ABSTRACT
@#[摘 要] 神经胶质瘤是人脑中最常见的原发性肿瘤，占中枢神经系统恶性肿瘤的81%，当前标准疗法仍是手术切除及术后放化疗。因神经胶质瘤具有高侵袭性、分子异质性、治疗后耐药肿瘤干细胞可再生，以及化疗药物难以通过血脑屏障（BBB）达到足够高的治疗浓度等特点，导致其预后非常差，患者中位存活期仅为15个月。近年来，新兴的溶瘤病毒免疫疗法治疗神经胶质瘤的研究备受关注并取得一定进展，但依然面临诸如BBB、免疫“冷”微环境、宿主抗病毒反应和肿瘤高度异质性等挑战。这些问题限制了溶瘤病毒疗法的深入发展及进一步应用，但也给基础与临床研究者带来新的研究机遇。因此，本文从穿越BBB、改善肿瘤微环境（TME）、调控溶瘤病毒介导的宿主免疫反应和适应肿瘤异质性等四个方面，阐述溶瘤病毒在抗神经胶质瘤治疗研究中的存在问题及对策。
ABSTRACT
Herein, we found that serum concentration of superoxide dismutase 3 (SOD3) was significantly reduced inchildren with mycoplasma pneumonia (MP) infection. To study the roles of SOD3 in inflammatory regulationof MP infection, human A549 type II alveolar epithelial cells were stimulated with 107 CCU/ml of MP to buildMP infection in vitro. Secretion of pro-inflammatory cytokine interleukin (IL)-8 and tumor necrosis factor(TNF)-a were measured via enzyme-linked immunosorbent assay (ELISA) to assess the inflammatory responseof A549 cells. Levofloxacin (LVFX) was used as an anti-inflammatory drug while recombinant TNF-a wasused as an inflammatory promotor in MP-infected cells. Transcriptional activity of nuclear factor (NF)-rB wasassessed by detecting protein levels of nuclear NF-rB and cytoplasm NF-rB using Western blot analysis. Ourdata suggested that the expression of SOD3 mRNA and protein, as well as content of SOD3 in culturedsupernatant, were time-dependently inhibited in MP-infected A549 cells. However, lentiviruses-mediatedSOD3 overexpression alleviated inflammatory response of MP-infected A549 cells, and prevented the uncleartranslocation of NF-rB, as evidenced by obviously reducing the production of IL-8 and TNF-a in cell culturedsupernatant, as well as decreasing nuclear NF-rB while increasing cytoplasm NF-rB. Inspiringly, SOD3overexpression induced anti-inflammatory effect and the inactivation of NF-rB was similar to that of 2 lg/mlof LVFX, but reversed by additional TNF-a treatment. Therefore, we can conclude that transcriptional activityof NF-jB was the underlying mechanism, by which SOD3 regulated inflammatory response in MP infectionin vitro