PO.ET02.08 · 实验与分子治疗

电穿孔增强博来霉素递送治疗犬猫实质性器官肿瘤的可行性与安全性

Feasibility and safety of electroporation-enhanced bleomycin delivery for the treatment of parenchymal tumors in dogs and cats

海报缩略图:电穿孔增强博来霉素递送治疗犬猫实质性器官肿瘤的可行性与安全性
编号 3034 展板 25 时间 4/20 02:00–05:00 区域 Section 14 主讲 Sergio Salgado, DVM
分会场 Nanocarriers and Drug Delivery Systems
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作者与单位 Authors & Affiliations

Sergio Fernando Salgado1, Andrea Hatsumi Bazan2, Josmell David Mestanza2, Nandi Ken Candela2, Mitzi Westreicher2, Micaela Vizquerra2

1Universidad Peruana Cayetano Heredia, Lima, Peru,2Creo Vet, Lima, Peru

摘要 Abstract

中文摘要
引言:犬猫累及实质性器官的癌症带来治疗挑战,尤其是在多发病变或局部晚期疾病中,此时不适宜手术且药物治疗反应有限。电化学疗法(ECT)通过形成短暂的膜孔促进博来霉素进入细胞,提供精确的药物递送以增强细胞毒性疗效。本研究旨在报告ECT用于治疗两种动物实质性器官肿瘤的安全性和可行性。 材料与方法:纳入5例(4只犬和1只猫),均确诊为肝癌或胰腺癌且无可行治疗选择。记录的变量包括确诊病理、临床表现、治疗时长、临床反应及短期和长期不良反应。静脉给予博来霉素(15,000 IU/m2),随后使用Biotex EPV200电穿孔仪(阿根廷)施加电脉冲。对所有病变施加电脉冲(8个脉冲,100 μs,1,000 V/cm,5 kHz),术前通过计算机断层扫描进行规划。在治疗后30天和60天通过超声评估反应。 结果:4只犬中,3只确诊为多灶性肝细胞癌,1只为胰岛素瘤。此外,1只猫确诊为胰腺腺癌。所有病例均接受治疗。肝脏病变≤3 cm,位于不同肝叶,每位患者治疗2-3个结节。胰岛素瘤(2.66 x 0.88 cm)位于右胰叶,猫的腺癌(2.15 x 1.63 x 1.89cm)位于胰体,与十二指肠和胰十二指肠静脉接触。所有治疗均经剖腹手术进行。肝脏病变因位置较深使用可折叠针电极,而胰腺肿瘤选用板状电极以确保完全覆盖。从博来霉素输注开始的平均治疗时长为15分钟,肝脏病例耗时更长。所有患者均达到完全缓解:肝脏肿瘤在第60天达到完全缓解,猫的胰腺肿瘤在第30天表现为部分缓解,6个月时达到完全缓解。在肝脏病例中,一例出现一过性肝酶升高,另一例出现肝酶恢复正常。对于胰腺病例,治疗后特异性胰脂肪酶升高。所有动物均出现轻至中度疼痛,猫的疼痛略有延长。患胰岛素瘤的犬低血糖缓解,但后来发展为糖尿病需要药物管理,这是观察到的唯一长期不良结局。 结论:电穿孔介导的博来霉素递送是治疗恶性实质性器官肿瘤的一种可行且安全的选择。需要进一步研究以确认这些初步发现。
查看英文原文 English abstract
Introduction: Cancer affecting parenchymal organs in dogs and cats present a therapeutic challenge, particularly in cases of multiple lesions or locally advanced disease where surgery is not indicated and medical therapies offer limited response. Electrochemotherapy (ECT) facilitates bleomycin entry into cells through the formation of transient membrane pores, providing a precise drug delivery that enhances cytotoxic efficacy. The aim of this study was to report the safety and feasibility of ECT for the management of parenchymal tumors in both species. Materials and methods: Five patients (four dogs and one cat) diagnosed with hepatic or pancreatic cancer, for whom no therapeutic option was feasible, were included. Recorded variables included diagnosed pathology, clinical presentation, treatment duration, clinical response, and short-and long-term adverse effects. Bleomycin (15,000 IU/m2) was administered intravenously, followed by electric pulse application using a Biotex EPV200 electroporator (Argentina). Electric pulses (eight pulses of 100 μs, 1.000 V/cm, 5 kHz) were delivered to all lesions, planned preoperatively via computer tomography. Response was evaluated by ultrasonography at 30 and 60 days post-treatment. Results: Among the four dogs, three were diagnosed with multifocal hepatocellular carcinoma and one with insulinoma. Additionally, a cat was diagnosed with pancreatic adenocarcinoma. All cases were treated. Hepatic lesions were ≤3 cm, located in different lobes, with 2-3 nodules treated per patient. The insulinoma (2.66 x 0.88 cm) was located in the right pancreatic lobe, and the feline adenocarcinoma (2.15 x 1.63 x 1.89cm) was found i the pancreatic body in contact with the duodenum and the pancreaticoduodenal vein. All treatments were performed via laparotomy. A foldable needle electrode was used for hepatic lesions due to deeper access, while plate electrodes were selected for pancreatic tumors to ensure complete coverage. The mean treatment duration was 15 minutes from bleomycin infusion, with longer times for hepatic cases. All patients achieved a complete response: hepatic tumors by day 60, the feline pancreatic tumor showed a partial response at day 30, and a complete response by 6 months. Among hepatic cases, one showed transient liver enzyme elevation, and another case showed normalization of liver enzymes. For pancreatic cases, the specific pancreatic lipase was elevated post-treatment. All animals experienced mild to moderate pain, slightly prolonged in the cat. The dog with insulinoma resolved hypoglycemia but later developed diabetes mellitus requiring medical management, the only long-term adverse outcome observed. Conclusions: Electroporation-mediated bleomycin delivery represents a viable and safe option for the treatment of malignant parenchymal tumors. Further studies are needed to confirm these preliminary findings.
利益披露 Disclosure
S. F. Salgado, None.. A. H. Bazan, None.. J. D. Mestanza, None.. N. K. Candela, None.. M. Westreicher, None.. M. Vizquerra, None.

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