Immunosuppressive Tumor Microenvironment and Immunotherapy of Epstein–Barr Virus-Associated Malignancies

The Epstein–Barr virus (EBV) can cause different types of cancer in human beings when the virus infects different cell types with various latent patterns. EBV shapes a distinct and immunosuppressive tumor microenvironment (TME) to its benefit by influencing and interacting with different components in the TME. Different EBV-associated malignancies adopt similar but slightly specific immunosuppressive mechanisms by encoding different EBV products to escape both innate and adaptive immune responses. Strategies reversing the immunosuppressive TME of EBV-associated malignancies have been under evaluation in clinical practice. As the interactions among EBV, tumor cells, and TME are intricate, in this review, we mainly discuss the epidemiology of EBV, the life cycle of EBV, the cellular and molecular composition of TME, and a landscape of different EBV-associated malignancies and immunotherapy by targeting the TME.     

Moderate Hypofractionated Helical Tomotherapy for Older Patients with Localized Prostate Cancer: Long-term Outcomes of a Phase I–II Trial

BackgroundOur previous study showed that two different regimens of moderate hypofractionated radiotherapy (HFRT) delivered with helical tomotherapy (HT) are well tolerated in older prostate cancer patients. We provide a longterm efficacy and toxicity after > 7 years of follow-up.Patients and methodsThe study recruited 33 patients from February 2009 to July 2011 (76 Gy/34F; Group-1); and 34 from July 2011 to February 2014 (71.6 Gy/28F; 50.4 Gy/25F for the risk of pelvic lymph nodes involvement (LNI) >15%; Group-2). The primary outcomes were biochemical failure (BF), biochemical failure and clinical disease failure (BCDF), progression-free survival (PFS), overall survival (OS), late genitourinary (GU) and gastrointestinal (GI) toxicity.ResultsThe average ages of two groups were 80 and 77 years and the proportions of patients with LNI > 15% were 69.7% and 73.5%, respectively. At the final follow-up in February 2020, 27.3% and 20.6% cases experienced BF, with a median time until BF of 3.3 years. A total of 38.8% patients reached primary endpoints, in which 18 deaths were reported BCDF events (45.5% vs. 32.4%, p = 0.271). There was no significant difference in 7-year PFS (68.6% vs. 74.8%, p = 0.591), BCDF (45.5% vs. 32.4%, p = 0.271) and OS (71.9% vs. 87.5%, p = 0.376) for full set analysis and for subgroup analysis (all p > 0.05). The incidence of grade ≥ 2 late GU (6.2% vs. 6.3%, p = 0.127) and GI toxicities (9.4% vs. 15.6%, p = 0.554) was comparable.ConclusionsIn older patients with localized prostate cancer, two moderate hypofractionated regimens were all well tolerated with similar, mild late toxicities and satisfactory survival, without necessity of prophylactic pelvic node irradiation.Key words: helical tomotherapy, radiation dose hypofractionation, progression-free survival, follow-up studies, prostatic neoplasms, adenocarcinoma     

松茸不同提取部位的体外抗肿瘤作用

摘 要 目的： 研究松茸不同提取部位的体外抗肿瘤活性。 方法: 采用MTT法测定松茸乙醇提取物各部位及多糖部位对HepG-2细胞、Hela细胞和MCF-7细胞的抑制作用;采用流式细胞术检测多糖部位诱导HepG-2细胞和Hela细胞凋亡的作用。结果:松茸多糖部位体外对3种肿瘤细胞的IC₅₀分别为53.77μg·ml^-1(HepG-2)、40.04 μg·ml^-1(Hela)、100.65 μg·ml^-1(MCF-7),抑制作用均优于其他各部位,且对HepG-2细胞和Hela细胞抑制作用呈现良好的时间与浓度依赖性;松茸多糖部位能诱导HepG-2细胞和Hela细胞凋亡。结论: 松茸多糖部位能显著抑制HepG-2和Hela等肿瘤细胞的生长,具有诱导凋亡的作用,为松茸抗肿瘤的主要活性部位。     

戊二酰辅酶A脱氢酶基因沉默及高浓度赖氨酸对BRL肝细胞活性的影响

目的探讨戊二酰辅酶A脱氢酶(GCDH)基因沉默和赖氨酸代谢物蓄积对肝细胞活性的影响。方法将BRL肝细胞分为正常对照组、阴性对照组和GCDH沉默组。构建含靶向沉默GCDH基因的sh RNA慢病毒载体,分别用该病毒和阴性对照病毒感染GCDH沉默组和阴性对照组BRL肝细胞。感染后细胞再用含5 mmol/L赖氨酸培养基培养。免疫荧光技术检测慢病毒感染效率;Western blot法检测GCDH蛋白表达水平;MTT法检测细胞活性,Hoechest 33342染色检测细胞凋亡,Western blot法检测细胞凋亡的经典指标Caspase3水平。结果构建的慢病毒可有效沉默肝细胞GCDH表达(P0.01)。MTT及Hoechest 33342染色检测各组间细胞活性及细胞凋亡比较差异无统计学意义(P0.05)。Caspase3蛋白表达在各组间比较差异亦无统计学意义(P0.05)。结论 GCDH基因沉默和赖氨酸代谢物蓄积对肝细胞无明显损伤作用。     

