酰胺连接局部麻醉剂改变非小细胞肺腺癌复杂人体组织模型的肿瘤生物学。

IF 2.6 3区 生物学 Q3 MATERIALS SCIENCE, BIOMATERIALS
Juliane Krömer, Sebastian Krämer, Ngoc Anh Hoang, Doreen Sittig, Isabella Metelmann, Uta-Carolin Pietsch, Sebastian N Stehr, Sonja Kallendrusch, Tobias Piegeler
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引用次数: 0

摘要

在各种临床前研究中,酰胺局麻药(LA)可能通过其抗炎特性影响肿瘤负荷。然而,将其转化为临床证据仍然缺乏。本研究利用9例非小细胞肺癌患者的肿瘤切片培养的人离体肿瘤模型,评估了临床相关浓度的LA的作用。肿瘤培养4天,在没有/有顺铂的情况下用LA治疗。利用免疫荧光成像技术评估肿瘤细胞的增殖和凋亡,以及细胞间粘附分子-1的表达和巨噬细胞极化。与未处理的切片相比,当肿瘤标本的增殖和/或凋亡变化bb50 %时,肿瘤标本被认为是“应答者”。9个样本中有5个是“应答者”,其中LA发挥了与顺铂相当的作用。即使在临床上相关的LA浓度下,在肿瘤微环境结构复杂的患者源性肿瘤切片培养中也可以观察到很强的抗肿瘤作用,突出了LA对肿瘤本身及其周围环境的作用,而不受其他白细胞或神经元刺激的干扰。对LA治疗的不同反应也强调了生物标志物在确定肿瘤表型方面的重要性,这可能从LA治疗中受益。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Amide-Linked Local Anesthetics Alter Tumor Biology in a Complex Human Tissue Model of Non-Small Cell Lung Adenocarcinoma.

Amide local anesthetics (LA) affect tumor burden in various preclinical studies, possibly via their anti-inflammatory properties. However, a translation into clinical evidence is still lacking. Here, effects of LA at clinically relevant concentrations are assessed using a human ex vivo tumor model of patient-derived tumor slice cultures from nine patients with non-small cell lung cancer. Tumors are cultivated for four days and treated with LA in absence/presence of cisplatin. Tumor cell proliferation and apoptosis as well as expression of intercellular adhesion molecule-1 and macrophage polarization are assessed using immunofluorescent imaging. Tumor specimens are considered to be "Responders", when a change in proliferation and/or apoptosis by >50% compared to untreated slices occurred. Five of nine samples are "Responders", in which the LA exerted effects comparable to cisplatin. Even at clinically relevant concentrations of LA, a strong anti-tumoral effect is observable in patient-derived tumor slice cultures with complex structures of the tumor microenvironment highlighting the LA effect on the tumor itself and its surroundings, without any interference by other leukocytes or neuronal stimulation. The diverse reaction to LA treatment also emphasizes the importance of biomarkers to determine the tumor phenotypes, which may benefit from LA treatment.

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来源期刊
Advanced biology
Advanced biology Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
6.60
自引率
0.00%
发文量
130
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