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:Efficacy analysis of TACE in combination with anlotinib and sintilimab in the treatment of unresectable hepatocellular carcinoma.
Efficacy analysis of TACE in combination with anlotinib and sintilimab in the treatment of unresectable hepatocellular carcinoma.
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探讨TACE联合安罗替尼和信迪利单抗治疗不可切除肝细胞癌的有效性。选取2020年1月至2023年12月我院收治的210例原发性不可切除肝细胞癌(PAC)患者作为研究对象,采用信封法将其分为两组,每组105例,信封为连续编号、不透光、密封,内含计算机生成的随机分配方案。对照组采用TACE联合安罗替尼治疗,研究组在对照组基础上加用信迪利单抗治疗,所有患者均随访18个月或至死亡或失访,比较两组患者的治疗效果、安全性、肿瘤标志物、肿瘤生长因子及患者恢复情况的差异。研究组的DCR和ORR分别为81.90%和49.52%,显著高于对照组的61.90%和35.24%,差异有统计学意义(P = 0.042和P = 0.029)。研究组的PFS(12.54 0.39个月)和OS(17.52 0.98个月)显著高于对照组(8.65 0.97个月)和OS(12.94 1.55个月),差异有统计学意义(P = 0.001),研究组患者12个月和18个月生存率分别为75.24%和53.33%,显著高于对照组的70.48%和31.43%,差异有统计学意义(P = 0.013和P = 0.011)。
研究组1~3级不良反应中骨髓抑制和肝功能损害的发生率明显高于对照组,差异有统计学意义(P = 0.035和P = 0.021)。无患者发生4~5级不良反应。两组治疗前CEA、AFP、CD3+、CD4+、CD4+/CD8+、NK细胞、VEGF、PDGF、KPS及QLQ-C30评分差异均无统计学意义(P > 0.05),且KPS评分明显高于治疗前,VEGF、PDGF、CEA、AFP、CD3+、CD4+、CD4+/CD8+、NK细胞及QLQ-C30水平明显低于治疗前,差异有统计学意义(P < 0.001),研究组CD3+、CD4+、CD4+/CD8+、NK细胞水平及KPS评分明显高于对照组,VEGF、PDGF、CEA、AFP及QLQ-C30评分明显低于对照组,差异有统计学意义(P < 0.001)。TACE联合安罗替尼和信迪利单抗治疗中期不可切除肝细胞癌患者,可有效提高近期和远期治疗效果,不良反应患者可耐受,并能有效降低肿瘤标志物水平,减少肿瘤血管生成,改善患者免疫功能,提高患者生存率。
To investigate the effectiveness of TACE in combination with anlotinib and sintilimab in the treatment of unresectable hepatocellular carcinoma. A total of 210 patients with primary unresectable hepatocellular carcinoma (PAC) in our hospital from January 2020 to December 2023 were selected as the study subjects, and they were divided into two groups of 105 cases each by the envelope method using sequentially numbered, opaque sealed envelopes containing computer-generated random allocations. The control group was treated with TACE combined with anlotinib, and the study group was treated with sintilimab on the basis of the control group, and all patients were followed up for 18 months or until death or loss to follow-up, and the differences in treatment efficacy, safety, tumor markers, tumor growth factors and patient recovery between the two groups were compared. The DCR and ORR of the study group were 81. 90% and 49. 52%, which were significantly higher than those of the control group (61. 90%) and 35. 24%, and the difference was statistically significant(P = 0. 042 and P = 0. 029, respectively). The PFS (12. 54 0. 39 months) and OS (17. 52 0. 98 months) in the study group were significantly higher than those in the control group (8. 65 0. 97 months) and OS (12. 94 1. 55 months), and the difference was statistically significant (P = 0. 001), and the survival rates of patients in the study group were 75. 24% and 53. 33% after 12 months and 18 months, which were significantly higher than those in the control group (70. 48% and 31.
43%), and the difference was statistically significant(P = 0. 013 and P = 0. 011, respectively). The incidence of myelosuppression and liver damage in grade 1 ~ 3 adverse reactions in the study group was significantly higher than that in the control group, and the difference was statistically significant(P = 0. 035 and P = 0. 021, respectively). No patient experienced grade 4 5 adverse reactions. There was no significant difference in the scores of CEA, AFP, CD3+, CD4+, CD4+/CD8+, NK cells, VEGF, PDGF, KPS and QLQ-C30 between the two groups before treatment (P > 0. 05), and the KPS scores were significantly higher than those before treatment, and the levels of VEGF, PDGF, CEA, AFP, CD3+, CD4+, CD4+/CD8+, NK cells and QLQ-C30 were significantly lower than those before treatment.
The difference was statistically significant (P < 0. 001), the CD3+, CD4+, CD4+/CD8+, NK cell levels and KPS scores in the study group were significantly higher than those in the control group, and the scores of VEGF, PDGF, CEA, AFP and QLQ-C30 were significantly lower than those in the control group, and the difference was statistically significant (P < 0. 001).
The treatment of TACE combined with anlotinib and sintilimab in patients with intermediate-stage unresectable hepatocellular carcinoma can effectively improve the short-term and long-term treatment efficacy, and adverse reactions can be tolerated by patients, and can effectively reduce the level of tumor markers, reduce tumor angiogenesis, improve patients immune function, and improve the survival rate of patients.
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