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  1. Fulltext Viral persistence in colorectal cancer cells infected by Newcastle disease virus
    Chia SL, Yusoff K, Shafee N
    Virol J, 2014 May 16;11:91.
    PMID: 24886301 DOI: 10.1186/1743-422X-11-91
    BACKGROUND: Newcastle disease virus (NDV), a single-stranded RNA virus of the family Paramyxoviridae, is a candidate virotherapy agent in cancer treatment. Promising responses were observed in clinical studies. Despite its high potential, the possibility of the virus to develop a persistent form of infection in cancer cells has not been investigated. Occurrence of persistent infection by NDV in cancer cells may cause the cells to be less susceptible to the virus killing. This would give rise to a population of cancer cells that remains viable and resistant to treatment.

    RESULTS: During infection experiment in a series of colorectal cancer cell lines, we adventitiously observed a development of persistent infection by NDV in SW480 cells, but not in other cell lines tested. This cell population, designated as SW480P, showed resistancy towards NDV killing in a re-infection experiment. The SW480P cells retained NDV genome and produced virus progeny with reduced plaque forming ability.

    CONCLUSION: These observations showed that NDV could develop persistent infection in cancer cells and this factor needs to be taken into consideration when using NDV in clinical settings.

    Matched MeSH terms: Oncolytic Viruses/growth & development*; Oncolytic Viruses/isolation & purification
  2. Oncolytic viruses as a promising therapeutic strategy against the detrimental health impacts of air pollution: The case of glioblastoma multiforme
    Kazemi Shariat Panahi H, Dehhaghi M, Lam SS, Peng W, Aghbashlo M, Tabatabaei M, et al.
    Semin Cancer Biol, 2022 Nov;86(Pt 3):1122-1142.
    PMID: 34004331 DOI: 10.1016/j.semcancer.2021.05.013
    Human livelihood highly depends on applying different sources of energy whose utilization is associated with air pollution. On the other hand, air pollution may be associated with glioblastoma multiforme (GBM) development. Unlike other environmental causes of cancer (e.g., irradiation), air pollution cannot efficiently be controlled by geographical borders, regulations, and policies. The unavoidable exposure to air pollution can modify cancer incidence and mortality. GBM treatment with chemotherapy or even its surgical removal has proven insufficient (100% recurrence rate; patient's survival mean of 15 months; 90% fatality within five years) due to glioma infiltrative and migratory capacities. Given the barrage of attention and research investments currently plowed into next-generation cancer therapy, oncolytic viruses are perhaps the most vigorously pursued. Provision of an insight into the current state of the research and future direction is essential for stimulating new ideas with the potentials of filling research gaps. This review manuscript aims to overview types of brain cancer, their burden, and different causative agents. It also describes why air pollution is becoming a concerning factor. The different opinions on the association of air pollution with brain cancer are reviewed. It tries to address the significant controversy in this field by hypothesizing the air-pollution-brain-cancer association via inflammation and atopic conditions. The last section of this review deals with the oncolytic viruses, which have been used in, or are still under clinical trials for GBM treatment. Engineered adenoviruses (i.e., DNX-2401, DNX-2440, CRAd8-S-pk7 loaded Neural stem cells), herpes simplex virus type 1 (i.e., HSV-1 C134, HSV-1 rQNestin34.5v.2, HSV-1 G207, HSV-1 M032), measles virus (i.e., MV-CEA), parvovirus (i.e., ParvOryx), poliovirus (i.e., Poliovirus PVSRIPO), reovirus (i.e., pelareorep), moloney murine leukemia virus (i.e., Toca 511 vector), and vaccinia virus (i.e., vaccinia virus TG6002) as possible life-changing alleviations for GBM have been discussed. To the best of our knowledge, this review is the first review that comprehensively discusses both (i) the negative/positive association of air pollution with GBM; and (ii) the application of oncolytic viruses for GBM, including the most recent advances and clinical trials. It is also the first review that addresses the controversies over air pollution and brain cancer association. We believe that the article will significantly appeal to a broad readership of virologists, oncologists, neurologists, environmentalists, and those who work in the field of (bio)energy. Policymakers may also use it to establish better health policies and regulations about air pollution and (bio)fuels exploration, production, and consumption.
