Department of Ultrasonography, Shanghai Jiao Tong University Affiliated No. 6 Hospital, Shanghai, 200233, People's Republic of China.
Shanghai Institute of Ultrasound in Medicine, Shanghai, 200233, People's Republic of China.
Cytometry A. 2020 Sep;97(9):900-908. doi: 10.1002/cyto.a.24014. Epub 2020 Apr 19.
We examined our hypothesis that high-intensity focused ultrasound (HIFU) treatment of pancreatic ductal adenocarcinoma (PDAC) in nude mice models may lead to an increased occurrence of hematogenous metastasis. The human PDAC cell line BxPC-3 transfected with mCherry was implanted into nude mice to establish orthotopic and subcutaneous xenograft (OX and SX) tumor models. Mice were exposed to HIFU when tumor sizes reached approximately 200-300 mm . The OX and SX tumor models were monitored continuously for tumor growth characteristics and hematogenous metastasis using in vivo flow cytometric (IVFC) detection of circulating tumor cells (CTCs) from the pancreas. We chose an appropriate mouse model to further examine whether or not HIFU increases the potential risk of hematogenous metastasis, using IVFC detection. Our results showed that the CTC number was greater in the OX model than in the SX model. The CTC number in the OX model increased gradually over time, whereas the CTC number in the SX model remained low. Therefore, the OX model was better for studying tumor metastasis by IVFC detection. We found significantly decreased CTC numbers and tumor volume after HIFU ablation. Our results showed the applicability of the PDAC OX tumor model for studying the occurrence of tumor metastasis due to the generation of CTCs. HIFU ablation substantially restricted PDAC hematogenous metastasis and provided effective tumor control locally. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals Inc., on behalf of International Society for Advancement of Cytometry.
我们检验了我们的假设，即高强度聚焦超声（HIFU）治疗裸鼠模型中的胰腺导管腺癌（PDAC）可能导致血液转移的发生率增加。将 mCherry 转染的人 PDAC 细胞系 BxPC-3 植入裸鼠中，建立原位和皮下异种移植（OX 和 SX）肿瘤模型。当肿瘤大小约为 200-300mm 时，用 HIFU 照射小鼠。使用胰腺中循环肿瘤细胞（CTC）的体内流式细胞术（IVFC）检测，连续监测 OX 和 SX 肿瘤模型的肿瘤生长特征和血液转移。我们选择了一个合适的小鼠模型，通过 IVFC 检测进一步研究 HIFU 是否增加了血液转移的潜在风险。我们的结果表明，OX 模型中的 CTC 数量大于 SX 模型。OX 模型中的 CTC 数量随时间逐渐增加，而 SX 模型中的 CTC 数量保持较低水平。因此，OX 模型更适合通过 IVFC 检测研究肿瘤转移。我们发现 HIFU 消融后 CTC 数量和肿瘤体积明显减少。我们的结果表明，由于 CTC 的产生，PDAC OX 肿瘤模型适用于研究肿瘤转移的发生。HIFU 消融显著限制了 PDAC 的血液转移，并在局部提供了有效的肿瘤控制。
