Organotypic slice cultures of human gastric and esophagogastric junction cancer

离体 细胞角蛋白 顺铂 体内 病理 癌症 细胞毒性T细胞 生物 癌症研究 免疫组织化学 医学 体外 化疗 内科学 生物化学 生物技术
作者
Justus Koerfer,Sonja Kallendrusch,Felicitas Merz,Christian Wittekind,Christoph Kubick,Woubet Tefera Kassahun,Guido Schumacher,Christian Moebius,Nikolaus Gaßler,Nikolas Schopow,Daniela Geister,Volker Wiechmann,Arved Weimann,Christian Eckmann,Achim Aigner,Ingo Bechmann,Florian Lordick
出处
期刊:Cancer Medicine [Wiley]
卷期号:5 (7): 1444-1453 被引量:57
标识
DOI:10.1002/cam4.720
摘要

Abstract Gastric and esophagogastric junction cancers are heterogeneous and aggressive tumors with an unpredictable response to cytotoxic treatment. New methods allowing for the analysis of drug resistance are needed. Here, we describe a novel technique by which human tumor specimens can be cultured ex vivo , preserving parts of the natural cancer microenvironment. Using a tissue chopper, fresh surgical tissue samples were cut in 400 μ m slices and cultivated in 6‐well plates for up to 6 days. The slices were processed for routine histopathology and immunohistochemistry. Cytokeratin stains ( CK 8, AE 1/3) were applied for determining tumor cellularity, Ki‐67 for proliferation, and cleaved caspase‐3 staining for apoptosis. The slices were analyzed under naive conditions and following 2–4 days in vitro exposure to 5‐ FU and cisplatin. The slice culture technology allowed for a good preservation of tissue morphology and tumor cell integrity during the culture period. After chemotherapy exposure, a loss of tumor cellularity and an increase in apoptosis were observed. Drug sensitivity of the tumors could be assessed. Organotypic slice cultures of gastric and esophagogastric junction cancers were successfully established. Cytotoxic drug effects could be monitored. They may be used to examine mechanisms of drug resistance in human tissue and may provide a unique and powerful ex vivo platform for the prediction of treatment response.
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