    Matched MeSH terms: Oncolytic Viruses*
  3. Fulltext Safety and clinical usage of newcastle disease virus in cancer therapy
    Lam HY, Yeap SK, Pirozyan MR, Omar AR, Yusoff K, Suraini AA, et al.
    J Biomed Biotechnol, 2011;2011:718710.
    PMID: 22131816 DOI: 10.1155/2011/718710
    Newcastle disease virus (NDV) is an avian virus that causes deadly infection to over 250 species of birds, including domestic and wild-type, thus resulting in substantial losses to the poultry industry worldwide. Many reports have demonstrated the oncolytic effect of NDV towards human tumor cells. The interesting aspect of NDV is its ability to selectively replicate in cancer cells. Some of the studies have undergone human clinical trials, and favorable results were obtained. Therefore, NDV strains can be the potential therapeutic agent in cancer therapy. However, investigation on the therapeutic perspectives of NDV, especially human immunological effects, is still ongoing. This paper provides an overview of the current studies on the cytotoxic and anticancer effect of NDV via direct oncolysis effects or immune stimulation. Safety of NDV strains applied for cancer immunotherapy is also discussed in this paper.
    Matched MeSH terms: Oncolytic Viruses/genetics; Oncolytic Viruses/immunology*
  4. Towards targeted cancer therapy: Aptamer or oncolytic virus?
    Tan KX, Danquah MK, Sidhu A, Ongkudon CM, Lau SY
    Eur J Pharm Sci, 2017 Jan 01;96:8-19.
    PMID: 27593990 DOI: 10.1016/j.ejps.2016.08.061
    Cancer is a leading cause of global mortality. Whilst anticancer awareness programs have increased significantly over the years, scientific research into the development of efficient and specific drugs to target cancerous cells for enhanced therapeutic effects has not received much clinical success. Chemotherapeutic agents are incapable of acting specifically on cancerous cells, thus causing low therapeutic effects accompanied by toxicity to surrounding normal tissues. The search for smart, highly specific and efficient cancer treatments and delivery systems continues to be a significant research endeavor. Targeted cancer therapy is an evolving treatment approach with great promise in enhancing the efficacy of cancer therapies via the delivery of therapeutic agents specifically to and into desired tumor cells using viral or non-viral targeting elements. Viral oncotherapy is an advanced cancer therapy based on the use of oncolytic viruses (OV) as elements to specifically target, replicate and kill malignant cancer cells selectively without affecting surrounding healthy cells. Aptamers, on the other hand, are non-viral targeting elements that are single-stranded nucleic acids with high specificity, selectivity and binding affinity towards their cognate targets. Aptamers have emerged as a new class of bioaffinity targeting elements can be generated and molecularly engineered to selectively bind to diverse targets including proteins, cells and tissues. This article discusses, comparatively, the potentials and impacts of both viral and aptamer-mediated targeted cancer therapies in advancing conventional drug delivery systems through enhanced target specificity, therapeutic payload, bioavailability of the therapeutic agents at the target sites whilst minimizing systemic cytotoxicity. This article emphasizes on effective site-directed targeting mechanisms and efficacy issues that impact on clinical applications.
    Matched MeSH terms: Oncolytic Viruses*
  5. Fulltext Newcastle disease virus strain AF2240 as an oncolytic virus: A review
    Kalyanasundram J, Hamid A, Yusoff K, Chia SL
    Acta Trop, 2018 Jul;183:126-133.
