3,525 results match your criteria adenovirus e1a


AXL is crucial for E1A-enhanced therapeutic efficiency of EGFR tyrosine kinase inhibitors through NFI in breast cancer.

Environ Toxicol 2021 Mar 18. Epub 2021 Mar 18.

Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.

AXL which is a chemosensitizer protein for breast cancer cells in response to epidermal growth factor receptor-tyrosine kinase inhibitor and suppresses tumor growth. The clinical information show nuclear factor I (NFI)-C and NFI-X expression correlate with AXL expression in breast cancer patients. Following, we establish serial deletions of AXL promoter to identify regions required for Adenovirus-5 early region 1A (E1A)-mediated AXL suppression. Read More

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Heat Shock Protein 90 Chaperones E1A Early Protein of Adenovirus 5 and Is Essential for Replication of the Virus.

Int J Mol Sci 2021 Feb 18;22(4). Epub 2021 Feb 18.

Department of Experimental Pharmacology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland.

Adenovirus infections tend to be mild, but they may pose a serious threat for young and immunocompromised individuals. The treatment is complicated because there are no approved safe and specific drugs for adenovirus infections. Here, we present evidence that 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG), an inhibitor of Hsp90 chaperone, decreases the rate of human adenovirus 5 (HAdV-5) replication in cell cultures by 95%. Read More

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February 2021

Analysis of E1A domains involved in the enhancement of CDK2 activity.

Biochem Biophys Res Commun 2021 Apr 25;548:98-103. Epub 2021 Feb 25.

Department of Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan. Electronic address:

E1A is an adenoviral protein which is expressed at the early phase after viral infection and contains four conserved regions (CR1, CR2, CR3 and CR4). Our previous work suggests that E1A facilitates the formation of cyclin A-CDK2 complex and thereby enhances CDK2 activity. However, the molecular function of E1A in CDK2 activation has been unclear. Read More

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Evaluation of tumor immunity after administration of conditionally replicative adenoviral vector in canine osteosarcoma patients.

Heliyon 2021 Feb 10;7(2):e06210. Epub 2021 Feb 10.

Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, USA.

Osteosarcoma is one among the most common neoplasms in dogs. Current treatments show limited efficacy and fail to prevent metastasis. Conditionally replicative adenoviruses (CRAd) replicate exclusively in targeted tumor cells and release new virus particles to infect additional cells. Read More

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February 2021

Autophagy promotes oncolysis of an adenovirus expressing apoptin in human bladder cancer models.

Invest New Drugs 2021 Feb 3. Epub 2021 Feb 3.

Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Liuying west road, 666, Jingyue Economic & Technological Development Zone, Changchun, Jilin, 130122, People's Republic of China.

As a potential cancer therapy, we developed a recombinant adenovirus named Ad-VT, which was designed to express the apoptosis-inducing gene (apoptin) and selectively replicate in cancer cells via E1a manipulation. However, how it performs in bladder cancer remains unclear. We examined the antitumor efficacy of Ad-VT in bladder cancers using CCK-8 assays and xenograft models. Read More

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February 2021

Optimization of an E1A Gene Expression Cassette in an Oncolytic Adenovirus for Efficient Tumor Cell Killing Activity.

Anticancer Res 2021 Feb;41(2):773-782

Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan;

Background/aim: Oncolytic adenoviruses (OAds) have attracted much attention as novel anticancer therapeutics. The proper design of an expression cassette containing the E1A gene, which is indispensable for self-replication of the Ad genome, is crucial for efficient tumor cell-specific infection of an OAd. Various types of oncolytic adenoviruses (OAds) possessing different types of the E1A gene expression cassettes have been developed, but their oncolytic activities and safety profiles have not been systematically evaluated. Read More

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February 2021

The immunological impact of adenovirus early genes on vaccine-induced responses in mice and nonhuman primates.

J Virol 2021 Jan 13. Epub 2021 Jan 13.

Department of Biology, Howard University, Washington, DC, USA

Adenovirus (Ad) is being explored for use in the prevention and treatment of a variety of infectious diseases and cancers. Ad with a deletion in early region 3 () provokes a stronger immune response than Ad with deletions in early regions 1 and E3 (). The ΔE1/ΔE3 Ads are more popular because they can carry a larger transgene and because of the deleted E1 (E1A and E1B), are perceived safer for clinical use. Read More

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January 2021

Differential Splicing of Human Adenovirus 5 E1A RNA Expressed in versus in .

