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.

scholarly journals Adaptation of the Newcastle Disease Virus to Cell Cultures for Enhancing Its Oncolytic Properties

Acta Naturae ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 66-73
Author(s):  
K. S. Yurchenko ◽  
Yi. Jing ◽  
A. M. Shestopalov
Keyword(s):  
Newcastle Disease Virus ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Disease Virus ◽  
Cell Cultures ◽  
Newcastle Disease ◽  
Human Cancer ◽  
Genetic Material ◽  
Human Tumor ◽  
Natural Strains

This study focuses on the adaptation of natural Newcastle disease virus (NDV) strains isolated from wild birds to human tumor cells. Many candidates for virotherapy are viruses pathogenic for human. During recombination of genetic material, there always exists a risk of getting a virus with an unstable genome. This problem can be solved by using natural apathogenic viruses as oncolytic agents. The Newcastle disease virus is the causative agent of contagious avian diseases. Its natural strains exhibit an antitumor effect and are considered safe for humans. As shown in earlier studies, the oncolytic properties of natural strains can be enhanced during adaptation to cell cultures, without interference in the virus genome. This study demonstrates that serial passaging increases the viral infectious titer in cancer cells. Moreover, the viability of tumor cells decreases post-infection when Newcastle disease virus strains are adapted to these cell cultures. The findings of this study complement the well-known data on the adaptation of the Newcastle disease virus to human cancer cells. Hence, it is possible to obtain a NDV strain with a more pronounced oncolytic potential during adaptation. This should be taken into account when choosing a strategy for designing anticancer drugs based on this virus.

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.

scholarly journals Synergy between hemagglutinin 2 (HA2) subunit of influenza fusogenic membrane glycoprotein and oncolytic Newcastle disease virus suppressed tumor growth and further enhanced by Immune checkpoint PD-1 blockade

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Seyed Mohammad Miri ◽  
Mir Saeed Ebrahimzadeh ◽  
Elahe Abdolalipour ◽  
Mahsa Yazdi ◽  
Hassan Hosseini Ravandi ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Gene Therapy ◽  
Newcastle Disease Virus ◽  
Tumor Cells ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Oncolytic Viruses

Abstract Background Newcastle disease virus (NDV) has shown noticeable oncolytic properties, especially against cervical cancer. However, in order to improve the spread rate and oncotoxicity of the virus, employment of other therapeutic reagents would be helpful. It has been shown that some viral fusogenic membrane glycoproteins (FMGs) could facilitate viral propagation and increase the infection rate of tumor cells by oncolytic viruses. Additionally, immune checkpoint blockade has widely been investigated for its anti-tumor effects against several types of cancers. Here, we investigated for the first time whether the incorporation of influenza hemagglutinin-2 (HA2) FMG could improve the oncolytic characteristics of NDV against cervical cancer. Next, we added anti-PD-1 mAb to our therapeutic recipe to assess the complementary role of immune checkpoint blockade in curbing tumor progression. Methods For this purpose, TC-1 tumor cells were injected into the mice models and treatment with NDV, iNDV, HA2, NDV-HA2, iNDV-HA2 began 10 days after tumor challenge and was repeated at day 17. In addition, PD-1 blockade was conducted by injection of anti-PD-1 mAb at days 9 and 16. Two weeks after the last treatment, sample mice were sacrificed and treatment efficacy was evaluated through immunological and immunohistochemical analysis. Moreover, tumors condition was monitored weekly for 6 weeks intervals and the tumor volume was measured and compared within different groups. Results The results of co-treatment with NDV and HA2 gene revealed that these agents act synergistically to induce antitumor immune responses against HPV-associated carcinoma by enhancement of E7-specific lymphocyte proliferation, inducement of CD8+ T cell cytotoxicity responses, increase in splenic cytokines and granzyme B, decrease in immunosuppressive cytokines and E6 oncogene expression, and upregulation of apoptotic proteins expression, in comparison with control groups. Moreover, incorporation of PD-1 blockade as the third side of our suggested therapy led to noticeable regression in tumor size and augmentation of cytokine responses. Conclusions The invaluable results of synergy between NDV virotherapy and HA2 gene therapy suggest that tumor-selective cell killing by oncolytic NDV can be enhanced by combining with FMG gene therapy. Moreover, the adjunction of the PD-1 blockade proves that checkpoint blockade can be considered as an effective complementary therapy for the treatment of cervical cancer.

scholarly journals Evaluation of Newcastle disease virus mediated dendritic cell activation and cross‐priming tumor‐specific immune responses ex vivo

2019 ◽  
Vol 146 (2) ◽  
pp. 531-541 ◽  
Author(s):  
Qi Xu ◽  
Udaya S. Rangaswamy ◽  
Weijia Wang ◽  
Scott H. Robbins ◽  
James Harper ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Immune Responses ◽  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Cell Activation ◽  
Ex Vivo ◽  
Dendritic Cell Activation

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 eIF2α-CHOP-BCl-2/JNK and IRE1α-XBP1/JNK signaling promote apoptosis and inflammation and support the proliferation of Newcastle disease virus

2019 ◽  
Vol 10 (12) ◽  
Author(s):  
Yanrong Li ◽  
Weiyu Jiang ◽  
Qiaona Niu ◽  
Yingjie Sun ◽  
Chunchun Meng ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Nuclear Translocation ◽  
Human Cancer ◽  
Cell Types ◽  
Signaling Cascades ◽  
Jnk Signaling ◽  
Induced Apoptosis ◽  
Cytokines Secretion

AbstractNewcastle disease virus (NDV) causes severe infectious disease in poultry and selectively kills tumor cells, by inducing apoptosis and cytokines secretion. In this report, we study the mechanisms underlying NDV-induced apoptosis by investigating the unfolded protein response (UPR). We found that NDV infection activated all three branches of the UPR signaling (PERK-eIF2α, ATF6, and IRE1α) and triggered apoptosis, in avian cells (DF-1 and CEF) and in various human cancer cell types (HeLa, Cal27, HN13, A549, H1299, Huh7, and HepG2). Interestingly, the suppression of either apoptosis or UPR led to impaired NDV proliferation. Meanwhile, the inhibition of UPR by 4-PBA protected cells from NDV-induced apoptosis. Further study revealed that activation of PERK-eIF2α induced the expression of transcription factor CHOP, which subsequently promoted apoptosis by downregulating BCL-2/MCL-1, promoting JNK signaling and suppressing AKT signaling. In parallel, IRE1α mediated the splicing of XBP1 mRNA and resulted in the translation and nuclear translocation of XBP1s, thereby promoting the transcription of ER chaperones and components of ER-associated degradation (ERAD). Furthermore, IRE1α promoted apoptosis and cytokines secretion via the activation of JNK signaling. Knock down and overexpression studies showed that CHOP, IRE1α, XBP1, and JNK supported efficient virus proliferation. Our study demonstrates that the induction of eIF2α-CHOP-BCL-2/JNK and IRE1α-XBP1/JNK signaling cascades promote apoptosis and cytokines secretion, and these signaling cascades support NDV proliferation.

scholarly journals Detection of Free Peritoneal Cancer Cells in Gastric Cancer Using Cancer-Specific Newcastle Disease Virus

2009 ◽  
Vol 14 (1) ◽  
pp. 7-14 ◽  
Author(s):  
Joyce Wong ◽  
Allison Schulman ◽  
Kaitlyn Kelly ◽  
Dmitriy Zamarin ◽  
Peter Palese ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Newcastle Disease Virus ◽  
Cancer Cells ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Peritoneal Cancer
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