    PMID: 29626432 DOI: 10.1016/j.actatropica.2018.04.007
    The discovery of tumour selective virus-mediated apoptosis marked the birth of an alternative cancer treatment in the form of oncolytic viruses. Even though, its oncolytic efficiency was demonstrated more than 50 years ago, safety concerns which resulted from mild to lethal side effects hampered the progress of oncolytic virus research. Since the classical oncolytic virus studies rely heavily on its natural oncolytic ability, virus manipulation was limited, thereby, restricted efforts to improve its safety. In order to circumvent such restriction, experiments involving non-human viruses such as the avian Newcastle disease virus (NDV) was conducted using cultured cells, animal models and human subjects. The corresponding reports on its significant tumour cytotoxicity along with impressive safety profile initiated immense research interest in the field of oncolytic NDV. The varying degree of oncolytic efficiency and virulency among NDV strains encouraged researchers from all around the world to experiment with their respective local NDV isolates in order to develop an oncolytic virus with desirable characteristics. Such desirable features include high tumour-killing ability, selectivity and low systemic cytotoxicity. The Malaysian field outbreak isolate, NDV strain AF2240, also currently, receives significant research attention. Apart from its high cytotoxicity against tumour cells, this strain also provided fundamental insight into NDV-mediated apoptosis mechanism which involves Bax protein recruitment as well as death receptor engagement. Studies on its ability to selectively induce apoptosis in tumour cells also resulted in a proposed p38 MAPK/NF-κB/IκBα pathway. The immunogenicity of AF2240 was also investigated through PBMC stimulation and macrophage infection. In addition, the enhanced oncolytic ability of this strain under hypoxic condition signifies its dynamic tumour tropism. This review is aimed to introduce and discuss the aforementioned details of the oncolytic AF2240 strain along with its current challenges which outlines the future research direction of this virus.
    Matched MeSH terms: Oncolytic Viruses/genetics*
  6. Turning cold tumours hot: oncolytic virotherapy gets up close and personal with other therapeutics at the 11th Oncolytic Virus Conference
    Dyer A, Baugh R, Chia SL, Frost S, Iris, Jacobus EJ, et al.
    Cancer Gene Ther, 2019 03;26(3-4):59-73.
    PMID: 30177818 DOI: 10.1038/s41417-018-0042-1
    The 11th International Oncolytic Virus Conference (IOVC) was held from April 9-12, 2018 in Oxford, UK. This is part of the high-profile academic-led series of meetings that was started back in 2002 by Steve Russell and John Bell, with most of the previous meetings being held in North America (often in Banff). The conference brought together many of the major players in oncolytic virotherapy from all over the world, addressing all stages of research and development-from aspects of basic science and cellular immunology all the way through to early- and late-phase clinical trials. The meeting welcomed 352 delegates from 24 countries. The top seven delegate countries, namely, the UK, US, Canada, The Netherlands, Germany, Japan and South Korea, contributed 291 delegates while smaller numbers coming from Australia, Austria, Bulgaria, China, Finland, France, Iraq, Ireland, Israel, Italy, Latvia, Malaysia, Poland, Slovenia, Spain, Sweden and Switzerland. Academics comprised about half of the attendees, industry 30% and students 20%. The next IOVC is scheduled to be held on Vancouver Island in autumn 2019. Here we share brief summaries of the oral presentations from invited speakers and proffered papers in the different subtopics presented at IOVC 2018.
    Matched MeSH terms: Oncolytic Viruses/immunology*
  7. Fulltext Group B adenovirus enadenotucirev infects polarised colorectal cancer cells efficiently from the basolateral surface expected to be encountered during intravenous delivery to treat disseminated cancer
    Chia SL, Lei J, Ferguson DJP, Dyer A, Fisher KD, Seymour LW
    Virology, 2017 05;505:162-171.
    PMID: 28260622 DOI: 10.1016/j.virol.2017.02.011
    Enadenotucirev (EnAd) is a group B oncolytic adenovirus developed for systemic delivery and currently undergoing clinical evaluation for advanced cancer therapy. For differentiated carcinomas, systemic delivery would likely expose virus particles to the basolateral surface of cancer cells rather than the apical surface encountered during natural infection. Here, we compare the ability of EnAd and adenovirus type-5 (Ad5) to infect polarised colorectal carcinoma cells from the apical or basolateral surfaces. Whereas Ad5 infection was more efficient via the apical than basolateral surface, EnAd readily infected cells from either surface. Progeny particles from EnAd were released preferentially via the apical surface for all cell lines and routes of infection. These data further support the utility of group B adenoviruses for systemic delivery and suggest that progeny virus are more likely to be released into the tumour rather than back through the basolateral surface into the blood stream.
