研究动态
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基于患者来源的原代细胞,通过HDS筛查指导食管鳞状细胞癌的体内和体外个体化治疗。

HDS screening with patient-derived primary cells guided individualized therapy for esophageal squamous cell carcinoma-in vivo and vitro.

发表日期:2023
作者: Xing He, Hezhong Yan, Jie Hu, Xiaowei Duan, Mingjin Zhang, Haiqing Li, Jiaoxue Wang, Qian Gao, Senyuan Yu, Xilu Hou, Guobin Liao, Shicun Guo, Jin Li, Yurong Ge, Xiaolan Chen, Wenchao Wang, Jun Tang
来源: PHYSICAL THERAPY & REHABILITATION JOURNAL

摘要:

分析和评价高通量药物敏感性(High-throughput Drug Sensitivity,HDS)筛选策略在鉴定食管鳞癌(esophageal squamous cell carcinoma,ESCC)高敏感药物中的作用。共有80例进展中的ESCC患者随机分为观察组(40例)和对照组(40例)。观察组分离主要的ESCC细胞采用胃镜从肿瘤组织中,使用HDS方法对来自40例ESCC病例的细胞进行了药物敏感性筛选,然后在患者源性肿瘤异种移植(patient-derived tumor xenograft,PDX)小鼠模型中进行验证。最后,比较了观察组(经筛选药物治疗)和对照组(紫杉醇联合顺铂方案治疗)在化疗后12个月和18个月时间点的治疗效果差异(癌胚抗原(CEA)、细胞角蛋白19-1(CYFRA21-1)、鳞癌相关抗原(SCCA)的水平以及总生存率、局部进展率和远处转移率)。 对于40例ESCC患者筛选了九种不同高敏感性的化疗药物,其中大部分显示对硼替佐米敏感。动物模型实验显示,HDS筛选药物治疗的PDX小鼠肿瘤组织质量明显低于紫杉醇治疗的小鼠(p < 0.05),观察组的治疗效果优于对照组(p < 0.05)。 HDS筛选技术可以在筛选ESCC晚期患者中获得高疗效的抗癌药物,从而减少危重病患者的药物毒性。此外,本研究为治疗晚期ESCC患者提供了一条新的途径,以取得更好的治疗效果。 版权所有©2023年He, Yan, Hu, Duan, Zhang, Li, Wang, Gao, Yu, Hou, Liao, Guo, Li, Ge, Chen, Wang和Tang。
To analyze and evaluate the role of the High-throughput Drug Sensitivity (HDS) screening strategy in identifying highly sensitive drugs against esophageal squamous cell carcinoma (ESCC).A total of 80 patients with progressive ESCC were randomly divided into the observation (40 cases) and the control groups (40 cases). In the observation group, primary ESCC cells were isolated from the tumor tissues with a gastroscope, and drug sensitivity screening was performed on cells derived from the 40 ESCC cases using the HDS method, followed by verification in a patient-derived tumor xenograft (PDX) mouse model. Finally, the differences in the therapeutic efficacy (levels of CEA, CYFRA21-1, SCCA after chemotherapy and the rates of overall survival, local progression, and distant metastasis at 12 months and 18 months time points after chemotherapy) were compared between the observation group (Screened drug-treated) and the control group (Paclitaxel combined with cisplatin regimen-treated).Forty ESCC patients were screened for nine different high-sensitive chemotherapeutics, with the majority showing sensitivity to Bortezomib. Experiments on animal models revealed that the tumor tissue mass of PDX mice treated with the HDS-screened drug was significantly lower than that of the Paclitaxel-treated mice (p < 0.05), and the therapeutic efficacy of the observation group was better than the control group (p < 0.05).HDS screening technology can be beneficial in screening high-efficacy anticancer drugs for advanced-stage ESCC patients, thereby minimizing adverse drug toxicity in critically ill patients. Moreover, this study provides a new avenue for treating advanced ESCC patients with improved outcomes.Copyright © 2023 He, Yan, Hu, Duan, Zhang, Li, Wang, Gao, Yu, Hou, Liao, Guo, Li, Ge, Chen, Wang and Tang.