钙或博来霉素电穿孔:首次应用于体内葡萄膜黑色素瘤患者衍生异种移植模型

Pharmaceuticals Pub Date : 2024-07-07 DOI:10.3390/ph17070905
Ralitsa Anastasova, M. Fiorentzis, Hongtao Liu, Sami Dalbah, N. E. Bechrakis, Berthold Seitz, U. Berchner‐Pfannschmidt, Theodora Tsimpaki
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引用次数: 0

摘要

葡萄膜黑色素瘤(UM)是一种罕见的葡萄膜道肿瘤,由于转移风险高,预后较差。尽管葡萄膜黑色素瘤的治疗取得了进展,但其死亡率仍然很高,因此迫切需要新的治疗策略。本研究基于绒毛膜异种移植(PDX)模型,首次对钙离子电穿孔(CaEP)与博来霉素电化学疗法(ECT)的治疗潜力进行了体内分析。实验采用 5 或 10 mM 氯化钙或 1 或 2.5 µg/mL 博莱霉素结合 EP 或单独 EP 的单一疗法。CaEP和ECT诱导的增殖活性、新生血管和黑素细胞扩张的减少程度相似。与未经处理的肿瘤移植物相比,CaEP的剂量依赖性效应可显著诱导坏死,而使用1 µg/mL博莱霉素的ECT可显著增加凋亡反应。我们的研究结果概述了CaEP和博莱霉素ECT作为UM辅助治疗的前瞻性应用,有助于充分控制局部肿瘤,并有可能提高转移率和总生存率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Electroporation with Calcium or Bleomycin: First Application in an In Vivo Uveal Melanoma Patient-Derived Xenograft Model
Uveal melanoma (UM) represents a rare tumor of the uveal tract and is associated with a poor prognosis due to the high risk of metastasis. Despite advances in the treatment of UM, the mortality rate remains high, dictating an urgent need for novel therapeutic strategies. The current study introduces the first in vivo analysis of the therapeutic potential of calcium electroporation (CaEP) compared with electrochemotherapy (ECT) with bleomycin in a patient-derived xenograft (PDX) model based on the chorioallantoic membrane (CAM) assay. The experiments were conducted as monotherapy with either 5 or 10 mM calcium chloride or 1 or 2.5 µg/mL bleomycin in combination with EP or EP alone. CaEP and ECT induced a similar reduction in proliferative activity, neovascularization, and melanocytic expansion. A dose-dependent effect of CaEP triggered a significant induction of necrosis, whereas ECT application of 1 µg/mL bleomycin resulted in a significantly increased apoptotic response compared with untreated tumor grafts. Our results outline the prospective use of CaEP and ECT with bleomycin as an adjuvant treatment of UM, facilitating adequate local tumor control and potentially an improvement in metastatic and overall survival rates.
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