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血浆氧化盐水(POS)在艾氏腹水癌模型中的体内外抗癌疗效

The Anticancer Efficacy of Plasma-Oxidized Saline (POS) in the Ehrlich Ascites Carcinoma Model In Vitro and In Vivo.

作者信息

Brito Walison Augusto Silva, Freund Eric, Nascimento Thiago Daniel Henrique do, Pasqual-Melo Gabriella, Sanches Larissa Juliani, Dionísio Joyce Hellen Ribeiro, Fumegali William Capellari, Miebach Lea, Cecchini Alessandra Lourenço, Bekeschus Sander

机构信息

ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany.

Department of General Pathology, State University of Londrina, Rodovia Celso Garcia Cid, Londrina 86051-990, Brazil.

出版信息

Biomedicines. 2021 Jul 31;9(8):932. doi: 10.3390/biomedicines9080932.

Abstract

Cold physical plasma, a partially ionized gas rich in reactive oxygen species (ROS), is receiving increasing interest as a novel anticancer agent via two modes. The first involves its application to cells and tissues directly, while the second uses physical plasma-derived ROS to oxidize liquids. Saline is a clinically accepted liquid, and here we explored the suitability of plasma-oxidized saline (POS) as anticancer agent technology in vitro and in vivo using the Ehrlich Ascites Carcinoma (EAC) model. EAC mainly grows as a suspension in the peritoneal cavity of mice, making this model ideally suited to test POS as a putative agent against peritoneal carcinomatosis frequently observed with colon, pancreas, and ovarium metastasis. Five POS injections led to a reduction of the tumor burden in vivo as well as in a decline of EAC cell growth and an arrest in metabolic activity ex vivo. The treatment was accompanied by a decreased antioxidant capacity of Ehrlich tumor cells and increased lipid oxidation in the ascites supernatants, while no other side effects were observed. Oxaliplatin and hydrogen peroxide were used as controls and mediated better and worse outcomes, respectively, with the former but not the latter inducing profound changes in the inflammatory milieu among 13 different cytokines investigated in ascites fluid. Modulation of inflammation in the POS group was modest but significant. These results promote POS as a promising candidate for targeting peritoneal carcinomatosis and malignant ascites and suggest EAC to be a suitable and convenient model for analyzing innovative POS approaches and combination therapies.

摘要

冷物理等离子体是一种富含活性氧(ROS)的部分电离气体,作为一种新型抗癌剂正受到越来越多的关注,其作用方式有两种。第一种是直接将其应用于细胞和组织,第二种是利用物理等离子体产生的ROS来氧化液体。生理盐水是临床上认可的液体,在此我们使用艾氏腹水癌(EAC)模型在体外和体内探索了等离子体氧化生理盐水(POS)作为抗癌剂技术的适用性。EAC主要以悬浮形式生长在小鼠腹腔中,这使得该模型非常适合测试POS作为一种针对结肠、胰腺和卵巢转移中常见的腹膜癌的假定药物。五次POS注射导致体内肿瘤负担减轻,同时EAC细胞生长下降,体外代谢活性停滞。该治疗伴随着艾氏肿瘤细胞抗氧化能力的降低和腹水上清液中脂质氧化的增加,同时未观察到其他副作用。奥沙利铂和过氧化氢用作对照,分别介导了更好和更差的结果,前者在腹水中研究的13种不同细胞因子中诱导了炎症环境的深刻变化,而后者没有。POS组的炎症调节作用适度但显著。这些结果表明POS是靶向腹膜癌和恶性腹水的有希望的候选药物,并表明EAC是分析创新POS方法和联合疗法的合适且方便的模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28dd/8394252/589657c4d028/biomedicines-09-00932-g001.jpg

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