多焦点人工晶状体的临床应用研究

目的　探讨多焦点人工晶状体 (MIOL)在白内障治疗中的作用。方法　在小切口超声乳化白内障吸除术中 ,30例 (36只眼 )白内障患者植入MIOL(试验组 ) ,32例 (40只眼 )白内障患者植入单焦点人工晶状体 (SIOL) (对照组 )。观察患者的术后视力、焦距深度、角膜散光度数、对比敏感度和眩光敏感度、手术并发症及视觉不良症状 ,随访时间 6 0～ 18 0个月。结果　术后 6个月裸眼近视力≥ 0 5者试验组占 80 6 % (2 9/36 ) ,对照组占 2 5 0 % (10 /4 0 ) ,两组比较差异有显著意义 (P <0 0 5 ) ;矫正近视力和远视力、裸眼远视力两组比较 ,差异均无显著意义 (P >0 0 5 )。在 1 0 0～ - 1 0 0D调节范围内 ,视力≥ 0 5者试验组占 97 2 % (35 /36 ) ,对照组占 97 5 % (39/4 0 ) ,差异无显著意义 (P >0 0 5 ) ;在 - 1 5 0D和 - 2 5 0～ - 3 5 0D调节范围内 ,视力≥ 0 5者试验组 [97 2 % (35 /36 )、88 9% (32 /36 ) ]明显多于对照组 [0 0 % (0 /4 0 )、0 0 % (0 /4 0 ) ](P <0 0 5 )。在视力≥ 0 5的术眼中 ,焦距深度试验组为4 5 0D ,对照组为 2 0 0D。术后 1周、1个月、3个月、6个月两组角膜散光度数与术前比较 ,差异均无显著意义 (P >0 0 5 )。低频段对比敏感度和眩光敏感度试验组 (2 8 4 9± 6 4 5和     

乳兔雪旺细胞对成兔视神经挫伤修复的作用

目的 研究乳兔雪旺细胞(Schwann cell,SC)对成兔视神经挫伤修复的作用。 方法 建立成兔视神经挫伤模型,伤后24 h分别向伤眼玻璃体腔内注入SC悬液(A组)、生理盐水(B组)各0.1 ml。伤后不同时间点进行视网膜节细胞(retinal ganglion cell,RGC)、轴突染色记数及闪光视觉诱发电位(flash visual evoked potentials,FVEP)检测。 结果 伤后4周A、B组RGC平均记数分别为(19.89±3.79) /mm和(12.67±4.12) /mm,轴突密度分别为(94.569±793) /mm ²和(36.085±285) /mm²,A组明显高于B组(P<0.01)。伤后3 d A组伤眼与健眼FVEP幅值比由48%上升至88%,8周时仍为78%,各时间点均明显高于B组(P＜0.01)。 结论 乳兔SC能够提高成兔视神经挫伤后RGC存活率,减轻轴突变性,显著促进视神经功能恢复,对视神经挫伤修复具有明显的促进作用。(中华眼底病杂志,2000,16:91-93)      

Silencing of Nesprin‐2 inhibits the differentiation of myofibroblasts from fibroblasts induced by mechanical stretch

Mechanical force plays a pivotal role in the pathogenesis of hypertrophic scar (HTS). Dermal fibroblasts and myofibroblasts are the key cells involved in HTS. Myofibroblasts in HTS possess different biochemical and biophysical characteristics by which myofibroblasts are often distinguished from fibroblasts. The role of mechanotransducers outside the nucleus in the pathogenesis of HTS has been reported in many studies. However, the role of Nesprin‐2 in HTS is not clear. Hence, we aim to construct a cell model of HTS and explore the role of Nesprin‐2 in this process. Myofibroblasts and fibroblasts were isolated from HTS and healthy skin tissues of the same patient. Fibroblasts were exposed to cyclic stretch with 10% magnitude and a frequency of 0.1 Hz for 3 days, 5 days, and 7 days, respectively. After the cell model was confirmed, fibroblasts transfected with siRNA targeting human Nesprin‐2 were exposed to cyclic stretch. The mechanical behaviour and biochemical reaction of the dermal fibroblasts were analysed. The stretched fibroblasts at day 5 showed the same mechanotransductive and biochemical features as unstretched myofibroblasts. Mechanical strain could induce the myofibroblasts differentiation and a cell model of HTS was established successfully at day 5. The expressions of lamin A/C, alpha‐smooth muscle actin, transforming growth factor beta 1, and collagen type I in fibroblasts were reduced by the silencing of Nesprin‐2. Mechanical strain could induce the myofibroblasts differentiation and silencing of Nesprin‐2 could block the mechanical stimulation of terminal myofibroblasts differentiation. Nesprin‐2 might be a potential target to treat the HTS.