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Oncolytic virus

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https://www.readbyqxmd.com/read/29146961/identification-of-host-dead-box-rna-helicases-that-regulate-cellular-tropism-of-oncolytic-myxoma-virus-in-human-cancer-cells
#1
Masmudur M Rahman, Eugenie Bagdassarian, Mohamed A M Ali, Grant McFadden
Myxoma virus (MYXV), a Leporipoxvirus, is being developed as an oncolytic virotherapeutic for the treatment of a variety of human cancers. MYXV tropism for human cancer cells is largely mediated by intracellular signaling networks that regulate viral replication or innate antiviral response pathways. Thus, MYXV is fully or partially permissive for the majority of human cancer cells that harbor defects in antiviral signaling, but a minority are nonpermissive because the virus infection aborts before its completion...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29146945/maraba-virus-vectored-cancer-vaccines-represent-a-safe-and-novel-therapeutic-option-for-cats
#2
Jeff Hummel, Dorothee Bienzle, Annette Morrison, Michelle Cieplak, Kyle Stephenson, Josepha DeLay, J Paul Woods, Brian D Lichty, Byram W Bridle
Direct killing of malignant cells combined with induction of tumour-specific immune responses makes oncolytic vaccines attractive for cancer therapy. We previously developed a heterologous cancer immunization strategy that utilized a replication-defective adenovirus-vectored primary vaccine encoding a tumour antigen followed by boosting with a replication-competent Maraba virus expressing the same antigen. To assess the safety of oncolytic Maraba virus-based booster vaccines and inform the design of clinical trials, we conducted translational studies in cats, which have immune systems that are similar to people and spontaneously develop cancers of comparable types and etiologies...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29143726/recent-advances-in-vesicular-stomatitis-virus-based-oncolytic-virotherapy-a-5-year-update
#3
Sébastien A Felt, Valery Z Grdzelishvili
Oncolytic virus (OV) therapy is an anti-cancer approach that uses viruses that preferentially infect, replicate in and kill cancer cells. Vesicular stomatitis virus (VSV, a rhabdovirus) is an OV that is currently being tested in the USA in several phase I clinical trials against different malignancies. Several factors make VSV a promising OV: lack of pre-existing human immunity against VSV, a small and easy to manipulate genome, cytoplasmic replication without risk of host cell transformation, independence of cell cycle and rapid growth to high titres in a broad range of cell lines facilitating large-scale virus production...
November 16, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/29137714/checkpoint-blockade-plus-oncolytic-virus-a-hot-therapeutic-cancer-strategy
#4
Caroline Robert
How can we transform an immune desert into a 'hot tumor' that is prone to respond to anti-programmed death (PD)-1 immunotherapy? This might be possible by injecting an oncolytic virus, engineered to induce local immune stimulation, prior to anti-PD-1 therapy. A recent study demonstrated that this combination - evaluated in a Phase Ib metastatic melanoma clinical study - yields promising results.
November 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29137298/ing4-expressing-oncolytic-vaccinia-virus-promotes-anti-tumor-efficiency-and-synergizes-with-gemcitabine-in-pancreatic-cancer
#5
Yinfang Wu, Xiaozhou Mou, Shibing Wang, Xing-E Liu, Xiaodong Sun
With no effective treatments available for most pancreatic cancer patients, pancreatic cancer continues to be one of the most difficult malignancies to treat. Oncolytic virus mediated-gene therapy has exhibited ubiquitous antitumor potential. In this study, we constructed a novel oncolytic vaccinia virus harboring the inhibitor of growth family member 4 gene (VV-ING4) to investigate its therapeutic efficacy alone or in combination with gemcitabine against pancreatic cancer cells in vitro and in vivo. ING4 expression was determined via quantitative real-time polymerase chain reaction (qPCR) and western blot...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29132390/a-transwell-assay-that-excludes-exosomes-for-assessment-of-tunneling-nanotube-mediated-intercellular-communication
#6
Venugopal Thayanithy, Patrick O'Hare, Phillip Wong, Xianda Zhao, Clifford J Steer, Subbaya Subramanian, Emil Lou
BACKGROUND: Tunneling nanotubes (TNTs) are naturally-occurring filamentous actin-based membranous extensions that form across a wide spectrum of mammalian cell types to facilitate long-range intercellular communication. Valid assays are needed to accurately assess the downstream effects of TNT-mediated transfer of cellular signals in vitro. We recently reported a modified transwell assay system designed to test the effects of intercellular transfer of a therapeutic oncolytic virus, and viral-activated drugs, between cells via TNTs...
