Clinical efficacy and safety of tumor-specific individualized multi-target DC-CIK in the treatment of advanced non-small cell lung cancer / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：评价肿瘤特异性个体化多靶点树突状细胞-细胞因子诱导的杀伤细胞（DC-CIK）治疗晚期非小细胞肺癌（NSCLC）患者的临床疗效和安全性。方法：回顾性分析2019年10月1日至2022年10月31日东部战区总医院生物治疗科行肿瘤特异性个体化多靶点DC-CIK治疗晚期NSCLC患者的临床资料。统计NSCLC患者的临床疗效和不良反应，分析治疗前后血清中肿瘤标志物的变化，FCM检测患者治疗前后的淋巴细胞亚群和各种细胞因子的表达情况，用质谱仪检测治疗前后靶点的变化。结果: 共入组52例晚期NSCLC患者，其中女性21例、男性31例；年龄32~71岁，平均年龄（50.97±10.72）岁，中位年龄47.5岁。经DC-CIK治疗后，CR 0例，PR 0例，SD 27例，PD 25例。与治疗前比较，DC-CIK治疗后：（1）CEA和CYFRA21-1水平无显著改变，CA125水平显著低于治疗前（P<0.01）；（2）治疗后患者淋巴细胞亚群无显著变化；（3）治疗后患者外周血IL-2、IL-4、IFN-γ和TNF-α水平显著升高（均P<0.01），IL-6、IL-10及IL-17水平无明显变化；（4）治疗后靶点数下降明显。DC-CIK治疗过程中无严重不良反应发生。结论: 晚期NSCLC患者行肿瘤特异性个体化多靶点自体DC-CIK治疗是安全的，能使患者产生抗肿瘤免疫反应并得到一定的临床获益。

PARP1 promotes proliferation and 5-FU resistance of gastric cancer AGS cells by regulating N-glycosyltransferase FUT8 / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the effect of polyadenosine diphosphate ribose polymerase 1 (PARP1) on the proliferation and 5-FU resistance of gastric cancer cells and its potential mechanism. Methods: The tumor tissues and corresponding paracancerous tissues of 72 patients with gastric cancer who were treated in Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from May 2018 to December 2019 were collected. AGS cells were transfected with siFUT8 to knock down FUT8 gene expression. qPCR and immunohistochemistry were used to detect the expression of PARP1 in gastric cancer and adjacent tissues. CCK-8, flow cytometry, and colony formation assay were employed to detect the effects of AG14361 on the proliferation, apoptosis and colony formation of AGS cells. MTT assay was used to detect the effect of AG14361 on the 5-FU sensitivity of gastric cancer cells. The overall distribution of differential genes in AGS cells treated with AG14361 was analyzed by mRNA sequencing, and related signaling pathways were analyzed by KEGG enrichment. qPCR and WB were used to detect the expression of α-1,6-fucosyltransferase (FUT8) in AGS cells and the interference effect of FUT8. CCK-8, flow cytometry, and colony formation assay were employed to detect the effects of AG14361 on the proliferation, apoptosis, and colony formation of AGS cells disturbed by siFUT8. Results: Compared with paracancer tissues, PARP1 expression was significantly increased in gastric cancer tissues (P<0.001). AG14361 can significantly inhibit the proliferation and colony formation of AGS cells, thus promoting the apoptosis of AGS cells (all P<0.01). AG14361 treatment reduced the IC50 of 5-FU against gastric cancer cells, especially against AGS cells, with IC50 decreased by more than 60%. mRNA sequencing results showed that FUT8 was a key glycosyltransferase of AG14361 in inhibiting the proliferation of AGS cells (P<0.05). Compared with the siNC group, treatment of AG14361 with IC50 significantly reversed the promotion of AGS cells proliferation caused by inerference with FUT8, promoted apoptosis and BAX protein expression, decreased Bcl2 protein expression and inhibited the increase in AGS cell colony formation caused by interference with FUT8 (all P<0.01). Conclusion: PARP1 can promote malignant transformation of gastric cancer cells by regulating N-glycosyltransferase FUT8. AG14361 can enhance the chemotherapy sensitivity of 5-FU, and PARP1 may become a potential target for gastric cancer treatment.