang M, Wang J, Li C, Hu N, Wang K, Ji H, He D, Quan C, Li X, Jin N, Li Y Tags: Int J Oncol Source Type: research
The VHL tumor suppressor protein regulates tumorigenicity of U87-derived glioma stem-like cells by inhibiting the JAK/STAT signaling pathway.
The VHL tumor suppressor protein regulates tumorigenicity of U87-derived glioma stem-like cells by inhibiting the JAK/STAT signaling pathway.
Int J Oncol. 2013 Mar;42(3):881-6
Authors: Kanno H, Sato H, Yokoyama TA, Yoshizumi T, Yamada S
Abstract
The signal transducer and activator of transcription 3 (STAT3) factor plays an important role in the tumorigenicity of cancer stem cells. The purpose of this study was to investigate the inhibitory mechanism of this pathway acting through the tumor suppressor von Hippel-Lindau (VHL) protein in glioma cancer stem cells. We isolated floa...
Source: International Journal of Oncology - January 31, 2013 Category: Cancer & Oncology Authors: Kanno H, Sato H, Yokoyama TA, Yoshizumi T, Yamada S Tags: Int J Oncol Source Type: research
No tumour-initiating risk associated with scAAV transduction in newborn rat liver
& S Conchon (Source: Gene Therapy)
Source: Gene Therapy - January 31, 2013 Category: Genetics & Stem Cells Authors: V GauttierV PichardD AubertC KaeppelM SchmidtN FerryS Conchon Tags: adeno-associated virus rat newborn liver cancer Source Type: research
Hedgehog Signaling in Neonatal and Adult Lung.
Abstract
Sonic Hedgehog (Shh) signals from epithelium to mesenchyme during embryonic lung development, but the roles of Hedgehog (Hh) signaling in postnatal lung development and adult lung are not known. Using Gli1nlacZ reporter mice to identify cells with active Hh signaling, we found that Gli1nlacZ-positive mesenchymal cells are densely and diffusely present up to 2 weeks after birth and decline in number thereafter. In adult mice, Gli1nlacZ-positive cells are present around large airways and vessels and are sparse in alveolar septa. Hh-stimulated cells are mostly fibroblasts; only 10% of Gli1nlacZ-positive cells...
Source: American Journal of Respiratory Cell and Molecular Biology - January 31, 2013 Category: Molecular Biology Authors: Liu L, Kugler MC, Loomis CA, Samdani R, Zhao Z, Chen GJ, Brandt JP, Brownell I, Joyner AL, Rom WN, Munger JS Tags: Am J Respir Cell Mol Biol Source Type: research
Smoke Extract Impairs Adenosine Wound Healing: Implications of Smoke-Generated Reactive Oxygen Species.
In conclusion, our data suggest that cigarette smoke exposure impairs A2A-stimulated wound repair via a reactive oxygen species-dependent mechanism and provides a better understanding of adenosine signaling that may direct the development of pharmacological tools for treatment of chronic inflammatory lung disorders.
PMID: 23371060 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - January 31, 2013 Category: Molecular Biology Authors: Allen-Gipson DS, Zimmerman MC, Zhang H, Castellanos G, O'Malley JK, Alvarez-Ramirez H, Kharbanda K, Sisson JH, Wyatt TA Tags: Am J Respir Cell Mol Biol Source Type: research
Oral vaccination with an adenovirus-vectored vaccine protects against botulism.
Abstract
We have previously shown that an adenovirus vectored vaccine delivered intramuscularly or intranasally was effective in protection against botulism in a mouse model. The adenoviral vector encodes a human codon-optimized heavy chain C-fragment (H(C)50) of botulinum neurotoxin type C (BoNT/C). Here, we evaluate the same vaccine candidate as an oral vaccine against BoNT/C in a mouse model. To elicit protective immunity, the mice were orally vaccinated with a single dose of 1×10(4) to 1×10(7)plaque forming units (pfu) of the adenoviral vector. The immune sera, collected six weeks after oral vaccination with ...
Source: Vaccine - January 30, 2013 Category: Allergy & Immunology Authors: Chen S, Xu Q, Zeng M Tags: Vaccine Source Type: research
Regression of Schwannomas Induced by Adeno-Associated Virus-Mediated Delivery of Caspase-1
Human Gene Therapy , Vol. 0, No. 0. (Source: Human Gene Therapy)
Source: Human Gene Therapy - January 30, 2013 Category: Genetics & Stem Cells Tags: article Source Type: research
Antigen-coated poly α-hydroxy acid based microparticles for heterologous prime-boost adenovirus based vaccinations.
Abstract
Adenoviruses show promising potential as vectors for cancer vaccines, however, their high immunogenicity can be problematic when it comes to homologous prime-boost strategies. In the studies presented here we show that heterologous prime-boost vaccinations involving ovalbumin (OVA)-antigen-coated microparticles as a prime, and adenovirus encoding OVA (AdOVA) as a boost, were equally as effective as homologous AdOVA prime-boosts at generating OVA-specific CD8(+) T-cell responses, which translated into effective tumor protection. OVA-coated biodegradable poly α-hydroxy acid-based microparticles of varying c...
Source: Biomaterials - January 30, 2013 Category: Materials Science Authors: Lemke CD, Geary SM, Joshi VB, Salem AK Tags: Biomaterials Source Type: research
Effect of tumor suppressor PTEN gene on apoptosis and cell cycle of human airway smooth muscle cells.
Abstract
It is well established that hyperplasia and decreased apoptosis of airway smooth muscle cells (ASMCs) play an important role in the asthmatic airway remodeling. Tumor suppressor PTEN gene with phosphatase activity plays an important regulatory role in embryonic development, cell proliferation, and apoptosis, cell cycle regulation, migration (invasion) of the cytoskeleton. We hypotheses that PTEN gene could affect the growth and viability of ASMCs through the regulation of PI3K/Akt, MAPK, and cell cycle-related gene expression. We constructed a recombinant adenovirus to transfect ASMCs. Cells were divided i...
Source: Molecular and Cellular Biochemistry - January 28, 2013 Category: Biochemistry Authors: Luo L, Gong YQ, Qi X, Lai W, Lan H, Luo Y Tags: Mol Cell Biochem Source Type: research