J Virol 2021 02 24;95(6). Epub 2021 Feb 24.

Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada

Human adenovirus (HAdV) is used extensively as a vector for gene delivery for a variety of purposes, including gene therapy and vaccine development. Most adenoviral vectors used for these approaches have a deletion of early region 1 (E1), which is complemented by the cell line. Most commonly, these are 293 cells for HAdV serotype 2 or 5. Read More

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February 2021

Teratogenic Toxicity Evaluation of Bladder Cancer Specific Oncolytic Adenovirus on Mice.

Curr Gene Ther 2020 Dec 17. Epub 2020 Dec 17.

Gansu Nephro-Urological Clinical Center; Key Laboratory of Urological Diseases, Gansu Province (Lanzhou University); Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou. China.

Background: In our previous studies, we had demonstrated the efficiency and specificity of constructed bladder tissue specific adenovirus Ad-PSCAE-UPII-E1A-AR (APU-EIA-AR) on bladder cancer, we also investigated the virus biodistribution and body toxicity in nude mice. However, the safety of the bladder cancer specific oncolytic adenovirus on fetal mice and F1 mice should be under intense investigation.

Objectives: In order to evaluate the teratogenic toxicity of bladder cancer specific oncolytic adenovirus APU-EIA-AR on mice, in this study, we investigated the fetal mice weight, fetal body length and tail length, fetal skeleton development, as well as the F1 mice weight, growth curve, and major organ pathology. Read More

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December 2020

Characterization and oncolytic virus targeting of FAP-expressing tumor-associated pericytes in glioblastoma.

Acta Neuropathol Commun 2020 12 11;8(1):221. Epub 2020 Dec 11.

Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, MA, 02114, USA.

Cancer-associated fibroblasts (CAFs) are activated fibroblasts constituting the major stromal components in many types of cancer. CAFs contribute to hallmarks of cancer such as proliferation, invasion and immunosuppressive tumor microenvironment, and are associated with poor prognosis of patients with cancer. However, in glioblastoma (GBM), the most common and aggressive primary malignant brain tumor, our knowledge about CAFs or CAF-like stromal cells is limited. Read More

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December 2020

Anti-tumour effects of a dual cancer-specific oncolytic adenovirus on Breast Cancer Stem cells.

J Cell Mol Med 2021 Jan 11;25(2):666-676. Epub 2020 Dec 11.

College of Animal Science and Technology, Guangxi University, Nanning, China.

Apoptin can specifically kill cancer cells but has no toxicity to normal cells. Human telomerase reverse transcriptase (hTERT) can act as a tumour-specific promoter by triggering the expression of certain genes in tumour cells. This study aims to investigate the inhibitory effects and to explore the inhibitory pathway of a dual cancer-specific recombinant adenovirus (Ad-apoptin-hTERTp-E1a, Ad-VT) on breast cancer stem cells. Read More

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January 2021

The Human Adenovirus Type 2 Transcriptome: An Amazing Complexity of Alternatively Spliced mRNAs.

J Virol 2020 Nov 25. Epub 2020 Nov 25.

Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden

We have used the Nanopore long-read sequencing platform to demonstrate how amazingly complex the human adenovirus type 2 (Ad2) transcriptome is with a flexible splicing machinery producing a range of novel mRNAs both from the early and late transcription units. In total we report more than 900 alternatively spliced mRNAs produced from the Ad2 transcriptome whereof more than 850 are novel mRNAs. A surprising finding was that more than 50% of all E1A transcripts extended upstream of the previously defined transcriptional start site. Read More

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November 2020

CREG improves cardiac function by regulating cardiomyocytes' autophagy in diabetic myocardial infarction rats.

Eur Rev Med Pharmacol Sci 2020 11;24(21):11233-11242

Department of Endocrinology, Heze Municipal Hospital, Heze, China.

Objective: We aimed to observe the changes of cardiac function, cell morphology, cellular repressor of E1A-stimulated genes (CREG) and LC3-II after myocardial infarction (MI) in non-diabetic and diabetic rats, and to explore the relationship between myocardial damage and CREG and autophagy in diabetic rats.

Materials And Methods: Diabetic rat models were prepared by intraperitoneal injection of low concentration (50 mg/kg) streptozotocin (STZ). MI models were established in normal rats and diabetic rats. Read More

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November 2020

Adenoviral E1A Exploits Flexibility and Disorder to Target Cellular Proteins.

