| 42 | 0 | 11 |
| 下载次数 | 被引频次 | 阅读次数 |
目的 探讨肝动脉化疗栓塞术(TACE)联合替雷利珠单抗治疗原发性肝癌的效果及对促癌、抑癌基因的影响。方法 选取2018年10月至2023年3月就诊的原发性肝癌患者75例，采用随机数字表法分为对照组37例、观察组38例。2组均予以仑伐替尼治疗，在此基础上对照组给予TACE,观察组予以TACE联合替雷利珠单抗治疗。比较2组疗效、不良反应、短期生存率，以及治疗前后肿瘤标志物、血管生成相关因子、免疫功能指标、促癌和抑癌基因蛋白表达。结果 观察组客观缓解率、疾病控制率均高于对照组(P<0.05)。治疗后，观察组血清癌胚抗原、糖类抗原19-9、细胞角蛋白19、甲胎蛋白、酸性成纤维细胞生长因子、血管内皮生长因子、碱性成纤维细胞生长因子、基质金属蛋白酶-9水平均低于对照组(P<0.05)。治疗后，观察组外周血CD3+、CD4+/CD8+、CD4+高于对照组，外周血单核细胞半胱氨酰天冬氨酸特异性蛋白酶-3、磷脂酰肌醇3激酶蛋白表达水平高于对照组，B淋巴细胞瘤-2、细胞外信号调控激酶蛋白表达水平低于对照组(P<0.05)。2组各项不良反应发生率及治疗后生存率比较无明显差异(P>0.05)。结论 TACE联合替雷利珠单抗治疗原发性肝癌，可提高疗效，抑制新生血管生成，促进免疫功能恢复，且有一定安全性，其机制可能与调节促癌、抑癌基因表达有关，但未明显提高生存率。
Abstract：Objective To investigate the efficacy of transcatheter arterial chemoembolization(TACE) combined with Tislelizumab in the treatment of primary liver cancer and its impact on cancer-promoting and cancer-suppressing genes. Methods Seventy-five patients with primary liver cancer admitted from October 2018 to March 2023 were selected, and then assigned to the control group(n=37) and the observation group(n=38) using the random number table method. Both groups were treated with Lenvatinib. On this basis, the control group received TACE, while the observation group received TACE combined with Tislelizumab. The efficacy, adverse reactions, and short-term survival rate, as well as the changes in tumor markers, angiogenesis-related factors, immune function indicators, and the expression of cancer-promoting and cancer-suppressing genes proteins before and after treatment, were compared between the two groups. Results The objective response rate and disease control rate in the observation group were higher than those in the control group(P<0.05). After treatment, the levels of serum carcinoembryonic antigen, carbohydrate antigen 19-9, cytokeratin 19, alpha-fetoprotein, acidic fibroblast growth factor, vascular endothelial growth factor, basic fibroblast growth factor, and matrix metalloproteinase-9 in the observation group were lower than those in the control group(P<0.05). After treatment, the levels of peripheral blood CD3+, CD4+/CD8+, and CD4+ in the observation group were higher than those in the control group. The expression levels of peripheral blood monocyte cysteine aspartate-specific protease-3 and phosphatidylinositol 3-kinase proteins were higher in the observation group than in the control group, while the expression levels of B lymphocyte tumor-2 and extracellular signal-regulated kinase proteins were lower in the observation group than in the control group(P<0.05). There were no significant differences in the incidence of adverse reactions and post-treatment survival rates between the two groups(P>0.05). Conclusion In the treatment of primary liver cancer, TACE combined with Tislelizumab can improve the therapeutic effect, inhibit neovascularization, and promote immune function recovery, showing a certain degree of safety. Its mechanism may be related to regulating the expression of cancer-promoting and cancer-suppressing gene, but it does not significantly improve survival rate.
[1] WEI J,HU Y,YU J,et al.Predictive value of hepatic venous pressure gradient and efficacy and significance of early PTVE for gastrointestinal bleeding after TACE for liver cancer[J].J Cancer Res Ther,2022,18(7):1967-1972.
