An In Vitro Investigation into Cryoablation and Adjunctive Cryoablation/Chemotherapy Combination Therapy for the Treatment of Pancreatic Cancer Using the PANC-1 Cell Line.
An In Vitro Investigation into Cryoablation and Adjunctive Cryoablation/Chemotherapy Combination Therapy for the Treatment of Pancreatic Cancer Using the PANC-1 Cell Line.
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DOI：
10.3390/biomedicines10020450
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发表时间：
2022-02-15
期刊：
影响因子：
4.7
通讯作者：
Snyder KK
中科院分区：
文献类型：
--
作者：
Baust JM;Santucci KL;Van Buskirk RG;Raijman I;Fisher WE;Baust JG;Snyder KK
随着胰腺导管腺癌 (PDAC) 的发病率持续增长，对新治疗策略的需求也随之增加。正在评估的此类领域之一是冷冻消融。尽管前景广阔，但研究仍然有限，围绕基本剂量（最低致死温度）的问题，加上与进入 PDAC 肿瘤以及肿瘤接近脉管系统和胆管等相关的技术问题，限制了冷冻消融的使用。此外，由于化疗仍然是 PDAC 的一线治疗方法，因此关于冷冻与化疗相结合的影响的信息有限。因此，本研究研究了 PDAC 细胞系对冷冻、化疗以及化疗预处理和冷冻相结合的体外反应。 PANC-1 细胞和 PANC-1 肿瘤模型接受冷冻消融（冷冻损伤），并与非冷冻对照进行比较。此外，PANC-1细胞单独暴露于不同亚临床剂量的吉西他滨或奥沙利铂以及与冷冻相结合。结果表明，冷冻至-10°C并不影响活力，而-15°C和-20°C则导致冷冻后1天的活力分别降低至85%和20%，尽管两者在第7天都恢复到对照水平。在低于-25°C的单次冷冻后发现细胞完全丧失。 100 nM 吉西他滨 (1.1 mg/m2) 预处理和 -15 °C 单次冷冻相结合，在 7 天的评估间隔内导致细胞接近完全死亡（<5% 存活率）。 8.8 µM 奥沙利铂 (130 mg/m2) 预处理和单次 -15 °C 冷冻相结合，导致 PANC-1 细胞死亡增加的类似趋势。总之，这些体外结果表明，单独冷冻至 -25 °C 范围内的温度会导致 PDAC 高度破坏。此外，数据支持治疗 PDAC 的潜在组合化疗/冷冻治疗策略。这些结果表明，当与冷冻疗法联合治疗 PDAC 时，可能会减少化疗剂量。
As the incidence of pancreatic ductal adenocarcinoma (PDAC) continues to grow, so does the need for new strategies for treatment. One such area being evaluated is cryoablation. While promising, studies remain limited and questions surrounding basic dosing (minimal lethal temperature) coupled with technological issues associated with accessing PDAC tumors and tumor proximity to vasculature and bile ducts, among others, have limited the use of cryoablation. Additionally, as chemotherapy remains the first-line of attack for PDAC, there is limited information on the impact of combining freezing with chemotherapy. As such, this study investigated the in vitro response of a PDAC cell line to freezing, chemotherapy, and the combination of chemotherapy pre-treatment and freezing. PANC-1 cells and PANC-1 tumor models were exposed to cryoablation (freezing insult) and compared to non-frozen controls. Additionally, PANC-1 cells were exposed to varying sub-clinical doses of gemcitabine or oxaliplatin alone and in combination with freezing. The results show that freezing to −10 °C did not affect viability, whereas −15 °C and −20 °C resulted in a reduction in 1 day post-freeze viability to 85% and 20%, respectively, though both recovered to controls by day 7. A complete cell loss was found following a single freeze below −25 °C. The combination of 100 nM gemcitabine (1.1 mg/m2) pre-treatment and a single freeze at −15 °C resulted in near-complete cell death (<5% survival) over the 7-day assessment interval. The combination of 8.8 µM oxaliplatin (130 mg/m2) pre-treatment and a single −15 °C freeze resulted in a similar trend of increased PANC-1 cell death. In summary, these in vitro results suggest that freezing alone to temperatures in the range of −25 °C results in a high degree of PDAC destruction. Further, the data support a potential combinatorial chemo/cryo-therapeutic strategy for the treatment of PDAC. These results suggest that a reduction in chemotherapeutic dose may be possible when offered in combination with freezing for the treatment of PDAC.
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影响因子：
3.1
作者：
Baust, John G.;Snyder, Kristi K.;Baust, John M.
通讯作者：
Baust, John M.
影响因子：
2.8
作者：
Baust JM;Rabin Y;Polascik TJ;Santucci KL;Snyder KK;Van Buskirk RG;Baust JG
通讯作者：
Baust JG
影响因子：
11.2
作者：
Cha HR;Lee JH;Ponnazhagan S
通讯作者：
Ponnazhagan S
影响因子：
2.7
作者：
Baust, J;Gage, AA;Zhang, CM
通讯作者：
Zhang, CM
影响因子：
1.1
作者：
Baust, John M.;Robilotto, Anthony;Baust, John G.
通讯作者：
Baust, John G.