Biomolecules 2020 11 11;10(11). Epub 2020 Nov 11.

Department of Chemistry "Ugo Schiff" and Magnetic Resonance Center (CERM), University of Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino (Florence), Italy.

Direct interaction between intrinsically disordered proteins (IDPs) is often difficult to characterize hampering the elucidation of their binding mechanism. Particularly challenging is the study of fuzzy complexes, in which the intrinsically disordered proteins or regions retain conformational freedom within the assembly. To date, nuclear magnetic resonance spectroscopy has proven to be one of the most powerful techniques to characterize at the atomic level intrinsically disordered proteins and their interactions, including those cases where the formed complexes are highly dynamic. Read More

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November 2020

Efficacy of a novel double-controlled oncolytic adenovirus driven by the Ki67 core promoter and armed with IL-15 against glioblastoma cells.

Cell Biosci 2020 27;10:124. Epub 2020 Oct 27.

Brain Tumor Research Center, Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100070 P.R. China.

Background: Glioblastoma (GBM) is an immunosuppressive, highly vascular and devastating malignant brain tumor. Even with progressive combination treatment that includes surgery, radiotherapy, and chemotherapy, the prognosis for GBM patients is still extremely poor. Oncolytic adenovirus (OAd) can specifically replicate in GBM cells, permitting the rapid copy of the therapeutic genes it carries. Read More

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October 2020

Serinol-Based Benzoic Acid Esters as New Scaffolds for the Development of Adenovirus Infection Inhibitors: Design, Synthesis, and Biological Evaluation.

ACS Infect Dis 2020 Oct 19. Epub 2020 Oct 19.

Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, E41013 Seville, Spain.

Over the years, human adenovirus (HAdV) has progressively been recognized as a significant viral pathogen. Traditionally associated with self-limited respiratory, gastrointestinal, and conjunctival infections, mainly in immunocompromised patients, HAdV is currently considered to be a pathogen presenting significant morbidity and mortality in both immunosuppressed and otherwise healthy individuals. Currently available therapeutic options are limited because of their lack of effectivity and related side effects. Read More

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October 2020

Cell-to-cell and genome-to-genome variability of adenovirus transcription tuned by the cell cycle.

J Cell Sci 2020 Nov 9;134(5). Epub 2020 Nov 9.

Department of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland

In clonal cultures, not all cells are equally susceptible to virus infection, and the mechanisms underlying this are poorly understood. Here, we developed image-based single-cell measurements to scrutinize the heterogeneity of adenovirus (AdV) infection. AdV delivers, transcribes and replicates a linear double-stranded DNA genome in the nucleus. Read More

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November 2020

Structural Determinants within the Adenovirus Early Region 1A Protein Spacer Region Necessary for Tumorigenesis.

J Virol 2020 10 14;94(21). Epub 2020 Oct 14.

Institute for Cancer and Genetic Sciences, The Medical School, University of Birmingham, Birmingham, United Kingdom.

It has long been established that group A human adenoviruses (HAdV-A12, -A18, and -A31) can cause tumors in newborn rodents, with tumorigenicity related to the presence of a unique spacer region located between conserved regions 2 and 3 within the HAdV-A12 early region 1A (E1A) protein. Group B adenoviruses are weakly oncogenic, whereas most of the remaining human adenoviruses are nononcogenic. In an attempt to understand better the relationship between the structure of the AdE1A spacer region and oncogenicity of HAdVs, the structures of synthetic peptides identical or very similar to the adenovirus 12 E1A spacer region were determined and found to be α-helical using nuclear magnetic resonance (NMR) spectroscopy. Read More

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October 2020

Anti-tumor effect of a dual cancer-specific recombinant adenovirus on ovarian cancer cells.

Exp Cell Res 2020 11 20;396(1):112185. Epub 2020 Aug 20.

Institute of Military Veterinary Medicine, Academy of Military Medical Science, Changchun, 130122, PR China; Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, 130021, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, PR China. Electronic address:

Background: Apoptin can specifically kill cancer cells but has no toxicity to normal cells. Human telomerase reverse transcriptase (hTERT) acts as a tumor-specific promoter, triggering certain genes to replicate or express only in tumor cells, conferring specific replication and killing abilities. This study aimed at investigating the anticancer potential of the recombinant adenovirus Ad-apoptin-hTERTp-E1a (Ad-VT) in ovarian cancer treatment. Read More

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November 2020

Effect of brincidofovir on adenovirus and A549 cells transcriptome profiles.