[2] LIU L,LIANG X,XU X,et al.Magnetic mesoporous embolic microspheres in transcatheter arterial chemoembolization for liver cancer[J].Acta Biomater,2021,130:374-384.
[3] WU Z H,ZHANG H F,LI J Y,et al.Effectiveness and safety of brucea javanica oil assisted TACE versus TACE in the treatment of liver cancer:a systematic review and meta-analysis of randomized controlled trials[J].Front Pharmacol,2024,15:1337179.
[4] DIAO L,WANG C,YOU R,et al.Hepatic arterial infusion chemotherapy combined with lenvatinib and PD-1 inhibitors versus lenvatinib and PD-1 inhibitors for HCC refractory to TACE[J].J Gastroenterol Hepatol,2024,39(4):746-753.
[5] 童慧，邢鹏.替雷利珠单抗联合XELOX方案治疗晚期胃癌的临床研究[J].现代药物与临床，2024,39(3):700-704.
[6] WANG J,LAN H,MAO X,et al.Pituitary-adrenal axis dysfunction induced by tislelizumab immunotherapy for non-small cell lung cancer:a case series and literature review[J].BMC Pulm Med,2024,24(1):327.
[7] 中国抗癌协会肝癌专业委员会，中华医学会肝病学分会肝癌学组，中国抗癌协会病理专业委员会，等.原发性肝癌规范化病理诊断指南(2015年版)[J].解放军医学杂志，2015,40(11):865-872.
[8] SCHWARTZ L H,LITIERE S,DE VRIES E,et al.RECIST 1.1-Update and clarification:From the RECIST committee[J].Eur J Cancer,2016,62:132-137.
[9] SHAREN G,CHENG H,HU X,et al.M1-like tumor-associated macrophages enhance proliferation and anti-apoptotic ability of liver cancer cells via activating the NF-κB signaling pathway[J].Mol Med Rep,2022,26(5):331.
[10] WANG L,LIN L,ZHOU W.Efficacy and safety of transarterial chemoembolization combined with lenvatinib and PD-1 inhibitor in the treatment of advanced hepatocellular carcinoma:a meta-analysis [J].Pharmacol Ther,2024,257:108634.
[11] YAO Y,HUANG X,ZHAO C,et al.Summary of the evidence of best practices for the prevention and treatment of embolism syndrome after TACE in primary liver cancer[J].Front Oncol,2024,13:1274235.
[12] LIU J,WANG P,SHANG L,et al.TACE plus tyrosine kinase inhibitors and immune checkpoint inhibitors versus TACE plus tyrosine kinase inhibitors for the treatment of patients with hepatocellular carcinoma:a meta-analysis and trial sequential analysis[J].Hepatol Int,2024,18(2):595-609.
[13] LI X,WANG X,BAI T,et al.Conversion surgery for initially unresectable hepatocellular carcinoma using lenvatinib combined with TACE plus PD-1 inhibitor:a real-world observational study[J].Dig Liver Dis,2024,56(6):1078-1086.
[14] LUO C,LUO S,WUSIMANJIANG W,et al.Bladder-sparing treatment using tislelizumab combined with gemcitabine/cisplatin in selected patients with muscle-invasive bladder cancer:a real-world study[J].Clin Transl Oncol,2024,26(7):1759-1767.
[15] CHEN Q,SUN Q,ZHANG J,et al.Cost-effectiveness analysis of Tislelizumab vs Sorafenib as the first-line treatment of unresectable hepatocellular carcinoma[J].PLoS One,2024,19(3):e0295090.
[16] SUN Q,LONG L.Diagnostic performances of methylated septin 9 gene,CEA,CA19-9 and platelet-to-lymphocyte ratio in colorectal cancer [J].BMC Cancer,2024,24(1):906.
[17] LUAN F,XU S,CHEN K,et al.Prognostic effect of CEA,AFP,CA19-9 and CA242 for recurrence/metastasis of gastric cancer following radical gastrectomy[J].Mol Clin Oncol,2024,22(2):17.
