RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CD4/CD8 Ratio could be predictor of burden hepatocellular carcinoma in Egyptian chronic hepatitis C after combined sofosbuvir and daclatasvir therapy.
CD4/CD8 Ratio could be predictor of burden hepatocellular carcinoma in Egyptian chronic hepatitis C after combined sofosbuvir and daclatasvir therapy.
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HCV 治疗通过 DAAS 使 CHC 患者在治疗结束时 T 辅助细胞、T 细胞毒性细胞显著减少。26.6% 发生局灶性 HCC,CD4/CD8 为肿瘤负荷的独立预测因子。需要进一步开展大规模扩展人群研究以阐明这一问题。
在直接抗丙型肝炎病毒药物(DAAS)使用的头几年,若干研究报告称这一新的治疗时代与肝细胞癌(HCC)风险增加之间可能存在相关性。其发生可能得益于免疫微环境的变化以及使用这些药物根除HCV感染后细胞行为的不同。因此,本研究旨在探讨DAAS的免疫学效应。受试者与
前瞻性配对样本设计,对90例未接受过治疗的慢性HCV感染患者进行,在接受sofosbuvir 400 mg每日一次和daclatasvir 60 mg每日一次联合治疗12周之前和之后,并随访一年。免疫学检测包括:通过分别使用CD3、CD3/CD4、CD3/CD8和CD56的荧光素标记单克隆抗体,经多参数FACSCanto ™ II流式细胞仪(Becton Dickinson,美国)检测外周血中总T细胞计数、T辅助细胞计数、T细胞毒性细胞计数和NK 细胞计数。
关于免疫学变化,总T细胞(CD3+)、NK 细胞在治疗结束时呈非显著性下降,而辅助性T细胞(CD3+CD4+)和细胞毒性T细胞(CD3+CD8+)与治疗前值相比呈显著性下降。长期随访显示26.6%发生局灶性HCC,此外,多因素分析显示CD4/CD8比值以及性别可作为联合DAAS治疗后HCC早期发展的预测因素。
During the first years of the use of direct acting Hepatitis C antiviral drugs (DAAS), several studies reported a possible correlation between this new era of treatment and an increased risk of Hepatocellular carcinoma (HCC). Its development could possibly be favored by the changes in the immunological milieu and the different cellular behavior after eradication of HCV infection with them. For this reason, this study aimed to address the immunological effect of DAAS. SUBJECT &
Prospective paired -sample design, carried out on 90 naïve chronically infected HCV patients before and after receiving a combination therapy of sofosbuvir; at a dose of 400 mg once daily and daclatasvir; at a dose of 60 mg once daily for 12 weeks and follow up for one year. immunological tests including: total T cell count, T helper cell count, T cytotoxic cell count and natural killer cell count in peripheral blood through (CD3, CD3/CD4, CD3/CD8 and CD56 respectively) by Fluorochrome monoclonal antibodies labelled with specific dyes through Multiparameter, FACSCanto ™ II flow cytometer (Becton Dickinson, USA). RESULT: Concerning the immunological changes, total T cells (CD3+), Natural killer cells showed non-significant decrease at end of therapy while significant decrease in T helper cells (CD3+CD4+) T cytotoxic cells (CD3+CD8+) compared to pre-treatment value. Long follow up revealed 26.6% developed focal HCC, in more addition, multivariate analysis show CD4/CD8 ratio could be predictor as well as sex for early development of HCC after combined DAAS therapy.
HCV treatment by DAAS produces significant decrease in T helper, T cytotoxic cells in CHC patients at the end of therapy. 26.6% developed focal HCC with independent CD4/CD8 predictor for burden malignancy. Further large extended population study is needed for clarify this concern.
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