scholarly journals Regression of solid breast tumours in mice by Newcastle disease virus is associated with production of apoptosis related-cytokines

2018 ◽  
Author(s):  
Umar Ahmad ◽  
Juraimi Raihan ◽  
Yoke Keong Yong ◽  
Zolkapli Eshak ◽  
Fauziah Othman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Newcastle Disease Virus ◽  
Cancer Cells ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Tumour Growth ◽  
Breast Tumour ◽  
Tnf Α ◽  
4T1 Breast Cancer ◽  
Different Strains

AbstractBackgroundDifferent 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.MethodsA 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).ResultsThe results demonstrated that 4T1 breast cancer cells in allotransplanted mice treated with AF2240 showed a noticeable inhibition in tumour growth and induce apoptotic-related cytokines.ConclusionNDV AF2240 suppression of breast tumour growth is associated with induction of apoptotic-related cytokines.

scholarly journals Hexokinase inhibition using D-Mannoheptulose enhances oncolytic newcastle disease virus-mediated killing of breast cancer cells

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ahmed Ghdhban Al-Ziaydi ◽  
Ahmed Majeed Al-Shammari ◽  
Mohammed I. Hamzah ◽  
Haider Sabah kadhim ◽  
Majid Sakhi Jabir
Keyword(s):  
Breast Cancer ◽  
Newcastle Disease Virus ◽  
Cancer Cells ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Breast Cancer Cells

scholarly journals Evaluation of a Recombinant Newcastle Disease Virus Expressing Human IL12 against Human Breast Cancer

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Zahiah Mohamed Amin ◽  
Muhamad Alhapis Che Ani ◽  
Sheau Wei Tan ◽  
Swee Keong Yeap ◽  
Noorjahan Banu Alitheen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Newcastle Disease Virus ◽  
Cancer Cells ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Human Breast Cancer ◽  
Tumor Growth Inhibition ◽  
Human Breast ◽  
Chicken Cell

Abstract The Newcastle disease virus (NDV) strain AF2240 is an avian avulavirus that has been demonstrated to possess oncolytic activity against cancer cells. However, to illicit a greater anti-cancer immune response, it is believed that the incorporation of immunostimulatory genes such as IL12 into a recombinant NDV backbone will enhance its oncolytic effect. In this study, a newly developed recombinant NDV that expresses IL12 (rAF-IL12) was tested for its safety, stability and cytotoxicity. The stability of rAF-IL12 was maintained when passaged in specific pathogen free (SPF) chicken eggs from passage 1 to passage 10; with an HA titer of 29. Based on the results obtained from the MTT cytotoxic assay, rAF-IL12 was determined to be safe as it only induced cytotoxic effects against normal chicken cell lines and human breast cancer cells while sparing normal cells. Significant tumor growth inhibition (52%) was observed in the rAF-IL12-treated mice. The in vivo safety profile of rAF-IL12 was confirmed through histological observation and viral load titer assay. The concentration and presence of the expressed IL12 was quantified and verified via ELISA assay. In summary, rAF-IL12 was proven to be safe, selectively replicating in chicken and cancer cells and was able to maintain its stability throughout several passages; thus enhancing its potential as an anti-breast cancer vaccine.

scholarly journals Newcastle disease virus suppress glycolysis pathway and induce breast cancer cells death

VirusDisease ◽  
2020 ◽  
Vol 31 (3) ◽  
pp. 341-348
Author(s):  
Ahmed Ghdhban Al-Ziaydi ◽  
Ahmed Majeed Al-Shammari ◽  
Mohammed I. Hamzah ◽  
Haider Sabah Kadhim ◽  
Majid Sakhi Jabir
Keyword(s):  
Breast Cancer ◽  
Newcastle Disease Virus ◽  
Cancer Cells ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Breast Cancer Cells ◽  
Glycolysis Pathway ◽  
Cells Death

scholarly journals Persistent Newcastle disease virus infection in bladder cancer cells is associated with putative pro-survival and anti-viral transcriptomic changes

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lee-Chin Chan ◽  
Jeevanathan Kalyanasundram ◽  
Sze-Wei Leong ◽  
Mas Jaffri Masarudin ◽  
Abhi Veerakumarasivam ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Newcastle Disease Virus ◽  
Cancer Cells ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Persistent Infection ◽  
Signalling Pathways ◽  
Bladder Cancer Cells ◽  
Transcriptomic Changes

Abstract 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.

Rhein Augments Antiproliferative Effects of Atezolizumab Based on Breast Cancer (4T1) Regression

Planta Medica ◽  
2019 ◽  
Vol 85 (14/15) ◽  
pp. 1143-1149 ◽  
Author(s):  
Zhanyun Shen ◽  
Bo Zhu ◽  
Jiao Li ◽  
Luping Qin
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cd8 T Cells ◽  
Tumour Growth ◽  
The Other ◽  
Treatment Groups ◽  
Tnf Α ◽  
4T1 Breast Cancer ◽  
Apoptotic Factors ◽  
Breast Cancer Xenografts