November 13, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29118089/oncolytic-virotherapy-blockade-by-microglia-and-macrophages-requires-stat1-3
#7
Zahid M Delwar, Yvonne Kuo, Yan H Wen, Paul S Rennie, William Jia
The first oncolytic virotherapy employing HSV-1 (oHSV-1) was approved recently by the FDA to treat cancer, but further improvements in efficacy are needed to eradicate challenging refractory tumors such as glioblastomas (GBM). Microglia/macrophages comprising ~40% of a GBM tumor may limit virotherapeutic efficacy. Here we show these cells suppress oHSV-1 growth in gliomas by internalizing the virus through phagocytosis. Internalized virus remained capable of expressing reporter genes while viral replication was blocked...
November 8, 2017: Cancer Research
https://www.readbyqxmd.com/read/29109762/stability-analysis-on-the-radioactive-iodine-labelled-prostate-cancer-specific-recombinant-oncolytic-adenovirus
#8
Jiahe Zhou, Lin Hao, Zhenduo Shi, Songyi Ning, Houguang He, Yan Zhao, Yang Dong, Zhigang Li, Jiuxiang He, Guanghui Zang, Conghui Han
The aim of the present study was to construct the (125)I-replication-selective oncolytic adenovirus (RSOAds)-human telomerase reverse transcriptase (hTERT)/prostate specific antigen (PSA) nuclide-oncolytic virus marker by labelling the hTERT/PSA double-regulation replicative oncolytic adenovirus with (125)I nuclide, and investigate the influence of viral markers under various reaction conditions on labelling efficiency. N-bromosuccinimide (NBS) was used as the oxidizer for (125)I labelling, and the best conditions for labelling were identified through the reactions between oncolytic adenovirus at various concentrations and NBS...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29100290/cd133-targeted-oncolytic-adenovirus-demonstrates-anti-tumor-effect-in-colorectal-cancer
#9
Mizuho Sato-Dahlman, Yoshiaki Miura, Jing Li Huang, Praveensingh Hajeri, Kari Jacobsen, Julia Davydova, Masato Yamamoto
Oncolytic Adenoviruses (OAds) are one of the most promising anti-cancer agents that can induce cancer specific cell death. Recently, we generated infectivity-selective OAd, and the resultant OAd tumor-specific binding shows strong efficacy and mitigates toxicity. In this study, we applied this strategy based on adenovirus library screening system for generation of CD133-targeted OAd, and examined their oncolytic activity against colorectal cancer (CRC) in vitro and in vivo. CD133 (Prominin-1) is an important cell surface marker of cancer stem (like) cells (CSCs) in various cancers, including CRC...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29094723/liver-cancer-sensitizing-hepatocellular-carcinoma-to-oncolytic-virus-therapy
#10
Jennifer Altomonte
No abstract text is available yet for this article.
