Image-Guided Biomolecular Intervention Research & Division of Interventional Radiology, Department of Radiology, University of Washington School of Medicine, 850 Republican St., S470, Seattle, WA, 98109, USA.
Department of Radiology, The Affiliated People's Hospital of Ningbo University, Ningbo, China.
Cardiovasc Intervent Radiol. 2022 Dec;45(12):1812-1821. doi: 10.1007/s00270-022-03210-2. Epub 2022 Jul 28.
To investigate the effect of radiofrequency hyperthermia (RFH)-enhanced oncolytic immuno-virotherapy on in vitro pancreatic adenocarcinoma cell line and in vivo rat pancreatic cancer model.
Rat pancreatic adenocarcinoma cell line and 24 Lewis rats with orthotopic pancreatic adenocarcinomas underwent treatment with either (1) oncolytic virotherapy (talimogene laherparepvec [T-VEC]) plus RFH at 42 °C for 30 min; (2) oncolytic virotherapy-only; (3) RFH-only; or (4) saline (control). MTS assays and flow cytometry were used to analyze tumor cell viability and apoptosis levels 24 h after treatment. In the in vivo studies, bioluminescence optical/x-ray imaging and ultrasound imaging was used to assess tumor viability and size 7 and 14 days after treatment. Histopathologic analysis was performed after hematoxylin and eosin staining, TUNEL, Ki-67, and immunohistochemical staining with CD8 and ANK61.
Combination therapy (T-VEC + RFH) induced decreased cell viability and increased cell apoptosis compared to T-VEC alone, RFH alone, or control. Optical/x-ray imaging and ultrasound imaging demonstrated decreased tumor bioluminescent signal and tumor volume relative to baseline after combination therapy compared to T-VEC alone, RFH alone, or control. Histopathology demonstrated decreased tumor volume and cell proliferation, increased CD8 T cell and NK cell infiltration in tumors treated with the combination therapy compared to other three groups.
RFH enhances locally delivered oncolytic immuno-virotherapy for pancreatic adenocarcinoma, with decreased cell viability and increased apoptosis observed after combination therapy in vitro, and decreased cell viability and tumor volume and increased immune cell infiltrate observed after combination therapy in vivo.
研究射频热疗（RFH）增强溶瘤免疫病毒治疗对体外胰腺腺癌细胞系和体内大鼠胰腺癌模型的影响。
采用大鼠胰腺腺癌细胞系和 24 只原位胰腺腺癌大鼠，分别接受以下治疗：（1）溶瘤病毒治疗（talimogene laherparepvec[T-VEC]）联合 42°C 30 分钟 RFH；（2）单纯溶瘤病毒治疗；（3）单纯 RFH；或（4）生理盐水（对照）。24 小时后，采用 MTS 法和流式细胞术检测肿瘤细胞活力和凋亡水平。在体内研究中，采用生物发光光学/X 射线成像和超声成像评估治疗后 7 天和 14 天肿瘤的活力和大小。治疗后进行苏木精和伊红染色、TUNEL、Ki-67 以及 CD8 和 ANK61 免疫组化染色的组织病理学分析。
与 T-VEC 单药、RFH 单药或对照组相比，联合治疗（T-VEC+RFH）诱导的细胞活力降低和细胞凋亡增加。光学/X 射线成像和超声成像显示，与 T-VEC 单药、RFH 单药或对照组相比，联合治疗后肿瘤的生物发光信号和肿瘤体积均较基线下降。组织病理学显示，与其他三组相比，联合治疗组肿瘤体积和细胞增殖减少，CD8 T 细胞和 NK 细胞浸润增加。
RFH 增强了局部递送的溶瘤免疫病毒治疗胰腺腺癌的疗效，体外联合治疗后观察到细胞活力降低和凋亡增加，体内联合治疗后观察到细胞活力降低、肿瘤体积缩小和免疫细胞浸润增加。