    Matched MeSH terms: Oncolytic Viruses/classification; Oncolytic Viruses/metabolism*
  8. Fulltext Prospective Therapeutic Strategies for Cervical Cancer
    Nor Aini Lubis, Mhd Zain, Mohd Nasharudin, Razak, Mariatulqabtiah, Abdul Razak
    The Pertanika Journal of Scholarly Research Reviews, 2019;5(1):10-19.
    MyJurnal
    Cervical cancer is one of the leading causal cancer-related fatalities in the world. Cervical cancer patients can be treated by conventional treatment such as surgery, radiotherapy, chemotherapy, medications and combination treatments. Currently, more targeted treatments are being developed to cure cervical cancer. The treatments include immunotherapy, virotherapy and gene therapy which will be discussed in this paper. In immunotherapy, the synergy of CTLA-4 suppression and PD-1/PDL-1 immune checkpoint inhibition targeting their corresponding pathways enhanced the human immune system resulting a promising treatment effects. Oncolytic viruses such as Newcastle disease virus selectively infect and kill cancerous cells/tissues without harming normal cells/tissues. This character has made them a potential modality in combating cancer which popularly known as oncolytic virotherapy. Gene therapy delivers modified genetic materials to the target cancer cells via viral and non-viral vectors. It is used to target the abnormal gene, to increase cells’ susceptibility towards drugs or conventional therapy, to induce tumour cells apoptosis, to enhance tumour cell immunogenicity recognition and to inhibit the oncogene expression. The objective of this minireview is to add to the general knowledge on aforementioned therapeutic strategies against cervical cancer.
    Matched MeSH terms: Oncolytic Viruses
  9. Fulltext Zika Virus as Oncolytic Therapy for Brain Cancer: Myth or Reality?
    Su KY, Balasubramaniam VRMT
    Front Microbiol, 2019;10:2715.
    PMID: 31824472 DOI: 10.3389/fmicb.2019.02715
    The ability of self-replicating oncolytic viruses (OVs) to preferentially infect and lyse cancer cells while stimulating anti-tumor immunity of the host strongly indicates its value as a new field of cancer therapeutics to be further explored. The emergence of Zika virus (ZIKV) as a global health threat due to its recent outbreak in Brazil has caught the attention of the scientific community and led to the discovery of its oncolytic potential for the treatment of glioblastoma multiforme (GBM), the most common and fatal brain tumor with poor prognosis. Herein, we evaluate the neurotropism of ZIKV relative to the receptor tyrosine kinase AXL and its ligand Gas6 in viral entry and the RNA-binding protein Musashi-1 (MSI1) in replication which are also overexpressed in GBM, suggesting its potential for specific targeting of the tumor. Additionally, this review discusses genetic modifications performed to enhance safety and efficacy of ZIKV as well as speculates future directions for the OV therapy.
    Matched MeSH terms: Oncolytic Viruses
  10. Fulltext Viability reduction and Rac1 gene downregulation of heterogeneous ex-vivo glioma acute slice infected by the oncolytic Newcastle disease virus strain V4UPM
    Mustafa Z, Shamsuddin HS, Ideris A, Ibrahim R, Jaafar H, Ali AM, et al.
    Biomed Res Int, 2013;2013:248507.
