Key benefits of dexamethasone and antibody treatment in COVID-19 hamster models revealed by single-cell transcriptomics

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双特异性抗体研究进展

抗体药物具有特异性高、不良反应少的特点，已成为肿瘤治疗的热点。双特异性抗体（双抗）是指同时结合2个不同抗原或同一抗原2个表位的抗体。与单特异性抗体相比，双抗具有高度特异性，增强了治疗有效性和安全性，同时减少了不良反应。已有多种双抗药物获批上市，进入临床研究的双抗药物数量不断增加。双抗药物的形式持续在更新，应用范围也在扩大，在未来具有非常好的应用前景。此文就目前已有的双抗类型、作用机制及目前双抗制备上面临的困难等进行概述。     

The impact of the covalently closed circular DNA level on recurrence of hepatocellular carcinoma after initial hepatectomy: an analysis of patients with resolved hepatitis B virus infection

BackgroundWe assessed whether or not covalently closed circular DNA (cccDNA) levels in the background liver influence the recurrence of hepatocellular carcinoma (HCC) in patients with resolved hepatitis B virus (HBV) infection.MethodsAmong 425 patients who underwent initial hepatectomy for HCC between 2010 and 2018, a retrospective review was performed in 44 with resolved HBV infection. The clinicopathologic characteristics were analyzed for correlation with tumor recurrence. The HBV cccDNA levels were tested via a droplet digital polymerase chain reaction assay.ResultsHBV cccDNA was detected in 27 of 44 patients (61%), and the median level was 1.0 copies/1000 ng (range, 0-931.3 copies/1000 ng). Anti-HBc ≥8.9 S/CO was associated with cccDNA detection (odds ratio, 11.08; 95% confidence interval [95% CI], 2.48-49.46; P = 0.002). Twenty-eight patients (64%) developed HCC recurrence after hepatectomy. The overall 3- and 5-year recurrence-free survival rates were 45.7% and 34.3%, respectively.19 HBV cccDNA levels was not significantly associated with HCC recurrence, while the presence of multiple tumors was an independent risk fact or (hazard ratio, 6.53; 95% CI, 2.48-17.19; P < 0.001.ConclusionHBV cccDNA levels did not influence HCC recurrence after hepatectomy. Anti-HBc levels may be used as a surrogate marker for cccDNA.     

单抗N糖分析系统适用性对照品的建立

目的建立单抗N糖分析方法的系统适用性对照品,并设定相应的系统适用性要求。方法利用液质联用(LC-MS)仪对N糖系统适用性对照品进行N糖型的表征鉴别,并对对照品进行稳定性评价。结合方法特点和验证数据,对系统适用性要求进行设定。结果建立的系统适用性对照品具有良好的稳定性,其糖型涵盖了单抗主要的N糖型种类。针对3种药典拟收录的单抗N糖分析方法,设定了以下系统适用性要求,包括:图谱与典型图谱相似、G1F(1,6)和G1F(1,3)的分离度应满足具体要求、G0F%应在规定的范围内、G0F保留时间的RSD应≤4%。结论建立了单抗N糖系统适用性对照品,可配合3种2020年版《中国药典》拟收录的N糖分析方法使用。     

抗PD-1/PD-L1免疫检查点抑制剂的皮肤免疫相关不良反应的研究进展

随着免疫检查点抑制剂（immune checkpoint inhibitors，ICPI）在国内外临床试验和应用中的逐步推广，越来越多的患者从免疫治疗中获得显著的疗效。其中抗程序细胞死亡蛋白1（programmed death-1，PD-1）及其配体（PD-1 ligand，PD-L1）免疫检查点抑制剂已被美国食品药品管理局（FDA）批准用于恶性黑色素瘤、转移性鳞状非小细胞肺癌、晚期肾癌、头颈鳞状细胞癌、尿路上皮癌等肿瘤的治疗。但PD-1/PD-L1单抗也会引起免疫相关性皮肤、消化道、肝脏、内分泌、肺部等器官的不良反应，皮肤毒性如皮疹、白癜风、皮肤干燥症等是最常见也是最早发生的不良反应。     

一株靶向CD90+MHCC97-L细胞单克隆抗体治疗肝癌的实验研究

目的:研究抗人肝癌干细胞单抗28C10体内外功能，为肝癌干细胞的靶向治疗提供有应用价值的候选治疗剂。方法:采用无血清成球实验、侵袭实验和CCK-8方法等检测分析28C10单抗对MHCC97-L sphere的细胞自我更新、侵袭和耐药的影响。裸鼠体内治疗实验研究单抗28C10联合顺铂对MHCC97-L移植瘤生长的作用。Western-Blot方法鉴定该单抗识别抗原的分子量。结果:流式细胞检测结果显示单抗28C10能够识别MHCC97-L中CD90阳性细胞的比例为2.75%。体外功能实验结果显示单抗28C10能显著抑制MHCC97-L sphere细胞的无血清成球能力和侵袭能力，抑制率分别达33.33%和53.8%。28C10能显著抑制MHCC97-L sphere的顺铂耐药能力，其IC50为0.74 μg/ml，而对照组的IC50为1.42 μg/ml。抗体体内治疗实验结果显示，低、高剂量抗体28C10均能抑制肝癌移植瘤的生长，抑制率分别达到了24.0%和67.7%，单独顺铂组肝癌移植瘤的抑制率为35.9%，而顺铂联合高剂量抗体28C10组对肝癌移植瘤的抑制率达到70.1%。Western-Blot结果显示单抗28C10识别的抗原蛋白分子量约100 kD。结论:筛选获得了1株抗肝癌干细胞的功能性单抗，为靶向肝癌干细胞治疗肝癌奠定了重要的基础。     

Redefining synchronous colorectal cancers based on tumor clonality

To analyze the possible clonal origin of a part of Synchronous colorectal cancer (SCRC), we studied 104 paired-SCRCs from 52 consecutive patients without hereditary forms of CRC. We used a Single-Nucleotide Polymorphism array to characterize the genomic profiles, and subsequently used a statistical application to define them according to clonality within the same individual. We categorized the ensuing groups according to colonic location to identify differential phenotypes. The SCRC Monoclonal group (M) (19 cases) was divided into Monosegmental (MM) and Pancolonic (MP) groups. The SCRC Polyclonal group (P) (33 cases) was also divided into Monosegmental (PM) and Pancolonic (PP), the first exhibiting preference for left colon. The MM group showed a high rate of mucinous tumors, the lowest mean-number of tumors and associated-polyps, and the worst prognosis. The MP group included the largest mean-number of associated-polyps, best prognosis and familial cancer component. The PM group seemed to be a “frontier” group. Finally, the PP group also exhibited a mucin component, the highest mean-number of tumors (4.6) compared with the mean-number of polyps (7.7), poor prognosis and sporadic cases. Most relevant differential genomic regions within M groups were gains on 1q24 and 8q24, and deletions on 1p21 and 1p23 for MM, while within P were the gains on 7q36 and deletions on 1p36 for PM. The statistical application employed seems to define clonality more accurately in SCRC -more likely to be polyclonal in origin-, and together with the tumor locations, helped us to configure a classification with prognostic and clinical value.