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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Conclusion: We reported the synergistic anti-tumor efficacy of ZD55-IL-24 and DTX on prostate cancer. Our results suggest that chemotherapy combined with oncolytic adenovirus mediated gene therapy is a promising strategy for the treatment of advanced prostate cancer.
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
Publication date: Available online 23 October 2018Source: Journal of Theoretical BiologyAuthor(s): Michael A. Boemo, Helen M. ByrneAbstractTumour hypoxia has long presented a challenge for cancer therapy: Poor vascularisation in hypoxic regions hinders both the delivery of chemotherapeutic agents and the response to radiotherapy, and hypoxic cancer cells that survive treatment can trigger tumour regrowth after treatment has ended. Tumour-associated macrophages are attractive vehicles for drug delivery because they localise in hypoxic areas of the tumour. In this paper, we derive a mathematical model for the infiltration of...
Source: Journal of Theoretical Biology - Category: Biology Source Type: research
Paolo Ciana Oncolytic viruses (OV) are engineered to infect, replicate in and kill cancer cells. Currently, the OV therapeutic approach is mainly restricted to neoplasia amenable to direct local administration of viral particles, while the possibility of a systemic delivery of cancer-tropic viruses would extend the OV application to the treatment of metastatic neoplasia. Herein, we applied in vivo/ex vivo imaging to demonstrate that cancer tropism is achieved when OV are encapsulated inside extracellular vesicles (EV) administered intravenously (i.v.), but not when injected intraperitoneally (i.p.). Moreover, we show t...
Source: Viruses - Category: Virology Authors: Tags: Brief Report Source Type: research
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
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