Cancers, Vol. 12, Pages 798: External Beam Radiation Therapy and Enadenotucirev: Inhibition of the DDR and Mechanisms of Radiation-Mediated Virus Increase

Cancers, Vol. 12, Pages 798: External Beam Radiation Therapy and Enadenotucirev: Inhibition of the DDR and Mechanisms of Radiation-Mediated Virus Increase Cancers doi: 10.3390/cancers12040798 Authors: Tzveta D. Pokrovska Egon J. Jacobus Rathi Puliyadi Remko Prevo Sally Frost Arthur Dyer Richard Baugh Gonzalo Rodriguez-Berriguete Kerry Fisher Giovanna Granata Katharine Herbert William K. Taverner Brian R. Champion Geoff S. Higgins Len W. Seymour Janet Lei-Rossmann Ionising radiation causes cell death through the induction of DNA damage, particularly double-stranded DNA (dsDNA) breaks. Evidence suggests that adenoviruses inhibit proteins involved in the DNA damage response (DDR) to prevent recognition of double-stranded viral DNA genomes as cellular dsDNA breaks. We hypothesise that combining adenovirus treatment with radiotherapy has the potential for enhancing tumour-specific cytotoxicity through inhibition of the DDR and augmentation of virus production. We show that EnAd, an Ad3/Ad11p chimeric oncolytic adenovirus currently being trialled in colorectal and other cancers, targets the DDR pathway at a number of junctures. Infection is associated with a decrease in irradiation-induced 53BP1 and Rad51 foci formation, and in total DNA ligase IV levels. We also demonstrate a radiation-associated increase in EnAd production in vitro and in a pilot in vivo experiment. Given the current limitations of in vitro techniques in assessing for synergy...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

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Background and objective Flubendazole is an anthelmintic and categorized in benzimidazole. Previous evidence indicates its suppression on proliferation of colon cancer and breast cancer cells. Our study aims to explore the effects of flubendazole on non-small cell lung cancer A549 and H460 cell lines and the underlying mechanism. Methods CCK-8 assay was used to detect the effect of flubendazole at different concentrations on viability of both cell lines A549 and H460. We used western blot to detect the expression levels of autophagy-related proteins p62 and LC3 after flubendazole treatment. Cells were transfected with tand...
Source: Chinese Journal of Lung Cancer - Category: Cancer & Oncology Source Type: research
In this study, oncolytic adenovirus infection foci were found within pimonidazole-reactive, oxygen-poor areas in a colorectal xenograft tumour, where the expression of VEGF, a target gene of the hypoxia-inducible factor (HIF), was attenuated. We hypothesised that adenovirus infection interferes with the HIF‑signalling axis in the hypoxic tumour niche, possibly modifying the local vascular supply. In vitro, enadenotucirev (EnAd), adenovirus 11p and adenovirus 5 decreased the protein expression of HIF‑1α only during the late phase of the viral life cycle by transcriptional down‑regulation and not post‑trans...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Publication date: Available online 23 October 2019Source: Microvascular ResearchAuthor(s): Chen Chen, Yan Li, Shiqiang Hou, Pierre M. Bourbon, Liuliang Qin, Kevin Zhao, Taiyang Ye, Dezheng Zhao, Huiyan ZengAbstractPathological angiogenesis is a hallmark of many diseases. Previously, we reported that orphan nuclear receptor TR3/Nur77 was a critical mediator of angiogenesis to regulate tumor growth, sepsis and skin wound healing. However, none of the TR3/Nur77 targeting molecule has been in clinical trial so far. Here, we designed and generated novel TR3 shRNAs and two minigenes that had therapeutic potential for cancer trea...
Source: Microvascular Research - Category: Biochemistry Source Type: research
ConclusionsThe combination of EnAd and nivolumab has a manageable toxicity profile supporting further investigation in study expansion. Favourable OS outcome in a highly refractory CRC population was noted and may suggest delayed immune antitumor activity in this population.Clinical trial identification2017-001231-39.Legal entity responsible for the studyPsiOxus Therapeutics Ltd.FundingPsiOxus Therapeutics Ltd; Bristol-Myers Squibb.DisclosureP. Basciano: Full / Part-time employment: Bristol-Myers Squibb. R. Brown: Shareholder / Stockholder / Stock options, Full / Part-time employment: PsiOxus Therapeutics Ltds. O. Arogunda...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Stem Cells and Development, Ahead of Print.
Source: Stem Cells and Development - Category: Stem Cells Authors: Source Type: research
Conclusion and Future Perspectives This review illustrates our current knowledge of USP7, including its source and characterization, structure, binding partners and substrates in various biological processes. Besides, how USP7 regulates various aspects of a cell under both normal and pathological states are elaborated in detail. As the processes of ubiquitination and deubiquitination are extremely dynamic and context-specific, a series of studies have linked USP7 to different cancers. The biology, particularly the immune oncology mechanisms, reveal that USP7 inhibitors would be useful drugs, thus it is vital to develop hi...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Michal Yalon1†, Amos Toren1,2†, Dina Jabarin2, Edna Fadida3, Shlomi Constantini3 and Ruty Mehrian-Shai1* 1Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel 2The Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel 3Department of Pediatric Neurosurgery, Dana Children's Hospital, Tel-Aviv-Sourasky Medical Center, Tel Aviv, Israel Pediatric brain tumors are the most common solid tumor type and the leading cause of cancer-related death in children. The immune system plays an important r...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions and Future Perspectives It is now evident that NK/ILC family plays a pivotal role in the immune defenses. Recent studies in murine and human settings demonstrated that the expression of several inhibitory checkpoints, that may be detrimental in the tumor context, is not restricted to T lymphocytes, revealing an important, yet poorly appreciated, contribution of their expression on innate immune cells. Thus, in the recent years different immunotherapy approaches, based on the blockade of inhibitory NK cell receptors, have been developed in order to unleash NK cell cytotoxicity. This is particularly important in...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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