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.
METHODS: 45 rats at 6 weeks of age, were randomly assigned to nine groups with 5 rats in each group, both azoxymethane (AOM) and 5-Fluorouracil (5-FU) were given to rats according to the body weight. NDV virus strains (AF2240 and V4-UPM) doses were determined to rats according to CD50 resulted from MTT assay. After 8 doses of NDV strians and 5-FU, tissue sections preparations and histopathological study of rats' organs were done.
RESULTS: In this article morphological changes of rats' organs, especially in livers, after treatment with a colon carcinogen (azoxymethane) and Newcastle disease virus strains have been recorded. We observed liver damage caused by AOM evidenced by morphological changes and enzymatic elevation were protected by the oncolytic viruses sections. Also we found that combination treatment NDV with 5-FU had greater antitumor efficacy than treatment with NDV or 5-FU alone.
CONCLUSION: We noted morphological changes in liver and other rats' organs due to a chemical carcinogen and their protection by NDV AF2240 and NDV V4-UPM seems to be most protective.
AIM: In the current study, for further validation, we initiated a comprehensive epidemiological study to identify the dominant NDV genotype(s) circulating within the country. Collection of samples was executed between October 2017 and February 2018 from 108 commercial broiler farms which reported clinical signs of respiratory disease in their broilers.
RESULT: We report that 38 of the farms (> 35%) tested positive for NDV. The complete F gene sequences of seven of the isolates are shown as representative sequences in this study. According to the phylogenetic tree constructed, the recent broiler farm isolates clustered into the newly designated cluster VII(L) together with the older Iranian backyard poultry isolates in our previous work. All the sequences shared the same virulence-associated F cleavage site of 112RRQKR↓F117.
CONCLUSION: Our phylogenetic analysis suggested that the NDV subgenotype VII(L) may have been derived from subgenotype VIId, and contrary to popular belief, subgenotype VIId may not be the dominant subgenotype in Iran. Tracking of the subgenotype on BLAST suggested that the NDV subgenotype VII(L), although previously unidentified, may have been circulating in this region as an endemic virus for at least a decade. Other NDV genotypes, however, have also been reported in Iran in recent years. Hence, ongoing study is aimed at determining the exact dominant NDV genotypes and subgenotypes in the country. This will be crucial in effective mitigation of outbreaks in Iranian broiler farms.
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.