Antiviral Res 2020 10 5;182:104872. Epub 2020 Aug 5.

Université de Paris, INSERM U976, Insight Team, F-75010, Paris, France; Assistance-Publique des Hôpitaux de Paris, Microbiology Department, Virology Unit, Saint Louis Hospital, F-75010, Paris, France. Electronic address:

Objectives: Human adenovirus (HAdV) infections are associated with a high morbidity and mortality in transplant patients requiring the use of antiviral treatments. Brincidofovir (BCV), a cytidine analog, inhibits HAdV replication through viral DNA elongation termination and likely through other mechanisms. To elucidate if BCV regulates cellular antiviral pathways, we analyzed its impact on HAdV-infected and non-HAdV-infected lung epithelial cells. Read More

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October 2020

Absent in melanoma 2 enhances anti-tumour effects of CAIX promotor controlled conditionally replicative adenovirus in renal cancer.

J Cell Mol Med 2020 09 29;24(18):10744-10755. Epub 2020 Jul 29.

Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, China.

Conditionally replicative adenoviruses (CRAds) were promising approach for solid tumour treatment, but its oncolytic efficiency and toxicity are still not satisfactory for further clinical application. Here, we developed the CAIX promotor (CAIX )-controlled CRAd armed with a tumour suppressor absent in melanoma 2 (AIM2) to enhance its oncolytic potency. The CAIX -AIM2 adenoviruses (Ad-CAIX -AIM2) could efficiently express E1A and AIM2 in renal cancer cells. Read More

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September 2020

Inhibition of Human Adenovirus Replication by the Importin α/β1 Nuclear Import Inhibitor Ivermectin.

J Virol 2020 08 31;94(18). Epub 2020 Aug 31.

Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada

Human adenoviruses (HAdV) are ubiquitous within the human population and comprise a significant burden of respiratory illnesses worldwide. Pediatric and immunocompromised individuals are at particular risk for developing severe disease; however, no approved antiviral therapies specific to HAdV exist. Ivermectin is an FDA-approved broad-spectrum antiparasitic drug that also exhibits antiviral properties against a diverse range of viruses. Read More

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Multiple domains in the 50 kDa form of E4F1 regulate promoter-specific repression and E1A trans-activation.

Authors:
Robert J Rooney

Gene 2020 Sep 11;754:144882. Epub 2020 Jun 11.

Department of Genetics, Duke University Medical Center, Durham, NC, USA. Electronic address:

The 50 kDa N-terminal product of the cellular transcription factor E4F1 (p50E4F1) mediates E1A289R trans-activation of the adenovirus E4 gene, and suppresses E1A-mediated transformation by sensitizing cells to cell death. This report shows that while both E1A289R and E1A243R stimulate p50E4F1 DNA binding activity, E1A289R trans-activation, as measured using GAL-p50E4F1 fusion proteins, involves a p50E4F1 transcription regulatory (TR) region that must be promoter-bound and is dependent upon E1A CR3, CR1 and N-terminal domains. Trans-activation is promoter-specific, as GAL-p50E4F1 did not stimulate commonly used artificial promoters and was strongly repressive when competing against GAL-VP16. Read More

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September 2020

Differential Effects of Human Adenovirus E1A Protein Isoforms on Aerobic Glycolysis in A549 Human Lung Epithelial Cells.

Viruses 2020 06 3;12(6). Epub 2020 Jun 3.

Department of Microbiology and Immunology, The University of Western Ontario, London, ON N6A 3K7, Canada.

Viruses alter a multitude of host-cell processes to create a more optimal environment for viral replication. This includes altering metabolism to provide adequate substrates and energy required for replication. Typically, viral infections induce a metabolic phenotype resembling the Warburg effect, with an upregulation of glycolysis and a concurrent decrease in cellular respiration. Read More

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Oncolytic Adenovirus Expressing ST13 Increases Antitumor Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Against Pancreatic Ductal Adenocarcinoma.

Hum Gene Ther 2020 08 30;31(15-16):891-903. Epub 2020 Jun 30.

College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, P.R. China.