    PMID: 23586025 DOI: 10.1155/2013/248507
    Oncolytic viruses have been extensively evaluated for anticancer therapy because this virus preferentially infects cancer cells without interfering with normal cells. Newcastle Disease Virus (NDV) is an avian virus and one of the intensively studied oncolytic viruses affecting many types of cancer including glioma. Nevertheless, the capability of NDV infection on heterogeneous glioma tissue in a cerebrospinal fluid atmosphere has never been reported. Recently, Rac1 is reported to be required for efficient NDV replication in human cancer cells and established a link between tumourigenesis and sensitivity to NDV. Rac1 is a member of the Rho GTPases involved in the regulation of the cell migration and cell-cycle progression. Rac1 knockdown leads to significant inhibition of viral replication. In this work, we demonstrated that NDV treatment led to significant reduction of tumour tissue viability of freshly isolated heterogeneous human brain tumour slice, known as an ex vivo glioma acute slice (EGAS). Analysis of gene expression indicated that reduced tissue viability was associated with downregulation of Rac1. However, the viability reduction was not persistent. We conclude that NDV treatment induced EGAS viability suppression, but subsequent downregulation of Rac1 gene may reduce the NDV replication and lead to regrowth of EGAS tissue.
    Matched MeSH terms: Oncolytic Viruses/genetics*
  11. Virotherapy: Current Trends and Future Prospects for Treatment of Colon and Rectal Malignancies
    Lee CL, Veeramani S, Molouki A, Lim SHE, Thomas W, Chia SL, et al.
    Cancer Invest, 2019;37(8):393-414.
    PMID: 31502477 DOI: 10.1080/07357907.2019.1660887
    Colorectal cancer (CRC) is one of the most common malignancies. In recent decades, early diagnosis and conventional therapies have resulted in a significant reduction in mortality. However, late stage metastatic disease still has very limited effective treatment options. There is a growing interest in using viruses to help target therapies to tumour sites. In recent years the evolution of immunotherapy has emphasised the importance of directing the immune system to eliminate tumour cells; we aim to give a state-of-the-art over-view of the diverse viruses that have been investigated as potential oncolytic agents for the treatment of CRC.
    Matched MeSH terms: Oncolytic Viruses/pathogenicity*
  12. Fulltext Newcastle disease virus degrades HIF-1α through proteasomal pathways independent of VHL and p53
    Abd-Aziz N, Stanbridge EJ, Shafee N
    J Gen Virol, 2016 Dec;97(12):3174-3182.
    PMID: 27902314 DOI: 10.1099/jgv.0.000623
    Newcastle disease virus (NDV) is a candidate agent for oncolytic virotherapy. Despite its potential, the exact mechanism of its oncolysis is still not known. Recently, we reported that NDV exhibited an increased oncolytic activity in hypoxic cancer cells. These types of cells negatively affect therapeutic outcome by overexpressing pro-survival genes under the control of the hypoxia-inducible factor (HIF). HIF-1 is a heterodimeric transcriptional factor consisting of a regulated α (HIF-1α) and a constitutive β subunit (HIF-1β). To investigate the effects of NDV infection on HIF-1α in cancer cells, the osteosarcoma (Saos-2), breast carcinoma (MCF-7), colon carcinoma (HCT116) and fibrosarcoma (HT1080) cell lines were used in the present study. Data obtained showed that a velogenic NDV infection diminished hypoxia-induced HIF-1α accumulation, leading to a decreased activation of its downstream target gene, carbonic anhydrase 9. This NDV-induced downregulation of HIF-1α occurred post-translationally and was partially abrogated by proteasomal inhibition. The process appeared to be independent of the tumour suppressor protein p53. These data revealed a correlation between NDV infection and HIF-1α downregulation, which highlights NDV as a promising agent to eliminate hypoxic cancer cells.
    Matched MeSH terms: Oncolytic Viruses/genetics; Oncolytic Viruses/physiology*
  13. Fulltext Regression of solid breast tumours in mice by Newcastle disease virus is associated with production of apoptosis related-cytokines
    Raihan J, Ahmad U, Yong YK, Eshak Z, Othman F, Ideris A
    BMC Cancer, 2019 Apr 04;19(1):315.
    PMID: 30947706 DOI: 10.1186/s12885-019-5516-5
    BACKGROUND: Different strains of Newcastle disease virus (NDV) worldwide proved to have tumouricidal activity in several types of cancer cells. However, the possible anti-cancer activity of Malaysian NDV AF2240 strain and its mechanism of action remains unknown. The ability of cytokine-related apoptosis-inducing NDV AF2240 to treat breast cancer was investigated in the current study.