November 2, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29093092/isolation-and-characterization-of-v%C3%AE-i3-confirms-that-the-vaccinia-virus-ssb-plays-an-essential-role-in-viral-replication
#11
Matthew D Greseth, Maciej W Czarnecki, Matthew S Bluma, Paula Traktman
Vaccinia virus is unusual among DNA viruses in replicating exclusively in the cytoplasm of infected cells. The ssDNA binding protein (SSB), I3, is among the replication machinery encoded by the 195 kb genome, although direct genetic analysis of I3 has been lacking. Herein, we describe a complementing cell line (CV1-I3) that fully supports the replication of a null virus lacking the I3 ORF (vΔI3). In non-complementing CV1-CAT cells, vΔI3 shows a severe defect in the production of infectious virus (≥200-fold reduction)...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29084163/atomic-resolution-structure-of-the-oncolytic-parvovirus-luiii-by-electron-microscopy-and-3d-image-reconstruction
#12
Nikéa Pittman, Adam Misseldine, Lorena Geilen, Sujata Halder, J Kennon Smith, Justin Kurian, Paul Chipman, Mandy Janssen, Robert Mckenna, Timothy S Baker, Anthony D'Abramo, Susan Cotmore, Peter Tattersall, Mavis Agbandje-McKenna
LuIII, a protoparvovirus pathogenic to rodents, replicates in human mitotic cells, making it applicable for use to kill cancer cells. This virus group includes H-1 parvovirus (H-1PV) and minute virus of mice (MVM). However, LuIII displays enhanced oncolysis compared to H-1PV and MVM, a phenotype mapped to the major capsid viral protein 2 (VP2). This suggests that within LuIII VP2 are determinants for improved tumor lysis. To investigate this, the structure of the LuIII virus-like-particle was determined using single particle cryo-electron microscopy and image reconstruction to 3...
October 30, 2017: Viruses
https://www.readbyqxmd.com/read/29076241/oncolytic-reovirus-therapy-pilot-study-in-dogs-with-spontaneously-occurring-tumours
#13
C C Hwang, M Igase, M Sakurai, T Haraguchi, K Tani, K Itamoto, T Shimokawa, M Nakaichi, Y Nemoto, S Noguchi, M Coffey, M Okuda, T Mizuno
Oncolytic virotherapy is a novel treatment involving replication-competent virus in the elimination of cancer. We have previously reported the oncolytic effects of reovirus in various canine cancer cell lines. This study aims to establish the safety profile of reovirus in dogs with spontaneously occurring tumours and to determine a recommended dosing regimen. Nineteen dogs with various tumours, mostly of advanced stages, were treated with reovirus, ranging from 1.0 × 10(8) to 5.0 × 10(9) TCID50 given as intratumour injection (IT) or intravenous infusion (IV) daily for up to 5 consecutive days in 1 or multiple treatment cycles...
October 27, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/29072600/protoparvovirus-cell-entry
#14
REVIEW
Carlos Ros, Nooshin Bayat, Raphael Wolfisberg, José M Almendral
The Protoparvovirus (PtPV) genus of the Parvoviridae family of viruses includes important animal pathogens and reference molecular models for the entire family. Some virus members of the PtPV genus have arisen as promising tools to treat tumoral processes, as they exhibit marked oncotropism and oncolytic activities while being nonpathogenic for humans. The PtPVs invade and replicate within the nucleus making extensive use of the transport, transcription and replication machineries of the host cells. In order to reach the nucleus, PtPVs need to cross over several intracellular barriers and traffic through different cell compartments, which limit their infection efficiency...
October 26, 2017: Viruses
https://www.readbyqxmd.com/read/29062886/activating-peripheral-innate-immunity-enables-safe-and-effective-oncolytic-virotherapy-in-the-brain
#15
Lukxmi Balathasan, Vera A Tang, Beta Yadollahi, Jan Brun, Melanie Labelle, Charles Lefebvre, Stephanie L Swift, David F Stojdl
The oncolytic mutant vesicular stomatitis virus VSVΔ51 achieves robust efficacy in multiple extracranial tumor models. Yet for malignancies of the brain, direct intratumoral infusion of VSVΔ51 causes lethal virus-induced neuropathology. Here, we have developed a novel therapeutic regime that uses peripheral immunization with a single sub-lethal dose of VSVΔ51 to establish an acute anti-viral state that enables the safe intracranial (IC) infusion of an otherwise lethal dose of VSVΔ51 within just 6 hr. Although type I interferons alone appeared insufficient to explain this protective phenotype, serum isolated at early time points from primed animals conferred protection against an IC dose of virus...
December 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/29061083/immuno-oncology-the-translational-runway-for-gene-therapy
#16
Ludger Weß, Frank Schnieders
Cancer therapy once again is experiencing a paradigm shift. This shift is based on extensive clinical experience demonstrating that cancer cannot be successfully fought by addressing single targets or pathways only. Even the combination of several neo-antigens in cancer vaccines is not sufficient for a successful, lasting tumor eradication. The focus therefore has shifted on the immune systems role in cancer and the striking abilities of cancer cells to manipulate and/or deactivate the immune system. Researchers and pharma companies have started to target the processes and cells known to support immune surveillance and the elimination of tumor cells...
