Hematological malignancies are important diseases that need more powerful therapeutics. Even with current targeting therapies, such as rituximab and other chemotherapeutic agents, there is a need to develop new treatment strategies. Combination therapy seems the best option to target the tumor cells by different mechanisms. Virotherapy is a very promising treatment modality, as it is selective, safe, and causes cancer destruction. The Iraqi strain of Newcastle disease virus (NDV) has proved to be effective both in vitro and in vivo. In the current work, we tested its ability on anti-hematological tumors and enhanced current treatments with combination therapy, and studied this combination using Chou–Talalay analysis. p53 concentration was measured to evaluate the mechanism of this proposed synergism. The results showed that NDV was synergistic with doxorubicin in low doses on plasmacytoma cells, with no involvement of p53 pathways, but involved p53 when the combination was used on non-Hodgkin lymphoma cells. NDV in combination with rituximab showed enhanced cytotoxicity that was p53-independent. In conclusion, this work proposes a novel combination modality for treatment of some hematological malignancies.
Hematological malignancies remain one of the leading causes of death worldwide despite advances in cancer therapeutics. Newcastle disease virus (NDV) is a member of Paramyxoviridae that elicits considerable interest as an anticancer agent because it can replicate up to 10 000 times faster in human cancer cells than in most normal cancer cells. Several NDV strains reportedly induce the cytolysis of cancerous cell lines. The attenuated Iraqi strain (AMHA1) of NDV is a novel oncolytic agent with promising antitumor characteristics, including apoptosis induction. This study aimed to evaluate the ability of the AMHA1 NDV strain to induce apoptotic cell death in hematological tumors through caspase-dependent or independent apoptotic pathways. The
... Show MoreObjective: We hypothesized that attacking cancer cells by combining various modes of action can hinder them from taking the chance to evolve resistance to treatment. Incorporation of photodynamic therapy (PDT) with oncolytic virotherapy might be a promising dual approach to cancer treatment. Methods: NDV AMHA1 strain as virotherapy in integration with aminolaevulinic acid (ALA) using low power He-Ne laser as PDT in the existing work was examined against breast cancer cells derived from Iraqi cancer patients named (AMJ13). This combination was evaluated using Chou–Talalay analysis. Results: The results showed an increased killing rate when using both 0.01 and 0.1 Multiplicity of infection (MOI) of the virus when combined with a dose of 617
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A number of disorders characterized by aberrant cell proliferation are referred to as cancers. Cancer is a complicated group of mutagenic diseases that can move or infiltrate to other parts of the body. It develops through a multi-step process. The need for new therapeutic strategies is driven by malignancies resistance to conventional therapies. Use of the Newcastle disease virus as an oncolytic agent has advanced and expanded in immunocompetent carcinoma tumor models by utilizing reverse genetics techniques. Preclinical investigations have shown that recombinant NDV (rNDV-GFP), which expresses foreign genes, is proven to be effective in cancer treatment. Green fluorescent protein gene is usually used as an expression reporter for certa
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Abstract: Recombinant Newcastle disease virus (rNDV) has shown an anticancer effect in preclinical studies, but has never been tested in a lung cancer models. In this study we explored the anticancer activity of genetically modified NDV expressing IL-2-P53 (rClone30–IL-2-P53) in lung cancer model. We have cloned IL-2 and P53 genes and inserted them in the viral genome of New Castle Disease Virus to create a genetically modified rNDV- IL-2-P53 virus and tested the anti-tumor activity of the new virus in vitro on different types of cancer cell lines by MTT assay. TheIL-2 and P53 gene were successfully cloned and inserted into the viral genome by using a Mlu I and Sfi I endonucleases, viral vector was constructed correctly and successf
... Show MoreThe oncolytic viruses are promising form of cancer therapy which is based on the selectively killing of the cancer cells. This study was aimed to investigate the role of Newcastle disease virus (NDV) Iraqi strain AD2141 in apoptosis. Firstly, the virulence of AD2141 was detected in embryonated chicken eggs after 48hrs of infection. It was observed a hemorrhage in the skin of infected embryos that led to death. Then, the ability of this strain for regression cancer cell lines was examined. By using cytotoxicity test, it was found 128 HAU/ml of AD2141 had a potent inhibition against growth of RD and AMN3 after 72hrs of exposure time; the inhibition rate was 86.8% and 86.98% respectively. Moreover, the apoptotic activity of AD2141 was exami
... Show MoreSystemic lupus erythematosus (SLE) is an autoimmune disease with polymorphic expression. B cells have an essential contribution in immune system activation via the production of different cytokines and functioning as potent antigen-presenting cells. Therefore, a drug that particularly targets B cells may represent an ideal therapeutic approach for SLE. Rituximab (RTX), an anti-CD20 monoclonal antibody causing transient B-cell depletion, has been used to manage SLE. This study aims to assess Rituximab effects on lupus nephritis (LN) patients when added to conventional immunosuppressants. Twenty four patients, 15-32 years old, with class III/IV/V LN were involved in this study. All were on steroids before lupus nephritis occurrence. They were
... Show MoreSystemic lupus erythematosus (SLE) is an autoimmune disease with polymorphic expression. B cells have an essential contribution in immune system activation via the production of different cytokines and functioning as potent antigen-presenting cells. Therefore, a drug that particularly targets B cells may represent an ideal therapeutic approach for SLE. Rituximab (RTX), an anti-CD20 monoclonal antibody causing transient B-cell depletion, has been used to manage SLE. This study aims to assess Rituximab effects on lupus nephritis (LN) patients when added to conventional immunosuppressants. Twenty four patients, 15-32 years old, with class III/IV/V LN were involved in this study. All were on steroids before lupus nephritis occurrence. They were
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Newcastle disease virus (NDV) is a wide-spectrum anti-tumor agent. The oncolytic selectivity of NDV, a family of Paramyxoviridae, depends on the differential type of inducing different death pathways. This work was conducted to further understand the oncolytic effect of LaSota strain. A mouse breast cancer model (Murine mammary adenocarcinoma cell line AMN3) was used in this study. Methyl Thiazolyl Tetrazolium (MTT) viability assay tested different NDV multiplicity of infection (MOI) values on mouse mammary adenocarcinoma cells incubated for 72 hours post-infection. The IC50 values and anti-tumor activity of LaSota strain against AMN3 cell line were determined. Following Hematoxylin and Eosin Stain, we examined t
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Newcastle Disease is one of the most important disease world wide distributions which invade the flock in different age resulting in large economic losses. This study aimed to evaluate the effect of treatment with 4 different concentrations (0.25, 0.5, 1.0 and 2.0 %) of Sodium deoxycholate (SDC) on the vaccinal virus (La Sota) using inoculation in the fragments of Chorioallantoic membrane. The treatment with each of the above 4 concentrations of SDC resulted in an increase in the Hemagglutination titer (HA) of the virus (28, 29.6, 211.6, 214.6) respectively as compared to the HA titer value for the untreated virus (26.6). No significant differences were noticed among all concentrations with regard to their effect on the HA titer, except
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