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Newcastle disease virus rituximab and doxorubicin combination as anti-hematological malignancy therapy

機譯:新城疫病毒利妥昔單抗和阿霉素組合作為抗血液系統(tǒng)惡性腫瘤治療

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摘要

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.
機譯:血液系統(tǒng)惡性腫瘤是需要更有效治療方法的重要疾病。即使采用目前的靶向療法,如利妥昔單抗和其他化療藥物,也需要開發(fā)新的治療策略。聯(lián)合治療似乎是通過不同機制靶向腫瘤細胞的最佳選擇。病毒療法是一種非常有前途的治療方法,因為它具有選擇性,安全性并且可導致癌癥破壞。事實證明,伊拉克新城疫病毒(NDV)株在體外和體內(nèi)均有效。在當前的工作中,我們測試了其抗血液學腫瘤的能力,并通過聯(lián)合療法增強了當前療法,并使用Chou-Talalay分析法研究了這種聯(lián)合療法。測量p53濃度以評估這種擬議的協(xié)同作用的機制。結(jié)果表明,NDV與阿霉素小劑量協(xié)同作用于漿細胞瘤細胞,無p53通路參與,但在非霍奇金淋巴瘤細胞上使用時與p53有關(guān)。 NDV與利妥昔單抗聯(lián)合顯示出增強的細胞毒性,這與p53無關(guān)??傊@項工作提出了一種用于治療某些血液系統(tǒng)惡性腫瘤的新型聯(lián)合療法。

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