胰腺癌免疫治疗的现状及前景CSCD

胰腺癌(胰腺导管腺癌)是一种恶性程度较高,诊断和治疗都较困难的消化系统恶性肿瘤。近年来,肿瘤免疫治疗在多种肿瘤中如黑色素瘤、膀胱癌、乳腺癌、非小细胞肺癌和肾癌等均取得了令人振奋的治疗效果,但是胰腺癌的免疫治疗策略尚在不断探索中。目前针对胰腺癌独特的肿瘤微环境设计了多种免疫治疗策略,包括强化/提高自身免疫反应(免疫调节剂、单克隆抗体、肿瘤疫苗和细胞治疗)以及抑制肿瘤免疫逃逸(免疫检查点抑制剂和肿瘤微环境)等。本文就胰腺癌免疫治疗的研究进展进行综述,着重探讨PD-1/PD-L1抑制剂在胰腺癌中的应用,并分析免疫治疗联合其他方式治疗胰腺癌的前景。     

瑞戈非尼联合XELOX化疗方案治疗结直肠癌的临床研究

目的 探究瑞戈非尼联合XELOX化疗方案治疗结直肠癌疗效及对血管新生指标、肿瘤免疫逃逸的影响。方法 选取2018年1月—2022年1月泸州市人民医院收治的80例结直肠癌患者,随机分为对照组和治疗组,每组各40例。对照组采用XELOX方案治疗,第1天静脉滴注注射用奥沙利铂130 mg/m²;第1～14天,口服卡培他滨片1 000 mg/m²,2次/d;21 d为1个周期。治疗组在对照组基础上口服瑞戈非尼片,160 mg/次,1次/d,用药21 d停用7 d,28 d为1个周期。病情进展或无法耐受停止用药。观察两组患者疾病控制率,比较治疗前后两组患者血清癌胚抗原(CEA)、大肠特异性抗原-2(CCSA-2)、糖类抗原19-9(CA19-9)、血管内皮生长因子(VEGF)、转化生长因子-β(TGF-β)、程序性死亡分子-1(PD-1)、程序性死亡分子配体-1(PD-L1)水平,及生存质量。结果 治疗后,治疗组疾病控制率(77.50%)较对照组(55.00%)明显升高(P<0.05)。治疗后,两组CA19-9、CCSA-2、CEA、TGF-β、...     

次级淋巴组织趋化因子浓度梯度抑制肿瘤细胞免疫逃逸

目的探讨人次级淋巴组织趋化因子(SLC)浓度梯度对肿瘤细胞免疫逃逸的影响。方法根据SLC浓度梯度,实验分6组;流式细胞术检测肿瘤细胞HLA-Ⅰ类分子的表达、肿瘤细胞凋亡,Western blot检测肿瘤细胞胞内BCL-2表达,ELISA检测肿瘤细胞培养上清中生长转化因子β(TGF-β)水平。结果在一定浓度范围内,随SLC浓度增加,肿瘤细胞的HLA-Ⅰ类分子表达增高,肿瘤细胞凋亡增多;BCL-2表达增高,而肿瘤细胞TGF-β分泌水平降低。结论SLC具有抑制肿瘤细胞免疫逃逸的作用。     

肿瘤细胞表面TLR在促肿瘤发展中的作用和机制

自Toll样受体(Toll-like receptors,TLRs)发现以来,大量的研究主要集中于TLRs在天然免疫反应和调节适应性免疫中发挥的作用和机制。然而,近年来发现,除了表达于免疫系统的各种细胞外,TLRs还表达于肿瘤细胞表面,于是人们对肿瘤细胞TLRs在促进肿瘤发展中的作用和机制进行了探讨,发现TLRs能通过免疫逃避,以及促进肿瘤细胞存活、增殖和迁移等机制促进肿瘤发生和发展。因此,本文就肿瘤细胞上TLR在促进肿瘤中所发挥的作用及其机制进行综述。     

CD80/IgG融合基因重组表达载体的构建及在CHO细胞中功能性表达的研究

目的 构建CD80/IgG真核表达载体,使其在中国地仓鼠卵巢细胞（Chinese hamster ovurm,CHO）中功能性表达,寻找消除白血病细胞免疫逃逸的有效方法.方法 采用定向分子克隆技术将小鼠CD80胞外段和IgG1 Fc段的cDNA串联至真核表达载体pcDNA3.0中,运用脂质体将所得的重组子转染CHO细胞,经免疫印迹、斑点ELISA检测其表达,免疫亲和层析法纯化其表达产物,用流式细胞术、MTT比色法及ELISA在体外检测该产物的生物学活性.结果 两段目的基因按预期设想克隆入空载体中并得到了表达,亲和层析纯化获得了高纯度目的蛋白,该蛋白能够将白血病细胞表面CD80分子密度提高5倍,并可显著增强同种异体小鼠淋巴细胞的增殖、对白血病细胞的杀伤以及Ⅱ-2的分泌.结论 成功构建了融合基因真核表达载体,其表达产物在体外具有相应的生物学功能,有希望成为消除白血病细胞免疫逃逸的有力工具.     

