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载奥沙利铂温敏液体栓塞剂在兔 VX2 胃癌 TACE 术中的应用。

Application of temperature-sensitive liquid embolic agent loaded with oxaliplatin in the TACE procedure for rabbit VX2 gastric cancer.

机构信息

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.

Department of Peripheral Vascular, Zhoukou Chinese Medicine Hospital, Zhoukou, 466000, People's Republic of China.

出版信息

Drug Deliv Transl Res. 2024 Mar;14(3):705-717. doi: 10.1007/s13346-023-01425-5. Epub 2023 Sep 5.


DOI:10.1007/s13346-023-01425-5
PMID:37668861
Abstract

As a promising drug delivery system, the temperature-sensitive liquid embolic agent (TempSLE) has yet to be reported in animal experiments in treating gastric cancer. We observed and compared computed tomography (CT) imaging changes, tumor volume, HE staining, and immunohistochemistry after transcatheter arterial chemoembolization (TACE) treatment in rabbit VX2 gastric cancer models to clarify the effectiveness of TempSLE loaded with oxaliplatin (TempSLE/Oxa) in treating gastric cancer. One milliliter TempSLE can be loaded with 20 mg oxaliplatin. The accumulative drug release rate at 30 min was 38.76%, and after 24 h, it reached more than 90%. CT examination 1 week after TACE revealed that the TempSLE/Oxa group presents unenhanced hypodense necrotic foci, the iodinated oil loaded with oxaliplatin (Ioil/Oxa) group presents shrinking tumors but still visible speckled foci of enhancement, and the normal saline (NS) group presents heterogeneous enhancement with larger tumors than before. In the postoperative autopsy of TACE, the tumor volumes of TempSLE/Oxa, Ioil/Oxa, and NS groups were 0.15 ± 0.06 cm, 0.37 ± 0.11 cm, and 1.19 ± 0.16 cm, respectively, all of which were statistically different. The positive vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) expression percentages in the TempSLE/Oxa, Ioil/Oxa, and NS groups were statistically different and lowest in the TempSLE/Oxa group. In conclusion, the TempSLE can load a high dose of oxaliplatin to meet the demand of clinical applications. TempSLE/Oxa could effectively inhibit tumor cell proliferation and angiogenesis. This study provides experimental evidence for the further clinical application of the TempSLE/Oxa.

摘要

作为一种有前途的药物输送系统,温度敏感型液体栓塞剂(TempSLE)在动物实验中尚未用于治疗胃癌。我们观察并比较了兔 VX2 胃癌模型经肝动脉化疗栓塞(TACE)治疗后 CT 成像变化、肿瘤体积、HE 染色和免疫组织化学,以阐明负载奥沙利铂的 TempSLE(TempSLE/Oxa)治疗胃癌的效果。1 毫升 TempSLE 可以负载 20 毫克奥沙利铂。30 分钟时的累积药物释放率为 38.76%,24 小时后超过 90%。TACE 后 1 周的 CT 检查显示,TempSLE/Oxa 组呈现未增强的低密度坏死灶,负载奥沙利铂的碘油(Ioil/Oxa)组呈现肿瘤缩小但仍可见点状增强灶,生理盐水(NS)组呈现异质性增强且肿瘤较前增大。TACE 术后剖检显示,TempSLE/Oxa、Ioil/Oxa 和 NS 组的肿瘤体积分别为 0.15±0.06cm³、0.37±0.11cm³和 1.19±0.16cm³,均有统计学差异。TempSLE/Oxa、Ioil/Oxa 和 NS 组的血管内皮生长因子(VEGF)和增殖细胞核抗原(PCNA)阳性表达百分比有统计学差异,且 TempSLE/Oxa 组最低。总之,TempSLE 可以负载高剂量的奥沙利铂以满足临床应用的需求。TempSLE/Oxa 可以有效抑制肿瘤细胞增殖和血管生成。本研究为 TempSLE/Oxa 的进一步临床应用提供了实验依据。

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本文引用的文献

[1]
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Drug Deliv. 2023-12

[2]
Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer.

Nat Commun. 2023-1-3

[3]
The safety and efficacy of oxaliplatin-loaded drug-eluting beads transarterial chemoembolization for the treatment of unresectable or advanced lung cancer.

Front Pharmacol. 2022-11-28

[4]
Gastric transcatheter chemoembolization can resolve advanced gastric cancer presenting with obstruction.

Front Surg. 2022-10-20

[5]
Oxaliplatin Eluting CalliSpheres Microspheres for the Treatment of Unresectable or Recurrent Hepatocellular Carcinoma.

Front Pharmacol. 2022-8-11

[6]
Cisplatin and oleanolic acid Co-loaded pH-sensitive CaCO nanoparticles for synergistic chemotherapy.

RSC Adv. 2022-5-16

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Hydrogels for localized chemotherapy of liver cancer: a possible strategy for improved and safe liver cancer treatment.

Drug Deliv. 2022-12

[8]
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J Biomed Mater Res B Appl Biomater. 2022-8

[9]
Development and validation of a novel online calculator for estimating survival benefit of adjuvant transcatheter arterial chemoembolization in patients undergoing surgery for hepatocellular carcinoma.

J Hematol Oncol. 2021-10-12

[10]
Neoadjuvant Docetaxel, Oxaliplatin, and S-1 in Resectable Advanced Gastric Cancer.

J Clin Oncol. 2021-12-1

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