    METHODS: A total of 90 mice were used and divided into 15 groups, each group comprising of 6 mice. Tumour, body weight and mortality of the mice were determined throughout the experiment, to observe the effect of NDV and NDV + tamoxifen treatments on the mice. In addition, the toxic effect of the treatments was determined through liver function test. In order to elucidate the involvement of cytokine production induced by NDV, a total of six cytokines, i.e. IL-6, IFN-γ, MCP-1, IL-10, IL12p70 and TNF-α were measured using cytometric bead array assay (plasma) and enzyme-linked immunosorbent spot (isolated splenocytes).

    RESULTS: The results demonstrated that 4 T1 breast cancer cells in allotransplanted mice treated with AF2240 showed a noticeable inhibition of tumour growth and induce apoptotic-related cytokines.

    CONCLUSIONS: NDV AF2240 suppression of breast tumour growth is associated with induction of apoptotic-related cytokines. It would be important to further investigate the molecular mechanism underlaying cytokines production by Newcastle disease virus.

    Matched MeSH terms: Oncolytic Viruses*
  14. Newcastle diseases virus strain V4UPM displayed oncolytic ability against experimental human malignant glioma
    Zulkifli MM, Ibrahim R, Ali AM, Aini I, Jaafar H, Hilda SS, et al.
    Neurol Res, 2009 Feb;31(1):3-10.
    PMID: 18937888 DOI: 10.1179/174313208X325218
    Newcastle disease virus (NDV) is a virus of paramyxovirus family and lately has been studied for the treatment of cancer in human. In this study, we successfully determined the oncolysis potential of NDV vaccine, V4UPM tested on the human glioblastoma multiform cell line (DBTRG.05MG) and human glioblastoma astrocytoma cell line (U-87MG) in vitro and in vivo. The V4UPM strain is a modified V4 strain developed as thermostable feed pellet vaccine for poultry.
    Matched MeSH terms: Oncolytic Viruses
  15. Fulltext Targeting bladder cancer stem cells using Newcastle disease virus
    Arcana Thirumorthy, De-Ming Chau, Khatijah Yusoff, Abhi Veerakumarasivam
    Malaysian Journal of Medicine and Health Sciences, 2019;15(108):24-24.
    MyJurnal
    Introduction: Bladder cancer is associated with high risk of tumour recurrence and therapeutic resistance. Cancer stem cells (CSC) within a particular tumour are postulated to drive tumorigenesis and influence tumour behaviour. Recent studies have shown that Newcastle disease virus (NDV) is able to selectively kill and exert a strong oncolytic effect against various cancer types. However little is known about the oncolytic effect of NDV against CSC. In this study, the oncolytic effect of NDV against putative bladder CSC was examined. Methods: Putative bladder CSC was selectively grown in the form of 3D-spheroids from six different bladder cancer cell lines. The spheroid cells were characterised for their stemness properties to ensure that these cells truly represent CSC. This was conducted via the analysis of CSC associated genes and cell surface markers expression. Subsequently, the oncolytic effect of the wild-type NDV-AF2240 strain against the bladder cancer spheroids was investigated. Results: All the spheroids expressed significantly high levels of CSC-associated genes. Flow-cytometry analysis revealed that the expression pattern of the CSC-associated surface markers was different in the spheroid cells; suggesting heterogeneity in the expression signatures of these cells. The infection of spheroids with NDV showed that the NDV was able to target bladder cancer spheroids but there was a spectrum of response across the different spheroids. Intriguingly, NDV was able to persistently infect bladder cancer spheroids that were not sensitive towards NDV infection as the presence of NDV viral genes were detected in the spheroid cells. The NDV persistently infected bladder cancer spheroids were resistant to superinfection and developed an antiviral state by expressing low levels of interferon-beta (IFN-b). NDV persistency of infection affects the process of epithelial to mesenchymal transition (EMT) of cancer cells as the spheroid forming ability of an established NDV persistently infected bladder cancer cell line, EJ28-PI was shown to be impaired. The EJ28-PI cells expressed significantly high levels of the EN2 gene. Knockdown of the EN2 expression reduced the viability of EJ28-PI cells; suggesting a role for EN2 in mediating NDV persistency of infection in cancer cells. Conclusion: Bladder CSC gene expression signatures influence the efficacy of NDV-mediated oncolysis. Our current work is focused on identifying genes and signalling pathways that influence NDV-mediated oncolysis us-ing whole-transcriptomic sequencing. The findings of this study can potentially be used to enhance the efficacy of NDV-mediated oncolysis and accelerate the translation of NDV as an oncotherapeutic agent in the clinic.