表皮葡萄球菌生物膜致病相关因子概述

近年来的流行病学调查显示,表皮葡萄球菌已成为医院获得性感染的重要病原菌,主要通过在机体留置医疗设备表面形成生物膜而致病.生物膜作为表皮葡萄球菌感染的主要致病因素,可阻碍抗生素的渗透、增强细菌耐药性及抵御宿主免疫系统的作用,从而导致慢性持续性感染.针对表皮葡萄球菌生物膜致病相关因子进行深入研究,有利于为临床开展相关治疗提供理论支持.     

Identification of Intellectual Disability Genes in Female Patients with a Skewed X‐Inactivation Pattern

Intellectual disability (ID) is a heterogeneous disorder with an unknown molecular etiology in many cases. Previously, X‐linked ID (XLID) studies focused on males because of the hemizygous state of their X chromosome. Carrier females are generally unaffected because of the presence of a second normal allele, or inactivation of the mutant X chromosome in most of their cells (skewing). However, in female ID patients, we hypothesized that the presence of skewing of X‐inactivation would be an indicator for an X chromosomal ID cause. We analyzed the X‐inactivation patterns of 288 females with ID, and found that 22 (7.6%) had extreme skewing (>90%), which is significantly higher than observed in the general population (3.6%; P = 0.029). Whole‐exome sequencing of 19 females with extreme skewing revealed causal variants in six females in the XLID genes DDX3X, NHS, WDR45, MECP2, and SMC1A. Interestingly, variants in genes escaping X‐inactivation presumably cause both XLID and skewing of X‐inactivation in three of these patients. Moreover, variants likely accounting for skewing only were detected in MED12, HDAC8, and TAF9B. All tested candidate causative variants were de novo events. Hence, extreme skewing is a good indicator for the presence of X‐linked variants in female patients.     

Computational Analysis of Mutations in the Receptor-Binding Domain of SARS-CoV-2 Spike and Their Effects on Antibody Binding

Currently, SARS-CoV-2 causing coronavirus disease 2019 (COVID-19) is responsible for one of the most deleterious pandemics of our time. The interaction between the ACE2 receptors at the surface of human cells and the viral Spike (S) protein triggers the infection, making the receptor-binding domain (RBD) of the SARS-CoV-2 S-protein a focal target for the neutralizing antibodies (Abs). Despite the recent progress in the development and deployment of vaccines, the emergence of novel variants of SARS-CoV-2 insensitive to Abs produced in response to the vaccine administration and/or monoclonal ones represent a potential danger. Here, we analyzed the diversity of neutralizing Ab epitopes and assessed the possible effects of single and multiple mutations in the RBD of SARS-CoV-2 S-protein on its binding affinity to various antibodies and the human ACE2 receptor using bioinformatics approaches. The RBD-Ab complexes with experimentally resolved structures were grouped into four clusters with distinct features at sequence and structure level. The performed computational analysis indicates that while single amino acid replacements in RBD may only cause partial impairment of the Abs binding, moreover, limited to specific epitopes, the variants of SARS-CoV-2 with multiple mutations, including some which were already detected in the population, may potentially result in a much broader antigenic escape. Further analysis of the existing RBD variants pointed to the trade-off between ACE2 binding and antigenic escape as a key limiting factor for the emergence of novel SAR-CoV-2 strains, as the naturally occurring mutations in RBD tend to reduce its binding affinity to Abs but not to ACE2. The results provide guidelines for further experimental studies aiming to identify high-risk RBD mutations that allow for an antigenic escape.     

Sodium alginate coating simultaneously increases the biosafety and immunotherapeutic activity of the cationic mRNA nanovaccine

The extraordinary advantages associated with mRNA vaccines,including their high efficiency,relatively low severity of side effects,and ease of manufacture,have enabled them to be a promising immunotherapy approach against various infectious diseases and cancers.Nevertheless,most mRNA delivery carriers have many disadvantages,such as high toxicity,poor biocompatibility,and low efficiency in vivo,which have hindered the widespread use of mRNA vaccines.To further characterize and solve these proble...     

Pulmonary delivery of siRNA against acute lung injury/acute respiratory distress syndrome

The use of small interfering RNAs (siRNAs) has been under investigation for the treatment of several unmet medical needs, including acute lung injury/acute respiratory distress syndrome (ALI/ARDS) wherein siRNA may be implemented to modify the expression of pro-inflammatory cytokines and chemokines at the mRNA level. The properties such as clear anatomy, accessibility, and relatively low enzyme activity make the lung a good target for local siRNA therapy. However, the translation of siRNA is restricted by the inefficient delivery of siRNA therapeutics to the target cells due to the properties of naked siRNA. Thus, this review will focus on the various delivery systems that can be used and the different barriers that need to be surmounted for the development of stable inhalable siRNA formulations for human use before siRNA therapeutics for ALI/ARDS become available in the clinic.