October 23, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29039746/preclinical-testing-of-an-oncolytic-parvovirus-standard-protoparvovirus-h-1pv-efficiently-induces-osteosarcoma-cell-lysis-in-vitro
#17
Carsten Geiss, Zoltán Kis, Barbara Leuchs, Monika Frank-Stöhr, Jörg R Schlehofer, Jean Rommelaere, Christiane Dinsart, Jeannine Lacroix
Osteosarcoma is the most frequent malignant disease of the bone. On the basis of early clinical experience in the 1960s with H-1 protoparvovirus (H-1PV) in osteosarcoma patients, this effective oncolytic virus was selected for systematic preclinical testing on various osteosarcoma cell cultures. A panel of five human osteosarcoma cell lines (CAL 72, H-OS, MG-63, SaOS-2, U-2OS) was tested. Virus oncoselectivity was confirmed by infecting non-malignant human neonatal fibroblasts and osteoblasts used as culture models of non-transformed mesenchymal cells...
October 17, 2017: Viruses
https://www.readbyqxmd.com/read/29039580/combination-of-oncolytic-adenovirus-and-luteolin-exerts-synergistic-antitumor-effects-in-colorectal-cancer-cells-and-a-mouse-model
#18
Boduan Xiao, Yun Qin, Chang Ying, Buyun Ma, Binrong Wang, Fei Long, Ruwei Wang, Ling Fang, Yigang Wang
In recent years, oncolytic viruses have attracted increasing interest due to their potent antitumor effects. Luteolin, a natural product, has additionally been observed to exhibit various pharmacological antitumor activities. Previously, a novel dual‑targeting oncolytic adenovirus, complement decay‑accelerating factor (CD55)‑tumor necrosis factor ligand superfamily member 10 (TRAIL), was constructed, which exhibited significant growth inhibitory effects in various types of tumor cell. The present study investigated whether the combination of luteolin and CD55‑TRAIL was able to exert a synergistic antitumor effect in colorectal carcinoma (CRC) cells...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29034314/targeting-an-oncolytic-influenza-a-virus-to-tumor-tissue-by-elastase
#19
Irina Kuznetsova, Tobias Arnold, Thomas Aschacher, Cornelia Schwager, Balazs Hegedus, Tamas Garay, Marina Stukova, Maria Pisareva, Stephan Pleschka, Michael Bergmann, Andrej Egorov
Oncolytic viruses are currently established as a novel type of immunotherapy. The challenge is to safely target oncolytic viruses to tumors. Previously, we have generated influenza A viruses (IAVs) containing deletions in the viral interferon antagonist. Those deletions have attenuated the virus in normal tissue but allowed replication in tumor cells. IAV entry is mediated by hemagglutinin (HA), which needs to be activated by a serine protease, for example, through trypsin. To further target the IAV to tumors, we have changed the trypsin cleavage site to an elastase cleavage site...
December 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/29034313/newly-characterized-murine-undifferentiated-sarcoma-models-sensitive-to-virotherapy-with-oncolytic-hsv-1-m002
#20
Eric K Ring, Rong Li, Blake P Moore, Li Nan, Virginia M Kelly, Xiaosi Han, Elizabeth A Beierle, James M Markert, Jianmei W Leavenworth, G Yancey Gillespie, Gregory K Friedman
Despite advances in conventional chemotherapy, surgical techniques, and radiation, outcomes for patients with relapsed, refractory, or metastatic soft tissue sarcomas are dismal. Survivors often suffer from lasting morbidity from current treatments. New targeted therapies with less toxicity, such as those that harness the immune system, and immunocompetent murine sarcoma models to test these therapies are greatly needed. We characterized two new serendipitous murine models of undifferentiated sarcoma (SARC-28 and SARC-45) and tested their sensitivity to virotherapy with oncolytic herpes simplex virus 1 (HSV-1)...
December 15, 2017: Molecular Therapy Oncolytics
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