[18] ZHU J,WU Y,ZHANG H,et al.Efficacy of lenvatinib in combination with PD-1 monoclonal antibody and interventional treatment for intermediate-stage hepatocellular carcinoma:impact on serum vascular endothelial growth factor and matrix metalloproteinase-9 levels:a retrospective study[J].Technol Cancer Res Treat,2024,23:15330338241256812.
[19] JIANG Y,HUANG J,HUANG Z,et al.ADAMTS12 promotes oxaliplatin chemoresistance and angiogenesis in gastric cancer through VEGF upregulation[J].Cell Signal,2023,111:110866.
[20] XIONG Z,XU X,ZHANG Y,et al.IFITM3 promotes glioblastoma stem cell-mediated angiogenesis via regulating JAK/STAT3/bFGF signaling pathway[J].Cell Death Dis,2024,15(1):45.
[21] DU Z,XIAO Y,DENG G,et al.CD3+/CD4+ cells combined with myosteatosis predict the prognosis in patients who underwent gastric cancer surgery[J].J Cachexia Sarcopenia Muscle,2024,15(4):1587-1600.
[22] AOKI T,NISHIDA N,KUREBAYASHI Y,et al.Two distinct characteristics of immune microenvironment in human hepatocellular carcinoma with Wnt/β-catenin mutations[J].Liver Cancer,2023,13(3):285-305.
[23] NIE J,ZHANG S,GUO Y,et al.Mapping of the T-cell landscape of biliary tract cancer unravels anatomic subtype-specific heterogeneity[J].Cancer Res,2025,85(4):704-722.
[24] JI Q,FU Y,ZHU X,et al.Effect of RFA and TACE combined with postoperative cytokine-induced killer cell immunotherapy in primary hepatocellular carcinoma[J].J BUON,2021,26(1):235-242.
[25] ZHOU N,CHEN Y,HUANG Q,et al.Pathological complete response to neoadjuvant tislelizumab plus chemotherapy in stage ⅢB small cell lung cancer:a case report and literature review[J].Front Immunol,2023,14:1111325.
[26] GUO Q,ZHAO M,WANG Q,et al.Glycyrrhetinic acid inhibits non-small cell lung cancer via promotion of Prdx6- and caspase-3-mediated mitochondrial apoptosis[J].Biomed Pharmacother,2024,173:116304.
[27] LEIPHRAKPAM P D,ARE C.PI3K/Akt/mTOR signaling pathway as a target for colorectal cancer treatment[J].Int J Mol Sci,2024,25(6):3178.
[28] ZHANG H P,JIANG R Y,ZHU J Y,et al.PI3K/AKT/mTOR signaling pathway:an important driver and therapeutic target in triple-negative breast cancer[J].Breast Cancer,2024,31(4):539-551.
[29] D'AGUANNO S,BRIGNONE M,SCALERA S,et al.Bcl-2 dependent modulation of Hippo pathway in cancer cells[J].Cell Commun Signal,2024,22(1):277.
[30] HUANG Y,ZHEN Y,CHEN Y,et al.Unraveling the interplay between RAS/RAF/MEK/ERK signaling pathway and autophagy in cancer:from molecular mechanisms to targeted therapy[J].Biochem Pharmacol,2023,217:115842.
[31] LIU Y,FENG Y,WANG X,et al.SPARC negatively correlates with prognosis after transarterial chemoembolization and facilitates proliferation and metastasis of hepatocellular carcinoma via ERK/MMP signaling pathways[J].Front Oncol,2020,10:813.
[32] 王渊，谭盼，张靖.替雷利珠单抗联合PC方案治疗晚期肺癌的疗效及对血清PI3K、Akt的影响[J].中国医院用药评价与分析，2023,23(3):268-271.
基本信息:
DOI：
中图分类号:R735.7
引用信息:
[1]赵仰光,李傲,张倩等.肝动脉化疗栓塞术联合替雷利珠单抗治疗原发性肝癌的效果及对促癌、抑癌基因的影响[J].临床误诊误治,2025,38(10):38-44.
基金信息:
河北省2021年度医学科学研究课题(20210772)