Adenovirus dampens host DNA damage response -- implications for control and cancer therapy

(PLOS) Adenoviruses (Ad) are everywhere, and while they pose limited threat in individuals with healthy immune systems, they cause significant disease burden in immunocompromised patients. A study published on Feb. 11 in PLOS Pathogens reports on a new mechanism by which the virus interferes with the host's ability to detect and eliminate viral intruders.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news

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Abstract In this review, we specifically focus on genetic modifications of oncolytic adenovirus 5 (Ad5)-based vectors that enhance replication, oncolysis/spread, and virus-mediated tumor immunosurveillance. The finding of negative regulation of minor core protein V by SUMOylation led to the identification of amino acid residues, which when mutated increase adenovirus replication and progeny yield. Suppression of Dicer and/or RNAi pathway with shRNA or p19 tomato bushy stunt protein also results in significant enhancement of adenovirus replication and progeny yield. Truncation mutations in E3-19K or i-leader sequen...
Source: Gene - Category: Genetics & Stem Cells Authors: Tags: Gene Source Type: research
Abstract The cellular internalization (infection of cells) of adenovirus 5 (Ad5) is mediated by the initial attachment of the globular knob domain of the capsid fiber protein to the cell surface coxsackievirus and adenovirus receptor (CAR), then followed by the interaction of the virus penton base proteins with cellular integrins. In tumors, there is a substantial intra- and intertumoral variability in CAR expression. The CAR-negative cells generally exhibit very low infectability. Since the fiber knob is a primary mediator of Ad5 binding to the cell surface, improved infectivity of Ad5-based vectors as oncolytic ...
Source: Virus Research - Category: Virology Authors: Tags: Virus Res Source Type: research
Publication date: 7 October 2018Source: Journal of Theoretical Biology, Volume 454Author(s): Adrianne Jenner, Chae-Ok Yun, Arum Yoon, Peter S. Kim, Adelle C.F. CosterAbstractThe use of viruses as a cancer treatment is becoming increasingly more robust; however, there is still a long way to go before a completely successful treatment is formulated. One major challenge in the field is to select which virus, out of a burgeoning number of oncolytic viruses and engineered derivatives, can maximise both treatment spread and anticancer cytotoxicity. To assist in solving this problem, an in-depth understanding of the virus-tumour ...
Source: Journal of Theoretical Biology - Category: Biology Source Type: research
Authors: Hulin-Curtis SL, Davies JA, Jones R, Hudson E, Hanna L, Chester JD, Parker AL Abstract Ovarian cancer is often termed a silent killer due to the late onset of symptoms. Whilst patients initially respond to chemotherapy, they rapidly develop chemo-resistance. Oncolytic adenoviruses (OAds) are promising anti-cancer agents engineered to "hijack" the unique molecular machinery of cancer cells enabling tumour-selective viral replication. This allows spread to adjacent cells and amplification of oncolysis within the tumour. OAds represent an excellent opportunity for ovarian cancer therapy via intra-pe...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Publication date: 7 October 2018 Source:Journal of Theoretical Biology, Volume 454 Author(s): Adrianne Jenner, Chae-Ok Yun, Arum Yoon, Peter S. Kim, Adelle C.F. Coster The use of viruses as a cancer treatment is becoming increasingly more robust; however, there is still a long way to go before a completely successful treatment is formulated. One major challenge in the field is to select which virus, out of a burgeoning number of oncolytic viruses and engineered derivatives, can maximise both treatment spread and anticancer cytotoxicity. To assist in solving this problem, an in-depth understanding of the virus-tumour inter...
Source: Journal of Theoretical Biology - Category: Biology Source Type: research
CONCLUSIONS:  Oncolytic Ad5NULL-A20 virotherapies represent an excellent vector for local and systemic targeting of αvβ6-over-expressing cancers, and exciting platforms for tumour selective over-expression of therapeutic anti-cancer modalities, including immune checkpoint inhibitors. PMID: 29798908 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Conclusions: These results indicate that expression of NIS under control of the midkine promoter can likely be used to achieve cancer-specific expression of NIS in lung cancer. In combination with radioiodine therapy, this strategy is a possible method of lung cancer therapy.
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Basic Science Posters (Oncology) Source Type: research
(Umea University) An international team of researchers led by professor Niklas Arnberg at Ume å University, shows that adenovirus binds to a specific type of carbohydrate that is overexpressed on certain types of cancer cells. The discovery opens up new opportunities for the development of virus-based cancer therapy. The study is published in the latest issue of the scientific journal " Proceedings of the National Academy of Sciences of USA " , PNAS PNAS April 19, 2018. 201716900
Source: EurekAlert! - Biology - Category: Biology Source Type: news
Authors: Liu Z, Sun X, Xiao S, Lin Y, Li C, Hao N, Zhou M, Deng R, Ke S, Zhong Z Abstract Liver cancer is a fatal disease with limited therapy options. The recombinant adenovirus expressing tumor-suppressor gene of PTEN (Ad5-PTEN) showed effective antitumor activity against liver cancer. However, its disadvantages produced great limitation on its application, especially its nonspecific and toxicity to normal cells and tissues. The epithelial cell adhesion molecule (EpCAM) is over-expressed in some liver cancer cells and an RNA aptamer EpDT3 could specially target to EpCAM-positive cells. Based on this founding, we ...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
(University of Zurich) Scientists from the University of Zurich have redesigned an adenovirus for use in cancer therapy. To achieve this they developed a new protein shield that hides the virus and protects it from being eliminated. Adapters on the surface of the virus enable the reconstructed virus to specifically infect tumor cells.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
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