    Matched MeSH terms: Oncolytic Viruses
  16. Fulltext Persistent Newcastle disease virus infection in bladder cancer cells is associated with putative pro-survival and anti-viral transcriptomic changes
    Chan LC, Kalyanasundram J, Leong SW, Masarudin MJ, Veerakumarasivam A, Yusoff K, et al.
    BMC Cancer, 2021 May 27;21(1):625.
    PMID: 34044804 DOI: 10.1186/s12885-021-08345-y
    BACKGROUND: Newcastle disease virus (NDV) is an oncolytic virus with excellent selectivity against cancer cells, both in vitro and in vivo. Unfortunately, prolonged in vitro NDV infection results in the development of persistent infection in the cancer cells which are then able to resist NDV-mediated oncolysis. However, the mechanism of persistency of infection remains poorly understood.

    METHODS: In this study, we established persistently NDV-infected EJ28 bladder cancer cells, designated as EJ28P. Global transcriptomic analysis was subsequently carried out by microarray analysis. Differentially expressed genes (DEGs) between EJ28 and EJ28P cells identified by the edgeR program were further analysed by Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) analyses. In addition, the microarray data were validated by RT-qPCR.

    RESULTS: Persistently NDV-infected EJ28 bladder cancer cells were successfully established and confirmed by flow cytometry. Microarray analysis identified a total of 368 genes as differentially expressed in EJ28P cells when compared to the non-infected EJ28 cells. GSEA revealed that the Wnt/β-catenin and KRAS signalling pathways were upregulated while the TGF-β signalling pathway was downregulated. Findings from this study suggest that the upregulation of genes that are associated with cell growth, pro-survival, and anti-apoptosis may explain the survivability of EJ28P cells and the development of persistent infection of NDV.

    CONCLUSIONS: This study provides insights into the transcriptomic changes that occur and the specific signalling pathways that are potentially involved in the development and maintenance of NDV persistency of infection in bladder cancer cells. These findings warrant further investigation and is crucial towards the development of effective NDV oncolytic therapy against cancer.

    Matched MeSH terms: Oncolytic Viruses
  17. Human renal carcinoma cells respond to Newcastle disease virus infection through activation of the p38 MAPK/NF-κB/IκBα pathway
    Ch'ng WC, Abd-Aziz N, Ong MH, Stanbridge EJ, Shafee N
    Cell Oncol (Dordr), 2015 Aug;38(4):279-88.
    PMID: 25930675 DOI: 10.1007/s13402-015-0229-5
    Newcastle disease virus (NDV) is an oncolytic virus that is known to have a higher preference to cancer cells than to normal cells. It has been proposed that this higher preference may be due to defects in the interferon (IFN) responses of cancer cells. The exact mechanism underlying this process, however, remains to be resolved. In the present study, we examined the antiviral response towards NDV infection of clear cell renal cell carcinoma (ccRCC) cells. ccRCC is associated with mutations of the von Hippel-Lindau tumor suppressor gene VHL, whose protein product is important for eliciting cellular responses to changes in oxygen levels. The most common first line treatment strategy of ccRCC includes IFN. Unfortunately, most ccRCC cases are diagnosed at a late stage and often are resistant to IFN-based therapies. Alternative treatment approaches, including virotherapy using oncolytic viruses, are currently being investigated. The present study was designed to investigate the mechanistic pathways underlying the response of ccRCC cells to oncolytic NDV infection.
    Matched MeSH terms: Oncolytic Viruses/physiology
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