Oncolytic adenoviruses (OAds) are promising agents for cancer therapy, representing a novel therapeutic strategy for pancreatic ductal adenocarcinoma (PDAC). However, there are challenges associated with the successful use of an OAd alone, involving the security of the viral vector and screening of an effective antitumor gene. In the present study, a novel OAd CD55-ST13-tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was constructed in which the dual therapeutic genes ST13 and TRAIL were inserted, featuring the carcinoembryonic antigen (CEA) as a promoter to control E1A and deletion of the 55 kDa E1B gene. Read More

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Adenovirus-mediated specific tumor tagging facilitates CAR-T therapy against antigen-mismatched solid tumors.

Cancer Lett 2020 09 23;487:1-9. Epub 2020 May 23.

Center for New Drug Safety Evaluation and Research, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, 211198, PR China. Electronic address:

Chimeric antigen receptor T (CAR-T) therapy faces at least two major obstacles in solid tumors, including to find specific antigen among the heterogeneous tumor mass and to overcome the inhibitory microenvironment. Developing novel strategies to overcome these difficulties has been the burning issue in immunotherapy. Here we came up with the concept of tagging cancer cells by tumor-targeting adenoviruses (Ad). Read More

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September 2020

Design, validation and evaluation of a SYBR green-based quantitative PCR array for comprehensive analysis of adenovirus type 5 transcriptional patterns.

J Virol Methods 2020 07 12;281:113880. Epub 2020 May 12.

Department of Microbiology, Immunology, and Parasitology, USA; Department of Ophthalmology, USA; The Stanley S. Scott Cancer Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA; The Louisiana Vaccine Center, New Orleans, LA, 70112, USA. Electronic address:

The adenoviral genome encodes coordinately expressed early and late gene transcriptional units that specify a complex collection of extensively spliced overlapping mRNAs. These complexities confound the generation of compatible, validated and optimized qPCR assays that permit comprehensive evaluation of adenoviral transcription. We have developed and evaluated a compilation of qPCR assays that represent the majority of the human adenovirus 5 (hAdV5) genome and allow for absolute and relative quantification of transcriptional activity. Read More

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Advantages of Using Paclitaxel in Combination with Oncolytic Adenovirus Utilizing RNA Destabilization Mechanism.

Cancers (Basel) 2020 May 12;12(5). Epub 2020 May 12.

Department of Molecular Oncology, Hokkaido University Faculty of Dental Medicine and Graduate School of Biomedical Science and Engineering, Sapporo 060-8638, Japan.

Oncolytic virotherapy is a novel approach to cancer therapy. Ad-ARE is a conditionally replicative adenovirus engineered by inserting AU-rich elements (ARE) in the 3'-untranslated region of the E1A gene. In this study, we examined the oncolytic activity of Ad-ARE and used it in a synergistic combination with the chemotherapeutic agent paclitaxel (PTX) for treating cancer cells. Read More

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Conditionally Replicative Adenovirus Controlled by the Stabilization System of AU-Rich Elements Containing mRNA.

Cancers (Basel) 2020 May 11;12(5). Epub 2020 May 11.

Department of Vascular Biology and Molecular Pathology, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8586, Japan.

AU-rich elements (AREs) are RNA elements that enhance the rapid decay of mRNAs, including those of genes required for cell growth and proliferation. HuR, a member of the embryonic lethal abnormal vision (ELAV) family of RNA-binding proteins, is involved in the stabilization of ARE-mRNA. The level of HuR in the cytoplasm is up-regulated in most cancer cells, resulting in the stabilization of ARE-mRNA. Read More

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The Effect of PEI-Mediated E1A on the Radiosensitivity of Hepatic Carcinoma Cells.

Asian Pac J Cancer Prev 2020 Apr 1;21(4):911-917. Epub 2020 Apr 1.

Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.

Objective: The study was undertaken to investigate the effects of polyethyleneimine (PEI)-mediated adenovirus 5 early region 1A (E1A) on radiosensitivity of human hepatic carcinoma cell in vitro and to disclosure the underlying mechanism.

Materials And Methods: Human hepatic carcinoma SMMC-7721 cell line was transfected with E1A gene using PEI vector. Untransfected cells (SMMC-7721 group), cells transfected with blank-vector (SMMC-7721-vect group), and cells transfected with E1A gene (SMMC-7721-E1A group) were treated with 6 MV X-ray irradiation at doses of 0, 1, 2, 4, 8 and Gy, respectively. Read More

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