AbstractRhein, an anthraquinone extracted from rhubarb, is used in traditional Chinese medicine for diuresis, diarrhoea, inflammation, and immune regulation. Atezolizumab, a programmed cell death ligand 1 monoclonal antibody, is mainly used to treat bladder cancer and non-small cell lung cancer unresponsive to chemotherapy. We explored the effects of rhein and atezolizumab in combination on breast cancer. Mice with established 4T1 breast cancer xenografts were administered rhein (10 mg/kg) and atezolizumab (10 mg/kg), alone and in combination, and the effects on tumour growth were evaluated. The proportion of CD8+ T cells in the spleen and tumour tissue, the levels of TNF-α, and interleukin-6 in serum as well as the mRNA levels of apoptotic factors (caspase-3, caspase-8, caspase-9, and Bax/Bcl-2) were also evaluated. All of the treatment groups had inhibitory effects on the xenograft tumour growth, with results that were significantly different from those in the control group. In addition, the proportion of CD8+ T cells in the spleen and tumour was significantly increased in the combination therapy group and was significantly different from the other treatment groups. The serum levels of TNF-α and IL-6 were significantly increased in the rhein and combination therapy groups. Finally, the levels of various apoptotic factors in tumour tissues were significantly higher in the combination treatment group than those in the other groups. Administration of rhein, atezolizumab, or their combination all had therapeutic effects on 4T1 breast cancer xenografts in mice, with the combination treatment having stronger effects.

In-vitroCharacterization and Evaluation of Apoptotic Potential of Bicistronic Plasmid Encoding HN Gene of Newcastle Disease Virus and Human TNF-α

2014 ◽  
Vol 26 (2) ◽  
pp. 112-119 ◽  
Author(s):  
R. S. Rajmani ◽  
Prafull Kumar Singh ◽  
G. Ravi Kumar ◽  
Shikha Saxena ◽  
Lakshya Veer Singh ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Tnf Α ◽  
Hn Gene

scholarly journals Analysis of PPI networks of transcriptomic expression identifies hub genes associated with Newcastle disease virus persistent infection in bladder cancer

2020 ◽  
Author(s):  
Umar Ahmad ◽  
De Ming Chau ◽  
Suet Lin Chia ◽  
Khatijah Yusoff ◽  
Syahril Abdullah ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Newcastle Disease Virus ◽  
Cancer Cells ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Persistent Infection ◽  
Ppi Network ◽  
Hub Genes ◽  
Persistently Infected ◽  
Bladder Cancer Cells

AbstractMotivationBladder cancer cells acquire persistent infection associated with oncolytic Newcastle disease virus (NDV) in which its molecular events are still unclear. This poses a potential problem for oncolytic virus application for cancer therapy. To unravel the molecular mechanism underlying the development of NDV persistent infection in bladder cancer, we used mRNA expression profile of the persistently infected bladder cancer cells to construct PPI network.ResultsBased on path and module exploring in the PPI network, the bridges were found mainly from pathways of p53 signalling, ECM-receptor interaction, and TGF-beta signalling by the upregulated mRNAs, to the antigen processing and presentation, protein processing in endoplasmic reticulum, completement and coagulation cascades by the downregulated mRNAs in NDV persistent TCCSUPPi cells. In persistent EJ28Pi cells comparatively, connections were identified mainly from pathways of renal carcinoma, viral carcinogenesis, Ras signalling and cell cycle by the upregulated mRNAs, to the Wnt signalling, HTLV-I infection and pathways in cancer by the downregulated mRNAs. This connection was mainly dependent on of RPL8- HSPA1A/HSPA4 in TCCSUPPi cells and EP300, PTPN11, RAC1 - TP53, SP1, CCND1 and XPO1 in EJ28Pi cells. Oncomine validation showed that the top hub genes identified in the network that includes RPL8, THBS1, F2 from TCCSUPPi and TP53 and RAC1 from EJ28Pi are involved in the development and progression of bladder cancer. Protein-drug interaction network, have identified several drugs targets that could be used to disconnect the linkages between modules and prevent bladder cancer cells from acquiring NDV persistent infection. This is the first time reporting the PPI network analysis of differentially expressed mRNAs of the NDV persistently infected bladder cancer cell lines which provide an insight into screening drugs that could be used together with NDV to manage bladder cancer resistance to therapy and progression.

scholarly journals Viability Reduction andRac1Gene Downregulation of HeterogeneousEx-VivoGlioma Acute Slice Infected by the Oncolytic Newcastle Disease Virus Strain V4UPM

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Zulkifli Mustafa ◽  
Hilda Shazana Shamsuddin ◽  
Aini Ideris ◽  
Rohaya Ibrahim ◽  
Hasnan Jaafar ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Cancer Cells ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Cell Cycle Progression ◽  
Ex Vivo ◽  
Human Cancer ◽  
Significant Inhibition ◽  
Oncolytic Viruses ◽  
Tissue Viability

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,Rac1is reported to be required for efficient NDV replication in human cancer cells and established a link between tumourigenesis and sensitivity to NDV.Rac1is a member of the Rho GTPases involved in the regulation of the cell migration and cell-cycle progression.Rac1knockdown 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 anex vivo glioma acute slice(EGAS). Analysis of gene expression indicated that reduced tissue viability was associated with downregulation ofRac1. However, the viability reduction was not persistent. We conclude that NDV treatment induced EGAS viability suppression, but subsequent downregulation ofRac1gene may reduce the NDV replication and lead to regrowth of EGAS tissue.

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